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Background: The biological effects of cigarette smoke are not fully known. To improve our understanding of the action of various chemical agents, we investigated the biodistribution of sodium pertechnetate (Na99mTcO4) in mice exposed to cigarette smoke. Methods: Fifteen BALB/c male mice were exposed to the smoke of nine whole commercial cigarettes per day, 3 times/day, for up to 10 days to whole body exposure in a chamber. A control group of 5 BALB/c male mice was sham-smoked. One day later, the exposed and control groups of mice received (7.4 MBq/0.3 ml) of Na99mTcO4 before being killed at 30 min. Bones, brain, heart, intestine, kidney, liver, lungs, muscle, pancreas, spleen, stomach, testis and thyroid were weighed and these organs and blood radioactivity recorded with a gamma counter. The percentage per gram of tissue of injected dose (%ID/g) was determined for each organ. Results: Cigarette smoke significantly decreased (p < 0.05) the %ID/g in red blood cells, bone, kidney, lung, spleen, stomach, testis and thyroid of the exposed mice. Conclusion: The toxic effects of cigarette smoke reduced the Na99mTcO4 biodistribution. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the gene and protein expression of key inflammasome mediators in venous blood and skin biopsy samples from Brazilian psoriatic patients treated at the Pedro Ernesto University Hospital (HUPE). Samples were collected from both psoriatic patients and healthy controls. Gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT‒PCR), while protein levels were assessed through immunohistochemistry and multiplex immunoassays. Compared with those from control individuals, blood and skin biopsy samples from psoriatic patients had significantly higher mRNA levels of nucleotide-binding domain leucine-rich repeat (NLR) family pyrin domain containing receptor 1 (NLRP1), caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). Immunohistochemical analysis revealed elevated protein levels of NLRP1, caspase-1, IL-1β, and IL-18 in psoriatic skin biopsies. Multiplex immunoassays revealed increased plasma levels of interferon-γ (IFN-γ), IL-1β, interleukin-17 A (IL-17 A), and tumor necrosis factor-α (TNF-α) in psoriatic patients. A positive correlation was observed between NLRP1 expression, disease severity, and the protein levels of IL-1β and TNF-α. In conclusion, in Brazilian psoriatic patients treated at HUPE, both blood and skin biopsy samples show increased expression of the NLRP1 inflammasome and its downstream mediators. Furthermore, NLRP1 expression is positively correlated with disease severity and the release of T helper 1-type cytokines, highlighting its potential role in the pathogenesis and progression of psoriasis. [ABSTRACT FROM AUTHOR]

Varicose veins alternate areas of phlebosclerosis and hypertrophy of the vein wall. In this study, samples of long saphenous veins obtained from patients submitted for aortocoronary saphenous vein graft or for surgical resection of varicose saphenous veins were examined. Histologic changes in the intima, muscle, and adventitial layers were quantified. Thicknesses of the venous wall layers were obtained by linear measurements, and the volumetric density of the connective tissue in the muscle layer was determined by point counting. The muscle layer thickness was 300 ± 13 and 581 ± 25 μm in normal and varicose veins, respectively. A more severe connective tissue accumulation within the muscle bundles was found in the varicose condition. The volumetric density of the connective tissue in the circular muscle layer (CmC/MmC) showed also a marked difference between varicose (0.67 ± 0.08) and normal veins (0.43 ± 0.02), P < 0.05. The authors suggest that the varicose condition is associated with a connective tissue uniform accumulation among muscle cells in the circular muscle layer. [ABSTRACT FROM AUTHOR]

Identification of the novel HLA‐DQA1*02:11 allele that differs from HLA‐DQA1*02:01:01:01 in exon 2. [ABSTRACT FROM AUTHOR]

Identification of the novel HLA‐A*30:162 allele that differs from HLA‐A*30:02:01:01 in exon 3. [ABSTRACT FROM AUTHOR]

Characterization and confirmation of an HLA‐DQA1*04:01:01 variant, HLA‐DQA1*04:01:01:09. [ABSTRACT FROM AUTHOR]

Characterization of an HLA‐C*04:01:01 variant, HLA‐C*04:01:01:76. [ABSTRACT FROM AUTHOR]

Characterization and confirmation of the first HLA‐DPA1*04:02 variant, called HLA‐DPA1*04:02:01:02. [ABSTRACT FROM AUTHOR]

Background: Black individuals have a great risk of developing chronic kidney disease (CKD) that is associated with high morbimortality, so it is important to classify them into the correct renal function group. Some equations used to estimate glomerular filtration rate (eGFR) divide patients only into two categories: African Americans and non-African Americans. The CKD-EPI equation was tested only in African Americans, and not Black patients from other regions, and takes into consideration self-reported color-race instead of genomic ancestry (GA) to determine the use of the ethnic correction factor. So far, this equation has not been evaluated in admixed populations, such as the Brazilian, using the percentage of GA to decide to apply the correction factor. The purpose of our study was to compare, in patients with type 1 diabetes (T1D), the eGFR calculated without the use of the correction factor, with the values obtained using the correction factor in patients presenting 50% or more of African GA. Methods: This cross-sectional, multicenter study enrolled 1279 patients from all geographic regions of Brazil. The CKD-EPI equation was used and CKD was defined as eGFR < 60 ml/min. GA were inferred using a panel of 46 AIM-INDEL, afterwards patients presenting an African GA ≥ 50% were selected. Results: Initially, all patients with African GA ≥ 50% (n = 85) were considered as non-African Americans when calculating the eGFR and afterwards the ethnic correction factor was applied to recalculate the eGFR. CKD was present in 23 patients and 56.5% of them were redefined as having normal renal function after using the correction factor, mainly women [11 of the 13 patients (84.6%)], with GFR between 52–59.3 ml/min. Conclusions: More than half of the patients in the study were reclassified to a normal renal function group, showing that GA may be an important tool to decide between the use of the ethnic correction factor in the CKD-EPI equation in a highly admixed population of patients with T1D. A large-scale study involving GA and eGFR in comparison to reference methods should be conducted to better establish whether or not the ethnic correction factor should be used in highly admixed populations. [ABSTRACT FROM AUTHOR]

To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6–<11 years, ≥11–<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self‐reported colour–race and identified a familiar history of T1D in first‐degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub‐Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as HLA‐DQB1*03:02g, ‐DQA1*03:01g, ‐02:01g, DRB1*04:05g and ‐04:02g were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as DRB1*07:01g, ‐13:03g, DQB1*06:02g and DQA1*02:01 were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self‐reported colour–race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype DRB1*03:01g~DQA1*05:01g~DQB1*02:01g did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high‐risk haplotype DRB1*04:05~DQA1*03:01~DQB1*03:02 was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles DQA1*01:02g, DQB1*06:02g, DRB1*07:01g and DRB1*13:03g and haplotypes DRB1*13:03g~DQA1*05:01g~DQB1*03:01g and DRB1*16:02g~DQA1*01:02g~DQB1*05:02g were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well‐known genomic risk or protection factors for T1D. [ABSTRACT FROM AUTHOR]

Background: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce.Methods: The genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated.Results: Lack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers.Conclusions: We did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms. [ABSTRACT FROM AUTHOR]

Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185–80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity. [ABSTRACT FROM AUTHOR]

Background/objectives: The primary aim of this study was to evaluate the prevalence of autoimmune diseases (AIDs) and its associated factors in an admixed Brazilian population of patients with type 1 diabetes (T1D). The secondary one was to determine the relationship between AIDs and the occurrence of diabetes-related chronic complications (DRCC). Methods: This cross-sectional, nationwide survey was conducted in 13 public clinics in 11 Brazilian cities. Overall, 1,760 patients were included; 967 females (55.9%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.8 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. AIDs were retrieved from medical records or self-report and stratified as follows: absence of AIDs, only autoimmune thyroid disease (AITD), and other AIDs including the combination with AITD (hyper or hypothyroidism). Results: The prevalence of AIDs was 19.5% being AITDs (16.1%), the most frequently found. A higher prevalence of hypertension, dyslipidemia and overweight or obesity was found in patients who had exclusively AITDs. A higher prevalence of diabetic retinopathy (DR) was observed in patients with AITDs and patients with other AIDs in combination with AITDs. Chronic kidney disease (CKD) was more prevalent in patients with only AITDs. Lower levels of HbA1C, were observed in patients with isolated AITDs or with other AIDs, regardless of the presence of AITD. Hierarchical multivariate analysis, showed that AIDs were associated with female gender, older age, and longer diabetes duration, self-reported color-race (White and Brown), geographic region (Brazilian North/Northeast region) and higher anti-TPO levels (≥ 35 UI/ml). Conclusions: In conclusion, Brazilian patients with T1D, belonging to a highly ethnically admixed population, had an important prevalence of AIDs, mostly AITDs, that was associated with female gender, self-reported color-race, older age and longer diabetes duration. Moreover, these patients also had a higher prevalence of DRCC. Even though we highlight the importance of investigating the presence of AIDs at diagnosis and at regular intervals, it is unclear whether screening and early detection of additional AIDs may improve the clinical outcomes in individuals with T1D. Future prospective studies are necessary to establish the interplay between T1D, AIDs and DRCC. [ABSTRACT FROM AUTHOR]

In this study our aim was to investigate the time courses of inflammation, oxidative stress and tissue damage after hyperoxia in the mouse lung. Groups of BALB/c mice were exposed to 100% oxygen in a chamber for 12, 24 or 48 h. The controls were subjected to normoxia. The results showed that IL-6 increased progressively after 12 ( P < 0.001) and 24 h ( P < 0.001) of hyperoxia with a reduction at 48 h ( P < 0.01), whereas TNF-α increased after 24 ( P < 0.001) and 48 h ( P < 0.001). The number of macrophages increased after 24 h ( P < 0.001), whereas the number of neutrophils increased after 24 h ( P < 0.01) and 48 h ( P < 0.001). Superoxide dismutase activity decreased in all groups exposed to hyperoxia ( P < 0.01). Catalase activity increased only at 48 h ( P < 0.001). The reduced glutathione/oxidized glutathione ratio decreased after 12 h ( P < 0.01) and 24 h ( P < 0.05). Histological evidence of lung injury was observed at 24 and 48 h. This study shows that hyperoxia initially causes an inflammatory response at 12 h, resulting in inflammation associated with the oxidative response at 24 h and culminating in histological damage at 48 h. Knowledge of the time course of inflammation and oxidative stress prior to histological evidence of acute lung injury can improve the safety of oxygen therapy in patients. [ABSTRACT FROM AUTHOR]

The novel HLA‐DRB1*16:79 allele, first described in an individual from Brazil. [ABSTRACT FROM AUTHOR]

COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies. [ABSTRACT FROM AUTHOR]

We aimed to identify HLA-DRB1, -DQA1, and -DQB1 alleles/haplotypes associated with European, African, or Native American genomic ancestry (GA) in admixed Brazilian patients with type 1 diabetes (T1D). This exploratory nationwide study enrolled 1599 participants. GA percentage was inferred using a panel of 46 ancestry informative marker-insertion/deletion. Receiver operating characteristic curve analysis (ROC) was applied to identify HLA class II alleles related to European, African, or Native American GA, and showed significant (p < 0.05) accuracy for identifying HLA risk alleles related to European GA: for DRB1*03:01, the area under the curve was (AUC) 0.533; for DRB1*04:01 AUC = 0.558, for DRB1*04:02 AUC = 0.545. A better accuracy for identifying African GA was observed for the risk allele DRB1*09:01AUC = 0.679 and for the protective alleles DRB1*03:02 AUC = 0.649, DRB1*11:02 AUC = 0.636, and DRB1*15:03 AUC = 0.690. Higher percentage of European GA was observed in patients with risk haplotypes (p < 0.05). African GA percentage was higher in patients with protective haplotypes (p < 0.05). Risk alleles and haplotypes were related to European GA and protective alleles/haplotypes to African GA. Future studies with other ancestry markers are warranted to fill the gap in knowledge regarding the genetic origin of T1D in highly admixed populations such as that found in Brazil. [ABSTRACT FROM AUTHOR]

• Bacillus Calmette-Guérin (BCG) could be effective against SARS-CoV-2 based on the concept of trained immunity. • COVID-19 vaccines and BCG can enhance the immune response represented by immunoglobulin G levels. • The cumulative incidence of COVID-19 was smaller in BCG-vaccinated participants. • Immunoglobulin G levels tend to be higher and longer in the group submitted to BCG vaccination. Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941). [ABSTRACT FROM AUTHOR]

Background: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19. Methods: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis. Results: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)–categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals. Conclusion: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*18:37:03 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQB1*06:02:62 allele, first described in an individual from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐A*33:01:21 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐C*01:273 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which manifests as a hyper inflammatory process with multiorgan involvement in predominantly healthy children in the weeks following mild or asymptomatic coronavirus disease 2019 (COVID-19). However, host monogenic predisposing factors to MIS-C remain elusive. Methods: Herein, we used whole exome sequencing (WES) on 16 MIS-C Brazilian patients to identify single nucleotide/InDels variants as predisposition factors associated with MIS-C. Results: We identified ten very rare variants in eight genes (FREM1, MPO, POLG, C6, C9, ABCA4, ABCC6, and BSCL2) as the most promising candidates to be related to a higher risk of MIS-C development. These variants may propitiate a less effective immune response to infection or trigger the inflammatory response or yet a delayed hyperimmune response to SARS-CoV-2. Protein–Protein Interactions (PPIs) among the products of the mutated genes revealed an integrated network, enriched for immune and inflammatory response mechanisms with some of the direct partners representing gene products previously associated with MIS-C and Kawasaki disease (KD). In addition, the PPIs direct partners are also enriched for COVID-19-related gene sets. HLA alleles prediction from WES data allowed the identification of at least one risk allele in 100% of the MIS-C patients. Conclusions: This study is the first to explore host MIS-C-associated variants in a Latin American admixed population. Besides expanding the spectrum of MIS-C-associated variants, our findings highlight the relevance of using WES for characterising the genetic interindividual variability associated with COVID-19 complications and ratify the presence of overlapping/convergent mechanisms among MIS-C, KD and COVID-19, crucial for future therapeutic management. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the reduction in the salivary viral load using oral antiseptic mouthwashes in patients testing positive for COVID‐19. Methods: Sixty‐three individuals were recruited after testing positive for COVID‐19 by real‐time RT‐PCR assay and divided into 5 groups. Group 1 received sterile water, group 2 received 1.5% hydrogen peroxide solution (HP), group 3 received 0.12% chlorhexidine (CHX), group 4 received 0.1% sodium hypochlorite solution (NaClO), and group 5 received sequential rinses using CHX and HP. After collecting the initial saliva sample, individuals were asked to use the designated mouthwash for 1 min. Additional saliva samples were collected immediately after rinsing, 15, and 30 min after rinsing. Real‐time RT‐PCR assays for RNA detection of SARS‐CoV‐2 were performed on the saliva samples. Results: There were no significant differences among the experimental groups and the control group in any period. Compared to the baseline values, there was a significant reduction in the number of copies of SARS‐CoV‐2 after 30 min in group 2 and immediately after the initial mouthwash in group 4. Conclusions: No experimental group demonstrated a significant reduction in the viral load compared to the control group. [ABSTRACT FROM AUTHOR]

Characterization of three novel HLA‐DQA1 alleles: HLA‐DQA1*01:02:01:15, ‐DQA1*03:03:01:15, and ‐DQA1*05:05:01:26. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*18:243 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐A*30:218 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. The novel viral lineages P.1 (Variant of Concern Gamma) and P.2, respectively identified in the Brazilian states of Amazonas and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed the whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraíba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) in order to monitor the spread of SARS-CoV-2 lineages in Brazil in the first months of 2021. Here, we showed a widespread dispersal of P.1 and P.2 across Brazilian regions and, except for Amazonas, P.2 was the predominant lineage identified in the sampled states. We estimated the origin of P.2 lineage to have happened in February, 2020 and identified that it has differentiated into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December and its origin was inferred to have happened in August 2020. We also confirmed the presence of lineage P.7, recently described in the southernmost region of Brazil, to have spread across the Northeastern states. P.1, P.2 and P.7 are descended from the ancient B.1.1.28 strain, which co-dominated the first phase of the pandemic in Brazil with the B.1.1.33 strain. We also identified the occurrence of a new lineage descending from B.1.1.33 that convergently carries the E484K mutation, N.9. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to identify novel variants of interest and monitor for vaccine effectiveness. Author summary: Since its first detection in December 2019, the SARS-CoV-2 has evolved into more than a thousand recognized lineages. Several of these lineages are known to have higher transmissibility or better escape from the immune system. One of them is the P.1 lineage, also known as the variant of concern Gamma. It was first discovered in Brazil in December 2020 and has quickly replaced the previous lineage dominating the country, P.2. We used genomic data from SARS-CoV-2 samples that were collected in the first months of 2021 to analyze how P.1, P.2 and other lineages had spread across Brazil. Our research has identified that P.1 lineage was already present in several states of Brazil almost two months before its first detection in the state of Amazonas. Our work sheds light on the importance of continuous monitoring of SARS-CoV-2 lineages in historically understudied regions to early detect and control the spread of new variants of concern. [ABSTRACT FROM AUTHOR]

Aims: The influence of genetic factors on the development and progression of diabetic retinopathy is still unclear. Previous studies showed controversial results. We aimed to characterize the relationship between genomic ancestry and self-reported color/race with severe diabetic retinopathy in patients with type 1 diabetes belonging to a highly admixed population. Methods: This study was a nested case–control based on data collected from a large cross-sectional, nationwide survey conducted in clinics from all five geographic regions of Brazil. For the present study, we included 414 individuals. Cases (n = 176) were considered if they had severe non-proliferative or proliferative diabetic retinopathy, and controls (n = 238) were type 1 diabetes patients without retinopathy, matched for diabetes duration by a range of 5 years. Indirect ophthalmoscopy was performed, and individual genomic ancestry was inferred using a panel of 46 ancestry informative markers. Results: The backward stepwise logistic regression analysis showed that African genomic ancestry (OR 3.9, p = 0.045), HbA1c (OR 1.24, p = 0.001), glomerular filtration rate (OR 0.98, p < 0.001) and hypertension (OR 2.52, p < 0.001) were associated with severe diabetic retinopathy after adjusting for clinical and demographic data. Self-reported color/race was not statistically associated with diabetic retinopathy. Conclusions: Genomic ancestry, as well as clinical variables such as hypertension, impaired glomerular filtration rate and poor diabetes control (HbA1c), was important risk factor for the development of severe diabetic retinopathy. Further studies are needed, especially in highly admixed populations, to better understand the role of genomic ancestry and possible genes that might be associated with the development and/or progression of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

• T1D patients, especially young, exhibit reduced frequencies of Treg cells and naive RTE within Treg cell pool. • Together with Treg cell changes, a great association with HLA risk alleles are also identified in T1D patients. • Treg cells and naive RTE within Treg cells could be relevant variables to distinct T1D patients from healthy controls. To control immune responses, regulatory CD4+CD25+Foxp3+ T cells (Treg) maintain their wide and diverse repertoire through continuous arrival of recent thymic emigrants (RTE). However, during puberty, the activity of RTE starts to decline as a natural process of thymic involution, introducing consequences, not completely described, to the repertoire. Type 1 diabetes (T1D) patients show quantitative and qualitative impairments on the Treg cells. Our aim was to evaluate peripheral Treg and RTE cell frequencies, in T1D patients from two distinct age groups (young and adults) and verify if HLA phenotypes are concomitant associated. To this, blood samples from Brazilian twenty established T1D patients (12 young and 8 adults) and twenty-one healthy controls (11 young and 10 adults) were analyzed, by flow cytometry, to verify the percentages of CD4, Treg (CD4+CD25+Foxp3+) and the subsets of CD45RA+ (naive) and CD31+(RTE) within then. Furthermore, the HLA typing was also set. We observed that the young established T1D patients feature decreased frequencies in total Treg cells and naive RTE within Treg cells. Significant prevalence of HLA alleles, associated with risk, in T1D patients, was also identified. Performing a multivariate analysis, we confirmed that the cellular changes described offers significant variables that distinct T1D patients from the controls. Our data collectively highlight relevant aspects about homeostasis imbalances in the Treg cells of T1D patients, especially in young, and disease prognosis; that might contribute for future therapeutic strategies involving Treg cells manipulation. [ABSTRACT FROM AUTHOR]

Air pollution caused by fuel burning contributes to respiratory impairments that may lead to death. We aimed to investigate the effects of biodiesel (DB) burning in mouse lungs. DB particulate matter was collected from the exhaust pipes of a bus engine. Mice were treated with 250 μg or 1000 μg of DB particulate matter by intranasal instillation over 5 consecutive days. We demonstrated that DB particulate matter penetrated the lung in the 250-μg and 1000-μg groups. In addition, the DB particulate matter number in pulmonary parenchyma was 175-fold higher in the 250-μg group and 300-fold higher in the 1000-μg group compared to control mice. The instillation of DB particulate matter increased the macrophage number and protein levels of TNF-alpha in murine lungs. DB particulate matter enhanced ROS production in both exposed groups and the malondialdehyde levels compared to the control group. The protein expression levels of Nrf2, p-NF-kB, and HO-1 were higher in the 250-μg group and lower in the 1000-μg group than in control mice and the 250-μg group. In conclusion, DB particulate matter instillation promotes oxidative stress by activating the Nrf2/HO-1 and inflammation by p-NF-kB/TNF-alpha pathways. [ABSTRACT FROM AUTHOR]

The Registries of Bone Marrow Donors around the world include more than 30 million volunteer donors from 57 different countries, and were responsible for over 17,000 hematopoietic stem cell transplants in 2016. The Brazilian Bone Marrow Volunteer Donor Registry (REDOME) was established in 1993 and is the third largest registry in the world with more than 4.3 million donors. We characterized HLA allele and haplotypes frequencies from REDOME comparing them with the donor self-reported race group classification. Five-locus haplotype frequencies (A~C~B~DRB1~DQB1) were estimated for each of the six race groups, resolving phase and allelic ambiguity using the expectation-maximization (EM) algorithm. The top 100 haplotypes in the race groups were separated into eight clusters of haplotypes, based on haplotype similarity, using CLUTO. We present HLA allele and haplotype frequency data from six race groups from 2,938,259 individuals from REDOME. The most frequent haplotype was the same for all groups: A*01:01g~C*07:01g~B*08:01g~DRB1*03:01g~DQB1*02:01g. Some frequent haplotypes such as A*02:01g~C*16:01g~B*44:03~DRB1*07:01g~DQB1*02:01g was not found in people with Preta (Sub-Saharan African descent). A cluster including Branca (European) and Parda or non-informed (admixed) could be distinguished from both Preta (SubSaharan) and Indígena (Amerindian) groups, and from the Amarela (Asian) ones, which clustered with their original population. These results have implications on cross-population matching and can help in donor searches and population-based recruitment strategies. [ABSTRACT FROM AUTHOR]

Aims: The development of type 1 diabetes (T1D) and its chronic complications may have a genetic background. The primary objective of our study was to characterize the relationship between self-reported color-race and genomic ancestry (GA) in patients with T1D. As secondary objective, we aimed to characterize GA of patients with T1D from different urban geographical regions of Brazil, compared to healthy Brazilian controls from the same regions.Methods: This was a cross-sectional, nationwide survey conducted in 14 public clinics from 10 Brazilian cities. Global and individual GA were inferred using a panel of 46 ancestry informative markers (AIMs) in 1698 T1D patients. Ancestry percentage was compared with published data of Brazilian healthy controls (n = 936) for the same AIMs.Results: A higher median individual European ancestry was observed in T1D patients in comparison to controls 67.8 [31.2] vs. 56.3 [25.7]%, respectively (median [IQR]; p < 0.001). As for self-reported color-race in T1D group, 923 (54.3%) participants reported to be White, 610 (35.9%) Brown, 132 (7.8%) Black, 18 (1.1%) Asian and 15 (0.9%) Indigenous. European GA prevailed in those who self-reported as White (74.6%) and Brown (61.1%) and constituted 39.1% in Black self-reported patients.Conclusions: Our study showed that T1D patients presented a higher percentage of European GA than the healthy population. Additionally, European GA was found in a considerable percentage of T1D patients who self-reported as non-White. Further studies are necessary to establish the influence of GA in the development of T1D as well its related chronic complications in admixed populations. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQB1*03:491 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐C*04:01:145 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*41:01:08 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

Long-term exposure to cigarette smoke (CS) results in alveolar parenchyma destruction due to chronic inflammatory response and the imbalance between oxidants and antioxidants, and proteases and antiproteases. Emphysema is the main symptom of chronic obstructive pulmonary disease. Current treatment focuses on relieving respiratory symptoms, and inflammation resolution failure is an important pathophysiological element of the disease. Specialized pro-resolving mediators (SPMs) synthesized endogenously during resolution processes demonstrated beneficial effects in murine models of airway inflammation. Here, we aimed to test the SPM AT-RvD1 in a murine model of CS-induced emphysema. AT-RvD1 restored elastic fibers and lung morphology, with reduction in MMP-3, neutrophils, and myeloperoxidase activity and increases in macrophages and IL-10 levels. AT-RvD1 also decreased levels of oxidative stress markers and ROS via upregulation of the Nrf2/Keap1 pathway. Therefore, we suggest that AT-RvD1 causes pro-resolutive action in our murine model of CS-induced emphysema by upregulation of the Nrf2/Keap1 pathway. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is an incurable and progressive disease. Emphysema is the principal manifestation of COPD, and the main cause of this condition is cigarette smoke (CS). Natural products have shown antioxidant and anti-inflammatory properties that can prevent acute lung inflammation and emphysema, but there are few reports in the literature regarding therapeutic approaches to emphysema. We hypothesized that supplementation with natural extracts would repair lung damage in emphysema caused by CS exposure. Mice were exposed to 60 days of CS and then treated or not with three different natural extracts (mate tea, grape and propolis) orally for additional 60 days. Histological analysis revealed significant improvements in lung histoarchitecture, with recovery of alveolar spaces in all groups treated with natural extracts. Propolis was also able to recovery alveolar septa and elastic fibers. Propolis also increased MMP-2 and decreased MMP-12 expression, favoring the process of tissue repair. Additionally, propolis recruited leukocytes, including macrophages, without ROS release. These findings led us to investigate the profile of these macrophages, and we showed that propolis could promote macrophage alternative activation, thus increasing the number of arginase-positive cells and IL-10 levels and favoring an anti-inflammatory microenvironment. We further investigated the participation of Nrf2 in lung repair, but no Nrf2 translocation to the nucleus was observed in lung cells. Proteins and enzymes related to Nrf2 were not altered, other than NQO1, which seemed to be activated by propolis in a Nrf2-independent manner. Finally, propolis downregulated IGF1 expression. In conclusion, propolis promoted lung repair in a mouse emphysema model via macrophage polarization from M1 to M2 in parallel to the downregulation of IGF1 expression in a Nrf2-independent manner. [ABSTRACT FROM AUTHOR]

Short-term cigarette smoke (CS) exposure does not cause emphysema; however, some pathogenesis hallmarks are maintained, such as oxidative stress and inflammation. This study aimed to test the efficacy of eucalyptol against short-term CS exposure in mice. C57BL/6 mice were exposed to 12 cigarettes per day for 5 days (CS group). The control group was exposed to sham smoking. Three groups of mice exposed to CS were treated to different concentrations of eucalyptol (1, 3, 10 mg/mL) via inhalation (15 min/daily) for 5 days (CS + 1 mg, CS+3 mg and CS+10 mg groups). CS group and control one were sham treated by using vehicle. The anti-inflammatory and antioxidant effects of eucalyptol were assessed 24 h after the last CS exposure by determining cell counts, measuring cytokine production and performing western blotting, biochemical and histological analyses. Eucalyptol at 3 mg/mL and 10 mg/mL concentrations reduced total leukocyte numbers compared to the CS group (p < 0.001), while macrophage numbers were reduced at all concentrations (p < 0.001). Myeloperoxidase, used as neutrophil marker, was reduced at 3 mg/mL (p < 0.01) and 10 mg/mL (p < 0.05) concentrations. Eucalyptol reduced cytokine levels (IL-1β, IL-6 and KC) at 3 mg/mL and 10 mg/mL concentrations (p < 0.01) compared to the CS group. The exception was TNF-α, with a reduction only at 10 mg/mL of eucalyptol compared to the CS group (p < 0.001). Additionally, eucalyptol decreased the NF-kappa B p65 subunit at 3 mg/mL and 10 mg/mL compared to the CS group (p < 0.01). Regarding oxidative stress, eucalyptol reduced reactive oxygen species, superoxide dismutase, catalase and malondialdehyde, mainly at 3 mg/mL and 10 mg/mL concentrations compared to the CS group (at least p < 0.05), parallel to reduced glutathione levels at the same concentrations (p < 0.001). Furthermore, treatment with eucalyptol attenuated CS-induced histopathological alterations. Collectively, these results indicate that eucalyptol acts through a mechanism involving decreased oxidative stress, inflammation and the NF-kappa B p65 subunit against CS-induced acute lung inflammation. Thus, eucalyptol may be a potential agent in the treatment of pulmonary inflammation caused by CS in humans. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1 U/mouse); elastase (using porcine pancreatic elastase (PPE) + bleomycin (3 U/mouse 14 days before 0.1 U/mouse of bleomycin; PPE + B); elastase (3 U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE + B group. In the PPE + B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE + B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase ( p < 0.05), catalase ( p < 0.01) and glutathione peroxidase ( p < 0.01) parallel with an increase in nitrite ( p < 0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced ( p < 0.05, p < 0.05 and p < 0.01, respectively) and increased ( p < 0.01) in the PPE + B group at 21 days compared with the control group. Interleukin (IL)-1β expression was upregulated ( p < 0.01) whereas IL-6 was downregulated ( p < 0.05) in the PPE + B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQA1*03:03:05 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

Abstract: Cord blood is a source of hematopoietic stem cells used in transplantation in which hematopoietic reconstitution is necessary. This transplant modality requires the cryopreservation of hematopoietic stem cells (HSCs). Dimethyl sulfoxide has been used as a cryoprotectant (CPA) in the cryopreservation of HSCs; however, it has been demonstrated that Me2SO exhibits toxic side effects to the human body. Due to its stability upon freezing, disaccharides such as trehalose have been investigated as a cryoprotectant. This study investigated the hypothesis that a cryopreservation solution containing intracellular and extracellular trehalose improves the recovery of stem cells after cryopreservation. After thawing, the cells were tested for their viability using the 7AAD stain, CD45+/CD34+ cells were assessed using flow cytometry and the MTT viability assay, and the proportion of hematopoietic progenitor cells was measured using the CFU assay. Our results showed the effectiveness of the solution containing intracellular and extracellular trehalose in the cryopreservation of cord blood cells, demonstrating that trehalose may be an optimal cryoprotectant when present both inside and outside of cells. [Copyright &y& Elsevier]

The novel HLA‐A*68:272 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]