Assessing COVID-19 pandemic excess deaths in Brazil: Years 2020 and 2021.

We estimated the impact of the COVID-19 pandemic on mortality in Brazil for 2020 and 2021 years. We used mortality data (2015-2021) from the Brazilian Health Ministry for forecasting baseline deaths under non-pandemic conditions and to estimate all-cause excess deaths at the country level and stratified by sex, age, ethnicity and region of residence, from March 2020 to December 2021. We also considered the estimation of excess deaths due to specific causes. The estimated all-cause excess deaths were 187 842 (95% PI: 164 122; 211 562, P-Score = 16.1%) for weeks 10-53, 2020, and 441 048 (95% PI: 411 740; 470 356, P-Score = 31.9%) for weeks 1-52, 2021. P-Score values ranged from 1.4% (RS, South) to 38.1% (AM, North) in 2020 and from 21.2% (AL and BA, Northeast) to 66.1% (RO, North) in 2021. Differences among men (18.4%) and women (13.4%) appeared in 2020 only, and the P-Score values were about 30% for both sexes in 2021. Except for youngsters (< 20 years old), all adult age groups were badly hit, especially those from 40 to 79 years old. In 2020, the Indigenous, Black and East Asian descendants had the highest P-Score (26.2 to 28.6%). In 2021, Black (34.7%) and East Asian descendants (42.5%) suffered the greatest impact. The pandemic impact had enormous regional heterogeneity and substantial differences according to socio-demographic factors, mainly during the first wave, showing that some population strata benefited from the social distancing measures when they could adhere to them. In the second wave, the burden was very high for all but extremely high for some, highlighting that our society must tackle the health inequalities experienced by groups of different socio-demographic statuses.

First characterization of PIWI-interacting RNA clusters in a cichlid fish with a B chromosome.

BACKGROUND: B chromosomes are extra elements found in several eukaryote species. Usually, they do not express a phenotype in the host. However, advances in bioinformatics over the last decades have allowed us to describe several genes and molecular functions related to B chromosomes. These advances enable investigations of the relationship between the B chromosome and the host to understand how this element has been preserved in genomes. However, considering that transposable elements (TEs) are highly abundant in this supernumerary chromosome, there is a lack of knowledge concerning the dynamics of TE control in B-carrying cells. Thus, the present study characterized PIWI-interacting RNA (piRNA) clusters and pathways responsible for silencing the mobilization of TEs in gonads of the cichlid fish Astatotilapia latifasciata carrying the B chromosome. RESULTS: Through small RNA-seq and genome assembly, we predicted and annotated piRNA clusters in the A. latifasciata genome for the first time. We observed that these clusters had biased expression related to sex and the presence of the B chromosome. Furthermore, three piRNA clusters, named curupira, were identified in the B chromosome. Two of them were expressed exclusively in gonads of samples with the B chromosome. The composition of these curupira sequences was derived from LTR, LINE, and DNA elements, representing old and recent transposition events in the A. latifasciata genome and the B chromosome. The presence of the B chromosome also affected the expression of piRNA pathway genes. The mitochondrial cardiolipin hydrolase-like (pld6) gene is present in the B chromosome, as previously reported, and an increase in its expression was detected in gonads with the B chromosome. CONCLUSIONS: Due to the high abundance of TEs in the B chromosome, it was possible to investigate the origin of piRNA from these jumping genes. We hypothesize that the B chromosome has evolved its own genomic guardians to prevent uncontrolled TE mobilization. Furthermore, we also detected an expression bias in the presence of the B chromosome over A. latifasciata piRNA clusters and pathway genes.

Meiotic behavior, transmission and active genes of B chromosomes in the cichlid Astatotilapia latifasciata: new clues about nature, evolution and maintenance of accessory elements.

Supernumerary B chromosomes (Bs) are dispensable genetic elements widespread in eukaryotes and are poorly understood mainly in relation to mechanisms of maintenance and transmission. The cichlid Astatotilapia latifasciata can harbor Bs in a range of 0 (named B -) and 1-2 (named B +). The B in A. latifasciata is rich in several classes of repetitive DNA sequences, contains protein coding genes, and affects hosts in diverse ways, including sex-biased effects. To advance in the knowledge about the mechanisms of maintenance and transmission of B chromosomes in A. latifasciata, here, we studied the meiotic behavior in males and transmission rates of A. latifasciata B chromosome. We also analyzed structurally and functionally the predicted B chromosome copies of the cell cycle genes separin-like, tubb1-like and kif11-like. We identified in the meiotic structure relative to the B chromosome the presence of proteins associated with Synaptonemal Complex organization (SMC3, SYCP1 and SYCP3) and found that the B performs self-pairing. These data suggest that isochromosome formation was a step during B chromosome evolution and this element is in a stage of diversification of the two arms keeping the self-pairing behavior to protect the A chromosome complement of negative effects of recombination. Moreover, we observed no occurrence of B-drive and confirmed the presence of cell cycle genes copies in the B chromosome and their transcription in encephalon, muscle and gonads, which can indicates beneficial effects to hosts and contribute to B maintenance.

Domestic cooking practices influence the carotenoid and tocopherol content in colored cauliflower.

Cauliflowers are generally associated with healthy diets due to their positive impact on health. This research aims to evaluate the effects of cooking processes (boiling, steaming and microwaving) and different preparation times, on the content of carotenoids and provitamin A and tocopherols, in cauliflowers and to verify the effect of the cooking process on maintaining the coloring. The results revealed that the thermal processinfluencedthe antioxidant compounds releaseindependent of genotype. The highest content of zeaxanthin and lutein was found in 'Verde di Macerata' after boiling for 20 min. 'Cheddar' presented the highest content of all carotenoids and when steamed for 20 min, the highest levels ofprovitamin Awere observed.Microwaved and bolied 'Grafitti' for longer times showed the highest retention of tocopherol. The cooking did not negatively affect the visual aspect. 'Verde di Macerata' and 'Cheddar' may be good sources of carotenoids and tocopherols.

Telomere-associated genes and telomeric lncRNAs are biomarker candidates in lung squamous cell carcinoma (LUSC).

In the past decade, research efforts were made to identify molecular biomarkers useful as therapeutic targets in Non-Small Cell Lung Cancer (NSCLC), the most frequent type of lung carcinoma. NSCLC presents different histological subtypes being the most prevalent LUSC (Lung Squamous Cell Cancer) and LUAD (Lung Adenocarcinoma), and only a subset of LUAD patients' present tumors expressing known targetable genetic alterations. Telomeres and its components, including telomerase, the enzyme that replenishes telomeres, have been considered potential cancer biomarkers due to their crucial role in cell proliferation and genome stability. Our study aims to quantify expression changes affecting telomere-associated genes and ncRNAs associated with telomere regulation and maintenance in NSCLC. We first assessed the transcriptome (RNA-Seq) data of NSCLC patients from The Cancer Genome Atlas (TCGA) and then we tested the expression of telomere-associated genes and telomeric ncRNAs (TERC, telomerase RNA component, and TERRA, telomere repeat-containing RNA) in Brazilian NCSLC patient samples by quantitative RT-PCR, using matched normal adjacent tissue samples as the control. We also estimated the mean size of terminal restriction fragments (TRF) of some Brazilian NSCLC patients using telomeric Southern blot. The TCGA analysis identified alterations in the expression profile of TERT and telomere damage repair genes, mainly in the LUSC subtype. The study of Brazilian NSCLC samples by RT-qPCR showed that LUSC and LUAD express high amounts of TERT and that although the mean TRF size of tumor samples was shorter compared to normal cells, telomeres in NSCLC are probably maintained by telomerase. Also, the expression analysis of Brazilian NSCLC samples identified statistically significant alterations in the expression of genes involved with telomere damage repair, as well as in TERC and TERRA, mainly in the LUSC subtype. We, therefore, concluded that telomere maintenance genes are significantly deregulated in NSCLC, representing potential biomarkers in the LUSC subtype.

Epigenetic DNA Modifications Are Correlated With B Chromosomes and Sex in the Cichlid Astatotilapia latifasciata.

Supernumerary B chromosomes are dispensable elements found in several groups of eukaryotes, and their impacts in host organisms are not clear. The cichlid fish Astatotilapia latifasciata presents one or two large metacentric B chromosomes. These elements affect the transcription of several classes of RNAs. Here, we evaluated the epigenetic DNA modification status of B chromosomes using immunocytogenetics and assessed the impact of B chromosome presence on the global contents of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) and the molecular mechanisms underlying these variations. We found that the B chromosome of A. latifasciata has an active pattern of DNA epimarks, and its presence promotes the loss of 5mC in gonads of females with B chromosome (FB+) and promotes the loss of 5hmC in the muscle of males with the B element (MB+). Based on the transcriptional quantification of DNA modification genes (dnmt, tet, and tdg) and their candidate regulators (idh genes, microRNAs, and long non-coding RNAs) and on RNA-protein interaction prediction, we suggest the occurrence of passive demethylation in gonads of FB+ and 5hmC loss by Tet inhibition or by 5hmC oxidation in MB+ muscle. We suggest that these results can also explain the previously reported variations in the transcription levels of several classes of RNA depending on B chromosome presence. The DNA modifications detected here are also influenced by sex. Although the correlation between B chromosomes and sex has been previously reported, it remains unexplained. The B chromosome of A. latifasciata seems to be active and impacts cell physiology in a very complex way, including at the epigenetic level.

Correction to: Culture of mesenchymal stem cells derived from equine synovial membrane in alginate hydrogel microcapsules.

The original article [1] contained a minor error regarding the mean diameter of the alginate microcapsules described in relation to Fig. 4 in the Results section. The microcapsules had an actual mean diameter of 3000 µm instead of 1000 µm as mistakenly mentioned in the original article.

Comparative bioavailability study with two chlorpropamide tablet formulations in healthy volunteers.

OBJECTIVE: The aim of this study was the assessment of the bioequivalence of two formulations (250 mg tablet) of chlorpropamide (CAS 94-20-2) in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval. Plasma samples were obtained over a 72-h period. Plasma chlorpropamide concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the chlorpropamide plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(inf) and C(max). RESULTS: The limit of quantification was 0.1 microg/mL for plasma chlorpropamide analysis. The geometric mean and respective 90 % confidence interval (CI) of Test/ Reference percent ratios were 93.99% (87.11%-101.41%) for C(max), 92.45% (85.96%-99.44%) for AUC(0-72h) and 90.30% (83.35%-97.82%) for AUC(0-inf). CONCLUSION: Since the 90 % CI for AUC(0-72h), AUC(0-inf) and C(max) ratios were within the 80-125%interval proposed by the US FDA, it was concluded that chlorpropamide 250 mg tablet (test formulation) was bioequivalent to the reference 250 mg tablet for of both the rate and extent of absorption.