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Human induced pluripotent stem cells (hiPSCs) hold promises to model and understand human diseases, including those associated with ageing. Here, we describe ABCRIi001-A, a hiPSC line generated from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female enrolled in a study for development of an ageing score (ALFA Score). PBMCs were reprogrammed using three Sendai virus-based reprogramming vectors (hKOS, hc-Myc, and hKlf4). ABCRIi001-A showed normal morphology and karyotype, viral clearance, absence of genomic aberrations, and their pluripotency was confirmed by expression of pluripotency-related markers and their ability to differentiate into the three germ layers. ABCRIi001-A is valuable for ageing-related studies.

Most studies aiming at unraveling the molecular events associated with cardiac congenital heart disease (CHD) have focused on the effect of mutations occurring in the nuclear genome. In recent years, a significant role has been attributed to mitochondria for correct heart development and maturation of cardiomyocytes. Moreover, numerous heart defects have been associated with nucleotide variations occurring in the mitochondrial genome, affecting mitochondrial functions and cardiac energy metabolism, including genes encoding for subunits of respiratory chain complexes. Therefore, mutations in the mitochondrial genome may be a major cause of heart disease, including CHD, and their identification and characterization can shed light on pathological mechanisms occurring during heart development. Here, we have analyzed mitochondrial genetic variants in previously reported mutational genome hotspots and the flanking regions of mt-ND1, mt-ND2, mt-COXI, mt-COXII, mt-ATPase8, mt-ATPase6, mt-COXIII, and mt-tRNAs (Ile, Gln, Met, Trp, Ala, Asn, Cys, Tyr, Ser, Asp, and Lys) encoding genes by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) in 200 patients with CHD, undergoing cardiac surgery. A total of 23 mitochondrial variations (5 missense mutations, 8 synonymous variations, and 10 nucleotide changes in tRNA encoding genes) were identified and included 16 novel variants. Additionally, we showed that intracellular ATP was significantly reduced (P=0.002) in CHD patients compared with healthy controls, suggesting that the mutations have an impact on mitochondrial energy production. Functional and structural alterations caused by the mitochondrial nucleotide variations in the gene products were studied in-silico and predicted to convey a predisposing risk factor for CHD. Further studies are necessary to better understand the mechanisms by which the alterations identified in the present study contribute to the development of CHD in patients.

Researchers at Universities generate and convey the knowledge acquired through communications in specialized (inter)national journals and congresses. An effort to share the scientific achievements with the general public is extremely important. For this purpose, we have launched the UALGORITMO, a journal freely accessible online, written in lay Portuguese language by Researchers of the University of the Algarve, to summarize recent communications published in peer reviewed journals. After submission, the manuscripts are revised by High Schools Students of the Algarve, under the guidance of a schoolteacher, for further simplification of the language and general improvement of the manuscript and figures. The revised manuscripts by the authors are edited and published, with an acknowledgment and a presentation of the reviewers at the end of each article. To maximize the outreach, the articles include a summarized biography of the authors, and links to their research centers and teaching courses. We believe that the UALGORITMO is a valuable instrument to promote scientific literacy and culture amongst all communities.

Cardiovascular diseases (CVDs) are pointed out by the World Health Organization (WHO) as the leading cause of death, contributing to a significant and growing global health and economic burden. Despite advancements in clinical approaches, there is a critical need for innovative cardiovascular treatments to improve patient outcomes. Therapies based on adult stem cells (ASCs) and embryonic stem cells (ESCs) have emerged as promising strategies to regenerate damaged cardiac tissue and restore cardiac function. Moreover, the generation of human induced pluripotent stem cells (iPSCs) from somatic cells has opened new avenues for disease modeling, drug discovery, and regenerative medicine applications, with fewer ethical concerns than those associated with ESCs. Herein, we provide a state-of-the-art review on the application of human pluripotent stem cells in CVD research and clinics. We describe the types and sources of stem cells that have been tested in preclinical and clinical trials for the treatment of CVDs as well as the applications of pluripotent stem-cell-derived in vitro systems to mimic disease phenotypes. How human stem-cell-based in vitro systems can overcome the limitations of current toxicological studies is also discussed. Finally, the current state of clinical trials involving stem-cell-based approaches to treat CVDs are presented, and the strengths and weaknesses are critically discussed to assess whether researchers and clinicians are getting closer to success.

Peritoneal protein loss (PPL) has been correlated with mortality, malnutrition and inflammation. More recently overhydration was brought to the equation. This study aims to review classic and recent factors associated with PPL. Prevalent and incident peritoneal dialysis (PD) patients were included. Dialysate and serum IL-6 was obtained during PET. Hydration and nutritional status were assessed by bio-impedance. Linear regression and Cox regression were performed. The 78 included patients presented median values of PPL 4.8 g/24 h, serum IL-6: 5.1 pg/mL, and IL-6 appearance rate 153.5 pg/min. Mean extracellular water excess (EWexc) was 0.88 ± 0.94 L, and lean body mass index (LBMI) 17.3 ± 2.4 kg/m2. After mean follow-up of 33.9 ± 29.3 months, 12 patients died. Linear univariable analysis showed positive associations between PPL and small solute transport, body composition (LBMI and EWexc), comorbidities and performing CAPD (vs. cycler). PPL correlated positively with dialysate appearance rate of IL-6, but not with serum IL-6. Linear multivariable analysis confirmed positive association between PPL and EWexc (p = 0.012; 95%CI: 4.162–31.854), LBMI (p = 0.008; 95%CI: 1.720–11.219) and performing CAPD (p = 0.023; 95%CI: 4.375–54.190). In survival analysis, no relationship was found between mortality and PPL. Multivariable Cox regression showed Charlson Comorbidity Index (HR: 1.896, 95%CI: 1.235–2.913), overhydration (HR: 10.034, 95%CI: 1.426–70.587) and lower PPL (HR: 0.576, 95%CI: 0.339–0.978) were predictors for mortality. Overhydration, was a strong predictor of PPL, overpowering variables previously reported as determinants of PPL, namely clinical correlates of endothelial dysfunction or local inflammation. PPL were not associated with malnutrition or higher mortality, emphasizing the importance of volume overload control in PD patients.

Background: Since patients with cystic fibrosis with different Cystic Fibrosis Transmembrane Regulator (CFTR) genotypes present a wide response variability for modulator drugs such as Orkambi®, it is important to screen variants in candidate genes with an impact on precision and personalized medicine, such as Solute Carrier Family 26, member 9 (SLC26A9) gene., Methods: Sanger sequencing for the exons and intron-exon boundary junctions of the SLC26A9 gene was employed in nine individuals with p.Phe508del homozygous genotype for the CFTR gene who were not under CFTR modulators therapy. The sequencing variants were evaluated by in silico prediction tools. The CFTR function was measured by cAMP-stimulated current (ΔIsc-eq-FSK) in polarized CFTR of human nasal epithelial cells cultured in micro-Ussing chambers with Orkambi®., Results: We found 24 intronic variants, three in the coding region (missense variants - rs74146719 and rs16856462 and synonymous - rs33943971), and three in the three prime untranslated region (3' UTR) region in the SLC26A9 gene. Twenty variants were considered benign according to American College of Medical Genetics and Genomics guidelines, and ten were classified as uncertain significance. Although some variants had deleterious predictions or possible alterations in splicing, the majority of predictions were benign or neutral. When we analyzed the ΔIsc-eq-FSK response to Orkambi®, there were no significant differences within the genotypes and alleles for all 30 variants in the SLC26A9 gene., Conclusions: Among the nine individuals with p.Phe508del homozygous genotype for the CFTR gene, no pathogenic SLC26A9 variants were found, and we did not detect associations from the 30 SLC26A9 variants and the response to the Orkambi® in vitro., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Patients with Down syndrome (DS) are more affected by the Coronavirus Disease (COVID)-19 pandemic when compared with other populations. Therefore, the primary aim of our study was to report the death (case fatality rate) from SARS-CoV-2 infection in Brazilian hospitalized patients with DS from 03 January 2020 to 04 April 2021. The secondary objectives were (i) to compare the features of patients with DS and positive for COVID-19 (G1) to those with DS and with a severe acute respiratory infection (SARI) from other etiological factors (G2) to tease apart the unique influence of COVID-19, and (ii) to compare the features of patients with DS and positive for COVID-19 to those without DS, but positive for COVID-19 (G3) to tease apart the unique influence of DS. We obtained the markers for demographic profile, clinical symptoms, comorbidities, and the clinical features for SARI evolution during hospitalization in the first year of the COVID-19 pandemic in Brazil from a Brazilian open-access database. The data were compared between (i) G1 [1619 (0.4%) patients] and G2 [1431 (0.4%) patients]; and between (ii) G1 and G3 [222,181 (64.8%) patients]. The case fatality rate was higher in patients with DS and COVID-19 (G1: 39.2%), followed by individuals from G2 (18.1%) and G3 (14.0%). Patients from G1, when compared to G2, were older (≥ 25 years of age), presented more clinical symptoms related to severe illness and comorbidities, needed intensive care unit (ICU) treatment and non-invasive mechanical ventilation (MV) more frequently, and presented a nearly two fold-increased chance of death (OR = 2.92 [95% CI 2.44-3.50]). Patients from G1, when compared to G3, were younger (< 24 years of age), more prone to nosocomial infection, presented an increased chance for clinical symptoms related to a more severe illness; frequently needed ICU treatment, and invasive and non-invasive MV, and raised almost a three fold-increased chance of death (OR = 3.96 [95% CI 3.60-4.41]). The high case fatality rate in G1 was associated with older age (≥ 25 years of age), presence of clinical symptoms, and comorbidities, such as obesity, related to a more severe clinical condition. Unvaccinated patients with DS affected by COVID-19 had a high case fatality rate, and these patients had a different profile for comorbidities, clinical symptoms, and treatment (such as the need for ICU and MV) when compared with other study populations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Single-nucleotide variant (SNV) is a single base mutation at a specific location in the genome and may play an import role in epilepsy pathophysiology. The aim of this study was to review case-control studies that have investigated the relationship between SNVs within microRNAs (miRs) sequences or in their target genes and epilepsy susceptibility from January 1, 2010 to October 31, 2020. Nine case-control studies were included in the present review. The mainly observed SNVs associated with drug-resistant epilepsy (DRE) risk were SNVs n.60G > C (rs2910164) and n.-411A > G (rs57095329), both located at miR-146a mature sequence and promoter region, respectively. In addition, the CC haplotype (rs987195-rs969885) and the AA genotype at rs4817027 in the MIR155HG/miR-155 tagSNV were also genetic susceptibility markers for early-onset epilepsy. MiR-146a has been observed as upregulated in human astrocytes in epileptogenesis and it regulates inflammatory process through NF-κB signaling by targeting tumor necrosis factor-associated factor 6 (TRAF6) gene. The SNVs rs2910164 and rs57095329 may modify the expression level of mature miR-146a and the risk for epilepsy and SNVs located at rs987195-rs969885 haplotype and at rs4817027 in the MIR155HG/miR-155 tagSNV could interfere in the miR-155 expression modulating inflammatory pathway genes involved in the development of early-onset epilepsy. In addition, SNVs rs662702, rs3208684, and rs35163679 at 3'untranslated region impairs the ability of miR-328, let-7b, and miR-200c binding affinity with paired box protein PAX-6 (PAX6), BCL2 like 1 (BCL2L1), and DNA methyltransferase 3 alpha (DNMT3A) target genes. The SNV rs57095329 might be correlated with DRE when a larger number of patients are evaluated. Thus, we concluded that the main drawback of most of studies is the small number of individuals enrolled, which lacks sample power., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) had bronchiectasis, and 29/37 (78.4%) had recurrent pneumonia. A total of 17/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.

Underreporting of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a global problem and might hamper Coronavirus Disease (COVID-19) epidemiological control. Taking this into consideration, we estimated possible SARS-CoV-2 infection underreporting in Brazil among patients with severe acute respiratory syndrome (SARS). An ecological study using a descriptive analysis of the SARS report was carried out based on data supplied by the Influenza Epidemiological Surveillance Information (SIVEP)-Flu (in Brazilian Portuguese, Sistema de Vigilância Epidemiológica da Gripe) in the period between January 2015 and March 2021. The number of SARS cases and related deaths after infection by SARS-CoV-2 or Influenzae was described. The estimation of underreporting was evaluated considering the relative increase in the number of cases with undefined etiological agent comparing 2020 to 2015−2019; and descriptive analysis was carried out including data from January−March/2021. In our data, SARS-CoV-2 infection and the presence of SARS with undefined etiological agent were associated with the higher number of cases and deaths from SARS in 2020/2021. SARS upsurge was six times over that expected in 2020, according to SARS seasonality in previous years (2015−2019). The lowest possible underdiagnosis rate was observed in the age group < 2 y.o. and individuals over 30 y.o., with ~50%; while in the age groups 10−19 and 20−29 y.o., the rates were 200−250% and 100%, respectively. For the remaining age groups (2−5 and 5−9 y.o.) underreporting was over 550%, except for female individuals in the age group 2−5 y.o., in which a ~500% rate was found. Our study described that the SARS-CoV-2 infection underreporting rate in Brazil in SARS patients is alarming and presents different indices, mainly associated with the patients’ age groups. Our results, mainly the underreporting index according to sex and age, should be evaluated with caution.

Introduction: The COVID-19 pandemic has affected several neglected populations such as the Indigenous peoples, which have suffered a high impact from the pandemic., Objectives: To analyze the impact on the health and disease process according to the COVID-19 evolution in the Brazilian Indigenous population., Methods: Data was collected from press releases by the Health Ministry and a descriptive analysis of the numbers of Indigenous individuals infected with the SARS-CoV-2 in Brazil was carried out., Results: In February 2021, there were 41,855 confirmed cases of Indigenous individuals infected by the SARS-CoV-2, including 4,387 active cases, 36,809 recovered cases, and 549 deaths. The Brazilian Indigenous population is distributed in over 300 ethnic groups and, due to the high number of deaths by the COVID-19, many of these groups are endangered. The elderly are the most affected age group, and they play a fundamental role among the Indigenous population for transmitting their customs mainly orally. Indigenous populations do not have proper access to transport to specialized health centers, since many areas are inaccessible and other cases require air or river transportation, which many times results in late assistance. When managing the COVID-19, it is important to emphasize the need for social isolation to prevent the virus from spreading among the Indigenous groups, mainly due to their contact with other ethnic groups represented by missionaries, hunters, and wood explorers, among others., Conclusion: The adoption of practices that can reduce the virus transmission among the Indigenous population and provide them with better access to treatment, mainly for the elderly, must be prioritized in Brazil., (© 2021. W. Montague Cobb-NMA Health Institute.)

The Human Development Index measures a region's development and is a step for development debate beyond the traditional, economic perspective. It can also determine the success of a country's response to the COVID-19 pandemic, mainly affecting the case fatality rate among severe cases of SARS-CoV-2 infection. We aimed to associate the Human Development Index with the case fatality rate due to COVID-19 in each Brazilian state and the Federal District, taking into account comorbidities and the need for invasive mechanical ventilation. We also evaluated the influence of the GINI index, number of intensive care unit beds, and occupied households in subnormal clusters on the case fatality rate. We performed an ecological study including two populations: COVID-19 individuals that did not require the mechanical ventilation protocol; and COVID-19 individuals under invasive mechanical ventilation. We performed a Pearson correlation test and a univariate linear regression analysis on the relationship between Human Development Index, Human Development Index-Education Level, Human Development Index-Life Expectancy, and Human Development Index-Gross National Income per capita and COVID-19 deaths. The same analyses were performed using the other markers. We grouped the patients with COVID-19 according to comorbidities and the need for invasive mechanical ventilation. Alpha = 0.05. We included 848,501 COVID-19 individuals, out of which 153,710 needed invasive mechanical ventilation and 314,164 died, and 280,533 COVID-19 individuals without comorbidity, out of which 33,312 needed invasive mechanical ventilation and 73,723 died. We observed a low negative Pearson correlation between the Human Development Index and death and a moderate negative Pearson correlation between the Human Development Index and deaths of individuals on invasive mechanical ventilation, with or without comorbidity. The univariate linear analysis showed the case fatality rate depends on at least 20-40% of the Human Development Index. In Brazil, regions with a low Human Development Index demonstrated a higher case fatality rate due to COVID-19, mainly in individuals who needed invasive mechanical ventilation, than regions with a higher Human Development Index. Although other indexes studied, such as intensive care unit beds and GINI, were also associated with the COVID-19 case fatality rate, they were not as relevant as the Human Development Index. Brazil is a vast territory comprising cultural, social, and economic diversity, which mirrors the diversity of the Human Development Index. Brazil is a model nation for the study of the Human Development Index's influence on aspects of the COVID-19 pandemic, such as its impact on the case fatality rate.

Several proteins are involved in cholesterol homeostasis, as scavenger receptor class B type I and ATP-binding cassette (ABC) transporters including ABCA1, ABCG1, ABCG5, and ABCG8. This study aimed to determine the effects of single nucleotide variants (SNVs) rs2275543 (ABCA1), rs1893590 (ABCG1), rs6720173 (ABCG5), rs6544718 (ABCG8), and rs5888 (SCARB1) on plasma lipids, lipoproteins, and adiposity markers in an asymptomatic population and its sex-specific effects. Volunteers (n = 590) were selected and plasma lipids, lipoproteins, and adiposity markers (waist-to-hip and waist-to-height ratios, lipid accumulation product and body adiposity index) were measured. Genomic DNA was isolated from peripheral blood cells according to the method adapted from Gross-Bellard. SNVs were detected in the TaqMan® OpenArray® Real-Time polymerase chain reaction platform and data analyses were performed using the TaqMan® Genotyper Software. The rs2275543*C point to an increase of high-density lipoprotein size in females while in males very-low-density lipoprotein, cholesterol, and triglycerides were statistically lower (P value < 0.05). The rs1893590*C was statistically associated with lower apolipoprotein A-I levels and higher activities of paraoxonase-1 and cholesteryl ester transfer protein (P value < 0.05). The rs6720173 was statistically associated with an increase in cholesterol and low-density lipoprotein cholesterol in males; moreover, rs6544718*T reduced adiposity markers in females (P value < 0.05). Regarding the rs5888, a decreased adiposity marker in the total population and in females occurred (P value < 0.05). Multivariate analysis of variance showed that SNVs could influence components of high-density lipoprotein metabolism, mainly through ABCG1 (P value < 0.05). The ABCA1 and ABCG5 variants showed sex-specific effects on lipids and lipoproteins, while SCARB1 and ABCG8 variants might influence adiposity markers in females. Our data indicate a possible role of ABCG1 on HDL metabolism., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)