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The activities of microbiomes in river sediments play an important role in sustaining ecosystem functions by driving many biogeochemical cycles. However, river ecosystems are frequently affected by anthropogenic activities, which may lead to microbial biodiversity loss and/or changes in ecosystem functions and related services. While parts of the Atlantic Forest biome stretching along much of the eastern coast of South America are protected by governmental conservation efforts, an estimated 89% of these areas in Brazil are under threat. This adds urgency to the characterization of prokaryotic communities in this vast and highly diverse biome. Here, we present prokaryotic sediment communities in the tropical Juliana River system at three sites, an upstream site near the river source in the mountains (Source) to a site in the middle reaches (Valley) and an estuarine site near the urban center of Ituberá (Mangrove). The diversity and composition of the communities were compared at these sites, along with environmental conditions, the former by using qualitative and quantitative analyses of 16S rRNA gene amplicons. While the communities included distinct populations at each site, a suite of core taxa accounted for the majority of the populations at all sites. Prokaryote diversity was highest in the sediments of the Mangrove site and lowest at the Valley site. The highest number of genera exclusive to a given site was found at the Source site, followed by the Mangrove site, which contained some archaeal genera not present at the freshwater sites. Copper (Cu) concentrations were related to differences in communities among sites, but none of the other environmental factors we determined was found to have a significant influence. This may be partly due to an urban imprint on the Mangrove site by providing organic carbon and nutrients via domestic effluents.

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Clopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0; 95% CI: 1,02-24,48; p: 0,03), rs2032582 (OR: 4,41; 95% CI: 1,20-16,12; p: 0,019), and rs1045642 (OR: 3,38; 95% CI: 0,96-11,9; p: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a "surrogate" biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population.

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BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (ß: 0.0456, P-value: 0.0140) and overt PolyA (ß: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

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Resumen El Trastorno de Tourette (TT) y el Trastorno por déficit de atención / hiperactividad (TDAH) son entidades neu ropsiquiátricas que usualmente inician en la infancia. Esta revisión busca colaborar con los clínicos, quienes suelen confrontarse al dilema de saber si existe una comorbilidad o un diagnóstico diferencial, ya que esta pregunta cobra vital importancia en el momento de decidir el tratamiento. Invitamos al colega a revisar nuestros hallazgos, soportados por bases moleculares, fisiológicas y neuroanatómicas, además de los datos epidemiológicos. Al final, brindamos una propuesta de algoritmo diag nóstico que podrá utilizar cuando se encuentre ante síntomas compartidos entre los dos diagnósticos. El TDAH y el TT deben ser intervenidos tempranamente, para mejorar la calidad de vida y funcionalidad del paciente y prevenir secuelas, no solo en niños, niñas y adolescentes (NNA), también a lo largo de la vida.

Abstract Tourette Disorder (TD) and attention deficit hyperac tivity disorder (ADHD) are both major neuropsychiatric conditions that usually begin during infancy. This revision aims to collaborate with pediatricians, who are often confronted with the question of co-mor bidity or differential diagnosis between ADHD and TD. The question becomes urgent when the clinician must decide if he/she can start ADHD or TD treatment. We encourage our colleagues to revise our findings, based in bimolecular and neuroanatomic shared issues in ad dition to updated epidemiological findings. The clinician will find an original proposed algorithm that they can use when the shared symptoms are pres ent in a little patient. TD and ADHD must be intervened early, so we can get better outcomes. The consequences of letting the symptoms increase can generate sequels and handicaps, that can interfere with the quality of life and functionality not only during infancy and adoles cence but also in adult life.

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STATEMENT OF PROBLEM: The gingival zenith (GZ) influences the line angle position in the emergence profile and the axial inclination of the crown. Irregularities in GZ symmetry and contour have a negative impact on dental esthetics. GZ location is not consistently distal to the crown's long axis; instead, it tends to be more distal in anterior teeth. The GZ levelling of the lateral incisor is often described as either level with or slightly above the zenith line connecting the central incisor and canine teeth, but there are also reports of GZ being aligned apically to the zenith line. Controversial reports persist regarding GZ positioning, magnitude, and location, potentially leading to inadequate positioning and levelling of the GZ in esthetic restorative therapy. PURPOSE: The purpose of this systematic review and meta-analysis was to assess the scientific evidence related to GZ level, position, and symmetry in maxillary incisors and canines. MATERIAL AND METHODS: This study adhered to the population, variable, outcome (PVO) criteria and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. Cross-sectional studies involving healthy adults with complete dentition of the maxillary anterior sextant were subjected to prevalence analysis and quantitative measurement to assess the gingival zenith level and position. Data were extracted, and methodological quality was appraised using the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Certainty of evidence was evaluated through the grading of recommendations, assessment, development, and evaluation (GRADE) system. RESULTS: The GZs were distally positioned, coinciding with the tooth axis or mesially positioned in, respectively, 96%, 3%, and 1% on central incisors; 84%, 14%, and 1% on lateral incisors; and 43%, 44%, and 5% on canines. GZ distal positioning was greater in central incisors, followed by lateral incisors and canines. In lateral incisors, the GZ was levelled coronally in 82% of the population. Contralateral symmetry was observed for GZ levelling and positioning. The certainty of the evidence was very low for all comparisons. CONCLUSIONS: The frequency and magnitude of the distal position of the GZ increased the more anterior the tooth. Axially, the GZ was frequently levelled coronally to the zenith line. The contralateral positioning and levelling of the GZ was symmetrical.

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Background and Aim: Stem cell therapy is considered a promising treatment for several neurodegenerative diseases. However, there are very few studies on the use of this therapy in glaucoma models. By detecting the changes produced by glaucoma early, cell therapy could help prevent the events that lead to blindness. In this study, early changes in the optic nerve head (ONH) as detected by optical coherence tomography (OCT) after the application of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) in an experimental model of ocular hypertension (OH) were evaluated. Materials and Methods: Fifteen New Zealand rabbits were randomly divided into the following three groups: G1: OH, G2: hWJ-MSCs, and G3: OH + hWJ-MSCs. An OH model was constructed, and the intraocular pressure (IOP) was measured regularly. At week 7, 105/100 µL hWJ-MSCs were intravitreally injected. Retinography and OCT were used to evaluate structural changes in ONH. Results: IOP increased significantly in G1 and G3 from week 3 onward. Retinography revealed more significant optic nerve changes, that is, papillary asymmetry suggestive of optic nerve excavation, vascular alterations, and irregular hypopigmentation peripheral to the optic disk margin, in G1 compared with G3. OH locates the hWJ-MSCs solution in the vitreous in front of the optic nerve. OCT revealed retinal nerve fiber layer (RNFL) reduction in all groups, reduced optic cup volume in G2 and G3 between weeks 1 and 9, and significant ganglion cell layer thickness reduction in G1 and a slight increase in G3. Conclusion: Intravitreal hWJ-MSCs injection produced changes in optic cup volume, which were detected early on by OCT; however, RNFL could not be restored in this OH model.

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Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.

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Tourette Disorder (TD) and attention deficit hyperactivity disorder (ADHD) are both major neuropsychiatric conditions that usually begin during infancy This revision aims to collaborate with pediatricians, who are often confronted with the question of co-morbidity or differential diagnosis between ADHD and TD. The question becomes urgent when the clinician must decide if he/she can start ADHD or TD treatment. We encourage our colleagues to revise our findings, based in bimolecular and neuroanatomic shared issues in addition to updated epidemiological findings. The clinician will find an original proposed algorithm that they can use when the shared symptoms are present in a little patient. TD and ADHD must be intervened early, so we can get better outcomes. The consequences of letting the symptoms increase can generate sequels and handicaps, that can interfere with the quality of life and functionality not only during infancy and adolescence but also in adult life.

El Trastorno de Tourette (TT) y el Trastorno por déficit de atención / hiperactividad (TDAH) son entidades neuropsiquiátricas que usualmente inician en la infancia. Esta revisión busca colaborar con los clínicos, quienes suelen confrontarse al dilema de saber si existe una comorbilidad o un diagnóstico diferencial, ya que esta pregunta cobra vital importancia en el momento de decidir el tratamiento. Invitamos al colega a revisar nuestros hallazgos, soportados por bases moleculares, fisiológicas y neuroanatómicas, además de los datos epidemiológicos. Al final, brindamos una propuesta de algoritmo diagnóstico que podrá utilizar cuando se encuentre ante síntomas compartidos entre los dos diagnósticos. El TDAH y el TT deben ser intervenidos tempranamente, para mejorar la calidad de vida y funcionalidad del paciente y prevenir secuelas, no solo en niños, niñas y adolescentes (NNA), también a lo largo de la vida.

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BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.

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[This corrects the article DOI: 10.3389/fimmu.2023.1241038.].

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Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Methods: Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Results: Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. Discussion: The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.

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The SARS CoV-2 antibody and CD4+ T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4+ T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4+ T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4+ T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4+ T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern.

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Introduction: The Human T-lymphotropic virus type 1 (HTLV-1) was the first described human retrovirus. It is currently estimated that around 5 to 10 million people worldwide are infected with this virus. Despite its high prevalence, there is still no preventive vaccine against the HTLV-1 infection. It is known that vaccine development and large-scale immunization play an important role in global public health. To understand the advances in this field we performed a systematic review regarding the current progress in the development of a preventive vaccine against the HTLV-1 infection. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA®) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO). The search for articles was performed in PubMed, Lilacs, Embase and SciELO databases. From the 2,485 articles identified, 25 were selected according to the inclusion and exclusion criteria. Results: The analysis of these articles indicated that potential vaccine designs in development are available, although there is still a paucity of studies in the human clinical trial phase. Discussion: Although HTLV-1 was discovered almost 40 years ago, it remains a great challenge and a worldwide neglected threat. The scarcity of funding contributes decisively to the inconclusiveness of the vaccine development. The data summarized here intends to highlight the necessity to improve the current knowledge of this neglected retrovirus, encouraging for more studies on vaccine development aiming the to eliminate this human threat. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42021270412).

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Wastewater treatment plant (WWTP) discharges alter water quality and microbial communities by introducing human-associated bacteria in the environment and by altering microbial communities. To fully understand this impact, it is crucial to study whether WWTP discharges affect water and sediments microbial communities in comparable ways and whether such effects depend on specific environmental variables. Here, we present a dataset investigating the impact of a WWTP on water quality and bacterial communities by comparing samples collected directly from the WWTP outflow to surface waters and sediments at two sites above and two sites below it over a period of five months. When possible, we measured five physicochemical variables (e.g., temperature, turbidity, conductivity, dissolved oxygen, and salinity), four bioindicators (e.g., Escherichia coli, total coliforms, Enterococcus sp., and endotoxins), and two molecular indicators (e.g., intI1's relative abundance, and 16S rRNA gene profiling). Preliminary results suggest that bioindicators correlate with environmental variables and that bacterial communities present in the water tables, sediments, and treated water differ greatly in composition and structure.

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BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

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The early diagnosis and appropriate stratification of sepsis continues to be one of the most important challenges in modern medicine. Single isolated biomarkers have not been enough to improve diagnostic and prognostic strategies and to progress toward therapeutic goals. The information generated by the human genome project has allowed a more holistic approach to the problem. The integration of genomics, transcriptomics, proteomics and metabolomics in sepsis has allowed us to progress in the knowledge of new pathways which are pathophysiologically involved in this disease. Thus, we have understood the importance of and complex interaction between the inflammatory response and the endothelium. Understanding the role of important parts of the microcirculation, such as the endothelial glycocalyx and its interaction with the inflammatory response, has provided early recognition elements for clinical practice that allow the rational use of traditional medical interventions in sepsis. This comprehensive approach, which differs from the classical mechanistic approach, uses systems biology to increase the diagnostic and prognostic spectrum of endothelial damage biomarkers in sepsis, and to provide information on new pathways involved in the pathophysiology of the disease. This, in turn, provides tools for perfecting traditional medical interventions, using them at the appropriate times according to the disease's pathophysiological context, while at the same time discovering new and improved therapeutic alternatives. We have the challenge of transferring this ideal scenario to our daily clinical practice to improve our patients' care. The purpose of this article is to provide a general description of the importance of systems biology in integrating the complex interaction between the endothelium and the inflammatory response in sepsis.

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Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.

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BACKGROUND: The immunopathological pathways enabling post-coronavirus disease 2019 (COVID-19) syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. METHODS: Thirty-three patients were included for longitudinal clinical and autoantibody analyses, 12 of whom were assessed for cytokines and lymphocyte populations. Patients were followed for 7-11 months after acute COVID-19. Autoimmune profile and immunological statuses were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. RESULTS: Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by up-regulated interferon-α, tumor necrosis factor-α, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-6, IL-1ß, and IL-13, whereas interferon-γ-induced protein 10 (IP-10) was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of immunoglobulin G S1-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remained elevated over time. CONCLUSIONS: The clinical manifestations of PCS are associated with the persistence of a proinflammatory and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

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OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

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O vírus linfotrópico T humano tipo 1 (HTLV-1) foi o primeiro retrovírus humano descoberto, descrito pela primeira vez há 41 anos. Esse retrovírus está associado ao desenvolvimento de duas doenças graves: a leucemia/linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). Este trabalho teve como objetivo analisar as atualizações sobre o HTLV-1, destacando os aspectos clínicos, os avanços e as limitações no tratamento e na prevenção da infecção pelo HTLV-1. Para isso, foi realizada uma revisão integrativa, por meio de coleta de dados nas plataformas PubMed, LILACS e SciELO, entre março e abril de 2021. Foram incluídos 61 artigos de diferentes países. O Brasil foi o país com maior número de publicações na área: 12. Os resultados obtidos mostram que existem avanços importantes no que diz respeito ao tratamento e à prevenção da infecção pelo HTLV-1. No entanto, a falta de estudos específicos sobre o vírus, que abordem os aspectos clínicos da infecção, foi um fator limitante para este estudo, o que reforça a necessidade de investimento em novas pesquisas sobre o tema.

The Human T-lymphotropic Virus 1 (HTLV-1) was the first human retrovirus discovered, described for the first time 41 years ago. This retrovirus is associated with the development of two serious diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (HAM/TSP). This study aimed to analyze the updates about HTLV-1, highlighting the clinical aspects, advances, and limitations in the treatment and prevention of HTVL-1 infection. To this end, an integrative review was carried out, with data collection on PubMed, LILACS, and SciELO platforms, between March and April 2021. A total of 61 articles from different countries were included. Brazil was the country with the largest number of publications in the area: 12. The results showed effective advances regarding treating and preventing HTLV-1 infection. However, the lack of specific studies about the virus, which address the clinical aspects of the infection, was a limiting factor for this study, which reinforces the need for investment in new research about this topic.

El virus linfotrópico T tipo 1 humano (HTLV-1) fue el primer retrovirus humano descubierto y se describió por primera vez hace 41 años. Este retrovirus está asociado con el desarrollo de dos enfermedades graves: leucemia/linfoma de células T del adulto (ATLL) e mielopatía asociada a HTLV-1/paraparesia espástica tropical (HAM/TSP). Este estudio tuvo como objetivo analizar las actualizaciones sobre HTLV-1, destacando los aspectos clínicos, los avances y limitaciones en el tratamiento y prevención de la infección por HTLV-1. Para ello, se realizó una revisión integradora, a través de la recolección de datos en las plataformas PubMed, LILACS y SciELO entre marzo y abril de 2021. Se incluyeron 61 artículos de diferentes países. Brasil fue el país con mayor número de publicaciones en el área: 12. Los resultados obtenidos muestran que existen avances efectivos en cuanto al tratamiento y prevención de la infección por HTLV-1. Sin embargo, la falta de estudios específicos sobre el virus que aborden los aspectos clínicos de la infección fue un factor limitante para el presente estudio, lo que refuerza la necesidad de invertir en nuevas investigaciones sobre este virus.

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