Prevalence, risk factors, and impact of long COVID in a socially vulnerable community in Brazil: a prospective cohort study.

Background: Long COVID is an emerging global public health issue. Socially vulnerable communities in low- and-middle-income countries were severely impacted by the pandemic and are underrepresented in research. This prospective study aimed to determine the prevalence of long COVID, its impact on health, and associated risk factors in one such community in Rio de Janeiro, Brazil. Methods: A total of 710 individuals aged 18 and older, with confirmed SARS-CoV-2 infection at least three months prior, were enrolled between November 25, 2021, and May 5, 2022. Participants were assessed via telephone or in person using a standardized questionnaire to evaluate their perception of recovery, symptoms, quality of life, and functional status. Findings: Twenty percent of participants did not feel fully recovered, 22% experienced new or persistent symptoms, 26% had worsened functional status, 18% had increased dyspnoea, and 32% reported a worse quality of life. Persistent symptoms included headache, cough, fatigue, muscle pain, and shortness of breath. Dyspnoea during the acute phase was the strongest independent predictor of worsening outcomes. Females and individuals with comorbidities were more likely to report worse recovery, functioning, dyspnoea, and quality of life. Interpretation: Our findings reveal a high burden of severe and persistent physical and mental health sequelae in a socially vulnerable community following COVID-19. Funding: UK Foreign, Commonwealth and Development Office and Wellcome Trust Grant (222048/Z/20/Z), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and the Centers for Disease Control and Prevention (CDC).

In Silico Drug Repurposing Uncovered the Antiviral Potential of the Antiparasitic Drug Oxibendazole Against the Chikungunya Virus.

Chikungunya virus (CHIKV) has been reported in over 120 countries and is the causative agent of Chikungunya fever. The debilitating nature of this disease, which can persist months to years after acute infection, drastically impacts the quality of life of patients. Yet, specific antivirals are lacking for the treatment of this disease, which makes the search for new drugs necessary. In this context, the nsP2 protease emerges as an attractive therapeutic target, and drug repurposing strategies have proven to be valuable. Therefore, we combined in silico and in vitro methods to identify known drugs as potential CHIKV nsP2 protease inhibitors with antiviral properties within DrugBank. Herein, we developed a hybrid virtual screening pipeline comprising pharmacophore- and target-based screening, drug-like, and pharmaceutical filtering steps. Six virtual hits were obtained, and two of them, capecitabine (CPB) and oxibendazole (OBZ), were evaluated against CHIKV replication in Vero cells. CPB did not present antiviral activity, whereas OBZ inhibited the replication of two different strains of CHIKV, namely, 181-25 (Asian genotype) and BRA/RJ/18 (clinical isolate from ECSA genotype). OBZ showed potent antiviral activity against the CHIKV BRA/RJ/18 (EC50 = 11.4 µM) with a high selectivity index (>44). Analogs of OBZ (albendazole, fenbendazole, and mebendazole) were also evaluated, but none exhibited anti-CHIKV activity, and further, their stereoelectronic features were analyzed. Additionally, we observed that OBZ acts mainly at post-entry steps. Hence, our results support further in vivo studies to investigate the antiviral potential of OBZ, which offers a new alternative to fight CHIKV infections.

Impact of the first year of COVID-19 vaccination strategy in Brazil: an ecological study.

OBJECTIVES: No consensus exists about the best COVID-19 vaccination strategy to be adopted by low-income and middle-income countries. Brazil adopted an age-based calendar strategy to reduce mortality and the burden on the healthcare system. This study evaluates the impact of the vaccination campaign in Brazil on the progression of the reported COVID-19 deaths. METHODS: This ecological study analyses the dynamic of vaccination coverage and COVID-19 deaths in hospitalised adults (≥20 years) during the first year of the COVID-19 vaccination roll-out (January to December 2021) using nationwide data (DATASUS). We stratified the adult population into 20-49, 50-59, 60-69 and 70+ years. The dynamic effect of the vaccination campaign on mortality rates was estimated by applying a negative binomial regression. The prevented and possible preventable deaths (observed deaths higher than expected) and potential years of life lost (PYLL) for each age group were obtained in a counterfactual analysis. RESULTS: During the first year of COVID-19 vaccination, 266 153 517 doses were administered, achieving 91% first-dose coverage. A total of 380 594 deaths were reported, 154 091 (40%) in 70+ years and 136 804 (36%) from 50-59 or 20-49 years. The mortality rates of 70+ decreased by 52% (rate ratio [95% CI]: 0.48 [0.43-0.53]) in 6 months, whereas rates for 20-49 were still increasing due to low coverage (52%). The vaccination roll-out strategy prevented 59 618 deaths, 53 088 (89%) from those aged 70+ years. However, the strategy did not prevent 54 797 deaths, 85% from those under 60 years, being 26 344 (45%) only in 20-49, corresponding to 1 589 271 PYLL, being 1 080 104 PYLL (68%) from those aged 20-49 years. CONCLUSION: The adopted aged-based calendar vaccination strategy initially reduced mortality in the oldest but did not prevent the deaths of the youngest as effectively as compared with the older age group. Countries with a high burden, limited vaccine supply and young populations should consider other factors beyond the age to prioritise who should be vaccinated first.

Non-Hermitian linear-response theory for spin diffusion in quantum systems.

Spin transport theory of non-Hermitian quantum systems, where the non-Hermiticity led to a series of exotic phenomena when the system experiences dissipation to an environment is proposed. The goal is a better understanding of the spin diffusion in the one-dimensional non-Hermitian XXZ model which allows the transport coefficients be computed analytically. Moreover, we analyzed the electric transport in the one-dimensional non-Hermitian Hubbard model which is a very important model of electrons strongly correlated, where we have investigated the effect of non-Hermitian parameters like the imaginary hopping on AC and DC conductivities of the system. We analyzed the large U limit of this model, where such non-Hermiticity contributes with a minus sign in the virtual exchange of quasiparticles and the behavior of the ground state energy and low-lying excitations is reversed.

Cloud point method applied to the extraction and preconcentration of thiabendazole pesticide from whole grape juice samples and amperometric detection by HPLC.

A cloud point method was developed and applied for the first time to extract and preconcentrate thiabendazole (TBZ) from commercial whole grape juice samples, with determination by high performance liquid chromatography coupled to electrochemical detection (HPLC/EC), using a cathodically pretreated boron-doped diamond electrode (BDD). The best conditions for extraction and preconcentration of TBZ by cloud point extraction (CPE) were performed at pH 6.0, by adding 1 mL of the surfactant Tergitol TMN-6 at 10% (mass-to-mass ratio), without heating (at 27 °C) and ultrasonic stirring time of (20 kHz) for 60 min. The HPLC/EC determination was duly validated in a C8 column, in mobile phase with a 69 : 31 ratio (V/V) of phosphate buffer (pH 7.0):ACN, at a flow rate of 1.2 mL min-1 and electrochemical detection with BDD electrode by applying 1.40 V × Ag/AgCl (3.0 mol L-1). Under these conditions, the procedure showed a preconcentration factor (FC) of 21.7, and limits of detection (LOD) and quantification (LOQ) of 6.64 × 10-9 mol L-1 (or 1.33 µg L-1) and 1.66 × 10-8 mol L-1 (or 3.34 µg L-1), respectively. The method provided a percent recovery of 81% to 98%, with a coefficient of variation between 3% and 15%.

Sofosbuvir Off-label Treatment of Yellow Fever Patients During an Outbreak in Brazil, 2018: A Cohort Study.

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.

Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma: New hopes on the horizon.

In this editorial, we comment on the article by Wang et al. This manuscript explores the potential synergistic effects of combining zanubrutinib, a novel oral inhibitor of Bruton's tyrosine kinase, with high-dose methotrexate (HD-MTX) as a therapeutic intervention for primary central nervous system lymphoma (PCNSL). The study involves a retrospective analysis of 19 PCNSL patients, highlighting clinicopathological characteristics, treatment outcomes, and genomic biomarkers. The results indicate the combination's good tolerance and strong antitumor activity, with an 84.2% overall response rate. The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL, particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B. Furthermore, the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring. In essence, the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL. The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes. While the findings suggest promise, the study's limitations should be considered, and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Complete phylogeny of Micrathena spiders suggests multiple dispersal events among Neotropical rainforests, islands and landmasses, and indicates that Andean orogeny promotes speciation.

The Neotropical region is the most diverse on the planet, largely owing to its mosaic of tropical rainforests. Multiple tectonic and climatic processes have been hypothesized to contribute to generating this diversity, including Andean orogeny, the closure of the Isthmus of Panama, the GAARlandia land bridge and historical connections among currently isolated forests. Micrathena spiders are diverse and widespread in the region, and thus a complete phylogeny of this genus allows the testing of hypotheses at multiple scales. We estimated a complete, dated phylogeny using morphological data for 117 Micrathena species and molecular data of up to five genes for a subset of 79 species. Employing eventc-based approaches and biogeographic stochastic mapping while considering phylogenetic uncertainty, we estimated ancestral distributions, the timing and direction of dispersal events and diversification rates among areas. The phylogeny is generally robust, with uncertainty in the position of some of the species lacking sequences. Micrathena started diversifying around 25 Ma. Andean cloud forests show the highest in-situ speciation, while the Amazon is the major dispersal source for adjacent areas. The Dry Diagonal generated few species and is a sink of diversity. Species exchange between Central and South America involved approximately 23 dispersal events and started ~20 Ma, which is consistent with a Miocene age for the Isthmus of Panama closure. We inferred four dispersal events from Central America to the Antilles in the last 20 Myr, indicating the spiders did not reach the islands through the GAARlandia land bridge. We identified important species exchange routes among the Amazon, Andean cloud forests and Atlantic forests during the Plio-Pleistocene. Sampling all species of the genus was fundamental to the conclusions above, especially in identifying the Andean forests as the area that generated the majority of species. This highlights the importance of complete taxonomic sampling in biogeographic studies.

PARROT BORNAVIRUSES IN PSITTACINES KEPT IN CAPTIVITY IN THE STATE OF SANTA CATARINA, BRAZIL.

Parrot bornaviruses are responsible for proventricular dilatation disease (PDD) in psittacines. This study aimed to determine the occurrence and factors associated with Parrot bornaviruses infection in psittacines kept in captivity in a state in the southern region of Brazil. A cross-sectional study was carried out with 192 birds from two facilities (A and B) in 2019, using choanal, esophageal, and cloacal swabs and feathers, totaling 768 samples subjected to reverse-transcription polymerase chain reaction (RT-PCR), for the matrix (M) protein gene with a final product of 350 base pairs (bp). Genetic sequencing of three positive samples was performed by the Sanger method. In the study, the overall virus occurrence was 35.9% (69/192), with 40.4% (42/104) in Facility A and 30.7% (27/88) in Facility B. Sequencing analysis of the samples revealed the presence of Parrot bornavirus 2 (PaBV-2) in both facilities. Swab samples from the choanal (40/69), esophageal (30/69), cloacal (35/69), and feather (15/69) tested positive, facilitating the molecular diagnosis of Parrot bornaviruses. The results indicated that there is no single ideal sample type for antemortem molecular diagnosis of this virus. Simultaneously testing all four samples at the same time point yielded more diagnoses than testing any single sample among the four. Most of the 29 sampled psittacine species were native, and 46.9% of the birds (90/192) consisted of endangered species. Among the psittacines that tested positive, 88.4% (61/69) were clinically healthy, and 8.7% (6/69) exhibited clinical or behavioral signs, including behavioral changes, alterations in feathering, and changes in body score at the time of collection. This study showcases the application of minimally invasive sampling for diagnosing Parrot bornaviruses, enabling sample collection when the birds are restrained for clinical evaluation. This approach facilitates a prompt and effective antemortem diagnosis, thereby serving as an efficient screening method for parrots kept in captivity.

Persistent high mortality rates for Diabetes Mellitus and Hypertension after excluding deaths associated with COVID-19 in Brazil, 2020-2022.

INTRODUCTION: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant public health challenge globally, with Brazil being no exception. Excess mortality during this period reached alarming levels. Cardiovascular diseases (CVD), Systemic Hypertension (HTN), and Diabetes Mellitus (DM) were associated with increased mortality. However, the specific impact of DM and HTN on mortality during the pandemic remains poorly understood. METHODS: This study analyzed mortality data from Brazil's mortality system, covering the period from 2015 to 2022. Data included all causes of death as listed on death certificates, categorized by International Classification of Diseases 10th edition (ICD-10) codes. Population data were obtained from the Brazilian Census. Mortality ratios (MRs) were calculated by comparing death rates in 2020, 2021, and 2022 to the average rates from 2015 to 2019. Adjusted MRs were calculated using Poisson models. RESULTS: Between 2015 and 2022, Brazil recorded a total of 11,423,288 deaths. Death rates remained relatively stable until 2019 but experienced a sharp increase in 2020 and 2021. In 2022, although a decrease was observed, it did not return to pre-pandemic levels. This trend persisted even when analyzing records mentioning DM, HTN, or CVD. Excluding death certificates mentioning COVID-19 codes, the trends still showed increases from 2020 through 2022, though less pronounced. CONCLUSION: This study highlights the persistent high mortality rates for DM and HTN in Brazil during the years 2020-2022, even after excluding deaths associated with COVID-19. These findings emphasize the need for continued attention to managing and preventing DM and HTN as part of public health strategies, both during and beyond the COVID-19 pandemic. There are complex interactions between these conditions and the pandemic's impact on mortality rates.

Air-Stable Cobalt(III) and Chromium(III) Complexes as Single-Component Catalysts for the Activation of Carbon Dioxide and Epoxides.

Cobalt(III) and chromium(III) salophen chloride complexes were synthesized and tested for the cycloaddition of carbon dioxide (CO2) with epoxides to obtain cyclic carbonates. The cat1, cat2, cat4, and cat5 complexes presented high catalytic activity without cocatalysts and are solvent-free at 100 °C, 8 bar, and 9 h. At these conditions, the terminal epoxides (1a-1k) were successfully converted into the corresponding cyclic carbonates with a maximum conversion of ∼99%. Moreover, cat5 was highlighted due to its capability of opening internal epoxides such as limonene oxide (1l) with a 36% conversion to limonene carbonate (2l), and from cyclohexene oxide (1m), cyclic trans-cyclohexene carbonate (2m) and poly(cyclohexene carbonate) were obtained with 15% and 85% selectivity, respectively. A study of the coupling reaction mechanism was proposed with the aid of electrospray ionization mass spectrometry (ESI-MS) analysis, confirming the single-component behavior of the complexes through their ionization due to epoxide coordination. In addition, crystallographic analysis of cat1 single crystals grown in a saturated solution of pyridine helped to demonstrate that the substitution of chloride ion by pyridine ligands to form an octahedral coordination occurs (Py-cat1), supporting the proposed mechanism. Also, a recyclability study was performed for cat5, and a total turnover number of 952 was obtained with only minor losses in catalytic activity after five cycles.

Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

Two new species of Fernandezina Birabn, 1951 (Araneae, Palpimanidae) from cave and epigean habitats in Brazil.

The South American palpimanid genus Fernandezina Birabn currently comprises 15 described species, all known from epigean environments. Representatives of Fernandezina are easily recognized by the unexpanded femora I in both sexes and by the dorsally extended opisthosomal scutum in males. Herein, F. fernandoi sp. nov. is described based on males and females from hypogean environments and F. angeloi sp. nov. is described based on a single male from a nearby epigean environment, both in Brazil. Additionally, we provide an identification key for the species of the genus.

Effects of Bradykinin B2 Receptor Ablation from Tyrosine Hydroxylase Cells on Behavioral and Motor Aspects in Male and Female Mice.

The kallikrein-kinin system is a versatile regulatory network implicated in various biological processes encompassing inflammation, nociception, blood pressure control, and central nervous system functions. Its physiological impact is mediated through G-protein-coupled transmembrane receptors, specifically the B1 and B2 receptors. Dopamine, a key catecholamine neurotransmitter widely distributed in the CNS, plays a crucial role in diverse physiological functions including motricity, reward, anxiety, fear, feeding, sleep, and arousal. Notably, the potential physical interaction between bradykinin and dopaminergic receptors has been previously documented. In this study, we aimed to explore whether B2R modulation in catecholaminergic neurons influences the dopaminergic pathway, impacting behavioral, metabolic, and motor aspects in both male and female mice. B2R ablation in tyrosine hydroxylase cells reduced the body weight and lean mass without affecting body adiposity, substrate oxidation, locomotor activity, glucose tolerance, or insulin sensitivity in mice. Moreover, a B2R deficiency in TH cells did not alter anxiety levels, exercise performance, or motor coordination in female and male mice. The concentrations of monoamines and their metabolites in the substantia nigra and cortex region were not affected in knockout mice. In essence, B2R deletion in TH cells selectively influenced the body weight and composition, leaving the behavioral and motor aspects largely unaffected.

Genomic glucocorticoid receptor effects guide acute stress-induced delayed anxiety and basolateral amygdala spine plasticity in rats.

Anxiety, a state related to anticipatory fear, can be adaptive in the face of environmental threats or stressors. However, anxiety can also become persistent and manifest as anxiety- and stress-related disorders, such as generalized anxiety or post-traumatic stress disorder (PTSD). In rodents, systemic administration of glucocorticoids (GCs) or short-term restraint stress induces anxiety-like behaviors and dendritic branching within the basolateral complex of the amygdala (BLA) ten days later. Additionally, increased arousal-related memory retention mediated by elevated GCs requires concomitant noradrenaline (NE) signaling, both acting in the BLA. It is unknown whether GCs and NE play a role in the delayed acute stress-induced effects on behavior and BLA dendritic plasticity. Here, inhibiting corticosterone (CORT) elevation during 2 h of restraint stress prevents stress-induced increases in delayed anxiety-like behavior and BLA dendritic spine density in rats. Also, we show that the delayed acute stress-induced effects on behavior and morphological alterations are critically dependent on genomic glucocorticoid receptor (GR) actions in the BLA. Unlike CORT, the pharmacological enhancement of NE signaling in the BLA was insufficient to drive delayed anxiety-related behavior. Nonetheless, the delayed anxiety-like behavior ten days after acute stress requires NE signaling in the BLA during stress exposure. Therefore, we define the essential roles of two stress-related hormones for the late stress consequences, acting at two separate times: CORT, via GR, immediately during stress, and NE, via beta-adrenoceptors, during the expression of delayed anxiety.

On one of the smallest Amazonian scorpions: a new species of Microtityus (Scorpiones, Buthidae) from Brazil, with amended diagnosis and potential distribution analysis for the genus

A new scorpion species, Microtityus adriki n. sp., is described based on adult specimens collected in Cantá, state of Roraima (RR), northern Brazil. Microtityus adriki n. sp. is the second species of Microtityus Kjellesvig-Waering, 1966 known from Brazil and is one of the smallest scorpion species (12.39-19.47 mm) in the Amazonian region. In this study, we propose an amended generic diagnosis and a specific diagnosis, describe the male hemispermatophore of Microtityus, give the sequence of COI barcode, and present a potential distribution analysis for the genus. The morphology of the male hemispermatophore of Microtityus differs from that of other Neotropical buthid genera, except for the number of lobes (three lobes), which is a character state shared with several genera. The potential distribution model generated by MaxEnt suggests high environmental suitability for the genus in the Antilles and northern South America, with scattered high suitability in several regions of Central America. However, the model did not indicate high suitability in areas where Brazilian species occur (i.e., Microtityus adriki n. sp. and Microtityus vanzolinii Lourenço & Eickstedt, 1983), and this could be explained by a sampling bias. Therefore, future studies, including extensive sampling, are required to better understand the biogeographic processes behind the distribution of this genus.

Joint spatial modeling of the risks of co-circulating mosquito-borne diseases in Ceará, Brazil.

Mosquito-borne diseases such as dengue and chikungunya have been co-circulating in the Americas, causing great damage to the population. In 2021, for instance, almost 1.5 million cases were reported on the continent, being Brazil the responsible for most of them. Even though they are transmitted by the same mosquito, it remains unclear whether there exists a relationship between both diseases. In this paper, we model the geographic distributions of dengue and chikungunya over the years 2016 to 2021 in the Brazilian state of Ceará. We use a Bayesian hierarchical spatial model for the joint analysis of two arboviruses that includes spatial covariates as well as specific and shared spatial effects that take into account the potential autocorrelation between the two diseases. Our findings allow us to identify areas with high risk of one or both diseases. Only 7% of the areas present high relative risk for both diseases, which suggests a competition between viruses. This study advances the understanding of the geographic patterns and the identification of risk factors of dengue and chikungunya being able to help health decision-making.

In Situ Transesterification from Soybean Seed Using Mechanochemical Methods toward Producing Biodiesel.

The research and development of new routes of biodiesel synthesis have been increasingly in line with the principles of green chemistry. In this sense, mechanochemistry is a promising technique, able to ally the energetic potential with reductions in the use of solvents and steps of treatment of the sample and the purification of the product. To date, this is the first work using mechanochemistry directly in extracting soybean oil from its seed and the in situ transesterification reaction by applying a reactive soybean oil extraction process. The presence of n-hexane was studied in different molar proportions (relative to the oil content), and a low solvent consumption in a 3:1 ratio was adopted. Mechanochemistry favored oil diffusion in the n-hexane solvent, resulting in a mean triglyceride content equal to 90%, against 66% obtained in the tests without spheres in the planetary ball mill. The catalyst content was also evaluated, and 4% NaOH (weight, concerning the oil) was the concentration that presented less residue of nontransesterified glycerides in the samples for ethyl ester preparation. Additionally, the protein content was determined on the residual soybean cake, with no loss of nutritional potential when subjected to the mechanochemical process.