The virome of bubaline (Bubalus bubalis) tonsils reveals an unreported bubaline polyomavirus.

Water buffalo (Bubalus bubalis) farming is increasing in many regions of the world due to the species' ability to thrive in environments where bovine cattle would struggle. Despite water buffaloes being known for their resistance to diseases, there is a lack of data about the diversity of the microbiome of the species. In this study, we examined the virome diversity in palatine tonsils collected from animals from the island of Marajó, northern Pará state, Brazil, which harbors the largest bubaline flock in the country. Tonsil fragments from 60 clinically healthy bubalines were randomly selected from a sample of 293 animals. The samples were purified, extracted, and randomly amplified with phi29 DNA polymerase. After amplification, the products were purified and sequenced. Circular DNA viruses were predominant in the tonsils' virome. Sequences of genome segments representative of members of the genera Alphapolyomavirus (including a previously unreported bubaline polyomavirus genome) and Gemycircularvirus were identified, along with other not yet classified circular virus genomes. As the animals were clinically healthy at the time of sampling, such viruses likely constitute part of the normal tonsillar virome of water buffaloes inhabiting the Ilha do Marajó biome.

Loxosceles amazonica Brown Spider venom: Insights into enzymatic activities, immunorecognition, and novel phospholipase D isoforms.

The Loxosceles genus represents one of the main arachnid genera of medical importance in Brazil. Despite the gravity of Loxosceles-related accidents, just a handful of species are deemed medically important and only a few have undergone comprehensive venom characterization. Loxosceles amazonica is a notable example of a potentially dangerous yet understudied Loxosceles species. While there have been limited reports of accidents involving L. amazonica to date, accidents related to Loxosceles are increasing in the North and Northeast regions of Brazil, where L. amazonica has been reported. In this work, we provide a complementary biochemical and immunological characterization of L. amazonica venom, considering its most relevant enzymatic activities and its immunorecognition and neutralization by current therapeutic antivenoms. Additionally, a cDNA library enriched with phospholipase D (PLD) sequences from L. amazonica venom glands was built and subsequently sequenced. The results showed that L. amazonica venom is well immunorecognised by all the tested antibodies. Its venom also displayed proteolytic, hyaluronidase, and sphingomyelinase activities. These activities were at least partially inhibited by available antivenoms. With cDNA sequencing of PLDs, seven new putative isoforms were identified in the venom of L. amazonica. These results contribute to a better knowledge of the venom content and activities of a synanthropic, yet understudied, Loxosceles species. In vivo assays are essential to confirm the medical relevance of L. amazonica, as well as to assess its true toxic potential and elucidate its related pathophysiology.

Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines-From the Synthesis to 3D-Cell Culture Effects.

Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC50 values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.

[WITHDRAWN] Chagas Cardiomyopathy and Aerobic Exercise: a Systematic Review / [RETIRADO] CARDIOPATIA CHAGÁSICA E EXERCÍCIO FÍSICO AERÓBICO: uma revisão sistemática

A cardiomiopatia chagásica é uma consequência crônica da doença de Chagas e representa uma das principais causas de morbidade e mortalidade na América Latina. O exercício físico aeróbico tem sido reconhecido pelos seus benefícios à saúde cardiovascular. Portanto, o estudo tem como objetivo avaliar os efeitos do exercício físico aeróbico na função cardíaca, capacidade de exercício e qualidade de vida em pacientes com cardiomiopatia chagásica. Foi utilizado um referencial teórico-metodológico baseado na análise de estudos encontrados nas bases de dados PubMed, Scopus e Web of Science durante um período de cinco anos. Os resultados indicam que o exercício físico aeróbio pode ser uma estratégia terapêutica complementar eficaz, contribuindo para a melhoria da função cardíaca, aumento da capacidade de exercício e melhoria da qualidade de vida dos pacientes. No entanto, é importante destacar a necessidade de mais estudos para padronizar os protocolos de exercício e identificar os mecanismos específicos pelos quais o exercício beneficia os pacientes com cardiomiopatia chagásica. Conclui-se que, apesar das limitações existentes, a prática de exercício físico aeróbico apresenta potencial significativo para reabilitação cardíaca em indivíduos acometidos pela doença de Chagas e deve ser considerada como parte do plano de tratamento.

A cardiopatia chagásica é uma consequência crônica da doença de Chagas e representa uma das principais causas de morbimortalidade na América Latina. O exercício físico aeróbico tem sido reconhecido por seus benefícios à saúde cardiovascular. Assim, o estudo tem como objetivo avaliar os efeitos do exercício físico aeróbico na função cardíaca, na capacidade de exercício e na qualidade de vida de pacientes com cardiopatia chagásica. Utilizou-se um referencial teórico-metodológico baseado na análise de estudos encontrados nas bases de dados PubMed, Scopus e Web of Science, em sete anos. Os resultados indicam que o exercício físico aeróbico pode ser uma estratégia terapêutica complementar eficaz, contribuindo para a melhoria da função cardíaca, aumento da capacidade de exercício e melhoria da qualidade de vida dos pacientes. No entanto, destaca-se a necessidade de mais estudos para padronizar protocolos de exercício e identificar os mecanismos específicos pelos quais o exercício beneficia pacientes com cardiopatia chagásica. Conclui-se que, apesar das limitações existentes, a prática de exercício físico aeróbico apresenta um potencial significativo para a reabilitação cardíaca em indivíduos acometidos pela doença de Chagas, devendo ser considerada como parte do plano de tratamento.

Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.

Variaciones en el consumo de medicamentos para la salud mental en una unidad de atención primaria brasileña: ¿hay influencia de la pandemia? / Variations in the consumption of mental health medications in a brazilian primary care unit: is there influence of the pandemic?

Introducción: La pandemia de COVID-19 ha generado la necesidad de ajustes y adaptaciones en diversas áreas, desde el comportamiento hasta la normativa, con grandes repercusiones en términos de salud pública. Objetivo: Comparar los consumos promedio mensuales (CPM) de medicamentos de control especial utilizados para la salud mental antes y durante la pandemia en una Unidad Básica de Salud (UBS) en el Distrito Federal, Brasil. Métodos: Los consumos se obtuvieron a través del sistema de gestión de inventarios local y el CPM (±desviación estándar) se calculó sin tener en cuenta los meses de desabastecimiento, considerando el período de 2020 a 2022. Como parámetro comparativo, se utilizó el CPM±DE de 2019. Resultados: Se analizaron los consumos de 32 medicamentos, siendo la mayoría antiepilépticos (N=10; 31,2 %), antidepresivos (N=10; 31,2 %) y antipsicóticos (N=8; 25,0 %). Se observó que más de la mitad de los medicamentos analizados (n=18; 56,3 %) mantuvieron un aumento en el consumo a lo largo de los años de la pandemia. Conclusión: Hubo una variación significativa en el consumo de medicamentos sujetos a control especial en la UBS durante la pandemia. Estos resultados pueden estar asociados a diversos factores, como el aumento de los cuadros clínicos que justifican su prescripción, en línea con la literatura actual sobre el impacto potencial del aislamiento social y las medidas tomadas por las autoridades competentes para contener la propagación del virus SARS-COV-2. (AU)

Introduction: The COVID-19 pandemic has generated the need for adjustments and adaptations in various areas, from behaviour to regulations, with significant repercussions in terms of public health. Objective: To compare the monthly average consumption (MAC) of special control medications used for mental health before and during the pandemic in a Basic Health Unit (UBS) in the Federal District, Brazil. Methods: Consumption data were obtained through the local inventory management system, and the MAC (±stan-dard deviation) was calculated excluding months of stockouts, considering the period from 2020 to 2022. The MAC±SD of 2019 was used as a comparative parameter. Results: Consumption of 32 medications was analyzed, with the majority being antiepileptics (N=10; 31.2 %), anti-depressants (N=10; 31.2 %), and antipsychotics (N=8; 25.0 %). It was observed that more than half of the analyzed medications (n=18; 56.3 %) maintained an increase in consumption throughout the pandemic years. Conclusion: There was a significant variation in the consumption of special control medications at the UBS during the pandemic. These results may be associated with various factors, such as the increase in clinical conditions justi-fying their prescription, in line with current literature on the potential impact of social isolation and measures taken by competent authorities to contain the spread of the SARS-CoV-2 virus. (AU)

The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control.

Introduction: We have reanalyzed the genomic data of the International Collaboration for the Genomics of HIV (ICGH), centering on HIV-1 Elite Controllers. Methods: We performed a genome-wide Association Study comparing 543 HIV Elite Controllers with 3,272 uninfected controls of European descent. Using the latest database for imputation, we analyzed 35,552 Single Nucleotide Polymorphisms (SNPs) within the Major Histocompatibility Complex (MHC) region. Results: Our analysis identified 2,626 SNPs significantly associated (p<5. 10-8) with elite control of HIV-1 infection, including well-established MHC signals such as the rs2395029-G allele which tags HLA-B*57:01. A thorough investigation of SNPs in linkage disequilibrium with rs2395029 revealed an extensive haploblock spanning 1.9 megabases in the MHC region tagging HLA-B*57:01, comprising 379 SNP alleles impacting 72 genes. This haploblock contains damaging variations in proteins like NOTCH4 and DXO and is also associated with a strong differential pattern of expression of multiple MHC genes such as HLA-B, MICB, and ZBTB12. The study was expanded to include two cohorts of seropositive African-American individuals, where a haploblock tagging the HLA-B*57:03 allele was similarly associated with control of viral load. The mRNA expression profile of this haploblock in African Americans closely mirrored that in the European cohort. Discussion: These findings suggest that additional molecular mechanisms beyond the conventional antigen-presenting role of class I HLA molecules may contribute to the observed influence of HLA-B*57:01/B*57:03 alleles on HIV-1 elite control. Overall, this study has uncovered a large haploblock associated with HLA-B*57 alleles, providing novel insights into their massive effect on HIV-1 elite control.

Circulation of Dengue Virus Serotype 1 Genotype V and Dengue Virus Serotype 2 Genotype III in Tocantins State, Northern Brazil, 2021-2022.

In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of cases of arboviral disease, particularly Dengue virus (DENV). This study aimed to deepen the knowledge on DENV circulation within that state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. There were a total of 8807 and 20,692 cases in 2021 and 2022, respectively, as reported by the state's Secretary of Health. Nucleotide sequencing confirmed the circulation of DENV serotype 1, genotype V and DENV serotype 2, genotype III in the State. Younger age groups (4 to 43 years old) were mostly affected; however, no significant differences were detected regarding the gender distribution of cases in humans. Phylogenetic analysis revealed that the circulating viruses belong to DENV-1 genotype V American and DENV-2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 genotype V genomes sequenced here are closely related to genomes previously sequenced in the state of São Paulo. Regarding the DENV-2 genotype III genomes, these clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. The findings reported here suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the importance of major population centers in Brazil on virus dispersion, such as those observed in other Latin American and North American countries. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here highlight the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of DENV and the relevance of surveillance efforts in supporting public health policies.

The Design, Development, and Usability Testing of an eHealth Program for Youths With Osteogenesis Imperfecta: Protocol for a 2-Phase User-Centered Mixed Methods Study.

BACKGROUND: Innovative approaches are needed to address the self-management needs of youths with osteogenesis imperfecta (OI) transitioning into adult-oriented health care systems. Using a sequentially phased research approach, the goal is to design, develop, and test the usability of an innovative eHealth program called "Teens Taking Charge: Managing OI Online," hereafter named "Teens OI." This program seeks to optimize self-management, facilitate a successful transition to adult care, and address a critical gap in the quality of care for youths with OI. OBJECTIVE: The study objectives are to (1) design and develop an English and French version of the Teens OI and (2) test the usability of the Teens OI in terms of efficiency, effectiveness, and satisfaction from the perspectives of youths with OI and their parents. METHODS: A user-centered design is presently in progress to design and develop Teens OI. A "Website Design and Development Council" (ie, Council) has been convened, with 20 youths and parent dyads recruited and global experts surveyed at an international meeting. With unanimous support from the Council, usability testing of the Teens OI will ensue in 4 iterative cycles with 32 youth-parent dyads. All sociodemographic and usability metrics will be descriptively analyzed. All recorded interview and focus group data are analyzed using content analysis techniques involving an iterative process of data reduction, data display, conclusion drawing, and verification. RESULTS: As of December 2022, an 8-person, interdisciplinary Teens OI council, comprising 4 health care professionals, 3 youths and young adults with OI, and 1 parent, has been convened to oversee the design and development of Teens OI. Two cycles of interviews have been conducted with 10 youths with OI with or without their parents (n=6) from December 2021 to September 2022. Data analysis has been in progress since April 2022. Aim 2 is ethically approved and will commence following the completion of content development, expected by late July 2023. Preliminary analysis indicates that the following topics need to be prioritized for the youths: mental health, pain, accessibility, medical care, education, community, and parental care. CONCLUSIONS: The proposed study will design and develop a self-management and transitional care program for youths with OI in partnership with patients, caregivers, and health care professionals. This study leverages youths' openness to adopt eHealth technologies to meet their needs and has the potential to actively engage them to autonomously manage their lifelong conditions, and facilitate a successful transition to adult health care. Finally, the proposed study will also address a critical gap in the quality of care and the growing concern that the OI population transitioning from pediatric to adult care is at risk of various adverse events associated with the transition. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47524.

Gene expression profiling of peripheral blood mononuclear cells from women with cervical lesions reveals new markers of cancer.

Cervical cancer (CC) is a multifactorial disease of which human papillomavirus (HPV) is the main etiological agent. Despite cervical Pap smear screening and anti­HPV vaccination, CC remains a major public health issue. Identification of specific gene expression signatures in the blood could allow better insight into the immune response of CC and could provide valuable information for the development of novel biomarkers. The present study performed a transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from Senegalese patients with CC (n=31), low­grade cervical intraepithelial neoplasia (CIN1; n=27) and from healthy control (CTR) subjects (n=29). Individuals in the CIN1 and CTR groups exhibited similar patterns in gene expression. A total of 182 genes were revealed to be differentially expressed in patients with CC compared with individuals in the CIN1 and CTR groups. The IL1R2, IL18R1, MMP9 and FKBP5 genes were the most upregulated, whereas the T­cell receptor α gene TRA was the most downregulated in the CC group compared with in the CIN1 and CTR groups. The pathway enrichment analysis of the differentially expressed genes revealed pathways directly and indirectly linked to inflammation. To the best of our knowledge, the present study is the first large transcriptomic study on CC performed using PBMCs from African women; the results revealed the involvement of genes and pathways related to inflammation, most notably the IL­1 pathway, and the involvement of downregulation of the T­cell receptor α, a key component of the immune response. Several of the stated genes have already been reported in other cancer studies as putative blood biomarkers, thus reinforcing the requirement for deeper investigation. These findings may aid in the development of innovative clinical biomarkers for CC prevention and should be further replicated in other populations.

Social and health indicators in an academic community: enteroparasites, nutritional, allergic and clinical aspects / Indicadores sociais e de saúde em uma comunidade acadêmica: enteroparasitos, aspectos nutricionais, alérgicos e clínicos

Objective: this study aimed to associate enteroparasitic infection with nutritional, allergic, and clinical repercussions and the sociodemographic aspects in an academic community in Santo Antônio de Jesus, Bahia, Brazil. Methods: the cross-sectional research was carried out between February 2018 and March 2020, with 121 participants. Spontaneous sedimentation and Rugai techniques were used for the parasitological diagnosis of fecal samples. Allergies and clinical issues and the sociodemographic aspects were studied via a questionnaire, and the nutritional status was obtained from the assessment of body mass index and arm and abdominal circumferences. Results: there was 38.2% positivity for intestinal parasites; 65.9% for female participants; with the majority of eutrophic, between 18-27 years old; heteronormative, and single. Besides, the Endolimax nana (78.7%) and Giardia duodenalis (21.3%) were the predominant species. Statistical significance was found between obesity rates and the presence of intestinal parasites and those with allergic aspects. Nervousness, headache, and back and abdominal pains were the most common symptoms. Conclusions: this study contributes to obtaining data on epidemiological and public health surveys in the Bahian territory, providing a reference for other researchers. The statistical association of these with nutritional and allergic aspects can support future research on this population.

Objetivo: este estudo teve como objetivo associar a infecção enteroparasitária com aspectos nutricionais, alérgicos, clínicos e sociodemográficos em uma comunidade acadêmica do município de Santo Antônio de Jesus, Bahia, Brasil. Método: a pesquisa transversal foi realizada entre fevereiro de 2018 e março de 2020, com 121 participantes. As técnicas de sedimentação espontânea e Rugai foram utilizadas para o diagnóstico parasitológico de amostras fecais. Alergias, questões clínicas e aspectos sociodemográficos foram estudados por meio de um questionário, e o estado nutricional foi obtido por meio da avaliação do índice de massa corporal e das circunferências braquial e abdominal. Resultados: houve 38,2% de positividade para parasitos intestinais; 65,9% para participantes do sexo feminino; com a maioria eutrófica, entre 18-27 anos; heteronormativa e sigle. Além disso, Endolimax nana (78,7%) e Giardia duodenalis (21,3%) foram as espécies predominantes. Foi encontrada significância estatística entre as taxas de obesidade e presença de parasitos intestinais e com aspectos alérgicos. Nervosismo, dor de cabeça, dores nas costas e abdominais foram os sintomas mais comuns. Conclusões: este estudo contribui para a obtenção de dados sobre inquéritos epidemiológicos e de saúde pública no território baiano, servindo de referência para outras pesquisas. A associação estatística destes com aspectos nutricionais e alérgicos pode subsidiar futuras pesquisas nesta população.

Moral experiences of children with medical complexity: A participatory hermeneutic ethnography in Brazil.

Children with medical complexity have been defined within the literature as chronically ill and medically fragile children with complex care needs. Care for these children raises significant ethical and moral considerations. Therefore, this participatory ethnographic study conducted with eight children and their families aimed to better understand the moral experiences of children with medical complexity, based on views of children as moral agents and capable of understanding and expressing interpretations about their lived experiences. Through our participatory hermeneutical ethnographic research, we were able to shed light on how children with medical complexity express their moral experiences within a complex sociopolitical context, perpetuating dominant outlooks on what is considered a "normal" child. Children with medical complexity described their resistance to these dominant views as they strive to be included in discussions about matters that affect them, reacting to painful medical procedures and treatments, and expressing their concerns about their future aspirations. The knowledge advanced by this study about moral experiences of children with medical complexity can inform understandings of children's interests based on their own interpretations within complex sociopolitical contexts that value their lives differently.

Genomic Epidemiology Reveals the Circulation of the Chikungunya Virus East/Central/South African Lineage in Tocantins State, North Brazil.

The chikungunya virus (CHIKV) is a mosquito-borne virus of the family Togaviridae transmitted to humans by Aedes spp. mosquitoes. In Brazil, imported cases have been reported since June 2014 through two independent introductions, one caused by Asian Lineage in Oiapoque, Amapá state, North Region, and another caused by East/Central/South African (ECSA) in Feira de Santana, Bahia state, Northeast Region. Moreover, there is still limited information about the genomic epidemiology of the CHIKV from surveillance studies. The Tocantins state, located in Northern Brazil, reported an increase in the number of CHIKV cases at the end of 2021 and the beginning of 2022. Thus, to better understand the dispersion dynamics of this viral pathogen in the state, we generated 27 near-complete CHIKV genome sequences from four cities, obtained from clinical samples. Our results showed that the newly CHIKV genomes from Tocantins belonged to the ECSA lineage. Phylogenetic reconstruction revealed that Tocantins' strains formed a single well-supported clade, which appear to be closely related to isolates from the Rio Grande do Norte state (Northeast Brazil) and the Rio de Janeiro state (Southeast Brazil), that experienced an explosive ECSA epidemic between 2016-2019. Mutation analyses showed eleven frequent non-synonymous mutations in the structural and non-structural proteins, indicating the autochthonous transmission of the CHIKV in the state. None of the genomes recovered within the Tocantins samples carry the A226V mutation in the E1 protein associated with increased transmission in A. albopictus. The study presented here highlights the importance of continued genomic surveillance to provide information not only on recording mutations along the viral genome but as a molecular surveillance tool to trace virus spread within the country, to predict events of likely occurrence of new infections, and, as such, contribute to an improved public health service.

Analysis of NGS data from Peruvian Loxosceles laeta spider venom gland reveals toxin diversity.

Accidents involving spiders from the genus Loxosceles cause medical emergencies in several countries of South America. The species Loxosceles laeta is ubiquitously present in Peru and is responsible for severe accidents in this country. To further characterize L. laeta venom components and to unveil possible variations in the Peruvian population, we provide an overview of the toxins-related transcripts present in the venom gland of Peruvian L. laeta. A dataset from a cDNA library previously sequenced by MiSeq sequencer (Illumina) was re-analyzed and the obtained data was compared with available sequences from Loxosceles toxins. Phospholipase-D represent the majority (69,28 %) of the transcripts related to venom toxins, followed by metalloproteases (20,72 %), sicaritoxins (6,03 %), serine-proteases (2,28 %), hyaluronidases (1,80 %) and Translationally Controlled Tumor Protein (TCTP) (0,56 %). New sequences of phospholipases D,sicaritoxins, hyaluronidase, TCTP and serine proteinases were described. Differences between the here-described toxin sequences and others, previously identified in venom glands from other spiders, were visualized upon sequence alignments. In addition, an in vitro hyaluronidase activity assay was also performed to complement comparisons between Peruvian and Brazilian L. laeta venom enzymatic activities, revealing a superior activity in the venom from Brazilian specimens. These new data provide a molecular basis that can help to explain the difference in toxicity among L. laeta venoms from different countries in South America.

Genomic Epidemiology of SARS-CoV-2 in Tocantins State and the Diffusion of P.1.7 and AY.99.2 Lineages in Brazil.

Tocantins is a state in the cross-section between the Central-West, North and Northeast regions of Brazilian territory; it is a gathering point for travelers and transportation from the whole country. In this study, 9493 genome sequences, including 241 local SARS-CoV-2 samples (collected from 21 December 2020, to 16 December 2021, and sequenced in the MinION platform) were analyzed with the following aims: (i) identify the relative prevalence of SARS-CoV-2 lineages in the state of Tocantins; (ii) analyze them phylogenetically against global SARS-CoV-2 sequences; and (iii) hypothesize the viral dispersal routes of the two most abundant lineages found in our study using phylogenetic and phylogeographic approaches. The performed analysis demonstrated that the majority of the strains sequenced during the period belong to the Gamma P.1.7 (32.4%) lineage, followed by Delta AY.99.2 (27.8%), with the first detection of VOC Omicron. As expected, there was mainly a dispersion of P.1.7 from the state of São Paulo to Tocantins, with evidence of secondary spreads from Tocantins to Goiás, Mato Grosso, Amapá, and Pará. Rio de Janeiro was found to be the source of AY.99.2 and from then, multiple cluster transmission was observed across Brazilian states, especially São Paulo, Paraiba, Federal District, and Tocantins. These data show the importance of trade routes as pathways for the transportation of the virus from Southeast to Northern Brazil.

A Brief History of Giant Viruses' Studies in Brazilian Biomes.

Almost two decades after the isolation of the first amoebal giant viruses, indubitably the discovery of these entities has deeply affected the current scientific knowledge on the virosphere. Much has been uncovered since then: viruses can now acknowledge complex genomes and huge particle sizes, integrating remarkable evolutionary relationships that date as early as the emergence of life on the planet. This year, a decade has passed since the first studies on giant viruses in the Brazilian territory, and since then biomes of rare beauty and biodiversity (Amazon, Atlantic forest, Pantanal wetlands, Cerrado savannas) have been explored in the search for giant viruses. From those unique biomes, novel viral entities were found, revealing never before seen genomes and virion structures. To celebrate this, here we bring together the context, inspirations, and the major contributions of independent Brazilian research groups to summarize the accumulated knowledge about the diversity and the exceptionality of some of the giant viruses found in Brazil.

Performances of rapid and connected salivary RT-LAMP diagnostic test for SARS-CoV-2 infection in ambulatory screening.

In the context of social events reopening and economic relaunch, sanitary surveillance of SARS-CoV-2 infection is still required. Here, we evaluated the diagnostic performances of a rapid, extraction-free and connected reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay on saliva. Nasopharyngeal (NP) swabs and saliva from 443 outpatients were collected simultaneously and tested by reverse-transcription quantitative PCR (RT-qPCR) as reference standard test. Seventy-one individuals (16.0%) were positive by NP and/or salivary RT-qPCR. Sensitivity and specificity of salivary RT-LAMP were 85.9% (95%CI 77.8-94.0%) and 99.5% (98.7-100%), respectively. Performances were similar for symptomatic and asymptomatic participants. Moreover, SARS-CoV-2 genetic variants were analyzed and no dominant mutation in RT-LAMP primer region was observed during the period of the study. We demonstrated that this RT-LAMP test on self-collected saliva is reliable for SARS-CoV-2 detection. This simple connected test with optional automatic results transfer to health authorities is unique and opens the way to secure professional and social events in actual context of economics restart.

Identification of potential new mosquito-associated viruses of adult Aedes aegypti mosquitoes from Tocantins state, Brazil.

Medically important arboviruses such as dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are primarily transmitted by the globally distributed mosquito Aedes aegypti. Increasing evidence suggests that the transmission of some viruses can be influenced by mosquito-specific and mosquito-borne viruses. Advancements in high-throughput sequencing (HTS) and bioinformatics have expanded our knowledge on the richness of viruses harbored by mosquitoes. HTS was used to characterize the presence of virus sequences in wild-caught adult Ae. aegypti from Tocantins (TO) state, Brazil. Samples of mosquitoes were collected in four cities of Tocantins state and submitted to RNA isolation, followed by sequencing at an Illumina HiSeq platform. Our results showed initially by Krona the presence of 3% of the sequenced reads belonging to the viral database. After further analysis, the virus sequences were found to have homology to two viral families found in insects Phenuiviridae and Metaviridae. Three possible viral strains including putative new viruses were detected and named Phasi Charoen-like phasivirus isolate To-1 (PCLV To-1), Aedes aegypti To virus 1 (AAToV1), and Aedes aegypti To virus 2 (AAToV2). The results presented in this work contribute to the growing knowledge about the diversity of viruses in mosquitoes and might be useful for future studies on the interaction between insect-specific viruses and arboviruses.

Análise ética dos impactos da pandemia de COVID-19 na saúde de crianças e adolescentes / An ethical analysis of the impacts of the COVID-19 pandemic on the health of children and adolescents / Análisis ético acerca dos impactos de la pandemia COVID-19 en la salud de niños y adolescentes

A pandemia de COVID-19 trouxe impactos significativos para a vida de crianças e adolescentes em todo o mundo. Considerando esse contexto, o objetivo deste artigo foi examinar como as crianças e os adolescentes no Brasil foram impactados pela pandemia à luz de uma análise ética. Para tanto, uma análise interpretativa de estudos brasileiros sobre a saúde da criança e do adolescente durante a pandemia foi realizada. A tarefa de reconhecer essa dimensão ética é importante para entender como as respostas a situações de crise, tais como a presente situação da pandemia de COVID-19, podem ser moldadas e identificar quais as prioridades de ação de acordo com todas as partes interessadas, situando a criança entre essas partes de interesse. A análise demonstrou que tanto os efeitos diretos quanto os indiretos implicam em processos de tomada de decisão que precisam utilizar e sustentar o direito de participação da criança para que a ação tomada esteja o máximo possível focada nos melhores interesses da criança. Contudo, a realidade brasileira tem demonstrado uma exclusão estrutural das vozes infantis. Recomenda-se que mais estudos sejam conduzidos a fim de aprofundar o conhecimento sobre os melhores interesses das crianças e sua participação nas ações tomadas durante a pandemia

The COVID-19 pandemic has impacted the lives of children and adolescents around the world. This article aims to examine how the pandemic has impacted children and adolescents in Brazil using an ethical analysis. An interpretive analysis of Brazilian studies on child and adolescent health during the pandemic was conducted. The task of recognizing this ethical dimension is important to understand how responses to crisis situations, such as the current situation of the COVID-19 pandemic, can be shaped and where are the priorities for action according to all stakeholders, situating the child between these parts of interest. Our analysis highlighted both direct and indirect effects surrounding the decision-making processes for children in the COVID-19 pandemic reality. These decisional processes must sustain the child's right to participation to ascertain that the action taken is in the child's best interests. However, Brazilian reality has shown a structural exclusion of children's voices in decisions that affect them, particularly related to the effects of the pandemics in their lives. More studies must be conducted to deepen the knowledge about children's best interests and their participation in actions planning during the pandemic

La pandemia de COVID-19 ha afectado las vidas de niños y adolescentes de todo el mundo. Este artículo tiene como objetivo examinar cómo la pandemia ha afectado a los niños y adolescentes en Brasil mediante un análisis ético. Se realizó un análisis interpretativo de los estudios brasileños sobre salud del niño y del adolescente durante la pandemia. La tarea de reconocer esta dimensión ética es importante para entender cómo las respuestas a situaciones de crisis, como la situación actual de la pandemia COVID-19, pueden configurarse y dónde están las prioridades de acción según todos los actores, situando al niño entre estas partes. de interés. Estos procesos de decisión deben sustentar el derecho del niño a la participación para asegurarse de que las medidas tomadas respondan al interés superior del niño. Sin embargo, la realidad brasileña ha mostrado una exclusión estructural de las voces de los niños en las decisiones que los afectan, particularmente en relación con los efectos de las pandemias en sus vidas. Se deben realizar más estudios para profundizar el conocimiento sobre el interés superior de los niños y su participación en la planificación de acciones durante la pandemia

High Rate of Mutational Events in SARS-CoV-2 Genomes across Brazilian Geographical Regions, February 2020 to June 2021.

Brazil was considered one of the emerging epicenters of the coronavirus pandemic in 2021, experiencing over 3000 daily deaths caused by the virus at the peak of the second wave. In total, the country had more than 20.8 million confirmed cases of COVID-19, including over 582,764 fatalities. A set of emerging variants arose in the country, some of them posing new challenges for COVID-19 control. The goal of this study was to describe mutational events across samples from Brazilian SARS-CoV-2 sequences publicly obtainable on Global Initiative on Sharing Avian Influenza Data-EpiCoV (GISAID-EpiCoV) platform and to generate indexes of new mutations by each genome. A total of 16,953 SARS-CoV-2 genomes were obtained, which were not proportionally representative of the five Brazilian geographical regions. A comparative sequence analysis was conducted to identify common mutations located at 42 positions of the genome (38 were in coding regions, whereas two were in 5' and two in 3' UTR). Moreover, 11 were synonymous variants, 27 were missense variants, and more than 44.4% were located in the spike gene. Across the total of single nucleotide variations (SNVs) identified, 32 were found in genomes obtained from all five Brazilian regions. While a high genomic diversity has been reported in Europe given the large number of sequenced genomes, Africa has demonstrated high potential for new variants. In South America, Brazil, and Chile, rates have been similar to those found in South Africa and India, providing enough "space" for new mutations to arise. Genomic surveillance is the central key to identifying the emerging variants of SARS-CoV-2 in Brazil and has shown that the country is one of the "hotspots" in the generation of new variants.