Cross-modal tumor segmentation using generative blending augmentation and self-training.

OBJECTIVES: Data scarcity and domain shifts lead to biased training sets that do not accurately represent deployment conditions. A related practical problem is cross-modal image segmentation, where the objective is to segment unlabelled images using previously labelled datasets from other imaging modalities. METHODS: We propose a cross-modal segmentation method based on conventional image synthesis boosted by a new data augmentation technique called Generative Blending Augmentation (GBA). GBA leverages a SinGAN model to learn representative generative features from a single training image to diversify realistically tumor appearances. This way, we compensate for image synthesis errors, subsequently improving the generalization power of a downstream segmentation model. The proposed augmentation is further combined to an iterative self-training procedure leveraging pseudo labels at each pass. RESULTS: The proposed solution ranked first for vestibular schwannoma (VS) segmentation during the validation and test phases of the MICCAI CrossMoDA 2022 challenge, with best mean Dice similarity and average symmetric surface distance measures. CONCLUSION AND SIGNIFICANCE: Local contrast alteration of tumor appearances and iterative self-training with pseudo labels are likely to lead to performance improvements in a variety of segmentation contexts.

Clinical practice guidelines for diagnostic and treatment of the chronic heart failure.

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.

Minimally invasive intraoral removal of mesiodens via a transnasal, non-endoscopic approach: a systematic review on the purpose of 10 cases.

Mesiodens, which emerge towards the nasal cavity, often require consultation in maxillofacial practice. Typically accessed through wide palatal flaps with ostectomy, this method involves limited visibility and poses the risk of damaging the roots and apex of adjacent dental structures. This study advocates a minimally invasive technique that involves vestibulotomy between the central incisors, facilitating direct and rapid access through nasal floor dissection, minimizing comorbidities. A systematic review was performed, following the PRISMA guidelines, apropos on ten clinical cases reported in this study. The MEDLINE/Pubmed and Web of Science databases were searched. Several variables were considered and are presented comprehensively in tables and figures. Additionally, 10 case reports with mesiodens in the maxilla were submitted to surgical treatment using a minimally invasive intraoral transnasal disinclusion. The initial literature search resulted in 37 articles, of which 9 met the inclusion criteria for the analysis. Regarding postoperative complications, no bone exposure, incisor root damage, extensive surgical approach, palatal or vestibular hematoma, or palatal necrosis was observed. However, 10% experienced superficial damage to the nasopalatine neurovascular, while 80% and 20% presented mild and moderate postoperative facial edema, respectively. Hypoesthesia in 20% of patients recovered in the first week, 40% in the first month and 40% at 3 months. The minimally invasive intraoral, transnasal, non-endoscopic approach emerges as a safe and predictable alternative to conventional surgical techniques. Presumes minimal postoperative complications, mitigating the risk of excessive bone removal and damage to adjacent structures.

Preservation of the inferior alveolar vasculonervous bundle in mandibular resective therapies: systematic review and report of two cases

Background: Segmental surgical resection is a frequently indicated procedure to treat aggressive mandibular tumors. One of the most important complications derived from this technique is permanent paresthesia of the inferior alveolar nerve (IAN), which significantly affects the quality of life of patients who experience it. This could be avoided through maneuvers that preserve the IAN. The objective of this paper is to review the main techniques for IAN preservation and to present 2 cases with the technique used by the author. Material and Methods: A systematic review was performed according to the PRISMA guidelines, apropos of two clinical cases reported in this study. The MEDLINE/PubMed and Scopus databases were searched. Several variables were considered and are presented in detail in the form of tables and figures. In addition, 2 case reports with NAI preservation techniques are presented. Results: 13 articles were finally obtained for analysis. 127 patients were evaluated, reporting mandibular resections associated with various pathologies. Various surgical techniques were used, all with the same goal of maintaining the IAN. In most of the patients, the maintenance of sensitivity was achieved, which was verified with different methods. Conclusions: Preservation of the IAN in maxillofacial surgical procedures where surgical resection of the mandibular bone has been performed is an alternative that has demonstrated successful results in terms of reducing postoperative sequelae and is currently positioned as a necessary and feasible procedure. (AU)

Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection.

Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs). Methods and results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. Conclusion: This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.

Dual-task kidney MR segmentation with transformers in autosomal-dominant polycystic kidney disease.

Autosomal-dominant polycystic kidney disease is a prevalent genetic disorder characterized by the development of renal cysts, leading to kidney enlargement and renal failure. Accurate measurement of total kidney volume through polycystic kidney segmentation is crucial to assess disease severity, predict progression and evaluate treatment effects. Traditional manual segmentation suffers from intra- and inter-expert variability, prompting the exploration of automated approaches. In recent years, convolutional neural networks have been employed for polycystic kidney segmentation from magnetic resonance images. However, the use of Transformer-based models, which have shown remarkable performance in a wide range of computer vision and medical image analysis tasks, remains unexplored in this area. With their self-attention mechanism, Transformers excel in capturing global context information, which is crucial for accurate organ delineations. In this paper, we evaluate and compare various convolutional-based, Transformers-based, and hybrid convolutional/Transformers-based networks for polycystic kidney segmentation. Additionally, we propose a dual-task learning scheme, where a common feature extractor is followed by per-kidney decoders, towards better generalizability and efficiency. We extensively evaluate various architectures and learning schemes on a heterogeneous magnetic resonance imaging dataset collected from 112 patients with polycystic kidney disease. Our results highlight the effectiveness of Transformer-based models for polycystic kidney segmentation and the relevancy of exploiting dual-task learning to improve segmentation accuracy and mitigate data scarcity issues. A promising ability in accurately delineating polycystic kidneys is especially shown in the presence of heterogeneous cyst distributions and adjacent cyst-containing organs. This work contribute to the advancement of reliable delineation methods in nephrology, paving the way for a broad spectrum of clinical applications.

Potentiating-antibiotic activity and absorption, distribution, metabolism, excretion and toxicity properties (ADMET) analysis of synthetic thiadiazines against multi-drug resistant (MDR) strains.

BACKGROUND: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. OBJECTIVES: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. METHODS: The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi-drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. RESULTS: There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti-inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi-drug resistant strains, indicating a possible synergistic action. CONCLUSIONS: Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti-inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out.

Multi-modal medical Transformers: A meta-analysis for medical image segmentation in oncology.

Multi-modal medical image segmentation is a crucial task in oncology that enables the precise localization and quantification of tumors. The aim of this work is to present a meta-analysis of the use of multi-modal medical Transformers for medical image segmentation in oncology, specifically focusing on multi-parametric MR brain tumor segmentation (BraTS2021), and head and neck tumor segmentation using PET-CT images (HECKTOR2021). The multi-modal medical Transformer architectures presented in this work exploit the idea of modality interaction schemes based on visio-linguistic representations: (i) single-stream, where modalities are jointly processed by one Transformer encoder, and (ii) multiple-stream, where the inputs are encoded separately before being jointly modeled. A total of fourteen multi-modal architectures are evaluated using different ranking strategies based on dice similarity coefficient (DSC) and average symmetric surface distance (ASSD) metrics. In addition, cost indicators such as the number of trainable parameters and the number of multiply-accumulate operations (MACs) are reported. The results demonstrate that multi-path hybrid CNN-Transformer-based models improve segmentation accuracy when compared to traditional methods, but come at the cost of increased computation time and potentially larger model size.

Neuroimmunology of rabies: New insights into an ancient disease.

Rabies is an ancient neuroinvasive viral (genus Lyssavirus, family Rhabdoviridae) disease affecting approximately 59,000 people worldwide. The central nervous system (CNS) is targeted, and rabies has a case fatality rate of almost 100% in humans and animals. Rabies is entirely preventable through proper vaccination, and thus, the highest incidence is typically observed in developing countries, mainly in Africa and Asia. However, there are still cases in European countries and the United States. Recently, demographic, increasing income levels, and the coronavirus disease 2019 (COVID-19) pandemic have caused a massive raising in the animal population, enhancing the need for preventive measures (e.g., vaccination, surveillance, and animal control programs), postexposure prophylaxis, and a better understanding of rabies pathophysiology to identify therapeutic targets, since there is no effective treatment after the onset of clinical manifestations. Here, we review the neuroimmune biology and mechanisms of rabies. Its pathogenesis involves a complex and poorly understood modulation of immune and brain functions associated with metabolic, synaptic, and neuronal impairments, resulting in fatal outcomes without significant histopathological lesions in the CNS. In this context, the neuroimmunological and neurochemical aspects of excitatory/inhibitory signaling (e.g., GABA/glutamate crosstalk) are likely related to the clinical manifestations of rabies infection. Uncovering new links between immunopathological mechanisms and neurochemical imbalance will be essential to identify novel potential therapeutic targets to reduce rabies morbidity and mortality.

Neglected no longer: Phylogenomic resolution of higher-level relationships in Solifugae.

Advanced sequencing technologies have expedited resolution of higher-level arthropod relationships. Yet, dark branches persist, principally among groups occurring in cryptic habitats. Among chelicerates, Solifugae ("camel spiders") is the last order lacking a higher-level phylogeny and have thus been historically characterized as "neglected [arachnid] cousins". Though renowned for aggression, remarkable running speed, and xeric adaptation, inferring solifuge relationships has been hindered by inaccessibility of diagnostic morphological characters, whereas molecular investigations have been limited to one of 12 recognized families. Our phylogenomic dataset via capture of ultraconserved elements sampling all extant families recovered a well-resolved phylogeny, with two distinct groups of New World taxa nested within a broader Paleotropical radiation. Divergence times using fossil calibrations inferred that Solifugae radiated by the Permian, and most families diverged prior to the Paleogene-Cretaceous extinction, likely driven by continental breakup. We establish Boreosolifugae new suborder uniting five Laurasian families, and Australosolifugae new suborder uniting seven Gondwanan families using morphological and biogeographic signal.

Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid ß peptide, ß catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.

Rabies virus variants from bats closely related to variants found in marmosets (Callithrix jacchus), a neglected source of human rabies infection in Brazil.

Rabies is a fatal viral zoonosis caused by rabies virus (RABV). RABV infects the central nervous system and triggers acute encephalomyelitis in both humans and animals. Endemic in the Brazilian Northeast region, RABV emergence in distinct wildlife species has been identified as a source of human rabies infection and as such, constitutes a public health concern. Here, we performed post-mortem RABV analyses of 144 encephalic tissues from bats sampled from January to July 2022, belonging to 15 different species. We identified phylogenetically distinct RABV from Phyllostomidae and Molossidae bats circulating in Northeastern Brazil. Phylogenetic clustering revealed the close evolutionary relationship between RABV viruses circulating in bats and variants hosted in white-tufted marmosets, commonly captured to be kept as pets and linked to human rabies cases and deaths in Brazil. Our findings underline the urgent need to implement a phylogenetic-scale epidemiological surveillance platform to track multiple RABV variants which may pose a threat to both humans and animals.

Interferome signature dynamics during the anti-dengue immune response: a systems biology characterization.

Dengue virus (DENV) infection manifests as a febrile illness with three distinct phases: early acute, late acute, and convalescent. Dengue can result in clinical manifestations with different degrees of severity, dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Interferons (IFNs) are antiviral cytokines central to the anti-DENV immune response. Notably, the distinct global signature of type I, II, and III interferon-regulated genes (the interferome) remains uncharacterized in dengue patients to date. Therefore, we performed an in-depth cross-study for the integrative analysis of transcriptome data related to DENV infection. Our systems biology analysis shows that the anti-dengue immune response is characterized by the modulation of numerous interferon-regulated genes (IRGs) enriching, for instance, cytokine-mediated signaling (e.g., type I and II IFNs) and chemotaxis, which is then followed by a transcriptional wave of genes associated with cell cycle, also regulated by the IFN cascade. The adjunct analysis of disease stratification potential, followed by a transcriptional meta-analysis of the interferome, indicated genes such as IFI27, ISG15, and CYBRD1 as potential suitable biomarkers of disease severity. Thus, this study characterizes the landscape of the interferome signature in DENV infection, indicating that interferome dynamics are a crucial and central part of the anti-dengue immune response.

Corrigendum to "Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities" [Heliyon 8 (11) (November 2022) Article e11368].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e11368.].

Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium.

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus). Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases. Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions.

Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Integrated control strategies for dengue, Zika, and Chikungunya virus infections.

Arboviruses are a major threat to public health in tropical regions, encompassing over 534 distinct species, with 134 capable of causing diseases in humans. These viruses are transmitted through arthropod vectors that cause symptoms such as fever, headache, joint pains, and rash, in addition to more serious cases that can lead to death. Among the arboviruses, dengue virus stands out as the most prevalent, annually affecting approximately 16.2 million individuals solely in the Americas. Furthermore, the re-emergence of the Zika virus and the recurrent outbreaks of chikungunya in Africa, Asia, Europe, and the Americas, with one million cases reported annually, underscore the urgency of addressing this public health challenge. In this manuscript we discuss the epidemiology, viral structure, pathogenicity and integrated control strategies to combat arboviruses, and the most used tools, such as vaccines, monoclonal antibodies, treatment, etc., in addition to presenting future perspectives for the control of arboviruses. Currently, specific medications for treating arbovirus infections are lacking, and symptom management remains the primary approach. However, promising advancements have been made in certain treatments, such as Chloroquine, Niclosamide, and Isatin derivatives, which have demonstrated notable antiviral properties against these arboviruses in vitro and in vivo experiments. Additionally, various strategies within vector control approaches have shown significant promise in reducing arbovirus transmission rates. These encompass public education initiatives, targeted insecticide applications, and innovative approaches like manipulating mosquito bacterial symbionts, such as Wolbachia. In conclusion, combatting the global threat of arbovirus diseases needs a comprehensive approach integrating antiviral research, vaccination, and vector control. The continued efforts of research communities, alongside collaborative partnerships with public health authorities, are imperative to effectively address and mitigate the impact of these arboviral infections on public health worldwide.

Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities.

Brazil experienced one of the most prolonged periods of school closures, and reopening could have exposed students to high rates of SARS-CoV-2 infection. However, the infection status of students and school workers at the time of the reopening of schools located in Brazilian cities is unknown. Here we evaluated viral carriage by RT-PCR and seroprevalence of anti-SARS-CoV-2 antibodies (IgM and IgG) by immunochromatography in 2259 individuals (1139 students and 1120 school workers) from 28 schools in 28 Brazilian cities. We collected the samples within 30 days after public schools reopened and before the start of vaccination campaigns. Most students (n = 421) and school workers (n = 446) had active (qRT-PCR + IgM- IgG- or qRT-PCR + IgM + IgG-/+) SARS-CoV-2 infection. Regression analysis indicated a strong association between the infection status of students and school workers. Furthermore, while 45% (n = 515) of the students and 37% (n = 415) of the school workers were neither antigen nor antibody positive in laboratory tests, 16% of the participants (169 students and 193 school workers) were oligosymptomatic, including those reinfected. These individuals presented mild symptoms such as headache, sore throat, and cough. Notably, most of the individuals were asymptomatic (83.9%). These results indicate that many SARS-CoV-2 infections in Brazilian cities during school reopening were asymptomatic. Thus, our study highlights the need to promote a coordinated public health effort to guarantee a safe educational environment while avoiding exacerbating pre-existent social inequalities in Brazil, reducing social, mental, and economic losses for students, school workers, and their families.

Terpenes as bacterial efflux pump inhibitors: A systematic review.

Managing antibiotic resistance is a significant challenge in modern pharmacotherapy. While molecular analyses have identified efflux pump expression as an essential mechanism underlying multidrug resistance, the targeted drug development has occurred slower. Thus, considering the verification that terpenes can enhance the activity of antibiotics against resistant bacteria, the present study gathered evidence pointing to these natural compounds as bacterial efflux pump inhibitors. A systematic search for manuscripts published between January 2007 and January 2022 was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and the following search terms: "Terpene"; AND "Efflux pump"; and "Bacteria." From a total of 101 articles found in the initial search, 41 were included in this review. Seventy-five different terpenes, 63 bacterial strains, and 22 different efflux pumps were reported, with carvacrol, Staphylococcus aureus SA-1199B, and NorA appearing most frequently mentioned terpene, bacterial strain, and efflux pump (EP), respectively. The Chi-Squared analysis indicated that terpenes are significantly effective EP inhibitors in Gram-positive and Gram-negative strains, with the inhibitory frequency significantly higher in Gram-positive strains. The results of the present review suggest that terpenes are significant efflux pump inhibitors and, as such, can be used in drug development targeting the combat of antibacterial resistance.

Vaccines against Emerging and Neglected Infectious Diseases: An Overview.

Neglected Tropical Diseases (NTDs) are a group of diseases that are highly prevalent in tropical and subtropical regions, and closely associated with poverty and marginalized populations. Infectious diseases affect over 1.6 billion people annually, and vaccines are the best prophylactic tool against them. Along with NTDs, emerging and reemerging infectious diseases also threaten global public health, as they can unpredictably result in pandemics. The recent advances in vaccinology allowed the development and licensing of new vaccine platforms that can target and prevent these diseases. In this work, we discuss the advances in vaccinology and some of the difficulties found in the vaccine development pipeline for selected NTDs and emerging and reemerging infectious diseases, including HIV, Dengue, Ebola, Chagas disease, malaria, leishmaniasis, zika, and chikungunya.