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Glioblastomas (GBM) are aggressive tumors known for their heterogeneity, rapid proliferation, treatment resistance, and extensive vasculature. Angiogenesis, the formation of new vessels, involves endothelial cell (EC) migration and proliferation. Various extracellular matrix (ECM) molecules regulate EC survival, migration, and proliferation. Culturing human brain EC (HBMEC) on GBM-derived ECM revealed a decrease in EC numbers compared to controls. Through in silico analysis, we explored ECM gene expression differences between GBM and brain normal glia cells and the impact of GBM microenvironment on EC ECM transcripts. ECM molecules such as collagen alpha chains (COL4A1, COL4A2, p < 0.0001); laminin alpha (LAMA4), beta (LAMB2), and gamma (LAMC1) chains (p < 0.0005); neurocan (NCAN), brevican (BCAN) and versican (VCAN) (p < 0.0005); hyaluronan synthase (HAS) 2 and metalloprotease (MMP) 2 (p < 0.005); MMP inhibitors (TIMP1-4, p < 0.0005), transforming growth factor beta-1 (TGFB1) and integrin alpha (ITGA3/5) (p < 0.05) and beta (ITGB1, p < 0.0005) chains showed increased expression in GBM. Additionally, GBM-influenced EC exhibited elevated expression of COL5A3, COL6A1, COL22A1 and COL27A1 (p < 0.01); LAMA1, LAMB1 (p < 0.001); fibulins (FBLN1/2, p < 0.01); MMP9, HAS1, ITGA3, TGFB1, and wingless-related integration site 9B (WNT9B) (p < 0.01) compared to normal EC. Some of these molecules: COL5A1/3, COL6A1, COL22/27A1, FBLN1/2, ITGA3/5, ITGB1 and LAMA1/B1 (p < 0.01); NCAN, HAS1, MMP2/9, TIMP1/2 and TGFB1 (p < 0.05) correlated with GBM patient survival. In conclusion, this study identified both established and novel ECM molecules regulating GBM angiogenesis, suggesting NCAN and COL27A1 are new potential prognostic biomarkers for GBM., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Liquid biopsy is a non-invasive method used to detect cancer and monitor treatment responses by analyzing blood or other bodily fluids for cancer biomarkers. Meningiomas are the most common primary central nervous system tumors, and biomarkers play a crucial role in their diagnosis, prognosis, and treatment monitoring. The World Health Organization (WHO) classifies meningiomas based on tumor grades and molecular alterations in genes such as in NF2, AKT1, TRAF7, SMO, PIK3CA, KLF4, SMARCE1, BAP1, H3K27me3, TERT promoter, and CDKN2A/B. Liquid biopsy, specifically cell-free DNA (cfDNA) analysis, has shown potential for monitoring meningiomas as it can detect ctDNA release in the blood, unaffected by the blood-brain barrier. MicroRNAs (miRNAs) have also been found to be deregulated in various cancers, including meningiomas, presenting potential as diagnostic biomarkers. Additionally, studying cytokines in the tumor microenvironment may aid in establishing prognostic or diagnostic panels for meningiomas., Methods: In the present study we analyzed the DNA coming from both the plasma and tumor samples, in addition to analyze miRNA-21 and cytokines in the plasma of 28 meningioma patients., Discussion and Conclusion: Our findings indicate that the detection of ctDNA in the plasma of meningioma patients is feasible. However, it's important to note that certain challenges persist when comparing plasma DNA analysis to that of tumor tissues. In our study, we observed a paired identification of mutations in only one patient, highlighting the complexities involved. Furthermore, we successfully identified miR-21 and cytokines in the plasma samples. Notably, our analysis of Interleukin 6 (IL-6) unveiled higher expression in the clear cell subtype compared to the other types. Despite the ongoing research, the clinical implementation of liquid biopsy in meningiomas remains somewhat limited. Nevertheless, our promising results underscore the need for further investigation., Competing Interests: FA was employed by Rede D'Or. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor PG declared a past collaboration with the author VM-N., (Copyright © 2024 Aran, Lyra Miranda, Heringer, Carvalho da Fonseca, Andreiuolo, Chimelli, Devalle, Niemeyer Filho and Moura-Neto.)

Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca 2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences., (© 2023 Wiley Periodicals LLC.)

The inner ear, the organ of equilibrium and hearing, has an extraordinarily complex and intricate arrangement. It contains highly specialized structures meticulously tailored to permit auditory processing. However, hearing also relies on both peripheral and central pathways responsible for the neuronal transmission of auditory information from the cochlea to the corresponding cortical regions. Understanding the anatomy and physiology of all components forming the auditory system is key to better comprehending the pathophysiology of each disease that causes hearing impairment. In this narrative review, the authors focus on the pathophysiology as well as on cellular and molecular mechanisms that lead to hearing loss in different neonatal infectious diseases. To accomplish this objective, the morphology and function of the main structures responsible for auditory processing and the immune response leading to hearing loss were explored. Altogether, this information permits the proper understanding of each infectious disease discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Capra, DosSantos, Sanz, Acosta Filha, Nunes, Heringer, Ximenes-da-Silva, Pessoa, de Mattos Coelho-Aguiar, da Fonseca, Mendes, da Rocha, Devalle, Niemeyer Soares Filho and Moura-Neto.)

Chikungunya virus (CHIKV) infection causes intense cytokine/chemokine inflammatory responses and debilitating joint pain. Indoleamine2,3-dioxygenase 1 (IDO-1) is an enzyme that initiates the tryptophan degradation that is important in initial host innate immune defense against infectious pathogens. Besides that, IDO-1 activation acts as a regulatory mechanism to prevent overactive host immune responses. In this study, we evaluated IDO-1 activity and cytokine/chemokine patterns in CHIKV patients. Higher IDO-1 (Kyn/Trp ratio) activation was observed during the early acute phase of CHIKV infection and declined in the chronic phase. Importantly, increased concentrations of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Interferon γ (IFN-γ), C-C motif chemokine ligand 2/Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and C-X-C motif chemokine ligand 10/Interferon Protein-10 (CXCL10/IP-10) were found in the acute phase of infection, while C-C motif chemokine ligand 4/Macrophage Inflammatory Protein 1 β (CCL4/MIP-1β) was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis had significantly higher concentrations of CCL4/MIP-1β compared to patients without arthritis. Taken together, these data demonstrated increased IDO-1 activity, possibly exerting both antiviral effects and regulating exacerbated inflammatory responses. CCL4/MIP-1β may have an important role in the persistent inflammation and arthritic symptoms following chikungunya infection.

Purpose: RAS genes are among the most frequently mutated genes in cancer, where their mutation frequency varies according to the distinct RAS isoforms and tumour types. Despite occurring more prevalent in malignant tumours, RAS mutations were also observed in few benign tumours. Pituitary adenomas are examples of benign tumours which vary in size and aggressiveness. The present study was performed to investigate, via liquid biopsy and tissue analysis, the presence of K-RAS mutations in a pituitary macroadenoma., Methods: Molecular analysis was performed to investigate K-RAS mutations using the droplet digital PCR (ddPCR) method by evaluating both plasma (liquid biopsy) and the solid tumour of a patient diagnosed with a giant clinically non-functioning pituitary tumour., Results: The patient underwent surgical resection due to visual loss, and the histopathological analysis showed a gonadotrophic pituitary macroadenoma. The molecular analysis revealed the presence of mutant K-RAS both in the plasma and in the tumour tissue which, to our knowledge, has not been previously reported in the literature., Conclusion: Our findings highlight the exceptional capacity of the digital PCR in detecting low frequency mutations (below 1%), since we detected, for the first time, K-RAS mutations in pituitary macroadenoma. The potential impact of K-RAS mutations in these tumours should be further investigated., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bone sarcomas, although rare, are associated with significant morbidity and mortality. The most frequent primary bone cancers include osteosarcoma, chondrosarcoma and Ewing sarcoma. The treatment approaches are heterogeneous and mainly chosen based on precise tumour staging. Unfortunately, clinical outcome has not changed significantly in over 30 years and tumour grade is still the best prognosticator of metastatic disease and survival. An option to improve this scenario is to identify molecular biomarkers in the early stage of the disease, or even before the disease onset. Blood-based liquid biopsies are a promising, non-invasive way to achieve this goal and there are an increasing number of studies which investigate their potential application in bone cancer diagnosis, prognosis and personalised therapy. This review summarises the interplay between clinical and molecular aspects of the three main bone sarcomas, alongside biomarker discovery and promising applications of liquid biopsy in each tumour context., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Circulating tumor DNA (ctDNA) in fluids has gained attention because ctDNA seems to identify tumor-specific abnormalities, which could be used for diagnosis, follow-up of treatment, and prognosis: the so-called liquid biopsy. Liquid biopsy is a minimally invasive approach and presents the sum of ctDNA from primary and secondary tumor sites. It has been possible not only to quantify the amount of ctDNA but also to identify (epi)genetic changes. Specific mutations in genes have been identified in the plasma of patients with several types of cancer, which highlights ctDNA as a possible cancer biomarker. However, achieving detectable concentrations of ctDNA in body fluids is not an easy task. ctDNA fragments present a short half-life, and there are no cut-off values to discriminate high and low ctDNA concentrations. Here, we discuss the use of ctDNA as a cancer biomarker, the main methodologies, the inherent difficulties, and the clinical predictive value of ctDNA., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Currently, Brazil lives a triple arboviruses epidemic (DENV, ZIKV and CHIKV) making the differential diagnosis difficult for health professionals. Here, we aimed to investigate chikungunya cases and the possible occurrence of co-infections during the epidemic in Amapá (AP) that started in 2014 when the first autochthonous cases were reported and in Rio de Janeiro (RJ) in 2016. We further performed molecular characterization and genotyping of representative strains. In AP, 51.4% of the suspected cases were confirmed for CHIKV, 71.0% (76/107). Of those, 24 co-infections by CHIKV/DENV, two by CHIKV/DENV-1, and two by CHIKV/DENV-4 were observed. In RJ, 76.9% of the suspected cases were confirmed for CHIKV and co-infections by CHIKV/DENV ( n = 8) and by CHIKV/ZIKV ( n = 17) were observed. Overall, fever, arthralgia, myalgia, prostration, edema, exanthema, conjunctival hyperemia, lower back pain, dizziness, nausea, retroorbital pain, and anorexia were the predominating chikungunya clinical symptoms described. All strains analyzed from AP belonged to the Asian genotype and no amino acid changes were observed. In RJ, the East-Central-South-African genotype (ECSA) circulation was demonstrated and no E1-A226V mutation was observed. Despite this, an E1-V156A substitution was characterized in two samples and for the first time, the E1-K211T mutation was reported in all samples analyzed.

Background: Dengue viruses (DENV) have emerged and reemerged in Brazil in the past 30 years causing explosive epidemics. The disease may range from clinically asymptomatic infections to severe and fatal outcomes. We aimed to describe the epidemiological, clinical and laboratorial aspects of the dengue fatal cases received by a Regional Reference Laboratory, Brazil in 30 years., Methods: A total of 1047 suspected fatal dengue cases were received from 1986 to 2015 and analyzed in the Laboratory of Flavivirus, FIOCRUZ. Suspected cases were submitted to viral detection, serological and molecular methods for cases confirmation. Influence of gender, age, serotype and type of infection (primary/secondary) on death outcome, as well the interactions between serotype and age or infection and age and type of infection were also studied., Results: A total of 359 cases (34.2%) were confirmed and DENV-1 (11.1%), DENV-2 (43.9%), DENV-3 (32.8%) and DENV-4 (13.7%) were detected. Overall, fatal cases occurred more often in primary infections (59.3%, p = 0.001). However, in 2008, fatal cases were mainly associated to secondary infections (p = 0.003). In 2008 and 2011, deaths were more frequent on children and those infected by DENV-2 presented a higher risk for fatal outcome. Moreover, children with secondary infections had a 4-fold higher risk for death., Conclusions: Dengue is a multifactorial disease and, factors such as viral strain/serotype, occurrence of secondary infections and co-morbidities may lead to a severe outcome. However, the high dengue incidence and transmission during epidemics, such as those observed in Brazil may overwhelm and collapse the public health services, potentially impacting on increased disease severity and mortality.

Dengue is a worldwide problem characterized by a multifactorial pathogenesis. Considering the viral components, it is known that high viremia or high levels of the secreted nonstructural protein 1 (NS1) may be associated with a more severe disease. We aimed to characterize the NS1 antigenemia and viremia in dengue fatal and non-fatal cases, as potential markers of progression to a fatal outcome. NS1 antigenemia and viremia were determined in Brazilian dengue fatal cases ( n = 40) and non-fatal cases ( n = 40), representative of the four dengue virus (DENV) serotypes. Overall, the fatal cases presented higher NS1 levels and viremia. Moreover, the fatal cases from secondary infections showed significantly higher NS1 levels than the non-fatal ones. Here, irrespective of the disease outcome, DENV-1 cases presented higher NS1 levels than the other serotypes. However, DENV-2 and DENV-4 fatal cases had higher NS1 antigenemia than the non-fatal cases with the same serotype. The viremia in the fatal cases was higher than in the non-fatal ones, with DENV-3 and DENV-4 presenting higher viral loads. Viral components, such as NS1 and viral RNA, may be factors influencing the disease outcome. However, the host immune status, comorbidities, and access to adequate medical support cannot be ruled out as interfering in the disease outcome.

The increase in severe dengue (SD) cases has caused great impact on public health and has concerned authorities of countries where the disease is endemic and epidemics reach high proportions. The recognition of progression signs of this severe disease during the initial febrile phase can be difficult, since the symptoms are often indistinguishable from other febrile diseases. The aim of this study was to evaluate the clinical manifestations and laboratory findings in patients from two dengue outbreaks and their association with the disease. The study was conducted in patients ( n = 153) with signs and symptoms consistent with dengue occurred during two distinct epidemics, 2010 and 2013, in the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. According to the 2009 World Health Organization criteria, patients were classified as dengue without warning signs ([DwoWS] 60.6%, 57/94), dengue with warning signs ([DwWS] 30.9%, 29/94), and SD (4.25%, 4/94). Patients with DwWS/SD presented lower platelet and leukocyte counts and higher transaminase levels when compared with the DwoWS ones. Interestingly, patients from the epidemic of 2010 caused by dengue virus 2 (DENV-2) had lower platelet counts than patients of the 2013 epidemic caused by DENV-4. Furthermore, plasma leakage, gastrointestinal bleeding, and pleural effusion, hallmarks for a more severe disease, were also more frequently observed in those cases. Although previous studies may have extensively reported the wide range of the clinical aspects of dengue, the characterization of DENV-4 is desirable considering the burden of the disease during epidemics, especially for the health units and hospitals performing patient's management.

Background: Due to the populations' susceptibility, DENV-4 introduction in 2010 led to the occurrence of explosive epidemics in the following years in Brazil. In 2011, DENV-4 was identified in Rio de Janeiro (RJ) and it was prevalent in 2012 and 2013. Here, we aimed to characterize clinical, epidemiological and laboratorial aspects of DENV-4 cases after this serotype introduction in an endemic scenario., Methods: Dengue suspected cases (n = 3727) were received and analyzed from January 2011 to December 2013, during outbreaks occurred in RJ, Brazil. Samples were submitted to virological, serological and molecular methods for case confirmation. DENV-4 cases (n = 705) were characterized according to the type of infection, disease severity and, viremia levels and NS1 antigenemia were accessed. Representative strains were partial sequenced for genotyping., Results: DENV-4 was identified in 44.2% (705/1593) of dengue positive cases, virus isolated in 48.7% of the cases. Anti-DENV IgM was detected in 39.4% of the cases, however an increased detection was observed in cases with ≥4 days of symptoms (57.0%). NS1 antigen was identified in 41.5% of DENV-4 cases however, after immune complexes dissociation, the detection significantly increased (87.6%). Females were more affected than males, so did children aged 11-15 years old. Primary cases were more frequently observed than secondary ones and most of them were classified as dengue. No differences on NS1 antigenemia and viraemia within the groups were observed. Despite the higher frequency of severe disease on individuals >65 years old, no differences were observed among the groups and type of infection. However, DENV-4 fatal cases were more frequent on secondary infections (57.1%). DENV-4 Genotype II was identified with a probable origin from Venezuela and Colombia., Conclusions: It has been shown that laboratorial diagnosis is still a reliable tool for the disease surveillance, detecting and confirming emerging epidemics. Despite the occurrence of secondary infections, most DENV-4 cases presented a mild disease. As RJ is endemic for dengue, high rates of secondary infections would be expected. Despite the existence of two genotypes, only Genotype II was identified in our study.

We present a novel approach for analyzing two-dimensional (2D) flow field data based on the idea of invariant moments. Moment invariants have traditionally been used in computer vision applications, and we have adapted them for the purpose of interactive exploration of flow field data. The new class of moment invariants we have developed allows us to extract and visualize 2D flow patterns, invariant under translation, scaling, and rotation. With our approach one can study arbitrary flow patterns by searching a given 2D flow data set for any type of pattern as specified by a user. Further, our approach supports the computation of moments at multiple scales, facilitating fast pattern extraction and recognition. This can be done for critical point classification, but also for patterns with greater complexity. This multi-scale moment representation is also valuable for the comparative visualization of flow field data. The specific novel contributions of the work presented are the mathematical derivation of the new class of moment invariants, their analysis regarding critical point features, the efficient computation of a novel feature space representation, and based upon this the development of a fast pattern recognition algorithm for complex flow structures.

Forty-four brackets were bonded "in vivo" using cotton roll and rubber dam isolation. Maxillary and mandibular premolars, to be extracted for orthodontic reasons, were used in this study. After bonding, the teeth were retained in the mouth for at least 30 days. They were extracted using surgical elevators. After extraction, the teeth were secured in plastic rings using gypsum and kept in water for 7 days until debonding. A Universal Instron Machine was used to produce a shear force at a speed of 0.1 cm/min until each bracket was removed. No statistically significant differences for debonding strength were observed between the two types of isolation, nor between the buccal and palatal surfaces of the teeth. One hundred percent of the failures occurred at the bracket/composite interface.