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ABSTRACTPremature infants lack a normal intestinal microbial community and also at risk of perinatal hypoxic-ischemic (HI) brain injury, which is considered to be one of the major factors for motor, sensory, and cognitive deficits. We hypothesized that neonatal gut microbiota composition modulated the immune reaction and severity of neonatal H-I brain injury. Neonatal C57BL/6J mouse pups were exposed to H-I protocol consisting of permanent left carotid artery ligation, followed by 8% hypoxia for 60 min. Microbial manipulation groups included 1) antibiotic treatment, E18 (maternal) to P5; 2) antibiotic treatment E18 to P5 + E. coli gavage; 3) antibiotic treatment E18 to P5 + B. infantis gavage; and 4) saline to pups with dams getting fresh water. The extent of brain injury and recovery was measured on MRI. Edematous injury volume was significantly higher in E. coli group than that in B. infantis group and in fresh water group. Gene expression in brains of pro-inflammatory cytokines (IL1β, IL6, IL2, TNF-α and toll-like receptors 2–6) were elevated to a greater extent in the E. coli group at P10, no injury, and at P13, 72 hours after H-I relative to sham control and B. infantis groups. Significant effects of microbiome and brain injury and interaction of these factors were found in abundance of major phyla. The neuroinflammatory response and brain injury after neonatal hypoxia-ischemia are affected by intestinal microbiota, providing opportunities for therapeutic intervention through targeting the early colonization and development of the gut microbiota.

En la selección mayor de Paraguay desde mediados del año 2020 se realizan perfiles por puestos que permiten entender un gold standard, y de esta manera comparar rápidamente perfiles de jugadores para relacionarlos con los modelos encontrados en la liga local. El objetivo de estudio fue determinar el rendimiento físico de los futbolistas de la liga local de Paraguay vs. de la Selección Nacional, relacionando el análisis por puesto entre marcadores de punta, marcadores centrales y extremos. La muestra estuvo constituida por 176 futbolistas profesionales; 149 del torneo local pertenecientes a 6 clubes de primera división, medidos con Electronic Performance and Tracking Systems (EPTS). Los datos de selección nacional correspondieron a 27 jugadores medidos en los partidos de competencia del Clasificatorio a Qatar 2022 y Copa América 2021. Los resultados indicaron que no existieron diferencias en velocidad máxima entre seleccionados y jugadores del torneo local. En distancia recorrida superior a 24 km/h, existió diferencia en los extremos en favor de los seleccionados. En distancia mayor a 18 km/h, no existió diferencia. En distancia de aceleración, tampoco existieron diferencias en los dos grupos analizados; por último, en distancia total recorrida, solo existió diferencia en marcadores centrales en favor del grupo local.

Global awareness of introduced species as one of the primary drivers of biodiversity change—causing environmental impacts, and economic and social effects—emphasizes the need to enhance our understanding of these species. Developing a comprehensive database will enable policymakers to identify global bioinvasion patterns and strengthen their capacity to manage them effectively. Aquatic mollusks play a crucial role in the ecosystems they inhabit, influencing food webs and nutrient cycling, and habitat formation and modification. They are also the dominant group in aquaculture, contributing significantly to the economy while also causing economic losses through macrofouling and posing health risks. Despite their importance, information on the introduction, establishment, and dispersal of mollusk species in South America remains scarce and is often confined to the grey literature. With the aim of organizing, increasing, and strengthening the knowledge of non-native and transplanted mollusks in general and aquatic mollusks in particular, 29 specialists in the introduced mollusks of South America, from seven countries, have been working collaboratively since 2016. Each member contributes expertise, data, and bibliographic resources to build the status of the introduced mollusks in South America and provide critical information to prevent future introductions and transplants. In aquatic environments, 41 non-native mollusk species and 18 transplanted species have been identified. Among them, the bivalve Limnoperna fortunei stands out with the greatest economic effect, while the gastropods Lymnaeidae and Thiaridae represent significant health concerns. Although this research represents a major step forward, it also highlights challenges such as the scarcity of taxonomic studies and the limited investigation of vast areas in South America. The information compiled in this review serves as a resource for researchers, policymakers, and the general public when addressing mollusk bioinvasions in South America.

Glioblastoma (GB) is a highly malignant brain tumor with a poor prognosis, with a median survival of only 14.6 months despite aggressive treatments. Resistance to chemotherapy, particularly temozolomide (TMZ), is a significant challenge. The DNA repair enzyme MGMT and glioblastoma stem cells (GSCs) often mediate this resistance. Recent studies highlight the therapeutic potential of natural compounds, particularly delphinidins, found in deep purple berries. Delphinidins are known for their ability to inhibit NF-κB signaling, a critical pathway for GB progression, chemoresistance, and MGMT expression. Our research demonstrates that glycosylated delphinidins have potential adjuvant use in the treatment of GB, offering a promising natural strategy to combat TMZ resistance. Specifically, we observed that delphinidin 3,5 di-glucoside has potent anticancer effects when used alone. Meanwhile, delphinidin 3 glucoside acted in synergy with temozolomide to decrease cell viability, highlighting its potential as an adjuvant. It also exerted a faster and more sustained inhibition of NF-κB, highlighting its potential for long-lasting therapeutic effects. These findings open new avenues for targeted therapies against glioblastoma, particularly to overcome treatment resistance.

Mercury (Hg) is a persistent pollutant highly bioaccumulated in the aquatic environment through the food chain reaching high concentration levels in the tissues of predator fishes. Among the relevant sources of anthropogenic mercury emissions in Latin America and the Caribbean (LAC), mining is one of the most important along with soil erosion due to deforestation and agricultural activities where pesticides are intensively used. Several reports have demonstrated an association between a fish-based diet with elevated Hg levels in the blood and neurotoxic effects in humans. In this systematic review with quantitative analysis data from 92 articles were compiled, providing evidence of Hg concentration in fishes that are commonly consumed in LAC. An assessment was conducted using three indices for health risk: the Minamata Initial Assessment (MIA), the Target Hazard Quotient (THQ), and the Meals per Week (MPW) index. Of the 410 fish species studied, 5.4% had concentrations above 0.95 μg g−1 of wet weight (ww), which is the recommended limit for Total Hg (THg) ingestion through fish consumption according to the MIA index, regardless of the water habitat (i.e., marine or freshwater). Additionally, the Target Hazard Quotient (THQ) calculation indicated high-risk values (THQ ≥ 1) in 15 out of the 19 countries studied, and very high-risk values (THQ ≥ 10) were obtained from Hg concentrations measured in 5 fish species inhabiting watersheds in Trinidad and Tobago, Suriname and Peru. Finally, recommendations on fish consumption were made based on the MPW index. This study reveals the need for updated biomonitoring studies of Hg concentrations in fish to perform more accurate human health risk analyses.

Autocracia e democracia se mesclam nos regimes políticos denominados de anocracia, diluem-se numa substância polimorfa, induzindo conscientemente os cidadãos à inconsciência, escamoteando a hipnose da aceitação passiva de práticas autoritárias. O texto traça um breve panorama dessas democracias parciais ou híbridas que revelam um cenário político no qual as elites econômicas e políticas fornecem os recursos necessários para a preservação do poder e para o incremento da militarização do controle social de forma que resta inviabilizada a preservação dos direitos mais elementares, porquanto territórios inteiros vivem sob o domínio do controle penal total e sem qualquer limite legal.

Abstract The Harpy Eagle (Harpia harpyja) is threatened with extinction throughout its distribution in the neotropical forests. In the Atlantic Forest, deforestation has reduced the number of suitable habitats, with only a few remnant forest fragments hosting active nests; currently, the only known nests in this region are in the Central Atlantic Forest Ecological Corridor (CAFEC), in Brazil. Little is known about Harpy Eagle diets in this region, despite this information being essential for developing effective conservation strategies. We classified the composition, frequency, richness, ecological attributes, and conservation status of the species that make up the Harpy Eagle’s diet in its last refuges in the CAFEC. Between 2017 and 2021, we collected and analyzed 152 prey remains and 285 camera trap photographs from seven active nests. We identified at least 16 mammal species (96.7%), one parrot and other bird remains (3.3%). The Harpy Eagle’s diet consisted mainly of medium-sized arboreal, folivorous, frugivorous, and diurnal mammals. Five prey species are currently threatened with extinction at global, six at national and seven at regional levels. The majority of the diet consists of Sapajus robustus, which is threatened, and Bradypus variegatus, which is not threatened. In addition to the effects of habitat loss and hunting, the Harpy Eagle may also suffer from the decline in the populations of their prey in the Atlantic Forest.

BackgroundChronic cerebral hypoperfusion (CCH) leads to memory and learning impairments associated with degeneration and gliosis in the hippocampus. Treatment with physical exercise carries different therapeutic benefits for each sex. We investigated the effects of acrobatic training on astrocyte remodeling in the CA1 and CA3 subfields of the hippocampus and spatial memory impairment in male and female rats at different stages of the two-vessel occlusion (2VO) model.MethodsWistar rats were randomly allocated into four groups of males and females: 2VO acrobatic, 2VO sedentary, sham acrobatic, and sham sedentary. The acrobatic training was performed for 4 weeks prior to the 2VO procedure. Brain samples were collected for morphological and biochemical analysis at 3 and 7 days after 2VO. The dorsal hippocampi were removed and prepared for Western blot quantification of Akt, p-Akt, COX IV, cleaved caspase-3, PARP, and GFAP. GFAP immunofluorescence was performed on slices of the hippocampus to count astrocytes and apply the Sholl's circle technique. The Morris water maze was run after 45 days of 2VO.ResultsAcutely, the trained female rats showed increased PARP expression, and the 2VO-trained rats of both sexes presented increased GFAP levels in Western blot. Training, mainly in males, induced an increase in the number of astrocytes in the CA1 subfield. The 2VO rats presented branched astrocytes, while acrobatic training prevented branching. However, the 2VO-induced spatial memory impairment was partially prevented by the acrobatic training.ConclusionAcrobatic training restricted the astrocytic remodeling caused by 2VO in the CA1 and CA3 subfields of the hippocampus. The improvement in spatial memory was associated with more organized glial scarring in the trained rats and better cell viability observed in females.

IntroductionDelays in prehospital care attributable to the call-taking process can often be traced back to miscommunication, including uncertainty around the call location. Geolocation applications have the potential to streamline the call-taking process by accurately identifying the caller's location.ObjectiveTo develop and validate an application to geolocate emergency calls and compare the response time of calls made via the application with those of conventional calls made to the Brazilian Medical Emergency System (Serviço de Atendimento Médico de Urgência-SAMU).MethodsThis study was conducted in two stages. First, a geolocating application for SAMU emergency calls (CHAMU192) was developed using a mixed methods approach based on design thinking and subsequently validated using the System Usability Scale (SUS). In the second stage, sending time of the geolocation information of the app was compared with the time taken to process information through conventional calls. For this, a hypothetical case control study was conducted with SAMU in the Maringá, Paraná, Brazil. A control group of 350 audio recordings of emergency calls from 2019 was compared to a set of test calls made through the CHAMU192 app. The CHAMU192 group consisted of 201 test calls in Maringá. In test calls, the location was obtained by GPS and sent to the SAMU communication system. Comparative analysis between groups was performed using the Mann-Whitney test.ResultsCHAMU192 had a SUS score of 90, corresponding to a "best imaginable" usability rating. The control group had a median response time of 35.67 seconds (26.00-48.12). The response time of the CHAMU192 group was 0.20 (0.15-0.24).ConclusionThe use of the CHAMU192 app by emergency medical services could significantly reduce response time. The results demonstrate the potential of app improving the quality and patient outcomes related to the prehospital emergency care services.

IntroductionFrailty is a geriatric syndrome frequently associated with executive dysfunction and white matter hyperintensities (WMH). But the relation between executive dysfunction and brain changes is poorly understood in frail subjects. Our hypothesis is that frontal-WMH mediates the association between frailty and executive dysfunction.MethodsA convenience sample of 113 subjects older than 65 years without dementia was studied with neuropsychological test, a structured clinical interview, physical examination and brain MRI. They were classified as robust or pre-frail and frail using the frailty phenotype score (0–5). The frontal WMH (F-WMH) were manually graduated (0–6) using the “Age-Related White Matter Changes score” from FLAIR sequences at a 3 Tesla brain MRI. A mediation analysis was done for testing whether F-WMH could act as a link factor between frailty phenotype score and executive dysfunction.ResultsThe group’s mean age was 74 ± 6 years, subjects with higher frailty score had more depressive symptoms and worse performance in executive function tests. A regression analysis that explained 52% of the variability in executive functions, revealed a significant direct effect of frailty score (Standardized βcoeff [95% CI] −0.201, [−0.319, −0.049], and F-WMH (−0.152[−0.269, −0.009]) on executive functions, while the F-WMH showed a small partial mediation effect between frailty and executive functions (−0.0395, [−0.09, −0.004]).DiscussionFrontal matter hyperintensities had a small mediation effect on the association between frailty and executive dysfunction, suggesting that other neuropathological and neurofunctional changes might also be associated with executive dysfunction in frail subjects.

Engineered heart tissues (EHTs) have shown great potential in recapitulating tissue organization, functions, and cell-cell interactions of the human heart in vitro. Currently, multiple EHT platforms are used by both industry and academia for different applications, such as drug discovery, disease modelling, and fundamental research. The tissues' contractile force, one of the main hallmarks of tissue function and maturation level of cardiomyocytes, can be read out from EHT platforms by optically tracking the movement of elastic pillars induced by the contractile tissues. However, existing optical tracking algorithms which focus on calculating the contractile force are customized and platform-specific, often not available to the broad research community, and thus hamper head-to-head comparison of the model output. Therefore, there is the need for robust, standardized and platform-independent software for tissues' force assessment. To meet this need, we developed ForceTracker: a standalone and computationally efficient software for analyzing contractile properties of tissues in different EHT platforms. The software uses a shape-detection algorithm to single out and track the movement of pillars' tips for the most common shapes of EHT platforms. In this way, we can obtain information about tissues' contractile performance. ForceTracker is coded in Python and uses a multi-threading approach for time-efficient analysis of large data sets in multiple formats. The software efficiency to analyze circular and rectangular pillar shapes is successfully tested by analyzing different format videos from two EHT platforms, developed by different research groups. We demonstrate robust and reproducible performance of the software in the analysis of tissues over time and in various conditions. ForceTracker's detection and tracking shows low sensitivity to common incidental defects, such as alteration of tissue shape or air bubbles. Detection accuracy is determined via comparison with manual measurements using the software ImageJ. We developed ForceTracker as a tool for standardized analysis of contractile performance in EHT platforms to facilitate research on disease modeling and drug discovery in academia and industry. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is a highly malignant brain tumor with a poor prognosis, with a median survival of only 14.6 months despite aggressive treatments. Resistance to chemotherapy, particularly temozolomide (TMZ), is a significant challenge. The DNA repair enzyme MGMT and glioblastoma stem cells (GSCs) often mediate this resistance. Recent studies highlight the therapeutic potential of natural compounds, particularly delphinidins, found in deep purple berries. Delphinidins are known for their ability to inhibit NF-κB signaling, a critical pathway for GB progression, chemoresistance, and MGMT expression. Our research demonstrates that glycosylated delphinidins have potential adjuvant use in the treatment of GB, offering a promising natural strategy to combat TMZ resistance. Specifically, we observed that delphinidin 3,5 di-glucoside has potent anticancer effects when used alone. Meanwhile, delphinidin 3 glucoside acted in synergy with temozolomide to decrease cell viability, highlighting its potential as an adjuvant. It also exerted a faster and more sustained inhibition of NF-κB, highlighting its potential for long-lasting therapeutic effects. These findings open new avenues for targeted therapies against glioblastoma, particularly to overcome treatment resistance. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and highly malignant brain tumor in adults. New targeted therapeutic approaches are imperative. EGFRvIII has appealing therapeutic targets using monoclonal antibodies. Thus, endeavors toward developing new mAbs therapies for GBM capable of targeting the tumor EGFRvIII biomarker must prevail to improve the patient's prognosis. Here, we isolated and characterized an anti-EGFRvIII vNAR from a non-immune freshwater stingray mixed library, termed vNAR R426. The vNAR R426 and pEGFRvIII interaction was demonstrated by molecular docking and molecular dynamics, and the recognition of EGFRvIII in vitro was further confirmed by cell immunofluorescence staining. Moreover, the vNAR R426 was shown to be an effective cisplatin drug carrier in the U87-MG glioma cell line. The cisplatin-coupled vNAR demonstrated highly significant differences when compared to free CDDP at 72 h. Notably, the cisplatin-vNAR carrier achieved better efficacy in the U87-MG cell line. Thus, we described the vNAR R426 internalization by receptor-mediated endocytosis and the subsequent COPI-mediated nuclear translocation of EGFRvIII and highlighted the importance of this shuttle mechanism to enhance the targeted delivery of cisplatin within the glioma cell's nucleus and improved cytotoxic effect. In conclusion, vNAR R426 could be a potential therapeutic carrier for EGFRvIII-targeted glioblastoma and cancer therapies. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most prevalent and fatal form of primary brain tumors. New targeted therapeutic strategies for this type of tumor are imperative given the dire prognosis for glioblastoma patients and the poor results of current multimodal therapy. Previously reported drawbacks of antibody-based therapeutics include the inability to translocate across the blood–brain barrier and reach intracellular targets due to their molecular weight. These disadvantages translate into poor target neutralization and cancer maintenance. Unlike conventional antibodies, vNARs can permeate tissues and recognize conformational or cryptic epitopes due to their stability, CDR3 amino acid sequence, and smaller molecular weight. Thus, vNARs represent a potential antibody format to use as intrabodies or soluble immunocarriers. This review comprehensively summarizes key intracellular pathways in glioblastoma cells that induce proliferation, progression, and cancer survival to determine a new potential targeted glioblastoma therapy based on previously reported vNARs. The results seek to support the next application of vNARs as single-domain antibody drug-conjugated therapies, which could overcome the disadvantages of conventional monoclonal antibodies and provide an innovative approach for glioblastoma treatment.