In light of Medical Hydrology, thermal waters (TW) are all-natural mineral waters that emerge inside a thermal resort and have therapeutic applications. Their beneficial effect has been empirically ...recognized for centuries, being indicated for symptom alleviation and/or treatment of several diseases, almost all associated with inflammation. Indeed, an anti-inflammatory effect has been attributed to many different Portuguese TW but there is no scientific validation supporting this empiric knowledge. In the present study, we aimed to investigate the anti-inflammatory properties of 14 TW pertaining to thermal centers located in the Central Region of Portugal, and grouped according to their ionic profile. Mouse macrophage cells stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, were exposed to culture medium prepared in TW. Metabolism, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression levels and the scavenging capacity of TW, were investigated in vitro. 11 out of 14 TW reduced NO production and/or iNOS expression, and/or scavenging activity, in macrophages exposed to LPS. The sulphated/calcic TW did not show any effect on at least one of the inflammatory parameters evaluated. Two sulphurous/bicarbonate/sodic TW and the sulphurous/chlorinated/sodic TW promoted an increase in NO production and/or iNOS expression. Our results validate, for the first time, the anti-inflammatory properties of Portuguese TW, supporting their therapeutic use in the treatment of inflammation-related diseases and promoting their putative application in cosmetic products and medical devices.
The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Aims
Brazil ranks high in the number of coronavirus disease 19 (COVID‐19) cases and the COVID‐19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated ...conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID‐19. In order to follow biosafety recommendations, we used ultrasound‐guided minimally invasive autopsy (MIA‐US), and we present the results of 10 initial autopsies.
Methods and results
We used MIA‐US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis.
Conclusions
MIA‐US is safe and effective for the study of severe COVID‐19. Our findings show that COVID‐19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.
Although it is well established that platelet-activated receptor (PAF) and protease-activated receptor 2 (PAR2) play a pivotal role in the pathophysiology of lung and airway inflammatory diseases, a ...role for a PAR2-PAFR cooperation in lung inflammation has not been investigated. Here, we investigated the role of PAR2 in PAF-induced lung inflammation and neutrophil recruitment in lungs of BALB/c mice. Mice were pretreated with the PAR2 antagonist ENMD1068, PAF receptor (PAFR) antagonist WEB2086, or aprotinin prior to intranasal instillation of carbamyl-PAF (C-PAF) or the PAR2 agonist peptide SLIGRL-NH
(PAR2-AP). Leukocyte infiltration in bronchoalveolar lavage fluid (BALF), C-X-C motif ligand 1 (CXCL)1 and CXCL2 chemokines, myeloperoxidase (MPO), and N-acetyl-glycosaminidase (NAG) levels in BALF, or lung inflammation were evaluated. Intracellular calcium signaling, PAFR/PAR2 physical interaction, and the expression of PAR2 and nuclear factor-kappa B (NF-КB, p65) transcription factor were investigated in RAW 264.7 cells stimulated with C-PAF in the presence or absence of ENMD1068. C-PAF- or PAR2-AP-induced neutrophil recruitment into lungs was inhibited in mice pretreated with ENMD1068 and aprotinin or WEB2086, respectively. PAR2 blockade impaired C-PAF-induced neutrophil rolling and adhesion, lung inflammation, and production of MPO, NAG, CXCL1, and CXCL2 production in lungs of mice. PAFR activation reduced PAR2 expression and physical interaction of PAR2 and PAFR; co-activation is required for PAFR/PAR2 physical interaction. PAR2 blockade impaired C-PAF-induced calcium signal and NF-κB p65 translocation in RAW 264.7 murine macrophages. This study provides the first evidence for a cooperation between PAFR and PAR2 mediating neutrophil recruitment, lung inflammation, and macrophage activation.
Land‐cover change and ecosystem degradation may lead to biotic homogenization, yet our understanding of this phenomenon over large spatial scales and different biotic groups remains weak. We used a ...multi‐taxa dataset from 335 sites and 36 heterogeneous landscapes in the Brazilian Amazon to examine the potential for landscape‐scale processes to modulate the cumulative effects of local disturbances. Biotic homogenization was high in production areas but much less in disturbed and regenerating forests, where high levels of among‐site and among‐landscape β‐diversity appeared to attenuate species loss at larger scales. We found consistently high levels of β‐diversity among landscapes for all land cover classes, providing support for landscape‐scale divergence in species composition. Our findings support concerns that β‐diversity has been underestimated as a driver of biodiversity change and underscore the importance of maintaining a distributed network of reserves, including remaining areas of undisturbed primary forest, but also disturbed and regenerating forests, to conserve regional biota.
This study evaluated the effect of dentin pretreatment with the polyphenols quercetin and resveratrol on the resin‐dentin microtensile bonding strength (μTBS) and collagen fibrils stability of the ...adhesive interface. Different concentrations (100, 250, 500, or 1,000 μg ml−1) of quercetin or resveratrol, or a mixture of quercetin and resveratrol (3:1, 1:1, 1:3; vol:vol), as well as distilled water or 2% chlorhexidine digluconate, were applied to etched dentin. Then, a two‐step etch‐and‐rinse adhesive was applied followed by composite restoration. Measurements of resin–dentin μTBS were made after 1 and 120 d. The stability of collagen fibrils in the hybrid layer was evaluated using transmission electron microscopy. The Student's t‐test and two‐way factorial anova with Tukey's test were used to analyze the effects of dentin pretreatment and storage time on μTBS values. Comparisons between μTBS measurements made on 1 and 120 d showed that resveratrol had the best performance, with significantly higher μTBS values after 120 d for all concentrations of resveratrol tested. Quercetin pretreatment resulted in a significant rise of μTBS when used at concentrations of 100 and 500 μg ml−1. Quercetin + resveratrol at the ratio of 1:1 performed better than when used at ratios of either 3:1 or 1:3. Resveratrol might represent a potential approach to achieve desirable bonding stability and reduce the frequent replacement of composite restorations.
The artificial intelligence (AI) tools based on large-language models may serve as a demonstration that we are reaching a groundbreaking new paradigm in which machines themselves will generate ...knowledge autonomously. This statement is based on the assumption that the ability to master natural languages is the ultimate frontier for this new paradigm and perhaps an essential step to achieving the so-called general artificial intelligence. Autonomous knowledge generation implies that a machine will be able, for instance, to retrieve and understand the contents of the scientific literature and provide interpretations for existing data, allowing it to propose and address new scientific problems. While one may assume that the continued development of AI tools exploiting large-language models, with more data used for training, may lead these systems to learn autonomously, this learning can be accelerated by devising human-assisted strategies to deal with specific tasks. For example, strategies may be implemented for AI tools to emulate the analysis of multivariate data by human experts or in identifying and explaining patterns in temporal series. In addition to generic AI tools, such as Chat AIs, one may conceive personal AI agents, potentially working together, that are likely to serve end users in the near future. In this perspective paper, we discuss the development of this type of agent, focusing on its architecture and requirements. As a proof-of-concept, we exemplify how such an AI agent could work to assist researchers in materials sciences.
This study was designed to characterize morphologic stages during neuroma development post amputation with an eye toward developing better treatment strategies that intervene before neuromas are ...fully formed. Right forelimbs of 30 Sprague Dawley rats were amputated and limb stumps were collected at 3, 7, 28, 60 and 90 Days Post Amputation (DPA). Morphology of newly formed nerves and neuromas were assessed via general histology and neurofilament protein antibody staining. Analysis revealed six morphological characteristics during nerve and neuroma development; 1) normal nerve, 2) degenerating axons, 3) axonal sprouts, 4) unorganized bundles of axons, 5) unorganized axon growth into muscles, and 6) unorganized axon growth into fibrotic tissue (neuroma). At early stages (3 & 7 DPA) after amputation, normal nerves could be identified throughout the limb stump and small areas of axonal sprouts were present near the site of injury. Signs of degenerating axons were evident from 7 to 90 DPA. From day 28 on, variability of nerve characteristics with signs of unorganized axon growth into muscle and fibrotic tissue and neuroma formation became visible in multiple areas of stump tissue. These pathological features became more evident on days 60 and 90. At 90 DPA frank neuroma formation was present in all stump tissue. By following nerve regrowth and neuroma formation after amputation we were able to identify 6 separate histological stages of nerve regrowth and neuroma development. Axonal regrowth was observed as early as 3 DPA and signs of unorganized axonal growth and neuroma formation were evident by 28 DPA. Based on these observations we speculate that neuroma treatment and or prevention strategies might be more successful if targeted at the initial stages of development and not after 28 DPA.
Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used ...microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity.
To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.
In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.
AIMS: To evaluate the ability of Candida parapsilosis and Candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from Brazilian red propolis (BZP‐BRP) as ...compared to fluconazole (FLC). To investigate possible synergy between BZP‐BRP and FLC and anidulafungin (AND). METHODS AND RESULTS: To analyse the development of resistance, isolates susceptible to these antifungals were cultured in increasing concentrations of FLC and BZP‐BRP. The increase in FLC minimum inhibitory concentration for all isolates was evident and the majority developed resistance, whereas none isolated became less susceptible to BZP‐BRP. Synergism was investigated by checkerboard method. BZP‐BRP demonstrated synergy with FLC and indifference with AND for most isolates. CONCLUSIONS: In conclusion, the synergism observed with FLC suggests that BZP‐BRP could be a possible therapeutic strategy for the treatment of infections related to FLC‐resistant Candida sp. SIGNIFICANCE AND IMPACT OF THE STUDY: The indiscriminate use of antifungals results in the emergence of drug‐resistant strains among previously susceptible populations. BZP‐BRP can become an alternative for the treatment of persistent infections caused by Candida sp.
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