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Tensile tests were assessed to evaluate the ageing effects on carbon fiber/epoxy resin laminates exposed to ozone and water immersion. Laminates with distinct fiber arrangements (unidirectional - UD and plain weave - PW) were tested under transversal and longitudinal tensile strength at room (22°C) and high (88°C) temperatures after conditioning. The transversal tensile strength tests of UD laminates performed at room temperature show that the water immersion decreased this property in 28% when compared to non-conditioned samples. Ozone atmosphere also deteriorates the tensile strength considerably, drop of 27%. It was expected a higher drop in water immersion conditioning than in ozone atmosphere due to this conditioning attacks preferentially the external surface of specimen contrariwise the water immersion has diffusion inside the epoxy matrix. Tensile strength at high temperature shows more accentuated degradation for UD specimens exposed to water immersion (50% drop) than ozone (25%). Higher temperatures favor the degradation of the polymeric matrix and fibers/matrix interface. Tensile strength of PW laminates non-conditioned and conditioned with ozone, tested at room temperature, presented tensile strength results slightly different, 17% lower. When submitted to water immersion the results have dropped 26%, which are similar to unidirectional composite. At high temperature, PW laminate attacked with ozone had tensile strength reduced in 7%, while after water immersion the drop achieved 18%. These results show that water immersion affected the composite much more than ozone. Fractographic analyses confirmed that the combination between high temperature and conditioning promoted the degradation of matrix and fiber/matrix interface. [ABSTRACT FROM AUTHOR]

Dental caries is a multifactorial disease, which depends on the fermentation of carbohydrates by microorganisms of the dental biofilm. Xylitol is a sugar-alcohol, which cannot be fermented by oral cariogenic bacteria. This article aimed to review the literature on the use of xylitol for prevention of dental caries. There is little conclusive scientific evidence about this subject, although several studies have been performed. The development of products and clinical protocols should be based on studies with sound experimental design, which will permit the understanding of clinical and laboratorial parameters, such as mecanisms of action, vehicles of delivery, dose-response effects, and frequency of use of the polyol. Clarification of the potential and limitations of the use of xylitol for prevention of dental caries would help clinicians to select preventive protocols more efficient and cost-effective for specific groups. [ABSTRACT FROM AUTHOR]

The aims were to assess the prevalence of HIV infection among young adult heroin users, including injecting heroin users (IHUs) and non-injecting heroin users (NIHUs), and to explore the differences by gender and other factors. The design was a cross-sectional cohort study between April 2001 and December 2003, which included 961 current heroin users (HU), aged 18-30 years: 422 in Madrid, 351 in Barcelona and 188 in Seville; 621 were IHUs and 340 were NIHUs. All were street-recruited by chain referral methods. Face-to-face interviews were conducted using a structured questionnaire with computer-assisted personal interviewing (CAPI). Samples for HIV testing (dried blood spot) were collected and tested with ELISA and Western Blot. Bivariate, logistic regression, and classification and regression tree analyses were performed. The overall prevalence of HIV infection among IHUs was 25.8% (95% CI 22.3-29.3) [32.4% (95% CI 26.6-38.1) in Madrid, 20.5% (95% CI 15.6-25.4) in Barcelona, and 20.6% (95% CI 9.8-31.4) in Seville], whereas in NIHUs it was 4.0% (95% CI 2.1-6.7), with no differences among cities. The prevalence was significantly higher in women than in men in NIHUs (10.9%, 95% CI 4.3-17.5 vs. 1.7%, 95% CI 0.5-4.2) and was non-significantly higher in IHUs (30.4%, 95% CI 23.0-37.8 vs. 24.1%, 95% CI 20.1-28.1). HIV prevalence in short-term IHUs was 12.9% (CI 8.8-17.02), with no differences among cities. In the logistic analysis, the variables associated with infection in IHUs were ever having injected with used syringes (OR 3.4, 95% CI 2.2-5.3), ever having been in prison (OR 2.6, 95% CI 1.6-4.0), and heroin as the first drug injected at least weekly (OR 2.3, 95% CI 1.1-4.5). Factors positively associated with HIV infection in NIHUs were female sex (OR 8.7, 95% CI 2.6-29.2) and age >25 years (OR 3.1, 95% CI 0.9-11.1), while primary educational level was inversely associated (OR 0.26, 95% CI 0.1-0.9). Although there are important geographic differences, HIV prevalence in IHUs remains high, even in short-term IHUs, whereas it was almost six times lower in NIHUs. The prevalence in women is higher than in men, particularly among NIHUs. A wide range of preventive strategies should be developed, aimed primarily at empowering women to negotiate safe sex. [ABSTRACT FROM AUTHOR]

Background: Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology.Methods: From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-alpha, IL-1alpha were searched and quantified.Results: We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the expression of these molecules ranged from absent to medium intensity. It was not observed any correlation between severity of the disease and these markers. There was a correlation between the number of Leishmania antigen positive cells and CD4+ T cells, and between the number of CD4+ T cells and CD8+ T cells. In dogs presenting different histopathological patterns of glomerulonephritis, parameters of proliferation and apoptosis were studied. Ki-67, a proliferative marker, was not detected locally, but fewer apoptotic cells and lower TNF-alpha expression were seen in infected animals than in non-infected controls.Conclusion: Immunopathogenic mechanisms of VL glomerulonephritis are complex and data in the present study suggest no clear participation of immunoglobulin and C3b deposits in these dogs but the possible migration of CD4+ T cells into the glomeruli, participation of adhesion molecules, and diminished apoptosis of cells contributing to determine the proliferative pattern of glomerulonephritis in VL. [ABSTRACT FROM AUTHOR]

This investigation demonstrates the effect of alkali modification of titanium on the metabolism of human osteoblasts. Polished titanium discs were subjected to alkalinization protocols with NaOH (5M) at 60°C or 120°C. Surface topography and roughness were evaluated using scanning electron microscopy (SEM). Osteoblasts were seeded onto titanium discs, followed by cell adhesion and viability analysis, total protein and collagen production, and alkaline phosphatase (ALP) activity. Gene expression of tumor necrosis factor-alpha (TNF-α) and beta-defensin 3 (HBD3) was evaluated after inflammatory stimulus with lipopolysaccharides (LPS) of Porphyromonas gingivalis (1 μg/mL) for 4 h. Discs subjected to modification with NaOH showed major irregularities, especially for 120°C-protocol. Increased adhered cell number was observed for surfaces modified by NaOH. Osteoblasts cultured on modified surfaces showed higher cell viability, total protein and collagen synthesis, and ALP activity than that of cells cultured on the polished discs. Osteoblast response to LPS exposure showed increased TNF-α gene expression by these cells when cultured on the polished discs, while increased expression of HBD3 was detected for all groups in the presence of LPS. Modification of titanium discs by NaOH at 60°C or 120°C promoted an increase in adhesion and metabolism of osteoblasts and favored the response to inflammatory stimulus.

Background: Individuals develop crucial survival knowledge in the juvenile phase, including understanding medicinal plants. The family context or contact with resources can influence this dynamic knowledge. By investigating the influence of these factors on young people's understanding of medicinal plants, we aimed to enhance our understanding of the knowledge-building process., Methods: The study was conducted in three communities in the State of Alagoas, Brazil: Lagoa do Junco, Serrote do Amparo, and Brivaldo de Medeiros. Semi-structured interviews were conducted with young people aged between 11 and 19 to assess their knowledge of medicinal plants. We used a generalized linear mixed model (GLMM) with the number of therapeutic targets and known medicinal species (knowledge proxy) as response variables. As predictors, we included the number of individuals per family unit and the gender distribution within the famimunícpily (family context proxy), as well as dependence on the use (contact proxy). Location (city) was added as a fixed effect to the model. We investigated how knowledge of medicinal plants correlates with the practice of collecting these species., Results: We did not identify a relationship between the number of individuals per household, gender distribution within the family, and the frequency of medicinal plant use with knowledge about these species. However, we observed a positive, albeit weak, correlation between knowledge of medicinal species and the number of species collected., Conclusion: These results highlight the importance of investigating how young people acquire knowledge about medicinal plants, emphasizing the complex interactions between humans and nature, and providing a basis for future research., (© 2024. The Author(s).)

Non-timber forest products (NTFPs) play an essential role in the Amazon region, contributing to the integration between biodiversity conservation and the enhancement of the bioeconomy. This study has examined the scope of NTFP research in the Amazon and pinpointed areas lacking scientific insight. From the 219 publications initially identified, 146 satisfied established inclusion criteria based on the methodology employed and the results achieved. It was found that the inaugural publication indexed by Scopus on Amazonian NTFPs dates to 1992. It was found that the inaugural publication indexed by Scopus on Amazonian NTFPs dates to 1992. Despite the extensive body of research, there is a noticeable deficit in studies addressing legal and regulatory frameworks within the NTFP production chain and public policy development. Research has predominantly concentrated on production, distribution, management, and economic aspects, often neglecting the social, normative, and political dimensions. Advancing the bioeconomy value chains in the Amazon necessitates empowering local communities to derive economic benefits from biodiversity. However, recognizing the complexity of these communities' relationships with the forest is important. Their interaction with the forest extends beyond economic considerations, embracing cultural, subsistence, and spiritual connections. These insights underscore the necessity for a comprehensive and sustainable approach to NTFP management in the Amazon, ensuring that biodiversity conservation and local community empowerment are integrally pursued. This holistic perspective is vital for fostering a resilient bioeconomy in the region., Competing Interests: Declaration of competing interest There is no conflict of interest between the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Espírito Santo state, in Brazil, is a dengue-endemic region predicted to suffer from an increase in temperature and drought due to climate change, which could affect the areas with active dengue virus transmission. The study objective was modeling climatic factors and climate change effects in zones suitable for dengue virus transmission in Espírito Santo state, Brazil. Data on dengue reports from 2022 were used to determine climatic variables related to spatial distribution. The climate change projections were generated for the 2030s, 2050s, 2070s, and 2090s for three distinct Shared Socioeconomic Pathways: SSP1-2.6, SSP2-4.5 and SSP5-8.5. A maximum entropy algorithm was used to construct the three models and projections, and the results were used to calculate the ensemble mean. Isothermality, the maximum temperature of the warmest month, precipitation of the wettest month, precipitation of the warmest quarter, and annual precipitation impacted the model. Projections indicated a change in areas suitable for dengue virus transmission, varying from -30.44% in the 2070s (SSP1-2.6) to +13.07% in the 2070s (SSP5-8.5) compared to 2022. The coastal regions were consistently suitable in all scenarios. Urbanized and highly populated areas were predicted to persist with active dengue transmission in Espírito Santo state, posing challenges for public health response., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Chikungunya (CHIK) emerged in Brazil in 2014 and since then several epidemics have been observed. This study aims to describe the spatial, social and demographic characteristics of individuals affected by CHIK in Espírito Santo state., Methods: A cross-sectional study was performed using data from individuals with a confirmed diagnosis of CHIK in Espírito Santo state, Brazil, from 2018 to 2020. Monthly incidence was calculated and annual spatial distribution maps were constructed. Statistical analysis using the χ2 test identified associations between disease occurrence and sociodemographic variables., Results: In the period and area analysed, a CHIK epidemic occurred in 2020, with an incidence of 219.8 cases per 100 000 inhabitants. The southern and central regions of Espirito Santo state harboured a risk five times greater than the others in the epidemic region. Females (odds ratio [OR] 1.65 [95% confidence interval {CI} 1.58 to 1.72]), black people (OR 1.22 [95% CI 1.13 to 1.33]), individuals with ≤11 y of education (OR 1.48 [95% CI 1.37 to 1.61]) and the elderly (OR 7.49 [95% CI 6.53 to 8.59]) had a greater risk for the disease., Conclusions: CHIK stands as an emerging public health problem in Brazil since its introduction in 2014. Espírito Santo suffered a substantial epidemic in 2020, possibly due to outbreaks in neighbouring states. The population at risk should be prioritized in healthcare, considering the morbidity potential of the disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The calcium dependent Calpain proteases are modulatory enzymes with important roles in cell cycle control, development and immunity. In the fly model Drosophila melanogaster Calpain A cleaves Cactus/IkappaB and consequently modifies Toll signals during embryonic dorsal-ventral (DV) patterning. Here we explore the role of Calpains in the hemiptera Rhodnius prolixus , an intermediate germband insect where the Bone Morphogenetic Protein (BMP) instead of the Toll pathway plays a major role in DV patterning. Phylogenetic analysis of Calpains in species ranging from Isoptera to Diptera indicates an increase of Calpain sequences in the R. prolixus genome and other hemimetabolous species. One locus encoding each of the CalpC, CalpD and Calp7 families, and seven Calpain A/B loci are present in the R. prolixus genome. Several predicted R. prolixus Calpains display a unique architecture, such as loss of Calcium-binding EF-hand domains and loss of catalytic residues in the active site CysPc domain, yielding catalytically dead Calpains A/B. Knockdown for one of these inactive Calpains results in embryonic DV patterning defects, with expansion of ventral and lateral gene expression domains and consequent failure of germ band elongation. In conclusion, our results reveal that Calpains may exert a conserved function in insect DV patterning, despite the changing role of the Toll and BMP pathways in defining gene expression territories along the insect DV axis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

The use of exotic grasses of African origin for pastures in Brazil has been a major advancement in livestock production, but little is known about the responses of these grasses to nitrogen fertilizers associated with shading. In this study, the morphogenetic, structural, and leaf anatomical characteristics of Megathyrsus maximus cultivars' Tamani and Quênia were investigated as a function of N dose and shade. Morphogenetic and structural characteristics and leaf anatomy were studied under three shading levels (0, 30, and 50 %) and four N doses (0, 100, 200, and 300 kg N ha -1 ) to simulate growth in a silvopastoral system. When comparing the cultivars, Quênia was more efficient in terms of phyllochron up to fertilization with 100 kg N ha -1 . The leaf senescence rate of Tamani was higher than that of Quênia at the 30 and 50 % shade levels. The total area (TA) occupied by leaf tissues decreased in Quênia as a function of the increase in N fertilization, whereas the TA of Tamani did not change. The thickness of the adaxial epidermis was greater in Quênia (0.68 µm) than in Tamani (0.50 µm) when not fertilized. The area occupied by the mesophyll was greater in both cultivars when they received fertilization equivalent to 300 kg N ha -1 . Quênia grass has a smaller phyllochron than Tamani grass, due to the rapid reconstruction of its photosynthetic apparatus, especially when it receives higher levels of nitrogen fertilization. However, Tamani grass has a greater distribution of plant tissues. The mesophyll area is larger in Tamani grass due to the greater presence of chloroplasts, which facilitates digestion by animals. The Tamani modified the leaf anatomical tissues more significantly in relation to shading, whereas the Quênia modified them in relation to N fertilization, which reinforces the suggestion of a more appropriate use of Tamani in silvopastoral systems., 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 © 2024 Lopes, Lage Filho, do Rêgo, Domingues, Silva, Faturi, Silva and da Silva.)

Femoral neck fractures are extremely common injuries, especially in the elderly, who often have multiple associated comorbidities. Despite advances in surgical technique and implant technology, neglected fractures are still a reality in developing countries due to the lack of access to healthcare services or socioeconomic conditions of patients. This case report presents a 61-year-old male patient referred from a rural area to a trauma referral hospital with a neglected femoral neck fracture. The patient had multiple comorbidities, and during the surgical approach for total hip arthroplasty, the intraoperative finding of an extensive gouty tophus led to an increase in surgical time and modifications in the surgical procedure. The epidemiological profile of the patient in question fits the pattern of patients with diffuse gouty arthropathy, warranting suspicion of hip involvement when manifested in other joints. Performing complementary exams in patients preoperatively with proximal femur fractures and coxarthrosis can be an indispensable tool for the successful implementation of the therapeutic plan. This report presents these findings and the outcome of the method used., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Longo et al.)

We analyzed here the in silico biological activities of caffeine, (+)-catechin, and theobromine. For this, the PubChem database of the NIH (National Institutes of Health) was used to obtain the SMILE canonical form of the bioactive molecules, and the free software PASS Online (Prediction of Activity Spectra for Substances) from the Way2Drug portal. Also, we conducted an in vitro experiment using a chronic myeloid leukemia (CML) cell line (K562) to confirm some results found in in silico investigation. These cells were exposed to different concentrations of caffeine, (+)-catechin, and theobromine for 72 h. The results found in this in silico study suggested that caffeine, (+)-catechin, and theobromine showed excellent biological properties, such as antioxidant, anti-inflammatory, and anticarcinogenic, as well as protection against cardiovascular, diabetes, neurological, allergic, respiratory, and other therapeutic activities. These findings can be elucidated through the modulation exerted by these bioactive molecules in many biochemical pathways involved in organism homeostasis, such as free radical scavenger action, oxidoreductase inhibitor, membrane permeability inhibitor, and lipid peroxidase inhibitor. In addition, we have found here that caffeine, (+)-catechin, and theobromine have a remarkable anti-inflammatory activity which plays an important role in the therapeutic approach of COVID-19. Moreover, our in vitro findings confirmed the in silico results regarding anticancer activity since these molecules reduce cell proliferation at all tested concentrations. Therefore, since these molecules exhibit important medicinal activities, further investigations should be conducted to reveal new therapies to improve the treatments and prevention of numerous disorders and, consequently, promote human health., Competing Interests: Conflict of interestThe authors have no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In this study, we analyzed the potential of viral infections in the species Homo sapiens as environmental causes of orofacial clefts (OFCs). A scoring system was adapted for qualitatively assessing the potential of viruses to cause cleft lip and/or palate (CL/P). This assessment considered factors such as information from the literature, nucleotide and amino acid similarities, and the presence of Endogenous Viral Elements (EVEs). The analysis involved various algorithm packages within Basic Local Alignment Search Tool 2.13.0 software and databases from the National Center for Biotechnology Information and the International Committee on Taxonomy of Viruses. Twenty significant viral species using different biosynthesis strategies were identified: Human coronavirus NL63 , Rio Negro virus , Alphatorquevirus homin9 , Brisavirus , Cosavirus B , Torque teno mini virus 4 , Bocaparvovirus primate2 , Human coronavirus HKU1 , Monkeypox virus , Mammarenavirus machupoense , Volepox virus , Souris mammarenavirus , Gammapapillomavirus 7 , Betainfluenzavirus influenzae , Lymphocytic choriomeningitis mammarenavirus , Ledantevirus kern , Gammainfluenzavirus influenzae , Betapolyomavirus hominis , Vesiculovirus perinet , and Cytomegalovirus humanbeta5 . The evident viral etiological potential in relation to CL/P varies depending on the Baltimore class to which the viral species belongs. Given the multifactorial nature of CL/P, this relationship appears to be dynamic.

The monoclonal antibody (mAb) industry is becoming increasingly digitalized. Digital twins are becoming increasingly important to test or validate processes before manufacturing. High-Throughput Process Development (HTPD) has been progressively used as a tool for process development and innovation. The combination of High-Throughput Screening with fast computational methods allows to study processes in-silico in a fast and efficient manner. This paper presents a hybrid approach for HTPD where equal importance is given to experimental, computational and decision-making stages. Equilibrium adsorption isotherms of 13 protein A and 16 Cation-Exchange resins were determined with pure mAb. The influence of other components in the clarified cell culture supernatant (harvest) has been under-investigated. This work contributes with a methodology for the study of equilibrium adsorption of mAb in harvest to different protein A resins and compares the adsorption behavior with the pure sample experiments. Column chromatography was modelled using a Lumped Kinetic Model, with an overall mass transfer coefficient parameter (k ov ). The screening results showed that the harvest solution had virtually no influence on the adsorption behavior of mAb to the different protein A resins tested. k ov was found to have a linear correlation with the sample feed concentration, which is in line with mass transfer theory. The hybrid approach for HTPD presented highlights the roles of the computational, experimental, and decision-making stages in process development, and how it can be implemented to develop a chromatographic process. The proposed white-box digital twin helps to accelerate chromatographic process development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aim: Polymyxin B (PMB) is one of the few therapeutic options for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the emergence of PMB-resistant CR-GNB strains has prompted the exploration of antibiotic adjuvants as potential therapeutic avenues. Thus, this study evaluates the potential of 3,5-dinitrobenzoic acid derivatives (DNH01, DNH11, DNH13 and DNH20) and isoniazid- N -acylhydrazones (INZ1-7, INZ9 and INZ11) as adjuvants to enhance PMB efficacy against CR-GNB. Materials & methods: MIC, MBC and drug combination assays were conducted using multidrug-resistant clinical isolates of Enterobacterales and Acinetobacter baumannii . In addition, the effects of PMB and PMB + DNH derivatives were assessed through flow cytometry and scanning electron microscopy (SEM). Results: DNH01, DNH11 and DNH20, unlike the INH-acylhydrazones, significantly restored PMB activity (MIC ≤ 2 μg/ml) in 80% of the tested isolates. Flow cytometry and SEM assays confirmed that DNH derivatives rescued the activity of PMB, yielding results comparable to those expected for PMB alone but at 256-fold lower concentrations. Conclusion: These findings suggest DNH derivatives hold substantial promise as PMB adjuvants to combat PMB-resistant CR-GNB infections.

Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1 -/- ) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1 -/- female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2-dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub-acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH-induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase-3) in colonic crypts. Of note, at week 37, Panx1 -/- animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated., (© 2023 Company of the International Journal of Experimental Pathology (CIJEP).)

The identification of key concepts within unstructured data is of paramount importance in practical applications. Despite the abundance of proposed methods for extracting primary topics, only a few works investigated the influence of text length on the performance of keyword extraction (KE) methods. Specifically, many studies lean on abstracts and titles for content extraction from papers, leaving it uncertain whether leveraging the complete content of papers can yield consistent results. Hence, in this study, we employ a network-based approach to evaluate the concordance between keywords extracted from abstracts and those from the entire papers. Community detection methods are utilized to identify interconnected papers in citation networks. Subsequently, paper clusters are formed to identify salient terms within each cluster, employing a methodology akin to the term frequency-inverse document frequency (tf-idf) approach. Once each cluster has been endowed with its distinctive set of key terms, these selected terms are employed to serve as representative keywords at the paper level. The top-ranked words at the cluster level, which also appear in the abstract, are chosen as keywords for the paper. Our findings indicate that although various community detection methods used in KE yield similar levels of accuracy. Notably, text clustering approaches outperform all citation-based methods, while all approaches yield relatively low accuracy values. We also identified a lack of concordance between keywords extracted from the abstracts and those extracted from the corresponding full-text source. Considering that citations and text clustering yield distinct outcomes, combining them in hybrid approaches could offer improved performance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tohalino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To analyze the dynamics of the spatial and temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020., Method: This ecological study focused on the spatial pattern of visceral leishmaniasis cases in Brazil from 2007 to 2020 using data from the Information System for Notifiable Diseases (SINAN). The variables analyzed were the incidence rate of visceral leishmaniasis and the visceral leishmaniasis composite indicator (VLCI), from which triennial thematic maps were constructed. The global Moran index was calculated to assess the existence of spatial autocorrelation, and the local Moran index was used to identify areas with higher and lower risk of visceral leishmaniasis in Brazil., Results: During the study period, there were 48 705 cases of visceral leishmaniasis, with an incidence rate of 25.53 cases per 100 000 population. There was spatial autocorrelation in all triennial blocks, with municipalities in the North and Northeast regions having an incidence equal to or greater than 50 cases per 100 000 population. Regarding the VLCI there was an increase in the number of municipalities classified as low risk for transmission, and a growing presence of state capitals with a classification of very high risk., Conclusion: The incidence of visceral leishmaniasis varied over the trienniums. The border region between the states of Tocantins, Maranhão, and Pará, along with the state of Ceará, stood out in the spatial distribution of the disease incidence and risk stratification by VLCI. These areas should be a priority for surveillance and control efforts for the disease.

Renal neoplasms are highlighted as one of the 10 most common types of cancer. Renal cell carcinoma (RCC) is the most common type of renal cancer, considered the seventh most common type of cancer in the Western world. The most frequently altered genes described as altered are VHL, PBRM1, SETD2, KDM5C, PTEN, BAP1, mTOR, TP53, TCEB1 (ELOC), SMARCA4, ARID1A, and PIK3CA. RCC therapies can be classified in three groups: monoclonal antibodies, tyrosine kinase inhibitors, and mTOR inhibitors. Besides, there are targeted agents to treat RCC. However, frequently patients present side effects and resistance. Even though many multidrug resistance mechanisms already have been reported to RCC, studies focused on revealing new biomarkers as well as more effective antitumor therapies with no or low side effects are very important. Some studies reported that natural products, such as honey, epigallocatechin-3-gallate (EGCG), curcumin, resveratrol, and englerin A showed antitumor activity against RCC. Moreover, nanoscience is another strategy to improve RCC treatment and reduce the side effects due to the improvement in pharmacokinetics and reduction of toxicities of chemotherapies. Taking this into account, we conducted a systemic review of recent research findings on RCC hallmarks, drug resistance, and adjuvant therapies. In conclusion, a range of studies reported that RCC is characterized by high incidence and increased mortality rates because of the development of resistance to standard therapies. Given the importance of improving RCC treatment and reducing adverse effects, nanoscience and natural products can be included in therapeutic strategies., Competing Interests: The Authors have no conflicts of interest to report in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

In recent decades, health literacy has garnered increasing attention alongside a variety of public health topics. This study aims to explore trends in this area through a bibliometric analysis. A Random Forest Model was utilized to identify keywords and other metadata that predict average citations in the field. To supplement this machine learning analysis, we have also implemented a bibliometric review of the corpus. Our findings reveal significant positive coefficients for the keywords "COVID-19" and "Male", underscoring the influence of the pandemic and potential gender-related factors in the literature. On the other hand, the keyword "Female" showed a negative coefficient, hinting at possible disparities that warrant further investigation. Additionally, evolving themes such as COVID-19, mental health, and social media were discovered. A significant change was observed in the main publishing journals, while the major contributing authors remained the same. The results hint at the influence of the COVID-19 pandemic and a significant association between gender-related keywords on citation likelihood, as well as changing publication strategies, despite the fact that the main researchers remain those who have been studying health literacy since its creation.

Free-living amoebae (FLA) are amphizoic protozoans with a cosmopolitan distribution. Some strains of species are associated with infections in humans. They feed on microorganisms by phagocytosis; however, some of these can become endocytobionts by resisting this process and taking shelter inside the amoeba. The whole world is experiencing increasing shortage of water, and sewage is being reused, so the study of this environment is important in public health context. The objective of this work was to identify FLA present in sewage treatment plants in Porto Alegre, Brazil. About 1 L samples were collected from eight stations (raw and treated sewage) in January, February, July, and August 2022. The samples were sown in monoxenic culture, and the isolated amoebae were subjected to morphological and molecular identification. Polymerase chain reaction results indicated the presence of the genus Acanthamoeba in 100% of the samples. Gene sequencing showed the presence of Acanthamoeba lenticulata and Acanthamoeba polyphaga - T5 and T4 genotypes - respectively, which are related to pathogenicity. The environment where the sewage is released can be used in recreational activities, exposing individuals to potential interactions with these amoebae and their potential endocytobionts, which may pose risks to public health.

Seroprevalence of bovine alphaherpesvirus type 1 (BoAHV1) infections may be contaminated by crossreactive antibodies to bovine alphaherpesvirus type 5 (BoAHV5). To avoid such crossreactivity, an indirect enzyme-linked immunosorbent assay prepared with a recombinant glycoprotein C (gC) antigen (ELISA-gC1) was developed, aiming the detection of antibodies to BoAHV1, with no crossreactivity with BoAHV5 antibodies. The antigen for the ELISA-gC1 was the product of the expression of 219 bp from the N-terminal portion of the BoAHV1 gC gene, which bears low homology between the two virus types. The test was validated on 131 bovine serum samples, including 26 sera from BoAHV1-experimentally immunized, 38 sera from BoAHV5-experimentally infected or immunized calves, and 67 sera from calves seronegative for both BoAHV1 and BoAHV5, as determined by serum neutralization (SN). When compared to SN for BoAHV1, the ELISA-gC1 presented 100% sensitivity, 95.5 % specificity, 100 % negative predictive value, 89.6 % positive predictive value, 98.8 % precision, and a kappa correlation coefficient (κ) 0.95. None of the 38 BoAHV5-seropositive calves was detected by the ELISA-gC1. The ELISA-gC1 proved highly effective for the identification of BoAHV1-positive sera, with no crossreactivity with anti-BoAHV5 antibodies, thus able to distinguish serological responses from BoAHV1- and BoAHV5-seropositive cattle. Its capacity to detect BoAHV1-specific antibodies should allow the determination of the actual BoAHV1 prevalence in herds, which cannot be serologically determined in countries where BoAHV5 is also prevalent due to antibody crossreactivity. Apart from recognizing exclusively BoAHV1-infected cattle, the ELISA-gC1 may also be used in support of BoAHV5 epidemiological studies by allowing the exclusion of BoAHV1-seropositive animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Carbon emissions and associated global warming have become a threat to the world, the major contributor being the extensive use of fossil fuels and uncontrolled generation of solid wastes. Energy generation from renewable energy sources is considered an alternative to achieving carbon neutrality. Anaerobic digestion (AD) is a sustainable technology that has been endorsed as a low-carbon technology complimenting both waste management and renewable energy sectors. The AD technology recovers the volatile matter from waste biomass as much as possible to produce biogas, thus reducing carbon emission as compared to open dumping or burning. However, there is a need of compilation of information on how each subsystem in AD contributes to the overall carbon neutrality of the entire system and chances of achieving a circular economy along with it. Therefore, this article aims to clarify the associated internal and external factors that determine the low carbon characteristic of anaerobic digestion technology. From this review, the potential of AD system for energy-atmosphere-agriculture nexus has been explored. Carbon emission mapping of the potential entities involved in AD were identified and perspective to life cycle assessment and future research direction has been pointed out. Climate change impact and acidification potential are the two entities that can influence the overall environmental sustainability of an AD system. It was recognized that each stage of AD system starting from substrate supply chain, biogas production, upgradation, utilization, and digestate application had a remarkable effect on the overall carbon emission potential based on its design, operation, and maintenance. Selection of suitable substrates and co-digesting them together for improved biogas production rate with high methane content and proper digestate post-processing and storage can vastly reduce the carbon emission potential of the AD technology. Further, a case scenario of India was assessed considering the utilization of major surplus biomass available through AD. Re-routing the three major substrates such as agricultural crop residues, animal wastes and organic fraction of municipal solid wastes through AD can reduce at least 3.5-3.8 kg CO 2-eq per capita of annual carbon emission load in India. Furthermore, the pathways in which the policy and legislations over establishment of AD technology and how to explore linkages between achieving circular economy and low carbon economy for Indian scenario has been highlighted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

In this study, we investigate the COVID-19 epidemics in Brazilian cities, using early-time approximations of the SIR model in networks and combining the VAR (vector autoregressive) model with machine learning techniques. Different from other works, the underlying network was constructed by inputting real-world data on local COVID-19 cases reported by Brazilian cities into a regularized VAR model. This model estimates directional COVID-19 transmission channels (connections or links between nodes) of each pair of cities (vertices or nodes) using spectral network analysis. Despite the simple epidemiological model, our predictions align well with the real COVID-19 dynamics across Brazilian municipalities, using data only up until May 2020. Given the rising number of infectious people in Brazil-a possible indicator of a second wave-these early-time approximations could be valuable in gauging the magnitude of the next contagion peak. We further examine the effect of public health policies, including social isolation and mask usage, by creating counterfactual scenarios to quantify the human impact of these public health measures in reducing peak COVID-19 cases. We discover that the effectiveness of social isolation and mask usage varies significantly across cities. We hope our study will support the development of future public health measures.

During Trypanosoma cruzi infection, macrophages phagocytose parasites and remove apoptotic cells through efferocytosis. While macrophage 1 (M1) produces proinflammatory cytokines and NO and fights infection, M2 macrophages are permissive host cells that express arginase 1 and play a role in tissue repair. The regulation of M1 and M2 phenotypes might either induce or impair macrophage-mediated immunity towards parasite control or persistence in chronic Chagas disease. Here, we highlight a key role of macrophage activation in early immune responses to T. cruzi that prevent escalating parasitemia, heart parasitism, and mortality during acute infection. We will discuss the mechanisms of macrophage activation and deactivation, such as T cell cytokines and efferocytosis, and how to improve macrophage-mediated immunity to prevent parasite persistence, inflammation, and the development of chagasic cardiomyopathy. Potential vaccines or therapy must enhance early T cell-macrophage crosstalk and parasite control to restrain the pathogenic outcomes of parasite-induced inflammation in the heart., 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 Vellozo, Matos-Silva and Lopes.)

The aim of the current study was to investigate the effect of glutamine supplementation on the expression of HSP70 and the calcium-binding proteins from the S100 superfamily in the recovering extensor digitorum longus (EDL) muscle after injury. Two-month-old Wistar rats were subjected to cryolesion of the EDL muscle and then randomly divided into two groups (with or without glutamine supplementation). Starting immediately after the injury, the supplemented group received daily doses of glutamine (1 g/kg/day, via gavage) for 3 and 10 days orally. Then, muscles were subjected to histological, molecular, and functional analysis. Glutamine supplementation induced an increase in myofiber size of regenerating EDL muscles and prevented the decline in maximum tetanic strength of these muscles evaluated 10 days after injury. An accelerated upregulation of myogenin mRNA levels was detected in glutamine-supplemented injured muscles on day 3 post-cryolesion. The HSP70 expression increased only in the injured group supplemented with glutamine for 3 days. The increase in mRNA levels of NF-κB, the pro-inflammatory cytokines IL-1β and TNF-α, and the calcium-binding proteins S100A8 and S100A9 on day 3 post-cryolesion in EDL muscles was attenuated by glutamine supplementation. In contrast, the decrease in S100A1 mRNA levels in the 3-day-injured EDL muscles was minimized by glutamine supplementation. Overall, our results suggest that glutamine supplementation accelerates the recovery of myofiber size and contractile function after injury by modulating the expression of myogenin, HSP70, NF-κB, pro-inflammatory cytokines, and S100 calcium-binding proteins., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study explores the use of silica-coated bacterial nanocellulose (BC) scaffolds with bulk macroscopic yet nanometric internal pores/structures as functional supports for high surface area titania aerogel photocatalysts to design flexible, self-standing, porous, and recyclable BC@SiO 2 -TiO 2 hybrid organic-inorganic aerogel membranes for effective in-flow photo-assisted removal of organic pollutants. The hybrid aerogels were prepared by sequential sol-gel deposition of the SiO 2 layer over BC, followed by coating of the resulting BC@SiO 2 membranes with a porous titania aerogel overlayer of high surface area using epoxide-driven gelation, hydrothermal crystallization, and subsequent supercritical drying. The silica interlayer between the nanocellulose biopolymer scaffold and the titania photocatalyst was found to greatly influence the structure and composition, particularly the TiO 2 loading, of the prepared hybrid aerogel membranes, allowing the development of photochemically stable aerogel materials with increased surface area/pore volume and higher photocatalytic activity. The optimized BC@SiO 2 -TiO 2 hybrid aerogel showed up to 12 times faster in-flow photocatalytic removal of methylene blue dye from aqueous solution in comparison with bare BC/TiO 2 aerogels and outperformed most of the supported-titania materials reported earlier. Moreover, the developed hybrid aerogels were successfully employed to remove sertraline drug, a model emergent contaminant, from aqueous solution, thus further demonstrating their potential for water purification.

Infections caused by parasitic helminths rank among the most prevalent infections of humans and animals. Toxocariasis, caused by nematodes of the genus Toxocara, is one of the most widespread and economically important zoonotic parasitic infections that humans share with dogs and cats. Despite the completion of the Toxocara canis draft genome project, which has been an important step towards advancing the understanding of this parasite and the search for drug targets, the treatment of toxocariasis has been dependent on a limited set of drugs, necessitating the search for novel anthelmintic agents, specially against Toxocara larvae in tissues. Given that research, development, and innovation are crucial to finding appropriate solutions in the fight against helminthiasis, this paper reviews the progress made in the discovery of anthelmintic drug candidates for toxocariasis. The main compounds reported in the recent years regards on analogues of albendazole, reactive quinone derivatives and natural produts and its analogues. Nanoparticles and formulations were also reviewed. The in vitro and/or in vivo anthelmintic properties of such alternatives are herein discussed as well as the opportunities and challenges for treatment of human toxocariasis. The performed review clarify that the scarcity of validated molecular targets and limited chemical space explored are the main bottlenecks for advancing in the field of anti-Toxocara agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Understanding how studies have been carried out in the region helps to understand the Amazon rainforest potential in mitigating climate change. In addition, evaluating scientific production is essential to verify the main methods and places researched. Thus, this study objective was to build an overview and identify the main gaps regarding research related to biomass and carbon stocks with the coverage limit of the Amazon rainforest. Therefore, an analysis of the publications indexed in the Scopus database was developed until 2020, performing a bibliometric analysis and a systematic and state-of-the-art review. Initially 2042 publications were obtained, of which 786 met the inclusion criteria. The first work indexed in the Scopus database related to the theme was published in 1982. Over time, it was possible to observe an increasing behavior in relation to the interest in the theme. Natural environments were the most researched and change in the land use and occupation of the Amazon Rainforest is still poorly evaluated. Brazil is the country with the highest number of studies, followed by Peru and Colombia. Guyana and Suriname appear as possible scientific gaps and potential environments to be studied. Studies preferentially explore the biomass carbon, with the soil being little evaluated when compared to the total amount of papers found. When observing only the biomass studies, the aboveground biomass is the most evaluated, while the roots and necromass are little studied. The main variables used in biomass equations were diameter at 1.3 m above ground and total tree height. The biomass to carbon conversion factor has been widely used, but it can generate unreliable results. It is recommended to carry out local assessments of the carbon content, especially using the dry combustion method, which generates less waste, with more precise results and shorter execution time of the analyses. Such assessments present values for the location that can avoid false or misinterpretations of the biomass and carbon stocks in the Amazon Rainforest., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Postoperative pain is one of the main negative symptoms resulting from surgery and the use of new methods to control this symptom is of ever-increasing relevance. Opioid-sparing strategies, such as multimodal analgesia, are trends in this scenario. Pregabalin is a well-established treatment for neuropathic pain; however, it is still controversial in the surgical context for postoperative analgesia. This study investigated the effect of pregabalin on postoperative analgesia in patients undergoing abdominal hysterectomy. It is a prospective, randomised, double-blind, placebo-controlled clinical trial. Female patients undergoing abdominal hysterectomy were randomised to use pregabalin (group P1), 300 mg orally 2 h before surgery, or identical placebo pills (group P0). The main outcome includes the postoperative pain index by visual analogue scale (VAS) and McGill's pain questionnaire. Secondary outcomes include opioid consumption and the presence of adverse effects. A value of p < 0.05 was used to reject type I error. Fifty-five patients were randomised amongst the groups. Patients in group P1 had lower pain rates by VAS scale, both at rest and in active motion, than group P0. In McGill's questionnaire, patients from group P1 also had lower pain rates (12 × 28.5). There was approximately twice as much opioid consumption amongst patients in group P0. Regarding side effects, there was a difference between the two groups only for dizziness, being more incident in group P1. This study suggests that pregabalin is an important adjuvant drug in treating postoperative pain in patients with abdominal hysterectomy., (© 2022 John Wiley & Sons Australia, Ltd.)

Objective: To assess the effect of physical therapy on cancer-related fatigue (CRF) during cytotoxic anticancer treatment., Methods: Systematic review with meta-analysis of randomized clinical trials published from 2010 to 2021 (EMBASE, MEDLINE, PEDro; SciELO, and LILACS). Studies assessing the effect of supervised physical therapy (IG) for the management of CRF on adults undergoing anticancer treatment compared with a control group (CG) covering usual care or any uncontrolled practice, such as recommendations about exercise and health education, were included in this review., Results: A total of 22 studies were included in the SR and 21 in the meta-analysis, resulting in 1.992 individuals (CG = 973 and IG = 1.019). There was a reduction in general fatigue [SMD =  - 0.69; 95%CI (- 1.15, - 0.22) p < 0.01; I 2  = 87%; NNT = 3], with greater weight attributed to combined exercise (44%). Physical fatigue also reduced [SMD =  - 0.76; 95%CI (- 1.13, - 0.39) p < 0.01; I 2  = 90%; NNT = 2], with greater weight for resistance exercise (50%) and greater effect with combined exercise [SMD =  - 1.90; 95%CI (- 3.04, - 0.76) p < 0.01; I 2  = 96%]. There was reduction in general fatigue with moderate intensity (74%) [SMD =  - 0.89; 95%CI (- 1.61, - 0.17) p < 0.02; I 2  = 90%] and physical fatigue [SMD =  - 1.00; 95%CI (- 1.54, - 0.46) p < 0.01; I 2  = 92%], while high intensity reduced only general fatigue [SMD =  - 0.35; 95%CI (- 0.51, - 0.20) p < 0.01; I 2  = 0%]. The number of overall and weekly sessions has been shown to contribute to the reduction of CRF., Conclusion: Physical rehabilitation with moderate intensity promoted greater relief of general and physical fatigue. Even after controlling for high heterogeneity, the quality of evidence, summarized in GRADE, was considered moderate for general fatigue and low for physical fatigue., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microalgae such as Spirulina platensis have recently attracted the interest of the pharmaceutical, nutritional and food industries due to their high levels of proteins and bioactive compounds. In this study, we investigated the use of refractance window (RW) drying as an alternative technology for processing the microalga Spirulina biomass aiming at its dehydration. In addition, we also analyzed the effects of operating variables (i.e., time and temperature) on the quality of the final product, expressed by the content of bioactive compounds (i.e., total phenolics, total flavonoids, and phycocyanin). The results showed that RW drying can generate a dehydrated product with a moisture content lower than 10.0%, minimal visual changes, and reduced process time. The content of bioactive compounds after RW drying was found to be satisfactory, with some of them close to those observed in the fresh microalga. The best results for total phenolic (TPC) and total flavonoids (TFC) content were obtained at temperatures of around 70 °C and processing times around 4.5 h. The phycocyanin content was negatively influenced by higher temperatures (higher than 80 °C) and high exposing drying times (higher than 4.5 h) due to its thermosensibility properties. The use of refractance window drying proved to be an interesting methodology for the processing and conservation of Spirulina platensis , as well as an important alternative to the industrial processing of this biomass.

Adenosine, a purine nucleoside with neuromodulatory actions, is part of the purinergic signaling system (PSS). Caenorhabditis elegans is a free-living nematode found in soil, used in biological research for its advantages as an alternative experimental model. Since there is a lack of evidence of adenosine's direct actions and the PSS's participation in this animal, such an investigation is necessary. In this research, we aimed to test the effects of acute and chronic adenosine at 1, 5, and 10 mM on nematode's behaviors, morphology, survival after stress conditions, and on pathways related to the response to oxidative stress (DAF-16/FOXO and SKN-1) and genes products downstream these pathways (SOD-3, HSP-16.2, and GCS-1). Acute or chronic adenosine did not alter the worms' morphology analyzed by the worms' length, width, and area, nor interfered with reproductive behavior. On the other hand, acute and chronic adenosine modulated the defecation rate, pharyngeal pumping rate, and locomotion, in addition, to interacting with stress response pathways in C. elegans. Adenosine interfered in the speed and mobility of the worms analyzed. In addition, both acute and chronic adenosine presented modulatory effects on oxidative stress response signaling. Acute adenosine prevented the heat-induced-increase of DAF-16 activation and SOD-3 levels, while chronic adenosine per se induced DAF-16 activation and prevented heat-induced-increase of HSP-16.2 and SKN-1 levels. Together, these results indicate that exogenous adenosine has physiological and biochemical effects on C. elegans and describes possible purinergic signaling in worms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adaptive immunity controls Trypanosoma cruzi infection, but the protozoan parasite persists and causes Chagas disease. T cells undergo apoptosis, and the efferocytosis of apoptotic cells might suppress macrophages and exacerbate parasite infection. Nonetheless, the receptors involved in the efferocytosis of apoptotic lymphocytes during infection remain unknow. Macrophages phagocytose apoptotic cells by using the TAM (Tyro3, Axl, Mer) family of receptors. To address how the efferocytosis of apoptotic cells affects macrophage-mediated immunity, we employ here Axl receptor- and Mer receptor-deficient mouse strains. In bone marrow-derived macrophages (BMDMs), both Axl and Mer receptors play a role in the efferocytosis of proapoptotic T cells from T. cruzi-infected mice. Moreover, treatment with a TAM receptor inhibitor blocks efferocytosis and upregulates M1 hallmarks induced by immune T cells from infected mice. Remarkably, the use of Axl -/- but not Mer -/- macrophages increases T-cell-induced M1 responses, such as nitric oxide production and control of parasite infection. Furthermore, infected Axl -/- mice show reduced peak parasitemia, defective efferocytosis, improved M1 responses, and ameliorated cardiac inflammation and fibrosis. Therefore, Axl induces efferocytosis, disrupts M1 responses, and promotes parasite infection and pathology in experimental Chagas disease. Axl stands as a potential host-direct target for switching macrophage phenotypes in infectious diseases., (© 2022. The Author(s).)

Colorectal cancer (CRC), associated with an increased intake of processed red meats, saturated fats, and simple carbohydrates accompanied by low dietary fiber, fruits, and vegetables consumption, presents a high epidemiological burden. Connexin43 (Cx43) protein, which forms gap junctions or hemichannels, has tumor suppressor or oncogenic activities in a cancer type- and stage-dependent manner. Cx43 expression varies during colon carcinogenesis, and its functional role is not fully understood. Thus, we evaluated the implications of Cx43 heterologous deletion (Cx43 +/- ) during the early stages of a chemically induced model of colon carcinogenesis. Female C57BL/6J mice (wild-type or Cx43 +/- ) were submitted to a colon carcinogenesis model induced by 1,2 dimethylhydrazine (DMH). Mice were euthanized eight hours (week 7) or 30 weeks (week 37) after the last DMH administration to evaluate subacute colon toxicity outcomes or the burden of (pre)neoplastic lesions, respectively. At week 7, Cx43 deficiency inferred no alterations in the DMH-induced increase in systemic (peripheral blood), in situ (colonocytes) DNA damage, and apoptosis in the colonocytes. At week 30, Cx43 +/- mice presented an increase in preneoplastic aberrant crypt foci (ACF) multiplicity, while no alterations were observed in colorectal adenoma (CRA) occurrence, multiplicity, volume, proliferation, growth, and β-catenin immunoexpression. Similarly, an in silico analysis of human CRA showed decreased mRNA expression of Cx43 with no correlation with proliferation, apoptosis, and β-catenin markers. These findings indicate the discrete role of Cx43 in the early stages of chemically induced mouse colon carcinogenesis.

Biopharmaceuticals are becoming increasingly important in modern healthcare. Monoclonal antibodies (mAb) are one of the most widely used therapeutic proteins and are important for the treatment of cancer and autoimmune diseases, among others. After cell culture there are still large amounts of other impurities (e.g. host cell proteins) in solution. Chromatography is usually the first purification step, allowing to increase purity and reduce volume. This comes associated with high costs and chromatography accounts for a significant portion of total production costs for therapeutic proteins. Chromatographic process development may be time consuming and use large amounts of resins. Therefore, there is increased interest in finding cheaper techniques for chromatographic process development without compromising accuracy. This paper presents a highly sophisticated microfluidic chip approach for efficient adsorption isotherm determinations compared to current chromatographic process development. Implementation of an image analysis software ensures that chromatographic resin volume is accurately determined. The adsorption isotherm performance of microfluidics was compared to the robotic Liquid-handling Station (LHS) and labor intensive Eppendorf tubes. The microfluidic chip allows a 15-fold volume reduction and resin consumptions as low as 100/200 nl (200/100-fold reduction). The microfluidic chip performed comparably to the other miniaturized techniques, using less liquid and resin volume. For process development of expensive products (e.g. monoclonal antibodies), miniaturization (provided by the microfluidic chip) proved to be the most cost effective alternative whereas for less valuable products (e.g. lysozyme) automation (provided by the LHS) was the most cost effective alternative., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The protozoan parasite Leishmania (L.) amazonensis infects and replicates inside host macrophages due to subversion of the innate host cell response. In the present study, we demonstrate that TLR3 is required for the intracellular growth of L. (L.) amazonensis . We observed restricted intracellular infection of TLR3 -/- mouse macrophages, reduced levels of IFN1β and IL-10, and increased levels of IL-12 upon L. (L.) amazonensis infection, compared with their wild-type counterparts. Accordingly, in vivo infection of TLR3 -/- mice with L. (L.) amazonensis displayed a significant reduction in lesion size. Leishmania (L.) amazonensis infection induced TLR3 proteolytic cleavage, which is a process required for TLR3 signaling. The chemical inhibition of TLR3 cleavage or infection by CPB-deficient mutant L. (L.) mexicana resulted in reduced parasite load and restricted the expression of IFN1β and IL-10. Furthermore, we show that the dsRNA sensor molecule PKR (dsRNA-activated protein kinase) cooperates with TLR3 signaling to potentiate the expression of IL-10 and IFN1β and parasite survival. Altogether, our results show that TLR3 signaling is engaged during L. (L.) amazonensis infection and this component of innate immunity modulates the host cell response.

Background: Little is known about peripherally inserted central catheter (PICC) use, appropriateness and device outcomes in Brazil., Methods: We conducted an observational, prospective, cohort study spanning 16 Brazilian hospitals from October 2018 to August 2020. Patients ≥18 years receiving a PICC were included. PICC placement variables were abstracted from medical records. PICC-related major (deep vein thrombosis (DVT), central line-associated bloodstream infection (CLABSI) and catheter occlusion) and minor complications were collected. Appropriateness was evaluated using the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC). Devices were considered inappropriate if they were in place for < 5 days, were multi-lumen, and/or were placed in patients with a creatinine >2.0 mg/dL. PICCs considered appropriate met none of these criteria. Mixed-effects logistic regression models adjusting for patient-level and hospital-level characteristics assessed the association between appropriateness and major complications., Results: Data from 12 725 PICCs were included. Mean patient age was 66.4±19 years and 51.0% were female. The most common indications for PICCs were intravenous antibiotics (81.1%) and difficult access (62.7%). Most PICCs (72.2%) were placed under ultrasound guidance. The prevalence of complications was low: CLABSI (0.9%); catheter-related DVT (1.0%) and reversible occlusion (2.5%). Of the 12 725 devices included, a total of 7935 (62.3%) PICCs were inappropriate according to MAGIC. With respect to individual metrics for appropriateness, 17.0% were placed for < 5 days, 60.8% were multi-lumen and 11.3% were in patients with creatinine >2.0 mg/dL. After adjusting for patient and hospital-level characteristics, multi-lumen PICCs considered inappropriate were associated with greater odds of major complications (OR 2.54, 95% CI 1.61 to 4.02)., Conclusions: Use of PICCs in Brazilian hospitals appears to be safe and comparable with North America. However, opportunities to improve appropriateness remain. Future studies examining barriers and facilitators to improving device use in Brazil would be welcomed., Competing Interests: Competing interests: FRFdES has been a speaker for the BD-BARD since 2016., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. In this study, a simplified compound, N -(4-methoxyphenyl)pentanamide (N4MP), based on the structure of the most widely used anthelmintic (albendazole), was chemically prepared using 4-anisidine and pentanoic acid. N -(4-Methoxyphenyl)pentanamide was evaluated in vitro against the nematode Toxocara canis, an ascarid roundworm of animals that can infect humans. Similar to albendazole, bioassays showed that N -(4-methoxyphenyl)pentanamide affected the viability of parasites in a time- and concentration-dependent manner. Interestingly, N -(4-methoxyphenyl)pentanamide showed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Pharmacokinetic, drug-likeness, and medicinal chemistry friendliness studies demonstrated an excellent drug-likeness profile for N -(4-methoxyphenyl)pentanamide as well as an adherence to major pharmaceutical companies' filters. Collectively, the results of this study demonstrate that the molecular simplification of albendazole to give N -(4-methoxyphenyl)pentanamide may be an important pipeline in the discovery of novel anthelmintic agents. IMPORTANCE Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. Considering this scenario, the present study reports the preparation of N -(4-methoxyphenyl)pentanamide (N4MP), a simplified molecule based on the structure of the most widely used anthelmintic (albendazole). N4MP was evaluated in vitro against the nematode Toxocara canis, a common ascarid roundworm of domestic animals that can infect humans. Similar to albendazole, bioassays showed that N4MP affected the viability of parasites in a time- and concentration-dependent manner but displayed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Therefore, this study demonstrates that the molecular simplification of albendazole to give N4MP may be an important pipeline in the discovery of novel anthelmintic agents.