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Cancer is a global public health problem, requiring the development of new and more effective drugs for treatment. Eremanthus crotonoides , is a common plant found in the Brazilian Cerrado and Atlantic Forest and is used as a traditional medicinal plant in some regions. This study evaluated the potential antitumor effect of centratherin, a compound isolated from E. crotonoides leaves, against cancer cells. In colorectal cancer cells, centratherin showed greater toxicity than carboplatin while maintaining comparable selectivity to the control. Although centratherin did not induce classical apoptotic phenotypes and was not inhibited by Zvad, it did induce elevated levels of reactive oxygen species (ROS) that was responsible for cell death explaining its toxicity. in silico analysis, showed that this substance has high oral bioavailability and intestinal absorption. Centratherin was found to be selective against colon cancer cells and, therefore may be considered for future studies on colorectal cancer (CRC) studies.

Background: Renal dysfunction is a known predictor of long-term functional dependency after anterior circulation large vessel occlusion (ACLVO) stroke. However, the impact of renal dysfunction on early infarct growth rate (IGR) has not been previously demonstrated. The objective of this study was to define the association of creatinine-based renal biomarkers with fast or slow progressor phenotypes and related clinical outcomes in ACLVO stroke., Methods: This retrospective study examined patients with acute intracranial internal carotid artery or middle cerebral artery-M1 occlusions admitted between 2014 and 2019. Patients were included if they received baseline CT perfusion (CTP) or MRI on presentation within 24 h of estimated stroke onset. Infarct growth rate (IGR) was determined by ischemic core volume on CTP or MRI divided by time from stroke onset to imaging. IGR was used to stratify fast progressor (IGR ≥10 mL/h) and slow progressor (IGR < 10 mL/h) status. Renal dysfunction was assessed based on serum creatinine and estimated glomerular filtration rate (eGFR) on presenting laboratories. Logistic regression models, adjusted for significant covariates, identified independent associations between renal dysfunction biomarkers, progressor status, and clinical outcomes based on modified Rankin Scale (mRS) at 90 days., Results: Among 230 patients with ACLVO, 29% were fast progressors, with median serum creatinine levels higher than slow progressors (1.1 vs. 0.9 mg/dL, p  < 0.05) and lower median eGFR (66.2 vs. 69.0 mL/min/1.73m 2 , p < 0.05). Elevated creatinine (≥1.2 mg/dL) was independently associated with fast progressor status (adjusted OR 2.37, 95% CI 1.18-4.77), worse 90-day mRS (adjusted OR 1.88, 95% CI 1.01-3.51) and mortality (adjusted OR 2.57, 95% CI 1.14-5.79). Reduced eGFR (<60 mL/min/1.73m 2 ) was independently associated with fast progressor status (adjusted OR 2.38, 95% CI 1.14-4.94), but not with 90-day mRS or mortality., Conclusion: Serum creatinine-based biomarkers of renal dysfunction were associated with fast progressor phenotype of ACLVO stroke, and worse clinical outcomes, which may help identify such patients earlier during emergency evaluation for expedited access to EVT. Future prospective studies are warranted to confirm and test implementation of these findings., Competing Interests: RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, Synchron, and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze. RGN is one of the principal investigators of the “Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)” trial. Funding for this project is provided by Cerenovus. RGN is the principal investigator of the “Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe (DUSK)” trial. Funding for this project is provided by Stryker Neurovascular. RGN is an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Vastrax, and Viseon. The remaining author declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rios Rocha, Kayyali, Mahat, Al-Qudah, Doheim, Al-Bayati, Bhatt, Starr, Song, Nogueira and Rocha.)

Visually impaired individuals actively utilize devices like computers, tablets, and smartphones, due to advancements in screen reader technologies. Integrating freely available deep learning models, image captioning can further enhance these readers, providing an affordable assistive tech solution. This research outlines the critical software requirements necessary for image captioning tools to effectively serve this demographic. Two qualitative investigations were conducted to determine these requirements. An online survey was first conducted to identify the main preferences of visually impaired users in relation to audio descriptive software, with findings visualized using word clouds. A subsequent study evaluated the proficiency of existing deep learning captioning models in addressing these stipulated requirements. Emphasizing the need for comprehensive image data, the results highlighted three primary areas: 1) characteristics of individuals, 2) color specifics of objects, and 3) the overall context of images. The research indicates that current captioning tools are not entirely effective for the visually impaired. Based on the delineated requirements and suggested future research paths, there is potential for the development of improved image captioning systems, advancing digital accessibility for the visually impaired.

Chronic pain, edema, and lipodystrophy are common issues in post-menopausal women, often linked to hormonal imbalances, metabolic dysfunctions, and chronic inflammation. Traditional treatments, such as hormone replacement therapy (HRT) and aesthetic procedures, frequently provide limited and temporary relief. This case series evaluates the effectiveness of radio electric asymmetric conveyor (REAC) technology specifically, the anti-cellulite treatment (ACT), circulatory optimization (CO), and metabolic optimization (MO) protocols in four post-menopausal women presenting with these conditions. Each patient underwent 18 sessions of ACT, CO, and MO protocols using the REAC Bio-Enhancer Neuro-Enhancer (BENE) 110 medical device (ASMED Srl, Scandicci Florence, Italy), with asymmetric conveyor probes (ACPs) symmetrically positioned on the quadriceps. The ACT protocol targeted skin and subcutaneous tissue biomechanical properties, the CO protocol focused on enhancing circulation and reducing edema, and the MO protocol aimed to restore metabolic balance. The results demonstrated significant improvements across all patients, with reductions in pain (9/10 to 3/10), edema, and lipodystrophy, as well as enhanced mood and overall well-being. Objective measures, such as reductions in thigh circumference and improvements in inflammatory markers, further supported the systemic benefits of REAC ACT, CO, and MO treatments. These findings suggest that REAC protocols offer a comprehensive and effective non-invasive treatment for chronic inflammatory and metabolic conditions in post-menopausal women., 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: S.R. and V.F., who are the authors of the REAC technology patent, declare(s) a patent from Rinaldi Fontani Institute. Intellectual property info: Rinaldi S and Fontani V are the authors of the REAC technology patent. 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, Higino Rocha et al.)

This case report presents a 67-year-old male with a history of metabolic syndrome, uncontrolled diabetes mellitus, hypertension, and prostate cancer, who underwent radio electric asymmetric conveyer (REAC) biomodulation treatments, specifically anti-cellulite treatment (ACT), circulatory optimization (CO), and metabolic optimization (MO). The patient initially presented with severe pain and edema in the left lower limb, requiring morphine. Over three months, he received a combination of ACT, CO, and MO protocols. Remarkable improvements were observed in pain intensity, edema reduction, balance, and overall quality of life, with a reduced reliance on morphine. This report highlights the potential of REAC biomodulation therapies in managing complex conditions associated with metabolic syndrome., 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: S.R. and V.F. are the authors of the REAC technology patent declare(s) a patent from Rinaldi Fontani Institute. Intellectual property info: Rinaldi S and Fontani V are the authors of the REAC technology patent. 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, Higino Rocha et al.)

Introduction: Predicting which species are susceptible to viruses (i.e., host range) is important for understanding and developing effective strategies to control viral outbreaks in both humans and animals. The use of machine learning and bioinformatic approaches to predict viral hosts has been expanded with advancements in in-silico techniques. We conducted a scoping review to identify the breadth of machine learning methods applied to influenza and coronavirus genome data for the identification of susceptible host species., Methods: The protocol for this scoping review is available at https://hdl.handle.net/10214/26112. Five online databases were searched, and 1,217 citations, published between January 2000 and May 2022, were obtained, and screened in duplicate for English language and in-silico research, covering the use of machine learning to identify susceptible species to viruses., Results: Fifty-three relevant publications were identified for data charting. The breadth of research was extensive including 32 different machine learning algorithms used in combination with 29 different feature selection methods and 43 different genome data input formats. There were 20 different methods used by authors to assess accuracy. Authors mostly used influenza viruses ( n  = 31/53 publications, 58.5%), however, more recent publications focused on coronaviruses and other viruses in combination with influenza viruses ( n  = 22/53, 41.5%). The susceptible animal groups authors most used were humans ( n  = 57/77 analyses, 74.0%), avian ( n  = 35/77 45.4%), and swine ( n  = 28/77, 36.4%). In total, 53 different hosts were used and, in most publications, data from multiple hosts was used., Discussion: The main gaps in research were a lack of standardized reporting of methodology and the use of broad host categories for classification. Overall, approaches to viral host identification using machine learning were diverse and extensive., 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 Alberts, Berke, Rocha, Keay, Maboni and Poljak.)

Drug-resistant epilepsy has a high prevalence worldwide despite efforts such as the Epilepsy Therapy Screening Program conducted by the National Institute of Neurological Disorders and Stroke. It is indicated that drug-resistant epilepsy has various manifestations, and each pattern of manifestation can be modeled using precise experimental models. However, the experimental models used to identify new antiseizure medications to control drug-resistant epilepsy to date do not typically take into account various clinical factors associated with this condition. These factors include comorbidities, sex, age, frequency of seizures and neuroinflammation. It is accordingly necessary to identify the proper characteristics of each type of drug-resistant epilepsy to be mimicked in preclinical models. The use of preclinical models mimicking the characteristics of the different patterns of drug-resistant epilepsy will allow identifying new therapeutic strategies to control this disorder. It is also essential to consider the heterogeneity of clinical factors involved in the condition of drug resistance in epilepsy to get the proper preclinical models., 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 Elsevier Inc. All rights reserved.)

The Brazilian western Amazon is experiencing its largest laboratory-confirmed Oropouche virus (OROV) outbreak, with more than 6,300 reported cases between 2022 and 2024. In this study, we sequenced and analyzed 382 OROV genomes from human samples collected in Amazonas, Acre, Rondônia and Roraima states, between August 2022 and February 2024, to uncover the origin and genetic evolution of OROV in the current outbreak. Genomic analyses revealed that the upsurge of OROV cases in the Brazilian Amazon coincides with spread of a novel reassortant lineage containing the M segment of viruses detected in the eastern Amazon region (2009-2018) and the L and S segments of viruses detected in Peru, Colombia and Ecuador (2008-2021). The novel reassortant likely emerged in the Amazonas state between 2010 and 2014 and spread through long-range dispersion events during the second half of the 2010s. Phylodynamics reconstructions showed that the current OROV spread was driven mainly by short-range (< 2 km) movements consistent with the flight range of vectors. Nevertheless, a substantial proportion (22%) of long-range (>10 km) OROV migrations were also detected, consistent with viral dispersion by humans. Our data provide a view of the unprecedented spread and evolution of OROV in the Brazilian western Amazon region., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: We sought to identify systemic factors influencing door-to-puncture times (DTP) among patients with pre-arrival notifications presenting directly to a comprehensive stroke center (CSC) and undergoing emergent mechanical thrombectomy (MT)., Methods: In this retrospective analysis of a prospectively maintained registry of acute ischemic stroke (AIS) patients undergoing MT at two CSCs between January 2021 and October 2023, we included consecutive AIS patients presenting directly to the CSC with pre-arrival notifications via emergency medical services (EMS) and who underwent emergent MT. We excluded patients with known confounders to DTP and divided this cohort into two groups: DTP ≤75 min and >75 min. We used variables with P value <0.2 in the univariate analysis to build a binary logistic regression model to identify their association with DTP >75 min, adjusting for door-to-CT time., Results: Of 900 patients, 605 were inter-facility transfers, 89 were excluded due to known confounders/missing prehospital notifications, leaving 206 qualifying patients. On multivariable analysis, not meeting American Heart Association (AHA) level 1 criteria (adjusted OR (aOR) 3.04, 95% CI 1.62 to 5.82, P<0.001), lack of Prehospital Stroke Severity Scale (PSSS) acquisition (aOR 2.2, 95% CI 1.19 to 4.11, P=0.01), and presentation after-hours (aOR 2.27, 95% CI 1.23 to 4.28, P=0.01) were associated with >75 min DTP times. Most patients (62.3%) had no clearly documented reasons for delay in MT, whereas 25.8% of delays were attributed to prolonged medical decision-making., Conclusion: Arrival outside business hours, not meeting AHA level 1 criteria, and lack of PSSS acquisition by EMS were associated with prolonged DTP. Impacting modifiable factors such as prehospital assessment of stroke severity is an optimal target for quality improvement., Competing Interests: Competing interests: RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, Synchron, and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse and Perfuze. RGN is one of the Principal Investigators of the 'Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)' trial. RGN is the Principal Investigator of the 'Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe (DUSK)' trial. RGN is an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Vastrax, and Viseon. Other authors report no relevant financial disclosures., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Fumonisins are mycotoxins produced primarily by the Fusarium fujikuroi species complex in maize, and contamination poses significant health risks and economic implications. This review explores Brazil's comprehensive approach to reducing fumonisin contamination in maize, particularly the strategies adopted by the Brazilian Surveillance Agency (ANVISA), thanks to its participation in and the work of the Codex Committee on Contaminants in Foods (CCCF). Through collaborative efforts with several stakeholders, Brazil has successfully reduced fumonisin levels over the past thirty years, improving food safety for its population and exports. The recorded data indicate that the mean levels of fumonisins were 2692.1 µg/kg during the years 1991-2010, while the mean levels decreased to 685.4 µg/kg from 2011 to 2022. Based on this, significant progress has been achieved; nevertheless, challenges persist, particularly concerning enforcement and compliance disparities across the country. In this respect, active engagement from academia, industry, and regulatory bodies is crucial for raising awareness about health and economic risks linked to mycotoxin contamination. Strengthening monitoring efforts and sustainable collaborations are also recommended to further increase fumonisin control and food safety., 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 Ltd.)

Peanut-based products have been associated with Salmonella foodborne outbreaks and/or recalls worldwide. The ability of Salmonella to persist for a long time in a low moisture environment can contribute to this kind of contamination. The objective of this study was to analyse the genome of five S. enterica enterica strains isolated from the peanut supply chain in Brazil, as well as to identify genetic determinants for survival under desiccation and validate these findings by phenotypic test of desiccation stress. The strains were in silico serotyped using the platform SeqSero2 as Miami (M2851), Javiana (M2973), Oranienburg (M2976), Muenster (M624), and Glostrup/Chomedey (M7864); with phylogenomic analysis support. Based on Multilocus Sequence Typing (MLST) the strains were assigned to STs 140, 1674, 321, 174, and 2519. In addition, eight pathogenicity islands were found in all the genomes using the SPIFinder 2.0 (SPI-1, SPI-2, SPI-3, SPI-5, SPI-9, SPI-13, SPI-14). The absence of a SPI-4 may indicate a loss of this island in the surveyed genomes. For the pangenomic analysis, 49 S. enterica genomes were input into the Roary pipeline. The majority of the stress related genes were considered as soft-core genes and were located on the chromosome. A desiccation stress phenotypic test was performed in trypticase soy broth (TSB) with four different water activity (a w ) values. M2976 and M7864, both isolated from the peanut samples with the lowest a w , showed the highest OD 570nm in TSB a w 0.964 and were statistically different (p < 0.05) from the strain isolated from the peanut sample with the highest a w (0.997). In conclusion, genome analyses have revealed signatures of desiccation adaptation in Salmonella strains, but phenotypic analyses suggested the environment influences the adaptive ability of Salmonella to overcome desiccation stress., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maristela da Silva do Nascimento reports financial support was provided by State of Sao Paulo Research Foundation. Otavio G. G. de Almeida reports financial support was provided by State of Sao Paulo Research Foundation. Elaine Cristina Pereira de Martinis reports financial support was provided by National Council for Scientific and Technological Development. Aline Morgan von Hertwig reports financial support was provided by Coordination of Higher Education Personnel Improvement. Maristela da Silva do Nascimento reports financial support was provided by National Council for Scientific and Technological Development. If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Objectives: Excess weight, measured by a high body mass index (BMI), is associated with the onset of many diseases, which can, in turn, lead to disability and premature death, subsequently placing a significant burden on healthcare services. This study analysed the burden of disease and the direct costs to the Brazilian Unified Health System (Sistema Único de Saúde [SUS]) attributable to high BMI in the Brazilian population., Study Design: Ecological study., Methods: This ecological study had two components: (1) a time-series assessment to analyse the burden of diseases attributable to high BMI from 1990 to 2019 in Brazil; and (2) a cross-sectional design to estimate the direct costs of SUS hospitalisations and outpatient procedures attributable to high BMI in 2019. Estimates from the Global Burden of Disease study and the costs of hospital admissions and outpatient procedures from the Department of Informatics of the Brazilian Unified Health System were used. Deaths, years of life lost to premature death (YLLs), years lived with disability (YLDs), and years of life lost adjusted for disability (DALYs) were analysed. The direct health cost was obtained in Brazilian Real (R$) and converted in international Dollars (INT$)., Results: The current study found a reduction in the number of DALYs, YLLs, and deaths per 100,000 population of cardiovascular disease (CVD) attributable to high BMI and an increase in YLD due to diabetes and cardiovascular disease attributable to high BMI from 1990 to 2019. In 2019, high BMI resulted in 2404 DALYs, 658 YLDs, 1746 YLLs, and 76 deaths per 100,000 inhabitants. In the same year, INT$377.30 million was spent on hospitalisations and high- and medium-complexity procedures to control non-communicable diseases attributable to high BMI. The states in the South and Southeast regions of Brazil presented the highest total cost per 10,000 inhabitants. CVDs and chronic kidney disease showed the highest costs per hospital admission, whereas neoplasms and CVDs presented the highest costs for outpatient procedures., Conclusions: High BMI causes significant disease burden and financial costs. The highest expenses observed were not in locations with the highest burden of disease attributable to high BMI. These findings highlight the need to improve current public policies and apply cost-effective intervention packages, focussing on equity and the promotion of healthier lifestyles to reduce overweight/obesity, especially in localities with low socioeconomic status., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

There are various diagnostic techniques available for chronic fasciolosis in ruminants. However, many of them exhibit low specificity and sensitivity, making them impractical for field use and in low-resource laboratories. The present study evaluates the usefulness of the Natural Sedimentation technique in diagnosing chronic fasciolosis in three domestic species conducted at the Laboratorio de Parasitología y Enfermedades Parasitarias, Facultad de Ciencias Veterinas, Universidad Nacional de Cajamarca. Fecal samples were collected from n = 323 cattle, n = 362 sheep, and n = 231 swine for Fasciola hepatica fecal egg counts. The visualization of adult parasites in animal livers post-mortem was considered the gold standard. Additionally, the sensitivity of the technique was evaluated using five different amounts of feces. In cattle, a sensitivity of 0.93 ± 0.03, specificity of 0.91 ± 0.06, positive predictive value of 0.96 ± 0.03, and negative predictive value of 0.86 ± 0.07 were obtained. In sheep, a sensitivity of 0.79 ± 0.05, specificity of 0.83 ± 0.07, positive predictive value of 0.90 ± 0.04, and negative predictive value of 0.66 ± 0.08 were observed. In swine, a sensitivity of 0.92 ± 0.06, specificity of 1.00 ± 0.00, positive predictive value of 1.00 ± 0.00, and negative predictive value of 0.96 ± 0.03 were found. There was no statistical difference in egg counts when using 1, 2, 3, 4, and 5 g of feces (p = 0.907). Furthermore, 1 to 688 fecal eggs of F. hepatica were counted in 1 g of feces. The Natural Sedimentation technique has both qualitative and quantitative applications with satisfactory results when using 1 g of feces in the diagnosis of chronic fasciolosis in domestic animals. Due to its simplicity, it can be implemented in field conditions and low-resource laboratories., 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.)

This work discusses the ongoing challenge of cancer, focusing on therapy issues such as chemotherapy resistance and adverse drug effects. It emphasizes the need for new anticancer agents with improved efficacy and fewer side effects, exploring natural products from plant sources. The Annonaceae family, specifically the Annona genus, is highlighted for its medicinal properties, including anti-inflammatory and anticancer effects. The study focuses on the isolation and elucidation of the substances present in Annona acutiflora leaves. The methodology involves chromatographic and spectroscopy techniques. The isolated compounds, (6S)-5'-oxohepten-1'E,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (1), (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (2) and (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (3) were investigated for cytotoxicity assays on cancer cell lines and normal cells. Results show promising cytotoxic activity, particularly with compound 3, demonstrating potential activity against oral cancer (43.18 μM), hepatocarcinoma (17.24 μM), melanoma (5.39 μM), and colon cancer (59.03 μM). The compound outperforms carboplatin in selectivity against oral cancer (S. I. 2.15) and melanoma (S. I. 17.22). The study concludes by suggesting the potential of these α-pyrones as effective and less toxic alternatives for cancer therapy., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Essential oils show several biological properties, such as antimicrobial activity, but have limitations regarding their availability and stability. To maximize their antimicrobial effect and protection against environmental conditions, Pickering-type emulsions were used to vehiculate oregano essential oil (OEO) using cellulose nanofibers (CNF) as emulsion stabilizer. Enzymatic hydrolysis was used to produce CNF from a food industry waste (cassava peel), obtaining an environmentally sustainable emulsion stabilizer. It was evaluated how the different properties of the nanofibers affected the stability of the emulsions. Furthermore, the composition of the dispersed phase was varied (different ratios of OEO and sunflower oil-SO) in view of the target application in biodegradable active coatings. Even at very low concentration (0.01 % w/w), CNF was able to form kinetically stable emulsions with small droplet sizes using oil mixtures (OEO + SO). The stabilization mechanism was not purely Pickering, as there was a reduction in interfacial tension. Excellent antimicrobial activity was observed against bacteria and the fungus Alternaria alternata, demonstrating the ability to apply these emulsions in active systems such as coatings and films. An improvement in the stability of emulsions was observed when using a mixture of oils, which is extremely advantageous considering costs and stability to heat treatments, since the desired antimicrobial activity is maintained for the final application., 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 Elsevier B.V. All rights reserved.)

Introduction: The mothers of newborns who are discharged from a neonatal intensive care unit (NICU) experience stress and anxiety due to the specialized care their child requires at home, affecting their perception of maternal self-efficacy., Objective: To evaluate the effect of the nursing intervention called Hospital Discharge Plan (HDP) on the promotion of self-efficacy in mothers of newborns discharged from the NICU., Method: Quantitative study, quasi-experimental design with pre-test/post-test in a single group, using the Parental Evaluation Scale applied to a convenience sample of 72 mothers of high-risk newborns from a NICU located in the city of Villavicencio (Colombia). The first measurement was taken between days 3 and 4 before discharge and at 15 days' post-discharge. Data processing was carried out using the statistical program SPSS, version 21. The intervention was based on the four concepts of self-efficacy by Barbara Resnick., Results: The perception of maternal self-efficacy before the intervention showed a median of 8.9 points (RI 7.6-9.5); after the intervention it showed a median of 9.6 points (RI of 10-8.7); a statistically significant p-value < 0.001 was obtained before and after the intervention with the Wilcoxon rank test., Conclusions: Education and follow-up promoted the development of knowledge and skills in mothers for the care of high-risk newborns. This contributed to the experience of mastery and vicarious experience from the teaching-learning process and contact with the experience of other mothers, which contributes to the effective development of motherhood., (Copyright © 2023 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Published by Elsevier España S.L.U. All rights reserved.)

Solid tumors are dense three-dimensional (3D) multicellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune-suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contribution of ILT2 and ILT4 to immune inhibition in the context of solid tumor tissue has not been fully explored. We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that although ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. In a 3D spheroid tumor model, dual ILT2/ILT4 blockade was required for the optimal activation of myeloid cells, including the secretion of CXCL9 and CCL5, upregulation of CD86 on dendritic cells, and downregulation of CD163 on macrophages. Humanized mouse tumor models showed increased immune activation and cytolytic T-cell activity with combined ILT2 and ILT4 blockade, including evidence of the generation of immune niches, which have been shown to correlate with clinical response to immune-checkpoint blockade. In a human tumor explant histoculture system, dual ILT2/ILT4 blockade increased CXCL9 secretion, downregulated CD163 expression, and increased the expression of M1 macrophage, IFNγ, and cytolytic T-cell gene signatures. Thus, we have revealed distinct contributions of ILT2 and ILT4 to myeloid cell biology and provide proof-of-concept data supporting the combined blockade of ILT2 and ILT4 to therapeutically induce optimal myeloid cell reprogramming in the tumor microenvironment., (©2024 American Association for Cancer Research.)

Background: Toll-like receptors (TLRs) play a critical role in initiating the innate immune response to infection or injury. Recent studies have uncovered their intriguing functions as moonlighting proteins involved in various biological processes, including development, learning, and memory. However, the specific functions of individual TLRs are still largely unknown., Aims: We investigated the effects of TLR3 and TLR9 receptor deficiency on motor, cognitive, and behavioral functions during development using genetically modified male mice of different ages., Methods: We evaluated the motor coordination, anxiety-like behavior, spatial learning, and working memory of male mice lacking the TLR3 and TLR9 genes at different ages (two, four, six, and eight months) using the rotarod, open field, water maze, and T-maze tests., Results: We observed that the deletion of either TLR3 or TLR9 resulted in impaired motor performance. Furthermore, young TLR3-deficient mice exhibited reduced anxiety-like behavior and spatial learning deficits; however, their working memory was unaffected. In contrast, young TLR9-knockout mice showed hyperactivity and a tendency toward decreased working memory., Conclusions: These findings provide valuable insights into the broader roles of the TLR system beyond the innate immune response, revealing its involvement in pathways associated with the central nervous system. Importantly, our results establish a strong association between the endosomal receptors TLR3 and TLR9 and the performance of motor, cognitive, and behavioral tasks that change over time. This study contributes to the growing body of research on the multifaceted functions of TLRs and enhances our understanding of their participation in non-immune-related processes., Competing Interests: Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the research., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Schistosomiasis is a neglected disease transmitted through contaminated water in populations with low basic sanitation. The World Health Organization recommends controlling the intermediate host snails of the Biomphalaria genus with the molluscicide niclosamide. This work aims to evaluate the biocidal potential of the nanoemulsion prepared with the essential oil of Ocotea indecora leaves for the control of the mollusk Biomphalaria glabrata, intermediate host of the Schistosoma mansoni, the etiologic agent of schistosomiasis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The proper establishment of plants is essential for the efficient use of resources such as water and light. Besides, even after seed storage and sowing the uniform establishment of plants is essential for their success. Crotalaria ochroleuca and Crotalaria spectabilis are important medicinal plants with poor seed germination rate, occasionally. The effects of seed priming in both C. ochroleuca and C. spectabilis were evaluated in seed performance even after seeds storage for up 90-days. Experimental assays were performed in a randomized design with gibberellic acid (GA3, 100 ppm), polyethylene glycol (PEG 6000, -0.2 MPa) and PEG (-0.2 MPa) + GA3 (100 ppm) solutions during seed priming in four replicates. Seeds not submitted to priming treatments constituted control. Seeds physiological performance were evaluated immediately and even after 30, 60 and 90-days seed dry-storage. The data obtained in each experiment were submitted to variance analysis (ANOVA) adopting a confidence level of 95%. The effects of seed priming with PEG and GA3 during seed ageing were significant for germination variables of C. ochroleuca and C. spectabilis. During dry storage, seed viability of both species gradually decreased and the first symptoms were delayed seed germination, especially more evident for C. ochroleuca, even in primed or non-primed seeds. Afterwards, C. ochroleuca seeds previously GA3 primed had higher results of root protrusion (86%), hypocotyls elongation (76%) and complete seedlings (75%) than non-primed seeds (control). These findings shown a good potential of hormopriming to attenuate damage during the seed aging of C. ochroleuca.

Background: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent., Methodology/principal Findings: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR., Conclusions/significance: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zini 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.)

The intensification of production systems has resulted in detrimental effects on sow welfare, which can have an adverse influence on their offspring. Considering the relevance of the microbiota-gut-brain axis, probiotics can mitigate such impacts. To investigate the effects of the dietary inclusion of probiotics on the welfare of sows and piglets, 147 multiparous sows were randomly assigned to two groups: a control group or a group supplemented with a multistrain probiotic from the beginning of pregnancy to the end of lactation. The human-animal relationship (HAR), stereotypic behavior, position changes, salivary cortisol, and plasma serotonin levels were assessed in the sows. The piglets' back test behavior and organ weight were analyzed. The probiotic-supplemented sows exhibited a better HAR index ( p = 0.017), which indicated reduced aversion towards humans. The frequency of stereotypies was not influenced by the treatments. However, the supplemented sows spent more time standing ( p = 0.054) and less time lying down ( p = 0.008). The cortisol level of the supplemented sows was 50% lower ( p = 0.047) and the serotonin levels were 11% higher ( p = 0.034) than control animals. The multistrain piglets were more passive and less resistant ( p = 0.076) in the back test. The organ weights were not influenced by treatments. In conclusion, the sows supplemented with probiotics showed less fear and more motivation indicators, while their piglets showed less aggression behaviors.

The present study sought to evaluate the antimicrobial and anti-adherent potential of Eucalyptus radiata essential oil against food-borne strains of Escherichia coli. The study was performed using the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). In addition, the disk diffusion technique was used to evaluate the association of Eucalyptus radiata essential oil with synthetic antimicrobials. The Minimum Inhibitory Adherence Concentration (MIC) was also performed. The results revealed that E. radiata showed antimicrobial activity against the E. coli strains tested, with MIC values ranging from 500 μg/mL to 1000 μg/mL and MBC values ranging from 500 μg/mL to 1,024 μg/mL. As for the associations, it was observed that E. radiata oil exhibited a synergistic effect for some antibiotics, especially Ceftriaxone, with greater interference from the essential oil. Furthermore, it was effective in inhibiting the adherence of bacterial strains of E. coli, showing a more significant antibiofilm effect than the antibacterial agent 0.12% chlorhexidine digluconate. In summary, the essential oil of E. radiata showed antimicrobial potential against strains of E. coli of food origin, and can therefore, through in-depth studies, be used alone or in association with synthetic antimicrobials to combat infections caused by this pathogen.

Objectives: This study aimed to assess the prevalence of blood-borne infectious agents in healthy, client-owned dogs from a blood donor population in Portugal and Spain, and to address the importance of a screening protocol on every donation., Materials and Methods: Client-owned healthy dogs were tested before each donation on a veterinary blood bank. Blood samples from new potential donors, and from regular donors, were tested by real-time polymerase chain reaction for Leishmania species, Ehrlichia species, Brucella species, Babesia species and Anaplasma species Serological tests were also performed for Leishmania species, Ehrlichia species and Dirofilaria immitis. All donors were tested for every infectious agent in each donation., Results: The study found that out of a total of 8036 donors and 35,120 samples tested, 3.9% of blood donors tested positive for at least one of the agents, with the most prevalent being Anaplasma species (2.1%). Serological tests also revealed positive results in 14.0% of donors, with the highest percentage for Leishmania species (7.7%). Moreover, the study found that 28.2% of positive results were from dogs with negative results in donations performed 3 to 12 months before, and 18.0% of positive results were recent infections., Clinical Significance: These findings indicate a high prevalence of infectious agents in seemingly healthy, selected dogs eligible to become blood donors in the Iberian Peninsula, highlighting the importance of regular testing on every donation. This study emphasises the importance of a regular screening protocol for every donation instead of annual testing, as is commonly performed in veterinary medicine., (© 2024 British Small Animal Veterinary Association.)

Pharmacy personnel that manipulate cytotoxic drugs are under continuous exposure risk. Therefore, training and strict adherence to recommended practices should always be promoted. The main objective of this study was to develop and apply a safe, effective and low-cost method for the training and assessment of the safe handling of cytotoxic drugs, using commercially available tonic water. To evaluate the potential of tonic water as a replacement marker for quinine hydrochloride, deliberate spills of 1 mL of four different tonic waters (one coloured and three non-coloured) were analysed under ultraviolet light (300-400 nm). The pigmented sample did not produce fluorescence under ultraviolet (UV) light. The three commercially available tonic waters that exhibited fluorescence were further analysed by UV/Vis spectrophotometry (300-500 nm). Afterwards, a protocol of simulated manipulation of cytotoxic drugs was developed and applied to 12 pharmacy technicians, that prepared 24 intravenous bags according to recommended routine procedures using tonic water. Participants responded to a brief questionnaire to evaluate the adequacy and applicability of the activity. Seven of the participants had spillages during manipulation, the majority of which recorded during manipulation with needles. All participants scored the tonic water manipulation simulation with 4 or 5 points for simplicity, efficiency and feasibility. The obtained results suggest that tonic water can be used to simulate the manipulation of cytotoxic drugs in training and assessment programs. By using this replacement marker for quinine hydrochloride, it is possible to perform a more cost-effective, yet equally effective, assessment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

ABSTRACT The brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases. Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting. Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults. Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.

Supplementing minerals beyond dietary requirements can increase the risk of toxicity and mineral excretion, making the selection of more bioavailable sources crucial. Thus, this work aimed to use metalloproteomics tools to investigate possible alterations in the hepatic proteome of broilers fed with diets containing two sources (sulfate and hydroxychloride) and two levels of copper (15 and 150 ppm) and manganese (80 and 120 ppm), totaling four treatments: low Cu/Mn SO 4 , high Cu/Mn SO 4 , low Cu/Mn (OH)Cl and high Cu/Mn (OH)Cl. The difference in abundance of protein spots and copper and manganese concentrations in liver and protein pellets were analyzed by analysis of variance with significance level of 5%. The Cu and Mn concentrations determined in liver and protein pellets suggested greater bioavailability of hydroxychloride sources. We identified 19 Cu-associated proteins spots, 10 Mn-associated protein spots, and 5 Cu and/or Mn-associated protein spots simultaneously. The analysis also indicated the induction of heat shock proteins and detoxification proteins in broilers fed with high levels of copper and manganese, suggesting the involvement of these proteins in metal tolerance and stress., (© 2024. The Author(s).)

Citrus bergamia is a citric species known as bergamot. The species is widely used due to its derivatives, such as juices, extracts, and essential oil. Specifically, the bergamot essential oil (BEO) is of great interest, with a chemical composition rich in terpenes and esters. Considering its chemical composition, bioactivity, and great economic potential, the characterization of BEO should be studied. However, this essential oil is almost unexplored in terms of a characterization associated with colloids. Chemical characterization was carried out by gas-chromatography coupled to a mass spectrometer and by gas-chromatography coupled to a flame ionization detector. Antibacterial activity against Staphylococcus aureus and Escherichia coli was carried out to confirm the bioactivity of this important essential oil. Dynamic light scattering analysis was performed to create a pattern of droplet size distribution of BEO. Major compounds of BEO were linalyl acetate, limonene, and linalool. The BEO was active against E. coli and presented a MIC value of 2.000 µg/mL, while values of MIC and MBC higher than 2.000 µg/mL were observed for S. aureus. The dynamic light scattering analysis revealed a mean hydrodynamic diameter of 65.7 ± 2.2 nm. After a 1:10 dilution it was observed reduction of mean diameter and enhancement of the percentagem of low size droplets, resepctively 44.1 ± 1.2 nm and 14.5 ± 0.5 nm (28.8 ± 1.2%). Higher droplets and reduced polydispersity index were observed after 1:100 dilution. In the present study, the chemical characterization was in accordance with the species, as the characteristic chemical markers of the species were found. Moreover, it has presented antibacterial activity as expected for the BEO. The analysis of the colloid showed a pattern of droplet size distribution following the Ostwald ripening mechanism after dilution.

Introduction: The Centers for Disease Control and Prevention's (CDC) National Center for Injury Prevention and Control (NCIPC) funds Injury Control Research Centers (ICRCs). These centers study injury and violence prevention through three core areas: (1) Research conducts cutting-edge, multidisciplinary research in the injury and violence prevention field; (2) Outreach translates injury and violence prevention research into action; and (3) Training educates and trains the next generation of injury and violence prevention professionals. We examined ICRC work from 2012 to 2019 to determine whether they fulfilled their goal of furthering injury and violence prevention research and practice., Methods: We created a database of core area accomplishments reported through annual and interim progress reports. These reports track core area accomplishments by injury and violence prevention topic area, publications, partnerships, and trainings., Results: From 2012 to 2019, ten ICRCs from two funding cycles received approximately $49 million. ICRCs reported 703 research, 1,432 outreach, and 660 training accomplishments. There were also 342 accomplishments contributing to a special tool or resource. These accomplishments focused on preventing traumatic brain injury, suicide, adverse childhood experiences, and transportation safety. ICRCs produced over 3,500 peer-reviewed publications. ICRCs reported over 3,600 accomplishments partnered with academic institutions, public health agencies, healthcare, and non-profit organizations. ICRCs created resources for audiences such as students, law enforcement, and policy makers. ICRCs trained 3,131 students and faculty., Practical Applications: ICRCs are the hubs of modern research and practice in the injury and violence prevention field. They successfully bring together stakeholders from disparate disciplines, perspectives, and agencies to join forces and tackle critical public health problems., Conclusion: ICRCs are an integral component of NCIPC's, CDC's and the Department of Health and Human Service's missions to protect and enhance the health of Americans. Research covered NCIPC research priorities over the funding period, furthering injury and violence prevention research and working as a foundation to practice and policy. Outreach and partnerships with an array of organizations put research into action. Trainings educated the new generation of injury and violence prevention professionals., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘This project was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the Centers for Disease Control and Prevention. Findings reported in this publication were partially supported by the Centers for Disease Control and Prevention (CDC) contract (HHSD2002013M53955B) with NORC at the University of Chicago’., (Copyright © 2023 National Safety Council and Elsevier Ltd. All rights reserved.)

Traumatic brain injury (TBI) represents one of the leading causes of disability and death worldwide. The annual economic impact of TBI-including direct and indirect costs-is high, particularly impacting low- and middle-income countries. Despite extensive research, a comprehensive understanding of the primary and secondary TBI pathophysiology, followed by the development of promising therapeutic approaches, remains limited. These fundamental caveats in knowledge have motivated the development of various experimental models to explore the molecular mechanisms underpinning the pathogenesis of TBI. In this context, the Lateral Fluid Percussion Injury (LFPI) model produces a brain injury that mimics most of the neurological and systemic aspects observed in human TBI. Moreover, its high reproducibility makes the LFPI model one of the most widely used rodent-based TBI models. In this chapter, we provide a detailed surgical protocol of the LFPI model used to induce TBI in adult Wistar rats. We further highlight the neuroscore test as a valuable tool for the evaluation of TBI-induced sensorimotor consequences and their severity in rats. Lastly, we briefly summarize the current knowledge on the pathological aspects and functional outcomes observed in the LFPI-induced TBI model in rodents., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training and similar technologies.)

As nephrology practice is evolving toward precision medicine, and genetic tests are becoming widely available, basic genetic literacy is increasingly required for clinical nephrologists. Yet, decisions based on results of genetic tests are seldom straightforward. We report a 37-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) who was referred for medically assisted reproduction with monogenic preimplantation genetic testing (PGT-M). The PKD1 and PKD2 genes were screened for pathogenic variants. Sequencing analysis revealed the presence of three novel missense single nucleotide variants, two in the PKD1 gene - c.349T&gt;G, p.(Leu117Val) and c.1736C&gt;T, p.(Pro579Leu); and the third in the PKD2 gene - c.1124A&gt;G, p.(Asn375Ser). Bioinformatic predictions of the functional effects of those three missense variants were inconsistent across different software tools. The family segregation analysis, which was mandatory to identify the relevant variant(s) for PGT-M, strongly supported that the disease-causing variant was PKD1 c.349T&gt;G p.(Leu117Val), while the other two were nonpathogenic or, at most, phenotypic modulators. Proving the pathogenicity of novel variants is often complex but is critical to guide genetic counseling and screening, particularly when discussing reproductive alternatives for primary prevention in the progeny of at-risk couples. The family reported herein illustrates those challenges in the setting of ADPKD, and the invaluable importance of a detailed family history and segregation analysis for proper clinical annotation of novel variants. Basic genetic knowledge and proper clinical annotation of novel allelic variants in genes associated with hereditary kidney disorders are increasingly necessary for the contemporary practice of clinical nephrology., (© 2024 S. Karger AG, Basel.)

Knowing the impacts of bisphenol A (BPA) on human health, this systematic review aimed to gather the analytical methods for the quantification of BPA release of BPA in dental materials in in vitro and in vivo (biological fluids) studies. A brief critical discussion of the impacts of BPA on human health and the possible association with BPA in dental materials was also presented. The research was carried out by three independent researchers, (according to PRISMA guidelines) in PUBMED and SCOPUS databases, by searching for specific keywords and articles published between January 2011 and February 2022. Seventeen articles met the eligibility criteria and were included in this systematic review: 10 in vitro and 7 in vivo . In in vitro studies, the highest amounts of BPA released were from flowable to conventional resins, followed by resin-modified glass ionomer. In contrast, the smallest amount was released from "BPA-free" composites and CAD-CAM blocks. Regarding in vivo studies, a higher concentration of BPA were found in saliva than urine or blood. The best analytical method for trace quantifying BPA is LC-MS/MS (Liquid Chromatography with Tandem Mass Spectrometry) due to its selectivity, low quantification limits, and the unequivocal identification. However, further studies are required to develop faster and more sensitive methods, in order to obtain more reliable results.

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy. Synaptic terminals (synaptosomes) were obtained from the epileptic neocortex of patients with drug-resistant temporal lobe epilepsy (DR-TLE, n = 10) or drug-resistant extratemporal lobe epilepsy (DR-ETLE, n = 10) submitted to epilepsy surgery. Synaptosomes highly purified by Percoll-sucrose density gradient were characterized by confocal microscopy and Western blot. Synaptosomes were used to estimate the high KCl (33 mM)-evoked glutamate release in the presence of CBD at different concentrations. Our results revealed responsive tissue obtained from seven patients with DR-TLE and seven patients with DR-ETLE. Responsive tissue showed lower glutamate release ( p < 0.05) when incubated with CBD at low concentrations (less than 100 µM) but not at higher concentrations. Tissue that was non-responsive to CBD (DR-TLE, n = 3 and DR-ELTE, n = 3) showed high glutamate release despite CBD exposure at different concentrations. Simultaneously, a block of the human epileptic neocortex was used to determine its viability through whole-cell and extracellular electrophysiological recordings. The electrophysiological evaluations supported that the responsive and non-responsive human epileptic neocortices used in the present study exhibited proper neuronal viability and stability to acquire electrophysiological responses. We also investigated whether the subchronic administration of CBD could reduce glutamate over-release in a preclinical model of temporal lobe epilepsy. Administration of CBD (200 mg/kg, p.o. every 24 h for 7 days) to rats with lithium-pilocarpine-evoked spontaneous recurrent seizures reduced glutamate over-release in the hippocampus. The present study revealed that acute exposure to low concentrations of CBD can reduce the glutamate over-release in synaptic terminals obtained from some patients with DRE. This effect is also evident when applied subchronically in rats with spontaneous recurrent seizures. An important finding was the identification of a group of patients that were non-responsive to CBD effects. Future studies are essential to identify biomarkers of responsiveness to CBD to control DRE.

Leishmaniasis is a vector-transmitted zoonosis caused by different species of the genus Leishmania, with a wide clinical spectrum. It is a public health problem aggravated by a series of limitations regarding treatment. In the search for new therapeutic alternatives, scorpion venoms are a source of multifunctional molecules that act against the natural resistance of pathogens. This work evaluated the antileishmanial potential of Brotheas amazonicus and Tityus metuendus venoms against the promastigote forms of Leishmania amazonensis e Leishmania guyanensis. The venoms of B. amazonicus and T. metuendus were evaluated for their constituents using Fourier Transform Infrared (FTIR). Growth inhibition and death of promastigotes were evaluated in the presence of diferente crude venom concentrations (100 µg/mL, 50 µg/mL, 10 µg/mL, 1 µg/mL) after one hour of incubation at 25 °C. The FTIR spectra of both venoms exhibited bands in approximate regions, revealing that both exhibit similar functional groups. Crude venom from both scorpion species showed similar or superior leishmanicidal effects to the standart drug N-methylglucamine antimoniate. At the highest concentration of 100 µg/mL, cultures of L. guyanensis treated with the venom of B. amazonicus showed the highest mortality percentages, above 28%, while T. metuendus venom showed the highest activity against L. amazonensis, with mortality above 7%. This preliminar study demonstrates that B. amazonicus and T. metuendus venoms can be important tools in the search for new drugs Against leishmaniasis. Next step involves evaluating the activity against the amastigote forms and purifying the venom proteins in order to identify the best anti-leishmania candidates.

Artepillin C is the most studied compound in Brazilian Green Propolis and, along with its acetylated derivative, displays neurotrophic activity on PC12 cells. Specific inhibitors of the trkA receptor (K252a), PI3K/Akt (LY294002), and MAPK/ERK (U0126) signaling pathways were used to investigate the neurotrophic mechanism. The expression of proteins involved in axonal and synaptic plasticity (GAP-43 and Synapsin I) was assessed by western blotting. Additionally, physicochemical properties, pharmacokinetics, and drug-likeness were evaluated by the SwissADME web tool. Both compounds induced neurite outgrowth by activating the NGF-signaling pathways but through different neuronal proteins. Furthermore, in silico analyses showed interesting physicochemical and pharmacokinetic properties of these compounds. Therefore, these compounds could play an important role in axonal and synaptic plasticity and should be further investigated., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DANs), and Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson's disease (PD) patients. Here, we obtained well-characterized DANs from hESCs and transplanted them into two parkinsonian monkeys to assess their behavioral and imaging changes. DANs from hESCs expressed dopaminergic markers, generated action potentials, and released dopamine (DA) in vitro. These neurons were transplanted bilaterally into the putamen of parkinsonian NHPs, and using magnetic resonance imaging techniques, we calculated the fractional anisotropy (FA) and mean diffusivity (MD), both employed for the first time for these purposes, to detect in vivo axonal and cellular density changes in the brain. Likewise, positron-emission tomography scans were performed to evaluate grafted DANs. Histological analyses identified grafted DANs, which were quantified stereologically. After grafting, animals showed signs of partially improved motor behavior in some of the HALLWAY motor tasks. Improvement in motor evaluations was inversely correlated with increases in bilateral FA. MD did not correlate with behavior but presented a negative correlation with FA. We also found higher 11C-DTBZ binding in positron-emission tomography scans associated with grafts. Higher DA levels measured by microdialysis after stimulation with a high-potassium solution or amphetamine were present in grafted animals after ten months, which has not been previously reported. Postmortem analysis of NHP brains showed that transplanted DANs survived in the putamen long-term, without developing tumors, in immunosuppressed animals. Although these results need to be confirmed with larger groups of NHPs, our molecular, behavioral, biochemical, and imaging findings support the integration and survival of human DANs in this pre-clinical PD model.

The rubber tree (Hevea brasiliensis (Willd. ex A.Juss.) Müll.Arg.), a native Amazonian species, is responsible for more than 50 thousand products and stands out as the world's main source of natural rubber. Commercial production is carried out by grafting, however, the technique has gaps in terms of time and quality for seedling production. Vegetative production via cuttings is an alternative, however, the species is difficult to root. Thus, the study tested the rooting induction, through a chemical method, with the hormonal regulator indolbutyric acid (IBA) of 5000 ppm, and a mechanical method, with the strangulation of stems, and the interaction between the methods, to analyze the survival and sprouting of rubber tree (Hevea brasiliensis) cuttings, as well as verifying the efficiency of breaking the sclerenchyma ring by strangulation. A randomized block design was used, with four treatments (control, with strangulation, with IBA, strangulation x IBA) distributed in six blocks with 36 cuttings. Data were submitted to ANOVA test and Tukey's post-test (p>0.05). The results obtained 12.5% of live cuttings, without rooting, during 68 days, being the combination of strangulation and IBA with greater survival and sprouting. No breakage of the sclerenchyma ring was observed by histological analysis. The data indicate strategic gains in combining chemical and mechanical techniques for species of difficult rooting in vegetative propagation, however, the test was not enough to affirm an answer in relation to each technique, the deepening of the technique on the behavior of the species remains the biggest challenge.

Despite progress in the development of anti-seizure medications (ASMs), one third of people with epilepsy have drug-resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies., (© 2023 International League Against Epilepsy.)

Introduction: Porto-sinusoidal vascular syndrome is characterised by specific histological changes that do not include cirrhosis, with or without portal hypertension. Patients are usually asymptomatic until development of portal hypertension complications., Case Description: A 69-year-old female with history of JAK2 positive essential thrombocythemia (ET) was referred to internal medicine consultation due to elevated liver enzymes. The patient had no previous history of liver disease. Seven months earlier, she had an ischaemic stroke and started treatment with atorvastatin. After discontinuing medication, liver enzymes returned to normal and atorvastatin-related drug-induced liver disease (DILI) was presumed.During a follow-up visit, iron deficiency anaemia was detected and an endoscopic study was performed. It revealed a gastric varix actively bleeding, which was successfully treated with cyanoacrylate.Two months later, the patient was admitted due to a new episode of variceal bleeding, and a portal hypertension complementary study was made., Discussion: Although the pathogenesis of porto-sinusoidal vascular disease (PSVD) remains poorly understood, vascular changes within the liver have been associated with several predisposing conditions, such as hypercoagulable states. Patients with ET, especially those with JAK2 mutation, are known to be at increased risk of non-cirrhotic vein thrombosis. Concerning PSVD, the association is not clear but it is believed that both PSVD and myeloproliferative neoplasms share a common denominator: a state characterised by hypercoagulability, inflammation, endothelial dysfunction and, in some cases, portal hypertension., Conclusion: Portal hypertension without cirrhosis is a rare condition, presenting diagnostic challenges and significant impact on the patient's prognosis., Learning Points: The suspicion of PSVD should be raised when signs of portal hypertension are present with normal or mildly elevated liver enzymes and normal liver stiffness measurement. A liver biopsy should be performed in this situation.Although the pathogenesis of PSVD is not clearly understood, it is based on the development of vascular changes within the liver and there might be several predisposing conditions such as coagulation disorders., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2023.)

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients., Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed., Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001)., Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults., Competing Interests: Authors AD and LA were employed by Fleury Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Fleury Group. The funder had the following role in the study: data acquisition and logistics., (Copyright © 2023 de Freitas Dias, Fieni Toso, Slhessarenko Fraife Barreto, de Araújo Gleizer, Dellavance, Kowacs, Teive, Spitz, Freire Borges Juliano, Januzi de Almeida Rocha, Braga-Neto, Ribeiro Nóbrega, Oliveira-Filho, Maciel Dias, de Oliveira Godeiro Júnior, Martins Maia, Barbosa Thomaz, Santos, Sousa de Melo, da Nóbrega Júnior, Lin, Graziani Povoas Barsottini, Endmayr, Coelho Andrade, Höftberger and Almeida Dutra.)

The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1-10-year-old (yo); adolescents:11-20 yo; adults 21-40 yo; and older adults: 41-75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1β, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1-10 yo and 11-20 yo), whereas in older ages (21-40 yo and 41-75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases., 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.)

Objective: Assess the perceived protection afforded by a range of COVID-19 vaccines in immune-mediated inflammatory diseases patients previously vaccinated against SARS-CoV-2., Study Design: Survey., Methods: On-line cross-sectional survey aimed at evaluating the perceived protection (and its determinants) afforded by a range of COVID-19 vaccines among immune-mediated inflammatory diseases previously vaccinated for COVID-19., Results: Out of 493 eligible respondents who lived in Brazil, 397 (80.5%) were confident that their primary vaccination series would protect them against severe COVID-19. In multivariate analysis, only overlapping immune-mediated inflammatory diseases remained (negatively) associated with the perception of protection., Conclusions: No influence was found between COVID-19 vaccine types and the perception of protection after initial vaccinations., Competing Interests: The authors declare that there is no conflict of 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., (© 2023 The Authors.)

Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the Schistosoma genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents. This work evaluates the effects of a nanoemulsion containing essential oil from Myrciaria floribunda leaves as a molluscicidal and cercaricidal agent against Biomphalaria glabrata mollusks and Schistosoma mansoni cercariae. The Myrciaria floribunda essential oil from leaves showed nerolidol, β-selinene, 1,8 cineol, and zonarene as major constituents. The formulation study suggested the F3 formulation as the most promising nanoemulsion with polysorbate 20 and sorbitan monooleate 80 (4:1) with 5% ( w / w ) essential oil as it showed a smaller droplet size of approximately 100 nm with a PDI lower than 0.3 and prominent bluish reflection. Furthermore, this nanoemulsion showed stability after 200 days under refrigeration. The Myrciaria floribunda nanoemulsion showed LC 50 values of 48.11 µg/mL, 29.66 µg/mL, and 47.02 µg/mL in Biomphalaria glabrata embryos, juveniles, and adult mollusks, respectively, after 48 h and 83.88 µg/mL for Schistosoma mansoni cercariae after 2 h. In addition, a survival of 80% was observed in Danio rerio, and the in silico toxicity assay showed lower overall human toxicity potential to the major compounds in the essential oil compared to the reference molluscicide niclosamide. These results suggest that the nanoemulsion of Myrciaria floribunda leaves may be a promising alternative for schistosomiasis control.

The influence of manganese modification on the spectroscopic features of manganese-doped CeO 2 systems synthesized by the microwave-assisted hydrothermal route and their correlation with the presence of O defective structures were verified, focusing on their interaction with poisonous atmospheres. Raman and electron paramagnetic resonance studies confirmed the presence of defective clusters formed by dipoles and/or quadrupoles. The number of paramagnetic species was found to be inversely proportional to the doping concentration, resulting in an increase in the Mn 2+ signal, likely due to the reduction of Mn 3+ species after the interaction with CO. X-ray photoelectron spectroscopy data showed the pure system with 33% of its cerium species in the Ce 3+ configuration, with an abrupt decrease to 19%, after the first modification with Mn, suggesting that 14% of the Ce 3+ species are donating one electron to the Mn 2+ ions, thus becoming nonparamagnetic Ce 4+ species. On the contrary, 58% of the manganese species remain in the Mn 2+ configuration with five unpaired electrons, corroborating the paramagnetic feature of the samples seen in the electron paramagnetic resonance study.

Anthropogenic impacts have affected the coastal environment and contributed to its contamination. Mercury (Hg) is widespread in nature and has been shown to be toxic in even the smallest amounts, negatively affecting not only the marine ecosystem but also the entire trophic chain due to its biomagnification. Mercury ranks third on the Agency for Toxic Substances and Diseases Registry (ATSDR) priority list and it is therefore imperative to develop more effective methods than those currently available to avoid the persistence of this contaminant in aquatic ecosystems. The present study aimed to evaluate the effectiveness of six different silica-supported ionic liquids (SIL) in removing Hg from contaminated saline water, under realistic conditions ([Hg] = 50 µg/L), and to ecotoxicologically evaluate the safety of the SIL-remedied water, using as test model the marine macroalga Ulva lactuca. The results revealed that SIL [Si][C3C1im][SCN] (250 mg/L) was the most effective in removing Hg from solution, with a efficiency up to 99 % in just 6 h, that enable to obtain < 1 µg/L Hg (European guideline in drinking water). U. lactuca exposed to either the SIL and/or the remedied water showed no significant changes in relative growth rate and chlorophyll a and b levels, compared to the control condition. Biomarker analysis (LPO, GSH, GSSG, SOD, GPx, CAT and GRed) also showed no significant changes in the biochemical performance of U. lactuca. Therefore, it could be assumed that water treatment with SIL or its presence in an aqueous environment does not pose toxicity levels that could inhibit the metabolism or cause cell damage to U. lactuca., 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 The Authors. Published by Elsevier B.V. All rights reserved.)