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Breast cancer stands as the most common form of malignancy among women globally, and it showcases commendable rates of cure when detected in early-stage and non-metastatic conditions. To overcome drug resistance and side effects observed in conventional chemotherapy, the present study aims to deliver rapamycin (RAP), a mTOR protein inhibitor, into a nanostructured lipid carrier (NLC) functionalized with folic acid for promoting active targeting to breast cancer cells. In the first step, the synthesis of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt) with folic acid (DSPE-PEG 2000 -FA) was successfully performed and characterized by UV spectroscopy, nuclear magnetic resonance, and infrared spectroscopy. Then, the folic acid-modified NLC loaded with RAP (FA-NLC-RAP) and the unmodified formulation (NLC-RAP) was developed and displayed a size of about 100 nm, negative surface charge, and high RAP encapsulation efficiency (94.92 % and 85.72 %, respectively). In vitro studies suggested that FA-NLC-RAP exhibited a higher degree of internalization in cancer cells (MCF-7) than in normal cells (MCF-10A), demonstrating the potential of folic acid as a ligand for promoting active targeting of RAP for breast cancer cells through folate receptors overexpressed in tumor cells FA-NLC-RAP significantly reduced tumor cell viability, similarly to that observed with the RAP solution. The release profile of the formulation was prolonged. Finally, studies in Caenorhabditis elegans evidenced the safety of FA-NLC-RAP characterized by a complete absence of toxicity in this animal model. Therefore, the findings imply that FA-NLC-RAP holds considerable promise for the treatment of breast cancer., 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.)

Objective  To evaluate the correlation between a radiographic scale of lumbar degenerative disease and the Oswestry Disability Index (ODI). Methods  A cross-sectional study in which the ODI quality of life questionnaire and the radiographic parameters for the classification of lumbar degenerative disease into different grades were compared to try to establish a relationship between them. Results  The relationship between the radiographic parameters and quality of life indicators does not behave homogeneously, considering the different grades of the lumbar grading scale. Grade-2 lumbar degenerative disease showed a statistically significant relationship with the worsening of the ODI quality of life score. Conclusion  The lumbar degenerative disease grading scale used in the present study showed a relevant clinical potential, as it presented a significant relationship with the quality of life measured by the ODI score in part of the groups evaluated., Competing Interests: Conflito de Interesses Os autores não têm conflito de interesses a declarar., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Hematological cancer treatment with hybrid kinase/HDAC inhibitors is a novel strategy to overcome the challenge of acquired resistance to drugs. We collected IC 50 datasets from the ChEMBL database for 13 cancer cell lines (72 h cytotoxicity, measured by MTT), known inhibitors for 38 kinases, and 10 HDACs isoforms, that we identified by target fishing and literature review. The data was subjected to rigorous biological and chemical curation leaving the final datasets ranging from 76 to 8173 compounds depending on the target. We generated Random Forest classification models, whereby 14 showed greater than 80% predictability after 5-fold external cross-validation. We screened 30 hybrid kinase/HDAC inhibitor analogs through each of these models. Fragment-contribution maps were constructed to aid the understanding of SARs and the optimization of these compounds as selective kinase/HDAC inhibitors for cancer treatment. Among the predicted compounds, 9 representative hybrids were synthesized and subjected to biological evaluation to validate the models. We observed high hit rates after biological testing for the following models: K562 (62.5%), MV4-11 (75.0%), MM1S (100%), NB-4 (62.5%), U937 (75.0), and HDAC6 (86.0%). This aided the identification of 6b and 6k as potent anticancer inhibitors with IC 50 of 0.2-0.8 µM in three cancer cell lines, linked to HDAC6 inhibition below 2 nM, and blockade of AKT2 phosphorylation at 2 μM, validating the ability of our models to predict novel drug candidates., Highlights: Novel kinase/HDAC inhibitors for cancer treatment were found using machine learning61 QSAR models for hematological cancers and its targets were built and validatedK562, MV4-11, MM1S, NB-4, U937, and HDAC6 models had hit rates above 62.5% in tests 6b and 6k presented potent IC 50 of 0.2-0.8 µM in three cancer cell lines 6b and 6k inhibited HDAC6 below 2 nM, and blockade of AKT2 phosphorylation at 2 μM.

Obesity increases serum triglycerides and decreases high-density lipoprotein cholesterol (HDL-C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1-OB) and III (G3-OB) obesity and effects of bariatric surgery on G3-OB. Fifteen G3-OB patients (43 ± 6 years, BMI 49 ± 3 kg/m 2 ) were studied before and 1 year after bariatric surgery; 15 G1-OB (32 ± 2 years, 32 ± 2 kg/m 2 ) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m 2 ) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3-OB had higher triglycerides and lower HDL-C; G1-OB had higher triglycerides than NW but HDL-C was equal. Compared to NW, HDL size was smaller in G3-OB but equal in G1-OB. One year after bariatric surgery, BMI and triglycerides of G3-OB decreased (p < .0001 and p = .0012, respectively) and HDL-C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3-OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL-C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions., (© 2024 World Obesity Federation.)

Introduction: The COVID-19 pandemic introduced a new set ofwork-related stressors for health care workers., Objectives: This study aimed to investigate the associations between exposure to violence and common mental disorders among health care workers in emergency care settings during COVID-19 in the city of São Paulo, Brazil., Methods: We randomly selected two emergency care units. The 12-item General Health Questionnaire was used to assess common mental disorders among emergency health care workers (n = 100). We examined the relationships between common mental disorders and COVID-19 pandemic-related variables, including availability of personal protective equipment, exposure to violence, discrimination, harassment, and confidence in the workplace to handle the pandemic. We used multivariate Poisson regression with robust variance to estimate prevalence ratios for common mental disorders., Results: Overall, 50% (95%CI 39.8-60.1) of participants had a common mental disorder. In addition, 71% reported being victims of at least one type of violence during the COVID-19 pandemic. Higher risks ofcommon mental disorders were found among those who reported lacking personal protective equipment, being victims of discrimination, violence, or harassment, and reporting less confidence in the workplace to handle the pandemic. Participants exposed to two types of violence and three types of violence had higher prevalence ratios, with prevalence ratios of 2.28 (95%CI 1.23-4.21) and 3.14 (95%CI 1.62-6.08), respectively., Conclusions: Promoting access to personal protective equipment, addressing mistreatment of health workers as well as promoting their well-being at work, and building confidence in the workplace to deal with the pandemic are critical., Competing Interests: Conflicts of interest: None

Objective: In order to study the scenario of respiratory infections in pediatrics after the emergence of SARS-CoV-2 in Brazil, this study aimed to compare characteristics of children admitted for SARS or upper airway infection caused by either RSV or SARS-CoV-2., Methods: This was a cross-sectional study involving children up to 48 months of age admitted to a tertiary pediatric hospital with a diagnosis of SARS or upper airway infection between April of 2020 and April of 2021. Respiratory secretion samples were collected 2-5 days after hospitalization, and antigen/PCR tests for viral etiologies were performed. In this analysis, patients with laboratorial diagnosis of SARS-CoV-2 and/or RSV were selected, and their clinical and epidemiological characteristics were compared using logistic regression., Results: Our sample initially comprised 369 participants. SARS-CoV-2 and RSV infections were confirmed in 55 (15%) and 59 children (16%), respectively. Mean age was 12 months (0-48 months), and 47 were female. The following characteristics were significantly more frequent in patients with RSV when compared with those with COVID-19: younger age (OR = 0.94; 95% CI: 0.90-0.98); lower frequency of fever (OR = 0.18; 95% CI: 0.05-0.66); and more frequent upper airway symptoms: cough (OR = 7.36; 95% CI: 1.04-52.25); and tachypnea (OR = 6.06; 95% CI: 1.31-28.0)., Conclusions: Children with RSV-related SARS were younger, had lower frequency of fever at admission, but had a higher frequency of signs of upper airway infection and lower systemic inflammation when compared with children hospitalized for COVID-19 during the first year of the pandemic.

The annual killifish Austrolebias charrua is an endangered species, endemic to the southern region of South America, which inhabits temporary ponds that emerges in the rainy season. The main anthropogenic threat driving the extinction of A. charrua stems from extensive agriculture, primarily due to the widrespread use of glyphosate-based herbicides near their habitats. Annual killifishes have been used as models for ecotoxicological studies but, up to now, there are no studies about reference genes in any Austrolebias species. This represents an obstacle to the use of qPCR-based technologies, the standard method for gene expression quantification. The present study aimed to select and validate potential reference genes for qPCR normalization in the annual killifish Austrolebias charrua considering different tissues, gender and environmental conditions. The candidate reference genes 18 s, actb, gapdh, ef1a, shox, eif3g, and the control gene atp1a1 were evaluated in male and female individuals in three different tissues (brain, liver, and gills) under two experimental conditions (control and acute exposition to Roundup Transorb ® ). The collected tissues were submitted to RNA extraction, followed by cDNA synthesis, cloning, sequencing, and qPCR. Overall, 18 s was the most stable reference gene, and 18 s and ef1a were the most stable combination. Otherwise, considering all variables, gapdh and shox were the least stable candidate genes. Foremost, suitable reference genes were validated in A. charrua, facilitating accurate mRNA quantification in this species, which might be useful for developing molecular tools of ecotoxicological assessment based on gene expression analysis for environmental monitoring of annual killifish., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors declare that they have no conflict of interest.

A two-year-old female crossbreed dog, previously a stray with no known owner, was adopted and subsequently spayed. The dog exhibited weight loss over a period of two months and died suddenly during a leashed walk. Upon necropsy, enlargement of the submandibular, prescapular, and popliteal lymph nodes was noted. The intrathoracic cavity contained a substantial volume of yellowish-white fluid. Lymph nodes in the mediastinal and ventral thoracic centers were also enlarged, hemorrhagic, and friable. Microscopic examination revealed significant architectural changes in the lymph nodes, characterized by a pronounced cellular infiltrate consisting of lymphocytes and histiocytes, along with macrophages containing intracytoplasmic Leishmania amastigotes. Immunohistochemical analysis of the lymph nodes confirmed positive staining for Leishmania amastigotes. This case represents the first report of canine leishmaniasis associated with acute pleural effusion and sudden death.

In drug delivery, it is common to use porous particles as carrier media, instead of dense particles, due to their high specific surface area and available entrapment volume, which allows a higher amount of drug to be encapsulated and then released. Chitosan microparticles are extensively used in drug delivery, but porous chitosan microparticles are scarcely reported. In this work, the preparation of porous chitosan microparticles using membrane emulsification is addressed, a technology that involves mild operating conditions and less energy consumption than traditional methods (such as ultrasound), and with higher control of the particle size. The dense structure is obtained by a water-in-oil emulsion. The porous structure is obtained by a gas-in-water-in-oil G/W/O double emulsion, where argon bubbles get entrapped in an aqueous chitosan solution that is further emulsified in a paraffin/petroleum ether mixture. Porous chitosan particles were obtained with sizes of 7.7 ± 1.6 μm, which was comparable with dense chitosan particles (6.2 ± 2.3 μm). The pore structure was optimized by varying the argon flow rate, being optimized at 0.24 L h -1 . The impact of drug loading by adsorption or encapsulation, and of the drug release behaviour when using porous and dense particles were assessed, using the protein bovine serum albumin (BSA) as a model drug. The results showed that by encapsulating BSA the loading efficiency was above 95 % for both types of particles, with the release being slightly slower for the dense particles. As for the adsorbed BSA, the loading efficiency was significantly higher for porous particles - 70 % - against the 40 % for dense particles. Porous chitosan particles were successfully obtained using the membrane emulsification technology and showed that these carriers are advantageous regarding drug loading and release., 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 Ltd.)

Backgrounds: COVID-19 pandemic led to a sharp decline in surgical volume worldwide due to the postponement of elective procedures. This study evaluated the impact of COVID-19 pandemic in surgical volumes and outcomes of abdominal surgery in high-risk patients requiring intensive care unit admission., Methods: patients admitted for postoperative care were retrospectively evaluated. Data concerning perioperative variables and outcomes were compared in two different periods: January 2017-December 2019 and January 2020-December 2022, respectively, before (period I) and after (period II) the onset of COVID-19 pandemic., Results: 1.402 patients (897 women, mean age 62+17 years) were investigated. Most of the patients underwent colorectal (n=393) and pancreato-biliary (n=240) surgery, 52% of elective procedures. Surgical volume was significantly lower in period II (n=514) when compared to period I (n= 888). No recovery was observed in the number of surgical procedures in 2022 (n=135) when compared to 2021(n=211) and 2020 (n=168). Subjects who underwent abdominal surgery in period II had higher Charlson comorbidity index (4,85+3,0 vs. 4,35+2,8, p=0,002), more emergent/urgent procedures (51% vs. 45%, p=0,03) and more clean-contaminated wounds (73,5% vs. 66,8%, p=0,02). A significant decrease in the volume of colorectal surgery was also observed (24% vs, 31%, p<0,0001) after the onset of COVID-19 pandemic, 125 (8,9%) died, no deaths due to COVID-19 infection. Mortality was higher in period II when compared to period I (11% vs. 8%, p=0,08)., Conclusions: COVID-19 pandemic was associated with a decrease in surgical volume of high-risk patients without apparent recovery in recent years. No influence of COVID-19 was noted in postoperative mortality.

Background: Blood plasma is the main source of extracellular vesicles (EVs) in clinical studies aiming to identify biomarkers and to investigate pathophysiological processes, especially regarding EV roles in inflammation and thrombosis. However, EV isolation from plasma has faced the fundamental issue of lipoprotein contamination, representing an important bias since lipoproteins are highly abundant and modulate cell signaling, metabolism, and thromboinflammation., Objectives: Here, we aimed to isolate plasma EVs after depleting lipoproteins, thereby improving sample purity and EV thromboinflammatory analysis., Methods: Density-based gradient ultracentrifugation (G-UC) was used for lipoprotein depletion before EV isolation from plasma through size-exclusion chromatography (SEC) or serial centrifugation (SC). Recovered EVs were analyzed by size, concentration, cellular source, ultrastructure, and bottom-up proteomics., Results: G-UC efficiently separated lipoproteins from the plasma, allowing subsequent EV isolation through SEC or SC. Combined analysis from EV proteomics, cholesterol quantification, and apoB-100 detection confirmed the significant reduction in lipoproteins from isolated EVs. Proteomic analysis identified similar gene ontology and cellular components in EVs, regardless of lipoprotein depletion, which was consistent with similar EV cellular sources, size, and ultrastructure by flow cytometry and transmission electron microscopy. Importantly, lipoprotein depletion increased the detection of less abundant proteins in EV proteome and enhanced thromboinflammatory responses of platelets and monocytes stimulated in vitro with EV isolates., Conclusion: Combination of G-UC+SEC significantly reduced EV lipoprotein contamination without interfering in EV cellular source, gene ontology, and ultrastructure, allowing the recovery of highly pure EVs with potential implications for functional assays and proteomic and lipidomic analyses., Competing Interests: Declaration of competing interests There are no conflicting interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Ensuring precise angle measurement during surgical correction of orientation-related deformities is crucial for optimal postoperative outcomes, yet there is a lack of an ideal commercial solution. Current measurement sensors and instrumentation have limitations that make their use context-specific, demanding a methodical evaluation of the field. A systematic review was carried out in March 2023. Studies reporting technologies and validation methods for intraoperative angular measurement of anatomical structures were analyzed. A total of 32 studies were included, 17 focused on image-based technologies (6 fluoroscopy, 4 camera-based tracking, and 7 CT-based), while 15 explored non-image-based technologies (6 manual instruments and 9 inertial sensor-based instruments). Image-based technologies offer better accuracy and 3D capabilities but pose challenges like additional equipment, increased radiation exposure, time, and cost. Non-image-based technologies are cost-effective but may be influenced by the surgeon's perception and require careful calibration. Nevertheless, the choice of the proper technology should take into consideration the influence of the expected error in the surgery, surgery type, and radiation dose limit. This comprehensive review serves as a valuable guide for surgeons seeking precise angle measurements intraoperatively. It not only explores the performance and application of existing technologies but also aids in the future development of innovative solutions.

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.

This study aimed to analyze the toxic effects of Roundup Transorb® on the endangered Neotropical annual killifish Austrolebias charrua through the assessment of molecular and biochemical biomarkers. The fish were collected in temporary ponds and exposed to environmentally realistic concentrations of the herbicide (5 mg.L -1 for 96 h). The production of ROS, lipid peroxidation, DNA damage, and membrane fluidity were evaluated in the blood cells by flow cytometry. The mRNA expression of the antioxidant-related genes sod2, cat, gstα, atp1a1, gclc, and ucp1 across the brain, liver, and gills was quantified. The acute exposure of annual killifish to Roundup significantly increased ROS production, lipid peroxidation, and DNA damage in their erythrocytes. Likewise, Roundup Transorb® decreased membrane fluidity in the blood cells of the exposed fish. Gene expression analysis revealed that Roundup exposure alters the relative expression of genes associated with oxidative stress and antioxidant defense. Our results give rise to new insights into adaptive mechanisms of A. charrua in response to Roundup. Since Brazilian annual killifishes strongly risk extinction, this study paves the way for developing novel biotechnologies applied to environmental monitoring and aquatic toxicology assessment., 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 Inc. All rights reserved.)

Dengue virus serotype 2 (DENV-2) is responsible for dengue epidemics on a global scale and is associated with severe cases of the disease. This study conducted a phylogenetic investigation of DENV-2 isolates from 2017 to 2021 originating from the northern states of Brazil. A total of 32 samples from DENV-2 isolates were analyzed, including 12 from Acre, 19 from Roraima, and one from Tocantins. Only one lineage of the Asian-American genotype and one lineage of the cosmopolitan genotype were observed: Lineage 1, Asian-American genotype (connection to Puerto Rico); Lineage 5, cosmopolitan genotype (connection to Peru). Our results provide important data regarding the study of DENV genotypes and lineage distribution and open up possibilities for probable introduction and dissemination routes.

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC 50  ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC 50  = 9.3-21.7 μM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t 1/2 : >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms., 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.)

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including β-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. β-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, β-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, β-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of β-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a β-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Background: Clinical features and outcomes of patients admitted to the intensive care unit due to acute abdomen are important to be investigated., Aims: To evaluate the outcomes of critically ill subjects with acute abdomen according to etiology, comorbidity and severity., Methods: Outcomes of 1,523 patients (878 women, mean age 66±18 years) consecutively admitted to a specialized gastrointestinal intensive care unit with different causes of acute abdomen from January 2012 to December 2019, were retrospectively evaluated according to etiology, comorbidity and severity., Results: The most common causes of acute abdomen were obstructive and inflammatory, particularly large bowel obstruction (27%), small bowel obstruction (18%) and acute pancreatitis (17%). Overall mortality was 13%. Surgery was required in 34% of patients. Median length of stay in the hospital was 9 [1-101] days. On univariate analysis mortality was significantly associated with age, APACHE II, Charlson comorbidity index, requirement for surgery and malignancy (p<0.0001), but only APACHE II, Charlson comorbidity index and surgical interventional remained significant on multivariate analysis., Conclusions: Critically ill patients admitted to the intensive care unit with acute abdomen constitute a heterogeneous group of subjects with different prognosis. Mortality is more related to the severity of the disease, comorbidity and need for surgery than to the etiology of the acute abdomen.

Oral cancer is one of the most prevalent types of cancer head and neck cancers worldwide. Photodynamic therapy (PDT) has demonstrated great potential against cancers, reducing long-term morbidity. In this study, we investigated the incorporation of methylene blue (MB) in a mucoadhesive liquid crystal precursor system (LCPS) for oral cancer treatment. The photostability and the in vitro release, permeation, and retention profile of MB-loaded LCPS (MB-LCPS) were investigated, as well as its in vitro PDT activity against normal (HaCaT) and tumoral (HSC-3) cell lines. LCPS increased the photostability of MB and exhibited a prolonged release profile of MB. In addition, LCPS increased the retention of MB in the porcine esophageal mucosa by around 3 times higher than the MB solution. The retention of MB in LCPS was around 2 times greater than its permeability, which is suitable for guaranteeing the maintenance of the therapy in the oral cavity. In vitro cytotoxicity assay indicated that MB-LCPS increased the antitumoral activity of MB after 20 min of irradiation at 660 nm and 12.5 J/cm 2 . The results obtained suggest that the developed formulation is an interesting strategy for the potential application in the treatment of oral cancer by PDT., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately., Methods and Results: We performed a pre-defined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open-label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m 2 ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05-2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men)., Conclusion: Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF., Clinical Trial Registration: ClinicalTrials.gov, unique identifier NCT00512759., (© 2023 European Society of Cardiology.)

This article presents the results of a qualitative study conducted to understand the barriers and facilitators in implementing a pilot trial of Critical Time Intervention-Task-Shifting-a time-limited, community-based, recovery-oriented intervention for individuals with psychosis-in Rio de Janeiro, Brazil, and Santiago, Chile. Data included 40 semi-structured interviews with service users, task-shifting providers, and administrators. Analysis proceeded in three iterative phases and combined inductive and deductive approaches. Coding frameworks for implementation factors, and whether or not they acted as barriers and facilitators, were developed and refined using many domains and constructs from the Consolidated Framework for Implementation Research. Barriers and facilitators were ultimately grouped into five domains: 1-Personal; 2-Interpersonal; 3-Intervention; 4-Mental Health System; and 5-Contextual. A rating system was also developed and applied, which enabled comparisons across stakeholders and study sites. Major facilitators included intervention characteristics such as the roles of the task-shifting providers and community-based care. Top barriers included mental health stigma and community conditions (violence). Nevertheless, the findings suggest that Critical Time Intervention-Task-Shifting is largely acceptable and feasible, and could contribute to efforts to strengthen community mental health systems of care for individuals with psychosis in Latin America, especially in advancing the task-shifting strategy and the recovery-oriented approach., Competing Interests: Conflict of interest The authors have no competing interests to declare that are relevant to the content of this article.

Due to the rapid advance of the pandemic caused by COVID-19, several countries perceived that human and material resources would be insufficient to meet the demand of infected patients. The aim of this study is to analyze the knowledge of health professionals working in the pandemic about the application of ethical criteria in decision-making in situations of resource scarcity. This is a cross-sectional, descriptive, and quantitative survey study, conducted from June to December 2020, with health professionals working in the COVID-19 pandemic in Brazil. We applied a questionnaire to assess the professionals' knowledge about ethical criteria in decision-making in the allocation of scarce resources during the pandemic, containing 14 questions and possible score from 0 to 70, which was developed by researchers from documents and protocols validated by organizations from various countries, available in the first months of the pandemic, a sociodemographic characterization questionnaire and a self-assessment questionnaire regarding knowledge about bioethics. A total of 197 health professionals participated in the study, 37.6% of whom were nurses and 22.8% of whom were physicians, working in the Family Health Unit (28.4%) with a degree at the level of specialization (46.2%). Moreover, (9.5%) of nurses, (18.2%) of dental surgeons and (24.4%) of physicians reported that they have no prior knowledge about bioethics. Physicians and hospital workers scored higher on the knowledge assessment questionnaire. The mean score of the participants was 45.4 (SD = 7.2). Investments in training and professional education in the field of health focused on Bioethics are necessary, considering models and ethical theories that help professionals, managers and society to better position themselves in the face of pandemic contexts., (© 2023. The Author(s) under exclusive licence to Monash University.)

We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a-d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro, mechanistic studies demonstrated target activity for PfHDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c, 7c, and 8c, identified as the most active in phenotypic assays and PfHDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of PfHDAC1, with an IC 50 value of 0.74 µM in the phenotypic screening on Pf3D7 and 0.8 µM against multidrug-resistant PfDd2 parasites. Despite its potent inhibition of PfHDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with PfHDAC1 and that this compound series could bind as well as in HsHDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs., (© 2023. The Author(s).)

Background: Hypericin (HYP) is a natural compound widely used as a food supplement. The encapsulation of HYP into nanosystems, such as nanostructured lipid carriers (NLC), is a promising strategy for delivering this lipophilic molecule and protecting it from degradation., Objective: This study aims to develop and validate an analytical method to quantify the encapsulation efficiency of HYP in NLC., Method: A reverse-phase high-performance liquid chromatography (HPLC) method was developed and validated according to the International Conference on Harmonization (ICH) guide Q2 (R1). NLC was prepared through the ultrasonication method, and HYP encapsulation efficiency was evaluated using the validated method., Results: Separation was achieved using an isocratic mobile phase composed of acetonitrile, methanol, and ammonium acetate buffer (10 mM, pH 5.0) (54:36:10, v/v/v) and a reverse stationary phase. The specificity, linearity, precision, accuracy, and robustness of the method were assessed and confirmed during the validation. Furthermore, the validated method was able to determine the encapsulation efficiency of HYP in NLC., Conclusions: The HPLC method was validated, and the results indicated the ability of NLC to deliver HYP compounds for further application as a food supplement., Highlights: HYP is used as a food supplement and for photodynamic therapy (PDT). The developed method was specific, linear, precise, accurate, and robust. NLCs showed a high ability to encapsulate HYP., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF., Methods: Multicenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection ("match") was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI., Results: The global analysis ( n  = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p  = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p  = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p  = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p  = 0.8. In the last stratum (KDPI higher than 85) with n  = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p  = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p  = 0.2., Discussion: The regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies., 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., (© 2023 Rodrigues, Tanno, Contti, Nga, Valiatti, Costa, Sandes-Freitas, Esmeraldo, Assunção, Tassi, Ferreira, Felipe, Medina Pestana, Silva and Andrade.)

In cancer, cell migration contributes to the spread of tumor cells resulting in metastasis. Heterogeneity in the migration capacity can produce individual cells with heightened capacity leading to invasion and metastasis. Our hypothesis is that cell migration characteristics can divide asymmetrically in mitosis, allowing a subset of cells to have a larger contribution to invasion and metastasis. Therefore, our aim is to elucidate whether sister cells have different migratory capacity and analyze if this difference is defined by mitosis. Through time-lapse videos, we analyzed migration speed, directionality, maximum displacement of each trajectory, and velocity as well as cell area and polarity and then compared the values between mother-daughter cells and between sister cells of three tumor cell lines (A172, MCF7, SCC25) and two normal cell lines (MRC5 and CHO·K1 cells). We observed that daughter cells had a different migratory phenotype compared to their mothers, and one single mitosis is enough for the sisters behave like nonrelated cells. However, mitosis did not influence cell area and polarity dynamics. These findings indicates that migration performance is not heritable, and that asymmetric cell division might have an important impact on cancer invasion and metastasis, by producing cells with different migratory capacity., Competing Interests: Declaration of competing interest None, (Copyright © 2023. Published by Elsevier Inc.)

Oxidative glutamate toxicity is regarded as one of the injurious mechanisms associated with ischemic stroke, which represents a major health problem and requires improved pharmacological treatments. We designed and synthesized two new probucol analogues [2,6-di- tert -butyl-4-selenocyanatophenol ( C1 ) and 4,4'-diselanediylbis (2,6-di- tert -butylphenol) ( C2 )] and investigated their effects against glutamate-induced neuronal oxidative toxicity in vitro in cultured HT22 cells, compared with their parental compound (probucol). In addition, C2 , which exhibited the lowest toxicity, was investigated in an in vivo rodent model of ischemic stroke. Glutamate caused concentration- and time-dependent cytotoxicity in HT22 neuronal cells, which was preceded by increased levels of oxidants and depletion of the antioxidant glutathione. The analogues ( C1 and C2 ), but not probucol, significantly decreased the levels of oxidants (including mitochondrial superoxide anion and lipid reactive oxygen species (ROS)) and protected against glutamate-induced cytotoxicity. In the in vivo model of ischemic stroke, which was based on central injections of the vasoconstrictor agent endothelin-1 (800 pmol/site), C2 (20 or 50 mg/kg/day, intraperitoneally, for 4 consecutive days after stroke) displayed significant beneficial effects against ischemic injury in vivo , improving rats' motor-related behavioral skills and decreasing stroke-related striatal gliosis. This is the first study to design, synthesize, and present a probucol analogue ( C2 ) with in vivo beneficial effects against ischemic stroke. This novel compound, which was able to mitigate glutamate-induced oxidative toxicity in vitro , represents a promising neuroprotective drug.

The current massive and indiscriminate agrochemicals usage, which is inexorably linked to the toxic consequences to the environment and people, represents a great concern. Our work aimed to compare the toxicity induced by chlorpyrifos in its pure form (CPF) with that of a commercial formulation containing allegedly inert ingredients (CBCF) using Caenorhabditis elegans as in vivo model. After a 48 h exposure period, CBCF was 14 times more lethal than CPF; Hatching, brood size, body length and motor-related behavioral parameters were decreased, but these effects were significantly higher in CBCF-exposed worms. Additionally, CBCF induced significant morphological changes in cholinergic neurons, which are associated with the motor-related behavioral parameters. Finally, by analyzing the CBCF, we detected the presence of potentially-toxic metals that were not specified in the label. The presented results highlight the toxicological relevance of components present in the commercial formulations of pesticides, which have been claimed as inert compounds., 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 B.V. All rights reserved.)

Background: Ovarian cancer is a highly aggressive disease that is frequently diagnosed in advanced stages. Melatonin, with its numerous antitumor properties, holds great promise in cancer treatment. Herein, we investigated the effects of melatonin on apoptosis, cell migration, and kinase levels in human ovarian carcinoma SKOV-3 cells and determined whether these effects are mediated by the activation of the MT1 receptor., Methods: SKOV-3 cells were exposed to different concentrations of melatonin based on the presence of MT1 receptor, and we also performed specific silencing of the melatonin receptor gene MTNR1A., Results: Our findings revealed that melatonin reduced cell viability as shown by the MTT assay, and flow cytometry analysis showed increased rates of apoptosis and necrosis in all melatonin-treated cells. Melatonin significantly decreased the migratory and invasive capacities of the cells. Propidium iodide labeling indicated that melatonin induced cell cycle arrest by reducing DNA content in the S and G2/M phases in SKOV-3 cells. Additionally, the levels of AKT, ERK1/2, JNK, CREB, p70S6K, STAT3/5, and p38 MAP kinase involved in cell survival, proliferation, motility, and stress responses were depressed by melatonin and further reduced after MT1 knockdown. These molecules were found to be associated with lower overall survival in ovarian cancer patients., Conclusions: Melatonin had obvious oncostatic actions on ovarian cancer cells, and MT1 receptor knockdown intensified its antitumor effect. The inhibition of the MT1 receptor resulted in a substantial reduction in the migratory and invasive capacities of the cells, suggesting its potential as a therapeutic target for the treatment of ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Dengue virus 2 (DENV-2) seriously contributes to dengue-related mortality. It includes five nonsylvatic genotypes, with cosmopolitan being the most widespread with a significant contribution to the total number of DENV-2 cases globally. In South America, the cosmopolitan genotype was first recorded in 2019 in Madre de Dios, Peru, and then in Goiás (Midwest Brazil) in November 2021. In this study, we tested 163 human serum samples from Acre (Northern Brazil) collected during a DENV outbreak between 2020 and 2021 for all DENV genotypes by RT-qPCR. Of the 163 samples, 139 were positive for DENV-2, and 5 were positive for DENV-1. Five DENV-2-positive samples from early 2021 were sequenced, and the sequences clustered with the three other DENV-2 cosmopolitan genotype sequences already recorded on the continent. These results create a geographical link, suggesting the possible route of introduction of the DENV-2 cosmopolitan genotype into Brazil through the border with Peru, from which it may have dispersed to Midwest Brazil.

Glioblastoma multiforme is the most common and most aggressive human brain cancer. GBM treatment is still a challenge because many drugs are not able to cross the blood-brain barrier, in addition to the increasing resistance to currently available chemotherapy. New therapeutic alternatives are emerging, and, in this context, we highlight kaempferol, a flavonoid with remarkable anti-tumor activity but with limited bioavailability due to its strong lipophilic property. A promising tool to improve the biopharmaceutical properties of molecules such as kaempferol is the use of drug-delivery nanosystems, such as nanostructured lipid carriers (NLC), which can facilitate the dispersion and delivery of highly lipophilic molecules. The present work aimed at the development and characterization of kaempferol-loaded NLC (K-NLC) and the evaluation of its biological properties using in vitro models. The K-NLC showed an average size of 120 nm, zeta potential of - 21 mV, and polydispersity index of 0.099. The K-NLC presented high kaempferol encapsulation efficiency (93%), a drug loading of 3.58%, and a sustained kaempferol release profile for up to 48 h. In addition to presenting a 7-fold increase in kaempferol cytotoxicity, its encapsulation in NLC promoted a cellular uptake of 75%, which corroborates with increased cytotoxicity in U-87MG cells, as observed. Together, these data reinforce the promising antineoplastic properties of kaempferol in addition to the key role of NLC as a platform for the efficient delivery of lipophilic drugs to neoplastic cells, which improved their uptake and therapeutic efficacy in glioblastoma multiforme cells., 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 B.V. All rights reserved.)

Gliomas are the most common type of brain cancer, and among them, glioblastoma multiforme (GBM) is the most prevalent (about 60% of cases) and the most aggressive type of primary brain tumor. The treatment of GBM is a major challenge due to the pathophysiological characteristics of the disease, such as the presence of the blood-brain barrier (BBB), which prevents and regulates the passage of substances from the bloodstream to the brain parenchyma, making many of the chemotherapeutics currently available not able to reach the brain in therapeutic concentrations, accumulating in non-target organs, and causing considerable adverse effects for the patient. In this scenario, nanocarriers emerge as tools capable of improving the brain bioavailability of chemotherapeutics, in addition to improving their biodistribution and enhancing their uptake in GBM cells. This is possible due to its nanometric size and surface modification strategies, which can actively target nanocarriers to elements overexpressed by GBM cells (such as transmembrane receptors) related to aggressive development, drug resistance, and poor prognosis. In this review, an overview of the most frequently overexpressed receptors in GBM cells and possible approaches to chemotherapeutic delivery and active targeting using nanocarriers will be presented., Competing Interests: J.C. is a co-founder and shareholder of TargTex S.A. Targeted Therapeutics for Glioblastoma Multiforme. All the other authors declare no competing interests., (© 2023 The Authors.)

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA, and R-loops, even in the absence of cohesin. Our results place SA1 on chromatin upstream of the cohesin ring and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease., Competing Interests: HP, YL, MN, MB, WV, LM, MC, DP, AB, SS, RJ, MC, SH No competing interests declared, (© 2023, Porter, Li et al.)

Aims: The development of rapamycin (RAP) and resveratrol (RSV) coloaded liposomes (RAP-RSV-LIP) for breast cancer therapy. Materials & methods: Liposomes were prepared using a high-pressure homogenization technique and evaluated according to their physicochemical characteristics, cellular uptake and cytotoxicity against tumoral and normal cells. Results & conclusion: The RAP-RSV-LIP showed negative surface charge, size around 100 nm, low polydispersity and high encapsulation efficiency for RAP and RSV (58.87 and 63.22%, respectively). RAP-RSV-LIP showed great stability over 60 days and a prolonged drug-release profile. In vitro studies indicated that RAP-RSV-LIP were internalized in an estrogen receptor-positive human breast cancer cell line (MCF-7, 34.2%) and improved cytotoxicity when compared with free drugs. Therefore RAP-RSV-LIP showed great antitumoral potential against breast cancer cells.

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications., (© 2022 The Ecological Society of America.)

Obesity causes low-grade inflammation that results in the development of comorbidities. In people with obesity, exacerbation of gastric lesion severity and delayed healing may aggravate gastric mucosal lesions. Accordingly, we aimed to evaluate the citral effects on gastric lesion healing in eutrophic and obese animals. C57Bl/6 male mice were divided into two groups: animals fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Gastric ulcers were induced using acetic acid (80%) in both groups. Citral (25, 100, or 300 mg/kg) was administered orally for 3 or 10 days. A vehicle-treated negative control (1% Tween 80, 10 mL/kg) and lansoprazole-treated (30 mg/kg) were also established. Lesions were macroscopically examined by quantifying regenerated tissue and ulcer areas. Matrix metalloproteinases (MMP-2 and -9) were analyzed by zymography. The ulcer base area between the two examined periods was significantly reduced in HFD 100 and 300 mg/kg citral-treated animals. In the 100 mg/kg citral-treated group, healing progression was accompanied by reduced MMP-9 activity. Accordingly, HFD could alter MMP-9 activity, delaying the initial healing phase. Although macroscopic changes were undetectable, 10-day treatment with 100 mg/kg citral exhibited improved scar tissue progression in obese animals, with reduced MMP-9 activity and modulation of MMP-2 activation.

Background: Streptococcus mutans and Candida albicans can colonize the teeth, the oral cavity as biofilm and can cause oral infections. Thus, strategies to prevent and control oral biofilms are requested. The present study aims the development and characterization of methylene blue (MB)-loaded polymeric micelles for antimicrobial photodynamic therapy (aPDT) against Streptococcus mutans and Candida albicans biofilms METHODS: MB-loaded polymeric micelles were produced and characterized by particle size, polydispersity index, morphology, zeta potential, stability, MB release profile, and antimicrobial effect against S. mutans and C. albicans biofilms., Results: MB-loaded polymeric micelles showed a reduced particle size, moderate polydisperse profile, spherical and neutral shape, which demonstrated to be promising features to allow micelles penetration into biofilms. Antimicrobial effect against bacterial and yeast biofilms was demonstrated once MB was irradiated by light under 660 nm (aPDT). Furthermore, MB-loaded polymeric micelles showed significant inhibition of S. mutans and C. albicans biofilms. Furthermore, the treatment with MB-micelles incubated with high pre-incubation times (15 and 30 min) were more effective than 5 min. It can be explained by the time required for this nanosystem to penetrate the innermost layer of biofilms and release MB for aPDT., Conclusion: MB-loaded polymeric micelles can effectively decrease the bacteria and yeast viability and it may cause positive impacts in the clinical practice. Thus, the developed formulation showed potential in the treatment to remove oral biofilms, but clinical studies are needed to confirm its potential., 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 B.V. All rights reserved.)

Nanomedicines have been investigated for delivering drugs to tumors due to their ability to accumulate in the tumor tissues. 2D in vitro cell culture has been used to investigate the antitumoral potential of nanomedicines. However, a 2D model cannot adequately mimic the in vivo tissue conditions because of the lack of cell-cell interaction, a gradient of nutrients and the expression of genes. To overcome this limitation, 3D cell culture models have emerged as promising platforms that better replicate the complexity of native tumors. For this purpose, different techniques can be used to produce 3D models, including scaffold-free, scaffold-based and microfluidic-based models. This review addresses the principles, advantages and limitations of these culture methods for evaluating the antitumoral efficacy of nanomedicines.

Background: Children from low-middle income countries (LMIC) are disproportionately affected by obesity, and low physical activity (PA) and high screen time (ST) are major contributors. Parents are key influencers on children's PA and ST, yet, no study has investigated relationships between parenting practices and children's PA and ST in LMIC families. This study examined parental influences on PA and ST among preschool-aged children from low-income families in Brazil. Methods: Parents completed a validated, culturally adapted interviewer-administered survey assessing child ST and parenting practices. Child sedentary time, total movement, and energetic play were measured by accelerometery. Results: Data were available on 77 parent-child dyads [mean age 4.6 years (standard deviation = 0.8), 53% male, and 41% mixed-race]. Parenting practices associated with greater PA were use of PA to reward/control behavior (rho = 0.34-0.49), limiting or monitoring ST (rho = 0.30), explicit modeling/enjoyment of PA (rho = 0.24), verbal encouragement for PA (rho = 0.30), and importance and value of PA (rho = 0.24-0.38; p  < 0.05). Parenting practices associated with higher ST were rules around active play indoor (rho = 0.23), use of ST to reward/control behavior (rho = 0.30), exposure to screens (rho = 0.40), and explicit modeling/enjoyment of ST (rho = 0.50; p  < 0.05). Conclusion: Recognized parenting practices such as explicit modeling of PA and ST, monitoring and limiting ST, and rules and restrictions about PA and ST are associated with young children's PA and ST in low-income Brazilian families. The findings identify potential targets for family-based interventions to promote healthy lifestyle behaviors and prevent childhood obesity.

Dental caries is the most common oral disease, with high prevalence rates in adolescents and low-income and lower-middle-income countries. This disease originates from acid production by bacteria, leading to demineralization of the dental enamel and the formation of cavities. The treatment of caries remains a global challenge and the development of effective drug delivery systems is a potential strategy. In this context, different drug delivery systems have been investigated to remove oral biofilms and remineralize dental enamel. For a successful application of these systems, it is necessary that they remain adhered to the surfaces of the teeth to allow enough time for the removal of biofilms and enamel remineralization, thus, the use of mucoadhesive systems is highly encouraged. Among the systems used for this purpose, liquid crystalline systems, polymer-based nanoparticles, lipid-based nanoparticles, and inorganic nanoparticles have demonstrated great potential for preventing and treating dental caries through their own antimicrobial and remineralization properties or through delivering drugs. Therefore, the present review addresses the main drug delivery systems investigated in the treatment and prevention of dental caries.

Cancer is one of the major public health problems worldwide. Despite the advances in cancer therapy, it remains a challenge due to the low specificity of treatment and the development of multidrug resistance mechanisms. To overcome these drawbacks, several drug delivery nanosystems have been investigated, among them, magnetic nanoparticles (MNP), especially superparamagnetic iron oxide nanoparticles (SPION), which have been applied for treating cancer. MNPs have the ability to be guided to the tumor microenvironment through an external applied magnetic field. Furthermore, in the presence of an alternating magnetic field (AMF) this nanocarrier can transform electromagnetic energy in heat (above 42 °C) through Néel and Brown relaxation, which makes it applicable for hyperthermia treatment. However, the low chemical and physical stability of MNPs makes their coating necessary. Thus, lipid-based nanoparticles, especially liposomes, have been used to encapsulate MNPs to improve their stability and enable their use as a cancer treatment. This review addresses the main features that make MNPs applicable for treating cancer and the most recent research in the nanomedicine field using hybrid magnetic lipid-based nanoparticles for this purpose.

Innovations and efficiencies in digital technology have lately been depicted as paramount in the green transition to enable the reduction of greenhouse gas emissions, both in the information and communication technology (ICT) sector and the wider economy. This, however, fails to adequately account for rebound effects that can offset emission savings and, in the worst case, increase emissions. In this perspective, we draw on a transdisciplinary workshop with 19 experts from carbon accounting, digital sustainability research, ethics, sociology, public policy, and sustainable business to expose the challenges of addressing rebound effects in digital innovation processes and associated policy. We utilize a responsible innovation approach to uncover potential ways forward for incorporating rebound effects in these domains, concluding that addressing ICT-related rebound effects ultimately requires a shift from an ICT efficiency-centered perspective to a "systems thinking" model, which aims to understand efficiency as one solution among others that requires constraints on emissions for ICT environmental savings to be realized., Competing Interests: M.B.-L. is the founder and principal consultant of Small World Consulting. C.C. works at Baillie Gifford, which is a commercial entity. G.S.B. is a member of the Patterns advisory board., (© 2023 The Author(s).)