Cardioprotective Effects of Aloysia polystachya Essential Oil on a Rat Model with Multiple Cardiovascular Risk Factors.

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A. polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A. polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A. polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A. polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A. polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

O uso do laser de alta e baixa intensidade para o tratamento de hipersensibilidade dentinária: uma revisão integrativa

Objetivo: Determinar as evidências científicas sobre a influência do uso de lasers de baixa e alta intensidade no tratamento da hipersensibilidade da dentina. Revisão de literatura: Foram realizadas buscas na Biblioteca Virtual em Saúde (BVS), incluindo as bases de dados: Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS); Bibliografia Brasileira de Odontologia (BBO); e National Library of Medicine (MEDLINE). A maioria dos estudos destacam a eficácia dos lasers na redução da HD, com o laser Nd:YAG mostrando-se eficaz na obliteração dos túbulos dentinários e proporcionando alívio a longo prazo. Apesar dos benefícios, alguns estudos alertam para possíveis danos à polpa dentária, especialmente com lasers de alta potência. Considerações finais: Embora os lasers tenham se mostrado eficazes na redução da HD, a escolha do laser deve ser personalizada para cada paciente, destacando a necessidade de aprimorar os protocolos clínicos e adquirir experiência relevante por parte dos profissionais especialistas.

Objective: To determine the scientific evidence on the influence of the use of low and high intensity lasers in the treatment of dentin hypersensitivity. Literature review: Searches were carried out in the Virtual Health Library (VHL), including the databases: Latin American and Caribbean Literature in Health Sciences (LILACS); Brazilian Bibliography of Dentistry (BBO); and National Library of Medicine (MEDLINE). Most studies highlight the effectiveness of lasers in reducing HD, with the Nd:YAG laser proving effective in obliterating dentinal tubules and providing long-term relief. Despite the benefits, some studies warn of possible damage to the dental pulp, especially with high-power lasers. Final considerations: Although lasers have been shown to be effective in reducing HD, the choice of laser must be personalized for each patient, highlighting the need to improve clinical protocols and acquire relevant experience on the part of specialist professionals.

Access to health and social protection policies by homeless people during the COVID-19 pandemic: a mixed-methods case study on tailored inter-sector care during a health emergency.

Introduction: The article analyzed homeless people's (HP) access to health and social protection policies and tailored inter-sector care, including emergency measures, during the COVID-19 pandemic in Belo Horizonte (BH), capital of Minas Gerais state, Brazil. It intended to provide data on HP and evaluate existing public policies focused on vulnerable populations during this health emergency. Methods: The study adopted a mixed-methods design with triangulation of quantitative and qualitative data. Results: Social cartography showed that in the early months of the pandemic, the health administration had difficulty reordering the health system, which experienced constant updates in the protocols but was nevertheless consolidated over the months. The evidence collected in the study showed that important emergency interventions in the municipality of BH involved activities that facilitated access by HP to the supply of services. Discussion: The existence of national guidelines for inter-sector care for HP cannot be ruled out as a positive influence, although the municipalities are responsible for their implementation. Significantly, a health emergency was necessary to intensify the relationship between health and social protection services. Roving services were among those with the greatest positive evidence, with the least need for infrastructure to be replicated at the local level. In addition, the temporary supply of various inter-sector services, simultaneously with the provision of day shelters by organized civil society, was considered a key factor for expanding and intensifying networks of care for HP during the emergency phase. A plan exists to continue and expand this model in the future. The study concluded that understanding the inter-sector variables that impact HP contributes to better targeting of investments in interventions that work at the root causes of these issues or that increase the effectiveness of health and social protection systems.

Intuitive eating has reduced the chances of being overweight in university students during the COVID-19 pandemic.

Introduction: University students have been particularly affected during the COVID-19 pandemic, and several sociodemographic and behavioral factors may be associated with the risk of overweight in this population. The aim of this study was to assess the impact of the pandemic on the eating behavior and nutritional status of university students, and the factors associated with these changes, especially the role of intuitive eating in this process. Methods: This is a repeated measures observational study with data collected in the first and third year of the COVID-19 pandemic in Brazil, from students over the age of 18 in the undergraduate programs of a federal university in southeastern Brazil. The survey was conducted using an online form. Eating behavior was assessed using the "Intuitive Eating Scale-2". Results: 251 university students took part, most of them female with a median age of 22. There was an increase in body mass index (BMI) and intuitive eating score between the two periods. In the first year of the pandemic, being female and using tobacco reduced the chances of students being overweight. Living in a marital relationship, worrying about weight gain and body dissatisfaction increased the chances of this outcome. In the third year of the pandemic, it was observed that practicing restrictive diets, having inadequate body perception, worrying about weight gain and living in a marital relationship increased the chances of students being overweight. Being female and eating more intuitively, in line with bodily needs, reduced these odds, demonstrating a protective role in this scenario. Conclusion: There was an increase in BMI and intuitive eating score during the pandemic. Sociodemographic, lifestyle and behavioral variables had both a positive and negative influence on nutritional status. Intuitive eating was shown to be a protective factor during this period, reducing the chances of being overweight in this population. Thus, more intuitive eating may favor greater weight stability, and may, therefore, have helped to reduce the impact of the pandemic on weight gain. In this way, people who ate more intuitively partially resisted the context that favored weight gain (stress, changes in diet and physical inactivity).

Desafios e possibilidades da jurimetria na judicialização em saúde: uma investigação em Minas Gerais do período 2014 a 2020 / Challenges and possibilities of jurimetry in health judicialization: an investigation in Minas Gerais state from 2014 2020 / Desafíos y posibilidades de la jurimetría en la judicialización de la salud: una investigación en Minas Gerais de 2014 a 2020

Objetivo: analisar os processos de saúde, de medicamentos e de medicamentos antineoplásicos em Minas Gerais, em 2014 a 2020, a partir da comparação de diferentes bases de dados. Metodologia: foram utilizadas técnicas de pareamento de bases de dados entre os processos existentes no Tribunal de Justiça do Estado de Minas Gerais e os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais, descreveram-se as dificuldades encontradas na identificação e quantificação desses processos, e os resultados encontrados foram comparados com informações provenientes de outras fontes. Resultados: nas bases do Tribunal de Justiça de Minas Gerais foram identificados 564.763 processos de saúde. Houve um aumento significativo do número de processos até 2017 e uma estabilização, em patamares altos, a partir de 2017. Ao comparar com os resultados obtidos pelo Instituto Superior de Ensino e Pesquisa e pelo Laboratório de Inovação, Inteligência e Objetivos de Desenvolvimento Sustentável, houve uma importante divergência nos números de processos. Tomando como exemplo a judicialização de saúde contra o estado de Minas Gerais, não foi possível encontrar de forma direta todos os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais nas diversas bases fornecidas pelo Tribunal de Justiça de Minas Gerais, tendo sido necessária uma integração entre as diferentes bases de dados e uma busca adicional para identificar todos os processos. Conclusão: recomendam-se a padronização e organização dos dados dos processos judiciais em saúde, já na entrada de dados, para facilitar a realização de estudos quantitativos sobre a judicialização da saúde.

Objective: to analyze the health, drug, and antineoplastic drug lawsuits in Minas Gerais, in 2014 to 2020, from the comparison of different databases. Methodology: database pairing techniques were used to link lawsuits from the Minas Gerais State Court of Justice with the processes received by the Minas Gerais Health State Department, the difficulties encountered in identifying and quantifying these processes were described, and the results found were compared with information from other sources. Results: in the Minas Gerais State Court of Justice databases, 564,763 health lawsuits were identified in the studied period. There was a significant increase in the number of processes until 2017 and a stabilization, at high levels, from 2017 onwards. In comparison with the results obtained by the Institute of Higher Education and Research and the Laboratory of Innovation, Intelligence and Sustainable Development Goals there was a great divergence in the number of processes found. Conclusion: taking the health judicialization against Minas Gerais state as an example, it was not possible to directly find all the processes received by Minas Gerais Health State Department in the various databases provided by the Minas Gerais State Court of Justice, requiring integration between the different databases and an additional search to identify all processes.

Objetivo: analizar los juicios de salud, drogas y medicamentos antineoplásicos en Minas Gerais, en 2014 a 2020, a partir de la comparación de diferentes bases de datos. Metodología: técnicas de emparejamiento de bases de datos fueron utilizadas para vincular los juicios existentes en el Tribunal de Justicia del Estado de Minas Gerais con los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais, las dificultades encontradas en la identificación y cuantificación de esos procesos fueron descritas, y los resultados encontrados fueron comparados con informaciones de otras fuentes. Resultados: en las bases del Tribunal de Justicia del Estado de Minas Gerais se identificaron 564.763 procesos de salud. Hubo un aumento significativo en el número de procesos hasta 2017 y una estabilización, en niveles altos, a partir de 2017. Sin embargo, al comparar con los resultados obtenidos por el Instituto Superior de Educación e Investigación y por el Laboratorio de Innovación, Inteligencia y Objetivos de Desarrollo Sostenible hubo una divergencia importante en el número de procesos. Conclusión: tomando como ejemplo la judicialización de la salud contra el estado de Minas Gerais, no era posible encontrar directamente todos los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais en las diversas bases de datos proporcionadas por el Tribunal de Justicia del Estado de Minas Gerais, lo que requería una integración entre las diferentes bases de datos y una búsqueda adicional a identificar todos los procesos.

Safety, Efficacy, and Immunogenicity of Therapeutic Vaccines for Patients with High-Grade Cervical Intraepithelial Neoplasia (CIN 2/3) Associated with Human Papillomavirus: A Systematic Review.

Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via viral clearance and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT.

Aortic Thrombosis Associated with Three Types of COVID-19 Vaccine.

Aortic thrombosis has been studied little in patients with COVID-19 and an association has recently been reported with the vaccine for this disease. The aim of the present study is to report five cases of aortic thrombosis at our institution within a three-month period associated with the COVID-19 vaccine. Five cases of aortic thrombosis were evaluated-three women and two men aged 29, 49, 51, 60, and 79 years. Four thrombi involved the thoracic aortic and one involved the abdominal aorta, with embolisms found in the kidneys, spleen, liver, upper limbs, and lower limbs. Embolectomy was performed on the limbs, and anticoagulant therapy was performed for the abdominal arteries. The patients recovered well and anticoagulant therapy was maintained. Aortic thrombosis is uncommon but was associated with the AstraZeneca vaccine in this case series.

Co-regulation of biofilm formation and antimicrobial resistance in Acinetobacter baumannii: from mechanisms to therapeutic strategies.

In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health Organization as a priority one for the need of new therapeutic agents. A. baumannii has the capacity to develop robust biofilms on biotic and abiotic surfaces. Biofilm development allows these bacteria to resist various environmental stressors, including antibiotics and lack of nutrients or water, which in turn allows the persistence of A. baumannii in the hospital environment and further outbreaks. Investigation into therapeutic alternatives that will act on both biofilm formation and antimicrobial resistance (AMR) is sorely needed. The aim of the present review is to critically discuss the various mechanisms by which AMR and biofilm formation may be co-regulated in A. baumannii in an attempt to shed light on paths towards novel therapeutic opportunities. After discussing the clinical importance of A. baumannii, this critical review highlights biofilm-formation genes that may be associated with the co-regulation of AMR. Particularly worthy of consideration are genes regulating the quorum sensing system AbaI/AbaR, AbOmpA (OmpA protein), Bap (biofilm-associated protein), the two-component regulatory system BfmRS, the PER-1 ß-lactamase, EpsA, and PTK. Finally, this review discusses ongoing experimental therapeutic strategies to fight A. baumannii infections, namely vaccine development, quorum sensing interference, nanoparticles, metal ions, natural products, antimicrobial peptides, and phage therapy. A better understanding of the mechanisms that co-regulate biofilm formation and AMR will help identify new therapeutic targets, as combined approaches may confer synergistic benefits for effective and safer treatments.

Deacetylation by sirtuins is important for Aspergillus fumigatus pathogenesis and virulence.

Protein acetylation is a crucial post-translational modification that controls gene expression and a variety of biological processes. Sirtuins, a prominent class of NAD + -dependent lysine deacetylases, serve as key regulators of protein acetylation and gene expression in eukaryotes. In this study, six single knockout strains of fungal pathogen Aspergillus fumigatus were constructed, in addition to a strain lacking all predicted sirtuins (SIRTKO). Phenotypic assays suggest that sirtuins are involved in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. AfsirE deletion resulted in attenuation of virulence, as demonstrated in murine and Galleria infection models. The absence of AfSirE leads to altered acetylation status of proteins, including histones and non-histones, resulting in significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.

Escherichia coli Phylogenetic and Antimicrobial Pattern as an Indicator of Anthropogenic Impact on Threatened Freshwater Mussels.

Freshwater bivalves are widely used as accumulation indicators and monitoring tools for assessing contaminant effects on different levels of biological integration. This pilot study aimed to explore the phylogenetic diversity of Escherichia coli isolated from freshwater mussels (Margaritifera margaritifera and Potomida littoralis) and characterize their phenotypes and antibiotic resistance profiles. Samples were collected in the Rabaçal and Tua Rivers, in the Douro basin, Portugal-two sites representing different levels of anthropogenic contamination. Antimicrobial susceptibility testing was performed via the disk diffusion method with 21 antibiotics. Results showed that 31% of isolates were multidrug-resistant (MDR). Thus, freshwater mussels provide an effective and time-integrated approach for identifying/quantifying fecal indicators, including MDR bacteria. PCR-based assays were designed for assessing phylogenetic E. coli groups. Among the E. coli isolates, the highest prevalence (44%) was observed in group D or E, followed by group E or Clade I (25%), group A (19%), and group B1 (13%). E. coli isolated from M. margaritifera predominantly exhibited a higher prevalence of phylogroups D or E, whereas E. coli from P. littoralis showed associations with phylogroups E or clade I, B1, A, and D or E. Our results provide new insights into the phylogenetic diversity of E. coli in freshwater bivalves. Additionally, the findings highlight the possible linkage of phylogroups with the host species, the geographical location in the water stream, and human activity. Using E. coli as a bioindicator isolated from freshwater mussels helps us grasp how human activities affect the environment. This study has important implications for those interested in safeguarding water resources, especially in tackling antibiotic resistance in aquatic ecosystems.

An Overview of Cefiderocol's Therapeutic Potential and Underlying Resistance Mechanisms.

Antimicrobial resistance continues to increase globally and treatment of difficult-to-treat (DTT) infections, mostly associated with carbapenem-resistant (CR) Pseudomonas aeruginosa, CR Acinetobacter baumannii, and CR- and third-generation-cephalosporins-resistant Enterobacterales remains a challenge for the clinician. The recent approval of cefiderocol has broaden the armamentarium for the treatment of patients with DTT infections. Cefiderocol is a siderophore cephalosporin that has shown excellent antibacterial activity, in part due to its innovative way of cell permeation. It is relatively stable compared to most commonly found carbapenamases. However, some resistant mechanisms to cefiderocol have already been identified and reduced susceptibility has developed during patient treatment, highlighting that the clinical use of cefiderocol must be rational. In this review, we summarize the current available treatments against the former resistant bacteria, and we revise and discuss the mechanism of action of cefiderocol, underlying the biological function of siderophores, the therapeutic potential of cefiderocol, and the mechanisms of resistance reported so far.

The Acinetobacter baumannii website (Ab-web): a multidisciplinary knowledge hub, communication platform, and workspace.

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Ab-web is a species-centric knowledge hub, initially with 10 articles organized into two main sections, 'Overview' and 'Topics', and three themes, 'epidemiology', 'antibiotic resistance', and 'virulence'. The 'workspace' section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas.

Electrochemical monitoring of levofloxacin using a silver nanoparticle-modified disposable device based on a lab-made conductive ink.

The emergence of bacteria genetically resistant to first- and second-generation fluoroquinolones has resulted in increased consumption of levofloxacin (LEV) in human and veterinary medicine. In this regard, the development of low cost and good sensitivity electrochemical devices has been highly required. Thus, in this work, we propose the development of a disposable electrochemical device (DED) using a lab-made conductive ink based on graphite powder and nail polish immobilized on a rigid polyvinyl chloride support (transparent sheet). Additionally, a simple and quick protocol for the electrodeposition of silver nanoparticles was used in order to improve the electroanalytical performance of the sensor (2.75-fold). A differential pulse voltammetry (DPV) method was optimized and the sensor was applied for LEV monitoring in pharmaceutical formulation samples, synthetic urine and simulated body fluid. The method showed a wide linear working range ranging from 0.5 to 50 µmol L-1 and a detection limit of 68.3 nmol L-1. Furthermore, the precision was adequate (RSD < 4.7%), while the accuracy was evaluated through spiked samples with percent recovery ranging from 93 to 103%. The sensor was also shown to be selective for LEV against other electroactive antibiotic species, thus demonstrating suitable characteristics for electroanalytical applications.

Ecotoxicological assessment of guanitoxin-producing cyanobacteria in Danio rerio and Daphnia similis.

Anthropogenic activity has dramatically deteriorated aquatic ecosystems in recent years. Such environmental alterations could change the primary producers' composition, exacerbating the proliferation of harmful microorganisms such as cyanobacteria. Cyanobacteria can produce several secondary metabolites, including guanitoxin, a potent neurotoxin and the only naturally occurring anticholinesterase organophosphate ever reported in the literature. Therefore, this study investigated the acute toxicity of guanitoxin-producing cyanobacteria Sphaerospermopsis torques-reginae (ITEP-024 strain) aqueous and 50% methanolic extracts in zebrafish (Danio rerio) hepatocytes (ZF-L cell line), zebrafish embryos (fish embryo toxicity - FET) and specimens of the microcrustacean Daphnia similis. For this, hepatocytes were exposed to 1-500 mg/L of the ITEP-024 extracts for 24 h, the embryos to 31.25-500 mg/L for 96 h, and D. similis to 10-3000 mg/L for 48 h. Non-target metabolomics was also performed to analyze secondary metabolites produced by the ITEP-024 using LC-MS/MS. Metabolomics indicated the guanitoxin presence just in the aqueous extract of the ITEP-024 and the presence of the cyanopeptides namalides, spumigins, and anabaenopeptins in the methanolic extract. The aqueous extract decreased the viability of zebrafish hepatocytes (EC(I)50(24h) = 366.46 mg/L), and the methanolic extract was not toxic. FET showed that the aqueous extract (LC50(96) = 353.55 mg/L) was more toxic than the methanolic extract (LC50(96) = 617.91 mg/L). However, the methanolic extract had more sublethal effects, such as abdominal and cardiac (cardiotoxicity) edema and deformation (spinal curvature of the larvae). Both extracts immobilized daphnids at the highest concentration analyzed. However, the aqueous extract was nine times more lethal (EC(I)50(48h) = 108.2 mg/L) than the methanolic extract (EC(I)50(48h) = 980.65 mg/L). Our results showed an imminent biological risk for aquatic fauna living in an ecosystem surrounded by ITEP-024 metabolites. Our findings thus highlight the urgency of understanding the effects of guanitoxin and cyanopeptides in aquatic animals.

Cerebellar contribution to the regulation of defensive states.

Despite fine tuning voluntary movement as the most prominently studied function of the cerebellum, early human studies suggested cerebellar involvement emotion regulation. Since, the cerebellum has been associated with various mood and anxiety-related conditions. Research in animals provided evidence for cerebellar contributions to fear memory formation and extinction. Fear and anxiety can broadly be referred to as defensive states triggered by threat and characterized by multimodal adaptations such as behavioral and cardiac responses integrated into an intricately orchestrated defense reaction. This is mediated by an evolutionary conserved, highly interconnected network of defense-related structures with functional connections to the cerebellum. Projections from the deep cerebellar nucleus interpositus to the central amygdala interfere with retention of fear memory. Several studies uncovered tight functional connections between cerebellar deep nuclei and pyramis and the midbrain periaqueductal grey. Specifically, the fastigial nucleus sends direct projections to the ventrolateral PAG to mediate fear-evoked innate and learned freezing behavior. The cerebellum also regulates cardiovascular responses such as blood pressure and heart rate-effects dependent on connections with medullary cardiac regulatory structures. Because of the integrated, multimodal nature of defensive states, their adaptive regulation has to be highly dynamic to enable responding to a moving threatening stimulus. In this, predicting threat occurrence are crucial functions of calculating adequate responses. Based on its role in prediction error generation, its connectivity to limbic regions, and previous results on a role in fear learning, this review presents the cerebellum as a regulator of integrated cardio-behavioral defensive states.

Health litigation and cancer survival in patients treated in the public health system in a large Brazilian city, 2014-2019.

BACKGROUND: Litigation for health care, also known as health judicialization, is frequent in Brazil. It involves recourse to the court system to access health services. The study aimed to evaluate whether cancer patients in Belo Horizonte, Minas Gerais, Brazil, increased their overall survival by increasing access to certain drugs or treatments through litigation, controlling for the effect of demographic and disease-related variables. METHODS: A retrospective cohort study was conducted. Patients with breast, prostate, brain, lung, or colon cancers from 2014 to 2019 were included. Survival analysis was performed using the Cox proportional hazards model. RESULTS: In the multivariate analysis, litigation was significantly associated with increased survival in cancers of breast (HR = 0.51, 95%CI 0.33-0.80), prostate (HR = 0.50, 95%CI 0.30-0.85), colon (HR = 0.59, 95%CI 0.38-0.93), and lung (HR = 0.36, 95%CI 0.22-0.60). Five-year survival rates of patients who sued for treatment were 97.8%, 88.7%, 59.3%, and 26.0%, compared to median survival of 95.7%, 78.7%, 41.2%, and 2.4%, respectively, among patient that did not resort to court action. The study suggests that litigation for access to cancer treatment may represent a step forward in obtaining more effective treatment. This study´s main limitations are the lack of patients´ clinical information for use as control variables and the lack of variables to assess patients´ quality of life. The study also found that many cases involved claims that could have been solved by administrative rather than legal action. Some claims thus reflect the lack of adequate administrative procedures. CONCLUSION: When based on scientific evidence, access to new therapies, combined with other technologies already available, can favor patient survival. Access to new therapies through litigation may increase health inequalities since low-income patients have limited access to legal recourse against the State to meet their needs. The timely approval of new effective therapies can mitigate the judicialization of cancer treatment.

Emergence of KPC-3- and OXA-181-producing ST13 and ST17 Klebsiella pneumoniae in Portugal: genomic insights on national and international dissemination.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains are of particular concern, especially strains with mobilizable carbapenemase genes such as blaKPC, blaNDM or blaOXA-48, given that carbapenems are usually the last line drugs in the ß-lactam class and, resistance to this sub-class is associated with increased mortality and frequently co-occurs with resistance to other antimicrobial classes. OBJECTIVES: To characterize the genomic diversity and international dissemination of CRKP strains from tertiary care hospitals in Lisbon, Portugal. METHODS: Twenty CRKP isolates obtained from different patients were subjected to WGS for species confirmation, typing, drug resistance gene detection and phylogenetic reconstruction. Two additional genomic datasets were included for comparative purposes: 26 isolates (ST13, ST17 and ST231) from our collection and 64 internationally available genomic assemblies (ST13). RESULTS: By imposing a 21 SNP cut-off on pairwise comparisons we identified two genomic clusters (GCs): ST13/GC1 (n = 11), all bearing blaKPC-3, and ST17/GC2 (n = 4) harbouring blaOXA-181 and blaCTX-M-15 genes. The inclusion of the additional datasets allowed the expansion of GC1/ST13/KPC-3 to 23 isolates, all exclusively from Portugal, France and the Netherlands. The phylogenetic tree reinforced the importance of the GC1/KPC-3-producing clones along with their rapid emergence and expansion across these countries. The data obtained suggest that the ST13 branch emerged over a decade ago and only more recently did it underpin a stronger pulse of transmission in the studied population. CONCLUSIONS: This study identifies an emerging OXA-181/ST17-producing strain in Portugal and highlights the ongoing international dissemination of a KPC-3/ST13-producing clone from Portugal.

TiO2-MWCNT nanohybrid: Cytotoxicity, protein corona formation and cellular internalisation in RTG-2 fish cell line.

Titanium dioxide nanoparticles-multiwalled carbon nanotubes (TiO2-MWCNT) nanohydrid has an enhanced photocatalytic activity across the visible light with promising applications in environmental remediation, solar energy devices and antimicrobial technologies. However, it is necessary to evaluate the toxicological effects of TiO2-MWCNT towards safe and sustainable development of nanohybrids. In this work, we studied the cytotoxicity, protein corona formation and cellular internalisation of TiO2-MWCNT on fibroblasts derived from gonadal rainbow trout tissue (RTG-2) for the first time. This nanohydrid did not show any toxicity effect on RTG-2 cells up to 100 mg L-1 after 24 h of exposure as monitored by alamar blue, neutral red and trypan blue assays (in presence or absence of foetal bovine serum, FBS). Futhermore, cryo-transmission electron microscopy analysis demonstrated that TiO2 particles is attached on nanotube surface after FBS-protein corona formation in cell culture medium. Raman spectroscopy imaging showed that TiO2-MWCNT can be internalised by RTG-2 cells. This work is a novel contribution towards better understanding the nanobiointeractions of nanohydrids linked to their in vitro effects on fish cells in aquatic nanoecotoxicology.

Association of Early Sports Practice with Cardiovascular Risk Factors in Community-Dwelling Adults: A Retrospective Epidemiological Study.

BACKGROUND: Sports practice in childhood and adolescence has been inversely related to the chances of developing cardiovascular risk factors (CRFs). However, it is not clear whether sports practice in childhood and adolescence could be inversely related to CRF in adult life. OBJECTIVES: This study aimed to analyze the association between early sports practice and cardiovascular risk factors in a randomized sample of community-dwelling adults. METHODS: For this, 265 adults aged ≥ 18 years composed the sample. Cardiovascular risk factors of obesity, central obesity, diabetes, dyslipidemia, and hypertension were collected. Early sports practice was retrospectively self-reported using an appropriate instrument. Total physical activity level was assessed by accelerometry. The association between early sports practice and cardiovascular risk factors in adulthood was analyzed by binary logistic regression, adjusted for sex, age, socioeconomic status, and moderate-to-vigorous physical activity. RESULTS: Early sports practice was observed in 56.2% of the sample. The prevalence of central obesity (31.5 vs. 50.0%; p = 0.003), diabetes (4.7% vs. 13.7%; p = 0.014), dyslipidemia (10.7% vs. 24.1%; p = 0.005), and hypertension (14.1% vs. 34.5%; p = 0.001) was lower in participants who reported early sports practice. Participants who reported early sports practice in childhood and adolescence were, respectively, 60% (OR = 0.40; 95% CI 0.19-0.82) and 59% (OR = 0.41; 95% CI 0.21-0.82) less likely to have hypertension in adult life when compared to those with no early sports practice, independently of sex, age, socioeconomic status, and habitual physical activity level in adulthood. CONCLUSION: Early sports practice in childhood and adolescence was a protective factor for hypertension in adulthood.