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BACKGROUND: The prevalence of mild cognitive impairment (MCI) and its subsequent progression to dementia has increased progression to dementia has increased worldwide, making it a topic of interest. of interest, and it has been observed that approximately 23% of cases are avoidable through preventable through vigorous exercise. METHODS: A systematic review with meta-analysis was conducted by searching in the PubMed, Scopus, CINAHL, and Web of Science databases. For inclusion, studies had to incorporate High Intensity Training (HIT) as a primary or significant component of the overall intervention for older adults with MCI. Out of the 611 articles identified, 14 randomized clinical trials met the criteria for inclusion in the review. RESULTS: Fourteen trials were included in the systematic review, and seven were included in the meta-analysis. A total of 1839 participants were included in the studies, with 1014 receiving a high-intensity training-based intervention, and 998 were considered in the meta-analysis. Compared to usual care or sedentary activities, the high-intensity training interventions had a positive effect on cognition, either improving it or delaying the decline (g = 0.710 (95% CI: 0.191 - 1.229; p = 0.007). Additionally, the meta-analysis determined that a frequency of 3 sessions per week (g = 0.964, CI = 0.091 - 1.837, p = 0.030) of approximately 60 minutes (g = 0.756, CI = 0.052 - 1.460, p = 0.035) each was the best dose to obtain better effects on global cognition. CONCLUSION: Low-frequency and short-duration high-intensity training interventions are sufficient to improve or at least delay the decline in global cognition.
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Fluazuron is a novel veterinary pour-on antitick formulation which can be applied simultaneously with bovine reproduction management strategies. Considering the economic importance of the livestock industry in many countries, it is important to know whether antiparasitics such as fluazuron may cause embryonic loss. The aim of this study was to evaluate the toxicological effect of fluazuron on bovine oocytes during in vitro maturation. The best fluazuron concentrations were determined in a preliminary experiment on Chinese hamster ovary (CHO)-K1 cells and further used to compare fluazuron toxicity in both study models. Results of the annexin V and alkaline single cell gel electrophoresis assays demonstrated that fluazuron caused cytotoxicity and genotoxicity in bovine cumulus cells at all the concentrations tested (50, 75 and 100 µg fluazuron/mL). The evaluation of cortical granules and mitochondria distribution showed that cytoplasmic maturation was not affected by fluazuron treatment. However, a decrease in metaphase II + polar body, degenerate oocytes as well as disorganized chromatin in polar body were observed at all concentrations tested. Whereas the fertilization process was not altered by 50 µg/mL fluazuron, the embryo development rate decreased significantly. No significant differences were observed in any of the oxidative stress parameters assessed. This study contributes to a better understanding of fluazuron in bovines, suggesting that the antiparasitic may affect bovine reproduction and might cause embryo loss.
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Técnicas de Maturação in Vitro de Oócitos , Oócitos , Compostos de Fenilureia , Animais , Bovinos , Oócitos/efeitos dos fármacos , Compostos de Fenilureia/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Células CHO , Cricetulus , Antiparasitários/farmacologia , Antiparasitários/toxicidade , FemininoRESUMO
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.
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Carcinoma de Células Escamosas , Mutação , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Telomerase/genética , Telomerase/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , CamundongosRESUMO
Zinc (Zn) plays essential roles in numerous cellular processes. However, there is limited understanding of Zn homeostasis within the bovine reproductive system. This study investigated the influence of estradiol (E2) and progesterone (P4) on Zn transporter expression and intracellular free Zn levels in bovine oviduct epithelial cells (BOEC). For this purpose, cells were harvested from slaughtered cows and cultured in vitro. Intracellular Zn concentrations were measured using FluoZin-3AM staining, while real-time polymerase chain reaction assessed Zn transporter gene expression and quantification. Overall, our results confirmed the gene expression of all the evaluated Zn transporters (ZIP6, ZIP8, ZIP14, ZnT3, ZnT7 and ZnT9), denoted and the active role of E2 and P4 in intracellular Zn regulation. Our findings suggest an interaction between Zn, E2 and P4.
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Proteínas de Transporte , Progesterona , Zinco , Feminino , Bovinos , Animais , Progesterona/farmacologia , Progesterona/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Oviductos/metabolismo , Células Epiteliais/metabolismo , Estrogênios/farmacologiaRESUMO
The discovery of antibiotics has significantly transformed the outcomes of bacterial infections in the last decades. However, the development of antibiotic resistance mechanisms has allowed an increasing number of bacterial strains to overcome the action of antibiotics, decreasing their effectiveness against infections they were developed to treat. This study aimed to evaluate the antibacterial activity of synthetic coumarins Staphylococcus aureus in vitro and analyze their interaction with the MepA efflux pump in silico. The Minimum Inhibitory Concentration (MIC) determination showed that none of the test compounds have antibacterial activity. However, all coumarin derivatives decreased the MIC of the standard efflux inhibitor ethidium bromide, indicating antibacterial synergism. On the other hand, the C14 derivative potentiated the antibacterial activity of ciprofloxacin against the resistant strain. In silico analysis showed that C9, C11, and C13 coumarins showed the most favorable interaction with the MepA efflux pump. Nevertheless, due to the present in silico and in vitro investigation limitations, further experimental research is required to confirm the therapeutic potential of these compounds in vivo.
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Cumarínicos , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Cumarínicos/farmacologia , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Staphylococcus aureus/metabolismo , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/metabolismoRESUMO
The increase in antibiotic resistance rates has attracted the interest of researchers for antibacterial compounds capable of potentiating the activity of conventional antibiotics. Coumarin derivatives have been reported to develop effective antibacterials with possible new mechanisms of action for treating infectious diseases caused by bacteria with a profile of drug resistance. In this context, the aim of the present study we have now prepared one variety of new synthetic coumarins evaluating the pharmacokinetic and chemical similarity in silico, their antimicrobial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), and potential for the modulation of antibiotic resistance against Staphylococcus aureus (SA10) and Escherichia coli (EC06) clinical isolate bacteria by in vitro assay. The antibacterial activity and antibiotic-enhancing properties were evaluated by the broth microdilution method and pharmacokinetically characterized according to the Lipinsk rule of 5 and had their similarity analyzed in databases such as ChemBL and CAS SciFinder. The results demonstrated that only compound C13 showed significant antibacterial activity (MIC ≤256 µg/mL), and all other coumarins did not display relevant antibacterial activity (MIC ≥1024 µg/mL). However, they did modulate the antibiotics activities to norfloxacin and gentamicin, except, compound C11 to norfloxacin against Staphylococcus aureus (SA10). The in silico properties prediction and drug-likeness results demonstrated that all coumarins presented a good drug-likeness score with no violations and promising in silico pharmacokinetic profiles showing that they have the potential to be developed into an oral drug. The results indicate that the coumarin derivatives showed good in vitro antibacterial activity. These new coumarin derivatives also demonstrated the capacity to modulate antibiotic resistance with potential synergy action for current antimicrobials assayed, as antibiotic adjuvants, to reduce the emergence of antimicrobial resistance.
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Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Norfloxacino/farmacologia , Escherichia coli , Cumarínicos/farmacologia , Cumarínicos/química , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Estafilocócicas/tratamento farmacológico , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
Veterinary drugs are potential environmental pollutants that interfere with male reproductive function. Infertility has increased, and it is known that environmental toxins contribute to declining sperm parameters. Amitraz {N,N-[(methylamino) dimeth-ylidyne] di-2,4-xylidine} (AMZ) is a formamidine pesticide widely used as an insecticide and an acaricide. The aim of this study was to evaluate the toxicity of AMZ in bovine sperm. Three experiments using frozen-thawed bovine semen incubated with AMZ for 2 h were carried out. Negative and solvent (dimethyl sulfoxide) controls were run simultaneously with treatments. In experiment 1, the AMZ concentrations used were 10, 15 and 25 µg AMZ/ml and the sperm parameters evaluated were viability, mitochondrial activity, acrosomal status, functional membrane integrity and apoptosis. In experiments 2 and 3, 25 µg AMZ/ml was used to evaluate fertilizing capacity, embryo development and blastocyst DNA damage. In experiment 1, 25 µg AMZ/ml decreased sperm viability (P = 0.01), reduced mitochondrial activity (P = 0.03) and induced apoptosis (P < 0.01). Also, 15 and 25 µg AMZ/ml affected functional membrane integrity (P < 0.01). In experiment 2, AMZ did not alter sperm-zona binding (P = 0.40) and pronucleus formation (P = 0.36). In experiment 3, 25 µg AMZ/ml decreased the rate of embryo development (P < 0.01) and increased apoptosis (P = 0.03). These results suggest that AMZ induced alterations in bovine sperm, probably affecting male fertility at concentrations that could be present in the environment.
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Análise do Sêmen , Preservação do Sêmen , Masculino , Animais , Bovinos , Análise do Sêmen/veterinária , Sêmen , Espermatozoides , Preservação do Sêmen/veterinária , Desenvolvimento Embrionário , Criopreservação/veterináriaRESUMO
In vitro embryo production has grown in recent decades due to its great potential for cattle production. However, the quality of in vitro-produced embryos is lower compared with those produced in vivo. The postfertilization culture environment has a major influence on bovine embryo quality. We hypothesize that the inclusion of the inclusion of alpha-lipoic acid (ALA) in the in vitro culture (IVC) medium during the first 24 h would have positive effects on embryo development in vitro and cryotolerance. The aims of this study were to evaluate the antioxidant effect of ALA in IVC medium for 24 h on bovine zygotes (21 h post in vitro fertilization, IVF), day 2 cleaved embryos (46 h post-IVF), and to assess embryo quality, developmental competence, and cryotolerance after vitrification. In all experiments, IVC medium was the Control, and 2.5 µM ALA was the treatment implemented. Viability and reactive oxygen species (ROS) levels in zygotes and day 2 embryos did not differ from the Control (P > 0.05). Supplementation with ALA increased total blastocyst and hatching rates (P < 0.05). It also improved embryo quality, evidenced by the increased blastocyst total cell number and the percentage of excellent-quality embryos observed (P < 0.05). In embryos cultured with ALA and then vitrified, ALA reduced intracellular ROS levels in warmed blastocysts (P < 0.05). In conclusion, ALA supplementation to IVC medium during 24 h is a new advantage in improving embryo quality for assisted bovine reproduction.
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Criopreservação , Ácido Tióctico , Bovinos , Animais , Criopreservação/veterinária , Ácido Tióctico/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Técnicas de Cultura Embrionária/veterinária , Vitrificação , Fertilização in vitro/veterinária , Blastocisto , Desenvolvimento EmbrionárioRESUMO
La sarcopenia está caracterizada por la baja masa y fuerza muscular en los adultos mayores. La implementación de técnicas de modificación de la conducta como la técnica de economía de fichas (TEF) puede fungir como estrategia para mejorar la adherencia al tratamiento. El objetivo fue evaluar el efecto de la TEF sobre las conductas de tratamiento: realizar la rutina de ejercicio de resistencia, consumir el suplemento de proteína y consumir el suplemento de vitamina D. Se realizó un estudio de caso de múltiples sujetos en ocho adultos mayores con sarcopenia. El estudio estuvo conformado por tres fases: pre-intervención, intervención conductual y post-intervención conductual. Se evaluó la frecuencia de las conductas de tratamiento en las tres fases, además de los cambios en masa y fuerza muscular. El análisis de los datos se realizó por medio de estadística descriptiva. Los resultados mostraron que la frecuencia de las conductas de tratamiento aumentó en el 100% de los participantes en la etapa de intervención conductual al comparar con la fase pre-intervención, valores que no regresaron a cero en la fase post-intervención conductual. El 83.3 % de los participantes dejaron de tener el diagnóstico de sarcopenia con base en los cambios de masa y fuerza muscular.
Sarcopenia is characterized by low muscle mass and strength in older adults. It is caused by decreased physical activity and quality of dietary intake. Therefore, the implementation of behavior modification techniques such as the token economy technique can serve as a strategy to improve treatment. The aim of the current study was to evaluate the effect of the token economy technique on treatment behaviors. A multiple case studies with an ABC-type design was conducted in eight older adults with sarcopenia. The intervention consisted of modification of treatment-related behaviors; in addition, changes in muscle mass and strength were assessed. The results showed that the frequency of target behaviors increased in 100% of the participants in the intervention stage compared to baseline. The frequency of the target behaviors did not return to the obtained baseline compared to the maintenance stage. 83.3% of the participants changed their sarcopenia diagnosis.
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Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Reforço por Recompensa , Sarcopenia/terapia , Resistência Física , Ingestão de Alimentos , Terapia por Exercício , Cooperação e Adesão ao TratamentoRESUMO
The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.
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During healthcare catastrophes, such as the current COVID-19 pandemic, nurses are exposed to highly stressful situations derived from their work and personal activity. Development of coping strategies for such situations can improve nurses' physical and mental health. This study analyzed nurses' adaptability to change, with attention to socio-demographic variables in a COVID-19 setting, and identified the repercussions on their health. This quantitative, observational and cross-sectional study had a sample of 351 nurses aged 22 to 64 with a mean age of 40.91 (SD = 10.98). The instruments used for the study were the ADAPTA-10 questionnaire and the General Health Questionnaire (GHQ-28). It was observed that age, sex, and having a stable partner significantly influenced scores on the emotional, cognitive-behavioral, and adaptation to change factors. Finally, the emotional factor mediated between positive COVID-19 in someone close and the presence of health problems. Understanding the elements that help adapt better to change and adversity enable effective interventions to be developed for improving emotional health of nurses, especially for those in whom there are positive cases of COVID-19 in their personal or work environment.
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Introduction: the public health crisis caused by COVID-19, a disease caused by SARS-CoV-2, has imposed physical threats and psychological suffering on both infected patients and individuals who experience social isolation and various governmental restrictions, leading to the appearance of symptoms like anxiety, depression, as well as insomnia, stress, and changes in biological rhythm. In face of this stressful scenario, interventions based on mindfulness (MBIs) have proved to be potentially adequate tools in reducing psychological suffering and generating well-being in the general population.Objective: to describe the effects of mindfulness-based interventions during the COVID-19 pandemic. Methods: A systematic literature review was conducted on the effects of mindfulness intervention in times of COVID-19. The articles were searched in four databases (Pubmed, Embase, Scopus, and Science direct) and the PRISMA protocol was used to conduct this review. In total, fourteen articles were included in the study.Results: the use of mindfulness techniques in the population with impaired mental health because of the COVID-19 pandemic proved to be beneficial, with improvement in emotional stress scores and reduction in anxiety symptoms, through formal mindfulness meditation practices such as mindful breathing, body scanning, and application of the mindfulness-based stress reduction strategy (MBSR). Strategies were also applied through smartphone applications that had the objective of promoting the increase of mindfulness and the development of the acceptance without judgment of the traumatic experiences already lived, in addition to an integrated intervention on the internet with the use of mindfulness, the training of respiratory relaxation, refuge skills and Butterfly Hug Method.Conclusion: with the pandemic going through, still with high mortality, continuity of social isolation, and, consequently, intensification of psychic suffering in the population and health professionals, interventions based on mindfulness (MBIs) are being effective to reduce this suffering, prevent the appearance of of chronic mental disorders and promote positive impacts on physical and mental well-being.
Introdução: a crise de saúde pública ocasionada pela COVID-19, doença causada pelo SARS-CoV-2, impôs ameaças físicas e sofrimento psíquico tanto aos pacientes infectados quanto aos indivíduos que vivenciam o isolamento social e as diversas restrições governamentais, propiciando o aparecimento de sintomas de ansiedade, depressão, além de insônia, estresse e alterações do ritmo biológico. Diante desse cenário estressor, as intervenções baseadas em atenção plena (MBIs), se mostraram ferramentas potencialmente adequadas na redução do sofrimento psicológico e na geração de bem-estar da população em geral.Objetivo: descrever os efeitos das intervenções baseadas em mindfulness em tempos da COVID-19.Método: foi realizada uma revisão sistemática da literatura sobre os efeitos da intervenção mindfulness em tempos da COVID-19. Os artigos foram pesquisados em quatro bases de dados (Pubmed, Embase, Scopus e Science direct) e o protocolo PRISMA foi utilizado para realização desta revisão. No total, quatorze artigos foram incluídos no estudo.Resultados: a utilização de técnicas de mindfulness na população com prejuízos na saúde mental em consequência da pandemia da COVID-19 mostraram-se benéficas, ocorrendo melhora no escore de estresse emocional e redução dos sintomas de ansiedade, através de práticas formais de meditação tipo mindfulness, como respiração consciente, escaneamento corporal, e aplicação da estratégia de redução do estresse baseada em atenção plena (MBSR). Estratégias também foram aplicadas através de aplicativos de smartphone que tiveram o objetivo de promover o aumento da atenção plena e o desenvolvimento da aceitação, sem julgamentos, das experiências traumáticas já vividas, além de intervenção integrada na internet com o uso da atenção plena, treinamento de relaxamento respiratório, habilidades de refúgio e método do abraço de borboleta. Conclusão: com o perpassar da pandemia, ainda com elevada mortalidade, continuidade dos isolamentos sociais, e, consequentemente, intensificação do sofrimento psíquico na população e profissionais de saúde, as intervenções baseadas em atenção plena (MBIs) estão sendo eficazes para diminuir esse sofrimento, prevenir aparecimento de transtornos mentais crônicos e promover impactos positivos no bem-estar físico e mental.
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OBJECTIVE: as a health care profession focused on caring for people, Nursing requires sound communication skills. Based on an international expert consensus, a proposal on learning outcomes in clinical communication for undergraduate Nursing education curricula in Spanish speaking countries is presented. METHOD: a steering committee, consisting of 5 nurses and experts in communication in health care sciences, drew up the first list of communication skills specific to the Nursing degree. Their proposal was reviewed and improved by a committee of 7 international scientific advisers. 70 experts from 14 countries were selected using a snowball sampling procedure and invited to participate in a distance modified Delphi consensus process in two survey rounds. Statistical analysis was carried out to establish the final consensus level for each item. RESULTS: a questionnaire with 68 learning outcomes in clinical communications was submitted for panel assessment. In the first Delphi round, the panel reached a statistical consensus on all the items assessed. There was no need for a second round to reconcile positions. CONCLUSION: an academic proposal, approved by a high level of international consensus, is presented to guide and unify the learning outcomes on the clinical communication curriculum for undergraduate Nursing studies in Spanish speaking countries.
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Bacharelado em Enfermagem , Estudantes de Enfermagem , Competência Clínica , Comunicação , Consenso , Currículo , Técnica Delphi , Humanos , Estados UnidosRESUMO
Sarcoptic mange epidemics can devastate wildlife populations. In 2014, mange was first detected in vicuñas (Vicugna vicugna) and guanacos (Lama guanicoe) in San Guillermo National Park (SGNP), Argentina. This study describes the temporal dynamics of the outbreak, its effects on the park's wild camelid populations between 2017-2019, and investigates the potential source of the epidemic. From May 2017 to June 2018, transect surveys indicated a sharp decrease in the density of living vicuñas and guanacos by 68% and 77%, respectively. By April 2019 no vicuñas or guanacos were recorded on transect surveys, suggesting their near-extinction in the park. Clinical signs consistent with mange (e.g., intense scratching, hyperkeratosis, alopecia) were observed in 24% of living vicuñas (n = 478) and 33% of living guanacos (n = 12) during surveys, as well as in 94% of vicuña carcasses (n = 124) and 85% of guanaco carcasses (n = 20) examined. Sarcoptes scabiei was identified as the causal agent by skin scrapings, and the cutaneous lesions were characterized by histopathology (n = 15). Genetic characterization revealed that mites recovered from seven vicuñas (n = 13) and three guanacos (n = 11) shared the same genotype, which is consistent with a single source and recent origin of the epidemic. Tracing the potential source, we identified a governmental livestock incentive program which introduced llamas (Lama glama) in areas adjacent to SGNP in 2009, some of which had alopecic scaling consistent with sarcoptic mange. Though at the time of our study no llamas with mange were available for confirmatory sampling, we hypothesize that the introduction of mange-infected llamas may have triggered the outbreak in wild camelids. This unprecedented event in SGNP had devastating effects on dominating herbivores with potentially profound cascading effects at the community and ecosystem levels.
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Parques RecreativosRESUMO
The aim of this study was to evaluate the association between plasma copper (Cu) concentration and ovarian function during a fixed-time artificial insemination (FTAI) protocol and the effect of parenteral Cu administration (100 mg) at the start of such protocol (day 0) on area of preovulatory follicle (APF); area of corpus luteum (ACL), plasma estradiol (E2), and progesterone (P4) concentrations; CL blood flow (CLBF); and pregnancy rate in beef heifers and cows. In cows, plasma Cu concentration on days 0 and 7 correlated positively with APF. Copper administration increased plasma Cu concentration and decreased APF and plasma E2 concentration (day 9), without modifying ACL, plasma P4 concentration, and CLBF (day 16) in cows. Pregnancy rate was higher in Cu-supplemented cattle on day 41 after FTAI as compared with controls (58.76 and 45.28%, respectively). In conclusion, Cu administration at the beginning of the FTAI protocol increased pregnancy rate in beef heifers and cows, modifying APF and plasma E2 concentration in the latter.
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Cobre , Sincronização do Estro , Animais , Bovinos , Cobre/farmacologia , Corpo Lúteo , Estradiol , Sincronização do Estro/métodos , Feminino , Inseminação Artificial/métodos , Inseminação Artificial/veterinária , Gravidez , Taxa de Gravidez , ProgesteronaRESUMO
Six complexes with the general formula [Cu(acylthioureato)(PPh3)2] were synthesized and characterized using spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), mass spectrometry, elemental analysis, and X-ray diffraction. Interpretation of the in vitro cytotoxicity data of Cu(I) complexes took into account their stability in cell culture medium. DFT calculations showed that NMR properties, such as the shielding of carbon atoms, are affected by relativistic effects, supported by the ZORA Hamiltonian in the theoretical calculations. Additionally, the calculation of the energies of the frontier molecular orbitals predicted that the structural changes of the acylthiourea ligands did not cause marked changes in the reactivity descriptors. All complexes were cytotoxic to the evaluated tumor cell lines [MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast cancer), and A549 (lung cancer)]. In the MDA-MB-231 cell line, complex 1 significantly altered the cytoskeleton of the cells, reducing the density and promoting the condensation of F-actin filaments. In addition, the compound caused an increase in the percentage of cells in the fragmented DNA region (sub-G0) and induced cell death via the apoptotic pathway starting at the IC50 concentration. Taken together, the results show that complex 1 has cytotoxic and apoptotic effects on TNBC cells, which is a cell line originating from an aggressive, difficult-to-treat breast cancer.
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Neoplasias de Mama Triplo NegativasRESUMO
BACKGROUND: Single-dose tafenoquine 300 mg is approved for Plasmodium vivax malaria relapse prevention in patients at least 16 years old. We aimed to determine appropriate oral tafenoquine paediatric dosing regimens, including a dispersible formulation, and evaluated tafenoquine efficacy and safety in children infected with P vivax. METHODS: This open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 study enrolled children (2-15 years) who weighed 5 kg or more, with glucose-6-phosphate dehydrogenase activity more than 70% of the local population median, and P vivax malaria infection, from three community health centres in Vietnam and one in Colombia. Patients received 3-day chloroquine plus oral single-dose tafenoquine as dispersible tablets (50 mg) or film-coated tablets (150 mg). Dosing groups were assigned by body weight, predicted to achieve similar median exposures as the approved 300 mg dose for adults: patients who weighed 5 kg or more to 10 kg received 50 mg, those who weighed more than 10 to 20 kg received 100 or 150 mg, those who weighed more than 20 to 35 kg received 200 mg, and patients who weighed more than 35 kg received 300 mg. Population pharmacokinetic analysis was done to develop a paediatric population pharmacokinetic model. The primary outcome was the tafenoquine area under the concentration-time curve extrapolated to infinity (AUC[0-∞]) by patient body weight in the pharmacokinetic population (all patients who received tafenoquine with at least one valid pharmacokinetic sample) estimated from a paediatric population pharmacokinetic model. A key prespecified secondary outcome was 4-month recurrence-free efficacy. This trial is registered with ClinicalTrials.gov, NCT02563496. FINDINGS: Between Feb 6, 2017, and Feb 17, 2020, 60 patients were enrolled into the study: 14 (23%) received tafenoquine 100 mg, five (8%) 150 mg, 22 (36%) 200 mg, and 19 (32%) 300 mg. The paediatric population pharmacokinetic model predicted adequate tafenoquine exposure at all doses. The predicted median AUC(0-∞) was 73·8 (90% prediction interval [PI] 46·9-117·0) µg × h/mL with the 50 mg dose for patients who weighed 5 kg or more to 10 kg, 87·5 (55·4-139·0) µg × h/mL with the 100 mg dose for body weight more than 10 to 20 kg, 110·7 (70·9-174·0) µg × h/mL with the 200 mg dose for body weight more than 20 to 35 kg, and 85·7 (50·6-151·0) µg × h/mL with the 300 mg dose for body weight more than 35 kg. 4-month recurrence-free efficacy was 94·7% (95% CI 84·6-98·3). Adverse events were consistent with previous studies, except for the seven (12%) of 60 patients who had post-dose vomiting or spitting with the 50 mg dispersed tablet. Following mitigation strategies, there were no additional occurrences of this adverse event. There were no deaths during the study. INTERPRETATION: For the prevention of P vivax relapse in children, single-dose tafenoquine, including a dispersible formulation, had exposure, safety, and efficacy consistent with observations in adolescents and adults, notwithstanding post-dose vomiting. FUNDING: GlaxoSmithKline and Medicines for Malaria Venture. TRANSLATIONS: For the Vietnamese and Spanish translations of the abstract see Supplementary Materials section.
Assuntos
Aminoquinolinas/administração & dosagem , Aminoquinolinas/farmacocinética , Aminoquinolinas/uso terapêutico , Antimaláricos/administração & dosagem , Antimaláricos/farmacocinética , Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Cloroquina/administração & dosagem , Feminino , Humanos , Masculino , Recidiva , Prevenção Secundária , ComprimidosRESUMO
Resumo Objetivo: como profissão orientada à atenção da saúde, focada no cuidado às pessoas, a Enfermagem precisa desenvolver habilidades de comunicação sólidas. Com base em um consenso internacional de especialistas, apresenta-se uma proposta sobre os resultados de aprendizagem na comunicação clínica para planos de estudos em cursos de Enfermagem em países hispanofalantes. Método: um comitê orientador, composto por 5 enfermeiros e especialistas em comunicação em ciências de atenção à saúde, elaborou a primeira lista de habilidades comunicacionais específicas para o curso de Enfermagem. Outro comitê de 7 assessores científicos internacionais revisou e melhorou a referida proposta. Foram selecionados 70 especialistas de 14 países pelo procedimento de amostragem "bola de neve", sendo convidados para participar em um processo de consenso Delphi modificado a distância em duas rodadas de pesquisa. Foi realizada a análise estatística para estabelecer o nível de consenso final correspondente a cada item. Resultados: foi apresentado um questionário com 68 resultados de aprendizagem em comunicações clínicas para serem avaliados pelo painel. Na primeira rodada Delphi, o painel chegou a um consenso estatístico em todos os itens avaliados. Não foi necessária uma segunda rodada para conciliar posições. Conclusão: apresenta-se uma proposta acadêmica aprovada com um elevado nível de consenso internacional a fim de orientar e unificar os resultados de aprendizagem nos planos de estudo sobre comunicação clínica para cursos de Enfermagem em países hispanofalantes.
Abstract Objective: as a health care profession focused on caring for people, Nursing requires sound communication skills. Based on an international expert consensus, a proposal on learning outcomes in clinical communication for undergraduate Nursing education curricula in Spanish speaking countries is presented. Method: a steering committee, consisting of 5 nurses and experts in communication in health care sciences, drew up the first list of communication skills specific to the Nursing degree. Their proposal was reviewed and improved by a committee of 7 international scientific advisers. 70 experts from 14 countries were selected using a snowball sampling procedure and invited to participate in a distance modified Delphi consensus process in two survey rounds. Statistical analysis was carried out to establish the final consensus level for each item. Results: a questionnaire with 68 learning outcomes in clinical communications was submitted for panel assessment. In the first Delphi round, the panel reached a statistical consensus on all the items assessed. There was no need for a second round to reconcile positions. Conclusion: an academic proposal, approved by a high level of international consensus, is presented to guide and unify the learning outcomes on the clinical communication curriculum for undergraduate Nursing studies in Spanish speaking countries.
Resumen Objetivo: en su carácter de profesión de atención de la salud enfocada en cuidar a las personas, la Enfermería requiere habilidades de comunicación sólidas. Sobre la base de un consenso internacional de expertos, se presenta una propuesta sobre resultados de aprendizaje en la comunicación clínica para planes de estudio de las carreras de grado de Enfermería en países de habla hispana. Método: un comité orientador, compuesto por 5 enfermeros y expertos en comunicación en ciencias de atención de la salud, elaboró la primera lista de habilidades de comunicación específicas para la carrera de Enfermería. Un comité de 7 asesores científicos internacionales revisó y mejoró dicha propuesta. Se seleccionó a 70 expertos de 14 países a través del procedimiento de muestreo "bola de nieve", y se los invitó a participar en un proceso de consenso Delphi modificado a distancia en dos rondas de encuesta. Se realizó un análisis estadístico para establecer el nivel de consenso final correspondiente a cada ítem. Resultados: se presentó un cuestionario con 68 resultados de aprendizaje en comunicaciones clínicas para que lo evaluara el panel. En la primera ronda Delphi, el panel llegó a un consenso estadístico en todos los ítems evaluados. No fue necesaria una segunda ronda para conciliar posiciones. Conclusión: se presenta una propuesta académica, aprobada con un elevado nivel de consenso internacional, a fin de orientar y unificar los resultados de aprendizaje en los planes de estudio sobre comunicación clínica para carreras de grado de Enfermería en países de habla hispana.
Assuntos
Humanos , Masculino , Feminino , Estudantes de Enfermagem , Competência Clínica , Comunicação , Consenso , Educação em Enfermagem , Relações Enfermeiro-Paciente , Técnica Delphi , CurrículoRESUMO
Resumen: El trabajo de campo etnográfico, que implica el encuentro con la otredad, es utilizado por la antropología médica para acercarse a la comprensión de problemáticas sociales relacionadas con la salud, la enfermedad, la atención y la muerte. El objetivo del trabajo fue realizar una reflexión ética de diversas situaciones conflictivas experimentadas por tres antropólogas durante sus investigaciones en México, a través del análisis de sus diarios de campo. Con este fin, se realizó un análisis grupal e interdisciplinario desde una perspectiva ética. Los conflictos encontrados se clasificaron en: 1. Dilemas éticos (como la sinceridad vs. ocultamiento de información); 2. Disonancias éticas (como la justicia en el acceso de los informantes a los servicios médicos, el acceso y la identidad del antropólogo en campo, los límites de la intervención, la reciprocidad y las emociones del investigador); y 3. Otros (conflictos éticos tales como la observación del paternalismo médico y las diferencias disciplinares entre el quehacer antropológico y el médico). Este análisis permitió comprender a través de una alerta ético-metodológica los posicionamientos epistemológicos, metodológicos y, principalmente, éticos de las investigadoras que, de manera subrepticia, guían la construcción del quehacer antropológico. Asimismo, la investigación permitió vislumbrar la responsabilidad de las acciones o inacciones del investigador frente a las personas observadas dentro de un contexto de atención en salud.
Abstract: Ethnographic fieldwork, which implies the encounter with otherness, is used by medical anthropology to approach the understanding of social problems related to health, illness, care and death. The objective of the work was to carry out an ethical reflection on various conflictive situations experienced by three anthropologists during their research in Mexico, by means of the analysis of their field diaries. To this end, a group and interdisciplinar y analysis was carried out from an ethical perspective. The conflicts found were classified as: 1. Ethical dilemmas (such as sincerity vs. concealment of information); 2. Ethical dissonances (such as fairness in informants' access to medical services, access and identity of the anthropologist in the field, limits of the intervention, reciprocity, and the emotions of the researcher); and 3. Others (ethical conflicts such as the observation of medical paternalism and the disciplinary differences between anthropological and medical work). This analysis allowed us to understand, through an ethical-methodological alert, the epistemological, methodological and, mainly, the ethical positions of the researchers who, surreptitiously, guide the construction of the anthropological task. Likewise, the investigation allowed us to glimpse the responsibility of the actions or inactions of the researcher vis a vis of the people observed within a context of health care.
Resumo: O trabalho de campo etnográfico, que implica o encontro com a alteridade, é utilizado pela antropologia médica para abordar a compreensão dos problemas sociais relacionados à saúde, doença, cuidado e morte. O objetivo do trabalho foi realizar uma reflexão ética sobre diversas situações conflituosas vivenciadas por três antropólogos durante suas pesquisas no México, por meio da análise de seus diários de campo. Para tanto, realizou-se uma análise grupal e interdisciplinar a partir de uma perspectiva ética. Os conflitos encontrados foram classificados em: 1. Dilemas éticos (como sinceridade x ocultação de informações); 2. Dissonâncias éticas (como equidade no acesso dos informantes aos serviços médicos, acesso e identidade do antropólogo em campo, limites de intervenção, reciprocidade e emoções do pesquisador); e 3. Outros (conflitos éticos como a observação do paternalismo médico e as diferenças disciplinares entre o trabalho antropológico e o médico). Essa análise permitiu compreender, por meio de um alerta ético-metodológico, as posições epistemológicas, metodológicas e, principalmente, éticas dos pesquisadores que, sub-repticiamente, orientam a construção da tarefa antropológica. Da mesma forma, a investigação permitiu vislumbrar a responsabilidade das ações ou omissões do pesquisador diante das pessoas observadas em um contexto de atenção à saúde.