RESUMO
Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively. Patients were categorized into the following age groups: 18-39, 40-59, 60-69 and ≥70 years. Of 728 patients evaluated at baseline, 686 (94%) completed HRQoL assessments. The median age at TKI discontinuation was 60 years. Our findings indicate that HRQoL and symptom trajectories may vary depending on specific age groups, with younger patients benefiting the most. Improvements in patients aged 60 years or older were marginal across several HRQoL and symptom domains. At the time of considering TKI discontinuation, physicians could inform younger patients that they may expect valuable HRQoL benefits. Considering the marginal improvements observed in patients aged 60 years or above, it may be important to further investigate the value of TFR compared to a lowest effective dose approach in this older group of patients.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Qualidade de Vida , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Europa (Continente) , Fadiga/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inquéritos e Questionários , Interrupção do TratamentoRESUMO
Mosquitoes (Diptera: Culicidae) pose a significant threat to public health worldwide, especially in tropical and subtropical regions, where they act as primary vectors in transmission of infectious agents. In Peru, 182 culicid species have been identified and several species of the genus Culex are known to transmit arboviruses. However, knowledge of mosquito diversity and distribution remains limited, with many studies focusing on specific regions only. Here, we describe a new morphological variation of Cx. (Culex) coronator Dyar and Knab, 1906, and report the presence of Culex (Carrollia) bonnei Dyar, 1921 in the central region of Peru, Huanuco. Specimens were obtained through larvae collections and identified through morphologic characterization, including dissection of male genitalia, and molecular analyses. In total, 17 mosquitoes were analyzed, and the genitalia of the male specimens allowed the identification of Cx. coronator and Cx. bonnei. Partial sequences of the CoxI gene corresponding to these two species were obtained (N = 10). Phylogenetic analysis revealed that the sequences of Cx. coronator grouped in a monophyletic clade with sequences ascribed to other species corresponding to the subgenus Carrollia, while Cx. bonnei specimens formed a monophyletic clade with homologous sequences from GenBank. This study underscores the importance of continued efforts to study the diversity and distribution of mosquitoes in Peru, including their potential role as vectors of human pathogens, to underpin effective disease control and prevention strategies, highlighting the importance of a complemented morphological and molecular analysis.
Assuntos
Culex , Animais , Peru , Culex/anatomia & histologia , Culex/classificação , Masculino , Larva/anatomia & histologia , Larva/classificação , Genitália Masculina/anatomia & histologia , Filogenia , Feminino , Mosquitos Vetores/anatomia & histologiaAssuntos
Teste de Esforço , Humanos , Brasil , Teste de Esforço/normas , Teste de Esforço/métodos , Adulto , Feminino , Masculino , Doenças CardiovascularesRESUMO
Plastic pollution in aquatic ecosystems is increasing and plastic particles may adsorb and transport a diverse array of contaminants, thereby increasing their bioavailability to biota. This investigation aimed to evaluate the effects of varying polyethylene microplastics (PE MPs) and naphthalene (NAPH) concentrations on the survival and feeding rates of the model organism, Artemia salina, as well as NAPH adsorption to microplastics at different salinity levels (17, 75, 35.5 and 52.75 g L-1) under selected climate change scenarios. Survival (48 h) and feeding rates (6 h) of A. salina were also monitored, revealing that the presence of higher PE and NAPH concentrations lead to decreased survival rates while also increasing the number and size of microplastic particles in the saline solutions. Higher PE concentrations negatively affected A. salina feeding rates and NAPH concentrations were positively correlated with particle number and size, as well as with NAPH and PE adsorption rates in solution. Our findings demonstrate that the co-occurrence of microplastics and NAPH in aquatic environments can result in detrimental zooplankton survival and feeding rate effects. Furthermore, this interaction may contribute to the accumulation of these contaminants in the environment, highlighting the need to simultaneously monitor and mitigate the presence of microplastics and organic pollutants, like NAPH, in aquatic environments.
Assuntos
Artemia , Microplásticos , Naftalenos , Polietileno , Salinidade , Poluentes Químicos da Água , Animais , Microplásticos/toxicidade , Polietileno/toxicidade , Polietileno/química , Poluentes Químicos da Água/toxicidade , Artemia/efeitos dos fármacos , Adsorção , Naftalenos/toxicidade , Naftalenos/químicaRESUMO
PURPOSE OF REVIEW: Both human-derived and naturally-occurring disasters stress the surge capacity of health systems and acute care facilities. In this article, we review recent literature related to having a disaster plan, facility planning principles, institutional and team preparedness, the concept of surge capacity, simulation exercises and advantages and disadvantages of each. RECENT FINDINGS: Evidence suggests that every institution should have a disaster plan and a dedicated team responsible for updating this plan. The disaster plan must be people-oriented and incorporate different perspectives and opinions so that all stakeholders feel included and can contribute to a joint response. Simulation exercises are fundamental for preparation so that the team functions seamlessly in uncommon times when disaster management transitions from a theoretical plan to one that is executed in real time. Notably, however, there are significantly different realities related to disaster management between countries and even within the same country or region. Unfortunately, key stakeholders such as hospital administration, board of directors and investors often do not believe they have any responsibility related to disaster management planning or response. Additionally, while a disaster plan often exists within an institution, it is frequently not well known or understood by many stakeholders. Communication, simple plans and well defined roles are some of the most important characteristics of a successful response. In extreme circumstances, adapting civilian facilities to manage high-volume warfare-related injuries may be adopted, but the consequences of this approach for routine healthcare within a system can be devastating. SUMMARY: Disaster management requires careful planning with input from multiple stakeholders and a plan that is frequently updated with repeated preparation to ensure the team is ready when a disaster occurs. Close communication as well as clearly defined roles are critical to success when transitioning from preparation to activation and execution of a disaster response.
Assuntos
Planejamento em Desastres , Capacidade de Resposta ante Emergências , Planejamento em Desastres/organização & administração , Humanos , Equipe de Assistência ao Paciente/organização & administração , ComunicaçãoRESUMO
Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing "immune classes" among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune "risk factors." By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.
Assuntos
Diafragma , Unidades de Terapia Intensiva , Músculo Quadríceps , Traqueostomia , Desmame do Respirador , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
New hippocampal neurons are continuously generated in the adult human brain. Several studies have demonstrated that the proliferation of hippocampal cells is strongly influenced by a variety of stimuli, including pesticides exposure. These effects are particularly important because neurogenesis dysregulation could be associated with the decline of neuronal and cognitive functions and the possible development of neuropsychiatric disorders.
Novos neurônios hipocampais são gerados continuamente no cérebro humano adulto. Vários estudos têm demonstrado que a proliferação de células do hipocampo é influenciada por uma variedade de estímulos, incluindo a exposição a pesticidas. Estes efeitos são particularmente importantes porque a desregulação da neurogênese pode estar associada ao declínio das funções neuronais e cognitivas e ao possível desenvolvimento de doenças neuropsiquiátricas.
Assuntos
Hipocampo , Neurogênese , Neurônios , Praguicidas , Praguicidas/toxicidade , Humanos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , AnimaisRESUMO
Babassu coconut (Attalea speciosa syn. Orbignya phalerata) contains an oil-rich nut and is primarily found in South America's Amazon region. Future market researchers predict an increase in the babassu oil market from USD 227.7 million in 2022 to USD 347.0 million by 2032, and the yield of babassu oil from babassu-processed waste could reach 90%. Of these, mesocarp flour is an underrated by-product used only for animal feed purposes by local producers. This comprehensive review focuses on advances in knowledge and understanding of phytochemicals from babassu oil by-products considering the mechanisms of action - covering antioxidant, antimicrobial, antiparasitic, anti-inflammatory, antithrombotic, immunomodulatory, and anticancer effects. Babassu coconut fruit contains free fatty acids, (poly)phenols, phytosterols, and triterpenes. Pytochemicals, antiparasitic and antibacterial activities of babassu mesocarp flour were shown, but fungi and viruses can get more attention. Beyond its antioxidant capacity, babassu mesocarp flour showed potential as a dietary food supplement. Aqueous suspensions of mesocarp flour with a higher preference for cancer cells than normal cells and an antithrombotic effect were also identified, probably related to the antioxidant capacity of its secondary metabolites. Mesocarp flour, a starch-rich fraction, is promising for application as biodegradable packaging to improve the oxidative stability of foods. Finally, low-added value fractions can be considered bio-waste/co-products, and their phytochemicals may attract interest for applications in medicine and nutrition. Toxicological concerns, trends, and gaps are discussed for the future of foods and related sciences.
Assuntos
Suplementos Nutricionais , Humanos , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Animais , Resíduos/análiseRESUMO
INTRODUCTION AND OBJECTIVES: Ischemic heart disease is the single most common cause of death in Europe. Mortality in patients presenting with ST-elevation myocardial infarction (STEMI) is associated with many factors, one of which is the time delay to treatment. The purpose of this work is to analyze the coronary pathway in our region in terms of timing, taking into consideration the place of first medical contact (FMC). METHODS: Consecutive patients admitted to our center with STEMI to undergo percutaneous coronary intervention (PCI) between 2013 and 2022 were analyzed. Age, gender, and time delays were collected. Analysis was performed with IBM SPSS version 28 for a significance level of 0.05. RESULTS: We found that non-PCI centers had a significantly greater FMC to diagnosis delay and diagnosis to wire delay compared to other places of origin. Only 2.2% of patients met the 10-min FMC to diagnosis target; 44.8% met the target of 90 min from diagnosis to wire in transferred patients, while 40.6% met the 60-min target for patients admitted to a PCI center. Median patient, electrocardiogram (ECG) and logistic delays are 92.0±146.0 min, 19.0±146.0 min and 15.5±46.3 min, respectively. CONCLUSION: A significant difference between state-of-the-art targets and reality was found, depending on the place of FMC, with the worst delays in non-PCI centers. Patient delay, ECG delay, FMC to diagnosis and logistic delay are identified as key areas in which to intervene.
RESUMO
Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.
RESUMO
Antivenom therapy is the only specific treatment for snakebite envenomation, and antivenom potency determination is key in the efficacy assurance quality control process. Nowadays, this process relies on the in vivo murine model - thus, the development of alternative in vitro methods is imperative. In the current study, the principle of the proposed method is the ability of Bothrops venom to induce cytotoxic effects in Vero cells, and the capacity to evaluate the inhibition of this cytotoxicity by the respective antivenom. After exposure to the venom/antivenom, the relative proportions of adherent (viable) cells were evaluated by direct staining with Coomassie Blue. The optical density (OD) of the lysed cell eluate was directly proportional to the number of adherent cells. This cytotoxicity-based alternative method could represent a potential candidate for validation as a replacement for the current in vivo test. The in vitro-determined cytotoxicity of the Brazilian Bothrops reference venom (expressed as the 50% effective concentration; EC50) was 3.61 µg/ml; the in vitro-determined 50% inhibitory concentration (IC50) of the Brazilian Bothrops reference antivenom was 0.133 µl/ml. From these two values, it was possible to calculate the potency of the reference antivenom. The results from the assays exhibited a good linear response, indicating that the method could be a potential candidate replacement method for use in antivenom quality control prior to lot release, subject to further validation.
Assuntos
Antivenenos , Bothrops , Chlorocebus aethiops , Camundongos , Animais , Antivenenos/farmacologia , Veneno de Bothrops jararaca , Bothrops jararaca , Células Vero , Modelos Animais de DoençasRESUMO
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The European Stop Kinase Inhibitors (EURO-SKI) study is the largest clinical trial for investigating the cessation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in stable deep molecular remission (DMR). Among 728 patients, 434 patients (61%; 95% CI, 57 to 64) remained in major molecular response (MMR) at 6 months and 309 patients of 678 (46%; 95% CI, 42 to 49) at 36 months. Duration of TKI treatment and DMR before TKI stop were confirmed as significant factors for the prediction of MMR loss at 6 months. In addition, the type of BCR::ABL1 transcript was identified as a prognostic factor. For late MMR losses after 6 months, TKI treatment duration, percentage of blasts in peripheral blood, and platelet count at diagnosis were significant factors in multivariate analysis. For the entire study period of 36 months, multiple logistic regression models confirmed duration of treatment, blasts, and transcript type as independent factors for MMR maintenance. In addition to the duration of treatment, transcript type as well as blasts in peripheral blood at diagnosis should be considered as important factors to predict treatment-free remission.