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1.
N Engl J Med ; 387(11): 967-977, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36018037

RESUMO

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores da Agregação Plaquetária , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Atorvastatina/efeitos adversos , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , AVC Isquêmico/prevenção & controle , Infarto do Miocárdio/complicações , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/terapia , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ramipril/efeitos adversos , Ramipril/uso terapêutico , Prevenção Secundária/métodos
2.
Neuropsychol Rev ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639881

RESUMO

Meta-analyses often present flexibility regarding their inclusion criteria, outcomes of interest, statistical analyses, and assessments of the primary studies. For this reason, it is necessary to transparently report all the information that could impact the results. In this meta-review, we aimed to assess the transparency of meta-analyses that examined the benefits of cognitive training, given the ongoing controversy that exists in this field. Ninety-seven meta-analytic reviews were included, which examined a wide range of populations with different clinical conditions and ages. Regarding the reporting, information about the search of the studies, screening procedure, or data collection was detailed by most reviews. However, authors usually failed to report other aspects such as the specific meta-analytic parameters, the formula used to compute the effect sizes, or the data from primary studies that were used to compute the effect sizes. Although some of these practices have improved over the years, others remained the same. Moreover, examining the eligibility criteria of the reviews revealed a great heterogeneity in aspects such as the training duration, age cut-offs, or study designs that were considered. Preregistered meta-analyses often specified poorly how they would deal with the multiplicity of data or assess publication bias in their protocols, and some contained non-disclosed deviations in their eligibility criteria or outcomes of interests. The findings shown here, although they do not question the benefits of cognitive training, illustrate important aspects that future reviews must consider.

3.
Nicotine Tob Res ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970413

RESUMO

INTRODUCTION: In recent years tobacco taxation in Spain has regressed, with its Tobacconomics tax scorecard falling from 3.9 points (out of 5) in 2014, to only 2.625 in 2020. The objective of this research is to provide a detailed analysis of the causes behind this deterioration and identify possible ways forward for reversing this trend. METHODS: A retrospective 2014-2022 analysis of manufactured cigarettes (FM) and roll-your-own tobacco (RYO) markets including tax structure/rates, affordability, retail price gaps across products, and price differentials with bordering countries. A market level simulation model to 2028 studied the impact of various tax policy scenarios on smoking prevalence, premature deaths averted, smoking intensity, product substitution, government revenue, sales, and industry profit. RESULTS: A lack of tax increases in a context of inflation and income growth during the past 8 years means FM and RYO have become 13% more affordable, with a constant differential of €2 between 20 FM and RYO sticks, and the price gap between Spain and neighbouring France increased. Modelling of two realistic reform scenarios that reduce/eliminate the price gap between FM and RYO suggest substantial increases in government revenues and up to 700,000 fewer smokers and 210,000 fewer premature deaths. CONCLUSIONS: Current European Union legislation on tobacco taxes leaves ample room for much needed tobacco tax reform. For the sake of both public health and the economy, Spain should increase its Minimum Excise Tax. This would not only save lives, but also bring much needed revenue for the government. IMPLICATIONS: The stance of Spain on tobacco taxes has deteriorated recently. This study argues that the failure of successive governments to raise minimum taxes in an inflationary context has made tobacco products more affordable, and quantifies the improvements in smoking prevalence and excise revenue that would accrue if the authorities act urgently increasing rates within realistic limits.Spain is representative of European countries where government inaction has rendered minimum tobacco taxes obsolete. Given the postponement of the revision of the European Union Tobacco Tax Directive, this study highlights the need to act unilaterally within the existing legal framework.

4.
BMC Med Educ ; 24(1): 167, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383416

RESUMO

BACKGROUND: Lesbian, gay, bisexual, transgender, intersex, queer, and other sexual and gender identities (LGBTIQ+) individuals face health inequities. Additionally, medical students report a lack of confidence in providing specific health care to LGBTIQ + individuals, and medical schools do not offer the breadth and depth of coverage needed to fully prepare and make them comfortable in caring for these individuals. This study aims to characterize the teaching of curricular content related to LGBTIQ + health issues in medical schools in Chile. METHODS: This was a cross-sectional descriptive mixed-methods study based on a 15-question survey sent to school directors of the 24 medical schools in Chile, conducted between October 2020 and July 2021. The questions included in the study were mostly based on two pre-existing questionnaires covering content, assessment methods, and identification of barriers to teaching this content. RESULTS: The validated questionnaire was answered by 14 of 24 Chilean medical schools, with 11 schools (78.9%) declaring that they included some training in their curriculum. The predominant range of time allocated to LGBTIQ + training in medical programs was between 1 and 5 h. The most addressed topics were HIV (92.85%), sexual orientation (78.57%), and chronic disease risk in LGBTIQ + populations (78.57%). Most schools, accounting for 71.5%, considered the content they delivered to be "moderately insufficient" or "insufficient". Regarding the teaching methodologies, the most used were lectures (92.8%), clinical cases (42.9%), and clinical simulation (28.6%). CONCLUSION: Most surveyed medical schools reported curricular spaces dedicated to teaching health issues of LGBTIQ + individuals, primarily during the pre-internship training period. However, the time allocated is insufficient, and there is little approach to topics beyond the patient's sexual history or sexual orientation. Given the crucial role of medical schools, they must adopt both local and national strategies to enrich training focused on the care of LGBTIQ + patients.


Assuntos
Minorias Sexuais e de Gênero , Pessoas Transgênero , Humanos , Feminino , Masculino , Estudos Transversais , Chile , Faculdades de Medicina , Identidade de Gênero , Comportamento Sexual
5.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38673972

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and ß-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.


Assuntos
Microbioma Gastrointestinal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Cirrose Hepática/microbiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fezes/microbiologia , Fígado/metabolismo , Fígado/patologia , Fígado Gorduroso/microbiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Progressão da Doença , Obesidade/microbiologia , Obesidade/complicações , Obesidade/metabolismo , Chile , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , Idoso
6.
Molecules ; 29(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38930784

RESUMO

The journey of drug discovery (DD) has evolved from ancient practices to modern technology-driven approaches, with Artificial Intelligence (AI) emerging as a pivotal force in streamlining and accelerating the process. Despite the vital importance of DD, it faces challenges such as high costs and lengthy timelines. This review examines the historical progression and current market of DD alongside the development and integration of AI technologies. We analyse the challenges encountered in applying AI to DD, focusing on drug design and protein-protein interactions. The discussion is enriched by presenting models that put forward the application of AI in DD. Three case studies are highlighted to demonstrate the successful application of AI in DD, including the discovery of a novel class of antibiotics and a small-molecule inhibitor that has progressed to phase II clinical trials. These cases underscore the potential of AI to identify new drug candidates and optimise the development process. The convergence of DD and AI embodies a transformative shift in the field, offering a path to overcome traditional obstacles. By leveraging AI, the future of DD promises enhanced efficiency and novel breakthroughs, heralding a new era of medical innovation even though there is still a long way to go.


Assuntos
Inteligência Artificial , Descoberta de Drogas , Humanos , Descoberta de Drogas/métodos , Desenho de Fármacos , Desenvolvimento de Medicamentos
7.
Crit Rev Food Sci Nutr ; 63(25): 7269-7287, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35234546

RESUMO

Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident.


Assuntos
Estilbenos , Humanos , Estilbenos/farmacologia , Resveratrol/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Anti-Inflamatórios/farmacologia
8.
J Epidemiol ; 33(6): 276-284, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34776500

RESUMO

BACKGROUND: Limited data on electronic cigarette prevalence, patterns, and settings of use are available from several European countries. METHODS: Within the TackSHS project, a face-to-face survey was conducted in 2017-2018 in 12 European countries (Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania and Spain). Overall, 11,876 participants, representative of the population aged ⩾15 years in each country, provided information on electronic cigarette. RESULTS: 2.4% (95% confidence interval [CI], 2.2-2.7%) of the subjects (2.5% among men and 2.4% among women; 0.4% among never, 4.4% among current- and 6.5% among ex-smokers) reported current use of electronic cigarette, ranging from 0.6% in Spain to 7.2% in England. Of the 272 electronic cigarette users, 52.6% were dual users (ie, users of both electronic and conventional cigarettes) and 58.8% used liquids with nicotine. In all, 65.1% reported using electronic cigarette in at least one indoor setting where smoking is forbidden; in particular, at workplaces (34.9%) and bars and restaurants (41.5%). Multivariable logistic regression analysis showed that electronic cigarette use was lower among older individuals (P for trend <0.001) and higher among individuals with high level of education (P for trend = 0.040). Participants from countries with higher tobacco cigarette prices more frequently reported electronic cigarette use (odds ratio 3.62; 95% CI, 1.80-7.30). CONCLUSION: Considering the whole adult population of these 12 European countries, more than 8.3 million people use electronic cigarettes. The majority of users also smoked conventional cigarettes, used electronic cigarettes with nicotine, and consumed electronic cigarettes in smoke-free indoor areas.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Adulto , Masculino , Humanos , Feminino , Idoso , Nicotina , Vaping/epidemiologia , Japão , Europa (Continente)/epidemiologia
9.
Tob Control ; 32(1): 30-35, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34031225

RESUMO

BACKGROUND AND AIMS: Despite the European Union (EU) Tobacco Tax Directive (TTD), a lack of convergence in EU tobacco prices promotes high levels of cross-border shopping and down-trading from factory-made (FM) to roll-your-own tobacco (RYO) cigarettes. This study presents a blueprint for reform, whereby minimum taxes are related to the overall price level in the EU and where taxation of RYO is related to that of FM. METHODS: Longitudinal data on prices and taxes on FM and RYO in 25 member states over 2011-2019 are used to estimate econometric models for their weighted average prices as a function of taxes. Two scenarios are simulated with the models' estimates: a baseline scenario for the actual tax stance pertaining to 2020 and a reform scenario implementing the blueprint. RESULTS: The baseline results show that, while the prices of both products have experienced a slight increase since 2016 in real terms, the dispersion in the prices of FM across countries has increased and the difference in the prices of RYO within countries has widened. The results for the reform scenario show dispersion would diminish both EU-wide and in hotspots for cross-border sales of FM. The reform would also lead to a substantial reduction in the price gap between FM and RYO. CONCLUSION: To promote price convergence and close the price gap between FM and RYO, the revised TTD should ensure minimum FM taxes track a measure of their average EU price, and RYO taxes are related to FM taxes.


Assuntos
Nicotiana , Produtos do Tabaco , Humanos , União Europeia , Impostos , Comércio
10.
Tob Control ; 32(5): 667-671, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35149599

RESUMO

BACKGROUND: The rules governing tobacco taxation in the European Union (EU) are currently under revision. Earlier research has proposed reforms aimed at stimulating price convergence across countries by linking national minimum taxes to a measure of average prices across the EU. This paper proposes that revised tax rules include an affordability criterion whereby minimum taxes are required to be no less than a common prespecified fraction of domestic average disposable income. METHODS: Longitudinal data on prices and taxes on factory-made cigarettes and roll-your-own tobacco in 24 EU member states and the UK between 2011 and 2019 are used to estimate econometric models for their weighted average prices as a function of taxes. Two scenarios are simulated with the models' estimates: a baseline scenario for the actual tax stance pertaining to 2020 and a reform scenario implementing an additional affordability criterion. RESULTS: The affordability criterion would significantly increase the price of both tobacco products, particularly in richer countries with relatively low tobacco prices that are often not affected by the increases in nominal minima mandated by the EU rules. There would also be some price convergence between the two tobacco products, both on average and in the majority of countries. CONCLUSIONS: Such results show an affordability criterion could be a potentially fruitful complement to the tax reforms proposed in earlier research.


Assuntos
Nicotiana , Produtos do Tabaco , Humanos , União Europeia , Comércio , Impostos , Custos e Análise de Custo
11.
Biomed Chromatogr ; 37(12): e5741, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37688464

RESUMO

Matrix effect and sample pretreatment significantly affect the percentage recovery of peptides in biological matrices, affecting the method robustness and accuracy. To counteract this effect, an internal standard (IS) is used; however, in most cases this is not available, which limits the analytical method. It is important to identify short peptides that can be used as ISs in the quantification of peptides in biological matrices. In this study, doping peptides GHRP-4, GHRP-5, GHRP-6, Sermorelin (1-11), Sermorelin (13-20) and Sermorelin (22-29) were synthesized using solid-phase peptide synthesis. Treatment with human blood, trypsin and chymotrypsin was used to determine the stability of the peptides. Products were evaluated using the high-performance liquid chromatography-diode array detector (HPLC-DAD) method. The analytical methodology and sample pretreatment were effective for the analysis of these molecules. A unique profile related to protein binding and enzymatic stability of each peptide was established. GHRP-4, GHRP-6 and Sermorelin (22-29) can be considered as in-house ISs as they were stable to enzyme and blood treatment and can be used for the quantification of peptides in biological samples. Peptides GHRP-6 and Sermorelin (22-29) were used to analyse a dimeric peptide (26 [F] LfcinB (20-30)2 ) in four different matrices to test these peptides as in-house IS.


Assuntos
Testes de Química Clínica , Dopagem Esportivo , Hormônio Liberador de Hormônio do Crescimento , Substâncias de Crescimento , Peptídeos/análise , Humanos , Soro/química , Estabilidade Proteica , Análise Química do Sangue/normas , Testes de Química Clínica/normas , Hormônio Liberador de Hormônio do Crescimento/análise , Substâncias de Crescimento/análise
12.
BMC Emerg Med ; 23(1): 116, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794327

RESUMO

INTRODUCTION: Stroke is the most common time-dependent pathology that pre-hospital emergency medical services (EMS) are confronted with. Prioritisation of ambulance dispatch, initial actions and early pre-notification have a major impact on mortality and disability. The COVID-19 pandemic has led to disruptions in the operation of EMS due to the implementation of self-protection measures and increased demand for care. It is crucial to evaluate what has happened to draw the necessary conclusions and propose changes to improve the system's strength for the future. The study aims to compare prehospital time and neuroprotective care metrics for acute stroke patients during the first wave of COVID-19 and the same periods in the years before and after. METHODS: Analytical, observational, multicentre study conducted in the autonomous communities of Andalusia, Catalonia, Galicia, and Madrid in the pre-COVID-19 (2019), "first wave" of COVID-19 (2020) and post-COVID-19 (2021) periods. Consecutive non-randomized sampling. Descriptive statistical analysis and hypothesis testing to compare the three time periods, with two by two post-hoc comparisons, and multivariate analysis. RESULTS: A total of 1,709 patients were analysed. During 2020 there was a significant increase in attendance time of 1.8 min compared to 2019, which was not recovered in 2021. The time of symptom onset was recorded in 82.8% of cases, and 83.3% of patients were referred to specialized stroke centres. Neuroprotective measures (airway, blood glucose, temperature, and blood pressure) were performed in 43.6% of patients. CONCLUSION: During the first wave of COVID-19, the on-scene times of pre-hospital emergency teams increased while keeping the same levels of neuroprotection measures as in the previous and subsequent years. It shows the resilience of EMS under challenging circumstances such as those experienced during the pandemic.


Assuntos
COVID-19 , Serviços Médicos de Emergência , Acidente Vascular Cerebral , Humanos , Pandemias , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/diagnóstico , Ambulâncias , Estudos Retrospectivos
13.
J Clin Psychol ; 79(1): 28-42, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35849418

RESUMO

BACKGROUND: The Florida Obsessive Compulsive Inventory (FOCI) and its pediatric version, the Children's Florida Obsessive Compulsive Inventory (C-FOCI), are instruments for evaluating obsessive-compulsive symptomatology. METHOD: A reliability generalization meta-analysis was conducted to estimate an average reliability of the scores and to identify study characteristics that explained the heterogeneity among scores. Using Kuder-Richardson 20 (KR-20) and Cronbach's α, a total of 23 and 20 independent samples were included in the meta-analysis for the FOCI and C-FOCI. RESULTS: We found an average KR-20 of 0.826 for the FOCI's Symptom Checklist and an α of 0.882 FOCI's Symptom Severity. An average KR-20 of 0.740 was found for the C-FOCI's Symptom Checklist, while an average α of 0.794 was found for the C-FOCI's Symptom Severity. Moderator analyses showed that the source of the coefficients (i.e., whether they were reported by the authors of the primary study or estimated by the meta-analysts) was an important variable for the FOCI Symptom Severity, and that the focus of the study (i.e., whether it was psychometric or applied) and the sample size were relevant for the C-FOCI Symptom Checklist. CONCLUSIONS: Considering that the FOCI and C-FOCI are scales characterized by their brevity and ease of use, and the reliabilities obtained here, both scales are well suited for screening purposes.


Assuntos
Transtorno Obsessivo-Compulsivo , Criança , Humanos , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Transtorno Obsessivo-Compulsivo/diagnóstico , Psicometria , Índice de Gravidade de Doença
14.
Int J Mol Sci ; 23(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36430510

RESUMO

Protein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establish whether PKCα acts as an oncogene or a tumor suppressor. Here, we analyzed the importance of PKCα in cellular processes such as proliferation, migration, or apoptosis by inhibiting its gene expression in a luminal A breast cancer cell line (MCF-7). Differential expression analysis and phospho-kinase arrays of PKCα-KD vs. PKCα-WT MCF-7 cells identified an essential set of proteins and oncogenic kinases of the JAK/STAT and PI3K/AKT pathways that were down-regulated, whereas IGF1R, ERK1/2, and p53 were up-regulated. In addition, unexpected genes related to the interferon pathway appeared down-regulated, while PLC, ERBB4, or PDGFA displayed up-regulated. The integration of this information clearly showed us the usefulness of inhibiting a multifunctional kinase-like PKCα in the first step to control the tumor phenotype. Then allowing us to design a possible selection of specific inhibitors for the unexpected up-regulated pathways to further provide a second step of treatment to inhibit the proliferation and migration of MCF-7 cells. The results of this study suggest that PKCα plays an oncogenic role in this type of breast cancer model. In addition, it reveals the signaling mode of PKCα at both gene expression and kinase activation. In this way, a wide range of proteins can implement a new strategy to fine-tune the control of crucial functions in these cells and pave the way for designing targeted cancer therapies.


Assuntos
Neoplasias , Proteína Quinase C-alfa , Humanos , Proteína Quinase C-alfa/genética , Proteína Quinase C-alfa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Proteína Quinase C/metabolismo , Proliferação de Células
15.
J Sci Food Agric ; 102(10): 4296-4303, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35043401

RESUMO

BACKGROUND: Gnetol is a stilbene whose characterization and bioactivity have been poorly studied. It shares some bioactivities with its analogue resveratrol, such as anti-inflammatory, anti-thrombotic, cardioprotective and anti-cancer activities. However, the low solubility of stilbenes may limit their potential applications in functional foods. Encapsulation in cyclodextrins could be a solution. RESULTS: The antioxidant activity of gnetol was evaluated by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation and ferric reducing antioxidant power methods (Trolox equivalents 13.48 µmol L-1 and 37.08 µmol L-1 respectively at the highest concentration) and it was higher than that of resveratrol, and depending on the method, similar or higher to that of oxyresveratrol. Spectrophotometric and spectrofluorimetric characterization of gnetol is published for the first time. Moreover, its water solubility was determined and improved almost threefold after its molecular encapsulation in cyclodextrins, as well as its stability after storage for a week. A physicochemical and computational study revealed that cyclodextrins complex gnetol in a 1:1 stoichiometry, with better affinity for like 2-hydroxypropyl-ß-cyclodextrin (KF  = 4542.90 ± 227.15 mol-1  L). Temperature and pH affected the encapsulation constants. CONCLUSION: These results could increase interest of gnetol as an alternative to the most studied stilbene, resveratrol, as well as aid in the development of more stable inclusion complexes that improve its aqueous solubility and stability so that it can be incorporated into functional foods. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Ciclodextrinas , Estilbenos , Antioxidantes/química , Antioxidantes/farmacologia , Ciclodextrinas/química , Resveratrol , Solubilidade , Estilbenos/química
16.
J Sci Food Agric ; 102(4): 1609-1618, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34405402

RESUMO

BACKGROUND: 2-Phenylethanol (PEA) is a higher aromatic alcohol with a rose-like odor, which is used in several industries. Although PEA can be synthesized, consumers are increasingly concerned about the toxicity of chemically synthesized products, and prefer natural aroma compound. PEA occurs naturally in the environment but concentrations are too low to justify extraction. RESULTS: The present study offers a novel biological source of PEA: the filamentous fungi Monochaetinula geoffroeana. We report the highest recorded yield of PEA of fungal origin to date: 6.52 g L-1 . The volatility and low water solubility of PEA can affect its use in many industries, for which reason complexation studies of PEA and cyclodextrins were carried out using the phase solubility technique. PEA formed 1:1 stoichiometric inclusion complexes with natural and modified CDs, the highest encapsulation constant being obtained with MßCD (K1:1  = 299.88 L mol-1 ). The complexation process significantly increased the water solubility of PEA. A computational study showed a high degree of correlation between computed scores and experimental values. Furthermore, this study reports the role of salicylic acid as an effective elicitor for improved PEA production by the studied fungi. Supplementation with 10 µmol L-1 salicylic acid increased PEA production from 6.52 to 10.54 g L-1 . CONCLUSION: The best treatment to enhance PEA production by M. geoffroeana under laboratory conditions was to use salicylic acid 10 µmol L-1 . Due to the commercial importance of PEA, further investigation is needed to improve PEA production by M. geoffroeana and to optimize culture conditions in order to standardize yields. © 2021 Society of Chemical Industry.


Assuntos
Ciclodextrinas , Álcool Feniletílico , Fungos , Ácido Salicílico , Solubilidade
17.
Rev Med Chil ; 150(4): 439-449, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36155753

RESUMO

BACKGROUND: The clinical teachers' attributes can be grouped into physician competencies, teacher competencies, and personal characteristics. Global performance is considered the clinical teacher's capacity to facilitate an active and stimulating learning process for medical students and a warm, supportive, and pleasant environment. AIM: To determine which attributes of the clinical teacher influence their global performance from the students' point of view. MATERIAL AND METHODS: The Role Model Apperception Tool questionnaire (RoMAT) was answered by 133 second-year medical students at the University of Chile during 2018. RESULTS: The students assessed 37 clinical teachers. Teaching competencies had the higher influence in global performance. Personal characteristics also had a significant influence. Physician competencies had an indirect influence on teaching competencies. The model obtained 88% of the explained variance of the teacher's global performance. CONCLUSIONS: This study showed that teacher competencies, personal characteristics, and physician competencies are qualities that influence the perception of the global performance of clinical teachers.


Assuntos
Estudantes de Medicina , Humanos , Inquéritos e Questionários
18.
Behav Res Methods ; 54(1): 334-349, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34173943

RESUMO

Meta-analysis is a powerful and important tool to synthesize the literature about a research topic. Like other kinds of research, meta-analyses must be reproducible to be compliant with the principles of the scientific method. Furthermore, reproducible meta-analyses can be easily updated with new data and reanalysed applying new and more refined analysis techniques. We attempted to empirically assess the prevalence of transparency and reproducibility-related reporting practices in published meta-analyses from clinical psychology by examining a random sample of 100 meta-analyses. Our purpose was to identify the key points that could be improved, with the aim of providing some recommendations for carrying out reproducible meta-analyses. We conducted a meta-review of meta-analyses of psychological interventions published between 2000 and 2020. We searched PubMed, PsycInfo and Web of Science databases. A structured coding form to assess transparency indicators was created based on previous studies and existing meta-analysis guidelines. We found major issues concerning: completely reproducible search procedures report, specification of the exact method to compute effect sizes, choice of weighting factors and estimators, lack of availability of the raw statistics used to compute the effect size and of interoperability of available data, and practically total absence of analysis script code sharing. Based on our findings, we conclude with recommendations intended to improve the transparency, openness, and reproducibility-related reporting practices of meta-analyses in clinical psychology and related areas.


Assuntos
Intervenção Psicossocial , Projetos de Pesquisa , Humanos , Metanálise como Assunto , Prevalência , Reprodutibilidade dos Testes
19.
BMC Plant Biol ; 21(1): 488, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696731

RESUMO

BACKGROUND: Salt stress is one of the main constraints determining crop productivity, and therefore one of the main limitations for food production. The aim of this study was to characterize the salt stress response at the physiological and molecular level of different Broccoli (Brassica oleracea L. var. Italica Plenck) cultivars that were previously characterized in field and greenhouse trials as salt sensitive or salt tolerant. This study aimed to identify functional and molecular traits capable of predicting the ability of uncharacterized lines to cope with salt stress. For this purpose, this study measured different physiological parameters, hormones and metabolites under control and salt stress conditions. RESULTS: This study found significant differences among cultivars for stomatal conductance, transpiration, methionine, proline, threonine, abscisic acid, jasmonic acid and indolacetic acid. Salt tolerant cultivars were shown to accumulate less sodium and potassium in leaves and have a lower sodium to potassium ratio under salt stress. Analysis of primary metabolites indicated that salt tolerant cultivars have higher concentrations of several intermediates of the Krebs cycle and the substrates of some anaplerotic reactions. CONCLUSIONS: This study has found that the energetic status of the plant, the sodium extrusion and the proline content are the limiting factors for broccoli tolerance to salt stress. Our results establish physiological and molecular traits useful as distinctive markers to predict salt tolerance in Broccoli or to design novel biotechnological or breeding strategies for improving broccoli tolerance to salt stress.


Assuntos
Brassica/genética , Brassica/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Salino/genética , Estresse Salino/fisiologia , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Genes de Plantas , Variação Genética , Genótipo , Prolina/metabolismo , Cloreto de Sódio/metabolismo
20.
Pediatr Res ; 90(1): 216-222, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33149260

RESUMO

BACKGROUND: Secondhand smoke (SHS) exposure at home and fetal SHS exposure during pregnancy are a major cause of disease among children. The aim of this study is quantifying the burden of disease due to SHS exposure in children and in pregnancy in 2006-2017 for the 28 European Union (EU) countries. METHODS: Exposure to SHS was estimated using a multiple imputation procedure based on the Eurobarometer surveys, and SHS exposure burden was estimated with the comparative risk assessment method using meta-analytical relative risks. Data on deaths and disability-adjusted life years (DALYs) were collected from National statistics and from the Global Burden of Disease Study. RESULTS: Exposure to SHS and its attributable burden stalled in 2006-2017; in pregnant women, SHS exposure was 19.8% in 2006, 19.1% in 2010, and 21.0% in 2017; in children it was 10.1% in 2006, 9.6% in 2010, and 12.1% in 2017. In 2017, 35,633 DALYs among children were attributable to SHS exposure in the EU, mainly due to low birth weight. CONCLUSIONS: Comprehensive smoking bans up to 2010 contributed to reduce SHS exposure and its burden in children immediately after their implementation; however, SHS exposure still occurs, and in 2017, its burden in children was still relevant. IMPACT: Exposure to secondhand smoke at home and in pregnancy is a major cause of disease among children. Smoking legislation produced the adoption of voluntary smoking bans in homes; however, secondhand smoke exposure at home still occurs and its burden is substantial. In 2017, the number of deaths and disability-adjusted life years in children attributable to exposure to secondhand smoke in the European Union countries were, respectively, 335 and 35,633. Low birth weight caused by secondhand smoke exposure in pregnancy showed the largest burden. Eastern European Union countries showed the highest burden.


Assuntos
Exposição Ambiental , Poluição por Fumaça de Tabaco , Criança , Anos de Vida Ajustados por Deficiência , Europa (Continente) , Feminino , Humanos , Recém-Nascido de Baixo Peso , Masculino , Gravidez
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