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Alzheimer's disease (AD) involves a neurodegenerative process that has not yet been prevented, reversed, or stopped. Continuing with the search for natural pharmacological treatments, flavonoids are a family of compounds with proven neuroprotective effects and multi-targeting behavior. The American genus Dalea L. (Fabaceae) is an important source of bioactive flavonoids. In this opportunity, we tested the neuroprotective potential of three prenylated flavanones isolated from Dalea species in a new in vitro pre-clinical AD model previously developed by us. Our approach consisted in exposing neural cells to conditioned media (3xTg-AD ACM) from neurotoxic astrocytes derived from hippocampi and cortices of old 3xTg-AD mice, mimicking a local neurodegenerative microenvironment. Flavanone 1 and 3 showed a neuroprotective effect against 3xTg-AD ACM, being 1 more active than 3. The structural requirements to afford neuroprotective activity in this model are a 5'-dimethylallyl and 4'-hydroxy at the B ring. In order to search the mechanistic performance of the most active flavanone, we focus on the flavonoid-mediated regulation of GSK-3ß-mediated tau phosphorylation previously reported. Flavanone 1 treatment decreased the rise of hyperphosphorylated tau protein neuronal levels induced after 3xTg-AD ACM exposure and inhibited the activity of GSK-3ß. Finally, direct exposure of these neurotoxic 3xTg-AD astrocytes to flavanone 1 resulted in toxicity to these cells and reduced the neurotoxicity of 3xTg-AD ACM as well. Our results allow us to present compound 1 as a natural prenylated flavanone that could be used as a precursor to development and design of future drug therapies for AD.

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INTRODUCTION: Chile is committed to actively involving patients in their healthcare. However, little is known about how this is translated into clinical encounters. Breast cancer (BC) is the first cause of cancer-related death in Chilean women. National policy guarantees standard care, and treatment decisions should be made along this process that can have long-term consequences for women. So, BC is a particularly well-suited case study to understand the complexity of patient participation in decision-making. OBJECTIVE: To identify the factors that affect the active involvement of patients in the BC treatment decision-making process, considering the perspectives and practices of health professionals and women facing the disease. METHOD AND ANALYSIS: We will conduct a mixed-method study through a convergent parallel design in three stages: (1) A qualitative study: non-participant observation of the tumour board (TB) meetings; semi-structured interviews with key informants from TBs; documentary analyses; semi-structured interviews with women facing BC; and non-participant observations of clinical encounters; (2) a cross-sectional study with 445 women facing BC stages I-III from three hospitals in Santiago, Chile. We will measure the level of expected participation, experienced participation, decisional conflict, quality of life (QoL) and satisfaction with healthcare. Descriptive analysis will be performed, and multivariable binary logistic regression models will be adjusted to identify factors associated with high levels of QoL or satisfaction; (3) an integration study will bring together the data through a joint display technique. ETHICS AND DISSEMINATION: The study has been conceived and will be conducted according to international and local agreements for ethical research. Ethical approval has been granted by two Ethics Committees in Chile.The results will be disseminated to scientific and lay audiences (publications in scientific journals and conferences, seminars and a website for plain language dissemination).

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OBJECTIVE: To identify a framework for risk communication during health crises by using the current pandemic as a case study. DESIGN: A qualitative study based on individual interviews. SETTING: Different countries with diverse levels of perceived success on risk communication during the COVID-19 health crisis. PARTICIPANTS: International experts with experience in health crisis management or risk communication. ANALYSIS: A thematic analysis was performed supported by Atlas.ti. RESULTS: Four men and six women took part in the study (three from Europe, two from Latin America, two from North America, one from Asia and two from Oceania). Three major themes emerged from the data: (1) institutionalising the communication strategy; (2) defining the problem that needs to be faced; (3) developing an effective communication strategy. CONCLUSION: Risk communication during a health crisis requires preparation of governments and of health teams in order to produce and deliver effective messages as well as to help communities to make informed and healthy decisions. This is particularly relevant for slow disasters, such as COVID-19, as the strategy must innovate to avoid information fatigue of the audience. The findings of this article could inform guidelines to best equip countries for a clear communication strategy for future crises. PROSPERO REGISTRATION NUMBER: CRD42021234443.

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Latinoamérica fue durante noviembre de 2020 una de las regiones más afectada por la pandemia de COVID-19 en cuanto a prevalencia y muertes atribuidas al virus. Por ello, el inicio de testeo de vacunas en ciudadanos de la región fue recibido con altas expectativas sobre su efectividad. Frente a lo cual es esencial tener en cuenta ciertos principios fundamentales que deben guiar este proceso asegurando su correcta implementación. El objetivo de este artículo es ofrecer consideraciones sobre el proceso de implementación de ensayos clínicos y acceso posensayo a vacunas para COVID-19 en Latinoamérica. En particular los relacionados con el respeto a la dignidad de los participantes, las tensiones históricas globales y regionales en materia de economía política de ensayos clínicos, algunos aspectos de la gobernanza global y el rol de la Organización Mundial de la Salud en la pandemia, y la necesidad de asegurar el acceso posensayo a la vacuna. Se concluye que la pandemia es una oportunidad para estrechar lazos de cooperación y solidaridad entre países latinoamericanos. Los ensayos clínicos son una instancia clave para reforzar la gobernanza local y regional con miras a fortalecer la transparencia y la vigilancia de la correcta realización de alianzas público-privadas en el desarrollo de terapias, en los que la Organización Mundial de la Salud y la Organización Panamericana de la Salud, tienen un rol importante para la implementación de estrategias de integración y acceso a vacunas(AU)

Latin America was during November 2020 one of the most affected regions by the COVID-19 pandemic in terms of prevalence and deaths attributed to the virus. Therefore, the start of vaccine testing in citizens of the region was received with high expectations about its effectiveness. Therefore, it is essential to take into account certain fundamental principles that should guide this process ensuring its correct implementation. The objective of this article is to provide considerations on the process of implementing clinical trials and post-trial access to COVID-19 vaccines in Latin America, in particular those related to respect for the dignity of participants, the historical global and regional tensions regarding the political economy of clinical trials, some aspects of global governance and the role of the World Health Organization in the pandemic, and the need to ensure post-trial access to the vaccine. It is concluded that the pandemic is an opportunity to strengthen bonds of cooperation and solidarity between Latin American countries. Clinical trials are a key instance to strengthen local and regional governance with a view to consolidate transparency and monitoring of the correct implementation of public-private partnerships in the development of therapies, in which the World Health Organization and the Pan American Health Organization have an important role for the implementation of integration strategies and access to vaccines(AU)

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INTRODUCTION: Palliative care (PC) for advanced cancer is guaranteed by law in Chile, but the formal training for it is insufficient. Training models have emerged internationally that enable professionals to be better prepared for the provision of psychotherapy in PC. The objective of this study is to explore health professionals' perceptions of the 'Managing Cancer and Living Meaningfully' (CALM) psychotherapy and the perceived barriers and facilitators to its implementation, based on a theoretical training. METHODS: A qualitative study was carried out with health professionals working in oncology and/or PC and participating in a CALM training. A focus group was conducted after to explore the experience of CALM training and the perceived barriers and facilitators to its implementation. A thematic analysis of the content and an analysis of the facilitators and barriers to the implementation of mental health services were carried out. RESULTS: Twenty four professionals participated in the training, six of whom were part of the subsequent focus group. There was a consensus that the training was a positive professional experience and that it is a culturally sensitive and feasible intervention for application in Chile. The barriers identified include institutional bureaucracy as resistance to change, the excess workload of the clinical teams and the absence of spaces for more in-depth training. CONCLUSIONS: CALM is a useful and relevant framework for the training of health professionals working in oncology and PC. In Chile, there is a need for training spaces on this topic. Future research and organisational studies should evaluate professionals' beliefs about, and resistance to, adopting evidence-based psychotherapeutic interventions.

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BACKGROUND: Breast cancer (BC) has a high mortality rate in developing countries due to a scarcity of early detection. Risk communication is critical to support women who face the decision to undertake BC screening. Thus, they can balance their perceived and real risk, and make informed choices. AIM: To describe experts' views on how the provision of information related to BC screening should be made. MATERIAL AND METHODS: A qualitative study with focus groups with national experts was conducted. Open coding was performed. RESULTS: Four categories on the way information about BC screening should be provided emerged: to communicate about the need of the exam; the pros and cons of the test; fear as a barrier for understanding; and involving women in the decision-making process. CONCLUSIONS: These findings emphasize the need to include risk communication strategies in the patient-provider relationship and encourage and respect women's autonomy when facing the BC screening decision.

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OBJECTIVE: To adapt and validate for the Chilean context the instrument Informed Choice (IC) to measure informed decision for mammography. LOCATION: Primary Health Care Center in southeast Santiago, Chile. DESIGN: Individual, transversal, analytical and psychometric adaptation and validation study. METHODS: We 1) translated and back-translated IC; 2) conducted a focus group for cultural/linguistic relevance; 3) reviewed content validity; 4) piloted the instrument; 5) applied IC for validation. Analysis was performed by using Cronbach alpha, correlation, Bartlett's test of sphericity, Kaiser-Meyer-Olkin measure and factor analysis. RESULTS: Three versions of the IC were developed, which included changes according to the views of users and experts. Validation was conducted in a sample of 70 women. Mean age was 54,4 years, 47,1% had completed secondary school and 92,9% have had at least one mammography. After factor analysis item 1 was removed and the final Cronbach Alpha was 0,79. CONCLUSIONS: The Chilean IC is reliable to measure decision women for mammography, this evaluate knowledge, attitude and intention towards the screening. The validation of an instrument to the cultural context is necessary and may have any variations to the original version according to local needs.

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Background: Breast cancer (BC) has a high mortality rate in developing countries due to a scarcity of early detection. Risk communication is critical to support women who face the decision to undertake BC screening. Thus, they can balance their perceived and real risk, and make informed choices. Aim: To describe experts' views on how the provision of information related to BC screening should be made. Material and Methods: A qualitative study with focus groups with national experts was conducted. Open coding was performed. Results: Four categories on the way information about BC screening should be provided emerged: to communicate about the need of the exam; the pros and cons of the test; fear as a barrier for understanding; and involving women in the decision-making process. Conclusions: These findings emphasize the need to include risk communication strategies in the patient-provider relationship and encourage and respect women's autonomy when facing the BC screening decision.

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INTRODUCTION: Developing instruments to screen for relevant aspects of advanced illness is key to identifying palliative needs and evaluating the effectiveness of interventions in this population. The objective of this project is to validate the Death and Dying Distress Scale in Spanish (DADDS-Sp) for screening anxiety about death and evaluating psychometric properties for people with advanced cancer. METHODS: DADDS is a 15-item self-administered questionnaire that assesses thoughts and feelings related to death and the process of dying. A cross-sectional, descriptive, psychometric validation study was conducted in two cancer centres in Santiago de Chile. Included were patients over 18 years of age with incurable and/or metastatic cancer, fluent in Spanish, and a life expectancy of more than 3 months. Reliability was analysed using Cronbach's alpha, and confirmatory factor analysis was performed following the model of the original scale. RESULTS: Seventy four patients participated in the study. The median age was 63 years. Of the sample, 59% identified themselves as women. On average, participants reported low anxiety about death (mean = 21, SD = 18). Women have more death anxiety. The reliability analysis yielded a value of α = 0.93 (IC = 0.91-0.95). Factor analysis with a one-factor structure yielded Comparative Fit Index (CFI) = 0. 0.972, Root Mean Square Error of Approximation (RMSEA) = 0.092, Standardized Root Mean Square Residual (SRMR) = 0.085 and Tucker-Lewis Index (TLI) = 0.968. The model with a two-factor structure yielded CFI = 0.989, RMSEA = 0.059, SRMR = 0.075 and TLI = 0.987, suggesting that the two-factor model has a better fit for the data studied. CONCLUSIONS: DADDS-Sp is psychometrically valid for use in a Spanish-speaking population, yielding high reliability and internal consistency. A majority of the Chilean patients reported a low level of anxiety about death although about 10% presented with severe anxiety, so their identification for adequate clinical management is fundamental.

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Alzheimer's disease (AD) is the most common form of dementia worldwide with an increasing prevalence for the next years. The multifactorial nature of AD precludes the design of new drugs directed to a single target being probably one of the reasons for recent failures. Therefore, dual binding site acetylcholinesterase (AChE) inhibitors have been revealed as cognitive enhancers and ß-amyloid modulators offering an alternative in AD therapy field. Based on the dual ligands NP61 and donepezil, the present study reports the synthesis of a series of indolylpiperidines hybrids to optimize the NP61 structure preserving the indole nucleus, but replacing the tacrine moiety of NP61 by benzyl piperidine core found in donepezil. Surprisingly, this new family of indolylpiperidines derivatives showed very potent and selective hBuChE inhibition. Further studies of NMR and molecular dynamics have showed the capacity of these hybrid molecules to change their bioactive conformation depending on the binding site, being capable to inhibit with different shapes BuChE and residually AChE.

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Resumen En el marco de los estudios sobre lugares de memoria vinculados a las violaciones a los derechos humanos cometidas por la dictadura cívico-militar en Chile (1973-1990), este artículo presenta el análisis de visitas a dos lugares de memoria de Santiago de Chile - Villa Grimaldi y Londres 38 - realizadas por personas de distintos grupos etarios. El análisis aborda la interacción de los visitantes con el lugar, considerando los afectos y percepciones que provoca la visita, y la interpelación que estos lugares hacen a las memorias que los visitantes construyen sobre el pasado reciente. Los resultados muestran que, si bien existe acuerdo en la condena a las violaciones a los derechos humanos y la importancia de una cultura de la memoria y los derechos humanos, se produce una distancia entre las generaciones al valorar conflictos del pasado que refieren a distintos momentos históricos.

Resumo No marco dos estudos sobre os lugares de memória vinculados às violações dos direitos humanos cometidos pela ditadura cívico-militar no Chile (1973-1990), este artigo apresenta a análise de visitas a dois lugares de memória de Santiago do Chile - Villa Grimaldi y Londres 38 - realizadas por pessoas de diferentes faixas etárias. O estudo aborda a interação dos visitantes com o lugar, considerando os sentimentos e as percepções que a visita provoca e a interpelação que estes lugares fazem às memórias que os visitantes constroem sobre o passado recente. Os resultados mostram que, embora haja acordo na condenação das violações dos direitos humanos e na importância de uma cultura de memória e dos direitos humanos, um distanciamento entre as gerações aparece ao avaliar conflitos do passado que se referem a diferentes momentos históricos.

Abstract In the framework of the studies on places of memory related to human rights violations committed by the Chilean military-civic dictatorship (1973-1990), this article presents the analysis of visits to two places of memory of Santiago de Chile - Villa Grimaldi and London 38 - made by people of different age groups. The analysis addresses the interaction of the visitors with the place, considering the affections and perceptions that the visit caused, and the interpellation that these places cause to the memories that the visitors build on the recent past. The results show that, although there is an agreement on the condemnation of human rights violations and the importance of a culture of memory and human rights, there is a distance among the generations when assessing past conflicts that refer to different historic moments.

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Cervical cancer is the fourth most common neoplasm in women worldwide and its incidence is associated with profound social inequities. In Chile, it is the second cause of death in women of reproductive age. The Chilean clinical guideline identifies the vaccine against Human Papillomavirus (HPV) as the main preventive measure. Since 2014, the Ministry of Health has implemented free immunization against HPV for girls and female adolescents. This article critically analyzes this public policy from the viewpoint of health equity, using as framework the Social Determinants of Health Model. Specifically, we address the structural determinants of income and gender, which act as material and social barriers for achieving immunization, affecting protection against cervical cancer. These barriers correspond to the high cost of the vaccine, and social attitudes/cultural beliefs towards sexual behavior in Latin America and Chile that affect the acceptability of vaccination. The Social Determinants of Health Model constitutes a useful tool for identifying health inequities and understanding public policy from an equity viewpoint that complements the biomedical and epidemiological understanding of disease. In this topic, the initiative aims to strengthen the idea of health as a human right and health promotion as an essential function of public health policy.

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Resumen: Existe gran desinformación sobre epilepsias; mitos, prejuicios y estigma institucionalizado en el sistema escolar. Además, dificultades de participación social en las personas con epilepsia. Todo esto produce un impacto negativo en la calidad de vida de las personas con epilepsia. El objetivo de este trabajo es probar un método para educar en Epilepsias a escolares, mediante técnicas audiovisuales adecuadas a su lenguaje, intereses, nivel de atención y comprensión. Capacitación directa de 1.000 niños. Se realiza, por expertos en epilepsia y profesionales con experiencia en material audiovisual, un guión de 4 capítulos, sobre una historia de crisis de epilepsia en un niño, representado por marionetas. Se presenta el video a establecimientos educacionales públicos y privados. Se aplica Pre y Post test de 10 preguntas, para medir nivel de conocimientos y aprendizajes básicos en epilepsias. Un año post presentación de video, se mide en una muestra de estudiantes, la persistencia de conocimientos enseñados. Hubo un total de 1.111 escolares. Las respuestas pre-test correctas, incorrectas y que no sabían fueron en un 44%, 37% y 19% respectivamente. Las respuestas post-test correctas, incorrectas y que no sabían fueron en un 94%, 5% y 1% respectivamente. El análisis estadístico con las pruebas de McNemar mostraron diferencias altamente significativas entre el pre y post test en cada una de las 10 preguntas (p<0.0001). El estudio de persistencia, un año después (2011) fueron las siguientes: Correctas: 74%. Incorrectas: 8%. No sabe: 18%.Hubo cambios significativos de adquisición de conocimientos entre el pre y post test, con niveles de persistencia de conocimientos aceptables, un año después. El mensaje que la epilepsia puede afectar a cualquier persona, se visualiza como potente para sensibilizar y mejorar las actitudes sociales.

There is a lack of information on Epilepsies, myths, prejudices and stigma institutionalized in the school system. In addition, people with epilepsy face a difficult time when trying to engage socially. All these produce a negative impact on the quality of life of people with epilepsy. The objective of this study is to test a method to educate schoolchildren in elementary and high school by audiovisual techniques appropriate to their language, interests, level of care and understanding in Epilepsies. Direct training of 1,000 children was performed by epilepsy experts and professionals with experience in audiovisual material through 4 chapters on a history of epileptic seizure in a child represented by puppets. The video was screened at public and private schools. A 10-item questionnaire was applied before and after the video, to measure level of knowledge and basic learning about Epilepsies. The knowledge about epilepsy was retested one year later in a sample of students. A total of 1,111 schoolage children participated. The results before the video screening were: correct 44%, incorrect 37%, and "I don't know" 19%. After the screening, there was a marked improvement, where correct answers were 94%, incorrect 5% and "I don't know" 1%. Statistical analysis with McNemar tests showed highly significant differences between the questionnaires before and after the video screening in each of the 10 questions (p < 0.0001). The test was repeated a year later (2011), with the following results: correct: 74%. Incorrect: 8%. I don't know: 18%. There was significant acquisition of knowledge after the video screening, with persistence of knowledge at acceptable levels a year later. The message that epilepsy can affect anyone is seen as potent to raise awareness and improve social attitudes.

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Cervical cancer is the fourth most common neoplasm in women worldwide and its incidence is associated with profound social inequities. In Chile, it is the second cause of death in women of reproductive age. The Chilean clinical guideline identifies the vaccine against Human Papillomavirus (HPV) as the main preventive measure. Since 2014, the Ministry of Health has implemented free immunization against HPV for girls and female adolescents. This article critically analyzes this public policy from the viewpoint of health equity, using as framework the Social Determinants of Health Model. Specifically, we address the structural determinants of income and gender, which act as material and social barriers for achieving immunization, affecting protection against cervical cancer. These barriers correspond to the high cost of the vaccine, and social attitudes/cultural beliefs towards sexual behavior in Latin America and Chile that affect the acceptability of vaccination. The Social Determinants of Health Model constitutes a useful tool for identifying health inequities and understanding public policy from an equity viewpoint that complements the biomedical and epidemiological understanding of disease. In this topic, the initiative aims to strengthen the idea of health as a human right and health promotion as an essential function of public health policy.

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Background: Quality of Life (QOL) assessment may evaluate the impact of diseases and their treatment on the overall well-being of patients. Aim: To assess QOL in Chilean breast cancer survivors. Patients and Methods: Ninety one female breast cancer patients aged 60 ± 10 years, who finished their oncologic treatment at least a year prior to the assessment, who were disease free and in medical follow-up were included in the study. They completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire and the breast cancer module QLQ-BR23. Results: Forty eight percent of respondents were long term survivors (more than five years). Global QOL scores were high (73.6 ± 18.2), emotional scale had the lowest scores in QLQ-C30 functional scales (72.1). Symptoms with the highest scores were: Insomnia (= 21.2), pain (= 20.8), and fatigue (= 19.1). Body image, sexual function, and concern about the future were the most relevant problems. Body image was superior in patients with breast-conserving surgery (p = 0.008), and cognitive function was better in patients in early disease stage (p = 0.03) and in those with more than five years of survival (p = 0.04). Conclusions: Even when global QOL scores were high, some symptoms were prevalent. Awareness about these problems and symptoms should improve their diagnosis and treatment.

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BACKGROUND: Quality of Life (QOL) assessment may evaluate the impact of diseases and their treatment on the overall well-being of patients. AIM: To assess QOL in Chilean breast cancer survivors. PATIENTS AND METHODS: Ninety one female breast cancer patients aged 60 ± 10 years, who finished their oncologic treatment at least a year prior to the assessment, who were disease free and in medical follow-up were included in the study. They completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire and the breast cancer module QLQ-BR23. RESULTS: Forty eight percent of respondents were long term survivors (more than five years). Global QOL scores were high (73.6 ± 18.2), emotional scale had the lowest scores in QLQ-C30 functional scales (72.1). Symptoms with the highest scores were: Insomnia (= 21.2), pain (= 20.8), and fatigue (= 19.1). Body image, sexual function, and concern about the future were the most relevant problems. Body image was superior in patients with breast-conserving surgery (p = 0.008), and cognitive function was better in patients in early disease stage (p = 0.03) and in those with more than five years of survival (p = 0.04). CONCLUSIONS: Even when global QOL scores were high, some symptoms were prevalent. Awareness about these problems and symptoms should improve their diagnosis and treatment.

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This article discusses the origin and implications of the "war on cancer" metaphor. Commonly present in mass media, the "war on cancer" notion circulates also among patients, their loved ones, their support networks, and oncological multidisciplinary teams. In our view when cancer is uprooted of its illness status, and conceptualized as an "enemy", myths about disease and those who suffer it (especially the idea of psychogenesis) are strengthened. Two topics in which the war metaphor is particularly problematic in the clinical context, are analyzed in depth. The first one is the relationship between the oncologic patient and his or her loved ones and support networks. When patients are insistently prompted to fight the disease and think positive, the expression of emotions associated to the adaptive process of receiving a diagnosis of cancer may be inhibited. Secondly, the war metaphor promotes an authoritarian view among the health teams and on the physician-patient relationship, undermining the patent's autonomy in the decision-making process, which may affect his global quality of life. Also, it encourages emotional isolation, concealment of psychiatric symptoms and conspiracies of silence. It is concluded that public policies to avoid the "war on" notion are required. Instead, education of the general population about wrong beliefs about cancer should be encouraged.

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Chilean women have the highest smoking rates in Latin America. Prevalence in this population is about 40%. There are no national programs for smoking cessation at the primary care level. This study explores the feasibility and effectiveness of a brief counseling intervention targeted to women smokers of childbearing age who seek primary care in Santiago, Chile. A quasi-experimental design was used to compare the effect of an intervention based on the '5A' model developed by the National Cancer Institute in the United States and the standard care provided in two control clinics. Women smokers seeking care at the three primary care clinics were contacted during a 2 months period and offer to participate in the study. Sampling was stratified according to the age groups to ensure comparability between cohorts. Quotas were calculated for each age group. Participants were asked about their willingness to quit, self-efficacy, smoking behavior, addiction level as well as support received for smoking cessation. After 18 months of intervention all women were re-evaluated. A total of 773 women were recruited for the study; 76% of them completed the trial. Women smokers are characterized by a large percentage of light smokers with a low self-efficacy for quitting and with very low information on where and how to get assistance to quit. At study end, 15.2% of women reported quitting smoking at least for 1 month in the intervention clinic versus 7.8% in one of the control clinics (p < 0.05) and 14.6% in the second control clinic (p = NS). Over 70% of women in the intervention clinic were asked, assessed and received advice for quitting in comparison with <15% in the control clinics (p < 0.01). To conclude, a primary care intervention based on the '5A' model for smoking cessation is feasible and can have a significant effect in reducing smoking prevalence in this population.

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