RESUMO

Population aging is a global health priority due to the dramatic increase in the proportion of older persons worldwide. It is also expected that both global life expectancy and disability-free life expectancy will increase, leading to a significant rise in the proportion of individuals with extreme longevity, such as non-agenarians and centenarians. The inaccuracy of clinical evidence on therapeutic interventions for this demographic could lead to biased decision-making, influenced by age-related beliefs or misperceptions about their therapeutic needs. This represents a potential clinical ageism scenario stemming from gaps in clinical evidence. Such biases can result in 2 significant issues that adversely affect the health status and prognosis of older persons: polypharmacy and therapeutic inertia. To date, documents on polypharmacy in non-agenarians and centenarians account for less than 0.35% of the overall available evidence on polypharmacy. Furthermore, evidence regarding therapeutic inertia is non-existent. The purpose of this letter is to discuss polypharmacy and therapeutic inertia as potential clinical ageism scenarios resulting from the clinical evidence gaps in extreme longevity.

Assuntos

Etarismo , Longevidade , Polimedicação , Humanos , Etarismo/psicologia , Longevidade/efeitos dos fármacos , Idoso de 80 Anos ou mais , Idoso , Expectativa de Vida/tendências

RESUMO

Maize lethal necrosis (MLN), which is caused by maize chlorotic mottle virus along with a potyvirus, has threatened the food security of smallholders in sub-Saharan Africa. Mutations in eukaryotic translation initiation factors (eIFs), which also facilitate virus genome translation, are known to confer variable resistance against viruses. Following phylogenetic analysis, we selected two eIF4E proteins from maize as the most likely candidates to facilitate MLN infection. A knockout (KO) of each of the corresponding genes in elite but MLN-susceptible maize lines conferred only partial protection. Our inability to knockout both the genes together suggested that at least one was required for survival. When we edited (ED) the eIF4E genes in Mini Maize, however, the plants with the eif4e1-KO became highly resistant, whereas those with the eif4e2-KO remained susceptible. Neither of the causal viruses could be detected in the MLN-inoculated eif4e1-KO plants. The eIF4E2 cDNA in Mini Maize lacked the entire 4th exon, causing a 22-amino acid in-frame deletion, which shortened the protein to 198 amino acids. When we introduced mutations in the 4th exon of the eIF4E2 gene in two elite, MLN-susceptible lines pre-edited for an eif4e1-KO, we obtained as strong resistance against MLN as in eif4e1-KO Mini Maize. The MLN-inoculated lines with eif4e1-KO/eIF4E2-exon-4ED performed as well as the uninoculated wild-type lines. We demonstrate that the C-terminal 38 amino acids of eIF4E2 are dispensable for normal plant growth but are required for the multiplication of MLN viruses. Our discovery has wide applications across plant species for developing virus-resistant varieties.

RESUMO

The world is facing a significant demographic transition, with a substantial increase in the proportion of older persons, as well as long-lived persons (especially nonagenarians and centenarians). One of the popular beliefs is that old age is synonymous with disease and disability. However, the successful aging hypothesis suggests that those older persons with advanced chronological age who maintain their functional capacity derive from it a delay in biological aging, enhancing the quality of organic aging and regulation. Therefore, regardless of chronological age, even in cases of extreme longevity, those older adults with a successful aging phenotype and favorable functional capacity would be expected to have satisfactory post-surgical recovery with a low risk of morbidity and mortality. Currently, there is a significant gap between the availability of high-certainty surgical evidence that allows for evidence-based interventions applicable to the long-lived population-taking into account the actual conditioning factors of the health phenotype in older persons-and, above all, predictors of satisfactory post-surgical evolution. The application of meta-research to geriatric surgery emerges as a fundamental tool to address this knowledge gap and reveals opportunities and limitations that need to be resolved in the near future to establish evidence-based surgical care for older persons. The aim of this manuscript was to present a real and globally relevant scenario related to surgical care, addressing the longevity, the availability, and the quality of surgical evidence applicable to this population, and also to present variables to consider in analysis and future perspectives in research and meta-research in geriatric surgery.

RESUMO

The human papillomavirus (HPV) is a non-enveloped DNA virus transmitted through skin-to-skin contact that infects epithelial and mucosal tissue. It has over 200 known genotypes, classified by their pathogenicity as high-risk and low-risk categories. High-risk HPV genotypes are associated with the development of different types of cancers, including cervical cancer, which is a leading cause of mortality in women. In clinical practice and the market, the principal tests used to detect HPV are based on cytology, hybrid detection, and qPCR. However, these methodologies may not be ideal for the required timely diagnosis. Tests have been developed based on isothermal nucleic acid amplification tests (INAATs) as alternatives. These tests offer multiple advantages over the qPCR, such as not requiring specialized laboratories, highly trained personnel, or expensive equipment like thermocyclers. This review analyzes the different INAATs applied for the detection of HPV, considering the specific characteristics of each test, including the HPV genotypes, gene target, the limit of detection (LOD), detection methods, and detection time. Additionally, we discuss the tests available on the market that are approved by the Food and Drug Administration (FDA). Finally, we address the challenges and potential solutions for the large-scale implementation of INAATs, particularly in rural or underserved areas.

RESUMO

Introducción. Las complicaciones posteriores a la reparación endovascular de aneurisma (EVAR) pueden resolverse con técnicas endovasculares. Sin embargo, cuando está indicada, la explantación de una endoprótesis es un procedimiento complejo, que se asocia a lesiones vasculares o viscerales, con alta morbimortalidad, en pacientes con edad avanzada y múltiples comorbilidades, y por lo tanto, alto riesgo quirúrgico. No existen dispositivos producidos por la industria para explantar las endoprótesis aórticas, por lo que el objetivo de este trabajo fue desarrollar un dispositivo para la explantación de endoprótesis aórticas. Métodos. Se llevó a cabo un estudio experimental, en fase preclínica, para desarrollar un dispositivo para la explantación de endoprótesis aórticas, con pruebas en modelos 3D y en un modelo animal porcino cadavérico. Resultados. Es factible desarrollar un modelo experimental de un nuevo dispositivo para explantar endoprótesis aórticas, denominado explantador de Cabrera, y comprobar su funcionamiento en un modelo animal cadavérico. El uso del explantador de Cabrera limitó el daño de la pared aórtica por parte de la endoprótesis en un 100 % al momento de su explantación en un modelo experimental ex vivo. Conclusión. Usando una jeringa septo, el explantador de Cabrera es superior a la técnica estándar de explantación de una endoprótesis al limitar la lesión de la pared aórtica, al colapsar y liberar los ganchos de fijación suprarrenal de forma controlada y segura al interior de la luz aórtica y, posteriormente, extraerla de forma rápida y efectiva, conservando la mayor cantidad de aorta sana para la posterior reconstrucción aorto-ilíaca.

---

Introduction. Complications after endovascular aneurysm repair (EVAR) can be resolved with endovascular techniques; however, when indicated, stent explantation is a complex procedure, which is associated with vascular or visceral injuries, with high morbidity and mortality in patients, with advanced age and multiple comorbidities, and therefore high surgical risk. There are no devices produced by the industry to explant aortic endoprostheses, so the objective of this work was to develop a device for the explantation of aortic endoprostheses. Methods. An experimental study was carried out, in the preclinical phase, to develop a device for the explantation of aortic endoprostheses, with tests in 3D models and in a cadaveric porcine animal model. Results. It is feasible to develop an experimental model of a new device for explanting aortic endoprostheses, called Cabrera explanter, and verify its operation in a cadaveric animal model. The use of the Cabrera explanter limited damage to the aortic wall by the endoprosthesis by 100% at the time of explantation in an ex vivo experimental model. Conclusions. Using a septum syringe, the Cabrera explanter is superior to the standard stent explantation technique by limiting injury to the aortic wall, collapsing and releasing the adrenal fixation hooks in a controlled and safe manner into the aortic lumen, and subsequently, extract it quickly and effectively, preserving the greatest amount of healthy aorta for the subsequent aorto-iliac reconstruction.

Assuntos

Humanos , Remoção de Dispositivo , Procedimentos Endovasculares , Correção Endovascular de Aneurisma , Aorta Abdominal , Próteses e Implantes , Aneurisma da Aorta Abdominal

RESUMO

Objective: Do-Not-Attempt-Resuscitation orders originated in the early 1960s with the establishment of advanced cardiopulmonary resuscitation. These orders aim to limit therapeutic efforts in cases where it may be futile. The decision not to resuscitate a patient is a process that involves a series of ethical, legal, and clinical considerations. Still, it also requires a process in which priority is given to the patients and their autonomy. The objective of this study was to describe the knowledge and attitudes of physicians working in Chile toward Do-Not-Attempt-Resuscitation orders. Methods: A cross-sectional study was conducted, in which a digital questionnaire was sent to physicians from different regions of Chile. Quantitative variables were analyzed using measures of central tendency and dispersion (e.g., median and interquartile range), while qualitative variables were evaluated using frequencies and percentages. Results: Four hundred and thirty-one physicians completed the survey. 85.4% were familiar with the ethical and legal guidelines for cardiopulmonary resuscitation and the rights and duties of the patient. 39.2% believed that patients should have the final decision Do-Not-Attempt-Resuscitation orders, especially if they themselves requested not to be resuscitated. 87.7% mentioned that the Do-Not-Attempt-Resuscitation orders should be reassessed if the patient's prognosis improves. In addition, it was found that the decision not to resuscitate was not always discussed with the patient or their family. Conclusions: The study revealed an ethical conflict regarding Do-Not-Attempt-Resuscitation orders and their management by Chilean physicians. Therefore, it is necessary to create recommendations and provide training to guide professionals in this process, which should also involve patients and their families.

RESUMO

Macrophytes and cladocerans represent the main antagonistic groups that regulate phytoplankton biomass; however, the mechanism behind this interaction is unclear. In laboratory conditions, we separately evaluated the effects of three submerged macrophytes (Ceratophyllum demersum, Myriophyllum aquaticum, and Stuckenia pectinata), as well as their exudates, and plant-associated microbiota (POM < 25 µm) + exudates on the population growth of Daphnia cf. pulex and Simocephalus cf. mixtus. Living Ceratophyllum, exudates, and POM < 25 µm + exudates exhibited the most robust positive effects on Simocephalus density and the rate of population increase (r). Subsequently, we examined the effects of Ceratophyllum on the filtration and feeding rates of Simocephalus and Daphnia, revealing significant (p < 0.001) promotion of filtration and feeding in Simocephalus but not in Daphnia. To elucidate the specific effects of this macrophyte on Simocephalus demography, we assessed selected life table variables across the same treatments. The treatments involving exudates and living Ceratophyllum resulted in approximately 40% longer survivorship and significantly (p < 0.01) enhanced fecundity. Our findings indicate that exudates from submerged macrophytes positively influence Simocephalus demography by increasing filtration rates, survivorship, and fecundity. This synergy suggests a substantial impact on phytoplankton abundance.

RESUMO

Prolactin has been recognized as neuroprotective hormone against various types of neuronal damage. This study was aimed to determine if prolactin protects against streptozotocin injury. A series of experiments were performed to determine neuronal survival by counting total neurons in medial hippocampus cortex and cerebellum. Astrogliosis was determined by immunofluorescence assays using GFAP, and behavioral improvement by prolactin after neuronal damage was determined by open-field and light-dark box tests. Results demonstrated that prolactin induced significant neuronal survival in both the hippocampus and cortex, but not in the cerebellum. No increase in astrogliosis was identified, but a significant reduction in anxiety levels was observed. Overall data indicate that prolactin may protect against a complex form of cell damage including oxidant stress and metabolic disruption by streptozotocin. Prolactin may be helpful strategy in the treatment of neuronal damage in neurological diseases.

Assuntos

Hipocampo , Neurônios , Fármacos Neuroprotetores , Prolactina , Estreptozocina , Animais , Prolactina/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Ratos , Neuroproteção/fisiologia , Neuroproteção/efeitos dos fármacos , Ratos Sprague-Dawley , Gliose/metabolismo , Cerebelo/metabolismo , Cerebelo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia

RESUMO

Breast cancer remains a significant cause of death for women globally, despite advancements in detection and treatment, low- and middle-income countries face unique obstacles. Role of Research Working Group (RWG) can expedite research progress by fostering collaboration between scientists, clinicians, and stakeholders. Benefits of a Global RWG include pooling resources and expertise to develop new research ideas, addressing disparities, and building local research capacity, with the potential to improve breast cancer research and outcomes.

Assuntos

Pesquisa Biomédica , Neoplasias da Mama , Humanos , Neoplasias da Mama/terapia , Feminino , Saúde Global , Países em Desenvolvimento

RESUMO

BACKGROUND: Centenarians are considered the most successful human biological aging model. However, the characteristics and patterns of research among centenarians have not been described or analyzed. Thus, this study aimed to disclose the historical landscape of global research on centenarians. METHODS: This bibliometric study investigated historical evidence on centenarian research published in the Scopus database. The bibliometrix package in R was used to perform visual and quantitative analyses of research metrics, trends, and patterns. RESULTS: Of the 2,061 documents included between 1887 and 2023, 84.2% (n=1,736) were published as articles with primary data. We identified international collaboration and annual growth rates of 21.4% and 3.15%, respectively. The United States published the highest number of papers on centenarians (n=786), whereas the publications from Italy had the highest impact (h-index of 90). Based on the frequency of keywords, mortality, genetics, dementia, Alzheimer's disease, and immunosenescence are a few of the most studied topics among centenarians, with emerging research related to mitochondrial DNA and comparison of results between nonagenarians and centenarians. Italy, the United States, and China lead the global research collaboration network, collaborating most frequently with Japan and European countries. CONCLUSION: Global research on centenarians has grown over the last 20 years, primarily led by Italy, the United States, and China. Latin American and African countries have conducted little or no research on centenarians. The most widely studied topics include mortality, cognition, immunosenescence, and genetics.

Assuntos

Bibliometria , Centenários , Idoso de 80 Anos ou mais , Humanos , Pesquisa Biomédica/história , Pesquisa Biomédica/tendências , História do Século XIX , História do Século XX , História do Século XXI , Longevidade

RESUMO

Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor for the onset of ADs. Theoretically, it is inferred that with organic and immune system aging, the loss of immune tolerance and specificity of immune activity becomes more intense, the probability of autoimmunity is increasing. However, there is a group of individuals whose prevalence of ADs is very low or non-existent, despite the biological aging. This paradox in autoimmunity raises questions. Centenarians, individuals who are over 100 years old, are possibly the most successful model of biological aging in humans. Most of these individuals exhibit a favorable health phenotype. To date, primary data evidence and potential hypotheses explaining this phenomenon are lacking globally, even though this paradox could provide valuable, original, and relevant information regarding the understanding of risk or protective factors, biological drivers, and biomarkers related to autoimmunity. Herein we discuss some hypothesis that may explain the absence of ADs in centenarians, including inflammaging, immunosenescence and immune resilience, immune system hyperstimulation, proteodynamics, and genetics.

RESUMO

Background: Cancer genomics, as an interdisciplinary research area within the Global Cancer Research agenda, genomics and precision medicine, its important in research and clinical practice in Latin America. To date, there has been no study investigating evolution of this area in this region. The aim of this study was to evaluate for first time, the historical evolution of cancer genomics research in Latin America. Methods: Bibliometric cross-sectional study of documents on cancer genomics published by Latin American authors until 2023 in Scopus was performed. Statistical and visual analysis was performed with R programming language. Results: A total of 1534 documents were obtained. The first document of cancer genomics research was published in 1997, marking the inception of a 26-year evaluation period that extended until 2023. Among the documents, 74.3% (n = 1140) constituted original articles, followed by 22.7% (n = 349) classified as reviews. International collaboration was observed in 6.5% (n = 100) of the articles. Within the compilation of the ten most prolific authors in this region, 90% of them are from Brazil. This observed pattern extends to affiliations as well, wherein the Universidade de São Paulo emerges as the most active institution (n = 255 documents). This arrangement firmly establishes Brazil's prominence as the preeminent country in the region concerning cancer genomics research, showcasing robust collaboration networks both regionally and intercontinentally. An important transition in the studied hot topics over the last 20 years was identified, from the exploration of the human genome and the characterization of genomic and proteomic cancer profiles (1997-2010) to an in-depth investigation of cancer stem cells and personalized medicine (2011-2023). Among the array of cancer types under study, predominant attention has been directed towards breast, lung, prostate, and leukemia. Conclusion: Over the course of the past 26 years, a favorable and notable evolution has characterized cancer genomics research within Latin America, with Brazil leading the way, which possess a robust network of regional and intercontinental collaboration. Furthermore, the lines of research and hot topics have change in harmony with the region's objectives, strategies, and requisites.

Assuntos

Pesquisa Biomédica , Humanos , Diversidade Cultural

Assuntos

Centenários , Longevidade , Idoso de 80 Anos ou mais , Humanos , Fatores Etários

RESUMO

Introduction: People living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) often experience discrimination from both other individuals and the health personnel who care for them. Chile has experienced a marked increase in the number of new HIV cases.Methods: Prospective cross-sectional study. The HIV/AIDS questionnaire for providers and health personnel was obtained from the International Planned Parenthood Federation, initially carrying out a pilot test and evaluating its validity.Results: A total of 784 health professionals answered the questionnaire correctly. Among them, 68.4% (n = 536) were women, and 36.2% (n = 284) were physicians. The study revealed that more than 90% of respondents had a positive attitude towards caring for people living with HIV, and more than 75% did not mind buying food from them or sharing services with them. Furthermore, more than 99% rejected the religiously endorsed labeling of people living with HIV/AIDS as immoral. Additionally, 95.5% (n = 749) mentioned that they did not feel anxious about knowing whether the next patient on their care list was living with HIV, and 76.9% (n = 603) of the respondents felt safe taking blood samples.Conclusions: Chilean health professionals have good knowledge about HIV infection and its mode transmission. Their attitudes towards people living with HIV are also generally positive.

Assuntos

Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Feminino , Masculino , Chile , HIV , Estudos Transversais , Estudos Prospectivos , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Inquéritos e Questionários

RESUMO

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: SLC6A4, SAT-1, TPH-2, ANKK1, GSHR, SCARA50, RGS10, STK33, COMT, and FKBP5. This systematic review shows the genetic studies conducted on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, in the future could be used as potential biomarkers to identify people at risk of suicide.

Assuntos

Proteínas RGS , Suicídio , Humanos , México/epidemiologia , Ideação Suicida , Biomarcadores , Proteínas da Membrana Plasmática de Transporte de Serotonina , Proteínas Serina-Treonina Quinases

RESUMO

RESUMEN Introducción: En la región del Caribe colombiano es escasa la evidencia sobre infección de pie diabético que apoye la toma de decisiones basada en datos propios y se desconoce el comportamiento microbiológico actual de este tipo de infección. Métodos: Estudio corte transversal que incluyó pacientes con infección de pie diabético atendidos en un hospital de referencia de tercer nivel de la región del Caribe colombiano, entre septiembre de 2021 y mayo de 2022. Se extrajeron datos sociodemográficos, clínicos y microbiológicos del paciente y su infección. Se realizó un análisis descriptivo y cálculo de razón de prevalencia (RP), para identificar factores asociados con desenlaces desfavorables. Resultados: Un total de 149 pacientes fueron incluidos. El 61,8 % de la muestra era de sexo masculino, con una mediana de edad de 61 años. Predominó la infección moderada a severa (67,8 %). Pseudomona aeruginosa (18,1%), Escherichia coli (13,5 %) y Staphylococcus aureus (12,8 %), fueron los agentes más frecuentes encontrados. El 44,2 % de los microorganismos demostró resistencia. El tabaquismo (p <0,001), antecedente de amputación (p <0,001), la cronicidad de la úlcera (p <0,001) y el ingreso a cuidado intensivo (p <0,001) se asociaron significativamente con mortalidad, amputación, resistencia microbiana y diagnóstico de osteomielitis por imagen. Conclusión: En la región del Caribe colombiano, la infección por pie diabético es predominante en hombres de mediana edad, con presentación moderada a severa, causada principalmente por bacterias gramnegativas y enterobacterias y, el tabaquismo y el ingreso a cuidado intensivo son los factores asociados de manera más significativa a desenlaces desfavorables.

---

ABSTRACT Introduction: In the Colombian Caribbean region, there is scarce evidence on diabetic foot infection to support decision making based on the patient's own data, and the current microbiological behavior of this type of infection is unknown. Methods: Cross-sectional study that included patients with diabetic foot infection treated at a third level referral hospital in the Colombian Caribbean region, between September 2021 and May 2022. Sociodemographic, clinical and microbiological data on the patient and his infection were extracted. A descriptive analysis and prevalence ratio (PR) calculation were performed to identify factors associated with unfavorable outcomes. Results: A total of 149 patients were included. The 61.8% of the sample was male, with a median age of 61 years. Moderate to severe infection predominated (67.8 %). Pseudomona aeruginosa (18.1 %), Escherichia coli (13.5 %), and Staphylococcus aureus (12.8 %) were the most frequent agents found. 44.2 % of the microorganisms showed resistance. Smoking (p <0.001), history of amputation (p <0.001), chronicity of ulcer (p <0.001) and admission to intensive care (p <0.001) were significantly associated with mortality, amputation, microbial resistance and diagnosis of osteomyelitis by imaging Conclusions: In the Colombian Caribbean region, diabetic foot infection is predominant in middle-aged men, with moderate to severe presentation, mainly caused by gram-negative bacteria and enterobacteria, and smoking and admission to intensive care are the factors most significantly associated with unfavorable outcomes.

RESUMO

Background: There is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs). Methods: An exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the ΔCEA, ΔOCT4, and ΔOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response. Results: Patients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median ΔCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (< -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated ΔCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p <0.001), and negative values of ΔOCT4 (p <0.001) (suggestive of poor therapeutic response) compared to those without this status. Conclusion: This study identified a significant and directly proportional association among the values of ΔCEA, ΔOCT4, and ΔOCT4/GUSB. These findings suggest that ΔCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression.