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We study the impact of money on households during the COVID-19 pandemic. In March 2020, Colombia rolled out a new unconditional cash transfer (UCT) to 1 million households in poverty worth US$19 (PPP US$55.6) and paid every five to eight weeks. Using a randomized control trial and linked administrative and survey data, we find the UCT had positive (albeit modest) effects on measures of household well-being (e.g., financial health, food access). Moreover, the UCT boosted support for emergency assistance to households and firms during the crisis and promoted social cooperation. Finally, we explore the bottlenecks in expanding mobile money during a pandemic.
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BACKGROUND: Gaps between evidence-based research and clinical-public health practice have been evident for decades. One of the aims of medical student research is to close this gap. Accordingly, evaluating individual and environmental factors that influence participation of medical students in research are needed to understand and identify potential targets for action. This study aims to identify characteristics of medical student researchers in Colombia and the associated factors with scientific publications. METHODS: A cross-sectional study of Colombian medical students involved in research using a validated, self-administered, online survey. The survey was distributed through the Colombian Association of Medical Students' Associations (ASCEMCOL). Data sets were analyzed using descriptive and summary statistics. Bivariate analysis and a multiple logistic regression model were conducted to identify predictors of scientific publications. RESULTS: A total of 133 responses were analyzed from students at 12 Colombian cities and 20 higher-education institutions. Although 94% of responders had at least one research proposal, only 57% had completed a project, and 17% had published their findings. Barriers for undertaking research included time restrictions and a lack of mentorship. Motivational factors included opportunity to publish findings and good mentorship. Students planning to do a specialization (OR = 3.25; 95% Confidence interval [CI] = 1.27-8.30), innovators (OR = 3.52; 95%CI = 1.30-9.52) and committed (OR = 3.39; 95%CI = 1.02-11.29), those who had previously published their findings (OR 9.13 IC95% 2.57-32.48), and were further in their medical education (OR 2.26 IC95% 1.01-5.07), were more likely to publish scientific papers. CONCLUSIONS: Our findings describe medical students understanding of the process of conducting research in Colombia. Although there appears to be motivation to participate in research, very few students achieve publication. Barriers such as time constraints and mentorship seem to play a critical role. This highlights opportunities where barriers to research can be overcome in medical school and other levels.
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Pesquisa Biomédica/estatística & dados numéricos , Internato e Residência , Publicações Periódicas como Assunto , Pesquisadores/educação , Faculdades de Medicina , Pesquisa Biomédica/educação , Colômbia/epidemiologia , Estudos Transversais , Medicina Baseada em Evidências , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Mentores , Guias de Prática Clínica como Assunto , Estudantes de Medicina , Adulto JovemRESUMO
Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax.
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Apoptose/efeitos dos fármacos , Biguanidas/farmacologia , Compostos de Bifenilo/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Nitrofenóis/farmacologia , Sulfonamidas/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Metformina/farmacologia , Mitocôndrias/metabolismo , Fenformin/farmacologia , Piperazinas/farmacologia , Rotenona/farmacologia , Células U937RESUMO
Here we report that leukemia cell lines and primary CD34+ leukemic blasts exposed to platelet rich plasma (PRP) or platelet lysates (PL) display increased resistance to apoptosis induced by mitochondria-targeted agents ABT-737 and CDDO-Me. Intriguingly, leukemia cells exposed to platelet components demonstrate a reduction in mitochondrial membrane potential (ΔΨM) and a transient increase in oxygen consumption, suggestive of mitochondrial uncoupling. Accompanying the ranolazine-sensitive increase in oxygen consumption, a reduction in triglyceride content was also observed in leukemia cells cultured with platelet components indicating that lipolysis and fatty acid oxidation may support the molecular reduction of oxygen in these cells. Mechanistically, platelet components antagonized Bax oligomerization in accordance with previous observations supporting an antiapoptotic role for fatty acid oxidation in leukemia cells. Lastly, substantiating the notion that mitochondrial uncoupling reduces oxidative stress, platelet components induced a marked decrease in basal and rotenone-induced superoxide levels in leukemia cells. Taken together, the decrease in ΔΨM, the transient increase in ranolazine-sensitive oxygen consumption, the reduction in triglyceride levels, and the reduced generation of superoxide, all accompanying the increased resistance to mitochondrial apoptosis, substantiate the hypothesis that platelets may contribute to the chemoprotective sanctuary of the bone marrow microenvironment via promotion of mitochondrial uncoupling.
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Objetivos: Describir tasas de remisión completa de pacientes con leucemia aguda refractaria o en recaída tratados con el esquema IDA-FLAG y establecer la supervivencia global y libre de evento, toxicidad y duración de la remisión completa en servicios rutinarios. Métodos: Estudio retrospectivo de pacientes mayores de 15 años. Se describen variables discretas y continuas mediante frecuencias y medidas de tendencia central. La supervivencia global y libre de evento se determinó por el método de Kaplan-Meir usando la prueba de log-Rank para la comparación entre estratos. Resultados: Fueron incluidos 64 pacientes. No hubo diferencias significativas en las tasas de remisión respecto al sexo, la edad, el tipo de leucemia o la duración de la primera remisión. La toxicidad fue principalmente hematológica y el 100% de los pacientes presentaron neutropenia febril posterior al inicio del tratamiento. La mediana de supervivencia global fue de 5,83 meses y la supervivencia libre de evento fue de 79 días. Se encontraron diferencias significativas en la supervivencia global entre el grupo de pacientes que logró y no logró remisión completa. Conclusiones: El tratamiento de rescate con el régimen IDA FLAG logra inducir remisión completa en un porcentaje significativo de pacientes con leucemia aguda en recaída, con una toxicidad aceptable siendo la principal hematológica. Es necesario realizar estudios prospectivos y con un diseño adecuado para validar la efectividad del mismo y confirmar nuestros hallazgos. © 2013 Instituto Nacional de Cancerología. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Objectives: To describe complete remission rates in patients with refractory or relapsed acute leukemia following the IDA-FLAG scheme, and establish the overall and event free survival, toxicity and duration of the complete remission. Methods: Retrospective analysis of patients over 15 years old. Discrete and continuous variables are described by using frequencies and measures of central tendency. Overall and event free survival were determined with the Kaplan-Meier method using the log-Rank test for comparison among categories. Results: A total of 64 patients were included. There were no significant differences in the remission rate as regards sex, type of leukemia, or duration of the first remission. The toxicity was mainly hematological, and 100% of the patients had subsequent febrile neutropenia at the start of the treatment. The median overall survival was 5.83 months, and the event free survival was 79 days. Significant differences were found in the overall survival between the patient group that achieved complete remission and those that did not. Conclusions: Rescue treatment with the IDA-FLAG scheme managed to induce a complete remission in a significant percentage of patients with relapsed acute leukemia, with an acceptable toxicity, which was mainly hematological. Prospective studies are needed with a design suitable for validating its efficacy and to confirm our results. © 2013 Instituto Nacional de Cancerología. Published by Elsevier España, S.L.U. All rights reserved.
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Humanos , Terapêutica , Leucemia , Toxicidade , Leucemia Mieloide AgudaRESUMO
Nearly 60 years ago Otto Warburg proposed, in a seminal publication, that an irreparable defect in the oxidative capacity of normal cells supported the switch to glycolysis for energy generation and the appearance of the malignant phenotype (Warburg, 1956). Curiously, this phenotype was also observed by Warburg in embryonic tissues, and recent research demonstrated that normal stem cells may indeed rely on aerobic glycolysis - fermenting pyruvate to lactate in the presence of ample oxygen - rather than on the complete oxidation of pyruvate in the Krebs cycle - to generate cellular energy (Folmes et al., 2012). However, it remains to be determined whether this phenotype is causative for neoplastic development, or rather the result of malignant transformation. In addition, in light of mounting evidence demonstrating that cancer cells can carry out electron transport and oxidative phosphorylation, although in some cases predominantly using electrons from non-glucose carbon sources (Bloch-Frankenthal et al., 1965), Warburg's hypothesis needs to be revisited. Lastly, recent evidence suggests that the leukemia bone marrow microenvironment promotes the Warburg phenotype adding another layer of complexity to the study of metabolism in hematological malignancies. In this review we will discuss some of the evidence for alterations in the intermediary metabolism of leukemia cells and present evidence for a concept put forth decades ago by lipid biochemist Feodor Lynen, and acknowledged by Warburg himself, that cancer cell mitochondria uncouple ATP synthesis from electron transport and therefore depend on glycolysis to meet their energy demands (Lynen, 1951; Warburg, 1956).
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El tema de la neurocirugía ablativa para las adicciones ha sido objeto de investigación desde diferentes perspectivas, tanto en su aspecto neurofisiológico como psiquiátrico. Losnuevos datos y conocimientos han demostrado la gran importancia de las conexiones entre las diferentes áreas del cerebro, cuya actividad funcional se altera durante el desarrollodel fenómeno adictivo; por eso, es importante vincular el conocimiento anatómico y neurofisiológico del sistema mesolímbico para desarrollar técnicas quirúrgicas como métodos curativos o paliativos para las adicciones. En la presente revisión sobre la neurocirugía ablativa para las adicciones, se analizan la anatomía y la neurofisiología del sistema límbico, particularmente del núcleo accumbens,y se discuten los alcances y las limitaciones de las técnicas quirúrgicas actuales, las cuales deben tenerse en cuenta para futuros avances en el campo neuroquirúrgico...
Ablative neurosurgery for addictions has been an object of investigation from different perspectives, in neurophysiology as well as in psychiatry. New knowledge and newevidence has proven the great importance that exists between different areas of the brain, in which functional activity alters during the development of the addictivephenomenon, that is why it is important to associate the anatomy and neurophysiology of the mesocorticolimbic system in order to develop new surgery techniques, for curative or palliative therapies regarding addiction disease. In this present review about ablative neurosurgery in the nucleus accumbens, it is analyzed the anatomy and physiology of the limbic system particularly of the nucleus accumbens, and it will be discussed the advantages and limitations of current surgery techniques which may be taken in consideration for future advances in neurosurgical field...