Background
Latin American countries are improving childhood cancer care, showing strong commitment to implement the Global Initiative for Childhood Cancer, but there are scant publications of the ...situation at a continental level.
Methods
As part of the International Society of Paediatric Oncology Global Mapping project, delegates of each country participating in the Latin American Society of Pediatric Oncology (SLAOP) and chairs of national pediatric oncology societies and cooperative groups were invited to provide information regarding availability of national pediatric cancer control programs (NPCCP), pediatric oncology laws, pediatric oncology tumor registries, and training programs and support to diagnosis and treatment.
Results
Nineteen of the 20 countries participating in SLAOP responded. National delegates reported nine countries with NPCCP and four of them were launched in the past 5 years. National pediatric tumor registries are available in eight countries, and three provided published survival results. Fellowship programs for training pediatric oncologists are available in 12 countries. National delegates reported that eight countries provide support to most essential diagnosis and treatments and 11 provide partial or minimal support that is supplemented by civil society organizations. Seven countries have a pediatric oncology law. There are three international cooperative groups and four national societies for pediatric oncology.
Conclusion
Despite many challenges, there were dramatic advances in survivorship, access to treatment, and availability of NPCCP in Latin America. Countries with highest social development scores in general provide more complete support and are more likely to have NPCCP, training programs, and reported survival results.
Background
The ongoing coronavirus 2019 disease (COVID‐19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first ...year.
Method
Four cross‐sectional surveys were electronically distributed among pediatric onco‐hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners.
Results
Four hundred fifty‐three pediatric onco‐hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio OR: 1.84, 95% CI: 1.19–2.8), surgeries (OR: 3, 95% CI: 1.9–4.6) and radiotherapy (OR: 6, 95% CI: 3.5–10.4). Suspension of surveillance consultations was higher in countries with COVID‐19 case fatality rates above 2% (OR: 3, 95% CI: 1.4–6.2) and SCT suspensions in countries with COVID‐19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6–7.45). Paradoxically, at the beginning of the second wave with COVID‐19 cases rising exponentially, most participants reported improvements in cancer services availability.
Conclusion
Our data show the medium‐term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.
Introduction: In Ecuador, there are 1708 cases of hemophilia in a population of 17,643,060 habitants; according to the World Federation of Hemophilia (WFH) Annual Global Survey Report 2020 released ...in October 2021. Eleven patients use emicizumab in Ecuador (ten patients under ministerial authorization, and one patient through private insurance); being the first administered in June 2021. Objectives: To describe the demographic characteristics of patients receiving emicizumab in Ecuador. To determine efficacy and response with emicizumab: based on annual bleeding rate (ABR), performance status assessment, activity, and participation. Methods: Population: Pediatric Severe Hemophilia A (PwHA) patients (<12 years) and adults/adolescents (>12 years), both from the public and private health sector. Study design: Retrospective, multicentric study, with a case-report research design. The sources of information were the medical records of the patients. Efficacy variables: ABR was calculated by: (number of bleeds/number of days times 365.25). Body structure and function was assessed with the Hemophilia Joint Health Score 2.1 (HJHS). Activity and participation were assessed with the Functional Independence Score in Hemophilia (FISH). Statistic analysis: Shapiro-Wilk test to know the distribution of the sample, t-Test paired tests (parametric), Wilcoxon statistic (non-parametric); Descriptive statistics: relative frequencies, measures of central tendency and dispersion, column graphs. Analysis and results: Ten patients with an average (Q1,Q3) age of 11.5 years (7.15) were registered. The youngest patient was one year old and the oldest, fifty years old. 90% (n:9) had hemophilia A with high-response inhibitors. Prior to starting emicizumab: 20% (n:2) presented Central Nervous System bleeding, 30% (n:3) had muscle bleeding, and 10% (n:1) developed catheter-associated infection. The mean ABR was 10 pre-emicizumab events, and 0.3 post-emicizumab events (p=0.002), with follow-ups at 22 months (n: 2), 17 months (n:2), 3 months (n:2 ), 4 months (n: 3), 5 months (n: 1). The mean HJHS (±SD, n) was 20.9 (± 20,096, 10) pre-emicizumab, and 9.7 (± 16.52, 10) (p=0.003) The mean by FISH (±SD, n) was 16.2 (± 8.59, 10) pre-emicizumab, and from 22.6 (± 11.62, 10) with the use of emicizumab. The use of the t-Test for paired samples determined that there are statistically significant differences between the pre-emicizumab and post-emicizumab groups for the variables ABR, HJHS and FISH (95% confidence level). Conclusion: The use of Emicizumab allowed better control of joint bleeding; and it contributed favorably in the evolutionary course of both the functional state and the activity. It is essential to corroborate these results with a longer follow-up and a larger sample size. Bibliography: 1. Alvarez Roman M: Spanish guidelines for the management of hemophilia. 2022, 1-190. 2. Callaghan M, Negrier C, Paz-Priel I, Chang T, Chebon S y col: Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242 3. Carcao M, Escurriola C, Santagostina E, Oldenburg J, Liesner R y col: The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia. 2019;25:676-684. 4. Ellsworth P, Ma A: Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?. Hematology Am Soc Hematol Educ Program. 2021, Dec 10;2021(1):219-225. 5. Young G: Management of children with hemophilia A: How emicizumab has changed the landscape. Journal of Thrombosis and Haemostasis. 2021 Jul;19(7):1629-1637
El presente estudio analiza el papel que juegan los personajes publicitarios como estrategia de comunicación visual en la promoción y difusión de productos de consumo; principalmente de café y ...chocolate. Centra su atención en la pasta de cacao orgánico que producen diversos emprendimientos rurales de la provincia del Guayas. El objetivo es determinar la influencia de los personajes publicitarios en la gestión de marca. Se utilizó un enfoque cualitativo mediante el estudio de casos, la investigación es de carácter exploratoria y descriptiva. Se realizaron visitas de campo a varias fincas donde observó los procesos de producción y como realizan la promoción de sus productos derivados de cacao de fino aroma, se emplearon instrumentos como la entrevista a los principales involucrados y a expertos en diseño y gestión de marca. Entre las principales conclusiones están el gran impacto visual que pueden generar los personajes publicitarios mediante la asociatividad, aportan mucho en la gestión de marca, pueden acompañar en campañas publicitarias de tipo impreso y audiovisual. A partir del análisis visual de varios personajes publicitarios de marcas de productos alimenticios a base de cacao se estableció parámetros para la creación de personajes publicitarios, se creó uno que represente los valores y cultura corporativa de los pequeños productores del cacao orgánico de la costa ecuatoriana.
La presente investigación tiene por objetivo medir la eficiencia productiva del Maíz Amarillo Duro en los distritos de Chongoyape, Lagunas - Mocupe y Nueva Arica durante el periodo de siembra del año ...2015, y a la vez responder sobre cuáles son los determinantes que la están causando. La metodología fue de tipo descriptiva y de diseño no experimental. La muestra estuvo conformada por 106 agricultores, asimismo la técnica utilizada fue la encuesta cuyo instrumento fue el cuestionario. Los resultados indicaron que el Distrito de Nueva Arica, es el que presenta mayores indicadores de eficiencia lo que hace que sea el distrito con un nivel de ineficiencia menor en comparación con los demás distritos en estudio. Tal es así que el agricultor con menor ineficiencia se encuentra en este distrito con un nivel de 0.03234645 y un rendimiento por hectárea 10.08 toneladas de MAD. Caso contrario ocurre con el distrito de Chongoyape en donde se encuentra mayor grado de ineficiencia con un 0.7100935. Se concluye que, las variables que explican la ineficiencia son la edad (eda) y el grado de instrucción alcanzado por el agricultor (gr), pues un mayor grado de instrucción en los agricultores les permitiría tener una mayor capacidad de adopción y un mejor manejo y uso de insumos de manera más óptima y eficiente. Lo que ayudaría a minimizar el nivel de ineficiencia técnica.
SUMMARY
Programmed cell death (PCD) is crucial for development and homeostasis of all multicellular organisms. In human cells, the double role of extra‐mitochondrial cytochrome c in triggering ...apoptosis and inhibiting survival pathways is well reported. In plants, however, the specific role of cytochrome c upon release from the mitochondria remains in part veiled yet death stimuli do trigger cytochrome c translocation as well. Here, we identify an Arabidopsis thaliana 14‐3‐3ι isoform as a cytosolic cytochrome c target and inhibitor of caspase‐like activity. This finding establishes the 14‐3‐3ι protein as a relevant factor at the onset of plant H2O2‐induced PCD. The in vivo and in vitro studies herein reported reveal that the interaction between cytochrome c and 14‐3‐3ι exhibits noticeable similarities with the complex formed by their human orthologues. Further analysis of the heterologous complexes between human and plant cytochrome c with plant 14‐3‐3ι and human 14‐3‐3ε isoforms corroborated common features. These results suggest that cytochrome c blocks p14‐3‐3ι so as to inhibit caspase‐like proteases, which in turn promote cell death upon H2O2 treatment. Besides establishing common biochemical features between human and plant PCD, this work sheds light onto the signaling networks of plant cell death.
Significance Statement
Common features of the cytochrome c‐dependent pathways leading to programmed cell death in plants and humans are herein revealed. In response to oxidative stress, cytochrome c is released from mitochondria to the cytoplasm to hamper the iota isoform of the 14‐3‐3 protein family, thereby decreasing the inhibition of caspase‐like activity and likely contributing to promote cell death in plants.
Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key ...regulators of damaged chromatin's transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chaperone SET/TAF-Iβ interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iβ to core histones, thereby locking its histone-binding domains and inhibiting its nucleosome assembly activity. In addition, we have used NMR spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iβ. Overall, these findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Iβ, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iβ's histone chaperone activity.
Cytochrome c (Cc) is a protein that functions as an electron carrier in the mitochondrial respiratory chain. However, Cc has moonlighting roles outside mitochondria driving the transition of ...apoptotic cells from life to death. When living cells are damaged, Cc escapes its natural mitochondrial environment and, once in the cytosol, it binds other proteins to form a complex named the apoptosome—a platform that triggers caspase activation and further leads to controlled cell dismantlement. Early released Cc also binds to inositol 1,4,5‐triphosphate receptors on the ER membrane, which stimulates further massive Cc release from mitochondria. Besides the well‐characterized binding proteins contributing to the proapoptotic functions of Cc, many novel protein targets have been recently described. Among them, histone chaperones were identified as key partners of Cc following DNA breaks, indicating that Cc might modulate chromatin dynamics through competitive binding to histone chaperones. In this article, we review the ample set of recently discovered antiapoptotic proteins—involved in DNA damage, transcription, and energetic metabolism—reported to interact with Cc in the cytoplasm and even the nucleus upon DNA breaks.
Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone ...chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-Iβ, was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of Arabidopsis thaliana after DNA breaks. In addition, this work establishes that NRP1 binds to cytochrome c, thereby preventing the former from binding to histones. Since NRP1 interacts with cytochrome c at its earmuff domain, that is, its histone-binding domain, cytochrome c thus competes with core histones and hampers the activity of NRP1 as a histone chaperone. Altogether, the results obtained indicate that the underlying molecular mechanisms in nucleosome disassembly/reassembly are highly conserved throughout evolution, as inferred from the similar inhibition of plant NRP1 and human SET/TAF-Iβ by cytochrome c during DNA damage response.
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