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The antagonistic effects of temozolomide and trichostatin a combination on MGMT and DNA mismatch repair pathways in Glioblastoma
No full textGlioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired
outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has
improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when
combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties
in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we
aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373
MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed
by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RTPCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed
antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell
line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated
in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment.
It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA
antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines
Reforma y devoción en los Andes orientales: cofradías eucarísticas en las doctrinas de Palca y Zongo, siglo XVII
Get PDFDurante su visita pastoral de la diócesis de La Paz (1634 -1635) el obispo Feliciano
de Vega estableció dos cofradías del Santísimo Sacramento en las doctrinas de Palca y
Zongo, en la vertiente oriental de los Andes. A partir de las constituciones de ambas corporaciones, se analizan su fundación, su funcionamiento y su papel en la promoción
del culto eucarístico en estas parroquias de indios. Estas hermandades compartieron parámetros propios de otras cofradías de indios: los indígenas principales ocuparon los
cargos más destacados y las corporaciones se abrieron también a hermanos simples,
indios e indias del común. Su principal competencia fue garantizar la dignidad del culto
eucarístico en la doctrina, tanto en aspectos cotidianos como en las solemnidades eucarísticas, entre las que destacaba la organización de la fiesta del Corpus con su procesión.
Junto a ello, fue esencial la atención de las exequias de los cofrades, común en todas las
hermandades. El análisis comparativo permite resaltar las singularidades propias de
cada cofradía. Las de Palca muestran una doctrina más estandarizada, por su cercanía
con la cabecera de la diócesis, frente a las particularidades de Zongo, ubicada en la
frontera chuncho-yunga, con una rica economía cocalera, que contó con cuotas de ingreso más elevadas -pagadas en parte con cestos de hoja de coca- e incorporó como
prioste al capitán de la frontera, un hacendado mestizo.During his pastoral visit to the diocese of La Paz (1634-1635) Bishop Feliciano de
Vega founded two brotherhoods of the Blessed Sacrament in the Indian parishes of Palca
and Zongo, on the eastern slope of the Andes. Based on the constitutions of both brotherhoods, their foundation, functioning, and role in the promotion of Eucharistic worship
in these indigenous parishes are analyzed. These were two brotherhoods that generally
shared parameters typical of other cofradías de indios: the indigenous leaders occupied the
most prominent positions, and the corporations were also open to simple brothers,
indigenous men, and women of the community. Their main purpose was to guarantee the
dignity of Eucharistic worship, both in daily aspects and in Eucharistic solemnities, among
which the organization of the Corpus Christi festival with its procession stood out. In
addition, the attention given to the funerals of the brotherhood members, common to all
fraternities, was essential. Comparative analysis allows us to highlight the singularities
specific to each brotherhood. In the case of Palca, the constitutions exhibit a more
standardized parish, owing to their proximity to the diocesan headquarters. However, the
Zongo brotherhood, belonging to a parish situated on the Chuncho-Yunga border with a
flourishing coca economy, showcases notable peculiarities. These include a less defined
set of norms, higher admission fees -partly paid with coca leaf baskets- and the
appointment of the mestizo landowner, who served as the captain of the border, as prioste
Plain language summary of the HIMALAYA study: tremelimumab and durvalumab for unresectable hepatocellular carcinoma (liver cancer)
No full textWhat is this summary about?: This is a summary of results from a phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose of a medication called tremelimumab combined with multiple doses of a medication called durvalumab (the STRIDE regimen) or multiple doses of durvalumab alone. These treatments were compared with a medication called sorafenib in participants with unresectable hepatocellular carcinoma (HCC). HCC is a type of liver cancer that is difficult to treat because it is often diagnosed when it is unresectable, meaning it can no longer be removed with surgery. Sorafenib has been the main treatment for unresectable HCC since 2007. However, people who take sorafenib may experience side effects that can reduce their quality of life, so alternative medicines are being trialed. Tremelimumab and durvalumab are types of drugs called immunotherapies, and they both work in different ways to help the body's immune system fight cancer.
What were the results of the study?: Participants who took STRIDE lived longer than participants who took sorafenib, whilst participants who took durvalumab alone lived a similar length of time as participants who took sorafenib. Participants who took STRIDE or durvalumab had a lower relative risk of experiencing worsening in their quality of life than participants who took sorafenib. The side effects that participants who received STRIDE or durvalumab experienced were expected for these types of treatments and could mostly be managed.
What do the results of the study mean?: Overall, STRIDE is more effective than sorafenib for people with unresectable HCC
The pricing strategies of online grocery retailers
Get PDFThis paper documents the differences in pricing strategies between online and offline (brick-and-mortar) channels. We collect price data for identical products from leading online grocery retailers in the United States and complement it with offline data for the same products from scanner data. Our findings reveal a consistent pattern: online retailers exhibit higher price dispersion than their offline counterparts. More specifically, online grocers employ price algorithms that amplify price discrimination in three key dimensions: (1) over time (through frequent price changes), (2) across locations (by charging varying prices based on delivery zipcodes), and (3) across sellers (by setting dispersed prices for identical products across rival retailers)
Longer breastfeeding duration is associated with lower consumption of ultraprocessed foods in a sample of Spanish preschoolers: the SENDO project
No full textBackground Breastfeeding has been linked to a higher consumption of fruit and veg-etables at ages 4 to 5 years. More recently, it has been suggested that it may also be associated with lower ultraprocessed food (UPF) consumption in childhood.Objective The aim of this study was to assess whether breastfeeding duration was associated with consumption of UPF in a sample of Mediterranean preschoolers.Design This study involved a cross-sectional analysis of baseline information of chil-dren in the Child Follow-Up for Optimal Development cohort. Children were enrolled at ages 4 to 5 years and information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative food frequency questionnaire and foods were classified based on the degree of processing according to the NOVA classification.Participants/setting This study used baseline information for 806 participants enrolled in the Child Follow-Up for Optimal Development cohort between January 2015 and June 2021 in Spain. Main outcomes measures Main study outcome measures were difference in grams per day and in the percentage of total energy intake from UPF consumption related to breastfeeding duration, and odds ratio that UPF represents a high percentage of total energy intake.Statistical analyses Crude and multivariable adjusted estimates were calculated with generalized estimating equations to account for intracluster correlation between siblings.Results The prevalence of breastfeeding in the sample was 84%. After adjusting for potential confounders, children who were breastfed for some time reported signifi-cantly lower consumption of UPF than children who were not breastfed at all. The mean differences were-19.2 g (95% CI-44.2 to 10.8) for children who were breastfed for 12 months had consistently lower odds of UPF representing more than 25%, 30%, 35%, and 40% of total energy intake.Conclusions Breastfeeding is associated with lower consumption of UPF in Spanish preschoolers
CO2 emissions in Latin America: a time series perspective based on fractional integration
Get PDFThis article deals with the analysis of [Formula: see text] emissions in Latin America by using a long memory process based on fractional integration. Using data of [Formula: see text] emission and [Formula: see text] emissions per capita, for 32 Latin American and Caribbean countries, the results show significant differences according to the variable examined, the model used, and the country under examination. In particular, for the [Formula: see text] emissions, mean reversion is found in Belize and also under some circumstances in Antigua and Barbuda, Colombia, Dominica, Dominican Republic, Ecuador, Grenada, Honduras, Nicaragua, Panama, Peru, and Uruguay. Thus, shocks in these series have a transitory effect. With respect to the time trends, only for some Caribbean countries, namely, Antigua and Barbuda, Aruba, Bahamas, Cuba, and Jamaica, the trend is insignificant; on the other hand, large countries like Brazil, Mexico, and Argentina display the highest time trend coefficients; for the [Formula: see text] emissions per capita, there are eleven countries where mean reversion is detected, and there are ten that share a lack of significance for the trend. The most significant trends now take place in Trinidad and Tobago, British Virgin Islands, Barbados, and Guyana. Policy implications of the results obtained are reported at the end of the paper
Association between COVID-19 and outstanding academic performance at a Spanish university
No full textBackgroundSARS-CoV-2 is the causative agent of COVID-19 identified in December 2019, an acute infectious respiratory disease that can cause persistent neurological and musculoskeletal symptoms such as headache, fatigue, myalgias difficulty concentrating, among others including acute cerebrovascular disease with a prevalence of 1-35%. The aim of this study is to evaluate the impact of COVID-19 in undergraduate students on their academic performance as an indicator of their intellectual ability and performance in a university that maintained 100% face-to-face teaching during the 2020-2021 academic year.MethodsA total of 7,039 undergraduate students were analyzed in a prospective cohort study at the University of Navarra. A questionnaire including sociodemographic and behavioral questions was sent. PCRs were performed throughout the academic year for the diagnosis of SARS-CoV-2 infection and students' academic results were provided by the academic center, adjusted descriptive and multivariate models were performed to assess the association.ResultsA total of 658 (9.3%) participants were diagnosed with COVID-19, almost 4.0% of them achieved outstanding academic results, while uninfected students did so in 7.3%. SARS-CoV-2 infection was associated with a significant decrease in having outstanding academic results (OR = 0.57; 95% CI: 0.38-0.86).ConclusionHaving COVID-19 disease, decreased academic performance in undergraduate students. Therefore, it is necessary to prevent infection even in the youngest sections of the population
First-line management of metastatic urothelial cancer: Current and future perspectives after the EV-302 and CcheckMate-901 studies
No full textThe standard of care for the first-line management of metastatic urothelial carcinoma has been recently challenged, with
the combination of pembrolizumab and enfortumab vedotin (P-EV) strongly arising as a practice-changing option from
classical platinum-based chemotherapies. With this paradigm shift on the horizon new questions, including the most
suitable second line of treatment for these patients, and the role that the molecular characterization of these tumours
will have when selecting these therapies will inevitably arise. Furthermore, after the negative results of the Keynote
361 and IMvigor 130 trials, the combination of nivolumab with platinum-based chemotherapy followed by nivolumab
maintenance (Nivo GC-Nivo) has also shown positive results when compared with chemotherapy alone. Translational
studies at a molecular, cellular, and functional level will be key to better explain these discordant results. In this Current
Perspective, we discuss the potential impact of these results in clinical practice and propose specific guidance for
prospective translational research
Ideación práctica y construcción creativa. El pabellón de España para la Feria Mundial de Nueva York de 1964-1965
Get PDFEl pabellón de España para la Feria Mundial de Nueva York de 1964-1965 constituye un hito en la carrera profesional de Javier Carvajal Ferrer (1926-2013). Recurriendo a las fuentes originales de archivos y a diversas entrevistas con varios de los técnicos que participaron en su diseño y construcción, en este artículo se explica y contextualiza el desarrollo de su ideación y edificación. Se pro-porcionan suficientes datos y fuentes de primera mano que señalan las complejas condiciones a las que hubo que adaptarse durante el proceso. Esas dificultades, que hay que calibrar junto con la elevada inversión y esfuerzo de propaganda del régimen español, lo convierten en un verdadero milagro de gestación a la par que confirman su condición paradigmática por sus aportaciones técnicas, singularmente de los procesos de obra y de las instalaciones, y metodológicas. La supervisión y coordinación entre todos los técnicos, el buen número de elementos prefabricados y los procesos de montaje, permitieron su erección en tiempo récord y después su total desmontaje y reconstrucción en otra localización.The Spanish pavilion for the 1964-1965 New York World’s Fair is a milestone in the professional career of Javier Carvajal Ferrer (1926-2013). Drawing on original archival sources and interviews with several of the technicians who participated in its design and construction, this article explains and contextualizes the development of its conception and construction. Sufficient data and first-hand sources are provided to testify the complex conditions that had to be faced during the process. These difficulties, which must be assessed with the high investment and propaganda effort of the Spanish regime, make it a true miracle of gestation while confirming its paradigmatic status for its technical and methodological contributions, particularly in the building processes and the facilities. The supervision and coordination between all the technicians, the large number of prefabricated elements and the assembly processes, allowed its erection in record time and later its total dismantling and reconstruction in another locatio
Risk of Second Primary Malignancies in Melanoma Survivors: A Population-Based Study
Get PDF(1) Introduction: The association between melanoma (MM) and the occurrence of second
primary neoplasms (SPNs) has been extensively studied, with reported incidence rates ranging from
1.5% to 20%. This study aims to evaluate the occurrence of SPNs in patients with a history of primary
MM and to describe the factors that make the risk higher in our population. (2) Material and Methods:
We conducted a prospective cohort study and calculated the incidence rates and relative risks (RR)
for the development of different SPNs in 529 MM survivors from 1 January 2005 to 1 August 2021.
Survival and mortality rates were obtained, and the Cox proportional hazards model was used to
determine the demographic and MM-related factors that influence the overall risk. (3) Results: Among
the 529 patients included, 89 were diagnosed with SPNs (29 prior to MM diagnosis, 11 synchronous,
and 49 after MM), resulting in 62 skin tumors and 37 solid organ tumors. The estimated probability
of developing SPNs after MM diagnosis was 4.1% at 1 year, 11% at 5 years, and 19% at 10 years.
Older age, primary MM location on the face or neck, and histologic subtype of lentigo maligna mm
were significantly associated with a higher risk of SPNs. (4) Conclusions: In our population, the
risk of developing SPNs was higher in patients with primary MM located on the face and neck
and with the histological subtype of lentigo maligna-MM. Age also independently influences the
risk. Understanding these hazard factors can aid in the development of MM guidelines with specific
follow-up recommendations for individuals with the highest risk