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The potential role of vitamin C in cancer prevention and treatment remains controversial. While normal human cells obtain vitamin C as ascorbic acid, the prevalent form of vitamin C in vivo, the uptake mechanisms by which cancer cells acquire vitamin C has remained unclear. The aim of this study is to characterize how breast cancer cells acquire vitamin C. For this, we determined the expression of vitamin C transporters in normal and breast cancer tissue samples, and in ZR-75, MCF-7, MDA-231 and MDA-468 breast cancer cell lines. At the same time, reduced (AA) and oxidized (DHA) forms of vitamin C uptake experiments were performed in all cell lines. We show here that human breast cancer tissues differentially express a form of SVCT2 transporter, that is systematically absent in normal breast tissues and it is increased in breast tumors. In fact, estrogen receptor negative breast cancer tissue, exhibit the most elevated SVCT2 expression levels. Despite this, our analysis in breast cancer cell lines showed that these cells are not able to uptake ascorbic acid and depend on glucose transporter for the acquisition of vitamin C by a bystander effect. This is consistent with our observations that this form of SVCT2 is completely absent from the plasma membrane and is overexpressed in mitochondria of breast cancer cells, where it mediates ascorbic acid transport. This work shows that breast cancer cells acquire vitamin C in its oxidized form and are capable of accumulated high concentrations of the reduced form. Augmented expression of an SVCT2 mitochondrial form appears to be a common hallmark across all human cancers and might have implications in cancer cells survival capacity against pro-oxidant environments.

Telemedicine has had a significant role during the outbreak of COVID-19. The experience in the United States has shown advantages and some challenges that need to be addressed to include telemedicine as an established part of the health system. This article aims to determine the United States' main challenges, associating them with the Chilean reality. In this study, we classify the barriers and difficulties for telemedicine into three areas: accessibility, cyber security, and medical liability.We argue that Chile will have to deal with similar obstacles to include telemedicine as a regular health service for the entire population.

Dos estudios evaluaron la capacidad de cuestionarios basados en la Teoría de la Sensibilidad al Reforzador (TSR) para predecir psicopatía primaria y secundaria. Los instrumentos se aplicaron a muestras no probabilísticas de estudiantes universitarios primer estudio n=769; segundo n=528). Las muestras se reunieron en universidades de la Ciudad de México. Con la finalidad de identificar predictores de las variables dependientes se usaron modelos de regresión lineal, inferencia no paramétrica y correlacionales. El primer estudio mostró que las escalas BIS/BAS (Carver & White, 1994) predicen ambas psicopatías. La psicopatía primaria es predicha por una combinación de razgos BIS y BAS; por su parte, solamente la escala BAS predice psicopatía secundaria. El segundo estudio mostró que el cuestionario RST-PQ (Corr & Cooper, 2016) predicen ambas psicopatías. Tanto psicopatía primaria como secundaria, son predichas por una combinación de escalas pertenecientes a los sistemas de inhibición, activación conductual y FFFS. Los hallazgos no apoyan la idea de que cada una de las psicopatías se encuentre asociada, de manera independiente, a alguno de los sistemas de la TSR.

The data presented in this article are related to the research paper entitled "Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer", available in Free Radical Biology and Medicine Journal [1]. In this article, we examined the SVCT2 transporter expression in various breast cancer cell lines using RT-PCR and Western blot assays. In addition, we analyzed the subcellular localization of SVCT2 by immunofluorescence colocalization assays and cellular fractionation experiments. Finally, an analysis of different cancer tissue microarrays immunostained for SVCT2 and imaged by The Human Protein Atlas (https://www.proteinatlas.org) is presented.

The DNA-dependent protein kinase (DNA-PK) plays a critical role in the non-homologous end joining (NHEJ) double stand break (DSB) repair pathway and the DNA damage response (DDR). Consequently, blocking DNA-PK kinase activity is a novel anti-cancer therapeutic strategy in combination with ionizing radiation (IR). Towards developing a series of a new class of DNA-PK inhibitors, our laboratory has exploited the mechanism of DNA-PK activation which requires binding to DNA termini via the Ku 70/80 heterodimer. We recently reported the development of Ku-DNA binding inhibitors (Ku-DBi’s) that act via this novel mechanism of action to inhibit DNA-PK catalytic kinase activity. Ku-DBi’s display nanomolar activity in vitro, possess cellular DNA-PK and NHEJ inhibitory activity and sensitize non-small cell lung cancer (NSCLC) cells to chemotherapeutics bleomycin and etoposide. In this study, we demonstrate that pre-incubation of our novel Ku-DBi’s can potentiate the cellular effects of IR. We demonstrate that the increase in IR sensitivity is preceded by a decrease in DNA-PKcs autophosphorylation events at the S2056 (pS2056) cluster. Using a combination of Western blot and immunofluorescence assays in the NSCLC NCI-H460 cell line, Ku-DBi 245 treatment in combination with IR showed a significant reduction of phosphorylation of DNA-PKcs at S2056 compared to IR alone. Analysis of gH2A.X also showed an inhibition of the DDR as a function of 245 treatment, evidenced by reduction of S139 phosphorylation. These results demonstrate that Ku-DBi 245 blocks DNA-break dependent DNA-PKcs autophosphorylation, resulting in an increased in radiation sensitivity. These data are consistent with Ku-DBi’s possessing a novel mechanism of action that abrogates autophosphorylation of DNA-PKcs and DDR signaling as part of an anticancer therapeutic strategy in combination with IR. Citation Format: Pamela Mendoza-Munoz, Navnath S. Gavande, Pamela S. VanderVere-Carozza, Katherine S. Pawelczak, Joseph R. Dynlacht, Joy Garrett, John J. Turchi. Impact of a novel Ku-DNA binding inhibitor on the IR-induced DNA damage response [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-023.

Latin America has been traditionally characterized as a region with high levels of income inequality. Since the early 2000s, however, inequality has started to decline in most countries, basically due to an expansion of the income share of the poorest deciles at the expense of the richest 10%. This paper addresses the question of whether the improvements are driven by long-term secular trends or structural changes which could be expected to continue to generate inequality-reducing effects for years to come; or alternatively, if the changes are driven by short-term variables which could move unexpectedly in the opposite direction and reverse the gains observed so far. From our statistical analysis, we conclude that the improvements are associated with both long- and short-term factors – with the short-term factors recently having greater inequality-reducing changes.

The 2000s decade represented a turning point in the increasing inequality trend that had been observed in Latin America during the second half of the twentieth century. This paper offers an analysis of the association between these shifts and short-, medium- and long-term factors. For our exploration we assemble a database on income distribution indicators systematically calculated directly from household surveys with emphasis on within-country consistency, methodology, definitions and coverage for the 1980–2013 years. This database allows observing clearly that the increases in inequality throughout the 1980s and 1990s decades have been counteracted by the improvements in the 2000s and the initial years of the 2010 decades. From our econometric exploration we find that (a) while there are short-term forces that are associated with underlying improvements in the distribution—including human capital accumulation and declines in the population dependency rate, (b) medium-term factors that could have...

espanolEl principal objetivo del presente trabajo es proponer a la necesidad terapeutica como criterio util en la determinacion del nivel obligacional exigible para el facultativo en el ejercicio de su actividad profesional. Se plantea como indispensable la distincion entre actividades medicas orientadas al tratamiento de patologias, de aquellas prestaciones sanitarias que no buscan dicha finalidad. En lo metodologico tal propuesta implica abordar la tematica apuntada desde un enfoque dogmatico, sistematico y hermeneutico a efecto de entregar soluciones a los principales problemas que se han planteado al respecto. Finalmente, se concluye que el mayor o menor nivel obligacional exigible al profesional de la salud se encuentra intimamente relacionado con la existencia o no de una finalidad asistencial en la actuacion medica, salvo, claramente, que los contratantes en virtud de su autonomia puedan llegar a pactos diversos. EnglishThe main objective of this work is to propose the therapeutic need as a useful criterion in determining the obligatory level required for the practitioner in the exercise of his professional activity. The distinction between medical activities for treatment of diseases and those health services that do not seek this purpose is considered essential. In the methodological aspect, this proposal implies approaching the topic from a dogmatic, systematic and hermeneutical approach in order to provide solutions to the main problems that have been raised in this regard. Finally, it is concluded that the greater or lesser obligatory level required of the health professional is closely related to the existence or absence of an assistance purpose in the medical action except, clearly, that the contractors, in virtue to their autonomy, can reach diverse agreements.

This paper explores families' investment in skills development through education in a high-inequality, low-education quality country such as Mexico, comparing it to a lower-inequality, higher-quality education country such as the United States. The paper uses a series of high-quality Household Income and Expenditure Surveys for both countries spanning around 20 years and different methodological approaches. Of particular interest is the analysis of education expenditure patterns along the income distribution. Policy implications for both cases are discussed. While in Mexico stimulating private spending in education through public resources might be regressive, the opposite might be the case in the United States.

The liver has an extraordinary regenerative capacity in response to partial hepatectomy (PHx), which develops with neither tissue inflammation response nor alterations in the whole organism. This process is highly coordinated and it has been associated with changes in glutathione (GSH) metabolism. However, there are no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and GSH act integrally as an antioxidant system that protects cells and tissues from oxidative damage and imbalance observed in a variety of diseases that affect the liver. Although rat hepatocytes are able to synthesize AA and GSH, which are the providers of AA for the whole organism, they also acquire AA from extracellular sources through the sodium-coupled ascorbic acid transporter-1 (SVCT1). Here, we show that hepatocytes from rat livers subjected to PHx increase their GSH and AA levels from 1 to 7 days post hepatectomy, whose peaks precede the peak in cell proliferation observed at 3 days post-hepatectomy. The increase in both antioxidants was associated with higher expression of the enzymes involved in their synthesis, such as the modifier subunit of enzyme glutamine cysteine ligase (GCLM), glutathione synthetase (GS), gulonolactonase (GLN) and gulonolactone oxidase (GULO). Importantly, rat hepatocytes, that normally exhibit kinetic evidence indicating only SVCT1-mediated transport of AA, lost more than 90% of their capacity to transport it at day 1 after PHx without evidence of recovery at day 7. This observation was in agreement with loss of SVCT1 protein expression, which was undetectable in hepatocytes as early as 2 h after PHx, with partial recovery at day 7, when the regenerated liver weight returns to normal. We conclude that after PHx, rat hepatocytes enhance their antioxidant capacity by increasing GSH and AA levels prior to the proliferative peak. GSH and AA are increased by de novo synthesis, however paradoxically hepatocytes from rat subjected to PHx also suppress their capacity to acquire AA from extracellular sources through SVCT1.

Although there is in vivo evidence suggesting a role for glutathione in the metabolism and tissue distribution of vitamin C, no connection with the vitamin C transport systems has been reported. We show here that disruption of glutathione metabolism with buthionine-( S,R )-sulfoximine (BSO) produced a sustained blockade of ascorbic acid transport in rat hepatocytes and rat hepatoma cells. Rat hepatocytes expressed the Na + -coupled ascorbic acid transporter-1 (SVCT1), while hepatoma cells expressed the transporters SVCT1 and SVCT2. BSO-treated rat hepatoma cells showed a two order of magnitude decrease in SVCT1 and SVCT2 mRNA levels, undetectable SVCT1 and SVCT2 protein expression, and lacked the capacity to transport ascorbic acid, effects that were fully reversible on glutathione repletion. Interestingly, although SVCT1 mRNA levels remained unchanged in rat hepatocytes made glutathione deficient by in vivo BSO treatment, SVCT1 protein was absent from the plasma membrane and the cells lacked the capacity to transport ascorbic acid. The specificity of the BSO treatment was indicated by the finding that transport of oxidized vitamin C (dehydroascorbic acid) and glucose transporter expression were unaffected by BSO treatment. Moreover, glutathione depletion failed to affect ascorbic acid transport, and SVCT1 and SVCT2 expression in human hepatoma cells. Therefore, our data indicate an essential role for glutathione in controlling vitamin C metabolism in rat hepatocytes and rat hepatoma cells, two cell types capable of synthesizing ascorbic acid, by regulating the expression and subcellular localization of the transporters involved in the acquisition of ascorbic acid from extracellular sources, an effect not observed in human cells incapable of synthesizing ascorbic acid.

To identify characteristics of pregnant women who refuse HIV testing and determine predictive factors and the reasons for refusal, we conducted face-to-face interviews of pregnant women at prenatal clinics of public and private hospitals. We found 8% (n=65) of 826 pregnant women interviewed refused HIV testing. In bivariate analysis, foreign-born pregnant women residing in Los Angeles County were twice more likely to refuse HIV testing than U.S.-born pregnant women (odds ratio [OR] = 1.97, 95% confidence interval [CI] 1.11-3.49, p

This study addresses why Mexico continues to show below-average economic growth rates in spite of displaying systematically higher domestic savings than other countries in the region. Using the wealth of relevant databases available for the country, the paper finds that a possible explanation is that household savings account for a majority of domestic savings, and that the main instrument used for savings is durable goods, which implies that savings are not directly injected into the financial system for fueling productive investment. The construction of a synthetic panel from household survey data shows that household savings in Mexico have a clear age-increasing trend and have been growing across generations during the past 30 years; it is thus probable that rates will increase in years to come. However, if those savings continue to elude the financial system, their influence on economic growth may remain limited.