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Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

Regulatory enforcement of product safety standards given health concerns, whether it is in romaine lettuce, smartphones or cars, is emerging to be a challenge for global public health. This is particularly true for developing economies with fragile institutions. In this context, recent studies on Indian pharmaceutical markets provide evidence suggesting that the sector is a hub for substandard quality of medicines. Departing from these prior studies which use randomly collected samples, we reinvestigate this question using novel pan-India market sales data of banned medicines from 0.75 million pharmacists and chemists in India. We find that indeed such medicines get sold in India even after bans are imposed on them in the period 2007 to 2013. However, there is a general decline in demand post ban for our focal molecules suggesting broad adherence to bans. We also observe regional heterogeneity in prevalence of banned medicines sold between rich and poor regions of India with the former counterintuitively showing more sales. That said, while Ozawa et al. (2018) argue that prevalence of substandard medicines is around 13% in low and middle-income countries, we find an infringement ratio which is more muted in India at about 5%. Finally, a regression-based examination suggests that prior firm presence in therapeutic markets and popularity of molecules positively impact the likelihood of sale of banned medicines in India. Our results are robust to alternative explanations and are substantiated with a theoretical set up examining firm trade-offs in the decision to infringe. India has recently been under the lens of the global access to medicines debate and our findings have important policy implications for global health., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The aim of this work is to show a methodological proposal for the analysis of soil intervention values in mine tailings in order to determine the intervention requirements in the commune of Andacollo in northern Chile. The purpose of this analysis is to guide the intervention policies of both private and public organizations. The evaluation method is based on the Dutch legislation. The usability of the proposed methods depends on the available geochemical data from soil samples; in particular, we tackle the case when information regarding clay percentage in the soil is not available. We use the concepts of a threshold factor and an adjusted threshold factor to calculate a weighted intervention ranking. In order to illustrate the utility of this methodological proposal, a case study is carried out with the prescribed approach. In particular, this work presents an analysis of the elements of environmental significance related to the mining activity (Hg, Cd, Pb, As, Cu, Ni, Zn, Cr) in the commune of Andacollo, Coquimbo Region, Chile. The analyzed samples are used to determine where the intervention of tailing deposits is necessary and where a solution to these environmental liabilities is required as soon as possible. Out of the 81 samples evaluated, it was found that 18 require a potential intervention, and of these samples, seven of them are associated with abandoned tailings that, in some cases, are located close to the town center itself, one sample is associated with active tailings and the other 10 with inactive tailings., Competing Interests: The authors declare that they have no competing interests.

Objective: To measure and explain income-related inequalities in health and health care utilization in the period 2000 - 2009 in Chile, while assessing variations within the country and determinants of inequalities., Methods: Data from the National Socioeconomic Characterization Survey for 2000, 2003, and 2009 were used to measure inequality in health and health care utilization. Income-related inequality in health care utilization was assessed with standardized concentration indices for the probability and total number of visits to specialized care, generalized care, emergency care, dental care, mental health care, and hospital care. Self-assessed health status and physical limitations were used as proxies for health care need. Standardization was performed with demographic and need variables. The decomposition method was applied to estimate the contribution of each factor used to calculate the concentration index, including ethnicity, employment status, health insurance, and region of residence., Results: In Chile, people in lower-income quintiles report worse health status and more physical limitations than people in higher quintiles. In terms of health service utilization, pro-rich inequities were found for specialized and dental visits with a slight pro-rich utilization for general practitioners and all physician visits. All pro-rich inequities have decreased over time. Emergency room visits and hospitalizations are concentrated among lower-income quintiles and have increased over time. Higher education and private health insurance contribute to a pro-rich inequity in dentist, general practitioner, specialized, and all physician visits. Income contributes to a pro-rich inequity in specialized and dentist visits, whereas urban residence and economic activity contribute to a pro-poor inequity in emergency room visits., Conclusions: The pattern of health care utilization in Chile is consistent with policies implemented in the country and in the intended direction. The significant income inequality in the use of specialized and dental services, which favor the rich, deserves policy makers' attention and further investigation related to the quality of these services.

An intravenous mouse infection model was used to compare the virulence of Enterococcus faecalis strains, to study bacterial localization and organ histopathology, and to examine the effects of Nramp1 and gamma interferon (IFN-gamma) on the course of infection. Infection of BALB/c mice with 5 x 10(8) CFU of E. faecalis JH2-2, MGH-2, 418, DS16C2, or OG1X revealed the following virulence ranking (from highest to lowest): MGH-2, 418, DS16C2, JH2-2, and OG1X. Discernible differences in the number of MGH-2 and JH2-2 bacteria were observed at 7 days (168 h) in the blood (P = 0.037), at 72 h in the liver (P = 0.002), and at 8 h in the spleen (P = 0.036). At these time points, the number of MGH-2 bacteria was higher in the blood and liver while the number of JH2-2 bacteria was higher in the spleen. At 72 h, livers from MGH-2-infected mice had higher numbers of coalescing aggregates of leukocytes and a greater degree of caseous necrosis than those from JH2-2-infected mice. These results indicate a correlation between the virulence of the E. faecalis strain, the number of bacteria in the liver, and the degree of histopathology of the liver at 72 h postinfection. IFN-gamma was important in E. faecalis infection, since IFN-gamma gene knockout mice had reduced mortality and massive coagulative necrosis was observed in wild-type mice. The contribution of Nramp1 was unclear, since Nramp1(-/-) mice and the respective control mice were innately resistant to E. faecalis. The mortality of mice in this model is probably due to induction of cytokine release and massive coagulative necrosis.

Prostaglandins of the E series inhibit the development of Th1 responses. When infected with Leishmania major, BALB/c mice fail to develop a Th1 response, but instead mount a Th2 response and die of the disease. Therefore, we treated L. major-infected BALB/c mice with indomethacin, which inhibits prostaglandin production. Indomethacin lessened disease severity (parasite burden and pathology), and promoted a Th1 response, but the mice still succumbed to infection. The explanation for these observations may be two-fold: (1) the beneficial effects of indomethacin were predominantly observed later in infection (beyond two weeks), a time at which indomethacin was unable to sufficiently block the development of a Th2 response; (2) indomethacin was unable to induce a Th1 response in BALB/c mice that was of the same magnitude as the Th1 response observed in C57BL/6 mice infected with L. major.