Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Abstract Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes

<i>In vitro</i> antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

BackgroundCurrent approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity.MethodsSARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19.ResultsDaclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 μM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans.ConclusionsDaclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy

Inorganic Phosphate in the Pathogenesis of Pregnancy-Related Complications

Inorganic phosphate (Pi) is an essential nutrient that fulfills critical roles in human health. It enables skeletal ossification, supports cellular structure and organelle function, and serves key biochemical roles in energetics and molecular signaling. Pi homeostasis is modulated through diet, intestinal uptake, renal reabsorption, and mobilization of stores in bone and extracellular compartments. Disrupted Pi homeostasis is associated with phosphate wasting, mineral and bone disorders, and vascular calcification. Mechanisms of Pi homeostasis in pregnancy remain incompletely understood. The study presented herein examined biological fluid Pi characteristics over the course of gestation. Correlations with gestation age, pregnancy number, preterm birth, preeclampsia, diabetes mellitus, and placental calcification were evaluated during the last trimester. The results support that maternal urinary Pi levels increased during the third trimester of pregnancy. Reduced levels were observed with previous pregnancy. Amniotic fluid Pi levels decreased with gestation while low second trimester levels associated with preterm birth. No significant difference in urinary Pi levels was observed between preeclampsia and controls (8.50 ± 2.74 vs. 11.52 ± 2.90 mmol/L). Moreover, increased maternal urinary Pi was associated with preexisting diabetes mellitus in preeclampsia. Potential confounding factors in this study are maternal age at delivery and body mass index (BMI)—information which we do not have access to for this cohort. In conclusion, Pi levels provide clinical information regarding the pathogenesis of pregnancy-related complications, supporting that phosphate should be examined more closely and in larger populations

Dietary Patterns Characterized by High Meat Consumption Are Associated with Other Unhealthy Life Styles and Depression Symptoms

Gregório, M. J. B., Rodrigues, A. M., Eusebio, M., Sousa, R. D., Dias, S., Andre, B., ... Canhao, H. (2017). Dietary Patterns Characterized by High Meat Consumption Are Associated with Other Unhealthy Life Styles and Depression Symptoms. Frontiers in nutrition, 4, [25]. DOI: 10.3389/fnut.2017.00025We aimed to identify dietary patterns (DPs) of Portuguese adults, to assess their socioeconomic, demographic, lifestyle determinants, and to identify their impact on health.DESIGN: EpiDoC 2 study included 10,153 Portuguese adults from the EpiDoC Cohort, a population-based study. In this study, trained research assistants using computer-assisted telephone interview collected socioeconomic, demographic, dietary, lifestyles, and health information from March 2013 to July 2015. Cluster analysis was performed, based on questions regarding the number of meals, weekly frequency of soup consumption, vegetables, fruit, meat, fish, dairy products, and daily water intake. Factors associated with DP were identified through logistic regression models.RESULTS: Two DPs were identified: the "meat dietary pattern" and the "fruit & vegetables dietary pattern." After multivariable adjustment, women (OR = 0.52; p < 0.001), older adults (OR = 0.97; p < 0.001), and individuals with more years of education (OR = 0.96; p = 0.025) were less likely to adopt the "meat dietary pattern," while individuals in a situation of job insecurity/unemployment (OR = 1.49; p = 0.013), Azores island residents (OR = 1.40; p = 0.026), current smoking (OR = 1.58; p = 0.001), daily alcohol intake (OR = 1.46; p = 0.023), and physically inactive (OR = 1.86; p < 0.001) were positively and significantly associated with "meat dietary pattern." Moreover, individuals with depression symptoms (OR = 1.50; p = 0.018) and the ones who did lower number of medical appointments in the previous year (OR = 0.98; p = 0.025) were less likely to report this DP.CONCLUSION: Our results suggest that unhealthy DPs (meat DP) are part of a lifestyle behavior that includes physical inactivity, smoking habits, and alcohol consumption. Moreover, depression symptoms are also associated with unhealthy DPspublishersversionpublishe