The mediating role of Mediterranean diet on the association between Lp(a) levels and cardiovascular disease risk: A 10-year follow-up of the ATTICA study

ObjectiveΤo evaluate the combined modifying effect of dietary habits and/or features of healthy aging, on the lipoprotein-alpha [Lp(a)] and CVD risk association.Design and MethodsΤhe ATTICA is a prospective, population-based study conducted in the greater metropolitan area of Athens (Attica, Greece). During 2001–2002, 3042 CVD-free adults (men/women: 1514/1528, 18–89 years) agreed to participate. In 2011–2012, the 10-year study follow-up was performed, recording the fatal/non-fatal CVD incidence in 2020 participants (mean follow-up: 8.41 years). Various bio-clinical characteristics [including low-density lipoprotein-cholesterol (LDL-C), Lp(a)] were derived through standard procedures. Dietary habits were assessed through the MedDietScore (an index assessing adherence to the Mediterranean diet with theoretical range 0–55). A validated successful aging index (SAI), ranging from 0 to 10, was used to assess healthy aging.ResultsLp(a) levels were positively associated with 10-year CVD incidence (Hazard Ratio: 1.02, 95%CI 1.01–1.04); when MedDietScore was included in the model the observed association between Lp(a) levels and CVD risk disappeared (1.00, 95%CI 0.98–1.01), and a mediating effect of Mediterranean diet was revealed (Sobel's test p < 0.001). In the model that included both MedDietScore and SAI, the interaction effect of these two features on 10-year CVD risk was highly protective (p < 0.001), whereas the association between Lp(a) levels and CVD risk was further mediated (Sobel's test p < 0.001).ConclusionsAdherence to a healthy dietary pattern, like the Mediterranean diet seems to mediate the association between Lp(a) with CVD risk whereas a successful aging together with a healthy diet seems to further explain the previously mentioned association.     

New mechanisms of disease and parasite-host interactions

An unconventional interaction between a patient and parasites was recently reported, in which parasitic cells invaded host’s tissues, establishing several tumors. This finding raises various intriguing hypotheses on unpredicted forms of interplay between a patient and infecting parasites.Here we present four unusual hypothetical host-parasite scenarios with intriguing medical consequences. Relatively simple experimental designs are described in order to evaluate such hypotheses.The first one refers to the possibility of metabolic disorders in parasites intoxicating the host. The second one is on possibility of patients with inborn errors of metabolism (IEM) being more resistant to parasites (due to accumulation of toxic compounds in the bloodstream). The third one refers to a mirrored scenario: development of tumors in parasites due to ingestion of host’s circulating cancer cells. The last one describes a complex relationship between parasites accumulating a metabolite and supplying it to a patient with an IEM.     

The role of epigenetic therapies in colorectal cancer

Although developments in the diagnosis and therapy of colorectal cancer (CRC) have been made in the last decade, much work remains to be done as it remains the second leading cause of cancer death. It is now well established that epigenetic events, together with genetic alterations, are key events in initiation and progression of CRC. Epigenetics refers to heritable alterations in gene expression that do not involve changes in the DNA sequence. These alterations include DNA methylation, histone alterations, chromatin remodelers, and noncoding RNAs. In CRC, aberrations in epigenome may also involve in the development of drug resistance to conventional drugs such as 5-fluorouracil, oxaliplatin, and irinotecan. Thus, it has been suggested that combined therapies with epigenetic agents may reverse drug resistance. In this regard, DNA methyltransferase inhibitors and histone deacetylase inhibitors have been extensively investigated in CRC. The aim of this review is to provide a brief overview of the preclinical data that represent a proof of principle for the employment of epigenetic agents in CRC with a focus on the advantages of combinatorial therapy over single-drug treatment. We will also critically discuss the results and limitations of initial clinical experiences of epigenetic-based therapy in CRC and summarize ongoing clinical trials. Nevertheless, since recent translational research suggest that epigenetic modulators play a key role in augmenting immunogenicity of the tumor microenvironment and in restoring immune recognition, we will also highlight the recent developments of combinations strategies of immunotherapies and epigenetic therapies in CRC, summarizing preclinical, and clinical data to signify this evolving and promising field for CRC treatment.     

Compliance with a law to reduce alcoholic beverage sales and service in Zacatecas,Mexico

BackgroundResearch on the effects of restricting bar opening hours and alcohol sales in middle-income countries is very limited. We assessed compliance with and possible effects of a law enacted in Zacatecas, Mexico on December 30, 2017 and implemented in 2018 and 2019 that established a 2 AM bar closing time and 10 PM cut-off for alcohol sales by off-premises stores.MethodsMonthly observations of bars and off-premises stores and alcohol mystery shopping visits from 2018 to early 2020 were conducted to assess compliance with the law. Breath tests were conducted in 2018 and 2019 with samples of pedestrians in the nighttime entertainment districts of Zacatecas and a comparison city (Aguascalientes). Surveys of bar owners/managers and staff, emergency medical personnel (EMP), and police officers were conducted in Zacatecas in 2018 and 2019 to assess awareness and support of the law and possible effects of the law on alcohol-related problems such as violence and injuries.ResultsMonthly observations indicated that a substantial percentage of bars and off-premises package stores did not comply with the law. Pedestrian breath tests in 2018 and 2019 indicated significant reductions in blood alcohol concentration and heavy drinking among pedestrians in Zacatecas from 11 PM to 2 AM compared to Aguascalientes, but not after 2 AM. Surveys of bar owners/managers indicated that most were aware and supportive of the law. EMP surveys indicated reductions in incidents of physical fighting and drunk or injured customers during the annual September fair in Zacatecas.ConclusionsThis study suggests that restricting bar opening hours and alcohol sales may not result in full compliance by bars and off-premises stores, but may help to reduce excessive alcohol use and related harms in a middle-income country. A more rigorous evaluation with pre-intervention data is needed, however, to fully address this latter question.     

Clinical outcomes of catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy: Insights from the Johns Hopkins ARVC Program

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