Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants.

Sporadic thoracic aortic aneurysms (TAA) and dissections are one of the major causes of morbidity and mortality worldwide, especially in those older than 65 years. The presentation of TAA is varied and often silent. Thus, sporadic TAA detection is often fortuitous, with identification occurring during a routine physical examination or during an unrelated medical evaluation. Once suspected, confirmation by imaging clinical approaches is needed to allow the choose of the unique treatments for TAA, namely the surgery procedures, including elective surgery or endovascular repair before the onset of catastrophic and fatal complications, such as dissection or rupture. At present, there are no biomarkers available to identify TAAs before visible symptoms. However, recent progresses in understanding of molecular and cellular mechanisms involved in the patho-physiology of sporadic TAA are suggesting different molecular pathways and their genetic variants as potential biomarkers, which might be applied into TAA clinical practice in the near future. Here, we report literature evidence on some disease pathways and their genetic variants on TAA susceptibility and compliances, and their translation as promising TAA preventive and prognostic biomarkers and targets for new personalized therapeutic treatments

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

: Aorta diseases, such as ascending aorta aneurysm (AsAA), are complex pathologies, currently defined as inflammatory diseases with a strong genetic susceptibility. They are difficult to manage, being insidious and silent pathologies whose diagnosis is based only on imaging data. No diagnostic and prognostic biomarkers or markers of outcome have been known until now. Thus, their identification is imperative. Certainly, a deep understanding of the mechanisms and pathways involved in their pathogenesis might help in such research. Recently, the key role of oxidative stress (OS) on the pathophysiology of aorta disease has emerged. Here, we describe and discuss these aspects by revealing some OS pathways as potential biomarkers, their underlying limitations, and potential solutions and approaches, as well as some potential treatments

Toll-like receptor-4 signaling pathway in aorta aging and diseases: "its double nature"

Recent advances in the field of innate immunity have revealed a complex role of innate immune signaling pathways in both tissue homeostasis and disease. Among them, the Toll-like receptor 4 (TLR-4) pathways has been linked to various pathophysiological conditions, such as cardiovascular diseases (CVDs). This has been interrogated by developing multiple laboratory tools that have shown in animal models and clinical conditions, the involvement of the TLR-4 signaling pathway in the pathophysiology of different CVDs, such as atherosclerosis, ischemic heart disease, heart failure, ischemia-reperfusion injury and aorta aneurysm. Among these, aorta aneurysm, a very complex pathological condition with uncertain etiology and fatal complications (i.e. dissection and rupture), has been associated with the occurrence of high risk cardiovascular conditions, including thrombosis and embolism. In this review, we discuss the possible role of TLR-4signaling pathway in the development of aorta aneurysm, considering the emerging evidence from ongoing investigations. Our message is that emphasizing the role of TLR-4signaling pathway in aorta aneurysm may serve as a starting point for future studies, leading to a better understanding of the pathophysiological basis and perhaps the effective treatment of this difficult human disease

The impact of COVID-19 and associated policy responses on global food security

We analyze the impact of the COVID-19 pandemic and associated policy responses on the global economy and food security in 80 low- and middle-income countries. We use a global economy-wide model with detailed disaggregation of agricultural and food sectors and develop a business-as-usual baseline for 2020 and 2021 called “But-for-COVID” (BfC). We then shock the model with aggregate income shocks derived from the IMF World Economic Outlook for 2020 and 2021. We impose total-factor productivity losses in key sectors as well as consumption decreases induced by social distancing. The resulting shocks in prices and incomes from the CGE model simulations are fed into the USDAERS International Food Security Assessment (IFSA) model to derive the impact of the pandemic on food security in these 80 countries. The main effect of the pandemic was to exacerbate the existing declining trend in food security. Food insecurity increases considerably in countries in Asia through income shocks rather than prices effects.We also review trade policies that were put in place to restrict imports and exports of food, and we evaluate their potential for further disruption of markets focusing on the food-security implications

Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives

Advanced knowledge in the field of stem cell biology and their ability to provide a cue for counteracting several diseases are leading numerous researchers to focus their attention on \u201cregenerative medicine\u201d as possible solutions for cardiovascular diseases (CVDs). However, the lack of consistent evidence in this arena has hampered the clinical application. The same condition affects the research on endothelial progenitor cells (EPCs), creating more confusion than comprehension. In this review, this aspect is discussed with particular emphasis. In particular, we describe biology and physiology of EPCs, outline their clinical relevance as both new predictive, diagnostic, and prognostic CVD biomarkers and therapeutic agents, discuss advantages, disadvantages, and conflicting data about their use as possible solutions for vascular impairment and clinical applications, and finally underline a very crucial aspect of EPCs \u201ccharacterization and definition,\u201d which seems to be the real cause of large heterogeneity existing in literature data on this topic

Stem cells and new intervention measures as emerging therapy in cardiac surgery

Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. Several inflammatory pathway are involved in vascular ageing. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. In this review we analyzed the role of stem cells and new intervention measures as emerging drugs for vascular aging

Changes of Inflammatory Mediators in Obese Patients After Laparoscopic Cholecystectomy

Background Obesity is associated with the impairment of immunological functions. The aim of this study was to analyze some inflammatory mediators in obese subjects who underwent laparoscopic cholecystectomy. Methods Seventeen consecutive female patients with a BMI ranging from 35 to 45 kg/m2 (obese) and 17 consecutive female patients with BMI ranging from 20 to 25 kg/m2 (nonobese) were included in the study. All patients were affected by symptomatic gallbladder stone disease and underwent laparoscopic cholecystectomy. Changes in levels of leukocytes, neutrophils, IL-6, IL-10, leptin, and adiponectin were evaluated. Results We observed a significant increase in leukocyte and neutrophil levels in the obese subjects compared to the nonobese subjects. The serum levels of leptin and IL-6 were higher in the postoperative period (compared to the baseline values in both groups), and always higher in the obese. Both adiponectin and IL-10 increased in the postoperative period in nonobese subjects and was always higher than in the obese. Conclusions Obese patients have a stronger acute inflammatory response than do nonobese subjects in reaction to surgical stress

A GAMS/MPSGE implementation of the PET model

This paper describes a version of the Population-Economy-Technology (PET) model implemented in the GAMS/MPSGE programming language. The implementation of the model is comparable with the original fortran version of iPETS over a number of test cases. While a number of possible configurations exist for both model types, we demonstrate that there is a configuration that makes both implementations behave very similarly and the remaining difference can be traced to different implementations of dynamic agent behavior. This paper also serves as a methodological blueprint for model translation across different programming languages

Pro-inflammatory genetic markers of atherosclerosis

Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine