Sudden Cardiac Death-Etiology, Risk Factors and Demographic Characteristics: An Extensive Study of 1618 Forensic Autopsies.

BACKGROUND: Sudden cardiac death (SCD) is a major public health concern worldwide, affecting all age and social groups. METHODS: In this retrospective study, of the 8265 autopsies performed in the Institute of Legal Medicine, 1618 cases of SCD were included. The aim of this study is to identify demographic characteristics, etiological factors, epidemiological characteristics and risk factors that lead to SCD. RESULTS: The highest incidence of SCD was in age group 40-69 years (65.0%), 71.6% of this age group being men. Of the total number, 32.1% (520) occurred in the emergency room. The most common cause of sudden death is represented by coronary atherosclerotic disease, reported in 89.8% (1453) of cases, tricoronary lesions being found in 60% (870) of cases. Etiological factors of SCD encountered during autopsies were acute myocardial infarction in 13.9% (225), dilated cardiomyopathy 43.9% (710), cardiac hypertrophy 579 (36.07%), pericarditis 1.9% (30), myocarditis 1.73% (28) and adipositas cordis 5% (81). Along with epicardial fat and BMI, alcohol consumption was recorded in 17.9% (290), this being a potential trigger. CONCLUSIONS: Based on forensic autopsy and histological findings, a wide variety of factors are involved in the etiopathogenesis of SCD, some of which can be eliminated through preventive measures implemented early.

Heart Transplant Rejection: From the Endomyocardial Biopsy to Gene Expression Profiling.

Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the "gold standard" in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required.

Enhancing phenolic and lipid compound production in oat bran via acid pretreatment and solid-state fermentation with Aspergillus niger.

Oat (Avena sativa) processing generates a large amount of by-products, especially oat bran. These by-products are excellent sources of bioactive compounds such as polyphenols and essential fatty acids. Therefore, enhancing the extraction of these bioactive substances and incorporating them into the human diet is critical. This study investigates the effect of acid pretreatment on the solid-state fermentation of oat bran with Aspergillus niger, with an emphasis on the bioaccessibility of phenolic acids and lipid profile. The results showed a considerable increase in reducing sugars following acid pretreatment. On the sixth day, there was a notable increase in the total phenolic content, reaching 58.114 ± 0.09 mg GAE/g DW, and the vanillic acid level significantly rose to 77.419 ± 0.27 µg/g DW. The lipid profile study revealed changes ranging from 4.66 % in the control to 7.33 % on the sixth day of SSF. Aside from biochemical alterations, antioxidant activity measurement using the DPPH technique demonstrated the maximum scavenging activity on day 4 (83.33 %). This study highlights acid pretreatment's role in enhancing bioactive compound accessibility in solid-state fermentation and its importance for functional food development.

Targeting the sympathetic nervous system with the selective imidazoline receptor agonist moxonidine for the management of hypertension: an international position statement.

Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically. Selective imidazoline receptor agonists (SIRAs) effectively reduce BP with a favorable side effect profile compared with older centrally acting antihypertensive drugs. Hard outcome data in hypertension, such as prevention of stroke, heart and kidney diseases, are not available with SIRAs. However, in direct comparisons, SIRAs were as effective as angiotensin-converting enzyme inhibitors, ß-blockers, calcium channel blockers, and diuretics in lowering BP. Other beneficial effects on metabolic parameters in hypertensive patients with concomitant overweight and obesity have been documented with SIRAs. Here we review the existing evidence on the safety and efficacy of moxonidine, a widely available SIRA, compared with common antihypertensive agents and provide a consensus position statement based on inputs from 12 experts from Europe and Australia on SIRAs in hypertension management.

Recent advances and insights into the bioactive properties and applications of Rosa canina L. and its by-products.

Rosa canina L., commonly known as rosehip, is of notable scientific interest for its applications in nutrition, cosmetics, and pharmaceuticals. This review article highlights its health-promoting properties, including antioxidant, anti-inflammatory, hepatoprotective, and anticarcinogenic effects, attributed to its rich content of phenolic acids, carotenoids, tocopherols, and vitamins. With growing interest in sustainable practices, rosehip by-products are increasingly valorized. For instance, cold-pressed rosehip seed oil is a valuable source of polyunsaturated fatty acids, while incorporating rosehip pomace into snacks enhances their nutritional profile, positioning them as potential functional foods and dietary supplements. This article aims to provide a comprehensive overview of advancements in utilizing rosehip and its by-products, emphasizing their role in enriching food and pharmaceutical products with nutritional and functional bioactivities.

Genome-wide CRISPR screens identify the YAP/TEAD axis as a driver of persister cells in EGFR mutant lung cancer.

Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These 'persister' cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients.

Current strategies for the management of valuable compounds from hops waste for a circular economy.

World beer production generates large volumes of waste discharged with every brew. Recently, new methods of reducing and reusing hops waste: hot trub (HT), and brewer-spent hops (BSH) are being exploited to improve the circular economy processes. This review outlines the current achievements in the management of hops waste. Following an in-depth review of various scientific publications, current strategies are discussed as a sustainable alternative to food waste exploitation and an inexpensive source of valuable compounds. Moreover, key aspects concerning the nutritional value of hops waste and the potential to enhance the functional properties of food and beverages are highlighted. Due to their nutritional composition, hops residues may be used as prospective sources of added-value co-products or additives for food enrichment, especially for products rich in fat, or as a new source of vegetable protein.

Blackthorn-A Valuable Source of Phenolic Antioxidants with Potential Health Benefits.

Prunus spinosa L. fruit, commonly known as blackthorn, is a rich source of bioactive compounds, including flavonoids, anthocyanins, phenolic acids, vitamins, minerals, and organic acids, which exhibit significant antioxidant and antibacterial properties. Notably, flavonoids such as catechin, epicatechin, and rutin have been reported to have protective effects against diabetes, while other flavonoids, including myricetin, quercetin, and kaempferol, exhibit antihypertensive activity. Solvent extraction methods are widely used for the extraction of phenolic compounds from plant sources, owing to their simplicity, efficacy, and broad applicability. Furthermore, modern extraction techniques, such as microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), have been employed to extract polyphenols from Prunus spinosa L. fruits. This review aims to provide a comprehensive analysis of the biologically active compounds found in blackthorn fruits, emphasizing their direct physiological effects on the human body. Additionally, the manuscript highlights the potential applications of blackthorn fruits in various industries, including the food, cosmetics, pharmaceutical, and functional product sectors.

Doxorubicin-induced acute cardiotoxicity is associated with increased oxidative stress, autophagy, and inflammation in a murine model.

Drug-induced cardiotoxicity is a life-threatening side effect of doxorubicin (DOX) treatment that impacts patient prognosis and survival. In the majority of cases, the acute clinical form often remains asymptomatic, with few patients presenting rather nonspecific electrocardiographic abnormalities. While chronic toxicity has been more widely studied, the alterations appearing in acute cardiotoxicity are much less investigated. Thus, our in vivo study aimed to evaluate the process of DOX-induced acute myocardial toxicity by investigating oxidative stress and autophagy markers as mechanisms of myocardial toxicity in correlation with echocardiography and electrocardiography findings. Our results show that both autophagy and oxidative homeostasis were disrupted as soon as 7 days after DOX treatment, alterations that occurred even before the significant increase of NT-proBNP, a clinical marker for cardiac suffering. Moreover, we found a large number of alterations in the electrocardiography and echocardiography of treated rats. These findings suggest that DOX-induced myocardial toxicity started early after treatment initiation, possibly marking the initial phase of the unfolding process of cardiac damage. Further studies are required to completely decipher the mechanisms of DOX-induced cardiotoxicity.

Integrated Technology for Cereal Bran Valorization: Perspectives for a Sustainable Industrial Approach.

Current research focuses on improving the bioaccessibility of functional components bound to cereal bran cell walls. The main bioactive components in cereal bran that have major biological activities include phenolic acids, biopeptides, dietary fiber, and novel carbohydrates. Because of the bound form in which these bioactive compounds exist in the bran matrix, their bioaccessibility is limited. This paper aims to comprehensively analyze the functionality of an integrated technology comprising pretreatment techniques applied to bran substrate followed by fermentation bioprocesses to improve the bioaccessibility and bioavailability of the functional components. The integrated technology of specific physical, chemical, and biological pretreatments coupled with fermentation strategies applied to cereal bran previously-pretreated substrate provide a theoretical basis for the high-value utilization of cereal bran and the development of related functional foods and drugs.

Protective Effects of Wine Polyphenols on Oxidative Stress and Hepatotoxicity Induced by Acrylamide in Rats.

In recent years, it has been increasingly suggested that the consumption of natural polyphenols, in moderate amounts, is beneficial for health. The aim of this study was to investigate the efficacy of a red wine (the administered dose of 7 mL/kg/day being equivalent to ~16.5 mg/kg/day total polyphenols) compared to a white wine (the administered dose of 7 mL/kg/day being equivalent to ~1.7 mg/kg/day total polyphenols), on the prevention of acrylamide-induced subacute hepatic injury and oxidative stress in Wistar rats. Hepatic damage due to acrylamide intoxication (the administered dose being 250 µg/kg body weight, for 28 days, by intragastric gavage) was assessed by employing biochemical parameters (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and by histopathological studies. Markers of oxidative damage were measured in terms of plasma malondialdehyde (MDA), hepatic Thiobarbituric Acid Reactive Substances (TBARS) and glutathione (GSH) levels, and liver antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) activities. Regarding hepatic enzyme activities, treatment with red wine significantly decreased the AST values (p < 0.05), while for the ALT values only a normalization tendency was observed. Treatment with red wine and white wine, respectively, significantly prevented the increase in MDA and TBARS levels (p < 0.05), as well as the depletion of GSH (p < 0.05). Red wine treatment normalized the activities of the antioxidant enzymes CAT and SOD in rats intoxicated with acrylamide, while supplementing the diet with white wine did not produce significant differences in the antioxidant enzyme activities. Histopathological findings revealed a moderate protective effect of red wine after four weeks of daily consumption. Our findings provide evidence that red wine, having a higher phenolic content than white wine, has a significant protective effect on oxidative stress and liver injury induced by acrylamide in rats, through its antioxidative activity.

Anthocyanins from Agro-Industrial Food Waste: Geographical Approach and Methods of Recovery-A Review.

Drastic growth in the amount of global food waste produced is observed every year, not only due to incessant population growth but also economic growth, lifestyle, and diet changes. As a result of their increasing health awareness, people are focusing more on healthy diets rich in fruits and vegetables. Thus, following worldwide fruit and vegetable consumption and their processing in various industries (juice, jams, wines, preserves), significant quantities of agro-industrial waste are produced (pomace, peels, seeds) that still contain high concentrations of bioactive compounds. Among bioactive compounds, anthocyanins have an important place, with their multiple beneficial effects on health; therefore, their extraction and recovery from food waste have become a topic of interest in recent years. Accordingly, this review aims to summarize the primary sources of anthocyanins from food waste and the novel eco-friendly extraction methods, such as pulsed electric field extraction, enzyme-assisted extraction, supercritical fluid extraction, pressurized liquid extraction, microwave-assisted extraction, and ultrasonic-assisted extraction. The advantages and disadvantages of these techniques will also be covered to encourage future studies and opportunities focusing on improving these extraction techniques.

Physico-Chemical, Nutritional, and Sensory Evaluation of Two New Commercial Tomato Hybrids and Their Parental Lines.

Tomato (Solanum lycopersicum) is the globally most consumed vegetable. The objective of this research was to analyze physico-chemical, nutritional and sensorial components (taste and flavor) in two new commercial hybrids (AS 300 F1 and AS 400 F1) and their four F7 parental lines. Two widely grown F1 hybrids (Precos F1 and Addalyn F1) were used as controls. The results obtained for carbohydrates (HPLC-RID) indicated that the highest values (27.82 mg/g) were recorded in the paternal line AS 10 of the new hybrid AS 400 F1. The highest values of total organic acids (HPLC-VWD) were recorded in Addalyn F1 (5.06 m/g), while the highest value of phenolic compounds (HPLC-DAD-ESI⁺) were identified in the maternal line AS 09 of the hybrid AS 400 F1 (96.3 µg/g). Intrinsic sensory values were analyzed by male and female tasters of different ages using a hedonic scale. The tasters' perception revealed obvious taste differences between tomato genotypes. The study allowed determining genetic parameters of interest (heterosis and heterobeltosis) for the new hybrids, as well as a detailed characterization of the chemical composition and organoleptic quality of the parental breeding lines and their hybrids, which is useful in tomato breeding.

Reintegration of Brewers Spent Grains in the Food Chain: Nutritional, Functional and Sensorial Aspects.

Nowadays, the pandemic situation has encouraged the idea of sustainable healthy foods leading to new trends in food consumption. Brewers spent grain (BSG) represents a potential functional food rich in fiber, protein, lipids, mineral and phenols that needs to be further exploited. In this vein, five different BSG types were collected from local breweries and valorized in cookies manufacturing. Thus, proximate composition (protein, minerals, lipids, ash, crude fiber and carbohydrates) was analyzed using AACC (American Association of Cereal Chemists) methods, DPPH (2,2-Diphenyl-1-picrylhydrazyl), and Folin Ciocalteu methods were used to determined antioxidant activity and total phenols, while minerals and aroma volatile compounds were performed using inductively coupled plasma optical emission spectrometry (ICP-OES) and ITEX/GC-MS (in tube extraction gas chromatography-mass spectrometry) respectively. Color and physical characteristics, together with sensorial analysis, were also evaluated. The results highlighted a significant difference between BSG samples, mainly from the total phenols, antioxidant activity and aroma volatile compounds point of view. BSG volatiles compounds from the aldehydes group such as 2-methyl-propanal, 3-methyl-butanal and 2-methyl-butanal were identified also in the final baked goods, leading to a pleasant and appreciated consumers' taste and aroma. Furthermore, cookies sensorial analysis emphasized that the sample manufactured with BSG from light and dark malt mixture was more appreciated by consumers, attaining the highest hedonic scores.

Case Report: Acute Splenic Artery Thrombosis in a COVID 19, Postpartum Patient.

The incidence of thromboembolic disease is reported to be high in SARS-CoV2 disease. Pregnancy, an already physiologically hypercoagulable state, associated to COVID 19, generates even more concern regarding the potentially increased risk of thrombotic events. The exact incidence of such complications is yet unknown, but there is data suggesting that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Since the outbreak of the COVID 19 pandemics, the most common described thrombotic events associated with SARS-COV2 infection have been venous thromboembolism and disseminated intravascular coagulation, while arterial thrombotic events are less commonly described. Splenic infarction is a rare disorder that can be secondary to a hypercoagulable state. There are only few cases of splenic infraction described, but none with splenic artery thrombosis, in a post-partum patient, on therapeutic anticoagulation regimen. We present the case of a 31-year-old Caucasian, 26 weeks pregnant woman, with no prior medical history, admitted to the hospital with a severe form of COVID 19 pneumonia and who, during the course of the disease, developed a massive splenic infarction with splenic artery thrombosis.

Arguments for Using Direct Oral Anticoagulants in Cancer-Related Venous Thromboembolism.

(1) Background: Patients with cancer with a hypercoagulable state present an increased incidence of venous thromboembolism (VTE). Neoplastic patients with concurrent VTE undergoing anticoagulant treatment face a series of issues. (2) The aim of the present paper is to systematically summarize current VTE management in patients with neoplasia and to review the current clinical evidence from meta-analyses of randomized controlled trials and guidelines regarding the administration of direct oral anticoagulants (DOACs) for cancer-associated VTE. (3) Search Strategy: We performed a review on meta-analyses of randomized controlled trials and guidelines in favor of the administration of DOACs in patients with cancer-associated VTE published in the last 6 years in the Medline (PubMed) and Embase databases. (4) Results: 21 meta-analyses, 14 randomized controlled studies comparing DOACs to VKAs and LMWH, and 7 national and international guidelines were identified. We identified five studies that show the antineoplastic effect of DOAC on experimental models. (5) Conclusions: DOACs can be seen as the first choice for VTE treatment in neoplastic patients who have a low risk of bleeding, who do not have severe renal impairment, and who are not undergoing treatments that could interact with DOAC's mechanism of action.

Novel Delivery Systems of Polyphenols and Their Potential Health Benefits.

Liposome-based delivery systems have been studied and used more frequently in recent years due to their advantages, such as low toxicity, specificity, and the ability to protect the encapsulated substance from environmental factors, which could otherwise degrade the active compound and reduce its effectiveness. Given these benefits, many researchers have encapsulated polyphenols in liposomes, thus increasing their bioavailability and stability. Similarly, polyphenols encapsulated in liposomes are known to produce more substantial effects on targeted cells than unencapsulated polyphenols, while having minimal cytotoxicity in healthy cells. Although polyphenols play a role in preventing many types of disease and generally have beneficial effects on health, we solely focused on their chemopreventive effects on cancer through liposomes in this review. Our goal was to summarize the applicability and efficacy of liposomes encapsulated with different classes of polyphenols on several types of cancer, thus opening the opportunity for future studies based on these drug delivery systems.

Immune Checkpoint Inhibitors and the Heart.

Immune checkpoint inhibitors (ICIs) represent a break-through treatment for a large number of cancer types. This treatment is increasingly being recommended. ICIs are prescribed for primary tumours and for metastases, adjuvant/neo-adjuvant therapy. Thus, there is an increased need for expertise in the field, including the ways of response and toxicities related to them. ICIs become toxic because of the removal of self-tolerance, which in turn induces autoimmune processes that affect every organ. However, when relating to the heart, it has been noticed to be leading to acute heart failure and even death caused by various mechanisms, such as: myocarditis, pericarditis, arrhythmia, and Takotsubo cardiomyopathy. This review aims to address the above issues by focusing on the latest findings on the topic, by adding some insights on the mechanism of action of ICIs with a special focus on the myocardial tissue, by providing information on clinical manifestations, diagnosis and (wherever possible) treatment of the cardiotoxic events related to this therapy. The information is expanding and in many cases, the articles we found refer mainly to case-presentations and studies conducted on small populations. However, we consider that it is worthwhile to raise awareness of this new treatment, especially since it is widely now and it provides a significant increase in the survival rate in patients who receive it.

Modern markers for evaluating bone disease in multiple myeloma (Review).

Multiple myeloma (MM) is a bone marrow neoplasia with increasing incidence compared to previous years. Although new therapeutic molecules have been introduced, it remains an incurable disease with severe repercussions to patients. For many patients, bone disease represents a severe problem often causing pain, pathological bone fractures, and spinal cord compression, which affects the quality of life. This article analyzes the main markers of bone destruction in MM as well as risk factors for severe bone damage. Bone complications have a negative impact on the quality of life of patients with MM, along with other associated complications (renal failure, hypogammaglobulinemia, osteolytic bone disease, hypercalcemia, anemia). The markers of bone destruction described in this article include: interleukin (IL)-6, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX, CTX), human bone sialoprotein (BSP) and dickkopf-1 secreted glycoprotein (DKK1). The future practical applicability of this literature review would be the large-scale determination of markers of bone destruction that correlate with the negative evolution to complications of bone disease or the implications that these markers have in regards to treatment.

Macrophage activation syndrome: A diagnostic challenge (Review).

Macrophage activation syndrome (MAS) represents an acute and severe inflammatory syndrome, idiopathic (primary) or secondary to infections, rheumatic diseases, malignancies, or drugs. MAS is underdiagnosed, being confused with sepsis, adverse effects of anti-arthritic drugs or exacerbated symptoms of evolving rheumatologic or infectious diseases. Because of the late diagnosis, most patients do not benefit from effective therapy, leading to death. Elucidation of valid early diagnostic criteria of MAS would be a particularly important step in reducing the mortality due to this pathology. Thus, the purpose of this review based on 40 studies centered on the diagnostic criteria of MAS. We detailed the main diagnostic criteria and the few diagnostic scores or sets of criteria that have been recently published. The criteria most frequently encountered in the literature include: Fever, hepatosplenomegaly, hyperferritinemia, hepatopathy, coagulopathy, thrombocytopenia, hypertriglyceridemia, decrease in erythrocyte sedimentation rate and bone marrow hemophagocytosis. The most elaborate diagnostic score will result following an ongoing international project and consensus, the Delphi International Survey.