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Maturity-onset diabetes of the young (MODY) is a spectrum of clinically heterogenous forms of monogenic diabetes mellitus characterized by autosomal dominant inheritance, onset at a young age, and absence of pancreatic islets autoimmunity. This rare form of hyperglycemia, with clinical features overlapping with type 1 and type 2 diabetes mellitus, has 14 subtypes with differences in prevalence and complications occurrence which tailor therapeutic approach. MODY phenotypes differ based on the gene involved, gene penetrance and expressivity. While MODY 2 rarely leads to diabetic complications and is easily managed with lifestyle interventions alone, more severe subtypes, such as MODY 1, 3, and 6, require an individualized treatment approach to maintain a patient's quality of life and prevention of complications. This review summarizes current evidence on the presentation, diagnosis, and management of MODY, an example of a genetic cause of hyperglycemia that calls for a precision medicine approach. [ABSTRACT FROM AUTHOR]

Over the past 70 years, there has been extensive research focused on preventing chemotherapy-related cardiovascular complications. However, the current state of cardio-oncology research has raised more questions than answers. Experimental studies often present data that are difficult to compare and, at times, contradictory. One notable limitation in translating experimental findings to clinical practice is the reliance on models that administer only one chemotherapeutic drug to experimental animals, despite the common use of multidrug cancer treatments in real clinical settings. This article aims to discuss our own experience in modeling an experimental rat model of cardiomyopathy induced by the administration of two chemotherapeutic drugs, doxorubicin (adriamycin) and cyclophosphamide (AC mode of chemotherapy) – Avagimyan A., et al model, along with a subsequent review of morphological changes based on our personal archive. 1. AC - Doxorubicin (Adriamycin) + Cyclophosphamide 2. CaMKII - Calcium/Calmodulin-dependent protein kinase II 3. Circ-INSR - Circulating Insulin Receptor 4. CVDs - Cardiovascular Diseases 5. CP – Cardioprotector 6. GLUT - Glucose Transporter 7. HF – Heart Failure 8. ICAM - Intercellular Adhesion Molecule 9. IL - Interleukin 10. IκBα - Inhibitor of kappa B alpha 11. MMP - Matrix Metalloproteinase 12. MyD88 - Myeloid Differentiation Primary Response 88 13. NADP+ - Nicotinamide Adenine Dinucleotide Phosphate 14. NADPH - Nicotinamide Adenine Dinucleotide Phosphate Hydrogen 15. NF-κB - Nuclear Factor kappa B 16. NLRP3 - Nucleotide-binding domain, leucine-rich repeat containing protein 3 17. NOS - Nitric Oxide Synthase 18. Nrf2 - Nuclear factor erythroid 2-related factor 2 19. NT-proBNP - N-terminal pro-B-type natriuretic peptide 20. PLN - Phospholamban 21. RyR - Ryanodine receptor 22. SERCA2a - Sarco/Endoplasmic Reticulum Calcium ATPase 2a 23. Sirt3 - Sirtuin 3 24. SMAD3 - Mothers Against Decapentaplegic Homolog 3 25. TGF-β1 - Transforming Growth Factor beta 1 26. TLR4 - Toll-like receptor 4 27. TNF-α - Tumor Necrosis Factor alpha 28. VCAM - Vascular Cell Adhesion Molecule [ABSTRACT FROM AUTHOR]

• PCOS impacts approximatly 10% of reproductive-aged women, of whom about up to 50% are affected by obesity. • Long-term consequences of PCOS are mostly correlated with excessive body weight. • GLP-1 RAs offer a new unique opportunity to address various comorbid conditions and phenotypic presentations of PCOS. • GLP-1 RA should be integrated into the established management of women with PCOS and obesity. [ABSTRACT FROM AUTHOR]

The present systematic review aimed to synthesize available data from recently published randomized trials (RCTs) investigating the efficacy and safety of the novel, orally administered, small-molecule glucagon-like peptide 1 receptor agonists (GLP-1RAs) orforglipron and danuglipron for the treatment of type 2 diabetes mellitus (T2DM), obesity or both. Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until August 16, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with random effects meta-analysis. Totally, 1037 patients among seven RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB2). Novel GLP-1RAs led to significant reduction in HbA1c in patients with T2DM compared to controls (MD = −1.03 %; 95 % CI = [−1.29, −0.77]; P < 0.001). A significantly greater weight reduction was also noted both in patients with T2DM or obesity compared to controls (MD = −3.26 kg; 95 % CI = [−4.79, −1.72]; P < 0.001 and MD = −7.52 kg; 95 % CI = [−14.63, −0.41]; P = 0.038, respectively; P for subgroup differences = 0.25). Regarding safety, novel GLP-1RAs showed a neutral effect on the odds of severe hypoglycemia or serious adverse events (OR = 0.34; 95 % CI = [0.09, 1.31]; P = 0.11 and OR = 0.95; 95 % CI = [0.39, 2.34]; P = 0.91, respectively) and significantly higher odds of gastrointestinal, treatment-emergent adverse events (OR = 2.57; 95 % CI = [1.49, 4.42]; P < 0.001) and adverse events leading to discontinuation (OR = 2.89; 95 % CI = [1.22, 6.87]; P = 0.016). Preliminary evidence supports that orforglipron and danuglipron are efficient in glycemic control and weight reduction in T2DM, obesity or both. More longitudinal research is warranted in order to provide deeper insights into their efficacy, safety and tolerability before their potential incorporation in the pharmacological arsenal against T2DM or obesity. What is the key question? • Are the novel, GLP-1RAs orforglipron and danuglipron effective and safe in patients with T2DM and/or obesity? What are the new findings? • The novel GLP-1RAs demonstrated a significant reduction in HbA1c in patients with T2DM compared to controls. • A significantly greater weight reduction was also noted both in patients with T2DM and obesity compared to controls. How might this impact on clinical practice in the foreseeable future? • Orforglipron and danuglipron are effective for glycemic control and weight reduction in patients with T2DM, obesity or both. [ABSTRACT FROM AUTHOR]

Diabetes represents a pro-thrombotic condition. The primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding. We enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA 1c), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding. We did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients. DOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients. • Diabetes represents a pro-thrombotic condition. • There is need for a correct anticoagulant approach in this setting of patients. • Direct oral anticoagulants seem to be metabolically favourable in diabetic patients. • Direct oral anticoagulants seem better than Vitamin K Antagonist in diabetic patients for bleeding incidence. [ABSTRACT FROM AUTHOR]

The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment. Some evidence indicates a high rate of memory loss, while other evidence suggests a benefit in dementia prevention. This debate should not discourage appropriate statin and other lipid-lowering drug administration. However, prescribers should be aware of such potential drug-related side effects. Prospective controlled studies comparing the short- and long-term effects of different statins on cognitive function are warranted. The effects of intensive LDL-C lowering on neurocognition might be attributed to an off-target effect. It is also possible that pre-existing pathology and vascular risk may already be present outweighing any effect related to lipids. Gender, genetic, LDL-C-related genotypes and aging-related changes should also be considered. Some data indicate that carriers of apolipoprotein E (apoE) ε-4 allele, with low levels of apoA1 and high-density lipoprotein cholesterol have a distinct plasma lipid profile and may be more susceptible to neurocognitive dysfunction. Future research on lipid-lowering drugs and cognition is needed; careful study design and analysis will be critical. [ABSTRACT FROM AUTHOR]

Background: Statins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds.Purpose: This narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans.Main Evidence: This natural supplement may lead to effective lipid-lowering treatment. Its lipid-lowering activity is attributed to different flavonoids. However, the exact mechanisms involved remain unclear.Conclusion: It is expected that ongoing and future studies will confirm the benefit of bergamot in dyslipidemic and other cardiometabolic disorders, potentially leading to reduced overall CV risk. [ABSTRACT FROM AUTHOR]

Background: Currently a chronic inflammation is considered to be the one of the most important reasons of the atherosclerosis progression. A huge amount of researches over the past few decades are devoted to study the various mechanisms of inflammation in the development of atherosclerotic lesions.Purpose: To review current capabilities of anti-inflammatory therapy for the prevention and treatment of atherosclerosis and its clinical manifestations.Methods: Appropriate articles on inflammatory cytokines in atherosclerosis and anti-inflammatory prevention of atherosclerosis were searched in PubMed Database from their respective inceptions until October 2015.Sections: "The role of inflammatory cytokines in the development of atherosclerotic lesions" describes available data on the possible inflammatory mechanisms of the atherogenesis with a special attention to the role of cytokines. "Modern experience of anti-inflammatory therapy for the treatment of atherosclerosis" describes modern anti-inflammatory preparations with anti-atherosclerotic effect including natural preparations. In "the development of anti-inflammatory herbal preparation for atherosclerosis prevention" an algorithm is demonstrated that includes screening of anti-cytokine activity of different natural products, the development of the most effective combination and estimation of its effect in cell culture model, in animal model of the acute aseptic inflammation and in a pilot clinical trial. A natural preparation "Inflaminat" based on black elder berries (Sambucus nigra L.), violet tricolor herb (Viola tricolor L.) and calendula flowers (Calendula officinalis L.) possessing anti-cytokine activity was developed using the designed algorithm. The results of the following 2-year double blind placebo-controlled clinical study show that "Inflaminat" reduces carotid IMT progression, i.e. has anti-atherosclerotic effect.Conclusion: Anti-cytokine therapy may be a promising direction in moderation of atherogenesis, especially when it begins on the early stages of subclinical atherosclerosis. The use of herbal preparations with anti-cytokine mechanism of action is the most perspective for timely prevention of atherosclerosis, as they have no significant side effects and can be prescribed for long-term administration. [ABSTRACT FROM AUTHOR]

Background Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown. Objective To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (HDL) profiles in patients with NAFLD. Methods Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 ± 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 ± 6 years]). Exclusion criteria included robust alcohol consumption, infection with hepatitis B or C virus, body mass index ≥40 kg/m 2 , diabetes mellitus, and hypertension. Results Compared with simple steatosis, NASH patients had similar body mass index, homeostasis model assessment of insulin resistance index and plasma lipids, with increased levels of both aspartate aminotransferase and alanine transaminase. NASH subjects had lower levels of larger LDL1 (10 ± 4 vs 13 ± 4%, P = .010) and increased smaller LDL3 and LDL4 particles (9 ± 5 vs 5 ± 5%, P = .017 and 3 ± 3 vs 1 ± 2%, P = .012, respectively). No changes were found in the HDL subclass profile. By multiple regression analysis, we found that NASH was associated only with increased levels of LDL3 ( P = .0470). Conclusions The increased levels of small, dense LDL3 and LDL4 in NASH may help to at least partly explain the increased risk for atherosclerosis and cardiovascular diseases in these patients. [ABSTRACT FROM AUTHOR]

In order to further understand neonatal stress and, thus, control it efficaciously, there is a need for more information on the manifestations of stress at the molecular level in the newborn, with particular regard to oxidants, and anti-oxidant and anti-stress mechanisms, including mitochondrial heat shock protein-chaperones such as Hsp60. We investigated patterns of anti-oxidants, biomarkers of oxidative stress, and Hsp60 levels in sera from newborns and found significant associations between glutathione (GSH) levels and gestational age, delivery modality, and lipid hydroperoxydes (LOOH) level. LOOH levels and spontaneous (vaginal) delivery were independently associated with increased GSH levels when these were above the median. Hsp60 and LOOH levels were positively correlated whereas Hsp60 and GSH levels were inversely correlated in spontaneously delivered newborns; in contrast, Hsp60 and GSH levels were positively correlated in newborns delivered by cesarea. Our results point to new directions in the search for definite patterns of GSH, LOOH, and Hsp60 in the newborn's serum that might have functional and diagnostic significance and that could help in the monitoring of newborn health during and after delivery. In addition, the data provide a starting basis for investigating the precise roles and interplay of GSH and Hsp60 in the maintenance of an optimal redox balance at birth to cope with the stress inherent to delivery, and also for investigating the predictive value of any given pattern of GSH, LOOH, and Hsp60 at birth with regard to health status and risk of disease in adult life. [ABSTRACT FROM AUTHOR]

• NAFLD is the most common liver disease in children. • " Obesity-induced insulin resistance " in T1DM children could be a " driver " for NAFLD development. • There is an urgent need for more research in the field of NAFLD in childhood. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wall injury. HDL metabolism and the molecular constitution of HDL particles are highly complex and can change in response to both acute and chronic alterations in the metabolic milieu. To date, some of these interventions have been shown to positively impact rates of coronary artery disease progression. However, none of them have as yet been shown to significantly reduce risk for cardiovascular events. In the next 3–5 years a variety of pharmacologic interventions for modulating HDL metabolism and functionality will be tested in large, randomized, prospective outcomes trials. It is hoped that one or more of these therapeutic approaches will result in the ability to further reduce risk for cardiovascular events once low-density lipoprotein cholesterol and non-HDL-cholesterol targets have been attained. [Copyright &y& Elsevier]

The first observations linking a low serum level of HDL-C to increased risk for cardiovascular disease were made over 50 years ago. High serum levels of HDL-C appear to protect against the development of atherosclerotic disease, while low serum levels of this lipoprotein are among the most important predictors of atherosclerotic disease in both men and women and people of all racial and ethnic groups throughout the world. It has long been assumed that therapeutic interventions targeted at raising HDL-C levels would lower risk for such cardiovascular events as myocardial infarction, ischemic stroke, and death. Even after five decades of intensive investigation, evidence to support this assumption has been fleeting. A number of post hoc analyses of randomized controlled trials and meta-analyses suggest that HDL-C raising, particularly when coupled with aggressive LDL-C reduction, impacts risk for cardiovascular events and rates of progression of atherosclerotic disease. Unfortunately, four recent prospective trials performed with the intent of testing the “HDL hypothesis” (ILLUMINATE, dal-OUTCOMES, AIM-HIGH, and HPS2-THRIVE) failed to meet their primary composite endpoints. These results have lead many clinicians and investigators to question the validity of the assumption that HDL-C raising reduces risk for cardiovascular events. Additional trials with other drugs are underway. In the meantime, HDL-C cannot be considered a target of therapy. Given the complexity of the HDL proteome and lipidome, there is biological plausibility for how HDL particles might exert atheroprotection. We explore the evidence supporting the inverse relationship between HDL-C and cardiovascular disease risk, documented mechanisms by which HDL particles may exert atheroprotection, and the findings either supporting or negating specific therapeutic interventions in patients afflicted with low HDL-C. [Copyright &y& Elsevier]