The epidemic of obesity has increased worldwide and is associated with comorbidities as diabetes as cardiovascular disease. Strategies that modulate body weight and improves glycemic metabolism has increased, and the bariatric surgeries as Sleeve Gastrectomy (SG) has been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control are unknow. C57BL mice were submitted to a 10 weeks high fat-diet protocol and submitted to SG. Food intake, fed/fasted glycemia and hypothalamic anorexigenic and orexigenic gene expression were evaluated. SG reduces body weight, fasting glycemia, insulinemia and leptinemia in obese mice. Moreover, SG reduces food and total calorie intake with no alterations in the expression of anorexigenic and orexigenic gene expression. These data indicates that SG improves obesity associated alterations, at least in part, by reduction on food intake. This effect is not associated with the classic food intake pathway in hypothalamus, indicating the involvement of supplementary pathways in this process.

Background: The prognostic impact of non-cardiac comorbidities can vary in relation to the left ventricular ejection fraction (EF) in patients with ST-elevation myocardial infarction (STEMI). The aim was to analyze prevalence and long-term prognostic impact of non-cardiac co-morbidities in patients with reduced and preserved EF following STEMI. Method: 3115 STEMI patients undergoing primary PCI were divided in two groups: reduced EF <50% and preserved EF≥50%. Follow-up period was 8 years. Results: Preserved EF was present in 1726 (55.4%) patients and reduced EF was present in 1389 (44.5%) patients. Non-cardiac comorbidities were more frequent in patients with reduced EF as compared with patients with preserved EF (38.9% vs 27.4%, respectively, p<0.001). Lethal outcome was registered in 240 (17.2%) patients with reduced EF and in 40 (2.3%) patients with preserved EF, p<0.001. Diabetes and CKD were independent predictors for 8-year mortality in patients with preserved EF while in patients with reduced EF only CKD was independently associated with 8-year mortality. Conclusion: In the present study the prevalence of non-cardiac comorbidities is similar in patients with reduced and preserved EF after STEMI, but only DM and CKD are independently associated with long-term mortality.

Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p&lt;0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p&lt;0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p&lt;0.001), and were biologically older than COPD patients (p&lt;0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Aortic stenosis continues to be still the most frequently valvular pathology in the elderly population of the Western countries. According to the latest guidelines, the therapeutic choice of aortic stenosis depends on the age of the patient (&lt;75 years or &gt;75 years) and the risk class (STS-Prom/ Euroscore II &lt; o &gt; 4%). Therefore, if the surgical indication is clear in young and low risk patients and percutaneous treatment is the gold standard in older and high-risk patients, the therapeutic choice is still debated in intermediate-risk patients. In this group of patients the aortic valve stenosis treatment depends on the patient's global evaluation, on the experience of the center and no less important on the patient's will. Two main therapeutic options are debated: surgical aortic valve replacement with sutureless prosthesis versus transcatheter aortic valve implantation. In addition, the progressive development of mininvasive techniques for aortic valve surgery (right -anterior minitoracotomy) has also reduced the peri and post -operative risk in this group of patients. The goal of our review is to analyze the literature evidence of the best therapeutic choice in intermediate risk patients with severe aortic stenosis.

The European Green Deal poses a two-pronged challenge for the automotive industry: migrating to solutions based in light structures, requiring light weight concepts and light materials, while at the same time avoiding dependence towards the importation of these advanced materials. Aluminium alloys are lightweight and cost-effective materials that can successfully cover the requirements of many structural applications, however their production requires from bauxite and other Critical Raw Materials (CRM), such as Si and Mg. Aluminium alloys are fully recyclable, but scrap is usually contaminated and its use is related to an increment of impurities, tramp element and undesired inclusions. Traditionally, the use of secondary alloys has been restricted to low performance applications. The present work analyses the effect that the use of scrap has in the quantity of inclusions present in the alloy and in other properties relevant for the material processing. The study was carried out for common alloys belonging to 3 of the most common aluminium processes used in the car manufacturing industry: High Pressure Die Casting (HPDC) (EN AC-43500), extrusion (6063) and sheet metal forming (5754 and 6181). Reference alloy were mixed with different level of scrap (0, 20, 40, 60, 80 and 100%) trying to keep the chemical composition as unaffected as possible. The inclusions level of the alloy was characterized with the Prefil Foot-printer® test. In addition, the obtained materials, after being cast in an open mould, were subjected to metallographic characterization. Relevant properties to assess the formability quality of the alloys for the corresponding transforming process, were obtained: flowability test for HPDC alloy and high temperature compression for extrusion alloys. The results obtained suggest that the number of inclusions present in the melt highly increase with the amount of scrap used to produce the alloy. These inclusions are also related with an important lost of flowability, but do not have a noticeable impact on microstructure.

Tinnitus is a symptom often associated with hearing loss (HL) and is in many cases more burdening to the individual than the HL itself. Many approaches have been made to explain the development and chronification of the phantom percept as well as different treatment strategies to lower the tinnitus related burden. In many studies, the variance of the HL data is high and therefore the interpretation of specific data might be difficult. With this retrospective study, we attempt to explain a part of this variance by investigating specifically the effects of non-auditory comorbidity categories on pure-tone audiometric data in a tinnitus patient collective that was homogeneous with respect to auditory comorbidities. We found age dependent as well as number of non-auditory comorbidity (e.g. diabetes mellitus) dependent differences in the mean HL of the tinnitus patients as well as differences in the peak HL frequency relative to the tinnitus frequency. The analysis of the age dependent HL within the different non-auditory comorbidities revealed specific – partially opposed – effects of endocrine, circulatory, muscle-skeletal and digestive disease categories on the hearing thresholds of tinnitus patients. Taken together we argue that in future tinnitus (and non-tinnitus) patient studies also non-auditory comorbidities should be taken into account as possible covariables that might explain the variance found in the auditory threshold development of these patients.

Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

While the beneficial effects of using magnetic and electromagnetic treatment (ET) of brackish and saline waters on soil salinity reduction in the root zone were widely reported more studies are needed to answer questions about the soil salt leaching efficiency and the effect of the duration of the exposure to ET. For this aim, pot experiments were conducted using an Aqua-4DR physical water treatment device. The first experiment included two trials. The first considered 5 concentrations: C0:1.0; C1:4.5; C2:9; C3:13.5; and C4:18 dSm-1. The results revealed that the volume and the salt concentrations of the drained waters were significantly higher under irrigation with ET saline waters than those provided by untreated waters. The drained fraction of water varied from 20 to 26% under irrigation with untreated water and increased from 33 to 56% under irrigation with electromagnetized water indicating an improvement of salt leaching. The second trial was carried out with different irrigation doses. The result showed that the higher the dose, the more obvious and significant ET effect. The different treatment durations of water exposure revealed that the volume and salinity of drained water significantly increase as the ET duration increases. An increase in ET duration induces also an increase in soil water content of around 2.5%. Based on the experimental findings, we may conclude that the ET of saline water can reduce the adverse effect of salinity on the top soil, but these leached salts are carried away in depth and there is no concentration limit of water to the effect of the ET.

Background: Recently, minimally invasive access via right-anterolateral mini-thoracotomy (RAMT) has been gaining popularity in cardiac surgery. This approach is also an option for sur-geons performing aortic surgery. Aim of the study is to present our surgical method highlighting the total endoscopic minimally invasive approach via RAMT for replacement of the ascending aorta (AAR) with or without involvement of the aortic root and the aortic valve. Methods: Clini-cal data of 44 patients from three participating institutions with AAR with or without involving the aortic valve or aortic root via RAMT between April 2017 and February 2024 were retrospec-tively analyzed. According to surgical procedure patients were divided in group A with only AAR and group B with concomitant valve or root replacement. Operative time, length of ventila-tion, perioperative outcome, length of intensive care unit (ICU) as well as postoperative hospital stay, and mid- and long-term results were retrospectively analyzed. Results: Mean age was 61.4 ± 10.7 years old with a frequency of male gender (63.6%). Mean cardiopulmonary bypass (CBP) time and aortic cross-clamping time was 94.9 ± 32.5 min. and 63.8 ± 25.9 min., respectively. CPB and aortic clamp time were significantly lower in group A. In the first 24 hours the mean drain-age volume was 790.3 ± 423.6 ml. Re-thoracotomy due to bleeding was zero. Sternotomy could be avoided in all patients. Patients stayed 35.9 ± 23.5 hrs at ICU and were discharged 7.8 ± 3.0 days following surgery from hospital. Mean ventilation time was 5.8 ± 7.6 hrs. All patients survived and 30-day mortality was 0.0%. At a median follow-up time of 18.2 months, all patients were alive. The results were similar in both groups. Conclusions: The full endoscopic RAMT approach with 3D visualization is a safe and feasible technique which can be transferred in the field of aor-tic surgery without compromising surgical quality, postoperative outcomes, or patient safety when performed by an experienced team in a high-volume center.

In this work, studies were carried out on the extraction of silver and gold from cakes of pressure oxidation leaching of sulfide concentrate containing pyrite and arsenopyrite. The addition of gypsum at a consumption of 0.1 g/g of concentrate helps to increase silver extraction from 13.4 to 95–98% at the cyanidation stage, with no conditioning operation. Gold recovery was 99%. An increase in gypsum consumption contributes to the formation of BFAS with an increased content of sulfate sulfur, and a decrease in the As/S(sulfate) molar ratio in the cake from 3.7 down to 0.88 contributes to an increase in silver extraction at the cyanidation stage up to 98%, and its further decrease from 0.88 down to 0.58 leads to a gradual reducing silver transfer into solution from 98 down to 75.1% at the cyanidation stage. Basic ferric sulfate (BFS) is not formed in this case, since according to EDS mapping the distribution of arsenic and sulfur over iron-containing particles is uniform. According to TCLP analysis, the cake obtained after pressure oxidation leaching with the addition of gypsum and cyanidation is stable and suitable for disposal, since the final concentration of arsenic in the solution was 0.45 mg/dm3.

Objectives: Minimally invasive direct coronary artery bypass (MIDCAB) is an alternative for revascularisation of isolated left anterior descending (LAD) or as multi-vessel (MV) procedure for diagonal branch (RD) or circumflex artery (RCX) region. Methods: From 2021 to 2022 91 patients underwent MIDCAB procedure in our heartcenter. 80% were male. Eighty percent of the patients had two or three vessel coronary artery disease. Mean age was 65±10 years. The left internal mammary artery (LIMA) was anastomosed to the left anterior descending via left minithoracotomy approach in all patients. Fourteen patients received multi-vessel MIDCAB (15%) with two or three anastomoses a saphenous vein graft (as T-graft to LIMA) was anastomosed to RD or RCX. Results: Mean operation time was 2.6±0.8 hours. The 30-day mortality was 0. Mean required packed red blood cells (pRBC) was 0.4±1.2 unit. The intensive care unit stay (ICU) was 1.5±1.6 days mean. We observed two patients (2%) with wound infections postoperatively. Four patients underwent rethoracotomy because of bleeding. Mean follow-up time was 1.5±0.5 years. Seventy-eight patients (86%) were in New York Heart Association (NYHA) class 1, 11 patients (12%) were in NYHA class 2. One patient received percutaneous coronary intervention due to de novo stenosis of the RCA. Late mortality was 2%. The Kaplan-Meier survival rate was 98.8% at 1 and 2 years. Conclusion: MIDCAB is technically demanding. Our postoperative and short-term clinical results demonstrate that this procedure is safe and feasible. Optimal patient selection and an experienced surgical team are mandatory.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Approximately 300 million non-cardiac surgeries are performed each year. Perioperative mortality after non-cardiac surgery is estimated at 2% in patients over 45 years of age . Half of these deaths are attributable to cardiovascular complications, and most to perioperative myocardial infarction (MINS). Before introduction of cardiac biomarkers the diagnosis of postoperative myocardial infarction was based on symptoms and electrocardiographic changes and its incidence was largely underestimated. The incidence of MINS when standard troponin assay is used ranges between 8 and 19% but increases to 20-30% whit high sensitivity troponin assays. Higher troponin values sugegsting myocardial injury , both with or without definite diagnosis of myocardial infarction, are associated with increased 30 day and 1-year mortality . Diagnostic and therapeutic strategies are reported .

Mechanically homogenized composite of expanded graphite and cobalt(II) rhenate(VII) has been described. Cobalt(II) rhenate(VII) was obtained in a reaction of perrhenic acid with cobalt(II) nitrate. A simple mortar homogenization method was used to enhance intercalation of cobalt species within carbon matrix. The specific capacity of composite was enhanced by 50% in comparison to bare expanded graphite. The electrochemical characteristic was significantly improved including better cyclability, lower resistance of electrode material, lower iR drop, with respect to expanded graphite without cobalt(II) rhenate(VII) active species. Expanded graphite with its unique specific surface area and pore size diameter was proved as potential and cheap carbon support.

Sialylated milk oligosaccharides (SMOs) is the most important oligosaccharides in human milk oligosaccharides (HMOs), and have a multifunctional health benefit, and the most abundant SMOs are sialyllactose (SLs). The previous studies indicate that the growth of tumor cells, and angiogenesis on tumor tissues with Lewis lung carcinoma, melanoma, and colon carcinoma cells could be prevented by SL. Thus, it has been proposed that SL might be an ideal candidate for the development of anti-angiogenic drugs without any side effects. It has been proposed that the Sialic acid (Sia) can be produced through SL’s hydrolysis, and the dietary Sia is further transported to the brain and other tissues though blood for formation of CMP-Sia, the activated precursor of Sia, and then is catalyzed by polysialyltransferases (polySTs) for synthesis of polysialic acid (polySia) or polysialylation of neural cell adhesion molecule (NCAM). Thus, it’s necessary to study and develop new inhibitors, which not only modulate a proper balance between the gut health and neuros system development, but also inhibit the overexpression of polySia, and thus block the tumor cell migration. In this study, we proposed that 3’-SL and 6’-SL may be more ideal inhibitors comparing with two previous inhibitors, the low molecular weight heparin (LMWH) and cytidine monophosphate (CMP) in the previous studies.

Introduction Atherosclerotic disease is a major contributor to heart failure, stroke, and myocardial infarction, significantly lowering the quality of life and life expectancy, with a significant burden on healthcare. Not all lesions deemed non-significant are benign, and conversely, not all significant lesions are causative of ischemia. Fractional flow reserve (FFR) provides a functional assessment of coronary lesions, while optical coherence tomography (OCT) offers detailed imaging of plaque morphology, aiding in therapeutic decision-making. The objective of this study was to evaluate the utility of OCT and FFR as adjunctive tools in the catheterization laboratory for guiding therapeutic decisions in patients with multivessel disease for non-culprit vessels. Specifically, we aimed to assess how OCT and FFR influence therapeutic decision-making in patients with multi-vessel coronary artery disease. Methods 36 patients with acute coronary syndrome (ACS) and multivessel disease were randomized 1:1 into two groups: one guided by FFR alone, and the other by a combination of FFR and OCT. For the FFR group, revascularization decisions for non culprit lesions were based solely on FFR measurements. If the FFR was >0.8, the procedure concluded, and the patient received maximal medical treatment. If the FFR was ≤0.8, a stent was placed. For the FFR + OCT group, if the FFR was >0.8, the revascularization decision was based on OCT findings. If there were no vulnerable plaques (VP), the procedure concluded, and the patient received maximal medical treatment. If OCT imaging indicated VP, then the patient underwent revascularization. If the FFR was ≤0.8, the patient underwent revascularization regardless of OCT findings. Results OCT imaging altered the therapeutic decision in 11 cases where FFR measurements were above 0.8, but the lesions were characterized as VP. Analyzing the total change in the decision to stent, 4 cases in the FFR group and 15 cases in the FFR and OCT group (4 based on FFR and 11 on OCT) revealed a statistically significant difference (p = 0.0006; Relative Risk = 0.2556; 95% CI: 0.1013 to 0.5603). When analyzing the change in the total decision both to stent and not to stent, we observed a statistically significant difference, with Group 1 having 7 cases and Group 2 having 15 cases (p = 0.0153; Relative Risk = 0.4050; 95% CI: 0.2004 to 0.7698) Conclusion Based on the findings of this study, OCT significantly increases the percentage of stenting procedures by identifying vulnerable lesions. The use of intracoronary imaging facilitates the timely identification and treatment of these vulnerable lesions. This underscores the crucial role of OCT in enhancing the precision of coronary interventions by ensuring timely intervention for vulnerable lesions, thereby potentially improving patient outcomes Acknowledgment funding „This work was supported by the University of Medicine, Pharmacy, Science and Technology ,, George Emil Palade’’ of Targu Mures Research Grant number 510/14/17.01.2022”

Heart transplantation (HT) represents the mainstream therapy of end-stage heart failure for selected patients with a median survival of more than 10 years after surgery and substantial improvement in quality of life. Current guidelines suggest a variety of examinations including invasive (coronary angiography and endomyocardial biopsy (EBM) and non-invasive methods (echocardiography, stress echocardiography, computed tomography, PET and MRI) to monitor HT patients. Guidelines do not specify the timing of echocardiographic evaluations and do not recommend echocardiography as an alternative to serial EMB in rejection monitoring [2]. They still recommend as gold standard coronary angiography to be done 1 year after surgery and every 2 years after. In this review we will discuss the advantages of non-invasive techniques over the invasive ones for an adequate follow-up of HT patients.

Background/Objectives: Cardiovascular diseases are one of the leading causes of morbidity and mortality worldwide. Health-related quality of life is crucial to assess the impact of cardiovascular diseases and to guide therapeutic strategies. The Short Form 36 Health Survey and the RAND 36-Item Health Survey questionnaires are common tools for measuring health-related quality of life in patients with cardiovascular disease, but their reliability may vary according to the population studied. The aim of this study is to compare the reliability of the SF-36 and the RAND-36 in a population with cardiac pathology, addressing the question of which of these instruments offers a more consistent and useful measurement in this specific group. Methods: Cross-sectional observational study carried out at the University Hospital of Burgos (Spain). 413 patients with cardiovascular pathology referred to the Cardiac Rehabilitation Unit were included. Patients with incomplete data or who did not participate in the program were excluded. Internal consistency (Cronbach’s alpha), item-total correlation and reliability and a half-half analysis were performed. Results: Both questionnaires showed similar and adequate reliability for patients with cardiovascular pathology. Internal consistency, as measured by Cronbach’s alpha, was above 0.80 for most dimensions, supporting its robustness. Significant inter-item and inter-dimension correlations were found in both scales, except in some specific cases in the dimension ‘Physical Functioning’. The half-half analysis confirmed the good reliability of both scales. Conclusions: Both the SF-36 and the RAND-36 are highly reliable tools for assessing health-related quality of life in patients with cardiovascular disease. The results may have significant implications for clinical practice, helping in the selection of health-related quality of life monitoring instruments and in the evaluation of the efficacy of therapeutic interventions.

Athlete’s heart is characterised by structural, functional, and electrical remodelling. During an exercise session, the heart increases the use of oxygen, which is associated with decreased vascular resistance in the lungs’ circulation. Left ventricular hypertrophy is an echocardiographic modification especially met in endurance athlete’s heart. Moreover, left atrial dilatation represents another important characteristic of endurance athletes. Electrical modulation in the athletic heart induces neurological modifications leading to sinus arrhythmia, bradycardia, early repolarisation, and first-grade atrioventricular (AV) blocks. Athletes' nutritional status involves the assimilation of macronutrients such as proteins, carbohydrates, and fats. Depending on the duration of physical exercise, ATP can be obtained in aerobic or anaerobic conditions. This systematic review aims to find correlations between different evaluative methods of cardiac adaptation and present the metabolism in performance athletes.

The non-coding RNAs (ncRNAs) are indispensable for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases. Cardiac arrhythmia is a frequent cardiovascular disease, which has a complex pathology. Recent studies have shown that ncRNAs are also associated with cardiac arrhythmias. Many non-coding RNAs and/or genomes have been reported as a genetic background for cardiac arrhythmias. Arrhythmias may be affected by several functional and structural changes in the myocardium. Therefore, ncRNAs might be indispensable regulators of gene expression in cardiomyocytes, which could play a dynamic role in regulating the stability of cardiac conduction and/or in the remodeling process. Although it remains almost unclear how ncRNAs regulate the expression of molecules for controlling the cardiac conduction and/or in the remodeling process, gut microbiota and immune system within the intricate networks might be involved in the regulatory mechanisms. This study would discuss them and provide a research basis for ncRNAs modulation, which might support the development of emerging innovative therapies against cardiac arrhythmias.

Childhood obesity is a preventable multi-systemic disease that has become an epidemic. In this narrative review, we showed evidence, in the literature, of the affectation of body systems by obesity. Co-morbid conditions of obesity in the cardiovascular, nervous, dermatological, respiratory, endocrine, reproductive, musculoskeletal, gastrointestinal, and renal systems, and its effects on mental health are discussed. Obesity ultimately reduces the quality of life of children and is a leading cause of preventable deaths. Effective measures aimed at the prevention of obesity and the treatment of its co-morbid conditions should be taken.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

Abstract Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) receptor agonists, are a class of medications used to treat type 2 diabetes by mimicking the actions of incretin hormones in the body. These hormones are responsible for promoting insulin release from the pancreas in response to nutrient intake, as well as decreasing glucagon secretion, slowing gastric emptying, and promoting satiety. By imitating these actions, incretin mimetics help to regulate blood sugar levels in individuals with diabetes and glucose intolerance. One of the key benefits of incretin mimetics is its ability to lower blood sugar levels without causing hypoglycemia. This is especially important for individuals with diabetes who may experience dangerous drops in blood sugar levels when using other medications. Additionally, incretin mimetics have been shown to promote weight loss in some individuals, making them a valuable option for those struggling with obesity in addition to diabetes. Incretin mimetics are administered by injection, once or twice daily, depending on the specific medication. They are often combined with other diabetes medications, such as metformin or insulin, for optimal blood sugar control. These medications are generally well-tolerated, with common side effects including nausea, vomiting, and diarrhea, which usually diminish over time as the body adjusts to the medication. Studies have shown that incretin mimetics can help improve cardiovascular outcomes in individuals with diabetes, including reducing the risk of heart attacks and strokes. This is particularly significant given the increased risk of cardiovascular disease in individuals with diabetes. Incretin mimetics also have been shown to preserve pancreatic beta-cell function, which is responsible for producing insulin. This can help slow the progression of diabetes and reduce the need for higher insulin doses over time. Despite their many benefits, incretin mimetics are not without limitations. They can be expensive compared to other diabetes medications, which may make them less accessible for some individuals. Additionally, there have been concerns about the potential risk of pancreatitis and pancreatic cancer associated with the use of these medications. However, more research is needed to fully understand these risks. It is important for healthcare providers to carefully assess each individual's unique needs and medical history when considering the use of incretin mimetics. They may not be appropriate for everyone, particularly those with a history of pancreatitis or pancreatic cancer. Patients should also be educated about these medications' proper administration and potential side effects to ensure their safety and efficacy. Overall, incretin mimetics have emerged as an important therapeutic option for individuals with type 2 diabetes, offering a unique mechanism of action that can help improve blood sugar control, promote weight loss, and reduce cardiovascular risk. With ongoing research and development in this field, incretin mimetics continue to show promise as valuable tools in managing diabetes and its associated complications and comorbidities.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

Capsinoids (CAP) are potential antioxidant agents capable of reducing oxidative damage and the resulting complications triggered by obesity. Thus, the aim of this study was to investigate the effects of CAP on adiposity and biomarkers of cardiac oxidative stress in rats with obesity induced by a high-fat diet. Male Wistar rats were exposed to a high-fat diet for 27 consecutive weeks. After characterization of obesity (week 19), some of the obese (Ob) animals began to receive capsinoids (10 mg/kg/day) by orogastric gavage. Adiposity and comorbidities were assessed. In the heart, remodeling, injury and biomarkers of oxidative stress were determinated. The treatment did not reduce the adiposity induced d by obesity, but they were efficient in reducing cholesterol levels. CAP treatment did not cause a difference in heart and LV mass, despite having reduced troponin I concentrations. Furthermore, capisinoids did not reduce the increase in advanced oxidation of proteins products (AOPP) and carbonylated proteins (CBO) caused by obesity in cardiac tissue. Besides that, it was observed that ObCap rats presented high levels of malondialdehyde and greater activity of antioxidant enzymes compared to Ob. In conclusion, treatment with capsinoids did not lead to significant positive effects in reducing obesity-induced oxidative stress.

We propose novel spectrometer designs that aim to enhance the measured spectral range 1 of ions on a finite-sized detector. In contrast to the traditional devices that use uniform magnetic 2 field, in which the deflection of particles increases inversely proportional to their momentum, in a 3 gradient magnetic field, the deflection of particles will be decreased due to the reduction of the 4 magnetic field along their propagation. Low energy ions are particularly impacted, as they are 5 deflected less and are more likely to reach the detector compared to being driven out of it while 6 using a uniform magnetic field. By the means of a gradient magnetic field, the nonlinear dispersion 7 of ions in a homogeneous magnetic field can approach a nearly linear dispersion. Nonetheless, 8 the dispersion of low energy ions in a homogeneous magnetic field remains unnecessarily high. 9 In this article, we explore linear, quadratic, and higher-order field profiles in comparison to the 10 homogeneous field case. We discuss the employed methodology and present simulation results of 11 the spectrometer with an extended ion spectral range, focusing on the minimum detectable energy 12 (energy dynamic range) and energy resolution

Background: Endometriosis is a female chronic inflammatory disease in which endometrial tissue develops outside the uterine cavity. It is a complex pathology, that significantly contributes to morbidity in premenopausal women, leading to chronic pain, infertility, and subfertility negatively impacting the physical, and emotional well-being and overall quality of life. The public health burden of endometriosis remains elusive and challenging to determine, and this uncertainty can lead to inadequate healthcare services and treatments. Objective: To estimate the incidence and prevalence of endometriosis in Italy using the hospital discharge records database. Population-based retrospective study. Nationwide between 2011 and 2020. Methods: From the National Hospital Discharge Database were selected all admissions with a diagnosis of endometriosis (ICD-9-CM, codes 617.x), supported by the presence of a procedure code of laparoscopy or any other surgical procedure allowing direct visualisation of the lesions. Main outcomes measures Incidence and prevalence of endometriosis were estimated for the entire 2010-2020 period and by individual year, analysing the time trend and variability in different geographical areas of Italy. Results: A total of 134,667,646 women aged 15–50 years with one or more hospitalisations for endometriosis in all Italian hospitals. The incidence of endometriosis in Italy during this period was 0.839 per 1000 women (CI95% 0.834-0.844), exhibiting a statistically significant decreasing trend over the years. A discernible north-south gradient was observed, with higher rates documented in the northern regions. The prevalence rate stood at 14.0 per 1000 during the same period, and a similar north-south geographical gradient was identifiable in the prevalence rates as well. Conclusions: The utilization of national-level hospital data enables the generation of incidence and prevalence data for endometriosis without variations in methods and definitions, facilitating the evaluation of temporal trends and regional comparisons. Understanding and quantifying this phenomenon is essential for appropriate healthcare planning in various Italian regions.

(1) Background: In patients suffering from heart failure, the main causes of death are either he-modynamic failure, or ventricular arrhythmias. The only tool to significantly reduce arrhythmic sudden death is the implantable cardioverter defibrillator (ICD), but not all patients benefit to the same extend of these devices. (2) Methods: The primary outcome of this single center study was defined as cardiovascular death in patients with ischemic and non-ischemic heart failure who have benefited from ICD therapy. The secondary outcomes were death from any cause, sudden cardiac death, ICD-related therapies (appropriate antitachycardia pacing or shock therapy for ventricular tachycardia or fi-brillation) and recurrences of ventricular tachyarrhythmias. (3) Results: A total of 403 consecutive ICD recipients – symptomatic heart failure patients with ICD for the primary prevention of sudden cardiac death – were included retrospectively: 59% is-chemic cardiomyopathy (ICMP) and 41% non-ischemic cardiomyopathy (NICMP). Within a median follow-up period of 36 months, the incidence of cardiovascular mortality was not signif-icantly different in patients with NICMP and ICMP: the primary outcome had occurred in 9 pa-tients (5.4%) in the NICMP group and in 14 patients (5.9%) in the ICMP group (hazard ratio 1; 95%confidence interval [CI] 0.45 to 2.28; p =0.97). All-cause mortality occurred in 14 of 166 pa-tients (8.4%) in NICMP group and 18 of 237 patients (7.6%) in ICMP group. Sudden cardiac death occurred in 2 patients (1.2%) in the NICMP group and in 4 patients (1.7%) in the ICMP group (hazard ratio 0.71; 95% CI, 0.13 to 3.88; P=0.69). The rate of appropriate device therapies was comparable in both groups. (4) Conclusion: In this study, ICD implantation for primary prevention of sudden cardiac death in patients with symptomatic systolic heart failure was associated with similar rates of cardiovas-cular and all-cause mortality in patients with ischemic heart disease, and in patients with heart failure from other causes. NICMP and ICMP showed comparable rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlighting the clinical importance, underlying mechanisms, and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

Fibroblasts are differentiated to myofibroblasts and produce collagen and other extracellular matrix when the heart is exposed to stresses. Myocardial infarction and pressure overload-induced hypertrophy are major stresses to induce differentiation of fibroblasts. Since collagen can compensate the missing tissue due to injury, appropriate production of collagen is beneficial for the injured heart against rupture. However, excessive deposition of collagen is called fibrosis and causes cardiac dysfunction. After fibroblasts are differentiated to myofibroblasts, myofibroblasts can further change their phenotypes. In addition, myofibroblasts are found to have a new function other than collagen production. Myofibroblasts have macrophage-like functions that engulf dead cells and secrete anti-inflammatory cytokines. So far, research on fibroblasts has been delayed due to the lack of available markers for selective isolation of fibroblasts. In recent years, it has become possible to genetically label fibroblasts, sequence the cells at single cell levels, and manipulate function or the number of cells. Based on new technologies, the origin of fibroblasts and myofibroblasts, time-dependent changes of fibroblast states after injury, and heterogeneity have been demonstrated. Here, I will introduce recent advances in fibroblasts and myofibroblasts.

Cardiac arrest (CA) is a life-critical condition. Patients who survive after CA, they go into a defined post-cardiac arrest syndrome (PCAS). In this clinical context, the role of the echocardiogram in recent years has become increasingly important to assess the causes of arrest, the prognosis, and any direct and indirect complications dependent on cardiopulmonary resuscitation (CPR) maneuvers. The aim of our review is to evaluate the increasingly important role of the transthoracic and transesophageal echocardiogram in the CA phase and especially post-arrest, analyzing the data already present in the literature.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Percutaneous vertebroplasty procedure is of major importance, given the significant increasing aging population and higher number of orthopedic procedures related to vertebral compression fractures. Vertebroplasty is a complex technique involving injection of polymethylmethacrylate (PMMA) into the compressed vertebral body for mechanical stabilization of the fracture. Our understanding and ability to modify these mechanisms through alterations in cement material is rapidly evolving. However, the rate of cardiac complications secondary to PMMA injection and subsequent cement leakage has increased with time. The following review considers the main features of PMMA bone cement on the heart, and the extent of influence of materials on cardiac embolism. Clinically, cement leakage results in life-threatening cardiac injury. The convolution of this outcome through an appropriate balance of complex material properties is highlighted via clinical case report.

Arrhythmic sudden cardiac death (SCD) has an annual prevalence of 1 per 1000 while 75% of the victims suffer from ischemic and 10% from non-ischemic or hypertrophic cardiomyopathy. Altogether, these three entities account for more than 80% of the total SCD victims. Guidelines for implantable cardiac defibrillators are still dominated by LVEF<30% from the MADIT II study. In terms of arrhythmic risk stratification, the PRESERVE-EF study restored in clinical practice the two-step arrhythmic risk stratification approach based on Electrocardiographic non-invasive risk factors (NIRFs) guiding to electrophysiological study. In our times with the multiple cardiac imaging methods and artificial intelligence applications availability, this two-step approach based on integrated arrhythmia mechanisms detection, emerges as an efficient SCD risk stratification paradigm for these three entities but also for the patients with congenital heart disease.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.

Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in the disease pathomechanism. Unbalance between oxidants and antioxidant defense mechanisms not only amplifies the local inflammatory processes, but it also worsens cardiovascular health and contribute to the COPD related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced together with some suggestions for further research on the field.

Cardiac surgery is a modern science in the history of medicine. The impact in cardiac disease, in term of treatment and prognosis, has made this discipline indispensable in the global health. In recent decades, the greatest investment has been dispensed in technological and material improvement, for increase the life expectancy. This surgery must address different epidemiological aspects dictated by the geography and economic-social conditions of the global populations. For this reason, it is progressively important to address the cardiac surgery accessibility disparity. Many scientific paper and international meetings have studied how cardiac surgery can increase accessibility in various countries around the world. In this review we analyze all the challenges, solutions and suggestions to make this surgery accessible to the entire global population, with the purpose to reducing the disparity across the all seven continents. For a long time, high-income countries have invested in technological capabilities and experimental advancement, not caring about unequal access in the rest of the world. We believe that it is time to reverse the growth trajectory, placing – as a priority – the accessibility and distribution of a surgical science, too significant for the right to health of all the people of the world. This is the real new challenge in cardiosurgery.

Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibres. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualisation such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilise finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.

Objective: We reviewed the available literature on patients undergoing minimally invasive mitral valve surgery (MIMVS) with either transthoracic clamping (TTC) or endoaortic balloon occlusion (EABO). Methods: Original research studies that evaluated the perioperative outcomes of TTC versus EABO group were identified, from 2000 to 2024. The incidence of all-cause mortality, cerebrovascular accidents (CVA), and aortic dissections were the primary endpoints. The cardiopulmonary bypass (CPB), cross-clamp, and ventilation time, along with the incidence of conversion to sternotomy, re-exploration, new-onset atrial fibrillation (AF), postoperative acute kidney injury (AKI), ICU stay, and LOS were the secondary endpoints. Subgroup analyses were performed regarding EABO cannulation approach (femoral and aortic) and MIMVS approach (video-assisted and robotic-assisted). Sensitivity analyses were performed including risk-adjusted populations and with the leave-one-out method. Results: Sixteen studies were included in the qualitative and quantitative synthesis. After pooling data from 6,335 patients, both groups demonstrated similar outcomes on all primary and secondary endpoints in the non-adjusted and adjusted total cohort analyses. These outcomes were further validated by the leave-one-out sensitivity analysis. In addition, the aortic cannulation EABO was associated with lower cross-clamp time, followed by TTC and femoral cannulation EABO approach. Furthermore, in the video-assisted subgroup analysis, the EABO approach was associated with a higher incidence of CVA, conversion to sternotomy, and longer ICU stay compared to the TTC group. Conclusions: The present meta-analysis indicates that both aortic occlusion techniques are safe and feasible in the context of MIMVS. A future well-designed Randomized-Control Trial should further validate the current outcomes.

In this presented case, a 77 years old woman suffering from ongoing knee pain underwent a bone scan using 99mTc-hydroxydiphosphonate (HDP) in suspicious for bone infection. An incidental finding from this scan revealed diffuse cardiac uptake, necessitating further diagnostic procedures to exclude the possibility of cardiac amyloidosis. In the subsequent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and SPECT images, no perceptible cardiac uptake was observed at all. Upon retrospective review of the patient’s medical records, she had received 1000mg of ferric carboxymaltose for iron-deficient anemia, the day before the 99mTc-HDP bone scan. Therefore, it is assumed that the diffuse and temporary cardiac activity was due to the transient iron overload. We present and share this bone scan images in order to avoid possible future misinterpretation of cardiac amyloidosis.

(1) Background: Cardiac resynchronization therapy (CRT) is essential for patients with heart failure and ventricular conduction abnormalities. Cardiomyopathy often includes left bundle branch block (LBBB) marked by delayed activation of the LV lateral wall and a widened QRS complex. Following CRT, patients with heart failure and LBBB have better outcomes and quality of life improvements. Various electrocardiographic and clinical parameters are thought to predict this improvement. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a reliable tool for measuring the quality of life in these patients. (2) Methods: We performed an observational prospective study over 69 individuals diagnosed with cardiac failure and dilatative cardiomyopathy with low FE and major LBBB and analyzed the correlations between patient outcomes after the procedure and the demographic, clinical, and electrocardiographic parameters, which include systolic blood pressure, ECG morphology elements, QRS duration, QRS area and associated comorbidities. (3) Results: Following our analysis a correlation between QRS area, intraprocedural systolic blood pressure, QRS duration and CRT outcomes assessed by the KCCQ score was observed which reflected that CRT has a hemodynamic impact and also affects the severity of ventricular asynchrony.; (4) Conclusions: The significant correlations observed with the KCCQ score show how CRT therapy impacts patients' quality of life, symptom burden, and functional status.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

The present article seeks to study whether there is any relationship between the equation of the rhythmic figures (Lugos Abarca, 2023) and cardiac auscultation using Field's method, which consists of representing cardiac sounds by means of musical notation (Field, 2010). A new meaning is given to the equation, concluding a mathematical equality between the equation of the rhythmic figures and the formula for calculating the RR Interval.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

Pediatric chronic pain is an important public health issue given its notable impact on numerous domains of living. Pediatric chronic pain is also often comorbid with emotional, developmental, or behavioral conditions which can lead to more severe negative outcomes and an even greater reduction in positive outcomes compared to those without comorbidities. Flourishing is a positive outcome that chronic pain status has been shown to impact. We explored flourishing in children aged 6-17 years living with chronic pain as well as those with chronic pain and comorbidities using data from the 2018/2019 National Survey of Child Health. There were significant associa-tions between chronic pain condition status and all demographic variables (sex, age, race/ethnicity, poverty level, parental education, health insurance status). Results of hierarchical logistic regression found that chronic pain condition status significantly predicted flourishing. Children with chronic pain were 2.33 times less likely to flourish, and children with chronic pain plus an emotional, developmental, or behavioral comorbidity were 13 times less likely to flourish than typical peers. Given their significantly lower likelihood of flourishing, there is an urgent need for interventions targeted at children experiencing chronic pain and mental health comor-bidities.

Lung cancer (LC) continues to be an important public health problem being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never smoker early-onset LC patient does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer predisposing genes in non-smokers patients, giving experimental support to a model of a “private genetic epidemiology”. Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib’s model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bio-informatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: i) downregulation in LC tissue (indicating “second hit” in tumor suppressor genes); ii) upregulation in cancer tissue (likely oncogene); iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with functional effect in tumor predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of familial clustering of non-small cell lung cancer. In conclusion, these findings indicate that each patient has his/her own “predisposing signature” to cancer development and suggest the use of personalized therapeutic strategies in lung cancer.

This longitudinal study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n=40; 56.78±6.38 years). Participants were divided into two groups: one rowed in fixed seat rowing (FSR) boats (n=20; 56.35±4.89 years) and the other in sliding seat rowing (SSR) boats (n=20; 57.20±7.7 years). Both groups engaged in two 75-minute sessions per week for 24 weeks. Significant improvements were observed in both groups in resting heart rate (FSR: -10.65 bpm; SSR: -8.45 bpm), heart rate at the beginning of the 6-minute walk test (6MWT) (FSR: -10.7 bpm; SSR: -11.25 bpm), and heart rate at the end of the test (FSR: -13.85 bpm; SSR: -20.35 bpm). Blood pressure improved significantly in both diastolic blood pressure (FSR: -12.35 mmHg; SSR: -19.25 mmHg) and systolic blood pressure (FSR: -13 mmHg; SSR: -16.95 mmHg). Additionally, both groups increased the distance covered in the 6MWT (FSR: +63.05 m; SSR: +93.65 m). These results suggest that a rowing training program is a viable and safe activity for female breast cancer survivors, improving cardiac function, blood pressure, and cardiorespiratory capacity, particularly in sliding seat boats.

Background and Objectives: The risk of developing cardiovascular diseases (CVD) in patients suffering from rheumatoid arthritis (RA) is two times higher compared to the general population. The objective of this retrospective study was to determine the type of cardiovascular complications that can appear in men vs. women with rheumatoid arth-ritis. Early diagnosis and initiation of therapeutic measures to reduce the progression rate of rheumatoid arthritis, while also maintaining an active lifestyle, are the most important problems in young patients. Materials and Methods: We included a number of 200 pa-tients, divided in 2 groups according to gender (124 women and 76 men) with rheumatoid arthritis, presenting various stages of disease concomitant with cardiovascular complications. We assessed traditional and non-traditional risk factors, electrocardio-graphic and echocardiographic findings in both groups. Results: All patients presented an atherogenic coefficient over two, indicating a significant risk of atherogenesis. Men had elevated levels of total cholesterol compared with women (≥ 200 mg/dL; 77.6% - men vs. 25.8% - women, p<0.001). The participants presented cardiac arrhythmias, especially in the active stage of RA. Women had an increased risk of atrial fibrillation by 2.308 times compared with men (p=0.020). One of the most important complications in young women was pulmonary arterial hypertension (p=0.007). Conclusion: However, in daily clinical practice, the screening for RA is poorly done. Thus, patients are often undiagnosed, while the risk factors are not assessed and RA patients continue to present an increased risk of developing CVD.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

The focus of this work lies in the construction of monitoring system designed in the form of a patch using a long-lasting potentiometric electrolyte concentration sensor from metal electrodes, in a galvanic cell configuration Mg(s)|NaCl(aq)|Cu(s). Initially, a mathematical analysis was conducted on the expected sensor output through the Nernst equation. The experimental phase involved conducting controlled tests in the laboratory using various molar concentrations of sodium chloride (NaCl) in aqueous solution. Results showed that the electrolyte sensor allows for monitoring electrolyte levels in NaCl in the range of 0.02 to 1 M/L, with electrode lifespan exceeding 10 days. On the other hand, when patch is using human sweat during controlled exercise routines, it showed the sensor's capability for monitoring changes in the subjects' hydration levels in real time. The sensor output potential is greater than 1.7 volts when the sensor electrodes are in contact with human sweat, which is equivalent to measuring molar concentrations at normal hydration and moderately high hydration levels. Sensor results indicate that the system can function in a self-powered manner without external batteries. Additionally, the extended lifespan of its electrodes allows for continuous monitoring of imbalances in the human body, showcasing the system capability for long-term health assessment.

Antiviral therapy such as Oseltamivir has been recommended for hospitalized children with suspected and confirmed influenza for almost 20 years. The therapy is officially authorized for newborns two weeks of age or older, however, questions about its safety and effectiveness still surround it. Our goal was to assess the epidemiological features of two consecutive seasonal in-fluenza cases in children following the COVID-19 pandemic and also to observe the clinical ef-fectiveness and tolerability of oseltamivir in hospitalized children who were not vaccinated against influenza and who had different influenza subtypes, including A (H1N1), A (H3N2), and influenza B, and to identify specific comorbidities associated with influenza in children. We performed an observational study on 1300 children, enrolled between 1st October 2022 and 30th May 2023 and 1st October 2023-4th of May 2024, to the IX Pediatric Infectious Diseases Clinical Section of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș". During the 2022-2023 influenza sea-son, 791 pediatric patients tested positive for influenza and received Oseltamivir. Of these, 89% (704/791) had influenza A, with 86.4% subtypes A(H1N1) and 13.6% of cases had A(H3N2), and influ-enza B 11%(87/791) pediatric patients. Of the total group, 59% were male, and the median age was 2,4 years (1.02-9.28). For the 2023-2024 influenza season, 509 pediatric patients tested positive for influen-za, 56.9% were male gender and were treated with Oseltamivir. 81.6 % had Influenza A, and 18.4% had influenza B. Treatment with neuraminidase inhibitors like Oseltamivir, 2mg/kg/dose twice daily for 5 days, was well tolerated by the children, and we recorded no deaths. The duration of fever hospitaliza-tion after the Oseltamivir administration was significantly longer for patients with A(H1N1) infection than A(H3N2), during both seasons. We identified more complications in the 2022-2023 season and a decreasing number of Influenza B for the 2023-2024 season. Among children with comorbidities, the most common were asthma, gastrointestinal disorders, and metabolic and endocrine diseases. In terms of effectiveness, oseltamivir significantly reduced the intensity of influenza symptoms, thus reducing the number of days of hospitalization (p=0.001) as well as post-infection complications (p=0.005) in both groups. Oseltamivir was less effective in Influenza A (H1N1) than A(H3N2), (p=0.0035). In this study, we evaluated the clinical effectiveness of oseltamivir therapy for all influenza types/subtypes in children, and the length of hospitalization. We identified comorbidities associated with prolonged dura-tion of hospitalisation. Influenza vaccination should be the main tool in the prevention of influenza and its complications in children, especially with comorbidities.

Objectives: To study sociodemographic and clinical variables including psychiatric comorbidities in patients with irritable bowel syndrome. Methods: A total of 150 patients were screened to select 100 patients for the study who were attending a medical gastroenterology clinic in a tertiary care centre in north India. Diagnosis of IBS was made using Rome IV criteria and severity of symptoms were assessed by the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS). Clinical evaluation was done for screening of psychiatric comorbidities and diagnosis was made as per DSM 5. Depression, Anxiety and Stress Scale - 21 Items (DASS-21) and Somatic Symptom Scale–8 (SSS-8) were used to assess depression, anxiety, stress and somatic symptoms. Result: The mean age of cases was 35.6 years and majority were i.e., 38.0% in 18-29 years. Males were 62.0% and females were 38.0%. 61.0% of the cases were diagnosed with Moderate IBS. Evaluation on DASS-21 revealed 53.0% were in moderate category in depression, 43.0% were having moderate anxiety and 36.0% were having moderate stress. 48% cases were in high category in somatic symptom scale. Psychiatric comorbidities were present in 29.0% of cases. Depressive disorders were most common psychiatric comorbidity. Conclusion: Patients with IBS presenting to tertiary care centre in Northern India were mostly young males living in semi-urban area, belonging to hindu region, married and had a nuclear family. Patients with IBS commonly have associated psychiatric disorders; anxiety disorders and depression are most common.

Objective: To determine demographic predictors and comorbidities in hospitalized children with conduct disorder. Methods: A retrospective analysis was performed using Nationwide Inpatient Sample (2012–2014). All patients were ≤18 years and cases with primary diagnosis of conduct disorder (N = 32345) and a comparison group with another psychiatric diagnosis (N = 410,479) were identified using ICD-9-CM diagnosis codes. A logistic regression model was used to generate the Odds Ratio (OR) between both groups. Results: Children <11 years old have five times greater chances of admission for conduct disorder than adolescent (OR 5.339). African American males are more likely to be admitted for conduct disorder. Children with conduct disorder from low-income families have a 1.5 times higher likelihood for inpatient admission compared to high-income families. These children have about eleven times higher odds of comorbid psychosis (OR 11.810) and seven times for depression (OR 7.093) compared to the comparison group. Conclusion: Conduct disorders are more debilitating for children and families than many providers realize. African American male under 11 years is at the highest risk for inpatient management for conduct disorder. These patients have a higher risk of comorbid psychosis and depression which may further deteriorate the severity of illness and require acute inpatient care.

Microplastics (plastic particles &lt; 5 mm) are ubiquitous pollutants that pose the ability to carry microbiota, including pathogens. Microbial adhesion is usually a sign of pathogenicity, thus we investigated the adherent strains found on 4 mm nylon strips, which were ingested and excreted by wild fish specimens. Polymer analysis of the excreted samples shown no signs of degradation, nor have their controls, represented by the nylon strips submerged in the same water tanks. Both the ingested samples and controls presented pathogens in large numbers, revealing the fact that nylon microplastics can be physical carriers for pathogens in the aquatic environment.

Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The electromechanical, inflammatory, and autonomic changes due to amyloid deposition result in arrhythmias. Atrial fibrillation is by far the most common arrhythmia. Rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted irrespective of CHA2DS2Vasc score in patients with favorable bleeding profile; data on left appendage closure devices is still insufficient. Ventricular arrhythmias are also not uncommon and the role of implantable cardioverter-defibrillator in cardiac amyloidosis is controversial. There is no evidence of improvement in outcomes when used for primary prevention in these patients. Bradyarrhythmia is most commonly associated with sudden cardiac death in cardiac amyloidosis. Pacemaker implantation can help provide symptomatic relief but does not confer mortality benefit.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Background/Objectives: Periodontitis (P), a chronic inflammatory condition that affects the supportive tissues around the teeth, is 3 to 4 times more prevalent in individuals with diabetes mellitus (DM), with a direct correlation between its severity and the levels of glycosylated haemoglobin (HbA1c). This study aimed to evaluate the periodontal clinical parameters following non-surgical periodontal treatment (NSPT) in patients with and without type 2 DM and P. Methods: Forty patients with P were divided into two groups: Group DM/P and Group P. All patients were assessed at baseline, and 90 and 180 days after receiving NSPT. The parameters evaluated included HbA1c levels, plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BoP). Statistical analysis was performed with a significance level set at α = 5%. Results: There were significant differences in HbA1c levels between the DM/P and P groups at baseline, 90, and 180 days, as expected. Importantly, HbA1c levels did not change after NSPT. Group P showed a significant reduction in both PI and BoP values at 90 and 180 days (p &lt; 0.05). In contrast, group DM/P demonstrated a significant increase in the percentage of sites with PPD ≥ 5mm at 180 days (p &lt; 0.05). Additionally, group P exhibited an increase in sites with PPD ≤ 4mm and a decrease in sites with PPD ≥ 5mm at both 90 and 180 days (p &lt; 0.05). Conclusions: Our findings suggest that DM may compromise the effectiveness of NSPT, potentially hindering favorable outcomes during the follow-up period.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Introduction: Migraine is a highly disabling neurological condition with substantial variability in its clinical presentation. This study aimed to explore the influence of familial transmission of comorbid medical conditions on the phenotype of chronic and episodic migraine. Methods: A total of 500 patients who presented to a private tertiary headache clinic were categorized into episodic and chronic migraine groups based on the International Classification of Headache Disorders-3 criteria. Data on demographics, clinical symptoms, and familial medical history were collected. Statistical analysis included chi-square and independent sample t-tests to evaluate the impact of familial comorbidities on migraine phenotypes. Results: Of the participants, 63% were diagnosed with episodic migraine and 37% with chronic migraine. Significant findings included higher rates of medication overuse (63.31%) and allodynia (58.82%) in patients with chronic migraine. Notably, patients with a maternal history of hypercholesterolemia showed a higher prevalence of chronic migraine (78.6%), whereas those with both parents affected tended to have episodic migraine. Educational levels are inversely correlated with the prevalence of chronic migraine, suggesting a socioeconomic influence on migraine chronification. Discussion: This study highlights significant associations between familial health conditions and migraine phenotypes. The findings suggest that the maternal transmission of comorbidities, particularly hypercholesterolemia, may influence the development of chronic migraine. These results underscore the importance of considering familial medical history in the management and understanding of migraine.

The beating heart is subject to intrinsic mechanical factors, exerted by contraction of the myocardium (stretch and strain) and fluid forces of the enclosed blood (wall shear stress). The earliest contractions of the heart occur already in the 10-somite stage in the tubular as yet unsegmented heart. With development the looping heart becomes asymmetric providing varying diameters and curvatures resulting in unequal flow profiles. These flow profiles exert various wall shear stresses and as a consequence different expression patterns of shear responsive genes. In this paper we investigate the morphological changes of the heart after changes the blood flow by ligation of the right vitelline vein in a model chicken embryo and analyze the extended expression in the endocardial cushions of the shear responsive gene Tgfbeta receptor III. A major phenomenon is the diminished endocardial-mesenchymal transition resulting in hypoplastic (even absence of) atrioventricular and outflow tract endocardial cushions, that might be lethal in early phases. The surviving embryos exhibit several cardiac malformations including ventricular septal defects and malformed semilunar valves related to a malposition of the aortopulmonary septum and the enclosed neural crest cells. We discuss the results in the light of the interactions between several shear stress responsive signaling pathways including Vegf, Notch, Pdgf, Klf2, eNos, Endothelin and Tgfβ/Bmp/Smad.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

The anatomy of mature vertebrate hearts is marked by a looped design, which is roughly characterized by two components: (1), s-shaped (sigmoid) routing of the cardiac flow path(s), and (2,) bilaterally asymmetric (chiral) routing of the cardiac flow path(s). The looped heart design is regarded as a phylogenetically conserved feature among vertebrates and is thought to represent a significant determinant of the cardiac pumping function. It evolves during the embryonic period of development by a morphogenetic process called “cardiac looping”. During the past decades, remarkable progress has been made in the uncovering of the genetic, molecular, and biophysical factors contributing to cardiac looping. Thereby, a special focus was directed on the evolution of a bilaterally asymmetric (chiral) heart configuration, which is said to play a central role in the determination of the alignments and separations of the pulmonary and systemic flow paths in the multi-chambered hearts of tetrapods. In contrast to the recent progress made in uncovering of the biological driver of cardiac looping, our present knowledge about the functional consequences of cardiac looping is at an immature state. This article provides an overview and discussion of the currently available information about the looped design of vertebrate hearts and its functional implications.

Results: A total of 6270 individuals were assessed (1615 severe and 4655 non-severe patients). The median age was 63 (95% CI: 49-74) and 47 (95% CI: 19-63) years in the severe and non-severe groups, respectively. Moreover, about 41% of patients had comorbidities. Severity was higher in patients with history of cerebrovascular disease: OR 4.85 (95% CI: 3.11-7.57). The odds of being in severe group increase by 4.81(95% CI: 3.43-6.74) for history of cardiovascular disease (CVD). This was 4.19 (95% CI: 2.84-6.19) for chronic lung disease and 3.18, 95% CI: 2.09-4.82 for cancer .The odds ratio of a diabetes and hypertension were 2.61 (95% CI: 2.02-3.3), and 2.37( 95% CI: 1.80-3.13) respectively.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Background: Very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of VLCKD in patients with Cushing’s disease (CD) as adjunctive therapy to treatment for primary disease. Methods: We evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline and after 1 week and 3 weeks of VLCKD and further 2 weeks of low-carbohydrate ketogenic diet (LCKD). Results: After 5 weeks of diet a significant decrease in BMI (p=0.002), waist circumference (WC) (p=0.024), systolic (p=0.015) and diastolic blood pressure (p=0.005), ACTH (p=0.026), cortisone (p=0.025), total (p=0.006) and LDL cholesterol (p=0.017), triglycerides (p=0.016), alkaline phosphatase (p=0.008) and a significant increase in HDL cholesterol (p=0.017), vitamin D (p=0.015) and oral disposition index (Dio)(p=0.004) was observed in CD. A significant decrease in BMI (p=0.003), WC (p=0.002), systolic (p=0.025) and diastolic (p=0.007) blood pressure and total cholesterol (p=0.026) and increase in HDL cholesterol (p=0.001) and DIo (p&lt;0.001) was observed in controls. Conclusions: The current study confirms that ketogenic diet is effective in improving metabolic disorders and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities.

Pharmacogenomics may improve patient care by guiding drug selection and dosing, however this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe co-morbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV, and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using literature, a list of pharmacogenes vital in disposition of the top 20 drugs was constructed leading to drug-gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants and statins were frequently prescribed cholesterol lowering drugs. HIV was reported in 20.3% of the study participants with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Borderline Personality Disorder (BPD) is a complex and severe mental disorder. It is associated with greater use of medical services. It is characterized by intense fear of abandonment, recurring suicidal thoughts or self-harm, paranoid ideation or dissociation, identity difficulties, chronic feelings of emptiness, impulsive behavior and unstable moods and relationships. BPD is one of the most prevalent personality disorders with a higher diagnosis in females. For a diagnosis of BPD in patients, they must have a chronic pattern of functional impairment in addition to five of nine listed DSM-5 criteria. This review was a narrative literature search between 2000 to 2023 with a focus on BPD comorbidities. Results: Researchers observed a complex pattern of comorbidities with BPD that connects with other externalizing and internalizing disorders. BPD has a high comorbidity rate with mood disorders including bipolar I and II disorders, major depressive disorder, anxiety disorders, panic disorder alcohol use disorder, nicotine dependence, marijuana dependance, posttraumatic stress disorder, other personality disorders, binge eating disorder and ADHD. Diagnosis and management of BPD in presence of some of these disorders are discussed.

Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. This review offers a comprehensive overview of current advancements and strategies in cardiac regeneration, with a specific focus on regenerative medicine and tissue engineering-based approaches. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regeneration. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. Despite significant progress, several challenges persist in the field of cardiac regeneration. These include enhancing cell survival and engraftment, achieving proper vascularization, and ensuring the long-term functionality of engineered constructs. Overcoming these obstacles offering effective therapies to restore cardiac function could improve the quality of life for individuals with heart diseases.

In this paper we suggest a first ever construction of fractional integral and differential operators based on signed measures including a vector-valued case. The study focuses on constructing the fractional power of the Riemann-Stieltjes integral with a signed measure, using semigroup theory. The main result is a theorem that provides the exact form of a semigroup for the Riemann-Stieltjes integral with a measure having a countable number of extrema. The article provides examples of semigroups based on integral operators with signed measures and discusses the fractional powers of differential operators with partial derivatives.

Background The aims of this study were to assess the peri-operative morbidity, mortality and long-term survival of octogenarians undergoing ATAAD repair, and to compare open and closed distal anastomosis techniques. Methods This was a single-centre retrospective study (2007-2021). Open versus closed distal anastomosis were compared. Uni and multi-variable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Kaplan-Meier and Cox proportional hazards methods were used to compare long-term survival. Results Fifty octogenarians patients were included (median age - 82 years, closed distal – 22, open distal - 28). Median CPB time was 187 minutes (open distal vs closed distal group; 219 minutes vs 115.5 minutes, p30 days or return to theatre; HR; 4.1, p=0.02) predicted adverse survival. Open distal anastomosis did no impact survival. Conclusions – ATAAD repair in selected octogenarians has favourable short and long-term survival. There is no significant difference between open versus closed distal anastomosis strategies.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in ADL. Fractures in the elderly people are associated with bone fragility. Diabetes and chronic kidney disease are associated with bone fragility. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate and compare three different boosters in individuals who received two doses of the BBIBP-CorV vaccine including underlying diseases and healthy cases as control. One hundred forty subjects including 63 ones with at least one of three underlying diseases (UD) (including obesity, hypertension, and diabetes mellitus) and 77 healthy ones (HC) who had received a booster dose (either PastoCovac Plus or PastoCovac or BBIBP-CorV) were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 post-booster shot for evaluating safety outcomes. Significantly increased titers of anti-spike, anti-RBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose, although the titer rise of anti-spike IgG and anti-RBD IgG was insignificantly inferior in the UD group compared to the HC group. All antibodies’ titers declined, with no significant differences between the two groups over time. Notably, all specific antibodies persisted up to 180 days; particularly the neutralizing antibody in both groups. Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension sub-group. PastoCovac Plus and PastoCovac boosters induced higher antibodies’ fold rise in UD individuals than BBIBP-CorV booster recipients. Safety outcomes did not show any serious AEs after the booster injection. The overall incidence of AEs post the booster injection was higher in the UD group than the HC group. Furthermore, the highest systemic AEs rate was reported in the UD group receiving the BBIBP-CorV booster. In conclusion, administration of COVID-19 boosters can equally induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with 2-doses of the BBIBP-CorV. Protein-based boosters with higher antibodies' fold rise and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

Cardiomyopathy is the leading cause of morbidity and mortality among all complications of type 2 diabetes (T2D) and obese patients. Diabetic cardiomyopathy (DC) is characterized by changes in cardiac morphology with declines in both systolic and diastolic functions. No rodent models fully captured phenotypes of DC. The ZDSD rat, a new generation of T2D rat model with intact leptin signaling features with slow onset of diabetes and obesity, which closely mimics the development of the disease in patients. Age-matched male ZDSD and SD rats were monitored for blood pressure, glucose and cardiac function using echocardiography. Animals were also challenged with 1 mg/kg dobutamine for the assessment of cardiac reserve. ZDSD rats developed hypertension from age of 18 weeks with blood pressure significantly higher than controls. At resting state, ZDSD rats showed biphasic changes in left ventricular posterior wall thickness and cavity volume. Concomitantly, both ejection fraction (EF) and transmitral E/A ratio of LV declined at 34 weeks old. Upon treatment with dobutamine, ZDSD lost cardiac contractility. Therefore, ZDSD rats may serve as a suitable preclinical model to study potential therapeutic approaches to treat cardiomyopathy with presence of metabolic syndromes.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

This comprehensive review examines the role of fenoldopam, a selective dopamine-1 receptor agonist, in preventing and treating acute kidney injury (AKI) during cardiac surgery. AKI remains a significant complication in cardiac surgery, associated with increased morbidity, mortality, and healthcare costs. The review explores fenoldopam's pharmacological properties, mechanism of action, and clinical applications, synthesizing evidence from randomized controlled trials, meta-analyses, and observational studies. While some studies have shown promising results in improving renal function and reducing AKI incidence, others have failed to demonstrate significant benefits. The review discusses these conflicting findings, explores potential reasons for discrepancies, and identifies areas requiring further research. It also compares fenoldopam to other renoprotective strategies, including dopamine, diuretics, and N-acetylcysteine. The safety profile of fenoldopam, including common side effects and contraindications, is addressed. Current guidelines and recommendations for fenoldopam use in cardiac surgery are presented, along with a cost-effectiveness analysis. The review concludes by outlining future research directions and potential new applications of fenoldopam in cardiac surgery. By providing a thorough overview of the current state of knowledge, this review aims to facilitate informed decision-making for clinicians and researchers while highlighting areas for future investigation.

Rising child obesity rate creates a need for tools quantifying metabolic changes in obese children and adolescents for purposes of comorbidities early detection or prevention. A candidate for such role seem to be miRNAs – in vivo serving as the suppressing factors of the gene expression. The aim of this study was to review the recent discoveries in this field and to conclude directions of research or application of studied molecules. Repeated browsing of databases, followed by screening for eligibility of results, led to final approval of 9 articles. Filtered studies examined the differences in miRNA (miR) expression levels of obese subjects and children suffering from obesity comorbidities. Studies concerning the endothelial dysfunction (ED) identified miR-630 as a possible treatment option. Search for the alternative markers in diagnosis of non-alcoholic fatty liver disease (NAFLD) suggested value of miR-199a-5p and miR-122. MiR-486, miR-146b and miR-15b may serve as a panel of markers grading the development of type 2 diabetes mellitus (T2DM) in children, although further research raised doubts in that matter. Another panel of miRNA molecules was indicated as useful in early detection of alterations leading to metabolic syndrome (MetS). No valid link between studied miRNAs and atherosclerosis (AS) was found. MiRNAs seem to be promising prognostic markers for the diagnosis of NAFLD, T2DM and MetS in children. Further studies are required to support these findings.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul." The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability," on which the heartbeat depended and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of ARIs (acute respiratory infections) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 ARIs.

Mucinous breast carcinoma is a rare subtype of mammary neoplasm encountered in medical practice. It represents approximately 1-6% of all breast cancers and is more common in postmenopausal women. There are two subtypes of mucinous breast carcinoma: pure and mixed. We report the case of a 73-year-old Caucasian woman diagnosed with mucinous pancreatic cystadenoma in 2007. She underwent a surgical procedure involving pancreatectomy of the body and tail, along with multiple known cardiovascular and metabolic comorbidities. In November 2019, during a clinical-biological evaluation for associated diseases, a mucinous carcinoma of the right breast was accidentally detected and later confirmed through further investigations. For treatment, a surgical procedure was performed involving lower right quadrantectomy with right axillary lymph node dissection. The postoperative clinical course was favorable. In conclusion, we present the case of a patient diagnosed with mixed mucinous breast carcinoma, without axillary lymph node invasion. Postmenopausal women with diabetes, overweight, and obesity have an increased susceptibility to breast cancer, with our patient having all these risk factors. To date, no study has demonstrated the genetic or radiation implication in the occurrence of mucinous carcinomas, nor the possible development of mucinous carcinomas in series in the same patient. Current data are insufficient to provide recommendations for the screening of malignant mucinous tumors in subjects with significant cardiometabolic risk factors.

Background. Neoplastic diseases and infections have become the leading causes of death in SLE in recent decades. Cancers and infections were also precipitating factors in the development of catastrophic APS. Case summary. We describe two patients: one of them had definite antiphospholipid syndrome (APS) and melanoma and the other had definite systemic lupus erythematosus (SLE) with APS, melanoma, infiltrative tuberculosis and severe Herpes Zoster (HZ). Management of patients with SLE concurrent with APS is a rather difficult task in rheumatology practice. In addition to kidney damage and cardiovascular disease, infections and malignancies are a significant cause of death in this cohort. The risk of malignancy in SLE is of considerable interest, since the immune and genetic pathways underlying the pathogenesis of this disease, as well as the immunosuppressive therapy, can significantly alter the risk. Both patients still had reliable APS, confirmed by triple-positive aPL. Both were at high risk of thrombosis. Patients ' adherence to treatment with direct oral anticoagulants and relapse of thrombosis on the background of rivaroxaban were noted. Conclusion. The cases where cancer or tuberculosis develops in the presence of rheumatic diseases are not so common and complicate the possibilities of therapeutic approaches, limiting the use of drugs that are not regulated by clinical recommendations.

Apolipoprotein A (ApoA), an integral component of high-density lipoprotein (HDL) particles, plays a vital role in the transport and metabolism of lipids. It is implicated in both cardiovascular (CVD) and neurological diseases. In the context of CVD, ApoAs are pivotal in facilitating the reverse transport of cholesterol, mitigating inflammation, and preserving endothelial function. These char- acteristics highlight the crucial role of ApoA in averting the onset of CVDs. Moreover, ApoA has been implicated in the pathogenesis of several diseases, such as Alzheimer's disease (AD), Parkin- son's disease (PD), and multiple sclerosis (MS). Apart from its role in lipid metabolism, recent stud- ies have indicated the involvement of ApoA in neuroprotection, amyloid-beta clearance, and regu- lation of neuroinflammation. This paper addresses the research question: "How do different isoforms of Apolipoprotein A influence the development and progression of cardiovascular and neurological diseases, and what are the potential therapeutic implications of targeting ApoA in these conditions?" By providing a comprehensive review of current knowledge, this paper empha- sizes the importance of ApoA in understanding the intricate connections between cardiovascular and neurological health, suggesting that ApoA-targeted interventions may help treat diseases in both domains.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.