In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

A single coronary artery is a very rare condition, commonly associated with other congenital anomalies. It could be generally classified as neither benign nor malignant form of congenital coronary artery anomalies since its pathophysiological and clinical implications grossly depend on different anatomical patterns defined by the site of origin and distribution of the branches. By presenting the patient with an isolated single coronary artery, who underwent successful combined aortic valve replacement and coronary artery bypass grafting surgery, we intend to distinguish casual from causal in this extremely rare clinical and surgical scenario. This is the first-ever case published, combining such underlying pathology, clinical presentation, and surgical treatment.

Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF=5.37, AGFI=0.915, NNFI=0.945, IFI=0.952, RMSEA=0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p < 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Background: Coronary tortuosity is a common angiographic finding. Scarce data is available on clinical profile of patients with coronary tortuosity (CT) and its relation with coronary artery disease (CAD). Method: A total 224 patients undergoing angiography for suspected CAD were included in the study. CT was defined by the presence of ≥3 consecutive bends of > 45 degree measured at end-diastole in an epicardial artery ≥2 mm in diameter. CT was present in 45(20.08%) patients in the study and another 45 patients without CT was randomly selected as control (NCT group). Clinical profile of CT and NCT group was compared. Results: Incidence of CT was significantly higher in females (p=0.000) and hypertensives (p=0.001) patients. CT was most commonly seen in Left circumflex coronary artery. Incidence of CAD was significantly lower in CT group as compare to NCT group (0.02). Risk factors for CAD was associated with reduced incidence of CT. Majority (88.46%) patient with CT without CAD presented with chronic stable angina out of which (65.21%) had an objective evidence of myocardial ischemia. Conclusion: CT is more commonly seen females and hypertensive patients. It has negative correlation with CAD. Risk factors of CAD do not predict CT. CT itself can lead to myocardial ischemia.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Rationale:First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrates modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.Patient Concerns:This case describes a 63-year-old male who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line poly-pharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.Diagnosis:Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction (MI). He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow up and, despite medical management over the past 6 years, his UA became progressively debilitating.Interventions and Outcomes:In conjunction with his standard cardiac care, patient had a gradual lessening of UA related pain, including frequency and character, after using an edible form of medical cannabis (MC) (1:1 CBD:THC). Following continued treatment, he ceased long term morphine treatment and describes the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.Lessons:This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA; while concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.

Coronary angiography, long considered the gold standard for coronary imaging, faces limitations in assessing coronary vessel wall anatomy and guiding percutaneous coronary intervention (PCI). Despite its prevalence, studies have demonstrated that it is suboptimal in estimating the severity of coronary disease and physiologic significance of stenosis. Intracoronary imaging techniques, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT), offer promising alternatives to overcome these limitations. This review delves into the nuances of IVUS and OCT, highlighting their strengths and limitations as adjuncts to PCI. IVUS, utilizing ultrasound technology, and OCT, based on near-infrared light, each provide unique insights into coronary pathology. They differ in terms of temporal and spatial resolution, influencing their capabilities in plaque characterization and vessel assessment. The discussion navigates their historical evolution, technical specifications, and clinical utility. Meta-analyses and adjusted observational studies suggest that both IVUS and OCT-guided PCI correlate with reduced cardiovascular risks compared to angiographic guidance alone. While IVUS has demonstrated consistent benefits in terms of clinical outcomes, the evidence supporting OCT is less robust. However, the utilization of these imaging modalities remains variable across regions, with increasing adoption in recent years, particularly in IVUS-guided PCIs. Intravascular ultrasound's journey from early motion detection to current high-resolution mechanical systems is traced, including improvements in catheter size and compatibility. On the other hand, optical coherence tomography has advanced significantly, utilizing near infrared light to achieve unparalleled resolutions, albeit requiring temporary blood clearance for optimal imaging. In conclusion, IVUS and OCT offer valuable insights into coronary pathophysiology and guide interventions with improved precision compared to traditional angiography. While IVUS remains more extensively utilized, OCT's growing potential is underscored by advancements in technology, culminating in enhanced imaging capabilities. Both modalities demonstrate comparable clinical outcomes, emphasizing the need for tailored imaging choices based on individual clinical scenarios. The continued refinement and broader integration of intravascular imaging are expected to play a pivotal role in optimizing coronary interventions and patient outcomes.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Previous studies had shown that mRNA, miRNA and lncRNA were associated with cardiovascular diseases. The study was aimed to explore the differential expressions of mRNA, lncRNA and miRNA between coronary artery disease (CAD) and healthy control, and their interaction in CAD. We investigated the differential expression of ceRNA between CAD and healthy control through data collected from Gene Expression Omnibus (GEO) microarrays. Furthermore, we investigated the biological function of these differential expressions of ceRNAs by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein-protein interaction (PPI) network was created to identify the hub genes. Biosystems and literature search were performed for signaling pathways and their function of the included differential expression ceRNAs. A total of 456 miRNA expression profiles, 16,325 mRNA expression profiles, and 2,869 lncRNA expression profiles were obtained. Eleven Go and KEGG pathways (count ≥9), top 15 of PPI network node connectivity rank, and top 15 of ceRNA network node degree centrality rank were achieved at the statistical significance level (P<0.05). We further identified that several differential expressions of ceRNAs and their signaling pathways were associated with CAD through biosystems and literature search. Based on eleven Go and KEGG pathways, top 15 of PPI network node connectivity rank, and top 15 of ceRNA network node degree centrality rank in CAD population, our findings would contribute to further exploration for the molecular mechanism of CAD.

A significant portion of fatalities stemming from acute myocardial infarction (AMI) occur suddenly and without warning. This can be prevented through early detection of coronary stenosis. In recent years, coronary artery calcium (CAC) and computed tomography coronary angiography (CTCA) have been utilized. For instance, a 55-year-old interventional cardiologist had a CAC of 58 with 50% stenosis involving his left anterior descending (LAD) artery. Despite possibly having vulnerable plaque, which carries significant future cardiovascular events, the patient followed a plant-based diet (PBD), took supplements, and continued optimal medical therapy (OMT). After three years, there was a significant regression in both CAC and stenosis. During our discussion, we emphasized the importance of food selection, quantification, and how food is processed (raw) to achieve maximal benefit in regressing atherosclerosis. Additionally, we highlighted the importance of identifying the possibility of vulnerable plaque and the mechanism stabilizing it. The case supported the guidelines set by the American College of Cardiology (ACC) and the American Heart Association (AHA) for managing chronic coronary syndrome (CCS) by emphasizing OMT and lifestyle changes. We hope that in the future, more doctors and patients will take responsibility for implementing lifestyle changes rather than solely relying on medications and sophisticated medical technologies.

About half of the transcatheter aortic valve replacement (TAVR) recipients exhibit some degree of coronary artery disease (CAD), and controversial results have been reported regarding the impact of the presence and severity of CAD on clinical outcomes post-TAVR. In addition to coronary angiography, promising data has been recently reported on the use of both cardiac computed tomography angiography and the functional invasive assessment of coronary lesions whether by FFR or iFR in the work-up pre-TAVR. Despite mitigated available data, percutaneous revascularization of significant coronary lesions has been the routine strategy in TAVR candidates with CAD. Also, scarce data exists on the incidence, characteristics and management of coronary events post-TAVR, and increasing interest exist on potential coronary access challenges in patients requiring coronary angiography/intervention post-TAVR. This review provides an updated overview of the knowledge of CAD in TAVR recipients, focusing on its prevalence, clinical impact, pre- and post-procedural evaluation and management.

(1) Background: To identify the association between the presence or absence of raphe and aortic valve dysfunction as well as the presence of aortopathy in patients with bicuspid aortic valve (BAV); (2) Methods: This retrospective study enrolled 312 participants (mean [SD] age, 52.7 [14.3] years; 227 men [72.8%]) with BAV. The BAVs were divided into those with presence (raphe+) or absence (raphe-) of raphe. Valvular function was classified as normal, aortic regurgitation (AR), or aortic stenosis (AS) using TTE. The pattern of BAV aortopathy was determined by the presence of dilatation at the sinus of Valsalva and the middle ascending aorta using CCT.; (3) Results: BAVs with raphe+ had a higher prevalence of AR (148 [79.5%] vs. 48 [37.8%], P < .001) but a lower prevalence of AS (90 [48.6%] vs. 99 [78.0%], P < .001) compared with those with raphe-. The types of BAV aortopathy were significantly different (P = 0.021) according to those with BAV-raphe+ and BAV-raphe-.; (4) Conclusions: The presence of a raphe was significantly associated with a higher prevalence of AR but a lower prevalence of AS and combined dilatation of the aortic root and middle ascending aorta. The presence of raphe was an independent determinant of AR.

Fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive imaging modalities, such as Coronary Computed Tomography Angiography (CCTA), and invasive coronary angiography or intravascular imaging. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy in comparison to the invasive FFR using pressure wires. These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice. This review aims to present all the data on the studies and methodologies that have been presented for the virtual estimation of FFR, and the diagnostic execution of the virtual tools for the hemodynamic assessment of coronary lesions compared to the invasive FFR.

Background Coronary artery disease (CAD) is a widely recognized cardiovascular disease that is considered the leading cause of death worldwide, affecting people on a global scale. Percutaneous coronary intervention (PCI), which involves procedures such as balloon angioplasty or stenting, plays an important role in opening blocked arteries and minimizing damage to the cardiac muscle. While the use of drug-eluting stents (DESs) has significantly reduced the occurrence of coronary restenosis, the problem of in-stent restenosis (ISR) continues to pose a significant clinical challenge. Gaining a deeper understanding of the clinical predictors associated with ISR is vital for early detection and appropriate treatment. Hence, this study aimed to evaluate the clinical predictors of ISR specifically in Taiwanese patients. Methods We conducted a single-center, retrospective case-control study, enrolling 517 CAD patients undergoing previous coronary stenting and stable angina with positive stress test or acute coronary syndrome (ACS) during follow-up between January 2019 and December 2022 at National Taiwan University Hospital. The patients were categorized into two groups: the ISR group, consisting of individuals who received drug-coated balloon (DCB) treatment (n=177), and the non-ISR group, comprising patients who did not receive DCB treatment (n=340). To gather relevant data, we meticulously reviewed the medical records and analyzed the findings from coronary angiography to assess the clinical characteristics of the patients. Results Patients with three-vessel disease (3VD) exhibited a higher prevalence of underlying diseases and were more likely to be taking aspirin and clopidogrel. Moreover, our analysis revealed that age (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00 - 1.04, p = 0.037) and the presence of 3VD (adjusted odds ratio [aOR] 2.15, 95% confidence interval [CI] 1.03 - 4.46, p = 0.039) were significantly associated with an increased risk of coronary ISR. Conclusions Older age and 3VD were the independent predictors of coronary ISR in CAD patients receiving coronary stent implantation.

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring V. cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 cholera patients enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titers. At this saliva titer, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between Vibrio Cholerae saliva and serum antibodies (rho=0.66, p&lt;0.001). In conclusion, saliva-based diagnostic cholera tests has high diagnostic accuracy, and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.

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.

Background: Although persistent systemic inflammation is considered to be predictive for future cardiovascular events, it remains unclear whether or not C-reactive protein (CrP) plays an active role in coronary-plaque instability. Here, we report a case of a patient with failed and super-infected renal allograft as a source for systemic inflammation presenting with repeat acute coronary syndromes. Case presentation: A 52-years-old male type-2 diabetic with a failed kidney transplant who was hospitalized for acute urinary-tract infection. In the presence of other, classic cardiovascular risk factors, peak values of CrP coincided with episodes of unstable angina treated by percutaneous coronary interventions. Besides pyelonephritis, the histological examination of the kidney transplant revealed signs of chronic rejection and the presence of a renal cell carcinoma in situ. Once the renal allograft has been removed, systemic inflammation was attenuated, the patient was not re-hospitalized for acute-coronary syndrome within the next 12 months. Conclusion: In this case, systemic inflammation was paralleled by instability of coronary plaques as documented by repeat percutaneous coronary interventions.

Coronary revascularization is one of the most studied treatment modalities in cardiology, however, there is no consensus among experts about its indications in patients with stable coronary artery disease (SCAD). Contemporary data regarding the role of revascularization in SCAD are in clear conflict with the current European guidelines. This article discusses the main statements of the most significant American and European Guidelines on myocardial revascularization of the last decade, and also analyzes the appropriateness of revascularization to improve the prognosis and symptoms in CCS in the light of new research data, primarily the ISCHEMIA study (NCT01471522) and ACC/AHA 2021 Revascularization Guidelines based on them. Data on the revascularization in CCS obtained after the completion of ISCHEMIA (including the interim analysis of ISCHEMIA-EXTEND) and their potential significance are discussed. The results of ISCHEMIA sub-analyses in the most important ‘controversial’ subgroups (3-vessel disease, proximal left anterior descending artery (LAD) disease, strongly positive stress test, etc.) are reviewed, as well as the results of the ISCHEMIA-CKD substudy in patients with severe chronic kidney disease (CKD).

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Metabolic syndrome, diabetes and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise, and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. Also, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising biomarkers and therapeutic targets for these conditions. This systematic review conducts a thorough analysis of the literature, with a specific focus on investigating miRNA expression patterns in patients with CAD and hypertension. The review encompasses an unspecified number of eligible studies that employed a variety of patient demographics and research methodologies, resulting in diverse miRNA expression profiles. This review highlights the complex involvement of miRNAs in CAD and hypertension and the potential for advances in diagnostic and therapeutic strategies. Future research endeavours are imperative to validate these findings and elucidate the precise roles of miRNAs in disease progression, offering promising avenues for innovative diagnostic tools and targeted interventions.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of aerodynamic diameter < 10 μm (PM10) on the incidence of ACS. Results: Desert dust intrusion on days 0 to 5 after ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM10 concentrations 1, 2, 3, 3, 4 and 5 days before ACS onset (for changes of 10 µg/m3) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18) and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of premature coronary heart disease.

Percutaneous coronary intervention(PCI) with stenting for the treatment of acute coronary syndrome(ACS) is the contemporary standard of care. Such treatment is followed by Dual anti-platelet therapy(DAPT) comprising of aspirin and a P2Y12 inhibitor. The efficacy of this therapy has been well established but the optimal duration of DAPT remains elusive, and has thus far attracted a prodigious deal of scientific attention. Decision regarding DAPT duration can be challenging clinically in the modern era with the evolution of newer stents, more potent antiplatelet agents and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. Major societal guidelines have emphasized comprehensive assessment of ischemic and bleeding risk, in turn recommending individualization of DAPT duration, thus encouraging "shared decision making". The following review is aimed at critically evaluating the available evidence to help make these crucial clinical decisions regarding duration of DAPT and triple therapy.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

Heart disease is one of the most common diseases in middle-aged citizens. Among the vast number of heart diseases, coronary artery disease (CAD) is considered a common cardiovascular disease with a high death rate. The most popular tool for diagnosing CAD is the use of medical imaging, e.g., angiography. However, angiography is known for being costly and also associated with a number of side effects. Hence, the purpose of this study is to increase the accuracy of coronary heart disease diagnosis by selecting significant predictive features in order of their ranking. In this study, we propose an integrated method using machine learning. The machine learning methods of random trees (RTs), the decision tree of C5.0, support vector machine (SVM), the decision tree of Chi-squared automatic interaction detection (CHAID) are used in this study. The proposed method shows promising results and the study confirms that the RTs model outperforms other models.

Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and is ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful and which can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.

Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. This plaque accumulation obstructs blood flow to the heart, resulting in a heart attack. While distinct features of CAD have been identified, its causes remain largely unclear, with the exception of environmental and nutritional factors. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in one-carbon metabolism. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T&gt;C and 1170A&gt;G genotypes with CAD susceptibility. We observed that TS 1100T&gt;C polymorphisms increased disease susceptibility in several groups, while the TS 1170A&gt;G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the 3'-UTR miRNA binding site of the TS gene could serve as clinically useful biomarkers for the prevention, prognosis, and management of CAD.

Background: Thoracic endovascular aortic repair (TEVAR) has become the standard treatment for blunt thoracic aortic injury (BTAI). Some small observational studies revealed aortic morphological changes after TEVAR in patients with BTAI. However, these studies were limited by the rarity of the condition and small sample sizes. To address this gap, the current study aims to conduct a systematic review and meta-analysis of existing literature to provide evidence on the degree of immediate and long-term aortic diameter change following TEVAR for BTAI. Methods: This systematic review and meta-analysis of studies published up to March 2023, was conducted in accordance with the PRISMA statement. Studies eligible for inclusion were studies evaluating aortic diameter change post-TEVAR in BTAI patients. Results: 14 articles, including 353 patients, were included after review. Treatment and measurement protocols varied among individual studies resulting in high heterogeneity of the results. Our meta-analysis demonstrated an immediate post-intervention dilation 2.41 mm and 2.63 mm of the proximal and distal aortic necks’, respectively, as well as continuous dilation of the respective regions at a rate of 0.35 mm/year and 0.49 mm/year. Conclusion: TEVAR in BTAI leads to immediate post-intervention and continuous aortic dilation and morphological changes with possible future important clinical consequences.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Introduction: It is demonstrated that both a familial history and genetic risk score are associated with subclinical atherosclerosis and most recently have been shown to each provide independent information for future cardiovascular events that seems additive when both are present. The exact mechanism that is responsible for higher risk of patients with positive familial history is yet unknown. In order to find this relationship in Iranian population because of lack of data, we assessed pattern of CAD involvement in patients with positive familial history and without. Methods: This was a cross sectional study that was performed between April 2019 and April 2020 in Imam Rezan and Ghaem Hospitals, Mashhad, Iran. We enrolled all patients with typical chest pain and markedly CAD such as STEMI, non-STEMI, unstable angina, chronic stable angina or sudden cardiac death. Patients’ age were between 18 to 65 years of old. They were divided into 2 groups: patient with familial history of CAD and those without and evaluated for potential risk factors of CAD. Results: This study was performed on 300 patients with CAD who underwent coronary angiography. Of these patients, 180 of them had positive familial history and 120 of them were without familial history. One hundred seventy five of participants were male (58.3%) with mean age of 54.2 years old. Multivariate regression analysis of risk factors showed that age (OR: 1.04, P=0.014), gender (OR: 0.564, P=0.035) and hypertension (OR: 1.99, P= 0.008) are significantly different in two groups. Vessel involvement in both groups showed that multi-vessel involvement in patients with positive familial history (49.2%) was higher than in patients without (36.1%). Three vessel disease (OR: 2.55, P=0.013) was significantly higher in patients with previous familial history rather than patients without after adjusting for other risk factors. Conclusion: In conclusion, we found that a positive familial history of CAD is associated with the severity, morphology (non-calcified and mixed) and extent of coronary atherosclerosis.

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcifica-tion, inflammation, and plaque vulnerability. They also participate in the vascular re-sponse during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evalua-tion of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant atten-tion. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognos-tic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an in-flammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunc-tion, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quan-titative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovas-cular events (MACE) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying cor-onary inflammation and subsequent high-risk plaque. These findings have been sup-ported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door to a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary pre-vention and intensive secondary prevention in patients at higher risk of cardiac events.

To evaluate the efficacy of fish oil for protection against coronary heart disease (CHD), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of fish oil for protection against CHD. We retrieved relevant articles published from January 1966 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. RCTs of fish oil in preventing CHD were selected. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. The first selection involved 350 citations. After screening and evaluation of suitability, 19 RCTs adjusted for clustering were included in the meta-analysis. All selected manuscripts considered that fish oil was effective in preventing CHD, secondary outcome measures included angina, sepsis and death. Compared with the control group, fish oil may confer significant protection against CHD (odds ratio = 0.84; 95% confidence interval: 0.72–0.98). There was no significant difference in the incidence of secondary outcomes between the observation group and the control group (P > 0.05). The above results show that fish oil plays an important role in reducing CHD and cardiovascular events. However, because of the suboptimal quality of the studies included into the meta-analysis, these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients.

Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae (n=676) isolated from patients hospitalized in 13 intensive care units (ICUs) in 6 European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. Majority were colistin-susceptible (CS) (n=597, MIC 2 µg/ml). 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS K. pneumoniae. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type and O-antigen type. Overall, 92% (618/671) of the K. pneumoniae were MDR with high prevalence among CS (540/592) and CR (98.7%, 78/79) isolates. In contrast, proportion of carbapenemase-producing K. pneumoniae (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.1%, 173/594). Proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and CS isolates (MDR: 91%, 539/592; CP-Kpn: 29.1%, 153/59). WGS analysis of PAP isolates showed diverse insertion elements in mgrB or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high ST diversity (Simpson’s diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, P ≤ 0.003). The widespread nature of CHR among MDR K. pneumoniae in our study urge the development of rapid HR detection methods to inform on the need for combination regimens.

Pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and an aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients, who had coronary heart disease served as „healthy controls“ All patients were surgically operated in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1, MMP9 and TIMP1, TIMP2 as well. Vascularization was monitored by an CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found smallest changes in the intima area at all. An increase in MMP 1 and MMP 9 expression was detected in both media and adventitia in case of dissections. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In case of arteriosclerotic changes, intima had a capillarization, but not in the media. Opposite pattern was found in the dissected aortas. Whereas the intima appears empty, vascularization was found in the media and adventitia layers, as well. There are differences in the vascularization between between the aneurysm and dissection and the different layers as well, respectively. A different remodeling process of the ECM in comparison of the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, a disturbed nutrition and a dysfunctional vasa vasorum remodeling must be assumed as cause of dissection.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute cor-onary syndrome (NSTE-ACS) requiring revascularization remain undefined. Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included and 300 matched patients with normal renal function were selected as a control cohort. Results: Diagnostic performance for patients with severe CKD was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p=0.68) and the ROC-derived cutoff value at presentation was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3-hour changes, sensitivity increased to 98%, PPV and NPV improved up to 93% and 86%, re-spectively. (4) Conclusions: In patients with severe CKD and suspected ACS the diagnostic accu-racy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay specific cutoff levels combined with early absolute changes.

Background: A significant percentage of younger patients with myocardial infarction have premature coronary artery disease (CAD). The aims of this study were to analyze all-cause mortality and major adverse cardiovascular events (MACE- cardiovascular death, non-fatal reinfarction and stroke and target vessel revascularization) during eight-year follow-up in STEMI patients with premature CAD. Method: we analyzed 2,560 STEMI patients without previous CAD and without cardiogenic shock at admission who were treated with primary PCI. CAD was classified as premature in men aged <50 years and women <55 years. Results: Of the 2,560 patients analyzed 630(24.6%) patients had premature CAD. Patients with premature CAD have fewer comorbidities and better initial angiographic findings, as compared to patients without premature CAD. The incidence of non-fatal adverse ischemic events was similar to the incidence in older patients. Premature CAD was an independent predictor for lower mortality (HR 0.50, 95%CI 0.28-0.91) and MACE (HR 0.27, 95%CI 0.15-0.47). In patients with premature CAD, EF<40% was the only independent predictor of mortality (HR 5.59 95%CI 2.18-8.52) and MACE (HR 4.18, 95%CI 1.98-8.13). Conclusion: Premature CAD was an independent predictor for lower mortality and MACE. In patients with premature CAD, EF<40% was an independent predictor of eight-year mortality and MACE.

Aims: Chronic coronary syndrome is associated with several risk factors, such as dyslipidemia and hypertension. AIP has been demonstrated to be a biochemical risk factor for coronary artery disease (CAD). This study aimed to determine whether AIP is an effective parameter for estimating obstructive CAD. Methods and Results: A total of 345 patients (mean age 62,2±10,3; 63% male) who underwent coronary angiography were included in this study. Obstructive CAD is defined as having one or more vessels with a stenosis of≥50%. Depending on the presence of obstructive CAD, all patients were divided into two groups. The AIP was significantly higher in the obstructive coronary artery group (AIP; 0,49±0,26 vs. 0,58±0,27, p=0,002). In univariate analysis, AIP was significantly associated with obstructive coronary artery disease [OD:3,74 (CI95% 1,62-8,64), P=0,020]. The AIP was further adjusted for confounding risk factors in three multivariate analysis models. Therefore, all three models showed a significant association. According to ROC analysis, 0.49 is the cut-off value for AIP, and a value above 0.49 indicates 50% coronary artery stenosis Conclusions: AIP may be used in the assessment of cardiovascular risk in patients with stable angina pectoris, and it may also be used to estimate obstructive CAD.

We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and P-values were calculated through adaptive permutation tests. Over one-year therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm&lt;0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm&lt;0.05). In conclusion, the polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients.

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

Numerous studies were published suggesting that troponin level is related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from an unselected blood sample taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p=0.017; 2.30 (1.37-3.88, p=0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease and adherent to treatment, troponin level is independently associated with death and heart failure hospitalization in a medium-term follow up.

Background: The presence of single nucleotide polymorphisms in the gene encoding key en-zyme in the folate pathway methyltetrahydrofolate reductase (MTHFR), causes methylation disorders associated with CAD development. Methods: Study group: 42 patients with CAD con-firmed by coronary angiography. Controls: 16 patients without CAD symptoms or significant coronary artery stenosis, based on invasive coronary angiography or multislice computed to-mography with coronary artery calcification scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined by LC-MS. Results: c.[1286A>C];[1286A>C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to (CAD-) cohort and to the European population. The con-centration of 5-MTHF and folic acid in the subgroups of patients with methylation disorders di-vided by genotypes and (CAD+) was lower compared to (CAD-). Conclusions: The homozygous c.1286 A>C MTHFR variant can be considered as CAD genetic marker. In the subjects with the c.1286 A>C heterozygous and homozygous genotypes, lower concentrations of methyltetrahy-drofolate (5-MTHF) were observed. 5-MTHF can be considered as a biomarker of CAD. Identifi-cation of people at high risk of CAD using genetic tests can contribute to personalized therapy using active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymor-phisms.

Kawasaki disease is a form of acute febrile multisystem vasculitis. In Japan, the Kobayashi score is used to predict intravenous immunoglobulin resistance and subsequent complications, including coronary artery abnormalities, in children with Kawasaki disease. If the score is high, it is standard practice to use steroids in the initial treatment of the disease. In this study, we describe a pediatric case of coronary artery abnormality formation after acute steroid treatment for Kawasaki disease, despite the lack of an inflammatory response and Kawasaki disease symptoms. The use of steroids with acute Kawasaki disease patients can mask laboratory findings and clinical symptoms. Echocardiogram should be considered an equivalent technique to physical examination.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Cadmium (Cd) is a metal with no nutritional or physiological value, but is found in most people because it is a contaminant in nearly all food types. The intestinal absorption rate determines the body burden of Cd because humans lack a physiologic mechanism for excretion of the metal. Most acquired Cd accumulates in the kidneys, in which the Cd content increases through age 50 but falls thereafter. The decline from maximal kidney content is probably due to release of Cd from injured tubular cells into urine and replacement of destroyed nephrons by scar tissue. Chronic kidney disease is diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2, or when albuminuria is present. Albuminuria is defined as an albumin-to-creatinine ratio ≥ 30 mg/g creatinine in women or ≥ 20 mg/g creatinine in men that persists for at least 3 months. Generally, Cd-induced reductions in eGFR are not reversible, and Cd nephropathy may progress to end-stage kidney disease. There is no evidence that elimination of current environmental exposure can reverse Cd nephropathy, and no theoretical reason to believe that such a reversal is possible. This review provides an update of knowledge concerning CKD in population environmentally exposed to Cd. Special attention is devoted to mechanisms of Cd-induced albuminuria concurrently with eGFR reductions, and the difficult challenge of exposure guidelines sufficient to eliminate the risk of Cd-induced CKD is addressed.

Backgroundː Previous studies have shown that both serum creatinine and D-dimer levels were associated with atherosclerotic coronary artery disease (CAD). We aimed to determine whether DCR is associated with coronary Gensini score in patients with ST-elevation myocardial infarction (STEMI). Methodsː 337 STEMI patients with complete D-dimer and creatinine and other necessary information were included in the analysis. According to the values of the DCR, patients were divided into the lower DCR group (DCR ≤ 1.42, n = 173) and the higher DCR group (DFR > 1.42, n = 174), and the differences between the two groups were compared. Multivariate linear and multivariate logistic regression analyses were performed to determine independent predictors of Gensini score. Resultsː High DCR group had higher Gensini score compared with low DCR group (P < 0.05). DCR was positively correlated with Gensini score (r=0.493, P < 0.001). Multiple linear regression analysis showed that Previous MI (r=11.312, P=0.035) and DCR (r=5.129, P<0.001) were independent risk factors associated with Gensini score. Multivariate logistic regression analysis showed that, compared to the group 1, DCR is independent risk factor for Group 2, Group 3, Group 4 (P <0.001). DCR is positively correlated with coronary Gensini score in STEMI patients and can be used as an independent predictor of higher Gensini score. Conclusionsː As a new and useful clinical marker, DCR is positively correlated with coronary Gensini score in STEMI patients and can be used as an independent predictor of higher Gensini score.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: 1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; 2) to create a national database with information on health care in ACS patients treated in Kosovo; 3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, length of hospital stay, and quality of clinical care; and 4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (Unstable angina, NSTEMI or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the Registry.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Minimally invasive approaches to the aortic valve have been described since 1993, with great hopes that they would become universal and facilitate day-case cardiac surgery. The literature has shown that these procedures can be undertaken with equivalent mortality, similar operative time, comparative cost and some benefits in hospital length of stay. The competing efforts of the transcatheter aortic valve implantation for these same outcomes have provided an excellent range of treatment options for patients from the Heart Team. We describe the current state of the art, including technical considerations, caveats and complications of minimal access aortic surgery and predict future directions in this space.

Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particular vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a hard outcome to be targeted, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD however, the optimal intensity of such therapy is still topic of debate, particularly in the post-acute and long-term setting. Recent well powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and patients selection is a key issue. The aim of this review is therefore to discuss and summarize the most updated available evidences for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both type of atherosclerotic disease and comparing a higher versus a lower intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improving precision medicine.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16%-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1%-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and most optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Nowadays, several therapeutic options are available for aortic valve stenosis (surgical valve replacement , transcatheter valve implantation, balloon valvuloplasty, or medical therapy), but in presence of malignancy, the use of one of these versus the others should be decided on a case-by-case approach, depending on cancer stage and associated treatment, expected outcome, comorbidities and after an accurate physical examination and Doppler-echocardiography which are the key tools for diagnosing and evaluating aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer, and therapeutic options.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n=207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis” Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); N=5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; N=15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (N=5/group) or fludrocortisone (N=15/group) into male ApoE -/- mice fed a normal laboratory diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 5 had ascending/arch pathologies, 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Given the low incidence, only ascending aortic diameter in LDLR -/- mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. The findings in mouse studies have the potential to provide caution to people who are taking or have taken fludrocortisone that could have an increased risk of aortic pathologies.

Transcatheter aortic valve implantation (TAVI) has grown exponentially within the cardiology and cardiac surgical spheres. It has now become a routine approach for treating aortic stenosis. Several uncertainties have been raised about TAVI in comparison to conventional surgical aortic valve replacement (SAVR). The primary concerns are with regards to the longevity of the valves. Several factors have been identified that may predict poor outcomes following TAVI. These include the lesser-used finite element analysis (FEA) to quantify the properties of calcifications that affect TAVI valves. This can also be used in conjunction with other integrated software to ascertain the functionality of these valves. Other imaging modalities are now widely available such as Multi-detector row computed tomography(MDCT) which can accurately size the aortic valve annulus.. This may help reduce the incidence of paravalvular leaks and regurgitation which may necessitate further intervention. Structural valve degeneration (SVD) remains a key factor with varying results from current studies. The true incidence of SVD in TAVI compared to SAVR remains unclear with the lack of long term data. It is now widely accepted that both are part of the armamentarium and are not mutually exclusive. Decision-making for the appropriate intervention should be made via shared decision-making involving the heart team.

Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic and develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infract size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.

Background Few data exist on comparative long-term outcomes of severe aortic stenosis (AS) patients with different flow-gradient patterns undergoing transcatheter aortic valve implantation (TAVI). This study sought to evaluate the impact of pre-TAVI flow-gradient pattern on long-term clinical outcomes after TAVI and assess changes in left ventricular ejection fraction (LVEF) of different subtypes of AS patients following TAVI. Methods Consecutive patients with severe AS undergoing TAVI in our institution were screened and prospectively enrolled. Patients were divided in four subgroups according to pre-TAVI flow/gradient pattern: (i) low flow - low gradient (LF-LG): stroke volume indexed (SVi) ≤ 35ml/m2 and mean gradient (MG) < 40mmHg), (ii) normal flow - low gradient (NF-LG): SVi > 35ml/m2 and MG < 40mmHg, (iii) low flow - high gradient (LF-HG) : SVi ≤ 35ml/m2 and MG ≥ 40mmHg and (iv) normal flow - high gradient (NF-HG): SVi > 35 ml/m2 and MG ≥ 40mmHg. Transthoracic echocardiography was repeated at 1-year follow-up. Clinical follow-up was obtained at 12 months, and yearly thereafter until 5-year follow up was complete for all patients. Results A total of 272 patients with complete echocardiographic and clinical follow-up were included in our analysis. Their mean age was 80±7 years and the majority of patients (N=138, 50.2%) were women. 62 patients (22.8% of the study population) were distributed in LF-LG group, 98 patients (36%) were LF-HG patients, 95 patients (34.9%) were NF-HG, while 17 patients (6.3%) were NF-LG. There was a greater prevalence of comorbidities among LF-LG AS patients. One-year all-cause mortality differed significantly between the four subgroups of AS patients (log rank p: 0.022) and was more prevalent among LF-LG patients (25.8%) compared to LF-HG (11.3%), NF-HG (6.3%) and NF-LG patients (18.8%). At 5-year follow-up, global mortality remained persistently higher among LF-LG patients (64.5%) compared to LF-HG (47.9%), NF-HG (42.9%) and NF-LG patients (58.8%) (log rank p: 0.029). At multivariable Cox hazard regression analysis, baseline SVi (HR: 0.951, 95% C.I.; 0.918 – 0.984), the presence of at least moderate tricuspid regurgitation at baseline (HR: 3.091, 95% C.I: 1.645 - 5.809) and at least moderate paravalvular leak (PVL) post-TAVI (HR: 1.456 , 95% C.I.: 1.106 - 1.792 ) were significant independent predictors of late global mortality. LF-LG patients and LF-HG patients exhibited a significant increase in LVEF at 1-year follow-up. A lower LVEF (p<0.001) and a lower Svi (p<0.001) at baseline were associated with LVEF improvement at 1 year. Conclusions Patients with LF-LG AS have acceptable 1-year outcomes with significant improvement in LVEF at 1-year follow-up, but exhibit an exceedingly high 5-year mortality following TAVI. The presence of low transvalvular flow and at least moderate tricuspid regurgitation at baseline and significant paravalvular leak post-TAVI were associated with poorer long-term outcomes in the entire cohort of AS patients. The presence of a low LVEF or a low SVi predicts LVEF improvement at 1-year.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Background: Genome-wide association studies have identified the chromosome 9p21 locus as one of the most important genetic risk factors for cardiovascular disease. However, the mechanism by which this locus promotes disease remains unclear due to difficulty identifying the causal genes and lack of a suitable animal model. Methods and Results: A total of 180 coronary artery autopsy specimens were analyzed histopathologically. The genotype of 9p21 (rs1333049) was not associated with any coronary risk factors nor the vulnerable plaque phenotype, but carriers of 9p21 risk allele did demonstrate more lesional calcification. To extend these studies into an animal model, mice with a targeted deletion of the orthologous 70-kb non-coding interval on chromosome 4 (chr4^D70kb/D70kb) were bred onto ApoE^-/- and fed with high fat diet. Targeted deletion of the 9p21 risk interval increased susceptibility to atherosclerotic plaque progression, but did not affect plaque rupture in the tandem stenosis model. Coronary risk factors such as body weight, blood pressure, lipid, and glucose levels did not differ between genotypes. Von Kossa staining revealed that chr4^D70kb/D70kb, ApoE^-/- developed more calcification in the plaque compared with chr4^+/+, ApoE^-/- mice, and that this this change was accompanied by increased aortic mRNA expression of Runx2, a key osteogenic transcription factor. Primarily cultured smooth muscle cells from chr4^D70kb/D70kb were hyperproliferative, and showed a calcification-prone phenotype after exposure to high-phosphate medium. Treatment with Palbociclib, a selective inhibitor of cyclin-dependent kinase 4/6, reduced mRNA expression of osteogenic genes in smooth muscle cells. Conclusion: Results from human and mouse studies indicate that the 9p21 non coding risk interval is associated with larger atherosclerotic plaque burden, but not with plaque rupture. 9p21 may promote lesion expansion by inducing the proliferation of de-differentiated and osteogenic smooth muscle cells.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Major cardiovascular events (MACE) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques is diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation the affected blood vessel diameter in order to decide if intervention with stent colocation is suitable, where small blood vessels (&lt; 2.75 mm) are majorly left untreated; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for recurrence of MACE, and there are some limitations to the use of CAG that could be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain their underuse. To address this discrepancy and identify specific cases for its use, we conducted a retrospective study in patients who underwent PCI for MACE with at least one small blood vessel affected. The affected small blood vessels’ diameter was obtained with both CAG and IVUS, additionally we underwent a multivariate analysis to identify risk factors associated with a change in diameter. We included information from 48 patients with mean + SD age of 69.1 + 11.9 years and 34% were masculine gender. We found a significant positive low correlation in diameter measurements of small blood vessels (r=0.1242 p=0.014). Mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9-2.2), and 2.8 (2.8-3.0) the estimated difference was of 0.8 mm (95 % CI 0.7-0.9). In total 37 (77%) of patients had a reclassification of their blood vessels from a small to medium (2.75-3.00 mm) in 21 cases, or even large (&lt;3.00 mm) in 15 cases, after IVUS; this was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjusted in a multivariate analysis was DT2 (p=0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in the diabetes population, therefore at least in these cases the use of IVUS is recommended over CAG.

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.

Background: Ceramides are a new kind of lipid biomarkers and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague and has been addressed in the present study. Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the coronary event risk test (CERT) score which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). Results: Kaplan Meier survival curves revealed that the overall survival of patients has decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that every 1-step increase in category resulted in a 35% rise in overall mortality risk (HR=1.35 [1.16-1.58]). Multivariable adjustment, including amongst others age, T2DM, and statin treatment before baseline, did not abrogate this significant association (HR=1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin is significantly stronger in patients with a higher risk according to CERT. Conclusion: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

ABSTRACT Purpose: Tongue image analysis for disease diagnosis is an ancient traditional non-invasive diagnosis technique widely used by traditional medicine practitioners. Deep Learning based multi-label disease detection models offer tremendous potential to clinical decision support systems, by facilitating preliminary diagnosis. Methods: In this work, we propose a multi-label disease detection pipeline, where in observation and analysis of tongue images captured and received via smartphones assist in predicting the health status of an individual. All images are voluntarily given by subjects consulting collaborating physicians. Images thus acquired are first and foremost classified either into a diseased or a normal category by a 5-fold cross-validation algorithm using a convolution neural network (MobileNetV2) model for binary classification. Once the diseased label is predicted, the image is used to diagnose multiple diseases using the prediction algorithm based on DenseNet121. Results: Average accuracy of 93 % was achieved in classifying diseased from normal healthy tongue by detection model with MobileNetV2 architecture. Multilabel disease classification produced more than 90% accurate results for the seven class labels considered. Conclusion: AI based image analysis shows promising results and an extensive dataset could provide further improvements to this approach. Rather than employing high-cost sophisticated image capturing setup, experimenting with smartphone images opens opportunity to provide preliminary health status to individuals on smartphone prior to further line of treatment and diagnosis.

Minimal access cardiac surgery appears to be the future. It is increasingly desired by cardiologists and demanded by patients who perceive superiority. Minimal access coronary artery revascularisation has been increasingly adopted throughout the world. Here we review the history of minimal access coronary revascularization and see that it is almost as old as the history of cardiac surgery. Modern minimal access coronary revascularization takes a variety of forms – namely minimal access direct coronary artery bypass grafting (MIDCAB), hybrid coronary revascularisation (HCR) and totally Endoscopic Coronary Artery Bypass Grafting (TECAB). It is noteworthy that there is significant variation in nomenclature and approaches for minimal access coronary surgery and this truly presents a challenge to comparing the different methods. However, these approaches are increasing in frequency and proponents demonstrate clear advantages for their patients. The challenge that remains, as for all areas of surgery, is demonstrating superiority of these techniques over tried and tested open techniques which is very difficult. There is a paucity of randomized controlled trials to help answer this question, and the future of minimal access coronary revascularisation to some extent is dependent on such trials. Thankfully some are underway and the results eagerly anticipated.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

Apple replant disease (ARD) is a complex issue caused by various fungal, oomycetes pathogens and parasites which can differ in their abundance between sites within a geographic region. Knowledge of the specific etiology of ARD at a particular site is required in order to develop commercially viable soil management strategies to combat specific/individual components of the disease. In this study we analyzed the soil from six ARD sites for the presence of fungal, bacterial and oomycetes communities and plant parasitic nematodes. Five fungal, and 17 bacterial classes were differentially represented in the microbiomes from different locations. Mortierellomycetes was the most abundant fungal taxa represented followed by Sordariomycetes. Mortierella exigua a fungal endophyte was the most abundant fungal amplicon sequence variant (ASV) in the core microbiome. Proteobacteria was the most prevalent phylum identified in orchard soils. Several potential phytopathogenic fungi involved in ARD and endophytes including Fusarium oxysporum, F. solani, Nectria ramulariae, Ilyonectria robusta and Nectriaceae were identfied in the orchard soil. Pythium attrantheridium (Globisporangium attrantheridium), P. monospermum and P. ultimum (Globisporangium ultimum) were the most abundant oomycete taxa identified in these soil samples. Six different groups of plant-parasitic nematodes were found across the six orchards soil. Root-lesion nematodes, Pratylenchus spp., which are commonly associated with ARD, were identified in all orchards soil at population densities ranging from 12 to 33/100 cm3 soil. This research contributes valuable understanding of the ARD complex as the apple industry needs alternative approaches to combat the disease.

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. OSA is associated with cardiovascular diseases such as coronary artery disease (CAD) and arrhythmias with an increased risk of sudden cardiac death. Some changes in ECG markers are seen as an indicator of arrhythmogenicity, especially ventricular arrhythmias. The goal of this study was to investigate if OSA patients with CAD have QT dispersion and T peak to T end (TpTe) changes as a surrogate of arrhythmogenicity. Methods: We studied 75 patients with CAD who underwent polysomnographic studies. Patients were categorized into mild, moderate, and severe OSA according to the Apnea hypopnea index (AHI). Baseline ECG and echocardiography for assessing LV function and valvular heart disease were done for all of them. Results: Results showed that in patients with moderate and severe sleep apnea QT dispersion was higher in a group with more involvement of coronary artery disease, reduced ejection fraction, and a history of old MI. However, we didn’t find any significant statistical relationship between OSA and TpTe marker. Conclusion: Our results showed a positive relation between ECG arrhythmic indices such as QT dispersion and OSA severity in patients with CAD.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

Elevated serum uric acid (sUA) is associated with risk of developing cardiovascular disease (CVD). Here, we examined the prognostic significance of sUA and exercise capacity in 411 Japanese adults (age, ≥65; mean, 81 years) hospitalized for worsening CVD. Mean sUA was significantly higher in the 23% of patients on an sUA-lowering agent than in those not. When the patients were stratified by sUA into three groups (7.0 mg/dL), the high sUA group had significantly worse peak VO2 and composite endpoint (rehospitalization due to worsening CVD and all-cause mortality) compared with low and moderate sUA groups (P < 0.001). When the patients were stratified by sUA into five groups (sUA 10.0 mg/dL), the incidence of the composite endpoint was significantly higher in the highest sUA group compared with that in the reference group, but only in women. Univariate Cox regression analysis, but not a multivariate analysis, indicated that sUA was significantly associated with the composite endpoint. Although sUA and exercise capacity may have some degree of prognostic significance in older patients with CVD, this significance may differ between men and women.

Visual exploration of complex data helps interpretation, especially in the case of omics data analysis in life sciences and clinical research. Generating and analysing omics data requires bioinformatic skills, while they are interpreted by domain experts, for whom parsing large and complex data structures may be challenging. However, outcomes of visual analytics are often difficult to quantify, which emphasises precision and reproducibility, especially for research on human diseases. Here, we propose a workflow combining a reproducible computational environment with a dedicated visualisation functionality for systems biology diagrams. By linking the Galaxy with the MINERVA Platform, we visualise and explore COVID-19 transcriptomic data to demonstrate the utility of our workflow. Visualised data recapitulate findings of the original publication and offer new insights about the COVID-19 pathology. Our results offer a blueprint for quick prototyping of computational workflows that facilitate communication and exploration of complex data in biomedical research.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16-0.53) in specific parks, notably Wolfe’s Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function and their interplay have accumulated resulting in advanced knowledge on complex functional characteristics of the aortic valve (AV) and root. This shifted the vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved with a similar shift towards treatments options that are more hemodynamically centered such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress related stimuli. Many of these physiological and hemodynamical processes are under acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision-making.

Aortic rupture is known as one of the potential causes of sudden cardiac death in athletes. Nevertheless, adaptation strategies for aortic root dilation in athletes vary. The purpose of this study was to investigate aortic root adaptation to physical workload and to determine if aortic root’s and left ventricle sizes are contingent upon the physical workload. Echocardiography was applied to 151 subjects to measure the aortic root at aortic valve annulus (AA) and at sinus of Valsalva (VS). 122 were athletes (41 females and 81 males) and 29 were non-athletes (14 females and 15 males). Of the 41 female athletes, 32 were endurance athletes, and 9 strength athletes. From 81 male athletes, 56 were endurance athletes, and 25 were strength athletes. AA and VS mean values for the body surface area were presented as rAA and rVS. Left ventricle (LV) meaures incuded LV end-diastolic diameter (LVEDD), interventricular septum thickness in diastole (IVSTd), LV posterior wall thickness in diastole (LVPWTd), LV mass (LVM), LV mass index, LV end-diastolic diameter index (LVEDDI). Results indicated that VS was higher in female athletes (28.9±2.36mm) than in non-athletes (27.19±2.87mm, p=0.03). On the other hand, rAA was higher in strength athletes (12.19±1.48mm/m2) than in endurance athletes (11.12±0.99mm/m2, p=0.04). Additionally, rVS and rAA were higher in female strength athletes (17.19±1.78mm/m2, 12.19±1.48mm/m2) than female basketball players (15.49±1.08mm/m2, p=0.03, 10.75±1.06 mm/m2, p=0.02). Statistically significant positive moderate correlations were found between VS and LVEDD, LVM, IVSTd, LVPWTd, rVS and LVEDDI parameters in all athletes. The diameter of Valsalva sinus was greater in female athletes compared to non-athletes. The rAA mean value for body surface area was greater in female athletes practising strength sports as compared to their counterparts who were practising endurance sports. The diameter of the aortic root at sinuses positively correlated with the LV size in all athletes. Trial was registered at ClinicalTrials.gov Identifier: NCT03656861, September 3, 2018 (retrospectively registered).

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

Objectives: Endovascular aneurysm repair (EVAR) in hostile neck has been associated with adverse outcomes. We aimed to determine the association of infrarenal aortic neck angle and length and establish an optimal cutoff value to predict intraoperative neck complications and post-operative outcomes. Methods: This was a retrospective review of intact infrarenal abdominal aortic aneurysm (AAA) with severe neck angulation (> 60 degrees) who underwent EVAR from October 2010 to October 2018. Demographic data, aneurysm morphology, and operative details were collected. The ratio of neck angle and length was calculated the optimal cutoff value of the aortic neck angle-length index. Patients were classified into two groups using latent profile analysis. Intraoperative neck complications, adjunct neck procedures, and early and late outcomes were compared. Results: 115 patients were included. Group 1(G1), aortic neck angle-length index ≤ 4.8, had 95 patients and Group 2 (G2), aortic neck angle-length index > 4.8, had 20 patients. Demographic data and aneurysm morphology were not significantly different between groups except for neck length (P < 0.001). G2 had more intra-operative neck complications than G1 (21.1% vs 55%, P = 0.005). Adjunctive neck procedures were more common in G2 (18.9% vs 60%, P < 0.001). Thirty-day mortality rate was not statistically different. G1 patients had a 5-year proximal neck re-intervention free rate comparable to G2 patients (93.7%G1 vs 87.5%G2, P = 0.785). The 5-year overall survival rate was not statistically different (59.9%G1 vs 69.2%G2, P = 0.891). Conclusions: Patients with aortic neck angle-length index > 4.8 are at greater risk of intraoperative neck complications and adjunctive neck procedures than patients with an aortic neck angle-length index ≤ 4.8. The 5-year proximal neck re-intervention free rate and the 5-year survival rate were not statistically different. The aortic neck angle-length index is a reliable predictor of intra-operative neck complications during EVAR in AAA with severe neck angulation.

Transcatheter Aortic Valve Implantation (TAVI) now represents the mainstay in the treatment of severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as a cornerstone. Leveraging data from multiple randomized controlled trials, current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without, or with atrial fibrillation respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual-patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Background: Atherosclerotic plaque (AP) vulnerability can be assessed by coronary artery imaging techniques. Modern lipid-lowering therapy (LLT) has a stabilizing effect on the AP and reduces the likelihood of progression of vascular remodeling. Methods: Databases searched comprised PubMed, and the Web of Science up to April 2023. In total, 8 relevant articles were selected, and all of them are original clinical studies. Results Based on the results of ODISSEY-J-IVUS, there was a decrease in the percentage change in the normalized total volume of AP by 3.1% in the monotherapy group and by 4.8% in the combined LLT group (p = 0.23). According to GLACOV study normalized total atheroma volume decreased by 0.9 mm3 in the placebo group and by 5.8 mm3 in the evolocumab group (95% CI -7.3 -2.5; p<0.001). Plaque regression was observed in 64.3% of patients receiving evolocumab versus 47.3% of those on placebo. The dynamics of the minimum thickness of the fibrous cap varied within 18.0-62.67 microns while on combined LLT and 13.2-33.19 microns on monotherapy (PACMAN-AMI, Gao F). In the HUYGENS study, a lipid arc regression of 57.5° was obtained on combined LLT and by 31.4° with the statin alone. Conclusion: significant progress in the development of cardiovascular imaging has made it possible to expand our understanding of the morphology of AP, the features of coronary vessel remodeling, and the development of acute cardiovascular complications.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

Background and Objectives: Wilson disease (WD) is a disorder of copper metabolism caused by genetic muta-tions in the ATP7B gene which lead to the accumulation of copper in the body. The aim of the present study is to investigate the severity of WD in patients in Romania. Materials and Methods: This study was conducted us-ing an online questionnaire consisting of 32 questions in a group of patients suffering from Wilson disease. Results: The study included 67 people aged 7 to 56 with WD. The most common symptoms of the participants were hepatic and neurological in 22 cases (32.8%). The most common neurological symptom in the assessed cases was muscle stiffness (49.5%), followed by tremor (45%), and speech disorders (40.5%). The Kay-ser-Fleischer ring was present in 50.7% of the participants. The most commonly used drug treatment in the participants was D-penicillamine (77.61%). Conclusions: The severity of WD is based on many aspects, the most important being early diagnosis and access to treatment throughout the year. The prognosis is favorable with early diagnosis and treatment, but it is crucial to diagnose individuals before they develop major symp-toms. Therefore, advances in WD screening can lead to an earlier diagnosis and better results.

Introduction: The coronary flow reserve (CFR) is a sign of early-stage coronary artery disease (CAD). Plasma atherogenic index (PAI) is related to atherosclerosis and cardiovascular mortality. Therefore, our aim was to determine CFR and PAI in patients with primary hyperparathyroidism (PHPT) and investigate whether PAI can be used in the detection of early-stage CAD. Material and Methods: The sample was comprised of 44 patients with PTHT and 33 healthy volunteers. We defined CFR as the ratio of the hyperemic diastolic peak velocity to the baseline diastolic peak velocity. PAI values were calculated with the formula of log 10 triglyceride (TRG) / high-density lipoprotein (HDL). Result: The comparison of the groups for PAI and CFR demonstrated that PAI levels were significantly higher while CFR levels were significantly lower in the PTHT patients (p<0.01, p=0.01, respectively). The correlation analysis revealed that CFR was negatively correlated with PAI and TRG (PAI- p<0.0001 r=-0.537).The multivariate logistic regression analysis showed that only a high PAI level (OR: 151.6, 95% confidence interval (CI): 4.1-5480, p=0.006) was an independent predictor of reduction in CFR in PHPT patients. Conclusion: Overall, we found an independent correlation between PAI and CFR values. Hence, PAI may be useful in identifying PHPT patients facing a high risk of adverse cardiovascular events and may also allow early diagnosis of subclinical atherosclerosis.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.