Search Results (823)

Atrial fibrillation (AF) is the most common sustained arrhythmia, contributing to significant morbidity and healthcare burden worldwide. This review evaluates the role of early risk factor modification and timely catheter ablation in preventing AF progression and improving patient outcomes. A comprehensive literature search was conducted using PubMed, MEDLINE, and Google Scholar, focusing on studies published after the ESC 2020 guidelines for the diagnosis and management of AF up to the release of the updated ESC 2024 guidelines for the management of AF. Keywords included “atrial fibrillation”, “catheter ablation”, “risk factor management”, and “psychological stress”. Relevant clinical trials, randomized controlled trials, systematic reviews, and meta-analyses were included, with particular emphasis on novel studies contributing to the ESC 2024 updated recommendations. Traditional risk factors such as obesity, hypertension, diabetes, sleep apnea, alcohol consumption, and physical exertion are well established in AF progression. Early evidence also suggests a role for psychological stress and mood disorders, including depression and post-traumatic stress disorder (PTSD), in increasing AF susceptibility. Psychological stress and mood disorders are linked to AF primarily through behavioral changes such as poor medication adherence, unhealthy lifestyle choices, and increased substance use. Recent guidelines recommend early catheter ablation in selected patients to reduce AF burden, prevent atrial remodeling, and improve quality of life, particularly in those resistant to antiarrhythmic drugs or individuals with AF-induced cardiomyopathy. Furthermore, we highlight the importance of a patient-centered, multidisciplinary approach, integrating electrophysiologists, cardiologists, and primary care providers with structured risk factor interventions and shared decision-making. Despite these advances, gaps remain in defining optimal timing, patient selection, and long-term benefits of catheter ablation in persistent AF, necessitating the need for further research. By integrating early intervention, personalized treatment strategies, and collaborative care models, we may usher in a paradigm shift in AF management, improving long-term cardiovascular outcomes and patient quality of life. Full article

Background: Bipolar disorder (BD) is a chronic condition associated with treatment resistance, cognitive decline, structural brain changes, and an approximately 13-year reduction in life expectancy compared to the general population. Depression in BD substantially impairs quality of life, while neuroinflammation and excitotoxicity are thought to contribute to the recurrence of mood episodes and disease progression. Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal growth and function, with its dysregulation being linked to various psychiatric disorders. This study is an extension of a previously published clinical trial and was conducted to assess the effects of three BDNF and BDNF-AS gene polymorphisms (rs1519480, rs6265, and rs10835210) on treatment outcomes and serum BDNF levels in patients with treatment-resistant bipolar disorder depression (TRBDD) over an eight-week period. Methods: This study included 41 participants from a previously conducted randomized clinical trial, all of whom had available BDNF serum samples and genotype data. The participants, aged 21 to 65, were diagnosed with bipolar disorder, and treatment-resistant depression was assessed using the Maudsley Staging Method. Participants were randomly assigned to receive either escitalopram plus a placebo (ESC+PBO) or escitalopram plus celecoxib (ESC+CBX) over an 8-week period. Statistical analyses included a mixed ANOVA and chi-square tests to compare the minor allele carrier status of three SNPs with treatment response and remission rates. Results: Non-carriers of the rs6265 A allele (p = 0.005) and carriers of the rs10835210 A allele (p = 0.007) showed a significantly higher response to treatment with adjunctive celecoxib compared to escitalopram alone. Additionally, remission rates after adjunctive celecoxib were significantly higher in both carriers and non-carriers across all three SNPs compared to escitalopram alone. However, remission rates were notably higher in non-carriers of the rs1519480 G allele and rs10835210 A allele, as well as in carriers of the rs6265 A allele. Conclusions: This study suggests that genetic variations in BDNF and BDNF-AS genes significantly influence treatment response to and remission with escitalopram and celecoxib in bipolar disorder. Full article

Escherichia coli (E. coli) has the ability to induce clinical and subclinical mastitis in dairy cows, causing a huge loss for the dairy industry. In this study, 51 subclinical mastitis isolates and 36 clinical mastitis isolates from eight provinces of China between 2019 and 2021 were used to investigate the differences in their biological characteristics. The results showed that B1 (52.9%) and A (39.1%) were the predominant phylogroups; R1 (50.6%) was the predominant lipopolysaccharide (LPS) core type; and 44 STs (ST10 and ST58 were the most sequence-prevalent STs) and 2 new STs (ST14828 and ST14829) were identified; however, no significant difference was observed between the clinical and subclinical group strains. To compare the virulence gene differences between the clinical and subclinical mastitis-related isolates, 18 common virulence genes (including afaE, eaeA, papC, saa, sfa, ompA, aer, irp2, iucD, escV, sepD, east1, estB, stx2e, CNF1, cba, hlyA and traT) were determined using the PCR method. The results showed that the detection rates of traT, irp2 and iucD in clinical mastitis isolates were significantly higher than those in subclinical mastitis isolates (p ˂ 0.05). Meanwhile, subclinical-group E. coli had stronger biofilm formation abilities than the clinical group (p < 0.05) in 78 (89.7%) mastitis-related E. coli that could form biofilms. Furthermore, 87 mastitis-related E. coli showed severe resistance against tetracycline (37.9%), ampicillin (36.8%), streptomycin (34.5%) and cotrimoxazole (28.7%); their most prevalent resistance genes were blaCTX-M (33.3%), tetA (27.6%), sul2 (18.4%) and strB (28.7%). It was noteworthy that the clinical-group strains had a higher resistance against ampicillin and possessed higher amounts of the resistance gene blaCTX-M (p < 0.05) compared to the subclinical group. This study aims to provide references for preventing the E. coli isolates from inducing different types of mastitis. Full article

Background/Objectives: We conducted this study to evaluate the genotypic and phenotypic profiles of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, exhibiting resistance to cefiderocol (FDC), focusing on antibiotic susceptibility, β-lactamase production, the genetic environment of bla_CARB and bla_ESBL genes and molecular epidemiology. FDC is now a last-line antibiotic for severe infections due to CRKP. Methods: Susceptibility to a wide range of antibiotics was determined by the disk diffusion and broth microdilution method. Carbapenemases were screened by a modified Hodge test while carbapenem hydrolysis was investigated using mCIM and eCIM tests. The screening for β-lactamase and fluoroquinolone cluster resistance genes was carried out by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). An inter-array genotyping CarbaResist test and whole genome sequencing (WGS) were applied on selected isolates. Results: All of the 31 isolates studied exhibited high-level resistance to amoxicillin–clavulanate, piperacillin–tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESC), cefepime, ceftolozan–tazobactam and ciprofloxacin and the majority to gentamicin, and amikacin. Colistin and ceftazidime–avibactam preserved activity against 71% and 87% of the isolates, respectively. The combined disk method with clavulanic acid was positive in all but one isolate, indicating the production of an ESBL. Twenty-eight isolates carried one single carbapenemase-encoding gene, whereas three harbored double bla_CARB genes. Among the studied isolates, 61% carried bla_OXA-48, 29% bla_KPC and 12.9% bla_NDM genes. The inter-array genotyping CarbaResist test and WGS identified additional aminoglycoside-, sulphonamide- and trimethoprim-resistance genes. Conclusion: To our knowledge, this is the first study on FDC resistance in Croatia. The diffusion of FDC-resistant isolates was detected in both hospital and outpatient settings, emphasizing the need for a “One Health” approach. Full article

Ecosystem service connectivity (ESC) is the spatial and functional links among and within ecosystems that support unimpeded service flows, and that could play an important role in ecosystem stability enhancement and regional land planning. Understanding the relationships between landscape patterns and ESC is crucial to achieving certain sustainable development goals, but it has not yet received an adequate amount of attention. Here, we evaluated the changes and connectivity of five key types of ecosystem services from 2000 to 2020 and analyzed the correlations and spatial aggregations between the ESCs and landscape metrics in the wetlands of the Yellow River Delta, China. Various research methods, such as the InVEST model, spatial autocorrelation analysis, Spearman’s correlation, and self-organizing map, were applied. The results showed that water yield, water purification, and habitat quality showed high connectivity, but the overall ESC declined along with the restoration of the wetland area. Meanwhile, the High-High ESC cluster of water yield, water purification, and habitat quality had similar spatial distribution patterns, and both were dominated by tidal flats. Moreover, the ESC and landscape metrics showed significant correlations and spatial heterogeneity, and a potential connectivity between water yield and habitat quality was also found. These findings can assist decision-makers in developing effective ecosystem management strategies and provide a reference for future research on ecosystem service connectivity. Full article

Hypertensive heart disease (HHD) continues to be a leading cause of cardiovascular morbidity and mortality worldwide, necessitating the evolution of evidence-based management strategies. This literature review examines the most recent updates from the 2023 and 2024 hypertension guidelines issued by the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC). These guidelines are compared with previous key recommendations, such as the 2017 American College of Cardiology/American Heart Association guidelines and the 2018 ESC/ESH guidelines. The updated recommendations reflect a paradigm shift in the approach to hypertension diagnosis and management, including a stricter systolic blood pressure (BP) target of 120–129 mmHg, which underscores the importance of early and precise BP control. The difference between the classification of “elevated BP” and hypertension in the ESC versus ESH guidelines, particularly, regarding their implications for early detection and prevention of HHD, are critically examined, highlighting areas of clinical and academic debate. The introduction of a new “elevated BP” category (120–139/70–89 mmHg) highlights a proactive strategy aimed at identifying at-risk individuals earlier in the disease course to prevent progression to HHD. Additionally, the divergent roles of hypertension-mediated organ damage (HMOD), including HHD, in risk stratification as recommended by the ESC and ESH are discussed, emphasising their significance in tailoring management approaches. For patients with resistant hypertension, the 2023 and 2024 updates also endorse innovative therapies, such as renal denervation, an interventional procedure that has demonstrated significant promise in managing treatment-resistant cases. This review synthesises these updates, focusing on their implications for clinical practice in diagnosing and managing HHD. By emphasising aggressive intervention and the integration of novel treatment modalities, the review aims to bridge existing gaps in earlier approaches to hypertension management. The critical evaluation of guideline discrepancies and evolving evidence seeks to provide clinicians with a nuanced understanding to optimise outcomes for patients with HHD, particularly considering emerging therapeutic possibilities and more stringent BP control targets. Full article

DNA replication is a crucial biological process that ensures the accurate transmission of genetic information, underpinning the growth, development, and reproduction of organisms. Abnormalities in DNA replication are a primary source of genomic instability and tumorigenesis. During DNA replication, the assembly of the pre-RC at the G1-G1/S transition is a crucial licensing step that ensures the successful initiation of replication. Although many pre-replication complex (pre-RC) proteins have been identified, technical limitations hinder the detection of transiently interacting proteins. The APEX system employs peroxidase-mediated rapid labeling with high catalytic efficiency, enabling protein labeling within one minute and detection of transient protein interactions. MCM2 is a key component of the eukaryotic replication initiation complex, which is essential for DNA replication. In this study, we fused MCM2 with enhanced APEX2 to perform in situ biotinylation. By combining this approach with mass spectrometry, we identified proteins proximal to the replication initiation complex in synchronized mouse ESCs and NIH/3T3. Through a comparison of the results from both cell types, we identified some candidate proteins. Interactions between MCM2 and the candidate proteins CD2BP2, VRK1, and GTSE1 were confirmed by bimolecular fluorescence complementation. This research establishes a basis for further study of the component proteins of the conserved DNA replication initiation complex and the transient regulatory network involving its proximal proteins. Full article

Hypertension remains a critical global health challenge, significantly contributing to cardiovascular morbidity and mortality despite advancements in treatment. The 2024 ESC hypertension guidelines address persistent gaps in hypertension management by emphasizing comprehensive strategies encompassing early detection, socioeconomic barriers, lifestyle interventions, and personalized care. Enhanced screening protocols, including home and ambulatory blood pressure monitoring, aim for accurate diagnosis and risk stratification. Lifestyle recommendations now prioritize reducing sodium intake, increasing potassium consumption, and integrating tailored exercise regimens. Pharmacological updates advocate for single-pill combinations and stringent BP targets (<130/80 mmHg), emphasizing the benefits of sodium-glucose cotransporter-2 inhibitors for specific comorbidities. Minimally invasive therapies like renal denervation are explored for resistant hypertension, while digital tools such as telehealth and mobile applications enhance patient engagement and adherence. This multifaceted, patient-centered approach provides a roadmap for optimizing BP control, reducing cardiovascular risks, and addressing the complexities of hypertension in diverse populations. Full article

Left ventricular hypertrabeculation is one of the most debated conditions in modern cardiology. Many studies have tried to characterise this disease by addressing the various clinical risks and diagnostic tools, but its very nosological existence is currently being challenged. The latest ESC guidelines on cardiomyopathies state that it should be addressed as a morphologic trait rather than an intrinsic disease of the cardiac muscle. Despite the huge number of diagnostic criteria and possible phenocopies, no specific consensus identifies a specific flowchart regarding the management of patients with suspected hypertrabeculation. This review aims to provide a clinical approach for patients with a phenotypical appearance of excessive trabeculation. Full article

Background: The primary role of a pulmonary embolism response team (PERT) is to support decision-making processes regarding acute pulmonary embolism (PE) patients and provide advanced rescue therapies when needed. Despite a great need for its availability among physicians, PERT’s usefulness is yet to be proven. Objectives: Our goal was to establish whether patients benefit from qualification by PERT for admission to a tertiary cardiology ward. Methods: Data of all patients hospitalized due to PE for 12 months (July 2023–June 2024) were retrospectively analyzed. We aimed to compare patients admitted primarily via the emergency department with those consulted by PERT and eventually transferred from other hospitals. The primary outcome was the use of advanced therapies. Results: We identified 167 patients (50.3% women) hospitalized with PE. Out of them, 102 (61.1%) came from the emergency department, while 65 (38.9%) patients were transferred after PERT consultation. The transferred patients generally had more severe conditions, as indicated by the ESC death risk group classification (intermediate-high and high risk, OR 19.2, 95% CI 8.3–44.2). They were more often qualified for at least one of the advanced therapies than the emergency department patients (OR 23.2, 95% CI 9.3–58.1). We found no significant differences in in-hospital mortality (6.9% versus 1.5%, OR 4.7, 95% CI 0.6–39.3). Conclusions: Establishing PERT as a reference unit providing advanced treatment resulted in successfully delivering more complex treatment to severely ill PE patients. Despite their unfavorable basic characteristics, neither length of hospitalization nor in-hospital mortality seem to differ when compared to unselected, less compromised cases. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) is a complication of systemic sclerosis (SSc), and several screening algorithms have been proposed for the early detection of PAH in SSc. This study aimed to evaluate the predicting values of the DETECT algorithm for SSc-PAH screening in patients with SSc undergoing right heart catheterization (RHC) based on 2015 ESC/ERS echocardiographic criteria in a real-life setting. Methods: Patients fulfilling the 2013 ACR/EULAR classification criteria for SSc and with available data for PAH screening with the DETECT algorithm and the 2015 ESC/ERS echocardiographic criteria were retrospectively enrolled from January to June 2017 and then followed for 5 years. Baseline and annual clinical, laboratory, and instrumental data were collected. Results: A total of 33 out of 131 (25%) patients were selected based upon the ESC/ERS echocardiographic criteria, but 30 (23%) underwent RHC, while 51 (39%) patients with SSc were positive based on the DETECT algorithm. PAH diagnosis was confirmed in 28/30 cases (93.3%). The DETECT algorithm showed lower specificity and positive predictive value (PPV) (p < 0.0001) but higher sensitivity and negative predictive value (NPV) (p < 0.0001) than ESC/ERS criteria. Notably, patients with SSc with a negative DETECT screening at baseline had a low probability of developing PAH during a 5-year follow-up (OR 0.15, 95% CI 0.10–0.60—p < 0.0001). Conclusions: The DETECT algorithm has proven to be an easy, fast, and inexpensive tool for screening PAH in patients with SSc. Overall, a low probability of PAH using DETECT is highly predictive of a good prognosis. Full article

Background: Thanks to the evolution of laboratory medicine, point-of-care testing (POCT) for troponin levels in the blood (hs-cTn) has been greatly improved in order to quickly diagnose acute myocardial infarction (AMI) with an accuracy similar to standard laboratory tests. The rationale of the HEART POCT study is to propose the application of the 0/1 h European Society of Cardiology (ESC) algorithm in the pre-hospital setting using a POCT device (Atellica VTLi). Methods: This is a prospective study comparing patients who underwent pre-hospital point-of-care troponin testing (Atellica VTLi) with a control group that underwent standard hospital-based troponin testing (Elecsys). The primary objectives were to determine if the 0/1 h algorithm of the Atellica VTLi is non-inferior to the standard laboratory method for diagnosing AMI and to analyze rule-out/rule-in times and emergency department (ED) stay times. The secondary objective was to evaluate the feasibility of pre-hospital troponin testing. Results: The Atellica VTLi demonstrated reasonable sensitivity for detecting AMI, with sensitivity increasing from 60% at the first measurement (time 0) to 80% at the second measurement (time 1 h). Both the Atellica VTLi and the Elecsys method showed high negative predictive value (NPV), indicating that a negative troponin result effectively ruled out AMI in most cases. Patients in the Atellica VTLi group experienced significantly shorter times to diagnosis and discharge from the emergency department compared to the control group (Elecsys). This highlights a potential benefit of point-of-care testing: streamlining the diagnostic and treatment processes. Conclusions: POCT allows for rapid troponin measurement, leading to a faster diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI). This enables earlier initiation of appropriate treatment, potentially improving patient outcomes and the efficiency of emergency department operations. POCT could be particularly beneficial in pre-hospital settings, enabling faster triage and transportation of patients to appropriate care centers. Full article

Dominant optic atrophy (DOA) is the most commonly inherited optic neuropathy. The majority of DOA is caused by mutations in the OPA1 gene, which encodes a dynamin-related GTPase located to the mitochondrion. OPA1 has been shown to regulate mitochondrial dynamics and promote fusion. Within the mitochondrion, proteolytically processed OPA1 proteins form complexes to maintain membrane integrity and the respiratory chain complexity. Although OPA1 is broadly expressed, human OPA1 mutations predominantly affect retinal ganglion cells (RGCs) that are responsible for transmitting visual information from the retina to the brain. Due to the scarcity of human RGCs, DOA has not been studied in depth using the disease affected neurons. To enable studies of DOA using stem-cell-derived human RGCs, we performed CRISPR-Cas9 gene editing to generate OPA1 mutant pluripotent stem cell (PSC) lines with corresponding isogenic controls. CRISPR-Cas9 gene editing yielded both OPA1 homozygous and heterozygous mutant ESC lines from a parental control ESC line. In addition, CRISPR-mediated homology-directed repair (HDR) successfully corrected the OPA1 mutation in a DOA patient’s iPSCs. In comparison to the isogenic controls, the heterozygous mutant PSCs expressed the same OPA1 protein isoforms but at reduced levels; whereas the homozygous mutant PSCs showed a loss of OPA1 protein and altered mitochondrial morphology. Furthermore, OPA1 mutant PSCs exhibited reduced rates of oxygen consumption and ATP production associated with mitochondria. These isogenic PSC lines will be valuable tools for establishing OPA1-DOA disease models in vitro and developing treatments for mitochondrial deficiency associated neurodegeneration. Full article

Background/Objectives: This study assessed the proportion of secondary cardiovascular prevention patients who achieved low-density lipoprotein (LDL) cholesterol targets as per the 2019 ESC/EAS Dyslipidemia Guidelines. We also evaluated whether lipid-lowering therapies (LLTs) were adjusted in patients not meeting targets and analyzed the likelihood of these modifications achieving recommended levels. Methods: A multicenter, cross-sectional observational study retrospectively reviewed medical records of 1909 outpatients in 9 Italian cardiac rehabilitation/secondary prevention clinics from January 2023 to June 2024. Inclusion criteria included prior atherosclerotic cardiovascular disease (ASCVD) and recent LDL-cholesterol levels. Data included demographics, ASCVD presentation, lipid profiles, and LLTs. Patients at very high risk had LDL targets of ≤55 mg/dL, or ≤40 mg/dL for recurrent events within 2 years. Clinicians’ approaches to LLT modification in patients not at target were recorded, with LLT efficacy estimated based on percentage distance from LDL-cholesterol targets. Results: Of the 1909 patients, 41.3% met the LDL-cholesterol target. Predictors of achieving targets included male gender, cardiac rehabilitation, recent acute coronary syndrome, diabetes, and triple therapy (statin + ezetimibe + PCSK9 inhibitors). Conversely, a target of ≤40 mg/dL, lack of therapy, and monotherapy were negative predictors. Among 1074 patients not at target, LLT modifications were proposed for 48.6%. Predictors of LLT modification included recent ASCVD events, cardiac rehabilitation, and greater percentage distance from the LDL target, while advanced age and an LDL target of ≤40 mg/dL were negative predictors. However, only 42.3% of modified therapies were predicted to be effective in reaching LDL targets. Conclusions: Despite 2019 ESC/EAS guidelines, a significant proportion of high-risk patients did not achieve LDL targets, and proposed LLT modifications were often insufficient. More intensive LLT regimens are needed to improve outcomes in this population. Full article

Extremely severe cyclonic storms over the North Indian Ocean increased by approximately 10% during the past 30 years. The climatological characteristics of tropical cyclones for 38 years were assessed over the Bay of Bengal (BoB). A total of 24 ESCSs formed over the BoB, having their genesis in the southeast BoB, and the intensity and duration of these storms have increased in recent times. The Advanced Research version of the Weather Research and Forecasting (ARW) model is utilized to simulate the five extremely severe cyclonic storms (ESCSs) over the BoB during the past two decades using the Indian Monsoon Data Assimilation and Analysis (IMDAA) data. The initial and lateral boundary conditions are derived from the IMDAA datasets with a horizontal resolution of 0.12° × 0.12°. Five ESCSs from the past two decades were considered: Sidr 2007, Phailin 2013, Hudhud 2014, Fani 2019, and Amphan 2020. The model was integrated up to 96 h using double-nested domains of 12 km and 4 km. Model performance was evaluated using the 4 km results, compared with the available observational datasets, including the best-fit data from the India Meteorological Department (IMD), the Tropical Rainfall Measuring Mission (TRMM) satellite, and the Doppler Weather Radar (DWR). The results indicated that IMDAA provided accurate forecasts for Fani, Hudhud, and Phailin regarding the track, intensity, and mean sea level pressure, aligning well with the IMD observational datasets. Statistical evaluation was performed to estimate the model skills using Mean Absolute Error (MAE), the Root Mean Square Error (RMSE), the Probability of Detection (POD), the Brier Score, and the Critical Successive Index (CSI). The calculated mean absolute maximum sustained wind speed errors ranged from 8.4 m/s to 10.6 m/s from day 1 to day 4, while mean track errors ranged from 100 km to 496 km for a day. The results highlighted the prediction of rainfall, maximum reflectivity, and the associated structure of the storms. The predicted 24 h accumulated rainfall is well captured by the model with a high POD (96% for the range of 35.6–64.4 mm/day) and a good correlation (65–97%) for the majority of storms. Similarly, the Brier Score showed a value of 0.01, indicating the high performance of the model forecast for maximum surface winds. The Critical Successive Index was 0.6, indicating the moderate model performance in the prediction of tracks. It is evident from the statistical analysis that the performance of the model is good in forecasting storm structure, intensity and rainfall. However, the IMDAA data have certain limitations in predicting the tracks due to inadequate representation of the large-scale circulations, necessitating improvement. Full article