Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Background: Over the past decades, efforts have been made to improve the nutritional well-being in people with cystic fibrosis (pwCF). Due to the correlation observed between nutritional indices and lung function, prevailing recommendations consistently advocate for BMI percentile goals at or above the 50th percentile in pwCF. Recent global trends show a notable increase in overweight and obese statuses among pwCF. This study aims to explore the nutritional status of Italian pwCF. Methods: Data from the Italian CF Patient’s Registry were analysed to assess the proportion of individuals categorized as underweight, target weight, overweight, and obese from 2010 to 2021. Patient-level comparison data from 2021 were also examined to identify potential determinants of overweight and obesity. Results: Analysis spanning 2010 to 2021 reveals a decrease of approximately 40% in underweight status among adults, while the proportion of malnourished patients 90, and lower prevalence of Pseudomonas aeruginosa colonization. Conclusions: Our study confirms the evolving nutritional status landscape among Italian adult pwCF, with a significant shift towards overweight and obesity over the past decade. These trends highlight the need for proactive measures within CF standards of care to adapt and address the changing needs of patients.

Background: Atrial fibrillation (AF) is increasingly recognized in pediatric patients, presenting unique challenges in management due to its association with various underlying heart conditions. This study aimed to evaluate the prevalence, management strategies, and outcomes of AF in this population. Methods: A retrospective analysis was conducted at a tertiary pediatric cardiology center, including patients aged ≤18 years diagnosed with AF between January 2015 and December 2023. The study focused on demographic details, clinical presentations, treatments, and outcomes. Descriptive statistics were employed to assess treatment efficacy, recurrence rates, and complications. Results: The study included 36 pediatric patients (median age: 15 years, IQR: 13-17; 58% male). Of these, 52.8% had acquired heart disease, 16.7% had congenital heart anomalies, and 16.7% presented with lone AF. The initial management strategies involved electrical cardioversion in 53.3% of patients and pharmacological conversion with amiodarone in 46.7%. Rhythm control therapy was administered to over 80% of the cohort, and 63.9% were placed on oral anticoagulation, predominantly for rheumatic and congenital heart diseases. The overall success rate of rhythm control was 96.2%, with an AF recurrence rate of 3.8%. Ischemic stroke was the most common complication, occurring in three patients, all with underlying rheumatic heart disease. Conclusion: AF in pediatric patients is predominantly associated with rheumatic and congenital heart diseases, though a significant proportion of patients present with lone AF. Despite effective rhythm control in most cases, neurological complications, particularly ischemic strokes in patients with underlying heart disease, remain a critical concern. These findings underscore the need for more comprehensive studies to better understand the etiology, risk factors, and optimal management strategies for pediatric AF.

To compare and adjust activated clotting time (ACT) between two systems and to optimize ACT during atrial fibrillation (AF) ablation. Methods: Electromagnetic detection using a rotation tube (EM system; Hemochron Response, Soma Tech Intl, Bloomfield, CT, USA) and photo-optical detection using a cartridge immersed in blood (PO system; ACT CA-300TM, APEL) were compared. Results: The EM system showed an ACT of 320 ± 44 s (average ± 1 standard deviation), with a range of 156–487 s, from 3363 measurements in 1161 patients during uncomplicated procedures. An ACT >400 s was observed in 3.7% (124/3364) of patients. The pre-ablation ACT measured by the EM method was 143 ± 28 s. Cardiac tamponade was observed in 4/2085 ablations (0.19%) over 5 years. The ACT associated with cardiac tamponade ranged from 330 to 391 in the EM system. No thromboembolic or major bleeding complications were observed. Comparison of the two methods showed ACT-EM system = 1.19 × ACT-PO system + 9.03 (both regression coefficient and intercept, p<0.001, r = 0.90). In the Bland-Altman plots, the average difference between ACTEM and ACT-PO was 50 s. These differences increased with an increase in the average ACT value. This led to an adjustment of the recommended ACT target of 300–350 s for the EM system to 275–290 s for the PO system. Conclusions: The ACT obtained using the EM system aligned with the ACT recommended in the guidelines. However, the PO system showed significantly lower ACT values compared to those obtained with the electromagnetic system. This study clarifies that adjusting the optimal target ACT when switching between ACT measurement systems is essential.

Idiopathic pulmonary fibrosis, a chronic and fatal condition with no effective cure, is a challenging disease within the group of interstitial lung diseases. The pathogenic mechanisms of this disease are still not fully understood. In this context, the research on miRNAs, which are small non-coding RNAs that regulate messenger RNAs, is of utmost importance. These miRNAs, released into the circulation outside the cell through exosomes, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. The analysis of miRNAs in the serum/plasma of IPF patients has opened up new possibilities in the search for biomarkers. This review focuses on circulating miRNAs validated by real-time PCR in IPF and the evidence reported about the pulmonary fibrotic process.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

The main objective is to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one-year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective is to study the changes in total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective sin gle-center observational study was conducted at Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into Time 0 (ETI treatment initiation), Time 1 (T1 – 3 months of ETI therapy), Time 2 (T2 - 6 months of therapy) and Time 3 (T3 - 12 months of therapy). Demographic and clinical data were collected. The results were then stratified by genotype (F508del in homozygosity or heterozygosity). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T1 and T2, but not at T3, as for HbA1c. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin dependent CFRD patients after one year of only ETI treatment.

Background: Ensemble tree-based models such as Xgboost are highly prognostic in cardiovascular medicine, as measured by the Clinical Effectiveness Metric (CEM). However, their ability to handle correlated data, such as hospital-level effects, are limited. Objectives: The aim of this work is to develop a binary outcome mixed effects Xgboost (BME) model that integrates random effects at the hospital level. To ascertain how well the model handles correlated data in cardiovascular outcomes, we aims to assess its performance and compare it to fixed effects Xgboost and traditional logistic regression models. Methods: A total of 227,087 patients over 17 years of age, undergoing cardiac surgery from 42 UK hospitals between 1 Jan 2012 and 31 Mar 2019 were included. The dataset was split into two cohorts: Training/Validation (n = 157196; 2012-2016) and Holdout (n = 69891; 2017-2019). The outcome variable was 30 days mortality with hospitals considered as clustering variable. The logistic regression, mixed effects logistic regression, Xgboost and binary outcome mixed effects Xgboost (BME) were fitted to both standardized and unstandardized datasets across a range of sample sizes and the estimated prediction power metrics were compared to identify the best approach. Results: The exploratory study found high variability in hospital-related mortality across datasets, which supported the adoption of mixed effects models. Unstandardized Xgboost BME demonstrated marked improvements in predictor power over the Xgboost model at small sample size ranges, but performance differences decreased as dataset sizes increased. Generalized linear models (glm) and generalized linear mixed-effects models (glmer) models followed similar results, with Xgboost models excelling also at greater sample sizes. Conclusions: These findings suggest that integrating mixed effects into machine learning models can enhance their applicability in clinical settings where sample size is small such as rare conditions.

Introduction: The Fontan procedure, a palliative surgery for univentricular heart physiology, of-ten reduces exercise capacity and quality of life. This study aimed to evaluate the impact of cardiac rehabilitation (CR) on improving outcomes in Fontan patients to inform evidence-based care. Methods: Fontan patients aged 8-30 participated in a structured CR program for at least three months. The program included weekly aerobic and resistance training sessions, with educational and nutritional guidance. Baseline and post-CR assessments included cardiac function, fitness, daily activity, and health-related quality of life (HRQOL). Results: The cohort included ten Fontan patients, of whom six had a right systemic ventricle. CR significantly improved cardiorespiratory fitness, as seen in VO2 max (from 27.92 ± 5.15 to 34.69 ± 1.14 mL/kg/min, p = 0.0089) and per cent predicted VO2 (from 0.67 ± 0.18 to 0.90 ± 0.02, p = 0.005). VCO2 increased by +8.68 ± 8.59 mL/kg/min, but did not reach statistical significance (p = 0.05). Most haemodynamic and ventila-tory parameters showed no significant improvement. All the SF-36 questionnaire domains showed significant HRQOL gains (p < 0.001). High adherence (85-93%), no adverse events, and reduced NT-proBNP levels supported the program's safety. Conclusion: This study's findings have im-portant implications for the care of Fontan patients. CR significantly improved exercise capacity and HRQOL in Fontan patients across various anatomies, particularly in the right systemic ven-tricle. Integrating physical conditioning into standard care could reduce long-term morbidity and mortality; however, further research is needed to refine the protocols and confirm sustained ben-efits.

Understanding the molecular mechanism whereby an environmental chemical causes a disease is important for downstream purposes. In this study, an analytical workflow was designed to combine several publicly available datasets in order to identify CpG sites and genes that mediate the impact of exposure to environmental chemicals on cardiometabolic traits. Organophosphate and prenatal lead exposure were previously reported to change methylation level at the cg23627948 site. I found as cg23627948 site becomes methylated, the expression of GNA12 gene decreases and this leads to higher body fat percentage. Prenatal perfluorooctane sulfonate expo-sure was reported to increase the methylation level at cg21153102 site. The outcome of analyses revealed higher methylation at this site contributes to higher diastolic blood by changing the expression of CHP1 and GCHFR genes. Furthermore, HKR1 mediates the impact of B12 supple-mentation-cg05280698 hypermethylation on higher kidney function; while, CTDNEP1 mediates the impact of air pollution-cg03186999 hypomethylation on higher systolic blood pressure. This study reports CpG sites and genes that mediate the impact of environmental chemicals on cardiometabolic traits and describes a framework to investigate the underlying molecular paths using publicly available data.

Researchers have asserted that, as patients rely on external powerful sources to control their disorders, in addition to their own internal powers and virtues, examining their coping mechanisms can lead to a better understanding of the initiation and progression of chronic diseases and uncover potential opportunities to balance and enhance their psycho-spiritual well-being and possibly their treatment and recovery. This review serves as a user’s manual for investigators who choose to use the CSI-SF to conduct their research on coping behaviors. The CSI-SF that measures four coping strategies based on 16 items was first assessed using the Jackson Heart Study (JHS) cohort in 2007. The reliability and construct validity of the CSI-SF was also later assessed among hemodialysis patients across 13 countries. In this study, the CSI-SF was assessed to be a reliable and valid instrument for measuring coping strategies. The CSI-SF serves the purpose of developing an inner voice that can assist with understanding how people cope with everyday life. The information gathered from administration of the CSI-SF can inform investigators about environmental cues and triggers that can also impact individual health.

.Bacground: Sepsis remains a major health challenge worldwide, characterized by a dysre-gulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients. Method: This study retrospectively analyzed 309 sepsis patients admitted to the Internal Me-dicine and Anaesthesia ICUs between December 12, 2021, and December 15, 2023, to inves-tigate the relationship between FIB-4 levels, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) and clinical outcomes. Results: The study found that higher FIB-4 measurements were statistically significantly asso-ciated with increased 28-day mortality, with a cut-off value of 4.9 providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated Conclusion:FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.

Current Micro-Computed Tomography (Micro-CT) protocols for microvasculature analysis often necessitate organ dissection and non-clearable contrast agents. We describe a non-destructive technique for achieving high-resolution images of the human coronary microvasculature. Formalin-fixed human hearts were cannulated using venogram catheters designed for balloon occlusion. Catheters were anchored at the aortic root. Hearts were placed in sealable, radiolucent containers filled with insulating polyurethane foam. Iodine potassium iodide (IKI, Lugol's solution;6.3% Potassium Iodide, 4.1% Iodide) was injected into the coronary arteries. Contrast distribution was monitored using a North Star Imaging X3000 Micro-CT scanner with low-radiation settings, followed by high-radiation scans (3600 rad, 60 kV, 900 mA). We successfully imaged two intact human hearts with chronic total coronary occlusions of the right coronary artery. The scans enabled detailed analysis of the vasa vasorum surrounding stenosed and occluded segments. After imaging, both hearts were cleared of iodine and excess polyurethane foam and then returned to their initial formalin-fixed state for indefinite storage. Conclusions: This method allows for the non-destructive, high-resolution micro-CT imaging of coronary microvasculature in intact human hearts, paving the way for 3D microvascular reconstruction in a macrovascular context.

Following the era of GWAS studies, efforts are being made to identify genes underlying complex traits by merging eQTL and GWAS data and assessing the colocalization of eQTLs and GWAS signals. A problem that sometimes occurs in this context is the observation of association between several genes in a genomic region with a trait. This happens because genes in a region could be under the regulatory impact of common elements and coexpress. As such, computational approaches that rely on cis-eQTL information can not exactly pinpoint the causal gene. Here, I report an alternative solution, based on trans-eQTLs to test the association between a gene and a trait. Through the analyses applied to adjacent genes that coexpress and concordantly impact blood traits, I provide evidence that trans-eQTLs can resolve the problem of coexpression-causality without the interference of shared cis-regulatory SNPs.

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

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

Background We aimed to evaluate the effectiveness of the ALRYNGO channel-type video laryngoscope with an AI-based glottis guidance system in senior emergency medicine residents for endotracheal intubation. Methods We enrolled twenty patients would be adequate for each device (direct laryngoscope, Pentax-AWS, and ALRYNGO). Before intubation, six senior residents wore a personal protective equipment. To randomize the device in this clinical study, a sealed envelope containing a device-specific identification card was utilized. When intubation began, the person who measured the intubation time divided the total intubation time into three-time intervals. The primary outcome was the intubation time. The secondary outcomes were the glottis view using the Cormack-Lehane grade (C-L grade) and the glottis guidance performance of ALRYNGO’s artificial intelligence. Results In Pentax-AWS and ALRYNGO, all intubations were successful, but the intubation time was longer than with the direct laryngoscope. And among the three, the ALRYNGO and Pentax-AWS had the highest frequency of C-L grade I (easiest intubation) at 80%, and the direct laryngoscope had the lowest frequency of 10%. Conclusions Even if healthcare professionals without experience with the channel-type video laryngoscope improve their performance on airway mannequins after training, their intubation performance may differ when applied to actual patients.

(1) Background: Heart rate variability (HRV) has emerged as a potential prognostic tool in cardiovascular diseases, offering individualized insights into autonomic nervous system activity. However, real-time HRV data during the acute phase of STEMI, particularly during percutaneous coronary intervention (PCI), was not previously explored. (2) Methods: This single-center, observational cohort study included 104 STEMI patients undergoing primary percutaneous coronary intervention (PCI). HRV parameters were measured using a wearable device (CE marked) during PCI, capturing dynamic responses. The association between HRV parameters and adverse outcomes, including in-hospital mortality and major adverse cardiovascular events (MACE), were assessed. (3) Results: HRV parameters significantly decreased after myocardial revascularization, particularly SDNN, RMSSD, pNN50, HF, SD1, and SD2/SD1 ratio. Significant associations were found between reduced SD2/SD1 ratio, approximate entropy, and adverse outcomes, including increased in-hospital mortality and MACE. The SD2/SD1 ratio was significantly lower in patients who died during the hospital stay (p = 0.008) compared to survivors. Approximate entropy was also significantly lower in deceased patients (p = 0.019). (4) Conclusions: Real-time HRV monitoring using wearable technology offers valuable data regarding dynamic physiological changes during primary PCI. The integration of HRV into routine clinical practice, facilitated by wearable devices, could improve the risk stratification and event prediction in STEMI patients.

Background: The Advanced Lung Cancer Inflammation Index (ALI) is a novel, comprehensive index that integrates inflammation and nutritional status, incorporating parameters such as albumin, body mass index (BMI), and the neutrophil-to-lymphocyte ratio (NLR). Unlike traditional inflammation biomarkers, this study aims to evaluate the prognosis of IPF patients by considering both inflammation and nutritional status. Method: A total of 102 patients with IPF were included in the study. Clinical data were obtained from the patients’ medical records. NLR and ALI score were calculated based on data collected at the initiation of antifibrotic treatment using the following formula: Neut/Lym and albumin × BMI / NLR. Results: IPF subject subgroups in terms of ALI based on gender–age–physiology (GAP) stages (1,2,3), FVC (median split, <70% vs ≥70%), DLCO (<51% vs ≥51%), 6-Minute Walk Test (6MWT) (<350 vs ≥350) and CCI (≤1 vs >1). ALI showed significant difference depending on the categories of GAP stage, FVC, DLCO, and 6MWT but these differences were not observed based on the charlson comorbidity index (CCI) categories (sırasıyla p=0.000, p=0.000, p=0.000, p=0.001, p=0.233). Receiver Operating Characteristic (ROC) curve analysis was performed to evaluate the sensitivity and specificity of ALI, albumin, NLR, and BMI in determining the mortality risk in IPF patients. ALI demonstrated a sensitivity of 63.6% and a specificity of 98.9% at a threshold of 11.2 (AUC = 0.945, 95% CI 0.892–0.998, p < 0.000). Conclusion: We determined that ALI levels are significantly associated with disease severity and mortality in patients with IPF.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

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

Ambulatory heart rate (HR) monitors that acquire electrocardiogram (ECG) or/and photoplethysmographm (PPG) signals from the torso, wrists, or ears are notably less accurate in tasks associated with high levels of movement compared to clinical measurements. However, reliable estimation of HR can be obtained through data fusion from different sensors. These methods are especially suitable for multimodal hearable devices, where heart rate can be tracked from different modalities, including electrical ECG, optical PPG, and sounds (heart tones). Combined information from different modalities can compensate for single source limitations. In this paper, we evaluate the possible application of data fusion methods in hearables. We assess data fusion for heart rate estimation from simultaneous in-ear ECG and in-ear PPG, recorded on eight subjects while performing 5-minute sitting and walking tasks. Our findings show that data fusion methods provide a similar level of mean absolute error as the best single-source heart rate estimation but with much lower intra-subject variability, especially during walking activities. We conclude that data fusion methods provide more robust HR estimation than a single cardiovascular signal. These methods can enhance the performance of wearable devices, especially multimodal hearables, in heart rate tracking during physical activity.

This study aimed to investigate the diagnostic potential of circulating microRNAs (miRNAs) for detecting early myocardial fibrosis development in HFpEF patients. This observational study used a case-control research design. Peripheral blood samples were isolated from 25 HFpEF patients and 25 normal patients. They were measured for NTproBNP levels using ELISA, as well as MicroRNA-1, 21, and 29 levels using RT-PCR. All patients also underwent echocardiography for global longitudinal strain (GLS) to measure the myocardial fibrosis progression. Data were analyzed using SPSS 25.0. HFpEF patients had significantly higher GLS compared to the normal patients (-13±2.4% vs -19±3.2%; p &lt; 0.05), suggesting HFpEF patients tended to have myocardial fibrosis. HFpEF patients also had significantly higher microRNA-1 and microRNA-21 compared to the normal patients (p &lt; 0.05), but they had lower microRNA-1 (p &lt; 0.05). There was a positive correlation between microRNA-1 (r = 0.753; p &lt; 0.05) and microRNA-21 (r = 0.675; p &lt; 0.05) and an inverse correlation with microRNA-29 (r = -0.653; p &lt; 0.05) based on the GLS findings. By using a GLS cutoff of -15% for myocardial fibrosis, microRNA-1, microRNA-21, and microRNA-29 were found to be able to predict myocardial fibrosis based on GLS with a specificity of 78% and sensitivity of 75%. Increasing microRNA-1 and microRNA-21 followed by decreasing microRNA-29 in HFpEF patients suggest early myocardial fibrosis.

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 ml/kg delivered at 5 – 15 Hz equivalent to 300 – 900 breaths per minute. Few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease, therefore oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

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

Aortic stenosis (AS) is a prevalent valvular disorder that often requires surgical aortic valve replacement (SAVR) to alleviate symptoms and improve survival. However, the selection of an appropriate prosthetic valve size is crucial to avoid patient-prosthesis mismatch (PPM), which can lead to suboptimal hemodynamic outcomes. Von Willebrand factor (VWF), a key component of hemostasis, has been shown to be altered in AS patients and may contribute to the hemostatic imbalance observed following valve replacement. This prospective study aimed to investigate the impact of PPM on postprocedural VWF levels in patients undergoing SAVR for severe AS. The study included 31 consecutive patients diagnosed with severe AS who underwent SAVR. By focusing on the relationship between PPM and VWF dynamics, this study sought to provide valuable insights into the potential role of VWF as a marker for hemostatic changes associated with PPM, ultimately informing strategies for optimal valve selection and perioperative management to minimize complications.

The article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who was referred by her primary care physician for cardiological evaluation. The conduction disturbance was recognized at the age of 6 years and was asymptomatic. The disqualification from pacemaker implantation included detailed history of a patient’s symptoms, echocardiographic assessment of the heart, exercise testing and ECG Holter monitoring. The aid of salbutamol administered orally was also useful.

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Gastrointestinal bleeding (GIB) after heart transplantation (HT) remains a significant clinical issue. The study aimed to explore its incidence, trends, outcomes and clinical predictors of GIB in HT patients. Adult patients who underwent HT between 2015 and 2021 at Union Hospital were recruited and divided into two groups based on the presence or absence of postoperative GIB. Primary outcomes were evaluated by follow-up. Independent predictors of GIB after HT were identified by logistic regression analysis. A nomogram prediction model was constructed according to these independent variables, and the accuracy of the model was assessed using the receiver operating characteristic (ROC) curve and the calibration curve. Among 461 patients, 40 (8.7%) developed GIB post-HT. HT patients with postoperative GIB exhibited higher in-hospital, 30-day, 90-day and 1-year mortality (all P < 0.05). Multivariate analysis identified age, preoperative warfarin, postoperative continuous renal replacement therapy and postoperative nasogastric tube as independent risk factors for GIB following HT. The nomogram prediction model was performed using the 4 variables. The area under the curve (AUC) of this model was 0.852(95% CI: 0.787-0.917, P < 0.001) and the calibration curve was close to the ideal diagonal line. GIB following HT is associated with a poor clinical prognosis. The constructed nomogram, incorporating its independent risk factors, demonstrated a favorable predictive value for GIB.

This review brings together the current knowledge regarding the risk factors, and the clinical, radiologic and histological features of both post-COVID-19 interstitial pul-monary fibrosis (PCPF) and Idiopathic Pulmonary Fibrosis (IPF) with a particular fo-cus on describing the similarities and the disparities between the fibrotic changes in these two diseases. It is important to highlight the common points of PCPF and IPF to observe if they are some targetable changes to improve patient outcomes. The litera-ture review was performed using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists and researchers to make an accurate diagnosis, which can be useful in identifying the group of patients who can be selected for antifibrotic therapies, and future therapeutic perspectives.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

The Characteristics of the cardiac muscle cell are described as a rod-shaped structure, single nu-cleus, and intercalated discs which make the heart’s action practical for enhancing contraction ef-ficiency. Mitochondria within these cells are vital for ATP synthesis, redox balance, calcium ho-meostasis, and lipid synthesis. The crucial role of Hsp60 is in protein folding and immune re-sponses; Hsp60 is a mitochondrial chaperonin, and its expression rises when the heart is under a stress condition like myocardial infarction and heart failure. This review has tried to deeply un-derstand the structural resemblance between cardiac and skeletal muscle cells, the amplitude number of mitochondria, its roles in cardiomyocytes, and the polyhedral functions of Hsp60. In this review, by investigating various articles, we brighten up Hsp60's distribution within cells, its association with apoptosis, and its action as a Damage Associated Molecular Pattern (DAMP), interacting with Toll-like receptors to modulate immune responses. Cardiac remodeling and failure are linked to cardiac-specific micro-RNAs whose expression may be affected by dysregu-lation of Hsp60. In conclusion, targeting mitochondrial function and Hsp60 expression may be of therapeutic potential for heart diseases.

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.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 hour, patients took 50 mg lasmiditan within 2 hours of migraine onset. Patients recorded headache intensity and adverse events(AEs) caused by lasmiditan at 1, 2, and 4 hours after intake of additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p &lt; 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 hour after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 hour after lasmiditan intake. Our study revealed the significant headache reliefs provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short term. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

Commonly macrophages are categorized into M1 and M2 subsets. M1 macrophages are defined as inflammatory cells and may contribute to tissue injury, while, M2 macrophages play a central role in tissue remodeling and control of immune responses. It seems that the existence of these cells in graft location is effective for control of inflammation and improvement of transplantation consequences. Although the relative contribution of M2 cells in organ transplantation is not clear, the accumulation of these cells in acute and chronic injury models of transplantation was shown. In some cases, the depletion of M2 cells leads to the amelioration of disease; however in other causes, skewing the response in M2 cells leads to an augmentation of graft fibrosis and worsening of graft condition. In spite of these findings, the benefits of such strategies and their implications in human disease are not clearly understood. The purpose of this mini-review is to highlight the role of alternatively activated M2-type macrophages in the improvement or reduction of the kidney transplantation outcome.

Background: for patients with endocarditis, guidelines recommend repeating blood cultures until they become negative, but with very limited evidence. Methods: a literature review was done on the incidence and duration of persistent bacteremia and persistent fever in endocarditis patients, compared to their associations with persistent infection at day 7. Results: persistent bacteremia and persistent fever are common in the first few days after starting antibiotic therapy, a normal duration for either at or around < 3-7 days. Persistent bacteremia is more prevalent and longer lasting in Staphylococcus (especially MRSA) and Enterococcus species than in Streptococcus species. In one study the risk for persistent infection at day 7 was 50% in those with positive blood cultures at 48-72 hours while it was 32% in those with negativization of blood cultures. Both persistent bacteremia at 48-72 hours and persistent infection at day 7 are predictive of in-hospital mortality. Conclusion: persistent bacteremia after treatment for endocarditis is common and often accompanied by persistent fever. Persistent infection at 7 days (as indication for urgent surgery) cannot be reliably predicted by positive or negative blood cultures at 48-72 hours. The recommendation of performing survey blood cultures in all patients therefore needs to be reconsidered.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p&gt;5 × 10-8). Our results are consistent with prior finding regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, and allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy.

As cardiovascular diseases continue to be a leading cause of mortality, recent-ly, wearable devices for monitoring cardiac activity have gained much interest among medical community. This paper introduces an innovative ECG monitoring system based on a single – lead ECG machine enhanced with machine learning methods. The system only processes and analyses the ECG data, but also predict potential heart disease at an early stage. The wearable device was built on the ADS1298 and a microcontroller STM32L151xD. A server module based on REST API architecture style was designed to fa-cilitate interaction with web-based segment of the system. The module is responsible for receiving data in real time from microcontroller and their deliver to web – based segment. Algorithms for analyzing ECG signals have been developed, including band filter artifact removal, K-means clustering for signal segmentation, and PQRST analysis. Machine leaning methods as Isolation Forest have been employed for ECG anomaly detection. Moreover, a comparative analysis with various machine learning methods, including lo-gistic regression, random forest, SVM, XGBoost, decision forest and, CNNs was conducted to predict cardiovascular diseases. Convoluted Neural Networks (CNN) showed an accu-racy of 0.926, proving high effectiveness in ECG data process.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

Objective: Interstitial fibrosis / tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm in estimating the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1/1/2012 to 1/3/2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features which were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML-algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) have been included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. For IFTA ≥ 50%, AUCs in training cohort were 0.89, 0.84, 0.96, and in test cohort were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA>50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts.

Background: Anxiety disorders can be both an independent risk factor of many somatic conditions and the cause of complications of various organic disorders leading to poor prognosis. Objectives: The purpose of this study is to compare the heart rate variability (HRV) recorded both during the day and at night in patients with anxiety disorders and healthy individuals. Methods: The study was conducted on fifty consecutive outpatients with anxiety disorders who participated in intensive group psychotherapy. The diagnosis was made according to DSM-IV-TR criteria using the PSE-10 questionnaire. Out of 50 patients under study, 17 were diagnosed with panic disorder (PD) and 21 with generalized anxiety disorder (GAD). The control group consisted of 40 healthy people. The resulting three groups were compared in terms of circadian HRV using the Oxford Medilog Suprima Holter System. Results: The HRV analysis showed the nocturnal falls in the time and frequency parameters related to parasympathetic activity (rMSSD, pNN50, HF). The most unfavourable alterations were observed in the PD group, which comprised the disappearance of day vs. night amplitude of the majority of HRV parameters. Hence, the PD group was particularly susceptible to the arrhythmic events. It was noticeable that nocturnal vagotonia in the PD group was significantly lower as compared with the GAD and control group. Conclusions: The innovative aspect of the present study was to find a distinct profile of HRV with regard to the types of anxiety disorders because of the existing considerable differences between the nature of PD and GAD.

Smartwatches are one of the most relevant fitness trends of the past two decades, and they collect increasing amounts of health and movement data. The accuracy of these data may be questionable and requires further investigation. Therefore, the aim of the present study is to validate smartwatches for use in triathlon training. Ten different smartwatches were tested for accuracy in measuring heart rate, distance (via global navigation satellite systems, GNSS), swim stroke rates and the number of swim laps in a 50 m Olympic-size pool. The optical heart rate measurement function of each smartwatch was compared to that of a chest strap. Thirty participants (15 females, 15 males) ran five 3-minute intervals on a motorised treadmill to evaluate the accuracy of the heart rate measurements. Moreover, for each smartwatch, running und cycling distance tracking was tested over six runs of 4,000 m on a 400 m tartan stadium track, six hilly outdoor runs over 3.4 km, and four repetitions of a 36.8 km road bike course, respectively. Three swimming protocols ranging from 200 m to 400 m were performed in triplicate in a 50 m Olympic-size pool, evaluating tracked distance and detected number of strokes. The mean absolute percentage errors (MAPEs) for the average heart rate measurements varied between 3.1% and 8.3%, with the coefficient of determination ranging from 0.22 to 0.79. MAPE results ranged from 0.8% to 12.1% for the 4,000 m run on the 400 m track, from 0.2% to 7.5% for the 3.4 km outdoor run, and from 0.0% to 4.2% for the 36.8 km bike ride. For the swimming tests, in contrast, the deviations from the true distance varied greatly, starting at a 0.0% MAPE for the 400 m freestyle and reaching 91.7% for the 200 m medley with style changes every 25 m. In summary, for some of the smartwatches, the measurement results deviated substantially from the true values. Measurements taken while road cycling over longer distances with only a few curves were in relative terms more accurate than for outdoor runs and even more accurate than for the 400 m track. In the swimming exercises, the accuracy of the measured distances was severely deteriorated by the medley changes among the majority of the smartwatches. Altogether, the results of this study should help in assessing the accuracy and thus suitability of smartwatches for general triathlon training.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

The study´s goals were to determine the health status of a group of heart transplant recipients (HTR) and their level of physical activity and to compare the health status among them and with a group of healthy sedentary individuals. Fifty-four HTR and eighteen S were assigned to four groups, according to their level of physical activity (determined with The International Physical Activity Questionnaire); patients with a low, a moderate and a high level of physical activity (HTRL, HTRM and HTRH, respectively) and sedentary individuals (S). Participants underwent a basic blood analysis and several tests to assess their cardiovascular, neuromuscular, functional mobility condition and their quality of life. The S and HTRH were very similar in terms of BP, HR and blood analysis while HTRM and HTRL differed from both S and HTRH in these parameters. Regarding the cardiovascular, neuromuscular, functional mobility, and quality of life variables assessed in this study, HTRH showed the best results across all of them, followed by S, HTRM, and HTRL. It is suggested that the weekly level of physical activity of HTR should be high, what might help them to enhance their health and quality of life.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

The Cl- transporting proteins CFTR, SLC26A9, and anoctamin (ANO1; ANO6) appear to have more in common than anticipated initially. They all participate in the pathogenic process and clinical outcome of renal and airway diseases. In the present review we will therefore concentrate on recent findings concerning electrolyte transport in airways and kidney, and the role of CFTR, SLC26A9, and anoctamins (ANO1 and ANO6). A particular focus will be on the airway diseases cystic fibrosis and asthma, as well as renal alkalosis and polycystic kidney disease. In essence, latest findings are summarized that demonstrate CFTR as the only relevant secretory Cl- channel in airways under basal (non-stimulated) conditions and after stimulation by secretagogues. For proper CFTR function, expression of ANO1 and ANO6 appears to be a prerequisite. Evidence is summarized suggesting that the Cl- transporter SLC26A9 may have a reabsorptive rather than a Cl- secretory function in the airways. In renal collecting ducts bicarbonate secretion takes place due to synergistic tasks of CFTR and the Cl-/HCO3- transporter SLC26A4 (pendrin), which is likely to be supported by ANO1. Finally, in autosomal dominant polycystic kidney disease (ADPKD), the secretory function of CFTR in renal cyst formation might have been overestimated, while ANO1 as well as ANO6 turned out to be crucial in ADPKD, and therefore represent novel pharmacological targets for the treatment of polycystic kidney disease.

Despite prophylaxis and attempts to select a therapy, the frequency of preeclampsia does not decrease, and it still takes the leading position in the structure of maternal mortality and morbidity worldwide. In this review, we present a new theory of the etiology and pathogenesis of preeclampsia which is based on the interaction of Na/K-ATPase and its endogenous ligands including marinobufagenin. The signaling pathway of marinobufagenin involves an inhibition of transcriptional factor Fli1, a negative regulator of collagen synthesis, followed by deposition of collagen in the vascular tissues and altered vascular functions. Moreover, in vitro and in vivo neutralization of marinobufagenin is associated with restoration of Fli1. The inverse relationship between marinobufagenin and Fli1 opens new possibilities in the treatment of cancer: since Fli1 is a proto-oncogene, a hypothesis on suppression of Fli1 by cardiotonic steroids as potential anti-tumor therapeutic strategy is discussed as well. We propose a novel therapy of preeclampsia which is based on immunoneutralization of the marinobufagenin by monoclonal antibodies, which is capable to impair marinobufagenin-Na/K-ATPase interactions.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Introduction: congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of urinary collecting system, known as hydronephrosis or ureterohy-dronephrosis. Mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin 11 and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate expression of fibrosis related genes in obstructive and normal ureteral tissue. Material and methods: it is a monocentric study in which nineteen patients were selected prospec-tively. 17 patients of which underwent Hynes-Anderson pyeloplasty due to the PUJO, 2 patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO) and 6 patients were chosen for control group: 5 underwent nephrectomies due to the kidney tumor and 1- upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR to evaluate the relative expres-sion of Tgfb1, Mmp1, Timp1, Pai1, Ctgf and Vegfa was performed. Expression levels of Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and Wilcoxon rank-sum test was performed to determine statistical significance of the differences. Results: significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, Pai1 was found. Discussion and conclusions: These findings suggest that tissue fibrosis similar to other tissues and organs is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF ex-pression is indicative of developmental origin of obstruction.

Idiopathic Pulmonary Fibrosis (IPF) is most common idiopathic interstitial pneumonia. IPF is often seen in elderly men who smoke. Diagnosis of IPF requires integration of a detailed clinical history, specific physical examination, laboratory findings, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, and histopathology. IPF has a heterogeneous clinical course, from an asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). AE of IPF has several important differential diagnoses, such as heart failure and volume overload. The International working project proposed new criteria of AE of IPF in 2016 dividing it into triggered and idiopathic AE. On the basis of these criteria, physicians can detect AE of IPF more easily. The recent international IPF guideline emphasized the utility of chest HRCT. In addition, two anti-fibrotic agents have become available. We should attend not only to management of AE, but also to its prevention. The diagnostic process, laboratory findings, typical chest imaging, management and prognosis of AE are comprehensively reviewed.

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

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

Idiopathic pulmonary fibrosis [IPF] is a chronic progressive disease characterised by the accumulation of scar tissue in the lung parenchyma. It primarily occurs in middle-aged and elderly adults and results in significant morbidity and mortality worldwide. The disease occurs due to repetitive lung epithelial injury, subsequent fibroblast activation and myofibroblast differentiation, resulting in excessive extracellular matrix deposition. This leads to scar formation and subsequent loss of lung function. Current treatment options for patients with IPF include the two anti-fibrotic drugs, pirfenidone and nintedanib, which can slow disease progression; however, there are currently no known cures for the disease. As such, novel methods and drug targets are warranted. In this review, we provide an up-to-date account of the importance of specific cytokines and the potential role of regulatory immune cells. We discuss their role in the pathogenesis of IPF and address some of the key gaps in knowledge.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

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

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVD), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care.

Brain hemispheres develop rather symmetrically except in the case of pathology or intense training. As school experience is a form of training, the current study tested the influence of pedagogy on morphological development through the cortical thickness (CTh) asymmetry index (AI). First, we compared CTh AI of 111 students aged 4 to 18 with 77 adults aged > 20. Second, we investigated CTh AI in the students, as a function of schooling background (Montessori or traditional). At the whole-brain level, CTh AI was not different between the adult and student groups, even when controlling for age. However, the pedagogical experience was found to impact CTh AI in the temporal lobe, within the parahippocampal (PHC) region. The PHC has a functional lateralization, with the right PHC having a stronger involvement in spatiotemporal context encoding, while the left PHC is involved in semantic encoding. We observed CTh asymmetry toward the left PHC for participants enrolled in Montessori schools and toward the right for participants enrolled in traditional schools. As these participants were matched on age, intelligence, home life, and socioeconomic conditions, we interpret this effect found in memory-related brain regions to reflect differences in learning strategies. Pedagogy modulates how new concepts are encoded, with possible long-term effects on knowledge transfer.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

Introduction: Transesophageal echocardiography (TEE) is a vital diagnostic tool in clinical prac-tice, particularly in transcatheter interventions where it aids in both pre-operative planning and intra-operative guidance. Traditional TEE probes often require general anesthesia due to patient discomfort. However, the development of miniaturized TEE probes presents a promising alter-native, enabling routine examinations and interventions with minimal sedation. This study evaluates the feasibility of performing a complete 2D/4D TEE protocol with the new 4D-mini-TEE probe in echocardiography departments and its application in transcatheter interventions. Methods: This prospective, observational study included 30 consecutive patients from two high-volume European hospitals (Interbalkan Medical Center, Thessaloniki, Greece, and Rennes University, France) undergoing TEE or transcatheter interventions. The new 4D-mini-TEE 9VT-D probe (GE Healthcare) was utilized. The quality of the images and the tolerance of the probe were assessed in the Cath lab during interventions and in the echocardiography department during routine TEE examinations. Results: Direct comparison of the 4D-mini-TEE probe with the standard 6VT-D probe, confirmed the excellent image quality of this new pediatric probe. Most of the patients required minimal sedation or local oropharyngeal anesthesia, with satisfactory tolerance reported. Most of the transcatheter procedures did not require general anesthesia and intubation, resulting in shorter procedural time. Both 2D and 4D imaging modalities offered adequate intra-operative guidance for transcatheter procedures. Conclusions: The 4D-mini-TEE probe delivers exceptional imaging capabilities for routine ex-aminations and transcatheter interventions without needing sedation. Its use reduces esophageal trauma and the need for general anesthesia, enhancing patient comfort and safety.

Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often represents the evolution of pathological conditions, causes organ failure, and can, in extreme cases, compromises the functionality of the organs to the point of causing death. In recent years, considerable efforts have been made to understand the molecular mechanisms underlying fibrotic evolution and to identify possible therapeutic strategies. Great interest has been aroused by the discovery of a molecular association between epithelial to mesenchymal plasticity (EMP), in particular epithelial to mesenchymal transition (EMT), and fibrogenesis, which has led to the identification of complex molecular mechanisms closely interconnected with each other, which could explain EMT-dependent fibrosis. However, the result remains unsatisfactory from a therapeutic point of view. In recent years, advances in epigenetics, which is based on chromatin remodeling through various histone modifications or through the intervention of non-coding RNAs (ncRNAs), have provided more information on the fibrotic process, and this could represent a promising path forward for the identification of innovative therapeutic strategies for organ fibrosis. In this review, we summarize current research on epigenetic mechanisms involved in organ fibrosis, with a focus on epigenetic regulation of EMP/EMT-dependent fibrosis.

Pulmonary fibrosis is a chronic, progressive, and irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (EM) due to a persistently activated wound-repair response. The aberrant activation of myofibroblasts in the alveolar environment by Transforming Growth Factor beta (TGF-β) and other signaling molecules is considered a key event in the development and progression of fibrosis. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in extracellular matrix deposition. CTHRC1 is transcriptionally regulated by TGF-β and inhibits both TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 is vital in regulating tissue remodeling during wound repair. In this review, we will highlight recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, rheumatoid arthritis-interstitial lung disease, systemic sclerosis, and post-COVID lung fibrosis. Notably, the expression of CTHRC1 is responsive to antifibrotic drugs such as pirfenidone indicating its potential as a therapeutic target. Collectively, these findings suggest that CTHRC1 may present new opportunities for the diagnosis, stratification, and treatment of patients with lung fibrosis.

:Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate a limited efficacy. Advancing our understanding of pathogenic mechanisms of lung fibrosis provides a future path for the cure. Cellular senescence has gained substantial interest in the past decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence targeted signaling molecules and specific therapy to target senescent cells, known collectively as "senolytic" or “senotherapeutic” agents.

The essence of the sutta that is often stated as the heart sutta or the prajna-paramita, is the wisdom related to the absolute truth or the paramartha, that is experienced in the heart. It is referred to as the foundation stone of the Mahayana Buddhist teachings but in a grander aspect of the nature, truth can neither be labeled as buddhist or hindu or islamic or christian or sikh or tao or zen or parsi or quantum or social etc. When one meditates the identifications dissolve. It would be wrong for anyone to say that she/he would be a buddhist when her/his individuality is lost in emptiness during meditation. What remains is awareness and in awareness, all grasping and feverishness is lost. This knowledge which makes one transcend into the realms of Buddhahood or completely liberated state is revered as goddess also and given a name Bhagavati. So the mother of all Buddhas or the completely liberated ones is nothing but the absolute truth that is encased in the prajna-paramita-sutta. One is raising the female aspect of nature on a higher citadel and terming it as the mother of all Buddhas. Experiencing the absolute truth in heart takes time but it is packed into a verbalized contorted form of a few words. The sutta tries to capture the un-captured absolute and gives a way to explore the deeper realms of the truth at an experiential level. Note that both the former Buddha and the bodhisattva-mahasattva enter into emptiness, experience the knowledge in their entire mind-body complex and after the experience Siddhartha raises Avalokiteshvara to a higher platform and asks him to impart the experienced knowledge in a few words. After the teaching finishes, the Buddha puts a seal on what the bodhisattva has taught by saying "Well done! This is how it should be taught." One has experienced knowledge but one needs a seal of confirmation. The relevance of this knowledge is inexplicable given the magnanimity of conflicts and clashes that happen in the mind body complex pertaining to the spiritual journey one takes. The knowledge is of immense value to those who have experienced deep conflicting issues in their hearts, that have perturbed them regarding the subtle aspects of a spiritual journey. Prajna-paramita-sutta aims to assuage the deeper issues that troubles the heart of a spiritual seeker and makes the path easy enough to reach the goal. The Heart sutra contains the Mahasattipatthan sutra.

Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF. In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression. Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e. with ketones) and dietary strategies that impact ketogenesis. This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies to prevent progression and improve outcomes in the context of HF.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Background: beta blockers of three generations are first-line drugs in the treatment of chronic heart failure (CHF). However, to date there is no clear understanding of the effect of beta blockers on myocardial energy metabolism disorders in CHF. The aim of the study: to conduct a study of beta-blockers of different generations on myocardial energy metabolism in the experimental CHF. Methods: CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically – new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, metoprolol - 15 mg/kg, Nebivolol -10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined - ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, NAD-dependent malate dehydrogenase (NAD-MDH) activity. Results: traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties - Carvedilol and, especially, Nebivalol and Hypertril improved myocardial energy metabolism. Conclusions: obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

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

Heart failure (HF) has become a public health problem, but exact pathophysiology is still unknown. Western diet characterised with high sugar, high fat, red meat and processed meat, eggs, fried foods and sweetened beverages, may cause oxidative stress and inflammation, leading to oxidative dysfunction and adverse effects on cardiac-ultra-structure. However, only little is known about oxidative function of the of the myocardium and how oxidative dysfunction predispose Ca-overloading resulting in to physio-pathological remodelling leading to HF. Antioxidants such as flavonoids and polyphenolics, omega-3 fatty acids, vitamins, minerals as well as essential and nonessential amino acids that are rich in Indo-Mediterranean type of diets, may have protective roles in maintaining oxidative functions of the heart. The cardiac cells use fatty acids and glucose for the metabolic functions depending upon physiological and metabolic requirements. Apart from glucotoxicity, lipotoxicity is also damaging to cardiac cells which worsen in presence of deficiency of endogenous antioxidants and lower exogenous antioxidants in the diet. There is increased production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) due to high sugar and high fat diets, leading to oxidative dysfunction and Ca-overloading. The biological changes may begin with physiological remodelling to pathological remodelling due to oxidative damages. High fat diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve ejection fraction in a mouse model of HF. It is possible that increased supplementation of High Exogenous Antioxidant Restorative Treatment (HEART) diet; polyphenolics and flavonoids, vitamins, minerals, arginine, with omega-3 fatty acids, and cessation of red meat and egg may further improve the oxidative function of cardiac cells, resulting in the prevention and improvement in the earliest of the Six Stages of HF. Cohort studies and randomised, controlled trials would be necessary for demonstration of the role of HEART diet in the management of HF.

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.

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which has now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous study has demonstrated that Bruton's tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation;(2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish cardiac fibrosis animal model. Here, results showed that BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage proinflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by BTK、STAT3、NF-κB and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.

We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.

The burden of chronic liver disease is globally increasing at an alarming rate. Chronic liver injury leads to liver inflammation and fibrosis (LF) as critical determinants of long-term outcomes such as cirrhosis, liver cancer and mortality. LF is a wound-healing process characterized by excessive deposition of extracellular matrix (ECM) proteins due to the activation of hepatic stellate cells (HSCs). In the healthy liver, quiescent HSCs metabolize and store retinoids. Upon fibrogenic activation, quiescent HSCs transdifferentiate into myofibroblasts, lose their vitamin A, upregulate -smooth muscle actin, and produce pro-inflammatory soluble mediators, collagens, and inhibitors of ECM degradation. Activated HSCs are the main effector cells during hepatic fibrogenesis. In addition, the accumulation and activation of profibrogenic macrophages in response to hepatocyte death play a critical role in the initiation of HSC activation and survival. The main source of myofibroblasts is resident HSCs. Activated HSCs migrate to the site of active fibrogenesis to initiate the formation of a fibrous scar. Single-cell technologies revealed that quiescent HSCs are highly homogenous, while activated HSCs/myofibroblasts are much more heterogeneous. The complex process of inflammation results from the response of various hepatic cells to hepatocellular death and inflammatory signals related to intrahepatic injury pathways or extrahepatic mediators. Inflammatory processes modulate fibrogenesis by activating HSCs and, in turn, drive immune mechanisms via cytokines and chemokines. Increasing evidence also suggests that cellular stress responses contribute to fibrogenesis. Recent data demonstrated that LF can revert even at advanced stages of cirrhosis if the underlying cause is eliminated, which inhibits the inflammatory and profibrogenic cells. However, despite numerous clinical studies on plausible drug candidates, an approved antifibrotic therapy still remains elusive. This state-of-the-art review presents cellular and molecular mechanisms involved in hepatic fibrogenesis and its resolution, as well as comprehensively discusses the drivers linking liver injury to chronic liver inflammation and LF.

Nonalcoholic steatohepatitis (NASH), which is characterized by liver steatosis, inflammation and fibrosis, is the most severe variation of nonalcoholic fatty liver disease (NAFLD). This disease is a consequence of several metabolic alterations such as type 2 diabetes and dyslipidemia that trigger different pathways of cell dysfunction and systemic inflammation which ultimately affect the liver. Furthermore, those mechanisms activate a complex cascade of immune response after repeated cell aggression. In the liver cytokines and interleukins interact with network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), lymphocytes and hepatic stellate cells (HSC). These cells translate those signals into immune responses and pathologic hepatic changes during the development of NASH. In this scenario the development of fibrosis is the most important change since it is an adaptive mechanism that in the short time has the objective of repair the damaged tissue but after prolonged injury it progresses to parenchymal scarring, cellular dysfunction and finally to organ failure. Finally, since NASH is an important cause of liver cirrhosis; this review addresses the cellular pathways of fibrosis in the setting of NASH explained by the interaction between immune and hepatic cells.

Wound healing is a complex, dynamic process involving the coordinated interaction of diverse cell types, growth factors, cytokines, and extracellular matrix components. Despite emerging evidence highlighting their importance, dermal sheath cells remain a largely overlooked aspect of wound healing research. This review explores the multifunctional roles of dermal sheath cells in various phases of wound healing, including modulating inflammation, aiding in proliferation, and contributing to extracellular matrix remodeling. Special attention is devoted to the paracrine effects of dermal sheath cells and their role in fibrosis, highlighting their potential in improving healing outcomes, especially in differentiating between hairy and non-hairy skin sites. By drawing connections between dermal sheath cells activity and wound healing outcomes, this work proposes new insights into the mechanisms of tissue regeneration and repair, marking a step forward in our understanding of wound healing processes.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells and fibroblasts, that producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

Pulmonary fibrosis causes scar tissue formation that disrupts the functioning of the lungs. Uncaria gambir (Hunter) Roxb (hereafter gambir)—a plant native to West Sumatra in Indonesia—contains flavonoid (+)-catechin and has strong antioxidant activity, and it can be used to combat pulmonary fibrosis. This random in vivo experimental study analyzed the antifibrotic effect of gambir on the lungs of rats with bleomycin-induced fibrosis. The subjects were 10 groups of 10-week-old male rats weighing around 200–250 g. All groups were terminated at the end of the seventh week or on day 50. The lungs were cleaned, and tissues were taken to analyze inflammatory cell counts and TGF-β1 levels using bronchoalveolar lavage (BAL) with ELISA; type I collagen and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels using immunohistochemistry (IHC); and activation of NF-κB using ELISA and Western blot assays. The most severe histopathological characteristic based on the modified Ashcroft score was in the bleomycin group (BG), whereas the mildest was in the 262 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G262). The results showed a significant difference in the BAL inflammatory cell count (p = 0.017; p &lt; 0.05). AF G262 differed most from the other antifibrotic groups in terms of the number of inflammatory cells (0.63), TGF-β1 levels (3.80), and NF-κB levels (0.48), followed by the 131 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G131), which also differed most from other antifibrotic groups in terms of NF-κB (0.48), TIMP-1 (11.74), and collagen I (14.50) levels. Western blot analysis showed that the fibropreventive and antifibrotic groups had a specific band size of p65, whereas no specific band binding existed in the control group. This study concluded that the administration of AF G262 could improve fibrosis by lysing the extracellular matrix (ECM) in rat lungs.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p

Since the outbreak of the COVID-19 pandemic, patients infected with COVID-19 may experience abnormal heart rates, posing potential health risks. This study proposes a non-contact method for measuring heart rate (HR) and heart rate variability (HRV) to effectively reduce the risk of infection and assist healthcare professionals in more accurate diagnosis and treatment. In this study, except for the different image acquisition method, other research processes and methods are similar to the research methods in [15]. The image acquisition method is changed from forehead image to palm image. The new non-contact measurement performance of the proposed method can effectively not only avoid infection concerns but also obtain heart rate and HRV quickly and conveniently, providing higher accuracy for physiological parameters, root mean square error (RMSE), and mean absolute percentage error (MAPE) compared to those in recently published papers.

The aim of the article is to identify and illustrate the most used psychological techniques in the field of cystic fibrosis (CF) and to help clinicians choosing the appropriate strategy among the various possibilities. The disease and its medical treatments can be difficult to tolerate and can cause anxiety about health status or feelings of hopelessness and stress. The prevalence of depression and anxiety is 2.3 times higher in adults with CF than in community samples. A strong correlation has been identified between elevated psychological distress and unfavorable health outcomes, including, among others, impaired lung function, reduced BMI, an increased incidence of pulmonary exacerbations, and an elevated risk of transplantation. The use of psychological interventions is useful in addressing these common distress in CF patients. Aware of the necessity to identify efficacious interventions for all levels of depression and anxiety in CF patients, this study presents an overview of the research on psychological interventions for patients with CF, in order to complement the treatments suggested by the international guidelines on mental health in CF cases. In fact, the aim of this study is to conduct a review and quantitative synthesis of the psychological intervention techniques that are currently available for individuals with CF.

There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on immune system. There was a high incidence of COVID-19 induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity, long-term disability, and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show a significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF.

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, genetic conditions such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis, and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease from other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver cirrhosis.

Background: The adoption of self-care behaviors among patients with congestive heart failure (CHF) is essential for the management of their health condition. However, there is a lack of tools for estimating self-care in CHF patients. We aim to develop and validate the Hippocratic heart failure self-care scale (HHFSCS). Methods: the scale includes 22 items which are reviewed by a committee of experts. Individuals indicate the frequency at which they follow each self-behavior on a five-point Likert scale. Adult patients with CHF (n=250) from a General Hospital, in Athens, were participated in the study from June 2020 to March 2021. Reliability coefficients and Explanatory Factor Analysis (EFA), using a Varimax rotation and the Principal Components Method were used to assess the psychometric measurements. Results: The Cronbach’s alpha coefficient of the HHFSCS was 0.807. The exploratory factor analysis identified two domains that accounted for 88.44% of the variance of the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test-retest showed a significant strong correlation (r=0.973, p&lt;0.001). Conclusions: The HHFSCS is a reliable and valid tool for assessing self-behaviors in CHF patients. Health professionals can use it in their clinical practice to improve the management of patient’s health conditions.

Cardiovascular disease is the leading cause of death worldwide. A key factor in assessing the risk of cardiovascular disease is left ventricular functional evaluation. Left ventricular (LV) systolic function is evaluated by measuring the left ventricular ejection fraction (LVEF) using echocardiography data. Therefore, quick and accurate left ventricle segmentation is important for estimating the LVEF. However, it is difficult to accurately segment the left ventricle due to changes in the shape and area of the left ventricle during cardiac cycles. In this study, we proposed a framework that considers changes in the shape and area of the left ventricle during the cardiac cycle by applying the convolutional long short-term memory (CLSTM) approach. In addition, we evaluated the left ventricular segmentation and multidimensional quantification of the proposed system in comparison to manual and automated segmentation methods. In addition, to assess the validity of CLSTM, the values of multi-dimensional quantification metrics were compared and analyzed using graphs and Bland–Altman plots on a frame-by-frame basis. We demonstrated that the CLSTM method effectively segments the left ventricle by considering the LV activity. In conclusion, we demonstrated that LV segmentation based on our framework may be utilized to accurately estimate LVEF values.

Neonatal electronic cardiac monitoring in labor and delivery room (DR-ECG) is shown to be sustained at a tertiary care regional perinatal center despite COVID-19 and other complex organizational challenges. In this contemporary cohort, initial increase in chest compressions at birth associated with the introduction of DR-ECG monitoring was mitigated by focused educational interventions on effective ventilation with no difference in neonatal mortality. DR-ECG may help our understanding of human and system factors, identify potential better practices for optimal resuscitation team performance and assess impact of targeted training initiatives on clinical outcomes.

The thermocontextual interpretation (TCI) establishes a system’s exergy, entropic energy, and thermal entropy as thermocontextual properties of state, defined with respect to its positive temperature surroundings. This work extends previous applications of the TCI to irreversible and statistical transitions. The TCI defines statistical entropy as a transactional process of derandomization and transition to a negative-entropy state. Statistical measurements of a confined quantum particle’s position are detailed in terms of reversible processes of instantiation and actualization. The TCI then formalizes the MaxEnt as a fundamental physical principle. We apply MaxEnt and statistical entropy measurements to the double-slit experiment. Particles passing through parallel slits record a wave interference pattern, but a “which-slit” detector eliminates wave interference. Richard Feynman called the double-slit experiment the only mystery, at the heart of quantum mechanics. The TCI offers a simple explanation. The which-slit detector breaks the system’s symmetry, enabling particles to pass through one slit or the other, and MaxEnt selects the asymmetrical transition, which has no wave interference and a higher statistical entropy.

Myocardium transcriptomes of mouse left and right atria and ventricles were profiled separately to identify the differences that might be responsible for the distinct functional roles of the four heart chambers. In total, 16,886 distinct unigenes have been quantified in all 16 samples collected from four adult male mice from the same litter. 15.76% of the quantified genes on the left and 16.5% on the right exhibited differential expression between the corresponding atrium and ventricle of the same side, while 5.8% in atria and 1.2% in ventricles were differently expressed between the left and the right. Beyond the differentially expressed genes, the study revealed distinct expression control and coordination of ion channels and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/glucogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 (encoding ankyrin-B) oscillates in phase with all its binding partners in the left ventricle, the percentage of synergistically expressed partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis revealed also the high interventricular synchrony of the expression of ion channels.

Cardiac dynamics are traditionally linked to a left ventricle, right ventricle and septum morphology, a topography that differs from the heart’s 5-century-old anatomic description of containing a helix and circumferential wrap architectural configuration. Torrent Guasp’s helical ventricular myocardial band (HVMB) defines this anatomy and its structure, explains why the heart’s 6 dynamic actions of narrowing, shortening, lengthening, widening, twisting and uncoiling happen. This database raises questions about deductions behind “accepted cardiac mechanics”, and its functional aspects will challenge and overturn them. These suppositions include the LV, RV, and septum description, timing of mitral valve opening, isovolumic relaxation period, reasons for torsion/twisting, untwisting, reasons for longitudinal and circumferential strain, echocardiographic sub segmentation, resynchronization, RV function dynamics, and diastolic dysfunction’s cause and unrecognized septum impairment. Torrent Guasp’s revolutionary contributions may alter future understanding of the diagnosis and treatment of cardiac disease.

Predicting heart disease is crucial for early diagnosis and intervention, significantly improving patient outcomes and reducing mortality rates. This study compares various machine learning models, including Logistic Regression, Random Forest, Gradient Boosting, XGBoost, and Long Short-Term Memory (LSTM) networks, using the Cleveland Heart Disease dataset. Comprehensive preprocessing steps were undertaken, such as handling missing values, converting categorical variables to numeric forms, and binarizing the target variable for binary classification. Each model was rigorously evaluated using performance metrics, including accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC-ROC). SHapley Additive exPlanations (SHAP) values were employed to provide insights into feature importance, ensuring model transparency and interpretability. The results indicate that XGBoost outperformed all other models, achieving an accuracy of 90% and an AUC-ROC of 0.94, demonstrating its superior ability to capture complex patterns in the data through advanced optimization techniques and regularization. This study highlights the significant potential of advanced machine learning techniques, particularly ensemble methods like Gradient Boosting and XGBoost, in enhancing heart disease prediction. These models offer higher accuracy and valuable interpretability, making them practical tools for early diagnosis in clinical settings. Future research should focus on integrating these models into healthcare systems and exploring hybrid approaches to further improve predictive performance and clinical applicability.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.