Abstract Forensic institutions throughout the country house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, and nutrition led to unmatched longevity in this population which previously lived on average 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who had aged on dopamine blockers. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss, may contribute to the development of early dementia. Taken together, increased lifespan and subsequent cognitive deficit observed in long-term psychiatric institutions brought forth questions and dilemmas unencountered by the previous generations of clinicians, such as: 1. Does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? 2. Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? 3. Can patients with schizophrenia and dementia meet the Dusky standard and stand trial? 4. Should neurocognitive disorders in elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we describe strategies for potentially slowing the development of neurocognitive disorders in forensic patients with chronic mental illness by adopting a three-prong strategy: 1. Approaching lifelong psychosis from microbial and immunological perspective. 2. Identify modifiable risk factors for age-related diseases in forensic institutions. 3. Utilizing novel receptor-independent treatments for chronic psychosis.

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target actin-binding protein gelsolin that is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP2-binding domain of gelsolin in the gelsolin-actin complex through extensive ten microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP2-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

Sporadic colorectal cancer (CRC) develops through distinct molecular events. Loss of 18q chromosome is a conspicuous event in the progression of adenoma to carcinoma. There is limited information regarding the molecular effectors of this event. Earlier, we had reported ATP8B1 as a novel gene associated with CRC. ATP8B1 belongs to the family of P-type ATPases (P4 ATPase) that primarily function to facilitate the translocation of phospholipids. In this study, we attempt to implicate ATP8B1 gene located on chromosome 18q as a tumor suppressor gene. We studied indigenous patient data and confirmed the reduced expression of ATP8B1 in tumor samples. CRC cell lines were engineered with reduced and enhanced levels of ATP8B1 which provided a tool to study its role on cancer progression. Forced reduction of ATP8B1 expression either by CRISPR/Cas9 or shRNA was associated with increased growth and proliferation of CRC cell line - HT29. In contrast, overexpression of ATP8B1 resulted in reduced growth and proliferation of SW480 cell line. We generated a network of genes that are downstream of ATP8B1. Further, we provide predicted effect of modulation of ATP8B1 levels on this network and possible effect on fatty acid metabolism related genes. These results provide evidence in support of ATP8B1 being a tumor suppressor that may affect fatty acid metabolism in CRC.

Marburg virus (MARV) is a lipid-enveloped negative sense single stranded RNA virus, which can cause a deadly hemorrhagic fever. MARV encodes seven proteins, including VP40 (mVP40), a matrix protein that interacts with the cytoplasmic leaflet of the host cell plasma membrane. VP40 traffics to the plasma membrane inner leaflet, where it assembles to facilitate the budding of viral particles. VP40 is a multifunctional protein that interacts with several host proteins and lipids to complete the viral replication cycle, but many of these host-interactions remain unknown or are poorly characterized. In this study, we investigated the role of a hydrophobic loop region in the carboxy-terminal domain (CTD) of mVP40 that shares sequence similarity with the CTD of Ebola virus VP40 (eVP40). These conserved hydrophobic residues in eVP40 have been previously shown to be critical to plasma membrane localization and membrane insertion. An array of cellular experiments and confirmatory in vitro work strongly suggests proper orientation and hydrophobic residues (Phe281, Leu283, and Phe286) in the mVP40 CTD are critical to plasma membrane localization. In line with the different functions proposed for eVP40 and mVP40 CTD hydrophobic residues, molecular dynamics simulations demonstrate large flexibility of residues in the EBOV CTD whereas conserved mVP40 hydrophobic residues are more restricted in their flexibility. This study sheds further light on important amino acids and structural features in mVP40 required for its plasma membrane localization as well as differences in the functional role of CTD amino acids in eVP40 and mVP40.

SMAD ubiquitination regulatory factor 1 (Smurf1) is a Nedd4 family E3 ubiquitin ligase that regulates cell motility, polarity and TGFβ signaling. Smurf1 contains an N-terminal protein kinase C conserved 2 (C2) domain that targets cell membranes and is required for interactions with membrane-localized substrates such as RhoA. Here we investigated the lipid-binding mechanism of Smurf1 C2, revealing a general affinity for anionic membranes in addition to a selective affinity for phosphoinositides (PIPs). We found that Smurf1 C2 localizes not only to the plasma membrane but also to negatively charged intracellular sites, acting as an anionic charge sensor and selective PIP-binding domain. Site-directed mutagenesis combined with docking/molecular dynamics simulations revealed that the Smurf1 C2 domain loop region primarily interacts with PIPs and cell membranes, as opposed to the β-surface cationic patch employed by other C2 domains. By depleting PIPs from the inner leaflet of the plasma membrane, we found that PIP binding is necessary for plasma membrane localization. Finally, we used a Smurf1 cellular ubiquitination assay to show that the amount of ubiquitin at the plasma membrane interface depends on the lipid-binding properties of Smurf1. This study shows the mechanism by which Smurf1 C2 targets membrane-based substrates and reveals a novel interaction based on PI(4,5)P2 and PIP3 selectivity.

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) with hepatocytes targeting as carriers for the magnetic resonance imaging (MRI) contrast agent (i.e., magnetic nanostructured lipid carriers, MNLCs), and to evaluate the targeting ability of the MNLCs with T2-weighted MRI both in vitro and in vivo. Here, the galactose-octadecylamine (Gal-ODA) conjugates were synthesized by chemical coupling reaction between lactose acid (LA) and octadecylamine (ODA). Then the superparamagnetic iron oxide (SPIO) loaded nanostructured lipid carrier (conjugated by Gal-ODA, Gal-NLC-SPIO) was prepared by emulsification-ultrasonic method using monoglyceride as lipid materials. The Gal-NLC-SPIO with a diameter of about 50 nm could specifically internalize into LO2 (human hepatic cell line) cells. In vitro MRI results also proved the specific targeting ability of Gal-NLC-SPIO to LO2 cells. The in vivo MR imaging experiments using an orthotopic intrahepatic xenograft tumor model further validated the hepatocytes targeted effect of Gal-NLC-SPIO. The results of this study suggested that Gal-NLC-SPIO can be used as a contrast agent to aid in the diagnosis of hepatic diseases.

Objective. This study aimed to determine the correlation of colour M-mode velocity propagation in the assessment of left ventricular diastolic function among acute decompensated heart failure patients with preserved ejection fraction (HFpEF). Materials and Methods. This research is an observational analytical study using a cross–sectional study design conducted from April to June 2022. The subjects of this study were patients diagnosed with acute HFpEF and treated at Dr. Soetomo General Academic Hospital, Surabaya. Patients with heart rhythm disturbances, moderate to severe valvular heart disease, and congenital heart defects were excluded from this study. Patients were measured for diastolic function including mitral valve early mitral inflow velocity (MV E Velocity), mitral peak velocity of early filling (E’) (E' Septal and E' Lateral), left atrial volume index (LAVI), The maximal tricuspid regurgitation velocity (TR V Max), Vp, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/E'), the ratio between early and late ventricular filling velocity (E/A) and E/Vp Ratio. N-terminal-pro hormone B-type natriuretic peptide (NT–ProBNP) examination was also performed on study subjects as an additional diagnosis of acute heart failure. Results. There were 33 patients who met the inclusion and exclusion criteria and were included in our study. There were 26 patients (78.8%) with grade I diastolic dysfunction, 4 patients (12.1%) with grade II diastolic dysfunction, and 3 patients (9.1%) with grade III diastolic dysfunction. There is a strong positive correlation between Vp with parameters E' Septal (p = < 0.001; r = 0.636) and E' Lateral (p = < 0.001; r = 0.650). Vp is negatively correlated with the ratio E/E' (p = 0.029; r = –0.37). The PCWP estimate with E/Vp ratio had a strong correlation with the NT–Pro BNP value > 300 pg/ml in acute HFpEF patients (p = < 0.001; r = 0.726) compared to the PCWP estimate with E/E' (p = < 0.001; r = 0.549). Conclusion. There is no correlation between Vp value and degree of diastolic dysfunction in patients with acute HFpEF.

Background/Objectives: Body surface area is one of the most important anthropometric parameters in medicine. The study's primary objective is to compare the consistency of the BSA estimation results through applying available formulas. Other objectives include determining the ability of these formulas to discriminate between the deaths and living patients, comparing the formulas’ diagnostic features as well as investigating whether the risk associated with a low BSA is independent of BMI. Methods: The study included 1029 patients (median age: 54 years, female: 13.7%, NYHA I/II/III/IV: 6.3% / 36.5% / 47.7% / 9.5%) diagnosed with heart failure. For each patient, BSA was calculated using the 25 formulas. Over the 3-year observation period, 31.2% of the patients died. Results: The average BSA value of the optimal discrimination thresholds was 1.79 m2 ± 0.084 m2 and the BSA difference between the estimators with the lowest (BSAMeeh1879) and the highest (BSANwoye1989) optimal discrimination thresholds was 0.42 m2. The lowest mortality rate was 35.2% and occurred in the subgroup of individuals with BSA values below the optimal discrimination threshold using the BSASchlich2010 estimator. The highest mortality was observed when estimators BSAMeeh1879 or BSALivingston&Lee2001 were used. Conclusions: Our study has shown a relatively good concordance of 25 BSA estimators in BSA assessment in patients, without extremes of weight or height known to disrupt it. All BSA estimators presented a significant, although weak, ability to discriminate death from alive in 3-year follow-up. The higher risk of death in smaller patients as shown by BSA was independent of BMI in all but 2 BSA estimators.

Background/Objectives: Remote monitoring (RM) of cardiac implantable electronic devices for adults offers improved patient outcomes. However, bedside transmitters utilized so far are not optimal due to limited patient adherence. The goal of this study was to evaluate the efficacy of RM regarding the connectivity of smartphone app-based solutions, adherence to planned automatic follow-ups, and occurrence of alert-based events. Methods: We evaluated the adult heart failure (HF) population with implanted cardiac resynchronization therapy defibrillator (CRT-D) divided into two arms: with app-based RM (abRM) and without app-based RM (control). Results: A total of 81 patients (median age of 69.0) were included in our study. 65 patients received a CRT-D with abRM functionality, and 16 did not. 12 patients had no smartphone, and 2 provided no consent, resulting in their transfer to the control group. Finally abRM arm consisted of 51 patients, while 30 patients were in the control group. Median period of follow-up lasted 12 months. Among abRM patients, 98.0% successfully transmitted their first scheduled follow-up, and 80.4% were continuously monitored. Alert-based events were mainly related to arrhythmic events and device functionality with significantly shorter median time to notification (1 day vs. 101 days; p<0.0001) in the abRM group. Conclusions: Our study showed a high level of compliance with timely initial transmission and adherence to scheduled remote follow-ups. Patient enrollment eligibility was a major challenge due to the limited accessibility of smartphones in the population. App-based RM demonstrated an accurate notification of events and patient-initiated transmissions in emergencies, regardless of location.

Inherited heart diseases (IHDs) are caused by genetic mutations that disrupt the physiological structure and function of the heart. Understanding the mechanisms behind these diseases is crucial for developing personalised interventions in cardiovascular medicine. Development of induced pluripotent stem cells, which can then be differentiated to any nucleated adult cell type, has enabled the creation of personalised single-cell and multicellular models, providing unprecedented insights into the pathophysiology of IHDs. This review provides a comprehensive overview of recent advancements in human iPSC models used to dissect the molecular and genetic underpinnings of common IHDs. We examine multicellular models and tissue engineering approaches, such as cardiac organoids, engineered heart tissue, and multicellular co-culture systems, which simulate complex intercellular interactions within heart tissue. Recent advancements in stem cell models offer a more physiologically relevant platform to study disease mechanisms, enabling researchers to observe cellular interactions, study disease progression, and identify therapeutic strategies. By leveraging these innovative models, we can gain deeper insights into the molecular and cellular mechanisms underlying IHDs, ultimately paving the way for more effective diagnostic and therapeutic strategies.

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.

Deep hypothermic circulatory arrest (DHCA) is safe, but subtle neurodevelopmental deficits may persist far beyond the perioperative period. We investigated the relationship between DHCA duration and neurodevelopmental outcomes in young children undergoing cardiac surgery with DHCA. Children aged < 42 months, including neonates who underwent cardiac surgery using DHCA without regional perfusion techniques, were included as the DHCA group. Children in the same age range undergoing cardiac surgery without DHCA were included as the control group. All patients underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development (BSTID) by a trained pediatrician. Seventeen of 25 DHCA and six of 10 control patients completed the BSTID assessment. The groups showed no preoperative, operative, or postoperative significant differences. In adjusted multivariable analysis, prematurity and age at assessment were significant changing predictors of each of the BSTID components (p < 0.001), other than the gross motor component, where only age at assessment was a significant adjusting predictor. Longer DHCA was associated with lower fine and gross motor BSTID components; however, the association was not statistically significant (p = 0.06). Use of DHCA without regional perfusion techniques may be associated with less optimal neurodevelopmental outcomes if DHCA has a long duration.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

Diagnosing congenital heart disease (CHD) remains challenging because of its complex morphology. Representing the intricate structures of CHD on conventional two-dimensional flat screens is difficult owing to wide variations in the pathologies. Technological advancements, such as three-dimensional printed heart models (3DPHM) and virtual reality (VR), could potentially address the limitations of viewing complex structures using conventional methods. This study aimed to investigate the usefulness and clinical value of four visualization modalities across three different cases of CHD, including ventricular septal defect, double outlet right ventricle, and tetralogy of fallot. Seventeen cardiac specialists were invited to participate in this study, which was aimed at assessing the usefulness and clinical value of four visualization modalities, namely, DICOM images, 3DPHM, VR, and 3D PDF. Of these modalities, 76.4% of the specialists ranked VR as the best for understanding the spatial associations among cardiac structures and for presurgical planning. Meanwhile, 94.1% ranked 3DPHM as the best modality for communicating with patients and their families. Of the various visualization modalities, VR was the best tool for assessing anatomical locations and vessels, comprehending the spatial relationships among cardiac structures, and for presurgical planning. The 3DPHM models were the best tool for medical education as well as communication. In summary, both 3DPHM and VR have their own advantages and outperform the other two modalities, i.e., DICOM images and 3D PDF, in terms of visualizing and managing CHD.

Background: the study aimed at comparing the prognostic importance of Heart Rate (HR) and of QT corrected (QTc) according to Fridericia, Framingham and Bazett methods, in a large non-selected population. Methods: the analysis of digital Electrocardiograms archived from 2008 to 2022 in the metropolitan area of Modena, Italy, was made. The population under study was divided into three age-groups and survival analysis was performed. Results: 131.627 patients were enrolled and during the follow-up (mean 1641.4 days), all-cause mortality was 8.9%. Both HR and QTc were associated with mortality. All-cause mortality significantly increased from HR values greater than 81 BPM and from QTc values greater than 440 msec in young subjects and 455 msec in old subjects (values of the 75th percentiles/optimal operating point). Cox analysis confirmed the better prognostic value of Bazett’s QTc and of HR in the whole population and in the three age-groups. Conclusion: Bazett’s method performed better than other methods but unexpectedly HR had the same or a better correlation with all-cause mortality. Since HR is simple and readily available, its evaluation should be improved. However, reference values for QTc and for HR are difficult to define causing many confounding factors and further population-study are required.

There is increasing evidence that some adult mitral valve pathologies may have developmental origins involving errors in cell signaling and protein deposition during valvulogenesis. While early and late gestational stages are well-documented in zebrafish and small mammalian models, longitudinal studies in large mammals with a similar gestational period to humans are lacking. Further, the mechanism of chordae tendineae formation and multiplication remains unclear. This current study presents a comprehensive examination of mitral anterior leaflet and chordae tendineae development in a bovine model (with a gestational period of 9 months). Remarkably distinct from small mammals, bovine development displayed early branched chordae, with increasing attachments only until birth, while the anterior leaflet grew both during gestation and postnatally. Chordae also exhibited accelerated collagen deposition, maturation, and crimp development during gestation. These findings suggest that the bovine anterior leaflet and chordae tendineae possess unique compartmentalized processes of development despite being a continuous collagenous structure.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

Abstract The heart serves as the pivotal organ generating rhythmic contractions allowing blood ejection from the ventricles and its circulation in the cardiovascular system. Contractions of the heart requires oxygen and energy consumption and removal of metabolic factors from cardiac myocytes. The mechanical performance of the cardiac muscle and production of the vasoactive factors are significantly affected in cardiovascular and metabolic diseases, especially in the heart failure, hypertension and diabetes mellitus. The processes affecting coronary blood flow and cardiac contractility in these diseases are not fully recognized. The present review draws attention to specific role of angiotensin peptides, vasopressin and insulin in the regulation of the coronary blood flow and cardiac contractions. There is evidence for intracardiac production of some of these compounds and their importance in the regulation of the cardiac tissue oxygenation, energy production and metabolism, and generation of other cardiovascular compounds, such as nitric oxide, bradykinin and endothelin. Presence of receptors for angiotensin II, angiotensin-(1-7) and insulin in the coronary vessels and cardiomyocyes sets up conditions for interaction of these factors at the signaling level. Coronary vessels and cardiac muscle possess AT1 and AT2 receptors, angiotensin-1-7 receptor, vasopressin V1 receptor, and insulin receptor substrates. Expression of these receptors and responsiveness to angiotensins, vasopressin and insulin are altered during heart failure, hypertension, obesity and diabetes mellitus, especially when these diseases occur simultaneously. The survey of the literature presented in the review provides evidence for the belief that very individualized treatment, including interactions of angiotensins and vasopressin with insulin, should be selected for patients suffering simultaneously for cardiovascular and metabolic diseases.

The World Health Organization (WHO) has released reports indicating that heart disorders hold the unfortunate distinction of being the primary cause of death worldwide. Shockingly, an astonishing estimated 17.9 million lives are claimed by heart diseases annually, accounting for an alarming 31% of all global deaths. With all the flaws in the clinical situation, it is frequently challenging to assess the severity of cardiac disease and forecast its course of progression due to heterogeneity and complex interplay of factors. Therefore, early heart disease detection is essential for effective therapy. To address these challenges, Machine Learning (ML) boosting algorithms play a pivotal role as the main components of predictive analytics required to do this. The main objective of this study is to develop a comprehensive comparative framework to predict heart diseases using state-of-the-art machine learning with boosting techniques such as Decision Tree, Random Forest, Gradient Boosting, Catboost, XGboost, Light GBM, and Adaboost. To evaluate the performance of the models, a large heart disorders dataset is used from the UCI machine learning repository, comprised of 26 feature-based numerical and categorical attributes with 8763 samples from all over the globe. The Experimental results reveal that AdaBoost attained the highest accuracy of 95% and outperforms other algorithms concerning various performance measures like precision= 0.98, recall= 0.95, specificity= 0.95, f1-score=0.01, Negative predicted value= 0.83, False positive rate= 0.04, False negative rate= 0.04 and False Development rate= 0.01.

Autonomic dysregulation is associated with cardiovascular consequences in obstructive sleep apnea (OSA). This study aimed to investigate the effect of acute continuous positive airway pressure (CPAP) treatment on autonomic activity and to identify factors contributing to the heart rate variability (HRV) changes in OSA. Frequency domain HRV parameters were calculated and compared between the baseline polysomnography and during the CPAP titration in 402 patients with moderate to severe OSA. There were significant reductions in total power, very low-frequency band power, low-frequency band power, and high-frequency band power during the CPAP titration as compared to the baseline polysomnography. This tendency was more pronounced in men than in women, and in patients with severe OSA than those with moderate OSA. Multivariate analysis found that changes in apnea-hypopnea index and oxygen saturation were significantly associated with changes in sympathetic and parasympathetic activity, respectively. This study demonstrated that HRV parameters significantly changed during the CPAP titration, indicating a beneficial effect of CPAP in restoration of sympathetic and parasympathetic hyperactivity in OSA. Prospective longitudinal studies should determine whether long-term CPAP treatment aids in maintaining the long-lasting improvement of the autonomic functions, thereby contributing to the prevention of cardiovascular and cerebrovascular diseases in patients with OSA.

Abstract: The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ and Hippo signaling is also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if Hippo pathway acts as a mediator of TGFβ2 signaling. Immunofluorescence staining showed that TGFβ2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicated increased nuclear localization of Yes associated protein 1 (YAP1) following a similar treatment of TGFβ2. In collagen lattice formation assays, TGFβ2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in absence or presence of by exogenously added TGFβ2. To confirm the molecular mechanisms of verteporfin induced inhibition of TGFβ2-dependent extra-cellular matrix (ECM) reorganization we performed gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirmed that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked TGFβ2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFβ2 regulation of cushion mesenchymal cell be-havior and ECM remodeling is mediated by YAP1. Thus, TGFβ2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease.

Chronic Chagas Cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilized electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodeling and for examining the potential of anti-parasitic drugs to prevent or alleviate CCC development and progression.

Covid-19 pandemic has greatly affected the whole world since the beginning and it continues to affect it. The main aim of this study is to show how Covid-19 affect other mortal diseases; cancer, heart diseases, and diabetes in near future. With this purpose two mathematical models are proposed via Ordinary Differential Equations (ODEs); one for the relationship between Covid-19 and cancer and one for the relationship between Covid-19, diabetes and heart diseases. Afterwards, stability analyses of these models are demonstrated. In order to see the effect of parameters on the disease compartments, sensitivity analysis is applied. Results of sensitivity analysis revealed that huge percentage of people are still scared of visiting doctors and this may lead a massive increase in the diagnosis of other diseases for upcoming years. Moreover, figures displayed that there exists a relationship between diabetes and heart diseases. Especially, diabetes patients should be careful about their health situations and take care of their heart. In order to provide these, awareness of people should be developed.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Background: Acute heart failure (AHF) is a serious medical problem that necessitates hospitalisation and often results in death. Patients hospitalised to the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological predictors for AHF. Methods: In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients' demographic and hematological information was analyzed to determine AHF. Important risk variables for AHF diagnosis were identified using LASSO feature selection. To test the efficacy of the suggested prediction model (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were all computed to evaluate the model's efficacy. Permutation-based analysis and SHAP, were used to assess the importance and influence of the model's incorporated risk factors. Results: White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group (p<0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH) and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls (p <0.05). When XGBoost was used in conjunction with LASSO to estimate AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF. Conclusions: The XGBoost model demonstrated exceptional performance in accurately estimating Acute Heart Failure, and the application of Explainable Artificial Intelligence effectively provided intuitive explanations for the model's estimations. The suggested interpretable model holds potential for the identification of patients at high risk, thereby facilitating the optimization of treatment and planning for follow-up in cases of AHF.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.

Psilocybin-containing mushrooms, commonly known as magic mushrooms have antidepressant effect, however, their safety in cardiovascular diseases such as heart failure is not fully known and needs to be investigated. Cardiac hypertrophy is an independent risk factor for heart failure morbidity and mortality. Angiotensin II (Ang-II) plays a major role in the pathogenesis of cardiac hypertrophy. We investigated the cardiovascular safety of extracts of Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, and Psilocybe cubensis leucistic A+ strain mushrooms, well-known psilocybin-containing mushrooms in the Panaeolus and Psilocybe genus on Ang II-induced hypertrophy oxidative stress. The four mushrooms were grown, dried and extracted with 70% ethanol, cold and hot water. Extracts were tested for cytotoxicity on H9C2 cardiomyoblast cells. The cardiomyocytes were induced with (10 µM) AngII and treated with the three extracts of the four mushrooms over 48 hours. Control cells were serum starved but neither AngII induced nor treated while AngII cells were serum starved and stimulated with AngII but not treated. Losartan, an inhibitor of AngII type 1 receptor was used as positive control. Effects of the extracts on actin-filament labelling and cell surface area, mitochondrial activity, reactive oxygen species (ROS) and atrial natriuretic peptide levels were determined. Stimulation with AngII lowered cell viability, increased the cell width measurements and intracellular ROS levels significantly compared to control cells. The results indicated that the ethanol and water extracts of the four psilocybin mushrooms did not exacerbate the angiotensin II-induced hypertrophy conditions, but the extracts had cardio-protective activity against angiotensin II-induced oxidative stress. The phytochemical analysis of the extracts confirmed detections of known compounds with antioxidant and anti-inflammatory effects in the water and ethanol extracts of these four psilocybin mushrooms.

Neonatal apnoea has been treated with caffeine, affecting the central nervous and the cardiovascular system. Heart rate variability (HRV) reflects the activity of the autonomic nervous system (ANS) and might be used as a measure of ANS maturation in newborns. We aimed to establish the effect of caffeine on HRV in newborns and sought for a potential correlation between HRV and the postmenstrual age. In 25 newborns hospitalized due to apnoea and treated with caffeine (2.5 mg/kg), we assessed breathing frequency, arterial oxygen saturation, body temperature, and the heart rate, while they were sleeping. We assessed HRV by spectral analysis using fast Fourier transformation. The same protocol was reapplied 100 hours after caffeine withdrawal to assess control parameters. Caffeine increased breathing frequency (p=0.023) but did not affect any other parameter assessed including HRV. We established a positive correlation between postmenstrual age and HRV during treatment with caffeine as well as after caffeine had been withdrawn (total power: p=0.044; low-frequency band: p=0.039). Apparently, the maintenance dose of caffeine is too low to affect the heart rate and the HRV. A positive correlation between postmenstrual age and HRV might reflect maturation of ANS, irrespective of caffeine treatment.

Introduction and objectives: arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. Methods: A descriptive observational study that included 8 initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p. (Glu259Glyfs*77) variant in PKP2 gene. The genetic testing employed next-generation sequencing for the index cases, and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. Results: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years, and a median follow-up of 39 [24-59] months. Worthy of note are the high incidence of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9% respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (4 patients 16.7%) and biventricular (4 patients 16.7%); we found no statistical differences in any of the variables analysed. Conclusions: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in 8 families of our geographical area in Malaga (Andalusia, Spain), where we can establish a founder effect and describe the clinical and risk characteristics.

In recent years, there has been a rise in the prevalence of autism spectrum disorder (ASD). The diagnosis of ASD requires behavioral observation and standardized testing completed by highly trained experts. Early intervention for ASD can begin as early as 1-2 years of age, but ASD diagnoses are not typically made until ages 2-5 years, thus delaying the start of intervention. There is an urgent need for non-invasive biomarkers to detect ASD in infancy. While previous research using physiological recordings has focused on brain-based biomarkers of ASD, this study investigated the potential of electrocardiogram (ECG) recordings as an ASD biomarker in 3-6-month-old infants. We recorded heart activity of infants at typical and elevated familial likelihood for ASD during naturalistic interactions with objects and caregivers. After obtaining the ECG signals, features such as heart rate variability (HRV) and sympathetic and parasympathetic activities were extracted from them. Then we evaluated the effectiveness of multiple machine learning classifiers for the classification of ASD likelihood. Our findings support our hypothesis that infant ECG signals contain a significant amount of information about ASD familial likelihood. Among the various machine learning algorithms tested, XGBoost performed best according to sensitivity (0.76±0.12), f1-score (0.75±0.12), precision (0.79±0. 12), classification accuracy (0.77±0.12, p-value = 0.01) and AUC (0.76±0.12, p-value = 0.02). These results suggest that ECG signals contains relevant information about the likelihood of an infant to develop ASD. Future studies should consider the potential of information contained in ECG, and other indices of autonomic control, for the development of biomarkers of ASD in infancy.

Background: The prevalence of physical inactivity has been rising in many countries in recent years, adding to the burden of non-communicable diseases and affecting overall health worldwide. The aim of this study is to determine the impact of physical activity on mortality from ischemic heart disease (IHD) separately for those respondents who were diagnosed with IHD and for those who were not diagnosed with IHD in their baseline health survey. Methods: In the baseline survey (2006–2008), 7100 men and women ages 45–72 were examined within the framework of the international study Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE). 6770 participants were available for statistical analysis (after excluding 330 respondents due to missing information on study variables). Physical activity was determined by leisure-time physical activities (hours/week). All participants in the baseline survey were followed up for IHD mortality events until December 31, 2018. Results: Using multivariate Cox regression analysis, it was found that moderate and higher levels of physical activity significantly reduced the risk of IHD mortality (HR=0.54 and HR=0.60 respectively) in men who were not diagnosed with IHD at baseline compared with physically inactive subjects. It was found that among men and women who were diagnosed with IHD at baseline, physical activity reduced the risk of mortality from IHD compared with those who were physically inactive (HR=0.54 and HR=0.41 respectively). Using mediation analysis, was found that physical activity directly predicted statistically lower IHD mortality (P<0.05) in men and women. Conclusion: Physical activity was a significant factor that directly predicted statistically lower IHD mortality, regardless of whether subjects had IHD at baseline or not.

Heart failure (HF) diagnosis, phenotyping, prognosis, and treatment decisions are all based on the left ventricular ejection fraction (EF). Heart failure with mid-range EF (HFmrEF) is a third EF category for heart failure with an EF between 40 and 49 percent. Comparatively, heart failure with preserved EF or reduced EF has been largely unexplored. 10–25% of patients with HF have HFmrEF. Although HFmrEF has an intermediate clinical profile, it is more similar to HF with reduced EF, particularly because these patients have a high incidence of ischaemic heart disease. Heart failure with preserved EF has a lower risk of cardiovascular events than heart failure with reduced EF, which is milder. HFmrEF and HF with preserved EF patients have a similar or higher risk of non-cardiovascular adverse events than patients with HF with reduced EF. There is still a great deal of mystery surrounding HFmrEF. The purpose of this review is to describe the major pathophysiology of HFmrEF and its similarities and differences with the other two types of EF. It is the purpose of this paper to present a comprehensive overview of the currently available evidence in support of the pathophysiology of patients with HFmrEF. Further investigation of the pathophysiology, treatment, and prognosis of this condition will be needed in the future in order to better understand it.

Although renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF), it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated chronic congestive cardiopulmonary heart failure (CHF) by creating aorta-vena cava fistula (AVF) in C57BL/6J wild type (WT) mice. There are four ways to create experimental CHF: (1) myocardial infarction (MI) which is basically ligating coronary by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC), although it mimics systematic hypertension but TAC again constricts aorta on top of the heart and exposes the heart; (3) acquired CHF such as by dietary factors, diabetes/salt diets etc. but it is multifactorial, and finally (4) AVF, which is the only one wherein AVF is created ~1cm below the kidney where the aorta and vena cava share the common middle-wall. By creating fistula, the red blood enters vena cava without an injury to the heart. This model mimics CHF such as during aging where with age the preload keeps increasing than the aging heart can pump out due to the weakened cardiac myocytes. This also involves the right ventricle to lung to left ventricle flow, thus creating congestion. The heart in AVF goes to transition from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation but these are also injurious models. Our lab is one of the original labs in creating and studying the AVF phenotype. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers and renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO). Fibrosis was analyzed with trichrome staining. The results suggested that there was robust increase in exosomes’ level in AVF blood, suggesting compensatory systemic response during AVF-CHF. During AVF there was no change in cardiac eNOS, Wnt1 and β-catenin, however; during RDN there was robust increase in eNOS, Wnt1 and β-catenin compared to the sham group. As expected in HFpEF there was perivascular fibrosis, hypertrophy and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher that most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against renal stresses, and apoptosis. Our findings also suggest that RDN is cardioprotective during HFpEF via the preservation of eNOS and accompanied endocardial-endothelial function.

Bright morning light (BML) entrains the body clock, modulates circadian rhythm, and improves sleep-wake disturbances. However, its impact on the autonomic nervous system (ANS) at night remains unclear. Hence, we investigated the effects of BML exposure on activities of the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) at night. This non-randomized controlled pilot study included participants ≥60 years, diagnosed with a type of dementia or cognitive disorder. We excluded participants with pacemakers. The treatment group received 2500 lx BML, whereas the control group received approximately 200 lx of general lighting. We measured the heart rate variability to quantify ANS activity. The treatment group displayed significantly increased high-frequency (HF) power (Roy's largest root=2.44; P<.01) and insignificantly decreased normalized low-frequency (LF%) power. The corresponding low-frequency/high-frequency ratio (LF/HF), insignificant decrease, and cognitive function were correlated with PSNS activity (Roy's largest root=3.92; P<.01), which is effective for moderate dementia. BML exposure reduced SNS activity and enhanced PSNS activity at night, which consequently affected cognitive function. Furthermore, the light washout intervention markedly increased SNS activity at night. BML therapy may be a useful clinical tool for alleviating the deterioration of cognitive function.

Advancements in genomics, bioinformatics and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts have been directed towards investigating this process in heart development and failure. However, few studies have shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports have shown the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has not been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs’ roles in heart development and CHDs and discuss the impacts of perinatal splicing transition and its dysregulation in CHDs. We further summarize discoveries made of causal splicing variants in key transcription factors that have been implicated in CHDs. Improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.

Background: Congestive heart failure is the inability to pump blood throughout the body which causes the walls to be unable to pump adequately. Purpose: This study aimed to ascertain the effect of a contrast bath with a 30 º elevation on the reduction of edema in congestive heart failure patients at Ulin General Hospital, Banjarmasin. Methods: The design of this study was quasi-experimental with an unequal control group design. The population is patients with congestive heart failure, and the sample used is successive sampling. 34 respondents were divided into two groups, 17 respondents in the intervention group and 17 in the control group. Results: The Mann-Whitney result value P = 0.027 (P < 0.05) represented a significant reduction in Bath contrast edema with 30º feet elevation in the intervention group and control group patients with congestive heart failure. Conclusion: Based on the results of this study, it is expected to be able to apply contrast showers with an elevation of 30 º in nursing services to reduce the degree of edema in congestive heart failure patients.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and &lt;100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p&lt;0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p&lt;0.01); vs LT=2.74±0.84; (p&lt;0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p&lt;0.001), and LAVi (r=0.70; p&lt;0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily triggers an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.

Studies showed that introversion is the strongest personality trait related to perceived social isolation (loneliness), which can predict various complications beyond objective isolation such as living alone. Lonely individuals are more likely resort to social media for instantaneous comfort, but it is not a perpetual solution. Largely negative implications including poorer interpersonal relationship and depression were reported due to excessive social media usage. Conversational task is an established intervention to improve verbal communication, cognitive and behavioral adaptation among lonely individuals. Despite that behavioral benefits have been reported, it is unclear if they are accompanied by objective benefits underlying physiological changes. Here, we investigate the physiological signals from 28 healthy individuals during a conversational task. Participants were ranked by trait extraversion, where greater introversion is associated with increased susceptibility to perceived social isolation as compared to participants with greater extraversion as controls. We found that introverts had a greater tendency to be neurotic, and these participants also exhibited significant differences in task-related electrodermal activity (EDA), heart rate (HR) and HR variability (HRV) as compared to controls. Notably, resting state HRV among individuals susceptible to perceived loneliness was below the healthy thresholds established in literature. Conversational task with a stranger significantly increased HRV among individuals susceptible to isolation up to levels as seen in controls. Since HRV is also elevated by physical exercise and administration of oxytocin hormone (one form of therapy for behavioral isolation), conversational therapy among introverts could potentially confer physiological benefits to ameliorate social isolation and loneliness. Our findings also suggest that although the recent pandemic have changed how people are interacting typically, we should maintain a healthy dose of social interaction innovatively.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assign-ment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Background - Physiological helical flow in the ascending aorta has been well documented in the last two decades, accompanied by discussions on possible physiological benefits of such axial swirl. Recent 4D-MRI studies on healthy volunteers have shown indication of early generation of helical flow, early in the systole and already close to the valve plane. Objectives - Firstly, the aim of the study is to investigate the hypothesis of premature swirl existence in the ventricular outflow tract leading to already helical flow in the valve plane, and second to investigate the possible impact of two different mechanical valves design on the preservation of this early helical flow and its subsequent hemodynamic consequences. Methods - We use a pulse duplicator with an aortic arch and High Speed Particle Image Velocimetry to document the flow evolution in the systolic cycle. The pulse-duplicator is modified with a swirl-generating insert to generate early helical flow in the valve plane. Special focus is laid on the interaction of such helical flow with different designs of mechanical prosthetic heart valves, comparing a classical bileaflet mechanical heart valve, the St Jude Medical Regent valve (SJM Regent BMHV) with the Triflo trileaflet mechanical heart valve T2B version (Triflo TMHV). Results – When the swirl-generator is inserted, a vortex is generated in the core flow demonstrating early helical flow in the valve plane, similar as observed in the recent 4-D-MRI study taken for comparison. For the Triflo trileaflet valve, the early helical flow is not obstructed in the central orifice, similar as in the case of the natural valve. Conservation of angular momentum leads to radial expansion of the core flow and flattening of the axial flow profile downstream in the arch. Furthermore, the early helical flow helps to overcome separation at the outer and inner curvature. In contrast, the two parallel leaflets for the bileaflet valve impose a flow straightener effect, annihilating the angular momentum with negative impact on kinetic energy of the flow. Conclusion - The results imply better hemodynamics for the Triflo trileaflet valve based on hydrodynamic arguments under the discussed hypothesis. In addition, it makes the Triflo valve a better candidate for replacements in patients with pathological generation of nonaxial velocity in ventricle outflow tract.

This case study investigates the heart rate (HR) and heart rate variability (HRV) in a patient with coronavirus disease 2019 (COVID-19). We report the case of a 58-year old male who contracted COVID-19. During his disease, 24-hour Holter electrocardiography (ECG) was performed continuously. For comparison, his 24-hour Holter ECGs from the previous 10 years were available. In this patient, COVID-19 was associated with a decrease in HR and a paradoxical decline in HRV. An abrupt decline in HRV and a decrease in HR may signal the onset of COVID-19 before common symptoms such as dry cough or fever appear. In addition, HRV and HR measurements may help to evaluate the course of the disease.

In this paper, we aim to assess the electric current parameters and report the analysis of the associated degree of ventricular recovery during left ventricular assist device (LVAD) support. An assumption was made there is a linear relationship between ventricular recovery degree and the pump electric current pulsatility index (PI). The experimental study was carried out using the ViVitro Pulse Duplicator System with Sputnik 1 LVAD connected. Cardiac output (CO) and cardiac power output (CPO) were used as a measure of ventricular recovery degree. Different heart rates (HR) (59, 73, 86 bpm) and pump speeds (7600–8400 rpm in 200 rpm steps) were investigated. Ventricular stroke volumes in the range of 30–80 ml for each heart rate at certain pump speed were used. The obtained relationships of CO and CPO vs. PI was linear as the coefficients of determination for each regression curve were more than 0.8. CO vs. PI: R2=0.9218; 0.9271; 0.9172 and CPO vs. PI: R2=0.8517; 0.841; 0.8244 for HR=59 bpm; 73 bpm; 86 bpm, respectively. Study findings suggest that adequate interpretation of parameters could potentially serve as a valuable clinical tool to assess ventricular recovery based on LVAD infrastructure without requiring any special hemodynamic assessment.

Athletes are exposed to high-intensity loads to promote athletic performance, however without appropriate evaluation for its effects. This study investigates the effects of four types of exhaustion exercises on Heart Rate Variability (HRV) and Poincaré features as markers of central fatigue; Creatine Kinase (CK) and blood lactate concentrations ([LA-]b) as biomarkers of peripheral fatigue. To achieve this purpose, ten healthy volunteers were exposed to exhaustive exercise using isotonic-, isometric-, aerobic-, and anaerobic-fatigue protocols. HRV Poincaré features, standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) and standard deviation of continuous long-term R-R interval variability (SD2) variables were collected. Central fatigue was tested through the sympathetic stress index (SS) and the sympathetic and parasympathetic index (SS/SD1). Blood samples were collected at the beginning and at the end of the exercises to determine CK and [LA-]b. The SD1 decreased in each exercise protocol, while the SS and SS/SD1 increased. [LA-]b and CK increased at the end of each protocol and correlated with SD1 and SS/SD1. HRV, CK, and [LA^-]_b are acute markers to detect, both central and peripheral fatigue; sensitive to the type, duration, and intensity of exercise, being HRV a novel noninvasive marker, simple and useful for sports coaches and athletes.

Rapid diagnosis of acute myocardial infarction is critical for intervention and treatment to decrease morbidity and mortality. For this reasons, this study aimed to design a sensitive biosensor for cardiac troponin I (cTnI) for early prediction and intervention. The sensor was designed from golden plate immobilized with anti- cTnI antibody conjugated with horseradish peroxidase (HRP) enzyme. The rate of degradation of H2O2 is directly related to serum cTnI level. Serum cTnI level was quantified from 3 studied groups including; healthy subjects and patients with ischemic heart (IHD) diseases and myocardial infarction (MI) by ELISA and biosensor techniques to achieve the improved sensitivity of the biosensor. It was found that cTnI levels in healthy subjects ranged from 8-13 ng/dl and in patients with IHD ranged from 20 - 41 ng/dl and MI range from 57- 180 ng/dl. The sensitivity of biosensor was ranged from 85-95% compared with ELISA technique. The developed biosensor is promising in ICU hospitals for early diagnosis and prevent complications of the stroke. It is recommended to apply this biosensor in the large scale of patients with different stages of the cardiac disease.

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect changes in blood volume in the microvascular tissue bed. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features such as amplitude and pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least 5 minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude and PAT variability was then quantified in the time-domain using SD and IQR measures and in the frequency-domain bilaterally using Magnitude Squared Coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (IQR 0.0217-0.0744) vs PAD 0.0160 (0.0080-0.0338) (p<0.001) and significantly increased PAT variability (healthy control 0.0063 (0.0052-0.0086) vs PAD 0.0093 (0.0078-0.0144) (p<0.001) was demonstrated in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.

Objectives: 1) To describe the cardiovascular health of the construction workers in Hong Kong, 2) to examine the demographic differences in cardiovascular health, and 3) to examine the association between modifiable lifestyle behaviors and cardiovascular conditions. Methods: 626 registered construction workers were included in the analysis. Blood chemistry, blood pressure, weight and height were measured. Face-to-face questionnaire interview was conducted. T-tests and One-way ANOVAs were used to compare the cardiovascular health score, cardiovascular outcomes, and lifestyle behaviors by demographic characteristics. Logistic regressions were performed to assess the cardiovascular outcomes by lifestyle behaviors. Results: Two-thirds of the construction workers failed to achieve three out of the seven “ideal” cardiovascular health indicators. The younger, more educated, and female subjects had better cardiovascular health scores than their counterparts. The ideal fish and seafood consumption was associated with 1) ideal weight status and 2) ideal cholesterol level, whereas less soft drink consumption was associated with ideal cholesterol level. Conclusions: The findings highlighted the importance of promoting cardiovascular health in the construction industry. This study provided insights for future interventions, which should include increasing fish and seafood intake, decreasing soft drink consumption, and enhancing the health literacy amongst older, less educated, and male construction workers.

The purpose of the present study was to determine the relationship between healthy lifestyle behaviors, physical fitness and coronary risk factors in university students. 320 male and female (n_m:171; n_f:149) students from a university participated in this study voluntarily. For the determination of body composition and Body Mass Indexes (BMI), subjects’ height, body weight, and skinfold thickness were taken and body fat percentage (%Fat) was determined. Healthy lifestyle behaviors were determined using the healthy lifestyle behaviors questionnaire. Indicators of physical fitness included flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and a total of shuttle (TS), sprint performance, BMI, and body fat percentage (%fat). Coronary heart disease risk factors included mean arterial blood pressure (systolic (SBP) and diastolic (DBP)), fasting blood levels of triglycerides (TG), total cholesterol (TC), hematocrit (HT), and hemoglobin (HM). Results indicated subjects have normal body mass index, body fat percentage, SBP, DBP, TG, TCF, BS, KS. The results of the Pearson Product Moment Correlation Analysis, indicated that SBP, DBP, TG, TCF, BS, KS for male and female was significantly correlated with flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and total of shuttle (TS)), sprint performance. (p<0.01; p<0.05), In conclusion, the findings of the present study indicated that physical fitness and healthy lifestyle behaviors play a determinant role in coronary heart disease risk factors for male and female students from a university.

Heart failure with preserved ejection fraction (HFpEF) is a multifariousness syndrome, account-ing for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF, or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dys-function seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from an-imal models and human myocardial tissues from failed hearts shows that mitochondrial aberra-tions cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angioten-sin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodelling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and associ-ated signal molecules.

Background/Objectives: Consumption of a high energy density diet (HED) leads to increased body weight and fat mass, gut dysbiosis, and obesity. The aim of this study was to characterize the initial response to HED consumption, as well as identify any sex differences, on body composition, systemic inflammation, gut microbiome, and fecal fat excretion in rats. Methods: Male and female Sprague-Dawley rats were fed a low energy density (LED) for 10 days and then were switched to HED for four weeks. Food intake was measured twice a week, body weight and body composition were measured weekly. Serum samples were collected to measure inflammatory cytokines/chemokines. Fecal samples were collected for microbiome analysis and lipid content. Results: Both males and females experienced increases in body weight, fat mass and fecal fat excretion, while males were more susceptible to significant weight gain, particularly in the diet-induced obesity-prone (DIO-P) group. Males showed elevated TGF-β levels, while females exhibited increases in IP-10, RANTES, and FGFb. Changes in gut microbiota composition revealed a reduction in beneficial species like Bacteroides uniformis and Parabacteroides distasonis and an increase in species such as Akkermansia muciniphila. Sex differences in fat metabolism were shown in the greater fecal fat excretion observed in males. Conclusions: Our study demonstrates that short-term consumption of a high-energy diet elicits notable sex-specific differences in body weight, body composition, inflammatory markers, gut microbiota, and fat excretion in Sprague-Dawley rats. These findings underscore the importance of considering sex as a biological variable in studies of diet-induced obesity and its metabolic consequences.

(1) Background: In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILE). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic drugs (AE), has become increasingly evident. (2) Methods: Data spanning a 10-year period (2010-2020) was analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. The study focused on reviewing relevant case reports detailing successful Intravenous lipid emulsion (ILE) administration in pa-tients with acute intoxications with antiepileptics, specifically examining the impact of fat emul-sions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval con-cerning hemodynamic instability. (3) Results: The typical symptoms of antiepileptic toxicity in-clude central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion ap-plication resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. (4) Conclusions: This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

This study aimed to evaluate the positive effect of autumn olive berries (AOB) extract on aging delay by improving the lipid metabolism of middle-aged C. elegans who became obese due to high glucose (GLU) diet. As a result of investigating the total phenol content and DPPH radical scavenging ability of freeze- or spray-dried AOB, freeze-dried AOB showed better antioxidant potential. Afterward, through HPLC analysis, it was confirmed that catechin was the main compound in the polyphenols of AOB. Therefore, we used freeze-dried AOB in subsequent in vivo experiments. AOB inhibited lipid accumulation in both the young adult and middle-aged groups in a concentration-dependent manner under both normal and 2% GLU conditions. Additionally, AOB inhibited ROS accumulation in a concentration-dependent manner under normal and 2% GLU conditions in the middle-aged worms. In particular, AOB also increased the number of body bending and egg production in middle-aged worms. To confirm the intervention of genetic factors related to lipid metabolism in the effect of AOB, body lipid accumulation was confirmed using worms deficient in the daf-16, atgl-1, aak-1, and akt-1. Regarding the effect of AOB on reducing lipid accumulation, the impact was nullified in daf-16 deficient worms under the 2% GLU condition and nullified in both daf-16 and deficient worms under fasting conditions. This means that AOB regulates lipogenesis and lipolysis by mediating daf-16 and atgl-1 in middle-aged worms. Our results suggest that AOB contributes to the aging delay effect by improving lipid metabolism in metabolic impaired middle-aged worms.

Results showed that mulberry leaves could significantly reduce backfat thickness (P&lt;0.05) and increase intramuscular fat (IMF) content (P&lt;0.05). Lipidomics analysis showed that mulberry leaves improved lipid profile composition and increased the proportion of triglycerides (TG). Interestingly, IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG−005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, Limosilactobacillus, and so on. At the same time improve the L-tyrosine-baton rouge ester, Oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, Mulberrin relative abundance. In this study, we found that mulberry leaves could extremely significantly increasing the mRNA relative expression of lipoprotein lipase (LPL), fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ) in muscle (P＜0.01), significantly increasing mRNA relative expression of diacylglycerol acyltransferase 1 (DGAT1) (P＜0.05) and significantly decreasing the mRNA relative expression of acetyl CoA carboxylase (ACC) (P＜0.05), and aignificantly upregulated hormone-sensitive triglyceride lipase (HSL), peroxisome proliferators-activated receptor α (PPARα) mRNA relative expression (P＜0.05) in backfat. In addition mulberry leaves could increased serum leptin and adiponectin (P＜0.01). Ultimately lead to up-regulation of IMF and down-regulation of backfat.

Osteoarthritis (OA) is a pathology of great impact worldwide which its physiopathology is not completely known and usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. The study was performed with thirty rats, OA in all animals was induced by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction, and 28, 56 and 84 days following induction. Histological study confirmed OA in all samples. The results of this study allow the identification of several changes in the serum metabolome over time, including organic acids, benzenoids, heterocyclic compounds and lipids at T28, organic acids at T56 and lipid classes at T84. We conclude that OA induces serological changes in the metabolome and, more specifically, 18 metabolites which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.

In chemotherapy practice the dexamethasone is used as concomitant agent to mitigate the side effects of antitumor drug cisplatin. However, it is known, that both cisplatin and dexamethasone are capable to stimulate the production of reactive oxygen spacies, which targets various biomolecules, including lipids. This work is devoted to the study of quantitative changes in products of lipid peroxidation in the nuclei of cells of some tissues of rats after separate and combined use of cisplatin and dexamethasone. The amount of lipid peroxidation products was determined by spectrophotometric method after its extraction by heptan-isopropanol mixture. When used separately, cisplatin and dexamethasone enhance the formation of lipid peroxidation products in the studied tissues of rats to various degrees. As a result of these alterations, the values of the oxidation index in the studied nuclear preparations also changed accordingly. During the combined use of cisplatin and dexamethasone there is some antagonism in the action of these drugs. Instead of the supposed summation of the effects of enhancing lipid peroxidation processes, “masking” of the effect of cisplatin with dexamethasone is observed. Thus, it has been assumed that exactly such antagonism revealed during combined action helps mitigate the side effects of cisplatin with dexamethasone.

This research evaluated the role and feasibility of the granular nanocellulose particles (GNC) from sugarcane bagasse obtained from enzymatic hydrolysis in reducing lipid digestibility and permeability in the in vitro simulated gastrointestinal (GI) system. GNC concentration (0.02%, w/v) had significantly affected the released free fatty acid (FFA) reduction of approximately 20%. The Pick-ring emulsion of the GNC and olive oil simulation mixture revealed higher oil droplet size distribution and stability in the initial stage than the vortexed mixture formation. The difference in particle size distribution and zeta potential of the ingested GNC suspension and GNC-olive oil emulsion were displayed during the in vitro gastrointestinal simulation. GNC particles interacted and distributed surrounding the oil droplet leading to the interfacial emulsion. The GNC concentration (0.01-0.10%, w/v) showed low toxicity on the HIEC-6 cell, ranging from 80.0 to 99% of cell viability. The release of FFA containing the ingested GNC suspension and GNC-olive oil emulsion was about 30% reduction compared to without GNC digest solution. The FFA and triglyceride permeability through the HIEC-6 intestinal epithelium monolayer were deceased in the digesta containing the ingested GNC and emulsion. This work indicated that GNC represented a significantly critical role and properties in the GI tract and reduced lipid digestion and absorption. This GNC could be utilized as an alternative food additive or supplement in fatty food for weight control due to their inhibiting lipid digestibility and assimilation.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSIL) but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3-month supplementation with 600 mg of ALA on antioxidant- and lipid status param-eters in 100 patients with LSIL were investigated in randomized placebo-controlled study. Obtained results were discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). Obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted with small but statistically significant increase of serum low density lipoprotein (LDL) and observed effect was significantly affected by the initial lipid status of participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Application of exogenous jasmonate can stimulate the production of ethylene, carotenoids and aroma compounds, resulting in the acceleration of fruit ripening. These alterations improve fruit quality and make fruit desirable for human consumption, but overripening of a fruit results in large losses of fruit crops. In order to overcome this problem, 1-methylcyclopropene was ap-plied to the fruits due to its capacity to block the receptors of ethylene, resulting in the sup-pressed of fruit ripening. In this study, treatments only with 1-methylcyclopropene, and with both 1-methylcyclopropene and methyl jasmonate was conducted to observe if an exogenous methyl jasmonate can improve the levels of metabolites in their fruits with ethylene receptors blocked. Fruits were analyzed at 4, 10 and 21 day after harvest (DAH) and compared with the no treated fruits. The postharvest treatments affected primary metabolites (sugars, organic acids, amino acids and fatty acids) and secondary metabolites (carotenoids, tocopherols and phytoster-ols). However, the lipid metabolism of the tomato was the most impacted by the exogenous jasmonate. Fatty acids, carotenoids, tocopherols and phytosterols showed a delay in their pro-duction at 4 and 10 DAH. In contrast, at 21 DAH these non-polar metabolites exhibited an im-portant improvement in their accumulation.

Time-restricted feeding (TRF) showed a potent effect in preventing obesity and improving metabolic outcomes in several animal model of obesity; however, there is, as yet, scarce evidence about its effectiveness against obesogenic challenge that more accurately mimic the human Western diets, such as cafeteria diet. Moreover, the mechanism for its efficacy is poorly understood. White adipose browning has been linked to body weight loss. Herein, we tested whether TRF has the potential to induce browning of inguinal white adipose tissue (iWAT) and to attenuate obesity and associated dyslipidemia in cafeteria diet-induced obesity model. Male Wistar rats, fed normal laboratory chow (NC) or cafeteria diet (CAF) for 16 weeks, were subdivided into two groups that were subjected to either ad libitum (ad lib, A) or TRF (R) for 8 hours per day. Rats under TRF regimen had a lower body weight gain and adiposity compared with their diet-matched ad lib rats, despite equivalent levels of food intake and locomotor activity. In addition, TRF improved the deranged lipid profile [total cholesterol (TC); triglycerides (TG); high density lipoprotein (HDL-c); low density lipoprotein (LDL-c)] and atherogenic indices [atherogenic index of plasma (AIP); atherogenic coefficient (AC); coronary risk index (CRI)] in rats fed CAF diet. Remarkably, TRF resulted in decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes in iWAT of NC- and CAF-fed rats. Protein expression of browning markers, such as uncoupling protein-1 (UCP1) and peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC1α) in iWAT were also up-regulated in time restricted NC- or CAF-fed rats. These findings suggest that TRF regimen is an effective strategy to improve obesity and associated dyslipidemia induced by CAF-diet, probably via a mechanism involving WAT browning process.

Ucuùba fat is fat obtained from a plant found in South America, mainly in Amazonian Brazil. Due to its biocompatibility and bioactivity, the Ucuùba fat was used for production of ketoconazole-loaded nanostructured lipid carriers (NLC) in view of an application for the treatment of onychomycosis and other persistent fungal infections. The development and optimization of the Ucuùba fat based NLC were performed using a Box-Behnken design of experiment. The independent variables were surfactant concentration (% w/v), liquid lipids concentration (% w/v), solid lipids concentration (% w/v), while the outputs of interest were particle size, polydispersity index (PDI) and drug encapsulation efficiency (EE). The Ucuùba fat based NLC were produced and the process optimized determining a predictive mathematical model. Applying the model, two formulations with the pre-required particle size, i.e., 30 and 85 nm, were produced for further evaluation. The optimized formulations were characterized and showed a particle size in agreement to the predicted value, i.e. 33.6 nm and 74.6 nm, respectively. The optimized formulations were also characterized using multiple techniques in order to investigate the solid state of drug and excipients (DSC and XRD), particle morphology (TEM) and interactions between the formulation components (FTIR). Furthermore, particle size and surface charge of the formulations was studied during a one-month stability study and did not evidence any significative modification during storage.

Systems Chemistry has been a key component of origin of life research, invoking models of life’s inception based on evolving molecular networks. One such model is the Graded Autocatalysis Replication Domain (GARD) formalism embodied in a Lipid World scenario, which offers rigorous computer simulation based on defined chemical kinetics equations. GARD suggests that the first pre-RNA life-like entities could have been homeostatically-growing assemblies of amphiphiles, undergoing compositional replication and mutations, as well as rudimentary selection and evolution. Recent progress in Molecular Dynamics has provided an experimental tool to study complex biological phenomena such as protein folding, ligand-receptor interactions and micellar formation, growth and fission. The detailed molecular definition of GARD and its inter-molecular catalytic interactions make it highly compatible with Molecular Dynamics analyses. We present a roadmap for simulating GARD’s kinetic and thermodynamic behavior using various Molecular Dynamics methodologies. We review different approaches for testing the validity of the GARD model, by following micellar accretion and fission events and examining compositional changes over time. Near future computational advances could provide empirical delineation for further system complexification, from simple compositional non-covalent assemblies towards more life-like protocellular entities with covalent chemistry that underlies metabolism and genetic encoding.

The purpose of this paper is to review the involvement of mitochondria in the actions of nitroglycerin (glycerol trinitrate -GTN) and the redox disturbances underlying diseases it treats. The paper begins by explaining complex I as the initial site of formation of superoxide and the process whereby it leads to the development of glutathione dependent tolerance. Next, the paper describes new formulations for preventing tolerance. The paper ends by illustrating diseases that may benefit from treatment with novel glutathione based GTN formulations and treatment approaches.

Background: Chronic heart failure (CHF) often necessitates the use of high doses of diuretics, which can lead to side effects such as worsening renal function and electrolyte imbalances. Methods: A total of 102 patients (median age 75 years) were included in the study and divided into two groups based on the level of diuretic therapy. The diuretic group received the following average doses: furosemide — 39.1 ± 22.1 mg, torasemide — 7.4 ± 3 mg, and spironolactone — 42 ± 12.4 mg. Biochemical analyses were performed on days 1 and 7 of hospitalization, with measure-ments of sodium, potassium, glucose, urea, and plasma osmolality (eOSM). Results: By day 7, the plasma osmolality in the diuretic group increased from 300 [297; 304] to 302.2 [298.3; 305.8] mOsm/L (p = 0.039). Urea levels in the diuretic group rose to 7.95 [5.65; 9.90] mmol/L by day 7, while remaining stable in the non-diuretic group at 5.90 [5.05; 7.50] mmol/L (p = 0.012). The proportion of urea to plasma osmolality (PropUrea/eOSM) in the diuretic group in-creased to 2.63% [1.89; 3.28] compared to 2.00% [1.70; 2.50] in the non-diuretic group (p = 0.011). The proportion of sodium to plasma osmolality (PropNa/eOSM) in the diuretic group decreased to 46.46% [46.02; 46.74], compared to 46.68% [46.33; 46.89] in the non-diuretic group (p = 0.050). Analysis of PropNa/eOSM and PropUrea/eOSM on day 7 without considering salt intake yielded statistically significant results, though they were less robust compared to models including salt intake. For example, in the PropUrea/eOSM model, the odds ratio (OR) was 3.01 (95% CI 1.74, 5.89; p < 0.001), and in the PropNa/eOSM model, the OR was 0.19 (95% CI 0.07, 0.43; p < 0.001). Conclusion: The study confirmed that high salt intake and active diuretic therapy significantly influence the biochemical parameters of patients with chronic heart failure (CHF), contributing to the develop-ment of the aestivation phenomenon. This is characterized by an increase in nonionic osmolytes such as urea, which may represent a physiological adaptation to stress. Patients receiving diuret-ics and following a high-salt diet exhibited significant changes in plasma osmolality and urea levels, indicating a physiological adaptation that may worsen prognosis by increasing the risk of sarcopenia and cachexia. Further research is needed to better understand these mechanisms and develop strategies to mitigate the negative effects.

Introduction: Antenatal diagnosis of cardiac abnormalities and counselling parents about postnatal care requires a multidisciplinary team which includes a paediatric cardiologist a neonatologist and a fetal medicine physician. Some of this expertise is not available in all centres with fetal medicine expertise, however with modern technology, this could be provided remotely. Our objective was to assess the feasibility and outcomes of a pre-natal multidisciplinary tele-echocardiography diagnostic and counselling services Materials and Methods: Two centres based in separate countries provided a joint diagnostic and counselling service over a period of 14 months. The primary centre undertook the fetal echocardiography with a Voluson E10 machine and images transmitted live using Zoom OPS system with video-consultation and counselling. The fetal echo was performed using the ISUOG Guidelines check list. Results: There was an initial feasibility period of 2 months during which 10 women whose fetuses had normal hearts were scanned to test the workability of the system. Over a period of 12 months, 513 high risk fetuses were then scanned and out of these 27 had congenital malformations. The most common were hypoplastic left heart syndrome (HHLS) and atrio-ventricular septal defect. Tele-echocardiography and counselling was successful in all the cases. Satisfaction with the service was 3.8/4 with the main limitation being the need for further referral to a tertiary centre for delivery. Conclusion: Tele-echocardiography is reliable and when combined with live counselling and support from a paediatric cardiologist, is an option acceptable to patients. The greatest benefit was from being counselled by a team of experts at a single consultation rather than having to travel to another centre for consultation. With rapidly evolving technology, making video transmission easier and less expensive, we feel that consideration should be given not only to the development of tele-echocardiography but extended to other aspects of fetal medicine.

Cardiovascular disease is a leading cause of morbidity and mortality. New research elucidates in-creasingly complex relationships between cardiac and metabolic health, giving rise to new possible therapeutic targets. Sphingolipids are a heterogenous class of bioactive lipids with critical roles in normal human physiology. They have also been shown to play both protective and deleterious roles in the pathogenesis of cardiovascular disease. This review will explore the roles of Sphingolipids in vascular, cardiac, and metabolic pathologies and will evaluate the therapeutic potential in targeting Sphingolipids with the aim of prevention and reversal of cardiovascular disease, in order to improve long-term cardiovascular outcomes.

Children and adolescents (C&A) with congenital heart defects (CHD) have decreased functional capacity and executive functioning (EF) due to brain abnormalities and decreased oxygen saturation. Exercise may improve EF via increased cognitive demands and cerebral blood supply. The purpose of this review was to identify current evidence describing the impact of physical activity (PA) interventions on EF in C&A with CHD. The following databases were searched from 2014-present: MEDLINE, EMBASE, CINAHL, Scopus, CENTRAL, and PsycInfo. Article inclusion criteria consisted of participants from birth to 18 years with CHD, interventions related to PA, and EF as an outcome. Articles were excluded if: adults were included, translation to English was impossible, and full access was unavailable. As a result of the review, 431 studies were screened. Three articles underwent full analyzation and only one met all criteria and this study found that with exercise there were significant improvements on self-reported cognitive functioning and parent-reported social functioning. Despite theoretical benefits, only one published study has investigated the role that PA interventions have on EF in C&A with CHD. Further investigation of the effect PA interventions have on EF in C&A with CHD is needed.

Background: Pleural effusion (PE) is often classified as either a transudative or an exudative process. The aim of the study was to examine the causes of pleural effusions and the short- and long-term survival in the older patients hospitalized in the acute geriatric and internal medicine wards. Methods: Patients aged ≥ 65 years, who underwent thoracentesis, were included in this retrospective study. To distinguish between exudate and transudate PE, the Light’s criteria were applied. We compared medical indices and mortality in patients with exudate PE to those with transudate effusion according two age groups (65 - 85 vs. > 85 years). Results: The rates of the main etiologies of PE were congestive heart failure (CHF), 46%, lung infections, 25%, and malignancy, 12%, of the whole study population. Lung infections accounted for 53% of the exudate PE patients, with a higher presence among the >85 group of patients. The etiology of transudate PE was primarily CHF, more common among the patients of the >85 group. In malignancy, CHF and lung infections patients, the chances of dying within one year were 80.3%, 63.2%, and 45.5%, respectively. In transudate PE patients, ten-year survival of the 65-85 group of patients was significantly higher. In the exudate PE patients, there was no difference in survival between the two age groups. Right-sided and bilateral pleural effusions were associated with worse prognosis. Conclusion: Clinicians encountering patients with PE should be aware of their heightened mortality risks, and should carefully monitor their underlying etiology and employ appropriate optimal management.

Background: The key objective of this research was to identify the dominant parameters and determine the patient status of pediatric patients with congenital heart disease in the ICU. The data we collected from the Congenital Heart Disease (CHD) Surgery Unit (ICU) in the National Heart Foundation Hospital and Research Institute, Dhaka, Bangladesh. Data from 300 ICU patients was collected and analyzed. We choose patients who are less than 12 years old at the time of ICU admission and whose ICU stay is longer than 24 hours. (2) Methods: According to the doctor’s advice, the dependent and independent variables are selected. The relationship between these parameters in the ICU was selected by linear modeling, which is associated with mortality risk. These parameters are used in the linear regression model and the ARIMA model for prediction. The prediction model is used for pediatric congenital heart disease patients in the ICU. (3) Results: The relation between CVP and BP (95% CI=0.2113,0.353 r=0.2841249), PEEP, and FiO2 (95% CI=0.6992,0.770 r=0.7367744) is statistically significant (p value&lt;0.001). pH and PO2 were statistically significant, but there were correlations (95% CI=0.161,0.308 r=0.2362575). The statistically significant (p &lt; 0.001) parameters were selected for prediction. In this study, BP, FiO2, and PO2 parameters were used in the linear regression model and the ARIMA model for prediction. We predict the next-hour patient’s status. The ARIMA model was found to have less error than the linear regression model. (4) Conclusions: This study helps identify the important parameters that are measured in the ICU to monitor patient status and predict the future value of those parameters, with the ultimate goal of providing physicians with an early signal of future patient conditions.

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.

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

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.

In this study, we propose the Signal Integration Reconstruction Peak Detection (SIRPD) algorithm for reliable Cardiac Beat Interval (CBI) measurement using functional Near-Infrared Spectroscopy (fNIRS) signals. This algorithm enhances reliability by identifying a regular waveform in cerebral blood flow associated with heartbeats. The SIRPD algorithm assesses the Signal Quality Index (SQI) per channel, discards signals from unavailable channels, and interpolates oxygenated and total hemoglobin concentration signals, thereby boosting resolution and integrating the signal into a single channel. The integrated and smoothed signal is transformed to identify the most significant periodic waveform, from which the CBI is extracted. Validated with data from 20 healthy subjects who simultaneously recorded fNIRS and ECG signals, our findings confirm the equivalence of the CBI derived from ECG and calculated through the SIRPD algorithm from fNIRS (R^2 = .98, RMSE = .011, ICC = .991). We also extracted heart rate variability (HRV) features, confirming no significant difference in all features between ECG and fNIRS devices. Uniquely, this study regards the fNIRS heart signal not as an artifact source but as a valuable bio signal. The proposed method, which allows for the detection of cardiac beat intervals from cerebral blood flow oscillations, suggests the potential clinical applicability of fNIRS as an auxiliary indicator for various cardiovascular factors.

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

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.

This study aimed to determine the correlation of colour M-mode velocity propagation in the assessment of left ventricular diastolic function among acute decompensated heart failure patients with preserved ejection fraction (HFpEF). This research is an observational analytical study using a cross–sectional study design conducted from April to June 2022. The subjects of this study were patients diagnosed with acute HFpEF and treated at Dr. Soetomo General Academic Hospital, Surabaya. Patients with heart rhythm disturbances, moderate to severe valvular heart disease, and congenital heart defects were excluded from this study. Patients were measured for diastolic function including mitral valve early mitral inflow velocity (MV E Velocity), mitral peak velocity of early filling (E’) (E' Septal and E' Lateral), left atrial volume index (LAVI), The maximal tricuspid regurgitation velocity (TR V Max), Vp, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/E'), the ratio between early and late ventricular filling velocity (E/A) and E/Vp Ratio. N-terminal-pro hormone B-type natriuretic peptide (NT–ProBNP) examination was also performed on study subjects as an additional diagnosis of acute heart failure. There were 33 patients who met the inclusion and exclusion criteria and were included in our study. There were 26 patients (78.8%) with grade I diastolic dysfunction, 4 patients (12.1%) with grade II diastolic dysfunction, and 3 patients (9.1%) with grade III diastolic dysfunction. There is a strong positive correlation between Vp with parameters E' Septal (p = &lt; 0.001; r = 0.636) and E' Lateral (p = &lt; 0.001; r = 0.650). Vp is negatively correlated with the ratio E/E' (p = 0.029; r = –0.37). The PCWP estimate with E/Vp ratio had a strong correlation with the NT–Pro BNP value &gt; 300 pg/ml in acute HFpEF patients (p = &lt; 0.001; r = 0.726) compared to the PCWP estimate with E/E' (p = &lt; 0.001; r = 0.549). There is no correlation between Vp value and degree of diastolic dysfunction in patients with acute HFpEF.

Redox balance is increasingly identified as a major player in cellular signaling. A fundamentally simple reaction of oxidation and reduction of cysteine residues in cellular proteins is the central concept in this complex mode of protein function regulation. Oxidation of key cysteine residues occurs at the physiological levels of reactive oxygen species (ROS) but are reduced by a supply of thiol antioxidant molecules including glutathione, glutaredoxin and thioredoxin. While these molecules show complex compensatory roles in experimental conditions, transgenic animal models provide a comprehensive picture to pinpoint the role of each antioxidant. In this review we have specifically focused on the available literature on Thioredoxin-1 system transgenic models that includes Thioredoxin and Thioredoxin reductase proteins. As identification of Thioredoxin protein targets is technically challenging the true contribution of this system in maintaining cellular balance remains unidentified, including the role of this system in the brain.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

Infant electrocardiograms (ECG) and heart rates (HR) are very useful biosignals for psychological research and clinical work, but can be hard to analyze properly, particularly long form (≥5 minutes) recordings taken in naturalistic environments. Infant HRs are typically much faster than adult HRs, and so some of the underlying frequency assumptions made about adult ECGs may not hold for infants. However, the bulk of publicly available ECG approaches focus on adult data. Here, existing open-source ECG approaches are tested on infant datasets. The best performing open-source method is then modified to maximize its performance on infant data (e.g., including a 15Hz high pass filter, adding local peak correction). The HR signal is then subsequently analyzed, developing an approach for cleaning data with separate sets of parameters for the analysis of cleaner and noisier HR. A Signal Quality Index (SQI) for HR is also developed, providing insight into where a signal is recoverable and where it is not, allowing for more confidence in analysis performed on naturalistic recordings. The tools developed and reported in this paper provide a base for future analysis of infant ECG and related biophysical characteristics. Of particular importance, the proposed solutions outlined here can be efficiently applied to real-world large datasets.

In patients with prior Takotsubo syndrome (TTS), long lasting functional cardiac limitations were described as compared with normal subjects. Emotions-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable fac-tors. The aim of the present study was to assess long-term cardiac functional limitations in a co-hort of asymptomatic E-TTS patients. We enrolled n=39 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 [12-40] months median fol-low-up from the acute event. A cohort of n=39 individuals matched for age, sex, body mass index and comorbidities served as control. Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs 22.5 ± 6.5; P < 0.001 and 75.2 ± 14.1 % vs 100.6 ± 17.1%, P <0.001), VO2 at anaerobic threshold (AT) (11.1 [10.1-12.9] vs 14.4 [12.5-18.7]; P <0.001), peak O2 pulse (9.7 ± 2.5 vs 13.1 ± 3.5; P <0.001) and higher VE/VCO2 slope (30.4 ± 3.7 vs 27.2 ± 3.5; P <0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Despite its favorable out-come, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

Aims: The objective of this study was to assess the cost-effectiveness of the CardioMEMS HF system in a HF Clinic in Spain by evaluating the real-time remote monitoring of pulmonary artery pressures, which has shown to reduce heart failure (HF) related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods: This single-centre study enrolled all consecutive HF patients who had been implanted with a pulmonary artery pressure sensor (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA). The number of HF hospitalizations in the year before and the year after the sensor implantation was compared and quality-adjusted life years (QALY) gained based on a literature review of previous studies was calculated. Results: The rate of HF hospitalisations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 versus 1.10 events/patient-years, HR 0.22, p=0.001). At the end of first year, the usual management outperformed the CardioMEMS HF system, resulting in a net monetary value difference of 2,540€ per patient and a benefit-cost ratio of 0.38. However, by the end of the second year, the CardioMEMS system is estimated to reduce costs compared to usual management. Conclusions: Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF system represents a long-term cost-effective strategy in a healthcare setting in Southern Europe.

Due to the complex and variable anatomy of the left atrial appendage, percutaneous left atrial appendage closure (LAAC) can be challenging. In this study, we investigated the impact of fusion imaging (FI) on the LAAC learning curve of 2 interventionalists. The first interventionalist (IC 1) was initially trained without FI and continued his training with FI. The second interventionalist (IC 2) performed all procedures with FI. We compared the first 36 procedures without FI of IC 1 (group 1) with his next 36 interventions with FI (group 2). Furthermore, group 1 was compared to 36 procedures of IC 2 who directly started his training with FI (group 3). Group 1 demonstrated that the learning curve without FI has a flat course with weak correlations for fluoroscopy time, contrast volume, and procedure time, but not for dose area product. Group 2 with FI showed improvement with a steep course and strong correlations for all 4 parameters. In group 3 we also saw a steep progression with strong correlations. Furthermore, the mean measurements of the procedural parameters in the groups with FI decreased significantly as indicator for procedural efficacy. We demonstrated that FI may improve the learning curve of experienced and non-experienced ICs.

Background: Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart. Methods: We used high resolution all-optical electrophysiology on ex-vivo zebrafish hearts to assess the effects of IKs analogues on the cardiac action potential. Findings: We found that chromanol 293B (an IKs inhibitor) prolonged the action potential duration (APD) in the presence of E4031 (an IKr inhibitor applied to drug-induced LQT2) and to a lesser extent in the absence of E4031. Moreover, we show that PUFA analogues slightly shorten the APD of the zebrafish heart. However, PUFA analogues failed to reverse the APD prolongation in drug-induced LQT2. However, a more potent IKs activator, ML-277, partially reversed the APD prolongation in drug-induced LQT2 zebrafish hearts. Interpretation: Our results suggest that IKs plays a limited role in ventricular repolarizations in the zebrafish heart under resting conditions but plays a more important role when IKr is compromised, as if IKs in zebrafish serves as a repolarization reserve as in human hearts. This study shows that potent IKs activators can restore the action potential duration in drug-induced LQT2 in zebrafish heart.

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

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

This paper presents a framework to recognize the affective state of children with Autism Spectrum Disorder (ASD) in an in-the-wild setting using Heart Rate (HR) information. Our algorithm classifies a child’s emotion into positive, negative, or neutral states by analyzing the heart rate signal. The HR signal is obtained from a smartwatch in real-time using our smartwatch application. The heart rate data is acquired when the child learns to code a robot while interacting with an avatar that assists the child in communications skills and programming the robot. In this paper, we also present a comparison of using HR data for the classification of emotions with classification based on features extracted from HR signals using Discrete Wavelet Transform (DWT). Our experimental results show that the proposed method produces a comparable performance with the state-of-the-art HR-based emotion recognition techniques, despite the fact that our experiments are performed in an uncontrolled setting as opposed to a lab environment. This work contributes to real-world affect analysis of children with ASD using HR information.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the 1^st human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the 4^th post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19^th century but did not receive much recognition by embryologists.

The combination of statistical learning technologies with large databases of psychophysiological data has appropriately generated enthusiastic interest in future clinical applicability. It is argued here that this enthusiasm should be tempered with the understanding that significant obstacles must be overcome before the systematic introduction of psychophysiological measures into neuropsychiatric practice becomes possible. The nonspecificity of psychophysiological measures complicates their use in diagnosis. Low test-retest reliability complicates use in longitudinal assessment, and quantitative psychophysiological measures can normalize in response to placebo intervention. Ten cautionary observations are introduced and, in some instances, possible directions for remediation are suggested.

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). Follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals [CI] for the outcome in PhyS C and PhyS D were 1.84 (95% CI 0.73 to 4.61) and 7.88 (95% CI 1.54 to 40.41) respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.10 (95% CI 0.39 to 3.06) and 0.99 (95% CI 0.24 to 4.10) respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA receiving apixaban.

Heart attacks and strokes are one of the leading causes of death in the world today, and heart attacks caused by clogged arteries that carry blood to the heart muscle are a significant part of these strokes. These are caused by the accumulation of fat particles in the walls of the arteries and the reduction of blood flow through it over a long process. The process of fat penetration in the underlying layers of the Artery wall has been the focus of many researchers, and various researches and Simulations have been done on it, in each of them, the effect of specific parameters has been considered. In the present study, the effect of blood flow rate on the flow pattern in a bifurcate artery with two ducts has been investigated using FLUENT software with Computation fluid dynamic Method. The effect of the angle between the two ducts of the Artery on the flow pattern has been investigated.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.

Stress has been identified as one of the major causes of automobile crashes which then lead to high rates of fatalities and injuries each year. Stress can be measured via physiological measurements and in this study the focus will be based on the features that can be extracted by common wearable devices. Hence the study will be mainly focusing on the heart rate variability (HRV). This study is aimed to develop a good predictive model that can accurately classify stress levels from ECG-derived HRV features, obtained from automobile drivers, testing different machine learning methodologies such as K-Nearest Neighbor (KNN), Support Vector Machines (SVM), Multilayer Perceptron (MLP), Random Forest (RF) and Gradient Boosting (GB). Moreover, the models obtained with highest predictive power will be used as reference for the development of a machine learning model that would be used to classify stress from HRV features derived from HRV measurements obtained from wearable devices. We demonstrate that MLP was the ideal stress classifier by achieving a Recall of 80%. The proposed method can be also used on all applications in which is important to monitor the stress level e. g. in physical rehabilitation, anxiety relief or mental wellbeing.

Introduction: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n=204, AF group) or supraventricular tachycardia (n=34, control group) were analyzed (male n=183, 54±12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e’ (≥ 8) than in those with a low E/e’ (&lt; 8). LAPR at a pacing interval of 400ms and E/e' were positively correlated (r=0.373, p&lt;0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: The LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

Animal welfare remains a very important issue in the livestock sector but monitoring animal welfare in an objective and continuous way remains a serious challenge. Monitoring animal welfare based upon physiological measurements instead of audio-visual scoring of behaviour would be a step forward. One of the obvious physiological signals related to welfare and stress is heart rate. The objective of this research was to measure heart rate (beat per minutes) on pigs with technology that soon will be affordable. Affordable heart rate monitoring is done today at large scale on humans using the Photo Plethysmography (PPG) technology. We used PPG sensors on pig’s body to test whether it allows getting reliable heart rate signal. A continuous wavelet transform (CWT)-based algorithm is developed to decouple the cardiac pulse waves from the pig. Three different wavelets, namely 2^nd, 4^th and 6^th order Derivative of Gaussian (DOG, are tested. We show results of the developed PPG-based algorithm against electrocardiograms (ECG) as a reference measure for heart rate and this for an anesthetized versus a non-anesthetised animal. We tested three different anatomical body positions (ear, leg and tail) and give results for each body position of the sensor. In summary, it can be concluded that the agreement between PPG-based heart rate technique and reference sensor goes from 91 to 95 percentage. In this paper we showed the potential of using the PPG-based technology to assess pig’s hear rate.