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

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

This article presents raw data of biaxial tensile measurements of rat heart passive myocardium conducted in lab scale environment. The passive myocardium of the rat was divided into three regions, namely: left ventricle, mid-wall and right ventricle. The biaxial dataset of passive rat myocardia is presented as stress vs strain of the passive rat myocardium in various regions. The determination of valid material properties of the heart plays an important role in the development computational models. These computational models are useful in studying various scenarios and mechanisms of heart diseases. In addition, valid and accurate materials are critical in the development of new therapies. The dataset presented here is useful in the area of soft tissue mechanics including studying the mechanisms of heart diseases such as myocardial infarction. Accordingly, the evaluation of stress and strain in left ventricle, mid-wall and right ventricle was performed.

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.

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

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

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

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

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

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.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

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

Mitochondrial dysfunction is relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the heart of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n=8) or placebo (n=8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and abundance of mtDNA4834 deletion), and mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. TFAM binding to mtDNA regions involved in replication and deletion generation was increased following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling was found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the regulation of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats were used (according to Langendorff) to study the effects of capsaicin (CS), capsazepine (CZ) and CZ+CS treatments. The hearts were divided into three subgroups; 1) perfusion, 2) ischemia and 3) ischemia-reperfusion. In all groups we studied cardiac work and levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue. Western blots were used to determine the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac work and the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

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

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

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

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

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

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

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

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

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

Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modelled by administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo, or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102), but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Skeletal muscles are crucial for voluntary movements, and impairments in their function significantly impact our activity. Dysferlin, a protein predominantly present in skeletal muscle, is a focal point of extensive research due to its vital role in muscle repair and maintenance. This study investigates Dysferlin's levels and function in skeletal muscles, emphasizing its significance and the potential effects of its dysregulation on fast and slow muscle fibers. We employed Western blotting on two different rat muscles. The results revealed distinct expressions of Dysferlin in fast and slow fibers, as demonstrated by Western blotting. We propose that Dysferlin may have a metabolic role in addition to its involvement in the repair mechanism.

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

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

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

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

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

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

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

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

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

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

Expression of the breast cancer resistance protein (BCRP/ ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE, which closely resembles human PE. While many drugs are substrates of this important efflux transporter, the impact of BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (3 mg/kg) was administrated intravenously, and rats were sacrificed at time intervals between 0.5-6 hours. Placental expression of Bcrp and Oatp2b1 significantly decreased in PE rats. A corresponding increase in RSV levels was seen in fetal tissues and amniotic fluid of the PE group (p&lt;0.05), while maternal plasma concentrations remained unchanged. An increase in Bcrp expression and decreased RSV concentration, was seen in the livers of PE dams. This suggests that PE-mediated transporter dysregulation leads to significant changes in the maternal and fetal RSV disposition. Overall, our findings demonstrate that altered placental expression of transporters in PE can increase fetal accumulation of their substrates.

Purpose: The intervertebral disc is a leading avascular organ in the body that may gather nutrition through diffusion. It maintains homeostasis by the use of autophagy and apoptosis to survive in unfavorable conditions such as stress and mechanical force. Therefore, excessive force and stress beyond normal conditions may cause intervertebral disc degeneration. The purpose of this study was to examine which is the better method, either external fixator (EF) or saline injection (SI), for inducing autophagy and apoptosis-mediated nucleus pulposus (NP) cell death in the discs of rat tail’s. Methods: Sixteen, nine-weeks-old male Sprague–Dawley rat tails were treated with 0.9% saline and EF (two-cross Kirschner wires) for a period ofsix and twelve weeks. Treated discs were dissected to identify the participation of autophagy and apoptosis in intervertebral disc degeneration. For identification purposes, H&amp;E staining, Masson’s trichrome staining, and immunohistochemistry (IHC) for LC3, beclin-1, and P62 in addition to MMP-2, MMP-3, and TIMP-1 were performed. Furthermore, we performed real-time polymerase chain reaction (RT-PCR) to observe autophagy-related gene expression (beclin-1, LC3, and P62) and apoptosis-related gene expression (MMP-2, MMP-3, and TIMP-1). Results: TheEF group showed more insidious NP cell degeneration than the control (Ctrl) group. Degeneration was elevated with increasing compression duration of EF group, whereas the SI group could not distinguish the margin of annulus fibrosus (AF) and NP cells. LC3, beclin-1, and P62 showed the highest and lateral expression whilst MMP-2, MMP-3, and TIMP-1 showed up-regulated and central expression in both groups, although the SI group could not recognize the boundary between NP and AF cells. The EF group showed the highest autophagy-related gene expression whereas the SI group showed lower expression. In addition, the EF group showed more autophagy-accumulating materials than the SI group which elevated with increasing compression duration. Furthermore, the SI group induced the highest apoptotic gene expression, but the EF group showed the lowest expression. Conclusion: The EF method was better for studying autophagy and apoptosis because it enhanced intervertebral disc degeneration after compression, which is actively linked to autophagy and apoptosis. The degeneration process was elevated by increasing the compression duration, but SI could not distinguish AF and NP cell margins.

In this work, we tried to emphasize whole transcriptome expression changes in the Wistar rats brainstem two hours after acute stress. Most of the genes were upregulated. We detected massive shift of neuropeptides Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptors Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as Glutamate Grin3b, Grm2 and GABA Gpr156, Acetylcholine Chrm4,Chrne, Adreno- Adra2b receptors expression uprising. Intensive increase in expression of intermediate filaments Krt83/Krt86/Krt80/Krt84/Krt87/Krt4/Krt76 and motor proteins Myo7a, Klc3 was detected. Remarkably, at this time we also observed signs of microglia activation. Both expression of anti-inflammatory cytokines Il13, Ccl24 and proinflammatory cytokin’s receptors Il9r, Il12rb1, Tnfrsf14, Tnfrsf13c, Tnfrsf25, Tnfrsf1b were increased. In the Wnt signaling pathway, we have seen increased expression of ligands-receptors Wnt1, Wnt11, Ror2, and also negative regulators Notum, Sfrp5, Sost. Also we conducted cDNA libraries normalization with duplex specific nuclease and compared results. On the basis of our RNAseq data, we chose reference genes for RT-qPCR best suitable for experiments with acute stress.

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

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

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

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

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

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP, TRPC may form homo or heterotetrameric ion channel, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase of the expression of different TRPC isoforms has been observed in different animal model of heart infarcts, and in vitro experimental model of ischemia and reperfusion. TRPC-mediated increase of the intracellular Ca²⁺ concentration seems required for the activation of signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we will highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion, and to heart infarction.

This study was to explore the effects of glabridin and gymnemic acid on the structural changes of the choroidal layer as well as the expression of VEGF and CD31 in diabetic rats. The animals were separated into five groups: the control group (C), the diabetic group (DM), the diabetic rats treated with glabridin 40 mg/kg body weight (DM+GB), the diabetic rats treated with gymnemic acid 400 mg/kg body weight (DM+GM), and the diabetic rats treated with glyburide 4 mg/kg body weight (DM+GR). There has been an increase in the thickness of both the choroid layer and the wall of the arteries in the diabetic group. A decrease in vascularity and choroidal neovascularization can be found in DM rats. After eight weeks of experimentation, the choroidal thickness and wall of choroid arteries, as well as the diameter of the lumen of choroid arteries in the DM+GB, DM+GM, and DM+GR groups, had improved. The expression of VEGF and CD31 was lower compared to the DM group. According to the findings of the current research, glabridin and gymnemic acid can improve and reduce the damage to the choroid, which is a factor that can sometimes result in vision loss.

Purpose: Intervertebral disc is a leading avascular organ in the body. Hence, it may utilize autophagy and apoptosis to alive in unfavorable condition like stress and mechanical force. But excessive force and stress is a key cause to intervertebral disc degeneration (IVDD). Purpose of this study is to identify, external fixator (EF) and saline injection (SI) may induce autopahgy and apoptosis mediated nucleus pulposus (NP) cells death in rat tail’s disc and which method is better for studying autophagy and apoptosis. Methods: Sixteen 9-week-old male Sprague–Dawley rat tails were treated with 0.9% saline and EF (two-cross kirschner wires) for 6 weeks and 12 weeks as well. Treated discs were dissected for checking out participation of autopahgy and apoptosis to intervertebral disc degradation (IVDD). For identifying them, we performed H&E staining, Masson’s trichrome staining, and Immunohistochemistry (IHC) for LC3, Beclin-1and P62 as well as MMP-2, MMP-3 and TIMP-1.Furthermore, we performed quantitative polymerase chain reaction (qPCR)to check out autophagy related gene expression (beclin-1, LC3 and P62) and apoptosis related gene expression (MMP-2, MMP-3 and TIMP-1) respectively. Results: More insidious nucleus pulposus (NP) cell degeneration was indentified in (EF) group than in (Ctrl) control group. And rate of degradation was elevated with increasing duration of compression, but SI group cannot distinguish the margin of AF and NP cells. Highest along with lateral expression was found for LC3, Beclin-1, and P62 of both groups. Up-regulated and central expression was observed for MMP-2, MMP-3 and TIMP-1 of both groups, although SI group cannot recognize the margin between NP and AF cells. Utmost autophagy related gene expression was identified in EF group than in SI group. Besides, maximum autophagy accumulating materials was found in EF group than in SI group. And it was amplified along with increasing the duration of compression. Highest, apoptotic gene expression was observed in SI group, whereas, EF group showed lowest expression. Conclusion: External fixator (EF) method was better to study autophagy and apoptosis because it enhanced IVDD after compression which is actively linked with autophagy and apoptosis. Degeneration process was conversely proportional along with duration of compression. On contrary, saline injection (SI) could not distinguish AF and NP cell border.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

(1)Background:The purpose of the study was conducted to investigate the recovery of heart rate according to the performance level and rest interval conditions during 65%1RM bench press exercise;(2)Methods:The subjects of this study were eight healthy male college studentsin their 20 (years) attending University C. 1RM was measured before theexperiment, and the exercise sequence of six rest intervals (30sec, 1, 2, 3, 4,5min) was randomly selected and cross-distribution experiment. The experimental measurement was conducted a total of six times according to the rest interval condition (six conditions) once every 3 days to minimize the learning effect. The data was verified with repeated measures Two-way ANOVA and Contrast's repeated method was applied for post-comparison;(3)Results: First, the amount of exercise and the number of repetitions statistically substantially dropped (p&lt;.001) as the number of sets rose, and a greater decline was shown when the rest periods got shorter. Second, the heart rate after exercise was increased significantly (p&lt;.01) as the set progressed in the long rest interval conditions (4, 5min), and the heart rate after rest was increased statistically significantly (p&lt;,05) as the set progressed in the short rest interval conditions (30sec, 1min). Third, the heart rate recovery rate (%) was able to perform more repetitions than in the short rest interval condition due to the relatively high physiological recovery of the neuromuscular and circulatory system under the long rest interval condition;(4)Conclusions: Therefore, according to the rest conditionduring the 65%1RM bench press exercise conducted in this study, the restinterval condition of 2~3min may be effective in improving muscular endurance,and the rest interval condition of 4~5min may be effective in improving muscular hypertrophy. As a result of this study, there was a significant difference in exercise performance (repetition) and physiological recovery depending on the rest interval condition according to the set progress during the same intensity resistance exercise. Through this, it is judged that it is possible to adjust the amount of exercise appropriate for the purpose of training by adjusting not only the intensity during resistance exercise but also the rest interval between sets.

In order to overcome the disadvantages of existing treatments in heart valve tissue engineering, decellularization studies are carried out. The main purpose of decellularization is to eliminate the immunogenicity of biologically derived grafts and to obtain a scaffold that allows recellularization while preserving the natural tissue architecture. SD and SDS are detergent derivatives frequently used in decellularization studies. The aim of our study is to decellularize the pulmonary heart valves of young Merino sheep by using low-density SDS and SD detergents together, and then to perform their detailed characterization to determine whether they are suitable for clinical studies. Pulmonary heart valves of 4-6 month old sheep were decellularized in detergent solution for 24 hours. The amount of residual DNA was measured to determine the efficiency of decellularization. Then, the effect of decellularization on the ECM by histological staining was examined. In addition, the samples were visualized by SEM to determine the surface morphologies of the scaffolds. Uniaxial tensile test was performed to examine the effect of decellularization on biomechanical properties. The results showed DNA removal of 94% and 98% from the decellularized leaflet and artery portions after decellularization relative to the control group. No cell nuclei were found in histological staining and it was observed that the 3-layer leaflet structure was preserved. As a result of the tensile test, it was determined that there was no statistically significant difference between the control and decellularized groups in the UTS and elasticity modulus, and the biomechanical properties did not change. In conclusion, we suggest that the pulmonary valves of decellularized young Merino sheep can be used as a initial matrix in heart valve tissue engineering studies.

Febrile seizures in early childhood can lead to developmental disorders in the CNS. However, the specific mechanisms behind the impact of febrile seizures on the developing brain are not well-understood. To address this gap in knowledge, we employed a hyperthermic model of febrile seizures in 10-day-old rats and tracked their development over two months. Our objective was to determine the degree to which the properties of the hippocampal glutamatergic system are modified. We analyzed whether pyramidal glutamatergic neurons in the hippocampus die after febrile seizures. Our findings indicate that there is a reduction in the number of neurons in various regions of the hippocampus in the first two days after seizures. The CA1 field showed the greatest susceptibility, and the reduction in the number of neurons in post-FS rats in this area appeared to be long-lasting. Electrophysiological studies indicate that febrile seizures cause a reduction in glutamatergic transmission, leading to decreased local field potential am-plitude. This impairment could be attributable to diminished glutamate release probability as evidenced by decreases in frequency of miniature excitatory postsynaptic currents and increases in pair-pulse ratio of synaptic responses. We also found higher threshold current causing hindlimb extension in the maximal electroshock seizure threshold test of rats 2 months after febrile seizures compared to control animals. Our research suggests that febrile seizures can impair glutamatergic transmission, which may protect against future seizures.

Rat is one of the most commonly used model animals for biological research. The organs and systems of human being are somewhat similar to that of rat in structure as well as functions, making it a valuable choice for research experimentation in biological sciences. A number of studies have been conducted to evaluate the potential risks and toxicity of different elements on the physiology and histology of rats. There is need to address certain environmental factors affecting rats condition during experimentation. Reproduction along with its pathologies is under investigation on larger scale throughout the world, being central for the existence of a species. These studies focus on the major factors that influence reproductive function. Review of literature clearly indicated the unwanted consequences of over nutrition, malnutrition, high or low temperature, non-enriched housing, improper handling, intense or poor light exposure and environmental pollution on histology and hormonal profile of reproductive system of rats.

Background. A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. Methods. A longitudinal study was carried out in rats subjected to incisional myringotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7, 10, 14 and weekly thereafter until perforation closure, for up to 6 months. Results. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated with saline had a mean healing time of 8.5 days. At 8 weeks, 70.5% of these remained perforated and at 6 months this number fell to 21.4%. Conclusion. This technique is able to maintain more than 70% of tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.

Neural microprobes represent an important component of neural prosthetic systems where implanted microprobes record the electro-potentials generated by specific thoughts in the brain and convey the signals to algorithms trained to interpret these thoughts. Here, we present novel elongated multi-site neural probe that can reach depths greater than 10mm. We hypothesize that reaching such depth allows the recording of cognitive signals required to drive cognitive prosthetics. The impedance of the recording sites on the probes was on the order of 500 kΩ at 1 kHz, which is consistent with probes used for neurophysiological recordings. The probes were made porous using Xenon Difluoride (XeF₂) dry etching to improve the biocompatibility and their adherence to the surrounding neural tissue. Numerical studies were performed to determine the reliability of the porous probes. We implanted the elongated probe in rats and show that the elongated probes are capable of simultaneously recording both spikes and local field potentials (LFPs) from various recording sites.

Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.

Theta oscillations generated in hippocampal (HPC) and cortical neuronal networks are involved in various aspects of brain function, including sensorimotor integration, movement planning, memory formation and attention. Disruptions of theta rhythms are present in individuals with various disorders, including epilepsy and Alzheimer’s disease. Theta rhythm generation involves a specific interplay between cellular (ionic) and network (synaptic) mechanisms. HCN channels are theta modulators, and several medications are known to enhance their activity. We investigated how different doses of lamotrigine (LTG), an HCN channel activator, and antiepileptic and neuroprotective agent, would affect hippocampal theta rhythms in acute HPC slices (in vitro) and anaesthetized rats (in vivo). Whole-cell patch clamp recordings revealed that LTG decreased GABAA-fast transmission in CA3 and CA1 cells, in vitro. In addition, LTG directly depressed CA3 and CA1 pyramidal neuron excitability. These effects were partially blocked by ZD 7288, a selective HCN blocker, and are consistent with decreased excitability associated with antiepileptic actions. Lamotrigine also depressed hippocampal theta oscillations in vitro, also consistent with its neuronal depressant effects. In contrast, it exerted an opposite, enhancing effect, on theta recorded in vivo. The contradictory in vivo and in vitro results indicate that LTG increases ascending theta activating medial septum/entorhinal synaptic inputs that over-power the depressant effects seen in hippocampal neurons. These results provide new insights into LTG actions and indicate an opportunity to develop more precise therapeutics for the treatment of dementias, memory disorders and epilepsy.

Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify novel therapeutic agents. A rat IgAN model was established by administration of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, which simultaneously established blood stasis and a heat syndrome model. The animals were sacrificed to detect changes in protein levels in urine and blood. Immunofluorescence was performed to assess IgA deposition in the glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematology and eosin, periodic acid-Schiff, TUNEL, and immunohistochemical staining were performed to evaluate histopathological changes in kidney tissues. Additionally, target-related proteins were measured by western blotting. Periostracum cicadae resulted in a reduction in blood and urine protein levels. Serum TNF-α, IL-1β, and IL-6 levels significantly decreased in the periostracum cicadae-treated groups compared to the IgAN group. Furthermore, a reduction in MCP-1, TLR4, and IgA expression levels and a dose- dependent increase in caspace-3 expression were observed in response to periostracum cicadae treatment. TGF-β1 levels decreased, whereas that of Fas increased in the kidney tissues of the periostracum cicadae-treated groups. The findings of the present study indicate that periostracum cicadae induces apoptosis and improves kidney inflammation and fibrosis in IgA nephropathy rat models.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. Much of what we know about sarcopenia derive from studies on small rodents which serve as models for the human condition. Here we used outbred male rats to study the natural history of sarcopenia with the aim to compare behavioral motor deficits with degree of muscle wasting and to find processes underlying the preclinical phase of sarcopenia. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles in everyday life and significance for postural control. The results show that gait and coordination remain intact through middle age (12-18 months; 40%-60% of median lifespan) when muscle mass relative to body weight is largely maintained. The muscle, however, show multiple signs of remodeling with a shift in myofiber-type composition towards type I, increased number of hybrid fibers and fibers expressing embryonic myosin. In parallel with the shift in fiber type prevalence, fiber type clustering increased. The latter combined with a transcriptional upregulation of nicotinic acetylcholine receptor subunit  (CHRN ), NCAM and Myogenin (MYOG) suggests a remodeling driven by myofiber denervation. Additional stigmata were increased number of central nuclei, transcriptional upregulation of Smad3, FBXO32, and MuRF1mRNAs; unaltered density of satellite cells (SC) and Catenin mRNA. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate as loss of muscle mass progresses. In late middle age and early aging because of a type II atrophy (>50%), followed by type I atrophy (>50%). Number of myofiber did not correlate with this process. At advance age, the atrophy is accompanied by a decrease in SC and Catenin mRNA while several transcripts upregulated earlier-on were downregulated. In contrast, glial-derived nerve growth factor (GDNF) mRNA abundance peaked at endpoint. We conclude that sarcopenia in the rat as in humans, has a long preclinical phase where the muscle undergoes extensive remodeling to preserve muscle mass and function. The data supports the notion that myofiber denervation is the instigating mechanism, initially affecting large type II motor units (MUs) and at more advanced stage also the smaller type I MUs.

Congestion not only represents a cardinal sign of heart failure but is also now recognized as the primary cause for hospital admissions, rehospitalizations, and mortality among patients with acute heart failure. Congestion can manifest through various heart failure phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Complete decongestion is hardly achieved among patients with acute heart failure, as more than half still have residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with acute heart failure by highlighting insights into the pathophysiology mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion.

Transient Receptor Potential Vanilloid 4 (TRPV4) channel is a non-selective cation channel, mostly permeable to calcium (Ca2+), which participates to intracellular Ca2+ handling in cardiac cells. It is widely expressed through the body and is activated by a large spectrum of physico-chemical stimuli, conferring it a role in a variety of sensorial and physiological functions. With-in the cardiovascular system, TRPV4 expression was reported in cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs) where it modulates mitochondrial activity, Ca2+ ho-meostasis, cardiomyocytes electrical activity and contractility, cardiac embryonic development, fibroblast proliferation but also vascular permeability, dilatation and constriction. On the other hand, TRPV4 channels participate in several cardiac pathological processes such as development of cardiac fibrosis, hypertrophy, ischemia-reperfusion injuries, heart failure, myocardial infarc-tion, and arrhythmia. In this manuscript, we provide an overview of TRPV4 channel implica-tions in cardiac physiology and discuss the potential of TRPV4 channel as therapeutic target against cardiovascular diseases.

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

Transient receptor potential canonical (TRPC) channels are calcium channels with diverse expression profiles and physiological implications in the retina. Neurons and glial cells of rat retinas with photoreceptor degeneration caused by retinitis pigmentosa (RP) exhibit basal calcium levels that are above those detected in healthy retinas. Inner retinal cells are the last to degenerate and are responsible for maintaining the activity of the visual cortex even after complete loss of photoreceptors. We considered the possibility that TRPC1 and TRPC5 channels might be associated with both the high calcium levels and the delay in inner retinal degeneration. TRPC1 is known to mediate protective effects in neurodegenerative processes, while TRPC5 promotes cell death. In order to comprehend the implications of these channels in RP, the co-localization and subsequent physical interaction between TRPC1 and TRPC5 in healthy retina (Sprague-Dawley rats) and degenerating (P23H-1, a model of RP) retina were detected by immunofluorescence and proximity ligation assays. There was an overlapping signal in the innermost retina of all animals where TRPC1 and TRPC5 physically interacted. This interaction increased significantly as photoreceptor loss progressed. Both channels function as TRPC1/5 heteromers in the healthy and damaged retina, with a marked function of TRPC1 in response to retinal degenerative mechanisms. Furthermore, our findings support that TRPC5 channels also function in partnership with STIM1 in Müller and retinal ganglion cells. These results suggest that increase in TRPC1/5 heteromers may contribute to slowing of the degeneration of the inner retina during the outer retinal degeneration.

The hitologiy image of mouse xenograft of olfactory ensheating cells ( OECs) in to Albino Swiss Strain rats corticospinal tract lesion shows immunorejection after 10 days in grafted tissue . Moreover, the images of postoperative xenotransplanted OECs under daily subcutaneous injection of 100 ml of a dosage of 6 mg/kg/day avoid immunorejection in the misplace of GFP labeled transplanted OECs with the survival time of 4 weeks and there is no sign of inflammation. the result shows that the daily injection of 100ml diluted cyclosporine avoids immune attack and reduces inflammatory cells infiltrate in delayed CST ipsilateral rat model and also our study proved that stop of cyclosporine injection would not prevent DFR function and the regenerated fibers can still be visualised.

The thyroid-heart relationship has a long and articulated history of its own, a history that en-compasses physiological and pathophysiological knowledge, the latter particularly in the context of cardiac diseases such as heart failure, arrhythmias and ischaemic heart disease. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, being an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addi-tion, in the last few years, several studies have been carried out on the prognostic impact of al-terations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and therefore with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart-thyroid relation-ship.

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

Maximal heart rate (HRmax) is a widely used measure of cardiorespiratory fitness. Prediction of HRmax is an alternative to cardiopulmonary exercise testing (CPET), but its accuracy among endurance athletes (EA) requires evaluation. This study aimed to externally validate HRmax prediction models in the EA independently for running and cycling CPET. 4043 runners (age=33.58 (8.12) years; 83.53% males; BMI=23.66 (2.54) kg·m−2) and 1026 cyclists (age=36.88 (9.03) years; 89.67% males; BMI=24.04 (2.65) kg·m−2) underwent maximum CPET. Student t-test, mean absolute percentage error (MAPE), mean absolute error (MAE), and root mean square error (RMSE) were applied to externally validate 8 running and 5 cycling HRmax equations. HRmax was 184.60 (9.79) beats·min−1 and 182.66 (10.28) beats·min−1 respectively for running and cycling, p=0.001. Measured and predicted HRmax differed significantly (p=0.001) for 9 of 13 (69.23%) models. HRmax was overestimated by 8 (61.54%) and underestimated by 5 (38.46%) formulae. Overestimated HRmax ranged 0.08-4.94 beats·min−1 and underestimated HRmax ranged 0.03-4.90 beats·min−1. MAE and RMSE were 0.18-4.94 beats·min−1 and 9.13-10.47, respectively. MAPE ranged 3.95-4.69%. Prediction models do not allow for accurate estimation of HRmax. HRmax was more often underestimated than overestimated. Predicted HRmax can be implemented for EA as a supplemental method but CPET is the preferable approach.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

Background: Brain-derived neurotrophic factor (BDNF) has attracted increasing attention as a therapeutic agent because of its potentially biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully investigated. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. Methods: Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. Results: BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc. in both ST-2 and the MC3T3-E1 and ST-2 co-culture system. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Conclusion: Our study results showed positive effect of BDNF on osteogenesis. It provides essential evidence for clinical applications of BDNF in treating osteoporosis.

Cognitive deficit is a frequent non-motor symptom in Parkinson 's disease (PD) with an unclear pathogenesis. Recent research indicates possible involvement of insulin resistance and glutamate excitotoxicity in PD development. We investigated cognitive performance and the brain glutamate and insulin signaling in a rat model of PD induced by bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). Cognitive functions were assessed with Passive avoidance (PA) and Morris Water Maze (MWM) tests. The expression of tyrosine hydroxylase (TH) and proteins involved in insulin (IR, pI3K, ERK) and glutamate receptor (AMPAR, NMDAR) signaling was assessed in the hippocampus (HPC), hypothalamus (HPT) and striatum (S) by immunofluorescence, Western blot and ELISA. Three months after 6-OHDA treatment, cognitive deficit was accompanied by decreased AMPAR activity and TH levels (HPC, S), while levels of the proteins involved in insulin signaling remained largely unchanged. Spearman’s rank correlation revealed a strong positive correlation for pAMPAR-PA (S), pNMDAR-pI3K (HPC) and pNMDAR-IR (all regions). Additionally, a positive correlation was found for TH-ERK and TH-pI3K, and a negative one for TH-MWM/errors and pI3K-MWM/time (S). These results suggest a possible association between brain glutamate (but not insulin) signaling dysfunction and cognitive deficit in a rat PD model, detected three months after 6-OHDA treatment.

Heart myocardia are critical to the facilitation of heart pumping and blood circulating around the body. The biaxial mechanical testing of the Left Ventricle (RV) is utilised to build the computa-tional model of the whole heart with little importance given to the unique mechanical properties of Right Ventricle (RV) and Mid-wall (MDW). Most of those studies focussed on the LV of the heart, and then apply the obtained characteristics with a few modifications to the right side of the heart. However, that view has been contested over time with the realisation that the right side of the heart possesses its own unique mechanical properties that are widely distinct from that of the left side of the heart. This paper is aimed at reporting and evaluating the passive mechanical property dif-ferences in the three main walls of the rat heart based on biaxial tensile test data. Fifteen mature Wistar rats weighing 225 ± 25 g were euthanised by inhalation of 5 % halothane. The hearts were excised after which all the top chambers comprising the two atria, pulmonary and vena cava trunks, aorta and valves are all dissected out. Then 5 x 5 mm sections from the middle of each wall were carefully dissected with a surgical knife to avoid over-prestraining the specimens. The specimens were subjected tensile test. The elastic moduli, peak stresses in the toe region and stresses at 40 % strain, anisotropy indices as well as the stored strain energy in the toe and linear region up to 40 % strain are used for statistical significance tests. The following are the main findings of this study: (1) LV and MDW tissues have relatively shorter toe regions of 10 - 15 % strain as compared to RV tissue whose toe region extends up to twice as much as that (2) LV tissues have higher strain energy storage in the linear region despite being lower in stiffness than the RV (3) the MDW has the highest strain energy storage along both directions which might be directly related to its high level of anisotropy. These findings, though for a specific animal species at similar age and around the same body mass, emphasize the importance of application of wall specific material parameters to obtain accurate ventricular hyperelastic models. The findings further enhance our understanding of the desired mechanical behaviour of the different ventricle walls.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Cisplatin is an election chemotherapeutic agent for many cancer treatments. Its cytotoxicity against neoplastic cells is mirrored by that taking place in healthy cells and tissues, resulting in serious adverse events. A very frequent one is ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic treatments. Exacerbated oxidative stress is a main cytotoxic mechanism of cisplatin, including ototoxicity. Previous reports have shown antioxidant protection against cisplatin ototoxicity, but there is a lack of comparative studies on the otoprotectant activity and mechanism of antioxidant formulations. In this paper we report that a combination of vitamins A, C, E and Mg++ (ACEMg), previously shown to protect against noise-induced hearing loss, reverses auditory threshold shifts, promotes outer hair cell survival, and attenuates oxidative stress in the cochlea after cisplatin treatment, thus protecting against extreme cisplatin ototoxicity in the rat. The addition of 500 mg N-acetylcysteine (NAC), which administered individually also shows significant attenuation of cisplatin ototoxicity, to the ACEMg formulation, results in degradation of ACEMg otoprotection. Mg++ administered alone, as MgSO4, also prevents cisplatin ototoxicity, but in combination with 500 mg NAC, otoprotection also is greatly degraded. Increasing the dose of NAC to 1000 mg, also results in dramatic loss of otoprotection activity compared with 500 mg NAC. These findings support that single antioxidants or antioxidant combinations, particularly ACEMg in this experimental series, have significant otoprotection efficacy against cisplatin ototoxicity. However, an excess of combined antioxidants and/or elevated doses, above a yet to be defined “antioxidation threshold”, results in unrecoverable redox imbalance with loss of otoprotectant activity.

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.

Heart failure is a leading cause of death among people worldwide. The cost of treatment can be prohibitive, and early prediction of heart failure would reduce treatment costs to patients and hospitals. Improved prediction of readmission would also be of great help hospital, allowing them to better manage their treatment programs and budgets. This systematic review aims to summarize recent studies of predictive analytics models that have been constructed to predict heart failure and readmission. Some of these models use a statistical approach and others a machine learning approach. Electronic patient health records, including demography, physical and clinical values, and laboratory findings are used to design and build predictive models. Predictive analytics with good performance have become essential for clinicians and specialists. Choosing a suitable machine learning algorithm and data preprocessing technique will improve predictive model performance, including data imputation and class imbalance.

BackgroundHeart failure is a life-threatening disease affecting millions worldwide. Tolvaptan is the first FDA-approved orally active nonpeptide vasopressin 2 receptor antagonist to be used in hypervolemic hyponatremia, heart failure, cirrhosis, etc. In clinical trials, tolvaptan impacts short-term in increasing water excretion, and restoring Na+ and dyspnoea. Aims & ObjectivesThe objective is to analyze the outcomes of tolvaptan in existing cases of heart failure. MethodologyWe conducted a database search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and RCTs till 1st September 2019 were included following PRISMA guidelines after being matched with inclusion and exclusion criteria. 21 RCTs were included with 7,357 patients receiving tolvaptan and 7,273 patients being the control group. We used the MESH strings such as 'tolvaptan', 'vasopressin V2 receptor blocker', 'acute heart failure', and 'acute decompensated heart failure'. ResultsMeta-analysis showed that Tolvaptan was associated with a significant reduction in edema (RR = 1.05, 95% CI = 1.019-1.081, p=0.001) and significant body weight reduction (Control-SMD = -0.489, 95% CI =-0.637 to -0.342, p<0.001)&(Placebo-SMD = -0.425, 95% CI = -0.425 to -0.382, p<0.001) It shows significant decrease in serum sodium levels (SMD = 0.678, 95% CI = 0.609 to 0.748, p<0.001). There was no significant decrease in all-cause mortality (Control-RR = 0.855, 95% CI 0.470 to 1.555, p=0.607)(Placebo-RR= 0.972, 95% CI = 0.879-1.074, p=0.575). Results for Worsening renal function in heart failure (Placebo-RR = 0.798 95% CI 0.619 to 1.028, p=0.081)(Control-RR = 1.349, 95% CI=0.927-1.964, p=0.118). ConclusionAlthough tolvaptan may significantly reduce edema, congestive symptoms and decreased body weight, it has no impact on all-cause mortality and worsening renal function in heart failure.

Non-invasive heart rate (HR) monitoring is important in clinical settings as it plays a critical role in diagnosing a range of health conditions and assessing well-being. Presently, the gold standards for HR measurement are all based on sensors which require skin contact. Apart from inconvenience, contact sensors have proven problematic in certain scenarios – they cannot be used when mechanical isolation of the patient is imperative (burn victims, patients with shaky hands and feet), cause skin damage to premature babies in the ICU and increase the risk of spreading infections. Non-contact HR monitoring using a camera has been recently shown to be a viable alternative. It is now possible to record cardiac-synchronous blood volume variations from facial videos of human subjects under ambient lighting. These variations produce corresponding changes in skin reflectance which can be extracted as a raw reflectance photoplethysmography (rPPG) signal and processed to reveal HR. In this project, an algorithmic framework for webcam-based HR detection was successfully implemented in MATLAB. The investigation was based on 100 self-captured videos (dark-skinned subject) and 48 videos (from 12 subjects, all but one fair-skinned) obtained from COHFACE – an online database of facial videos and corresponding physiological signals. While the performance metrics (mean error, SNR) of the rPPG signals obtained from the self-captured videos were poor (best case mean error of 22%), they were good enough to demonstrate the success of the implementation. The poor results were primarily imputed to skin tone as rPPG SNR is known to be particularly low for dark tones. The results of the COHFACE videos were far superior, with mean error ranging from 3% to 15% (among 8 different rPPG signals) and 0% to 9% under ambient and dedicated lighting, respectively. This investigation sets the foundation for future research directed at optimizing rPPG performance metrics for dark-skinned subjects.

One of the oldest and common methods of diagnosing heart abnormalities is auscultation. Even for experienced medical doctors, it is not an easy task to detect abnormal patterns in the heart sounds. Most of the digital stethoscopes are now capable of recording and transferring the heart sounds. Moreover, it is proven that auscultation records can be classified as healthy or unhealthy via artificial intelligence techniques. In this work, an artificial intelligence-powered mobile application that works in a connectionless fashion is presented. According to the clinical experiments, the mobile application can detect heart abnormalities with approximately 92% accuracy which is comparable if not better than humans since only a small number of well-trained cardiologists can analyze auscultation records better than artificial intelligence. Using the diagnostic ability of artificial intelligence in a mobile application would change the classical way of auscultation for heart disease diagnosis.

The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and then identify decelerations and accelerations. These steps can potentially be automated and made more objective by signal processing analysis. Various methods have been described in the literature but there are no open-source programs for performing these steps. The MATLAB toolbox presented here comprises a standard signal pre-processing function, 11 re-coded literature methods for fetal heart rate analysis, a signal viewer (enabling annotation by an expert) and an evaluation procedure with various criteria measuring intrarater agreement.

(1) Objectives. Patients with heart failure (HF) who experience hospitalizations for worsening HF (HFH) are at high risk of subsequent events. We aimed to evaluate the impact of an outpatient care management program that includes a clinician-to-clinician e-consultation using an integrated electronic medical record in a healthcare area with a widely dispersed population on delay time in care, hospital admissions, and mortality in a high-risk group of patients with HF and previous episodes of HFH. (2) Methods. We selected 6,444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4,851 were attended in e-consult, and 2,008 in one-time in-person consultations. In 2,230 HF patients, there was documentation of a previous episode of HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the health care model in the group of patients with HFH and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). (3) Results. In the group of patients with previous HF hospitalizations, the introduction of e-consult substantially decreased waiting times to cardiology care. The time elapsed to care after e-consult implementation was significantly reduced compared with the previous in-person period (8.6 [8.7] vs 55.4 [79.9] days, p&lt;0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [CI95%]: 0,837 [0,840-0,833]), 0,900 [0,862-0,949] for CV and 0,699 [0,678-0,726] for all-cause hospitalizations. There was also lower mortality (iRR [CI95%]: 0.715 [0.657-0.798] due to HF, 0,737 [0.764-0.706] for CV and 0,687 [0.652-0,718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH and were independent of the patient’s clinical characteristics managed during the in-person or e-consultation periods. (4) Conclusions. In HF patients with previous HFH, an outpatient care program that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is impacted already during adolescence in a genetic rat model for obesity and type 2 diabetes. Cognitive functioning throughout adolescence and early adulthood was investigated in Zucker Diabetic Fatty (ZDF), ZDF lean and healthy outbred Long Evans rats using operant touchscreens. Blood glucose, insulin and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues and the prefrontal cortex. Adolescent ZDF obese rats outperformed lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in ZDF early adult obese rats. Histological analyses at early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent obese ZDF rats even display enhanced cognition despite their early diabetic profile.

Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

Parkinson’s-disease (PD) is an incurable age-related neurodegenerative disease and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient's quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD, however its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine, are the metabolites that significantly discriminate Parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, glucose-alanine cycle, the glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and Parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation.

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.

A new circuit model of the self-powered device for heart rate measurement is presented in this paper. This device consists of piezoelectric energy harvester (PEH), power management circuit (PMC) with energy storage, microcontroller, Photoplethysmography (PPG) sensor, and Wi-Fi module. The PEH is placed under the insole to harvest the pressure energy from human foot-step to generate ac power. In our model, a PEH is represented by sine voltage source, where its parameters were taken from experiments with 20 volunteers. The PMC is simplified by a switch with gain δ placed in series with the main circuit. The model of the main circuit is RC elements in parallel, where C is the capacitance of the storage device, and R is the equivalent parallel resistance of the microcontroller, PPG sensor, and Wi-Fi modules, respectively. The value of R depends on the power and current absorbed by those modules during sleep, deep sleep, sense, and transmit modes which collected from the datasheet. Finally, the proposed circuit model of the self-powered device was built and simulated in SPICE. The simulation results were compared with the laboratory experiment using commercial devices. Based on the results, the proposed model had small gaps compared to the real self-powered devices in terms of average current, voltage, power and efficiency.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor ac-tivity in combination with the commonly used six anticancer drugs namely cyclophosphane, fluorouracil, etoposide, cysplatine, ribomustine with different mechanisms of action was investi-gated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting on the С6 rat glioma model cells.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycemia. Plant-based therapies are characterized by low bioavailability in ocular tissues. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR, were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Fundus of retinal arterioles, retina histopathology and lens transmission electron microscopy (TEM), were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fiber disorganization. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately edematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA formation and increased antioxidant capacity. Retinal edema and disorganization in lens fibers were still present.

Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and the aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes accompanying severe primary headaches. To further decipher the effects of fremanezumab underlying these antinociceptive effects in rats, immunohistochemistry and ELISA techniques were used to analyse the content and concentration of CGRP in the trigeminal ganglion as well as the ratio of trigeminal ganglion neurons immunoreactive to CGRP and CGRP receptor components 1-10 days after subcutaneous injection of fremanezumab (30 mg/kg) compared to an isotype control antibody. After fremanezumab treatment, the fraction of trigeminal ganglion neurons immunoreactive to CGRP and the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was significantly lowered compared to the control. The content and concentration of CGRP in trigeminal ganglia were not significantly changed. A long-lasting reduction of CGRP receptors expressed in trigeminal afferents may contribute to the attenuation of CGRP signalling and antinociceptive effects of monoclonal anti-CGRP antibodies in rats.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

Mitochondria are essential to cell homeostasis, and alterations in mitochondrial distribution, segregation or turnover have been linked to complex pathologies such as neurodegenerative diseases or cancer. Understanding how these functions are coordinated in specific cell types is a major challenge to discover how mitochondria globally shape cell functionality. In this review, we will first describe how mitochondrial transport and dynamics are regulated throughout the cell cycle in yeast and in mammals. Second, we will explore the functional consequences of mitochondrial transport and partitioning on cell proliferation, fate acquisition, stemness, and on the way cells adapt their metabolism. Last, we will focus on how mitochondrial clearance programs represent a further layer of complexity for cell differentiation, or in the maintenance of stemness. Defining how mitochondrial transport, dynamics and clearance are mutually orchestrated in specific cell types may help our understanding of how cells can transition from a physiological to a pathological state.

The relative proportions between nutrients affects the fate of them for metabolic interconversion, storage and turnover or, essentially for energy, in a process of partition modulated by hormonal and metabolic factors. A basic common chow model was used: ST or standard diet, HF high-fat and HP or high-protein had a common substrate. A CF cafeteria-type diet was added for comparison. Rats (female and male) received the diet for 30d. Nutrient intake and body composition were measured. Plasma glucose, lactate, testosterone (T) and estradiol (E2) were measured. Common groups energy intake, was largely based in carbohydrates CH, yielding 6C units, which were fully oxidized or stored as 2C fragments (fatty acids). Lactate (3C) was partially stored as glycerol of TAG. Accrual of 2C far exceeded about ten-fold that of 3C. Amino acid (AA) catabolism yielded 2C, 3C and 4C-5C fragments, the latter acting as Krebs cycle anaplerotic intermediates (KCAI), that facilitated the oxidation of 2C in detriment of TAG accumulation Lactate levels, were related to lactic dehydrogenase activities in muscle and liver. TAG accrual was maximal in CF, quite differently from HF with similar diet lipid proportion. Maximal rates of lipid storage were found in ST (and CF) groups. Females showed a higher ability to oxidize CH and to store less TAG. T increased N and protein deposition, whilst E2 decreased them favoring AA oxidation and the availability of KCAI. In the rat, an effective energy partition scheme requires that about half of the energy is provided by CH (polysaccharide), and needs enough protein to provide KCAI for a smooth 2C oxidation.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

Chronic kidney diseases (CKD) and end stage renal disease (ESRD) are growing threats worldwide. Tissue engineering is a new hope to surpass the current limitations such as the shortage of donor. To do so, the first step would be fabrication of an intact decellularized kidney scaffold. In the current study, an automatic decellularization device was developed to perfuse and decellularize male rats' kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their efficacy in kidney decellularization and post-transplantation angiogenesis. After anesthesia, kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Masson’s trichrome, and alcian blue to determine cell removal and glycogen, collagen and glycosaminoglycans (GAGs) contents, respectively. Moreover, scanning electron microscopy (SEM) was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quantification assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility and bioactivity of the decellularized scaffolds, allotransplantation was performed in back muscle and angiogenesis was evaluated. Complete cell removal in both SLES and SDS groups was observed in SEM and DNA quantification assays. Moreover, the extracellular matrix (ECM) architecture of rat kidney in the SLES group was significantly preservation better than the SDS group was shown. The formation of blood capillaries and vessels were observed in the kidney allotransplantations in both SLES and SDS decellularized kidneys. In conclusion, we demonstrated that both SLES and SDS could be promising tools in kidney tissue engineering. The better preservation of ECM than SDS, introduces SLES as the solvent of choice for kidney decellularization. ¬¬