Miracle-dz/UniFAR-FTUs huggingface dataset:
Varicose vein and diastolic dysfunction: Is there an interaction?

Dear Editor, We have read with great interest the article published by Rusninovich Y and Rusinovich V and congratulate the authors for assessing and reporting the cardiac Doppler findings in patients with varicose vein (VV) for the first time. They have examined the characteristics of cardiac Doppler in patients with primary VVs of lower extremities and compared them with normal subjects without VV. Patients with primary VVs in comparison with normal controls have impaired relaxation of right and left ventricles documented by lower early diastolic mitral and tricuspid inflow velocities. Moreover, they have reported higher systolic mitral and tricuspid annular velocities. Eventually they have commented that increased atrial ejection fraction due to altered preload in patients with primary VVs are the possible mechanisms of these cardiac Doppler findings in patients with primary varicose veins. We would like to make further evaluation on their comments. Echocardiographic assessment of patients with varicose vein or chronic venous insufficiency would certainly improve our understanding on the pathophysiology and hemodynamic consequences of VVs. Beyond the limitations such as retrospective, single center design and low number of patients which have been already mentioned by the authors, cardiac Doppler findings give rise several issues which need to be discussed carefully. The association between the echocardiographic findings revealing impaired diastolic relaxation and VV might have been arisen from the influence of hemodynamic consequences of VV on the cardiac filling pressure and subsequent diastolic and systolic functions of the heart. Unfortunately we don’t have too much knowledge in literature regarding the effects of peripheral VV on cardiac filling pressures and volumes. Impaired relaxation might be attributed to increase in atrial volumes which results in forceful atrial contraction. However impaired diastolic relaxation, namely grade I diastolic dysfunction does not necessitate increased volume inflow into heart chambers. Impaired relaxation of right and left ventricles themselves is the other major mechanism of diastolic dysfunction. Recently, VV has been classified under the term of dilating venous diseases with the presumption that it is the local manifestation of systemic vascular wall abnormality. In this context, not only the hemodynamic changes but also the ultra-structural changes in vascular wall and extracellular matrix in heart chambers may be responsible for the impaired relaxation of the heart in patients with VV. Likewise coronary artery ectasia which has been defined as a member of dilating vascular disease, has shown to be associated with left ventricular diastolic dysfunction. However this issue needs to be clarified in future studies focusing on the cardiac filling volumes and pressures directly. Hemodynamic and morphologic changes of heart chambers in association with contribution of hemodynamic and morphologic changes of vena cava should be assesses in patients with VVs or dilating venous disease.
Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction

ABSTRACT Background: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients’ TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD. HIGHLIGHTS An elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.
Reduction of doxorubicin-induced cytotoxicity and mitochondrial damage by betanin in rat isolated cardiomyocytes and mitochondria

Doxorubicin (DOX) is an anticancer drug which is used for treatment of several types of cancers. But the clinical use of doxorubicin is limited because of its cardiotoxicity and cardiomyopathy. Mitochondrial-dependent oxidative stress and cardiac inflammation appear to be involved in doxorubicin-induced cardiotoxicity. Betanin as a bioactive compound in Beetroot (Beta vulgaris L.) displays anti-radical, antioxidant gene regulatory and cardioprotective activities. In this current study, we investigated the protective effect of betanin on doxorubicin-induced cytotoxicity and mitochondrial-dependent oxidative stress in isolated cardiomyocytes and mitochondria. Isolated cardiomyocytes and mitochondria were treated with three concentrations of betanin (1, 5 and 10 µM) and doxorubicin (3.5 µM) for 6 h. The parameters of cellular and mitochondrial toxicity were analyzed using biochemical and flow cytometric methods. Our results showed a significant toxicity in isolated cardiomyocytes and mitochondria in presence of doxorubicin which was related to reactive oxygen species (ROS) formation, increase in malondialdehyde (MDA), increase in oxidation of GSH to GSSG, lysosomal/mitochondrial damages and mitochondrial swelling. While betanin pretreatment reverted doxorubicin-induced cytotoxicity and oxidative stress in isolated cardiomyocytes and mitochondria. These results suggest that betanin elicited a typical protective effect on doxorubicin-induced cytotoxicity and oxidative stress. It is possible that betanin could be used as a useful adjuvant in combination with doxorubicin chemotherapy for reduction of cardiotoxicity and cardiomyopathy.
Plasma thiol and disulphide levels and their relationship with left ventricular systolic functions: A propensity score matching analysis.

OBJECTIVE Left ventricular (LV) systolic function measured through LV ejection fraction (LVEF) has prognostic implications in patients with cardiac and non-cardiac conditions. The balance of thiol and disulphide levels reflects oxidative status in the body. In this study, we aimed to investigate the relationship between plasma thiol and disulphide levels, and LVEF calculated by transthoracic echocardiography (TTE). METHODS This retrospective study included 1,048 patients referred for TTE examination and biochemical analyses, including plasma thiol and disulphide levels. After the application of exclusion criteria, the remaining 611 patients were included in the statistical analysis. Patients were classified into two groups, namely normal LVEF (n-LVEF) (n=446) and low LVEF (l-LVEF) (n=165) according to a cut-off level of LVEF 50%. To reduce sample selection bias and adjust for the influence of differences in patient characteristics on LVEF and oxidative status, 1: 1 propensity score matching analysis was applied. RESULTS Propensity score matching analysis yielded 125 patients in both groups with comparable demographics, medications, and blood parameters. Native thiol and total thiol levels were lower in l-LVEF patients than in n-LVEF patients (p<0.001 for both), whereas disulphide levels were higher in l-LVEF group (p=0.008). Native thiol (r=0.384, p<0.001), total thiol (r=0.35, p<0.001), and disulphide levels (r=-0.129, p=0.004) significantly correlated with LVEF. CONCLUSION Plasma thiol levels decrease and disulphide levels increase suggesting the presence of oxidative stress in patients with l-LVEF. Significant correlation between oxidative stress and LVEF sheds light about the possible pathogenetic role of thiol and disulphide in heart failure.
Pathology, bacteriology and molecular studies on caseous lymphadenitis in Camelus dromedarius in the Emirate of Abu Dhabi, UAE, 2015-2020

Caseous lymphadenitis (CLA) or pseudotuberculosis is a chronic zoonotic bacterial disease caused by Corynebacterium pseudotuberculosis, which affects livestock and humans. This study aimed to describe the pathology, bacteriology and confirm the identity of the pathogen by 16S rRNA gene sequencing in Camelus dromedarius. A total of 12 camels with suspected CLA in three regions of Abu Dhabi Emirate (Abu Dhabi, Al Ain and Al Dhafra), United Arab Emirate (UAE) were subjected to clinical and postmortem examinations from January 2015 to December 2020. Clinically, camels were emaciated and showed the presence of external caseous abscesses suggestive of CLA. Postmortem examination showed multiple abscesses of variable sizes with caseous material encapsulated by fibrous tissue in the liver, lungs, muscle, and lymph nodes. Following clinical and postmortem examination, blood, pus and different tissue samples were collected for subsequent analysis. Histopathological examination of all organs stained with Hematoxylin and Eosin (H&E) indicated a central caseo-necrotic core that was admixed with bacterial colonies and infiltration of chronic inflammatory cells, surrounded by a pyogenic membrane, and an outer fibrous connective tissue capsule. Bacterial culture identified the isolates of Corynebacterium pseudotuberculosis biotype ovis strain, and these isolates were shown to be sensitive to all antibiotics tested (penicillin, ampicillin, Co-trimoxazole, enrofloxacin and tetracycline). Moreover, the identity of the isolates was confirmed by partial sequencing of the 16S rRNA gene which showed a 100% identity to Corynebacterium pseudotuberculosis. Phylogenetic analysis based on 16S rRNA gene sequence clearly differentiates Corynebacterium pseudotuberculosis from other species of Corynebacterium. Briefly, this study provided the basic information for infection of Corynebacterium pseudotuberculosis in Camels and will help in controlling of this pathogen in the region.
miR-34a inhibits melanoma growth by targeting ZEB1

Melanoma is a highly lethal cutaneous cancer with the tendency for early invasion and metastasis. Integrated miRNA transcriptome sequence analysis of human melanoma tumors and adjacent control tissues identified 17 miRNAs differentially expressed in melanoma tissues: let-7a-5p, let-7b-5p, let-7c, miR-374a-3p, miR-100-5p, miR-7, miR-195, miR-1908, miR-214, miR-221, miR-199a-5p, miR-21, miR-18, miR-34a, miR-199a-3p, miR-92a and miR-106b. Among these, miR-34a was most significantly down-regulated in melanoma tissues, and its expression correlated with TNM melanoma stage. miR-34a overexpression inhibited expression and activity of the transcription factor ZEB1, resulting in decreased proliferation and migration of melanoma cells. Moreover, miR-34a overexpression inhibited ZEB1 expression and melanoma tumor growth in vivo, in a melanoma nude mouse model. Together, these findings demonstrate that miR-34a inhibits melanoma growth by targeting the proto-oncogene ZEB1 and suggest the miR-34a -ZEB1 axis may serve as a novel target for melanoma treatment.
Examination of the Social Emotional Assets and Resilience Scales (SEARS) Youth Report: Factor Structure, Measurement Invariance, and Validity

The Social and Emotional Assets and Resilience Scale (SEARS) is a promising instrument for prediction of resilience in youth; however, there is limited data to support its use. The purpose of the current study was to examine the factor structure, measurement invariance, internal consistency, and validity of the SEARS-Adolescent Report in youth 8 to 20 years of age. Two hundred and twenty-five childhood cancer survivors (Mage = 15.9, SD = 4.2; 51.4% male; 74.5% White) and 122 student controls without history of significant health problems (Mage = 14.2, SD = 3.5; 54.1% female; 79.5% White) 8 to 20 years of age completed the SEARS-A. The SEARS-A was found to have an adequate factor structure and model fit (χ2 = 1215.5, p < .001; root mean square error of approximation = .057; comparative fit index = .95; standardized root mean square residual = .06) and demonstrated invariance across domains of age, health status, gender, race, and socioeconomic status (Δ comparative fit index < −0.01). It also demonstrated excellent internal reliability, criterion validity, and current validity when compared with another well-established measure of psychological adjustment. As such, the SEARS-A has potential to be a useful, valid, and psychometrically sound tool for predicting social–emotional adjustment outcomes among at-risk youth 8 to 20 years of age.
Early adulthood obesity is associated with impaired left ventricular and right ventricular functions evaluated by speckle tracking and 3D echocardiography.

OBJECTIVE The prevalence of obesity is increasing globally. Obesity has been shown to be associated with adverse cardiac outcomes. Current knowledge on the impairment of cardiac function caused by obesity in young adult population is lacking. Therefore, we aimed to evaluate the effect of obesity on cardiac deformation parameters in healthy obese individuals in early adulthood using 2D deformation imaging and 3D echocardiography. METHODS Seventy-seven volunteers with a body mass index (BMI) above 25 kg/m2 who were between 18 and 30 years of age and a control group including 40 participants were included. Patients with a history of organic heart disease, poor image quality, or current pregnancy were excluded. Participants were classified as overweight (BMI of 25-29.9 kg/m2) and obese (BMI ≥ 30 kg/m2). Two dimensional and 3D appropriate echocardiographic images were recorded and further analyzed with a post-processing software to obtain the global longitudinal strain (GLS) of left (LV) and right ventricle (RV). RESULTS A total of 117 subjects without metabolic syndrome were enrolled. Conventional dimensional and functional parameters as well as 3D volumetric measurements showed no significant differences among the groups. Presence of epicardial fat tissue was higher in the obese group. Notable differences were found among the groups for both 2D speckle tracking derived and 3D LV GLS, RV GLS, RV free-wall LS (analysis of variance [ANOVA], p<0.05) showing lower deformation in obese subjects. LV torsion was found to be significantly higher (ANOVA, p<0.05) for the obese group. CONCLUSION Obesity causes subclinical dysfunction of LV and RV in healthy obese subjects in early adulthood. Risk stratification should be performed by considering possible mentioned impact of obesity on myocardial functions.
Do Simulated Hospital Admissions Reflect Reality? A Qualitative Study of Volunteer Well-Being During a 24-Hr Simulated Hospitalization

Objectives: This study aims to delineate if and how healthy volunteers admitted to simulated care can aid in understanding real well-being experiences of in-hospital surgical patients. Background: Scientific research is necessary to understand the mediating effect of healthcare design on patient outcomes. Studies with patients are, however, difficult to conduct as they require substantial funding, time, and research capacity, and recovering patients are often not willing or able to participate. If studies conducted with volunteers provide similar findings, such studies might serve as fruitful alternatives for future research. Method: A multimethod study was conducted between July 2017 and December 2017 with 17 volunteers who underwent a 24-hr simulated inpatient postsurgical care protocol. Data on value experiences, norms, and design requirements for an optimal healing environment were collected via diaries and semi-structured value-oriented interviews, focused on the values of spatial comfort, privacy, autonomy, sensory comfort, safety and security, and social comfort. Volunteers’ outcomes were compared to prior literature on similar patients’ outcomes. Results: Volunteers seem to experience their healing environment similarly to patients with regard to the values of spatial comfort, privacy, autonomy, sensory comfort, and social comfort related to contact with personnel and relatives. Less valuable insights were gained on the values of safety and security, and social comfort related to interaction with other patients, most probably due to the study design and because the participants did not truly experience a diseased bodily state. Conclusion: Simulated hospital admissions with volunteers provide a satisfactory alternative for studying real patient outcomes.
Optimization of light exposure and sleep schedule for circadian rhythm entrainment

The circadian rhythm, called Process C, regulates a wide range of biological processes in humans including sleep, metabolism, body temperature, and hormone secretion. Light is the dominant synchronizer of the circadian rhythm—it has been used to regulate the circadian phase to cope with jet-lag, shift work, and sleep disorder. The homeostatic oscillation of the sleep drive is called Process S. Process C and Process S together determine the sleep-wake cycle in what is known as the two-process model. This paper addresses the regulation of both Process C and Process S by scheduling light exposure and sleep based on numerical simulations of circadian rhythm and sleep mathematical models. This is a significant step beyond the existing literature that only considers the entrainment of Process C. Regulation of the two-process model poses several unique features and challenges: 1. Process S is non-smooth, i.e., the homeostatic dynamics are different in the sleep and wake regimes; 2. Light only indirectly affects Process S through Process C; 3. Light does not affect Process C during sleep. We consider two scenarios: optimizing light intensity as the control input with spontaneous (i.e., unscheduled) sleep/wake times and jointly optimizing the light intensity and the sleep/wake times, which allows limited delayed sleep and early waking as part of the decision variables. We solve the time-optimal entrainment problem for the two-process model for both scenarios using an extension of the gradient descent algorithm to non-smooth systems. To illustrate the efficacy of our time-optimal entrainment strategies, we consider two common use cases: transmeridian travelers and shift workers. For transmeridian travelers, joint optimization of the two-process model avoids the unrealistic long wake duration when only Process C is considered. The entrainment time also decreases when both the light input and the sleep schedule are optimized compared to when only the light input is optimized. For shift workers, we show that the entrainment time is significantly shortened by optimizing the night shift working light.
Human Absorbed Dose Evaluation of [177Lu]Lu-IBA as a Bone Palliative Candidate

Abstract The role of lutetium-177 among bone-seeking radionuclides in targeted therapy is noteworthy. The clinical pharmacokinetics of ibandronate (IBA) indicates that this bisphonate has powerful bone mineral affinity. The aim of this study was to evaluate of [177Lu]Lu-IBA efficacy as a new compound. The [177Lu]Lu-IBA was prepared by radiolabeling of IBA ligand to 177LuCl3 that was obtained by thermal neutron irradiation of enriched Lu2O3 sample. Produced [177Lu]Lu-IBA with high radiochemical purity was administered intravenously to mice. Biodistribution data were collected at 1, 4, 24, 48 h and 7 d post injections. With calculating accumulated activities in each organ and extrapolating mouse’s organs to human’s organs by the RADAR method and using OLINDA/EXM software the injected dose in various human organs was achieved. [177Lu]Lu-IBA was produced with radiochemical purity nearly 96 %. Its biodistribution data showed the high uptake and durability in the skeletal tissues without significant uptake in other major organs. The results showed that [177Lu]Lu-IBA has considerably good properties as a bone-seeking radiopharmaceutical and therefore can be a candidate for bone pain palliative therapy in skeletal metastases; however, further biological studies are still needed.
αB‐crystallin/HSPB2 is critical for hyperactive mTOR‐induced cardiomyopathy

Even though aberrant mechanistic target of rapamycin (mTOR) signaling is known to cause cardiomyopathy, its underlying mechanism remains poorly understood. Because augmentation of αB‐crystallin and hspB2 was presented in the cortical tubers and lymphangioleiomyomatosis of tuberous sclerosis complex patients, we deciphered the role of αB‐crystallin and its adjacent duplicate gene, hspB2, in hyperactive mTOR‐induced cardiomyopathy. Cardiac Tsc1 deletion (T1‐hKO) caused mouse mTOR activation and cardiomyopathy. Overexpression of αB‐crystallin and hspB2 was presented in the hearts of these mice. Knockout of αB‐crystallin/hspB2 reversed deficient Tsc1‐mediated fetal gene expression, mTOR activation, mitochondrial damage, cardiomyocyte vacuolar degeneration, cardiomyocyte size, and fibrosis of T1‐hKO mice. These cardiac‐Tsc1; αB‐crystallin; hspB2 triple knockout (tKO) mice had improved cardiac function, smaller heart weight to body weight ratio, and reduced lethality compared with T1‐hKO mice. Even though activated mTOR suppressed autophagy in T1‐hKO mice, ablation of αB‐crystallin and hspB2 failed to restore autophagy in tKO mice. mTOR inhibitors suppressed αB‐crystallin expression in T1‐hKO mice and rat cardiomyocyte line H9C2. Starvation of H9C2 cells activated autophagy and suppressed αB‐crystallin expression. Since inhibition of autophagy restored αB‐crystallin expression in starved H9C2 cells, autophagy is a negative regulator of αB‐crystallin expression. mTOR thus stimulates αB‐crystallin expression through suppression of autophagy. In conclusion, αB‐crystallin and hspB2 play a pivotal role in Tsc1 knockout‐related cardiomyopathy and are therapeutic targets of hyperactive mTOR‐associated cardiomyopathy.