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Nanomedicine holds great potential for revolutionizing medical treatment. Ongoing research and advancements in nanotechnology are continuously expanding the possibilities, promising significant advancements in healthcare. To fully harness the potential of nanotechnology in medical applications, it is crucial to conduct safety evaluations for the nanomedicines that offer effective benefits in the preclinical stage. Our recent efficacy studies indicated that rapamycin perfluorocarbon (PFC) nanoparticles showed promise in mitigating cisplatin-induced acute kidney injury (AKI). As cisplatin is routinely administered to ovarian cancer patients as their first-line chemotherapy, in this study, we focused on evaluating the safety of rapamycin PFC nanoparticles in mice bearing ovarian tumor xenografts. Specifically, this study evaluated the effects of repeat-dose rapamycin PFC nanoparticle treatment on vital organs, the immune system, and tumor growth and assessed pharmacokinetics and biodistribution. Our results indicated that rapamycin PFC nanoparticle treatment did not cause any detectable adverse effects on cardiac, renal, or hepatic functions or on splenocyte populations, but it reduced the splenocyte secretion of IL-10, TNFα, and IL12p70 upon IgM stimulation. The pharmacokinetics and biodistribution results revealed a significant enhancement in the delivery of rapamycin to tumors by rapamycin PFC nanoparticles, which, in turn, led to a significant reduction in ovarian tumor growth. Therefore, rapamycin PFC nanoparticles have the potential to be clinically beneficial in cisplatin-treated ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: The groundwater in arid countries such as Egypt represent the main water resources in the desert regions due to the long distance between these regions (oasis) and Nile River. Contamination of these limited water resources with toxic metals threaten the health of individuals in these regions. Methods: The current study integrates isotopic tracers, hydrogeochemistry, geophysical logs, positive matrix factorization (PMF model), and Monte Carlo (MCS) simulation for pollution source apportionment and health risks associated with heavy metals in the Nubian Sandstone aquifer (NSSA). Results and Discussion: The water resource used for drinking purposes (NSSA) is pale meteoric water (non-rechargeable aquifer). Silicate weathering, old trapped sea water, reverse ion exchange evaporation, and dissolution are the dominant mechanisms controlling water chemistry. PMF model showed that the major ions and heavy metals in groundwater of the NSSA originated from four significant sources (anthropogenic activities, dissolution of minerals, ironbearing minerals, mixing with old trapped seawater, and hydrothermal water). The total risk (HI) oral values highlighted significant non-carcinogenic dangers for adults and children through the oral exposure. At the same time, dermal contact posed a no risk for adults and a high risk for children. Most samples had carcinogenic risk (CR) values higher than the allowed limits (1.0E-4) for metals like Cadmium, chromium, and lead, suggesting carcinogenic effects across all age groups. The Monte Carlo approach-based health concern evaluation model assessed the 5th % CR oral values (child) as 0.00012, 0.0036, and 0.0088 for Cd, Cr, and Pb, respectively, indicating more significant potential dangers to children. Urgent and comprehensive water treatment measures are imperative to mitigate the identified carcinogenic and non-carcinogenic health risks in the study area. [ABSTRACT FROM AUTHOR]

Introduction: Bariatric surgery improves many obesity-related comorbidities, yet the literature remains inconclusive on the impact of bariatric surgery on asthma. Our primary objective was to identify the long-term impact of bariatric surgery on asthma severity and medication use. Methods: A retrospective review was completed of all patients with a diagnosis of asthma who underwent bariatric surgery over 10 years at a single institution. Primary outcomes were the number of asthma medications prescribed at five time points (preoperative, postoperative < 18 months, 19–36 months, 37–60 months, 60 + months) after bariatric surgery. Secondary outcomes were spirometry results and BMI. Results: There were 260 patients with 84.6% female predominance. There were 168 sleeve gastrectomy patients and 92 Roux-en-Y gastric bypass patients. Mean age was 47.6 ± 10.7 years, mean BMI was 46.0 ± 6.8 kg/m2, and 54.2% were previous tobacco users. The total number of patients on two or more asthma medications decreased from 46% preoperatively to 41% at 18 months, to 36% at 36 months, and to 32% at 60 months after surgery. The total number of patients free from asthma medication increased from 25% preoperatively to 33% at 60 months postoperatively. Asthma medication use decreased in both surgery groups, and neither operation demonstrated superiority. No significant improvement nor differences were found between groups at any time point regarding FEV1/FVC ratio spirometry measures. Conclusion: Bariatric surgery reduces the use of medications taken for management of asthma. The amount of asthma medication usage decreases with time and is sustained at 60 months after bariatric surgery. [ABSTRACT FROM AUTHOR]

Conduit arterial disease in chronic kidney disease (CKD) is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to humans with CKD stage 4-5. Parathyroid hormone (PTH) and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased, and vascular smooth muscle cell (VSMC) transdifferentiation was absent. The CKD mice were not hypertensive, and cardiac hypertrophy was absent. Freshly excised cardiac tissue respirometry (Oroboros) showed that ADP-stimulated O2 flux was diminished from 52 to 22 pmol/mg (P = 0.022). RNA-Seq of cardiac tissue from CKD mice revealed significantly decreased levels of cardiac mitochondrial oxidative phosphorylation genes. To examine the effect of activin A signaling, some Alport mice were treated with a monoclonal Ab to activin A or an isotype-matched IgG beginning at 75 days of life until euthanasia. Treatment with the activin A antibody (Ab) did not affect cardiac oxidative phosphorylation. However, the activin A antibody was active in the skeleton, disrupting the effect of CKD to stimulate osteoclast number, eroded surfaces, and the stimulation of osteoclast-driven remodeling. The data reported here show that cardiac mitochondrial respiration is impaired in CKD in the absence of conduit arterial disease. This is the first report of the direct effect of CKD on cardiac respiration. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relative contributions of handgrip and individual finger strength for the prediction of climbing performance in a bouldering competition. A secondary aim was to examine the influence of body size, bouldering experience, and training habits. Methods: Sixty-seven boulderers (mean [SD], age = 21.1 [4.0] y; body mass = 69.5 [9.8] kg) volunteered for this study. Data collection occurred immediately before an indoor bouldering competition and involved the assessment of handgrip and individual finger maximal force production using an electronic handheld dynamometer. The bouldering competition consisted of 70 routes graded V0 to V8, with higher point values awarded for completing more difficult routes. Stepwise multiple regression analysis was used to examine the relative contributions of handgrip and individual finger strengths, body mass, height, bouldering experience, and bouldering frequency to the prediction of performance scores in the competition. Results: Ring finger pinch strength, bouldering experience, and bouldering frequency significantly (P <.05) contributed to the model (R2 =.373), whereas body mass; height; full handgrip strength, as well as index, middle, and little finger pinch strengths did not. The β weights showed that ring finger pinch strength (β =.430) was the most significant contributor, followed by bouldering experience (β =.331) and bouldering frequency (β =.244). Conclusions: The current findings indicated that trainable factors contributed to the prediction of bouldering performance. These results suggest greater bouldering frequency and experience likely contribute to greater isolated individual finger strength, thereby optimizing preparation for the diverse handholds in competitive rock climbing. [ABSTRACT FROM AUTHOR]

Aims Right ventricular (RV) functional assessment is mainly limited to its longitudinal contraction. Dedicated three-dimensional echocardiography (3DE) software enabled the separate assessment of the non-longitudinal components of RV ejection fraction (EF). The aims of this study were (i) to establish normal values for RV 3D-derived longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their relative contributions to global RVEF, (ii) to calculate 3D RV strain normal values, and (iii) to determine sex-, age-, and race-related differences in these parameters in a large group of normal subjects (WASE study). Methods and results 3DE RV wide-angle datasets from 1043 prospectively enrolled healthy adult subjects were analysed to generate a 3D mesh model of the RV cavity (TomTec). Dedicated software (ReVISION) was used to analyse RV motion along the three main anatomical planes. The EF values corresponding to each plane were identified as LEF, REF, and AEF. Relative contributions were determined by dividing each EF component by the global RVEF. RV strain analysis included longitudinal, circumferential, and global area strains (GLS, GCS, and GAS, respectively). Results were categorized by sex, age (18–40, 41–65, and >65 years), and race. Absolute REF, AEF, LEF, and global RVEF were higher in women than in men (P < 0.001). With aging, both sexes exhibited a decline in all components of longitudinal shortening (P < 0.001), which was partially compensated in elderly women by an increase in radial contraction. Black subjects showed lower RVEF and GAS values compared with white and Asian subjects of the same sex (P < 0.001), and black men showed significantly higher RV radial but lower longitudinal contributions to global RVEF compared with Asian and white men. Conclusion 3DE evaluation of the non-longitudinal components of RV contraction provides additional information regarding RV physiology, including sex-, age-, and race-related differences in RV contraction patterns that may prove useful in disease states involving the right ventricle. [ABSTRACT FROM AUTHOR]

This study aims to assess how the performance of Change Control Boards (CCBs) influences the relationship between requirements uncertainty and the Time to Market (TTM) of software projects in emerging markets. We collected data through a structured questionnaire, conducting surveys in project-based IT organizations across various cities in Pakistan. This research adopts a quantitative approach, employing software project houses as the unit of analysis. We selected 38 software projects out of 50 using a multi-stage sampling method and analyzed the data using Smart PLS 4.0 and SPSS 23. The results reveal that requirements uncertainty has a significant impact on Time to Market (TTM) conditions. Our study concludes that the presence and effective performance of CCBs can substantially reduce TTM. Additionally, higher CCB performance can expedite TTM, particularly when requirements lack precision initially. The study underscores the profound influence of requirements uncertainty on TTM in software projects. It provides organizations with insights into the critical role of CCBs, the consequences of uncontrolled changes in the absence or ineffectiveness of CCBs, and how requirements uncertainty affects software project development and timelines. This research contributes to software management and product development processes by highlighting the importance of requirement engineering during the planning phase to address uncertainty issues and enhance CCB performance. [ABSTRACT FROM AUTHOR]

Background: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna® Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing. We also examined the impact of various PAM50 parameters on overall survival (OS) and progression-free survival (PFS). Results: We analyzed 42 unilateral breast cancer samples, with 18 classified as luminal A, 10 as luminal B, 8 as Human epidermal growth factor receptor 2 (HER2)-positive, and 6 as basal-like using PAM50. Interestingly, 17 out of the 42 samples (40.47%) showed discordant results between histopathological assessment and the PAM50 classifier. While routine IHC/FISH resulted in classification differences for a quarter to a third of samples within each subtype, all basal-like tumors were misclassified. Hormone receptor-positive tumors (hazard rate: 8.7803; p = 0.0085) and patients who had higher 10-year recurrence risk scores (hazard rate: 1.0539; p = 0.0201) had shorter OS and PFS. Conclusions: Our study supports the existing understanding of molecular subtypes in breast cancer and emphasizes the overlap between clinical characteristics and molecular subtyping. These findings underscore the value of gene expression profiling, such as PAM50, in improving treatment decisions for breast cancer patients. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a leading cause of morbidity and mortality particularly in older adults and patients with multiple metabolic comorbidities. Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with multisystem organ dysfunction in which patients develop symptoms of HF as a result of high left ventricular (LV) diastolic pressure in the context of normal or near normal LV ejection fraction (LVEF; ≤50%). Challenges to create and reproduce a robust rodent phenotype that recapitulates the multiple comorbidities that exist in this syndrome explain the presence of various animal models that fail to satisfy all the criteria of HFpEF. Using a continuous infusion of angiotensin II and phenylephrine (ANG II/PE), we demonstrate a strong HFpEF phenotype satisfying major clinically relevant manifestations and criteria of this pathology, including exercise intolerance, pulmonary edema, concentric myocardial hypertrophy, diastolic dysfunction, histological signs of microvascular impairment, and fibrosis. Conventional echocardiographic analysis of diastolic dysfunction identified early stages of HFpEF development and speckle tracking echocardiography analysis including the left atrium (LA) identified strain abnormalities indicative of contraction-relaxation cycle impairment. Diastolic dysfunction was validated by retrograde cardiac catheterization and analysis of LV end-diastolic pressure (LVEDP). Among mice that developed HFpEF, two major subgroups were identified with predominantly perivascular fibrosis and interstitial myocardial fibrosis. In addition to major phenotypic criteria of HFpEF that were evident at early stages of this model (3 and 10 days), accompanying RNAseq data demonstrate activation of pathways associated with myocardial metabolic changes, inflammation, activation of extracellular matrix (ECM) deposition, microvascular rarefaction, and pressure- and volumerelated myocardial stress. NEW & NOTEWORTHY Heart failure with preserved ejection fraction (HFpEF) is an emerging epidemic affecting up to half of patients with heart failure. Here we used a chronic angiotensin II/phenylephrine (ANG II/PE) infusion model and instituted an updated algorithm for HFpEF assessment. Given the simplicity in generating this model, it may become a useful tool for investigating pathogenic mechanisms, identification of diagnostic markers, and for drug discovery aimed at both prevention and treatment of HFpEF. [ABSTRACT FROM AUTHOR]

Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathways to limit myocardial IRI. Perfluorocarbon nanoparticles (PFC NP) were covalently coupled with an irreversible thrombin inhibitor, PPACK (Phe[D]-Pro-Arg-Chloromethylketone), and delivered intravenously to animals in a single dose prior to ischemia reperfusion injury. Fluorescent microscopy of tissue sections and 19F magnetic resonance images of whole hearts ex vivo demonstrated abundant delivery of PFC NP to the area at risk. Echocardiography at 24 h after reperfusion demonstrated preserved ventricular structure and improved function. Treatment reduced thrombin deposition, suppressed endothelial activation, inhibited inflammasome signaling pathways, and limited microvascular injury and vascular pruning in infarct border zones. Accordingly, thrombin inhibition with an extraordinarily potent but locally acting agent suggested a critical role for thrombin and a promising therapeutic strategy in cardiac IRI. [ABSTRACT FROM AUTHOR]

Despite the many advantages of isoproterenol (Iso)-induced models of cardiomyopathy, the extant literature suggests that the reproducibility of the Iso-induced stress cardiomyopathy phenotype varies considerably depending on the dose of Iso used, the mode of administration of Iso (subcutaneous vs. intraperitoneal), and the species of the animal that is being studied. Recently, we have shown that a single injection of Iso into female C57BL/6J mice provokes transient myocardial injury that is characterized by a brisk release of troponin I within 1 h, as well as a self-limited myocardial inflammatory response that is associated with increased myocardial tissue edema, inferoapical regional left ventricular (LV) wall motion abnormalities, and a transient decrease in global LV function, which were completely recovered by day 7 after the Iso injection (i.e., stress-induced reversible cardiomyopathy). Here we expand upon this initial report in this model by demonstrating important sexually dimorphic differences in the response to Iso-induced tissue injury, the ensuing myocardial inflammatory response, and changes in LV structure and function. We also provide information with respect to enhancing the reproducibility in this model by optimizing animal welfare during the procedure. The acute Iso-induced myocardial injury model provides a low-cost, relatively high-throughput small-animal model that mimics human disease (e.g., Takotsubo cardiomyopathy). Given that the model can be performed in different genetic backgrounds, as well as different experimental conditions, the acute Iso injury model should provide the cardiovascular community with a valuable nonsurgical animal model for understanding the myocardial response to tissue injury. [ABSTRACT FROM AUTHOR]

The present study aimed to assess: (1) whether a more active involvement of patients is associated with an improvement of clinical symptoms, global functioning, and quality-of-life; and (2) how patients' satisfaction with clinical decisions can lead to better outcome after 1 year. Data were collected as part of the study 'Clinical decision-making and outcome in routine care for people with severe mental illness (CEDAR)', a longitudinal observational study, funded by the European Commission and carried out in six European countries. Patients' inclusion criteria were: (a) aged between 18 and 60 years; (b) diagnosis of a severe mental illness of any kind according to the Threshold Assessment Grid (TAG) ≥ 5 and duration of illness ≥ 2 years; (c) expected contact with the local mental health service during the 12-month observation period; (d) adequate skills in the language of the host countries; and (e) the ability to provide written informed consent. The clinical decision-making styles of clinicians and the patient satisfaction with decisions were assessed using the Clinical Decision Making Style and the Clinical Decision Making Involvement and Satisfaction scales, respectively. Patients were assessed at baseline and 1 year after the recruitment. The sample consisted of 588 patients with severe mental illness, mainly female, with a mean age of 41.69 (±10.74) and a mean duration of illness of 12.5 (±9.27) years. The majority of patients were diagnosed with psychotic (45.75%) or affective disorders (34.01%). At baseline, a shared CDM style was preferred by 70.6% of clinicians and about 40% of patients indicated a high level of satisfaction with the decision and 31% a medium level of satisfaction. Higher participation in clinical decisions was associated with improved social functioning and quality-of-life, and reduced interpersonal conflicts, sense of loneliness, feelings of inadequacy, and withdrawal in friendships after 1 year (p < 0.05). Moreover, a higher satisfaction with decisions was associated with a better quality-of-life (p < 0.0001), reduced symptom severity (p < 0.0001), and a significantly lower illness burden associated with symptoms of distress (p < 0.0001), interpersonal difficulties (p < 0.0001), and problems in social roles (p < 0.05). Our findings clearly show that a higher involvement in and satisfaction of patients with clinical decision-making was associated with better outcomes. More efforts have to be made to increase the involvement of patients in clinical decision-making in routine care settings. [ABSTRACT FROM AUTHOR]

Sustainable consumption refers to the choice, purchase, use, and disposal of goods so as to enable all people to meet their present and future objective needs. However, panic caused by the gradual onset of the pandemic had a considerable impact on the behavior of consumption and purchase of medication, and the question remains whether sustainable consumption still matters during a crisis or not. The present study aims to analyze whether the pandemic has influenced the behavior of medication use among residents of Brasov County amid panic caused by the virus and to determine the primary sources of information on methods of the prevention and treatment of health conditions. The study focusses on the differences between the two target groups, young people, and adults, considering three socio-demographic factors, such as age, gender, and background. The present research uses two methods of data collection: an interview with 5 doctors and a questionnaire with 543 respondents. This research draws attention to the fact that the behaviors of purchasing and consuming medication during the COVID-19 pandemic has changed due to the spreading of the new virus and the state of emergency, as well as with medication use becoming less sustainable. The results showed that adults were more engaged in the panic buying of medication compared to young people during the pandemic; however, in normal times, young people use more medication. Our study shows that females tend to consume more medicines than males. Moreover, they are more susceptible for seeking media guidance and following advice from the digital realm, because they avoid going to the doctor, especially during the COVID-19 period. Depending on the environment of residence, it was found that people in rural areas generally tend to consume more medication than those in urban areas. However, during the pandemic, the drug use of this category of population has decreased because they do not tend to self-medicate and avoid visiting the doctor because of the fear of becoming contaminated. The results of the research could help to establish measures in order to prevent the panic buying of self-medication and pharmaceuticals, both during pandemics and in normal times, because such behaviors can have negative effects on both health and the environment. [ABSTRACT FROM AUTHOR]

Background: Data about the right ventricular (RV) mechanics adaptation to volume overload in patients with repaired tetralogy of Fallot (rToF) are limited. Accordingly, we sought to assess the mechanics of the functional remodeling occurring in the RV of rToF with severe pulmonary regurgitation.Methods: We used three-dimensional transthoracic echocardiography (3DTE) to obtain RV data sets from 33 rToF patients and 30 age- and sex- matched controls. A 3D mesh model of the RV was generated, and RV global and regional longitudinal (LS) and circumferential (CS) strain components, and the relative contribution of longitudinal (LEF), radial (REF) and anteroposterior (AEF) wall motion to global RV ejection fraction (RVEF) were computed using the ReVISION method.Results: Corresponding to decreased global RVEF (45 ± 6% vs 55 ± 5%, p < 0.0001), rToF patients demonstrated lower absolute values of LEF (17 ± 4 vs 28 ± 4), REF (20 ± 5 vs 25 ± 4) and AEF (17 ± 5 vs 21 ± 4) than controls (p < 0.01). However, only the relative contribution of LEF to global RVEF (0.39 ± 0.09 vs 0.52 ± 0.05, p < 0.0001) was significantly decreased in rToF, whereas the contribution of REF (0.45 ± 0.08 vs 0.46 ± 0.04, p > 0.05) and AEF (0.38 ± 0.09 vs 0.39 ± 0.04, p > 0.05) to global RVEF was similar to controls. Accordingly, rToF patients showed lower 3D RV global LS (-16.94 ± 2.9 vs -23.22 ± 2.9, p < 0.0001) and CS (-19.79 ± 3.3 vs -22.81 ± 3.5, p < 0.01) than controls. However, looking at the regional RV deformation, the 3D CS was lower in rToF than in controls only in the basal RV free-wall segment (p < 0.01). 3D RV LS was reduced in all RV free-wall segments in rToF (p < 0.0001), but similar to controls in the septum (p > 0.05).Conclusions: 3DTE allows a quantitative evaluation of the mechanics of global RVEF. In rToF with chronic volume overload, the relative contribution of the longitudinal shortening to global RVEF is affected more than either the radial or the anteroposterior components. [ABSTRACT FROM AUTHOR]

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams--Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams--Beuren syndrome deletions, which extended to include the NCF1 gene, were associated with lower blood pressure (BP) and reduced vascular stiffness. NCF1 encodes for p47phox, the regulatory component of the NOX1 NADPH oxidase complex that generates reactive oxygen species (ROS) in the vascular wall. Dihydroethidium and 8-hydroxyguanosine staining of mouse aortas confirmed that Eln heterozygotes (Eln+/-) had greater ROS levels than the wild-types (Eln+/+), a finding that was negated in vessels cultured without hemodynamic stressors. To analyze the Nox effect on ELN insufficiency, we used both genetic and chemical manipulations. Both Ncf1 haploinsufficiency (Ncf1+/-) and Nox1 insufficiency (Nox1-/y) decreased oxidative stress and systolic BP in Eln+/- without modifying vascular structure. Chronic treatment with apocynin, a p47phox inhibitor, lowered systolic BP in Eln+/-, but had no impact on Elnþ/þ controls. In vivo dosing with phenylephrine (PE) produced an augmented BP response in Eln+/- relative to Elnþ/þ, and genetic modifications or drug-based interventions that lower Nox1 expression reduced the hypercontractile response to PE in Eln+/- mice to Elnþ/þ levels. These results indicate that the mechanical and structural differences caused by ELN insufficiency leading to oscillatory flow can perpetuate oxidative stress conditions, which are linked to hypertension, and that by lowering the Nox1-mediated capacity for vascular ROS production, BP differences can be normalized. [ABSTRACT FROM AUTHOR]

The significance of cardiology screening of referees is not well established. Cardiovascular risk factors and diseases were examined in asymptomatic Hungarian elite handball referees undergoing extended screening: personal/family history, physical examination, 12-lead ECG, laboratory tests, body-composition analysis, echocardiography, and cardiopulmonary exercise testing. Holter-ECG (n = 8), blood pressure monitorization (n = 10), cardiac magnetic resonance imaging (CMR; n = 27) and computer tomography (CCT; n = 4) were also carried out if needed. We examined 100 referees (age: 29.6±7.9years, male: 64, training: 4.3±2.0 hours/week), cardiovascular risk factors were: positive medical history: 24%, overweight: 10%, obesity: 3%, dyslipidaemia: 41%. Elevated resting blood pressure was measured in 38%. Stress-ECG was positive due to ECG-changes in 16%, due to elevated exercise blood pressure in 8%. Echocardiography and/or CMR identified abnormalities in 19%. A significant number of premature ventricular contractions was found on the Holter-ECG in two cases. The CCT showed myocardial bridge or coronary plaques in one-one case. We recommended lifestyle changes in 58%, new/modified antihypertensive or lipid-lowering therapy in 5%, iron-supplementation in 22%. By our results, a high percentage of elite Hungarian handball referees had cardiovascular risk factors or diseases, which, combined with physical and psychological stress, could increase the possibility of cardiovascular events. Our study draws attention to the importance of cardiac screening in elite handball referees. [ABSTRACT FROM AUTHOR]

The article focuses on investigating vitamin D concentrations in patients with cluster headaches compared to those without cluster headaches. It study aimed to determine if there was a significant difference in vitamin D levels between the two groups and found that there was no substantial difference, suggesting that vitamin D deficiency may not play a significant role in cluster headache development.

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted. In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation. [ABSTRACT FROM AUTHOR]

Background: The quality of life (QOL) of the elderly can be influenced by numerous factors. We assessed QOL, cognitive functions, depression and clinical data in elderly aged 65 and over with the aim of analysing factors affecting their QOL. Methods: Semi-structured interviews were conducted with elderly over the age of 65, and their QOL, cognitive functions and depressive symptoms were assessed by validated clinical tests and screening tools. Results: The correlation between QOL scales and cognitive tests was not significant. In contrast, the results of depression scales showed significant negative correlation with the scores of the QOL scales. A better QOL was determined by lower age, lack of depressive symptoms, and higher scores in the QOL-AD (Alzheimer's disease) scale. Depressive mood has much more negative impact on the QOL of the elderly than cognitive impairment. Conclusions: Our results demonstrated a close correlation between QOL and depressive mood in the elderly. The early detection and effective management of affective and cognitive symptoms in the elderly can not only restore mental health but may also improve their QOL. [ABSTRACT FROM AUTHOR]

Dramatic cardiomegaly arising from gain-of-function (GoF) mutations in the ATP-sensitive potassium (KATP) channels genes, ABCC9 and KCNJ8, is a characteristic feature of Cantú syndrome (CS). How potassium channel over-activity results in cardiac hypertrophy, as well as the long-term consequences of cardiovascular remodeling in CS, is unknown. Using genome-edited mouse models of CS, we therefore sought to dissect the pathophysiological mechanisms linking KATP channel GoF to cardiac remodeling. We demonstrate that chronic reduction of systemic vascular resistance in CS is accompanied by elevated renin- angiotensin signaling, which drives cardiac enlargement and blood volume expansion. Cardiac enlargement in CS results in elevation of basal cardiac output, which is preserved in aging. However, the cardiac remodeling includes altered gene expression patterns that are associated with pathological hypertrophy and are accompanied by decreased exercise tolerance, suggestive of reduced cardiac reserve. Our results identify a high-output cardiac hypertrophy phenotype in CS which is etiologically and mechanistically distinct from other myocardial hypertrophies, and which exhibits key features of high-output heart failure (HOHF). We propose that CS is a genetically-defined HOHF disorder and that decreased vascular smooth muscle excitability is a novel mechanism for HOHF pathogenesis. [ABSTRACT FROM AUTHOR]

Both intrapersonal and interpersonal coordination dynamics have traditionally been investigated using relative phase patterns of in-phase (ϕ = 0°) and/or anti-phase (ϕ = 180°). Numerous investigations have demonstrated that coordination tasks that require other relative phase patterns (e.g., 90°) are difficult or near impossible to perform without extended practice. Recent findings, however, have demonstrated that an individual can produce a wide range of intrapersonal bimanual patterns within a few minutes of practice when provided integrated feedback. The present experiment was designed to directly compare intra- and interpersonal coordination performance and variability when provided Lissajous feedback or pacing metronome. Single participants (N = 12) and pairs of participants (N = 24, 12 pairs) were required to produce relative phase patterns between 0° and 180° in 30° increments using either pacing metronomes or Lissajous displays. The Lissajous displays involved a goal template and a cursor providing integrated feedback regarding the position of the two effectors. The results indicated both single and pairs of participants could effectively produce a large range of coordination patterns that typically act as repellers after only 6 min of practice when provided integrated feedback. However, single participants performed the in-phase coordination pattern more accurately and with less variability than paired participants, regardless of the feedback condition. These results suggest an advantage for intrapersonal coordination when performing in-phase coordination, possibly due to the stabilizing effect occurring via the neuro-muscular linkage between effectors. [ABSTRACT FROM AUTHOR]

Maternal obesity is correlated with cardiovascular disease in offspring, with a 1.3-fold increase in events observed in offspring of obese women. We have observed that obesity-exposed oocytes demonstrate impaired mitophagy and transmit damaged mitochondria to the offspring. Accordingly, we hypothesized that maternal obesity induces cardiac mitochondrial dysfunction in the offspring via transgenerational inheritance of abnormal oocyte mitochondria. We mated female mice fed a high-fat/high-sucrose (HFS) diet (or chow) with chow-fed males and assessed cardiac structure and function in their descendants that were chow fed in each generation. All F1 to F3 descendants bred via the female in each generation were non-obese and demonstrated cardiac mitochondrial abnormalities with crystal rarefaction and reduced oxygen consumption pointing to a transgenerational effect, while obese F0 dams’ hearts were unaffected. Furthermore, male offspring from F1 to F3 generations and female F1 and F2 offspring developed increased left ventricular (LV) mass (vs. chow-fed controls). Increased LV mass was also observed in offspring generated by in vitro fertilization of obesity-exposed oocytes and gestation in non-obese surrogates, ruling out a gestational environment effect. Contrary to our hypothesis, male F1 also transmitted these effects to their offspring, ruling out maternal mitochondria as the primary mode of transmission. We conclude that transmission of obesity-induced effects in the oocyte nucleus rather than abnormal mitochondria underlie transgenerational inheritance of cardiac mitochondrial defects in descendants of obese females. These findings will spur exploration of epigenetic alterations in the oocyte genome as potential mechanisms whereby a family history of maternal obesity predisposes to cardiovascular disease in humans. [ABSTRACT FROM AUTHOR]