bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effects of different types of bariatric surgeries on myocardial ischemia-reperfusion injury in non-obese non-diabetic rats
Authors: Polozov A S , Kornyushin O V , Sonin D L , Chervyak M V , Bulavinova M V , Masley V V , Istomina M S , Mukhametdinova D V , Neimark A E , Cheburkin Y V , Toropova Y G , Derkach K V , Shpakov A O , Galagudza M M 
Published: October 2021

Abstract

Introduction
Prior bariatric surgery (BS) significantly improves survival after myocardial infarction (MI). We assume that reduction in fatal MI after BSs could be attributed to the infarct size-limiting effect of the interventions and that this effect is not associated with an improvements in the diabetes mellitus and obesity.

Purpose
The aim of the study was to evaluate the infarct-limiting effect of various types of bariatric surgery in non-obese non-diabetic rats.

Methods
Rats were randomized into the following groups: no surgery (CON), sham surgery (SHAM), Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and ileal transposition (IT). 10 weeks after BS, the animals were subjected to ischemia-reperfusion, followed by histochemical determination of infarct area (IA) and no-reflow zone. At the 90th minute of reperfusion, all animals were injected intravenously with indocyanine green at a dose of 1 mg/kg to measure size of no-reflow zone.

Results
None of bariatric surgery procedures led to body weight reduction. A temporal high postprandial glucose was observed during oral glucose tolerance test (OGTT) in SG and RYGB rats at 30th minute followed by decrease at 120 minutes in comparison with SHAM. Blood insulin concentration increased at 60th minutes in response to OGTT glucose in the SG group compared to CON and SHAM. On the contrary, there was a decrease in insulin level in the IT group after 60 and 120 minutes. In RYGB, basal leptin was low at 120 minutes after glucose administration, while in SG it decreased at 60 and 120 minutes compared with CON and SHAM. Compared to the SHAM, the rats with RYGB and SG had lower IA by 22% and 10% and no-reflow size by 38% and 32%.

Conclusions
We demonstrated that both bariatric surgeries procedures, RYGB and SG, increase myocardial tolerance to ischemia-reperfusion injury in rats without diabetes and obesity. The infarct-limiting effect was accompanied by a significant decrease in basal plasma leptin level.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health Care of Russian Federation. Governmental funding research
Quantitative evaluation of coronary artery occlusion by 3D coronary volume reconstruction in a large animal model of acute myocardial infarction
Authors: Bruno V D , Sammut E , Gall A , Baz-Lopez D , Ascione R , Johnson T W 
Published: October 2021

Abstract

Background
Large animal models of acute myocardial infarction (MI) offer an important platform to test novel therapies. Consistency of infarct size between animals is critical to ensure an accurate assessment of therapies against control. However, anatomical variation challenges the ability to achieve a consistent infarct size and care must be taken to respect the principles of the 3Rs through minimisation of interventional fatalities.

Purpose
To standardise the approach of a closed chest model of balloon occlusion-facilitated MI. Novel 3-dimensional quantitative coronary angiography (3DQCA) software has been used retrospectively to identify a correlation between coronary volume occlusion and the extension of the myocardial scar.

Methods
Twenty-four Yorkshire pigs (mean weight 63.1±3 kg) underwent a closed chest MI model via percutaneous occlusion of the mid portion of the left anterior descending artery (LAD) for 60 minutes. The evaluation of the myocardial damage was obtained via cardiac magnetic resonance imaging (CMR) between 24 and 48 hours after the MI model (Acute) and at 4–5 weeks after MI (Chronic). Troponin I was also measured at multiple timepoints. 3DQCA reconstruction (QAngio XA 3D, Medis medical imaging systems NL) was generated from 2 angiographic projections with segmental analysis of all 3 major epicardial vessels including lumen volume, reference diameters, and segment length. The occlusive volume and vessel length was identified through co-registration of balloon position.

Results
At the short term timepoint, a significant correlation was found between the LAD volume occluded and the scar size as percentage of the LV mass (Spearman correlation 0.72, p value &lt;0.01, Fig. 1). Using Youden index analysis we identified a cut-off point of 32.8% of the LAD volume to determine a scar volume &gt;20% (Fig. 2). At chronic phase the correlation between these two variables was not significant, although there was a trend towards significance (p value = 0.06, Cor = 0.54). No significant correlation was found with serum Troponin I.

Conclusions
There is a significant correlation between the LAD volume occluded and the overall scar size in the acute phase and at least 32.8% of the LAD volume should be occluded to determine a scar volume &gt;20% of the entire LV. This indicates that a prospective measure of occluded LAD volume might minimise the intra-experimental variability in studies aiming to reduce infarct size and acute myocardial injury.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): This research work was supported by grants awarded to Professor Ascione: the British Heart Foundation (BHF) (BHF IG/14/2/30991, BHF RM/13/2/30158), and the Medical Research Council (MRC) (MRC MR/L012723/1).
Medical model of the diagnosis of multifocal atherosclerosis in patients with stable ischemic heart disease
Authors: Skorodumova E G , Kostenko V A , Skorodumova E A , Siverina A V , Rysev A V 
Published: October 2021

Abstract

Purpose
To build a model according to which it would be possible to predict the presence of multifocal atherosclerosis (MFA) in patients with stable forms of coronary heart disease.

Materials and results
The study included 102 patients with exertional angina, (62 men (60.8%) and 40 women (39.2%), mean age 64.2±12.7 years. A search was carried out among the parameters of the local register of patients with coronary artery disease (385 items), which had the strongest relationship and influenced the presence of MFA. These turned out to be: chronic obstructive pulmonary disease (r=0.270 at p=0.006, F-criterion 5.169 at p=0.07), chronic kidney disease (r=0.330 at p=0.001, F-criterion 12.203 at p=0.001), level of the coefficient of variation of erythrocytes (RDW-CV) (r=0.228 at p=0.004, F-criterion 2.022 at p=0.015), leukocyte count (r=0.243 at p=0.016, F-criterion 6.329 at p&lt;0.001), segmented neutrophils (r=0.231 at p=0.022, F-criterion 5.900 at p&lt;0.001), eosinophils (r=0.336 at p=0.02, F-criterion 1.900 at p=0.002), C-reactive protein (r=0.431 at p=0.01, F-criterion 3.40 at p=0.002) increase in liver density in the form of steatosis or fibrosis according to ultrasound scanning data (r=0.427 at p=0.042, F-criterion 5.579 at p=0.022), level blood sodium (r=0.476 at p=0.011, F-criterion 4.723 at p=0.011). The following parameters were combined into one integral model using the linear modeling method: RDW-CV, leukocyte count, segmented neutrophils, eosinophils, total blood cholesterol, increased liver density according to ultrasound scan data in the form of steatosis or fibrosis and chronic obstructive pulmonary disease. The F-criterion of the full model was 4.8, the coefficient of determination R2=0.407; R2&gt;0.3, significance level p=0.02. Thus, the resulting medical and mathematical model was generally acceptable. The threshold values of indicators were determined using the method of classification trees. This model visualized that the diagnostic levels of the scale values were: cholesterol level – 6.27 mmol/L, RDW-CV – 16.0%, neutrophils – 50%, eosinophils – 6%, leukocytes – 8.9%. In addition, the decision tree. shows that in individuals with cholesterol levels less than 6.27 mmol/l, without an increase in liver density according to ultrasound data, no obstructive pulmonary disease/RDW-CV level is less than 16%, only 1 patient had MFA, versus 24 patients who had cholesterol levels less than 6, 27 mmol/l, had an increase in liver density according to ultrasound, and the level of inflammatory granulocytes: neutrophils above 70%, eosinophils above 6% against the background of the total number of leukocytes 8.9x109 (l). In individuals with a GC above 6.27 mmol/L, MFA was observed in 14 people (100%)

Funding Acknowledgement
Type of funding sources: None. Diagnostic model
No dynamic changes in plasma ACE2 activity in patients with acute coronary syndrome
Authors: Hamilton G , Patel S K , Azraai M , Burrell L M 
Published: October 2021

Abstract

Background
Angiotensin converting enzyme 2 (ACE2) is expressed in the human myocardium and blood vessels and degrades the vasoconstrictor peptide angiotensin (Ang) II. Plasma ACE2 activity is elevated in patients with cardiovascular disease (CVD) and is a predictor of major adverse cardiovascular events (MACE) in obstructive coronary artery disease. However, it is unknown whether acute coronary syndrome (ACS) causes dynamic changes in plasma ACE2 activity.

Purpose
We investigated dynamic changes in serial troponin-T and plasma ACE2 activity in patients presenting with ACS who underwent invasive coronary angiography (ICA).

Methods
Consecutive patients admitted with ACS from October-November 2019 were screened. Those meeting the Fourth Universal Definition of Myocardial Infarction who had both ICA and serial troponin-T testing were included. The study was approved by the hospitals Human Research Ethics Committee. All patients had routine plasma samples taken over 3 time-points for measurement of troponin-T; the same sample was used to measure plasma ACE2 activity. Catalytic ACE2 activity was measured using a validated, sensitive quenched fluorescent substrate-based assay. Serial median troponin and ACE2 activity levels were analysed using the Friedman test for repeated measures.

Results
Forty-nine patients were included. The mean age of participants was 63.9±11.0 years, and 36 (74%) patients were male. Overall, 16 (36%) patients presented with ST-elevation myocardial infarction (STEMI) and 29 (74%) with non-ST-elevation myocardial infarction (NSTEMI). Twenty-nine (59%) patients had a history of hypertension and 14 (29%) a history of ischaemic heart disease; 13 (27%) with priorMI, 11 (22%) had previous PCI and 2 (4%) had prior coronary artery bypass grafting. Over the 3 time points, there was a clear rise in median troponin-T levels representing myocardial injury (p&lt;0.001), with no change in median plasma ACE2 activity (p=0.23, table 1). There was no difference in median ACE2 activity in those presenting with STEMI vs. NSTEMI (6.9 [2.1–9.5] vs. 6.0 [1.8–12.1], p=0.87), nor in those who underwent PCI to a culprit lesion compared to those who did not have a culprit lesion stented (5.8 [0.9–10.5] vs. 7.3 [2.8–14.9], p=0.37).

Conclusions
Patients with ACS had higher plasma ACE2 levels compared to levels previously reported in healthy controls. There were no dynamic changes in ACE2 activity in the setting of ACS, despite a significant rise in troponin-T. These results suggest that plasma ACE2 levels reflect underlying endothelial dysfunction rather than acute myocardial injury or infarction. Studies are now underway to assess if plasma ACE2 activity in ACS predicts MACE.

Funding Acknowledgement
Type of funding sources: None. Table 1
Chondroitin sulfate n-acetylgalactosaminyltransferase-2 (ChGn-2) plays a significant role in cardiac remodeling and heart failure following pressure overload
Authors: Haryono A , Ikeda K , Nugroho D B , Kitagawa H , Igarashi M , Hirata K , Emoto N 
Published: October 2021

Abstract

Background
Cardiac extracellular matrix (ECM) is critically involved in cardiac homeostasis by providing mechanical support as well as modulating growth factor signaling. Cardiac ECM dysregulation has been shown in heart failure pathogenesis, and accumulation of chondroitin sulfate glycosaminoglycans (CS-GAGs) was previously shown to exacerbate heart failure by augmenting inflammation and fibrosis at the chronic phase. However, it remains unclear whether and the mechanism by which CS-GAGs cause cardiac dysfunction, especially at the acute phase.

Purpose
The purpose of this study is to elucidate the role of CS-GAGs in heart failure.

Methods
In this study, we analyzed the role of CS-GAGs in heart failure using mice with target deletion of chondroitin sulfate N-acetylgalactosaminyltransferase (ChGn)-2 that elongates CS chains of GAGs. Heart failure was induced by transverse aortic constriction (TAC) in mice. Since cardiac fibroblasts (CFs) are the primary cells for ECM production in the heart, we explored the role of CF-derived ECM in cardiomyocyte apoptosis. CFs were given stretch stimuli that mimic pressure overload conditions.

Results
Significant CS-GAGs accumulation was detected in the heart of WT mice after TAC, which was substantially reduced in the heart of ChGn2−/− mice. Unexpectedly, loss of ChGn-2 deteriorated left ventricular systolic dysfunction accompanied by augmented cardiac hypertrophy and increased cardiomyocyte apoptosis. Stretch stimuli increased ChGn-2 expression and enhanced GAG production in CFs. Interestingly, only conditioned medium (CM) derived from stretched CFs showed protective effects on cardiomyocyte death induced by doxorubicin. Degradation of CS-GAGs in CFs-derived CM by using Chondroitinase ABC abolished its cardioprotective effect. Further experiments revealed that this cardioprotective effect is at least partially through CS-GAGs-derived PI3K/AKT pathway activation via CD44.

Conclusion
Our data revealed that CF-derived GAGs protect cardiomyocytes from death in the acute phase of heart failure due to pressure overload; thus, insufficient GAGs production caused by loss of ChGn-2 exacerbated heart failure.

Funding Acknowledgement
Type of funding sources: None.
The long non-coding RNA Heat4 is upregulated in heart failure and decreases the immune response of non-classical monocytes
Authors: Kneuer J , Meinecke T , Weiss R , Gaul S , Haas J , Meder B , Garfias-Veitel T , Von Haehling S , Kogel A , Keller T , Speer T , Thiele H , Lurz P , Laufs U , Boeckel J.-N 
Published: October 2021

Abstract

Background and purpose
Activation of the immune system correlates with the severity and the prognosis of patients with heart failure (HF). This study aims to identify and characterize long non-coding RNAs (lncRNAs) as a potential mechanistic link between the pathophysiology of HF and the activation of the immune system.

Methods and results
Next-generation sequencing (NGS) studies identified a 2.05-fold increase of the lncRNA Heat4 in the blood of patients with HF compared to controls, which was validated in a larger cohort (HF: N=63; Controls: N=38; p&lt;0.05). Interestingly, the lncRNA Heat4 is encoded in the well-known immune receptor locus CD300, together with 8 CD300-receptors which are associated with activation of the immune system. To determine the cellular origin of Heat4 in blood, we performed MACS and identified Heat4 to be enriched in non-classical monocytes compared to classical monocytes (3.37-fold, p&lt;0.05). The expression of Heat4 in non-classical monocytes was further validated by single-cell RNA sequencing. Overexpression of Heat4 in monocytes decreased levels of pro-inflammatory cytokines such as TNFα (38.6% reduction, p&lt;0.05). Conversely, the knockdown of Heat4 resulted in elevated levels of pro-inflammatory cytokines, including IL6 (10.83-fold, p&lt;0.05) and TNFα (4.14-fold, p&lt;0.05). In a larger cohort including patients with HF, Heat4 was able to determine the prevalence of heart failure by AUC=0.734 (p&lt;0.05). Moreover, in a 4-year follow-up of the same cohort, Heat4 predicted mortality by AUC=0.789 (HF: N=63, Dead=32; Controls: N=38, Dead=0; p&lt;0.05).

Conclusion
The long non-coding RNA Heat4 is elevated in the blood of HF patients. Mechanistically, Heat4 limits the extent of the inflammatory response of non-classical monocytes. Therefore, Heat4 may provide a regulatory link between inflammation and HF.

Funding Acknowledgement
Type of funding sources: None.
Genetic variants as determinants of outcome in lamin A/C-related cardiac disease
Authors: Garcia Hernandez S , Ortiz-Genga M , Ochoa J P , Lamounier A , Fernandez X , Cardenas I , Garcia-Giustiniani D , Brogger M N , Fernandez G , Valverde M , Monserrat L , McKenna W J 
Published: October 2021

Abstract

Background
Current guidelines for the diagnosis and management of familial dilated cardiomyopathy highlight the variables “male sex” and “non-missense type variants” as risk factors for malignant ventricular arrhythmias.

Objective
Quantitative evaluation of prognostic differences between different LMNA variants associated with cardio-laminopathy.

Method
Analysis of cardiac event-free survival (sudden death, major arrhythmic events, death from heart failure and transplantation) with Kaplan-Meier approach in relation to gender & variant LMNA type. The data come from a specific database containing information on more than 1200 carriers of disease-causing LMNA variants. In the first analysis, the groups of comparison were truncating-type variants (LMNAtv) VS the global of pathogenic missense variants in the gene associated with cardiolaminopathy (LMNAm), segregated by gender. In the second analysis, it was considered missense LMNA affecting different residues (p.Arg190, p.Arg377 and p.Arg541), located in different functional domains, with enough data for comparison and with statistically different clinical behavior from that of global pathogenic variants in the gene. They were compared with the group of LMNAtv variants, as reference. The variants included were p.Arg377Cys/His, p.Arg541Cys/Ser/Gly/Pro/His and p.Arg190Trp/Gln/Pro, all of them pathogenic and associated with cardio-laminopathy.

Results
No significant differences were observed in survival between LMNAtv versus LMNAm variants (log rank=0.56) with slightly worse outcomes in males (log rank 0.03). Median survival time was 56 years for men compared to 60 years for women with LMNAtv, and 55 years compared to 66 years, respectively, among carriers of LMNAm (analysis A). In analysis B, statistically significant differences were observed between the groups considered (Log Rank p&lt;0.001). These differences were also clinically relevant (median survival time in groups p.Arg377, LMNAtv, p.Arg190 and p.Arg541 was 60, 58, 50 and 35 years, respectively). Importantly, more than 70% of the cardiac events observed were related to major ventricular arrhythmic episodes.

Conclusions
This quantitative analysis demonstrates that certain missense variants in LMNA may have a similar and even more adverse clinical course than the set of truncation-type variants. These findings highlight the relevance of the specific variant rather than the variant type in guiding actionable therapies to prevent adverse outcomes. Regarding the differences observed between genders, even though they are statistically significant, their magnitude could be clinically not relevant.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Health in Code
Current litigation - what can we learn?
Authors: Harvey Richard 
Published: October 2021

Abstract
This presentation explores the issues raised in the first presentation by examining current cases before European courts: (i) Union of Swiss Senior Women for Climate Protection v. Swiss Federal Council and Others. The application was rejected by the Swiss Federal Supreme Court on legal standing grounds - the heat stress-related aspects were not specific enough. The case has been appealed to the European Court of Human Rights. (ii) Youth for Climate Justice v. Austria, et al The European Court of Human Rights has dismissed a coordinated effort by 33 governments to overturn its October 2020 decision to fast-track the case. Governments had until May 27 2021 to submit their defences. The current status of both cases will be reviewed and the lessons for strategic litigation discussed.
Nutritional psychiatry: implications for public health
Authors: Jacka F 
Published: October 2021

Abstract
With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. The 20th century has seen major shifts in dietary intakes globally, with a marked increase in the consumption of sugars, snack foods, take-away foods and high-energy foods. At the same time, the consumption of nutrient-dense foods, such as high-nutrient vegetables and raw fruits, is diminishing. Poor diet is now recognized as the leading risk factor for illness and early mortality globally. However, there is now overwhelming body of evidence to tell us that unhealthy diet is also a key risk factor for psychiatric illnesses, including depression, anxiety and dementia. Current evidence highlights major developments in understanding the mechanistic pathways linking diet to neurodevelopmental and neurodegenerative outcomes. New research activities are underway in this field, however there is already a strong evidence for diet as a key strategy for improving mental and brain health. There is a need to address all the recent advances in the public health and policy imperatives and for translating the evidence into improvements to individual and population health.
Magic bullet for public mental health: is cheap also cheerful?
Authors: Ali S 
Published: October 2021

Abstract
The Global Burden of Disease studies have consistently shown that mental health challenges are among the leading causes of lost disability-adjusted life years (DALYs), and represent one of the biggest public health problems of our time. The World Health Organization (WHO) estimates that around 450 million people struggle with mental health issues at any one time - this is only exacerbated by the current pandemic. Now, more than ever, there is strong argument for WHO proposition of ‘no health without mental health'. The current weapon for tackling the mental health crisis is largely based on a medical model. After decades of medication-based treatments, this model has seen a significant shift towards ‘talking therapies'. More so, the last few years, particularly during the pandemic, virtual care has become the significant mechanism of providing mental health support. Our research has identified a number of challenges in the current approach that remain unaddressed: 1) recovery rates from talking therapies are low and inequitably distributed; 2) improvements in mental health depend more on individual-level factors and circumstances than the person providing therapy; and 3) most people who recover from mental health problems relapse within a year. In this session, we will discuss these findings and ask: are we approaching mental health with the right approach, or is this time to rewrite the vows between public health and primary care to tackle the mental health crisis?