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In a mouse model, plasminogen activator inhibitor-1 prevented cardiac rupture after a heart attack, as did the matrix metalloproteinase-inhibitor TIMP-1. Cardiac rupture is a serious complication of heart attack, accounting for up to 31% of all in-hospital deaths.

The human transcriptome comprises a complex network of coding and non-coding RNAs implicated in a myriad of biological functions. Non-coding RNAs exhibit highly organized spatial and temporal expression patterns and are emerging as critical regulators of differentiation, homeostasis, and pathological states, including in the cardiovascular system. This review defines the current knowledge gaps, unmet methodological needs, and describes the challenges in dissecting and understanding the role and regulation of the non-coding transcriptome in cardiovascular disease. These challenges include poor annotation of the non-coding genome, determination of the cellular distribution of transcripts, assessment of the role of RNA processing and identification of cell-type specific changes in cardiovascular physiology and disease. We highlight similarities and differences in the hurdles associated with the analysis of the non-coding and protein-coding transcriptomes. In addition, we discuss how the lack of consensus and absence of standardized methods affect reproducibility of data. These shortcomings should be defeated in order to make significant scientific progress and foster the development of clinically applicable non-coding RNA-based therapeutic strategies to lessen the burden of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background In the UK, national directives have resulted in centralisation of oesophago-gastric cancer in large National Health Service (NHS) centres. NHS cancer centres have treatment pathway targets of 30 and 60 days to complete staging and start treatment. We have treated patients with oesophago-gastric cancer both in the NHS and private sector. The purpose of this study was to assess whether the treatment and outcome was different for patients treated in the private sector. Methods Data was collected prospectively of consecutive oesophago-gastrectomies for OGJ cancer performed by a single surgeon from 2003–2013. After diagnosis all cases were discussed in a multi-disciplinary meeting. Neo-adjuvant chemotherapy was offered to all patients deemed to have N1 or T3 disease according to MAGIC and OEO5 study protocols. Patients in these stage groups who declined neo-adjuvant chemotherapy were offered adjuvant chemotherapy or chemo-radiation. During the first 2 years oesophago-gastrectomy was performed by open surgery, where-after laparoscopic and thoracoscopic techniques were introduced. Data analysis was by logistic regression using SPSS software. Results 204 resections for OGJ cancer were performed during. The average age was 63 years (range 41–82), 85% had adenocarcinoma, and 78% of patients received neo-adjuvant chemotherapy. The pathological staging was pN1 64%, pT0 5%, pT1 17%, pT2 32%, pT3 42%, pT4 3%. The median hospital stay was 14 days (range 6–210), and the in-hospital mortality was 2.5%. 40 patients had their treatment in private hospitals. There was no difference in the demographics, histology, tumour stage, percentage receiving chemotherapy, type of chemotherapy or surgery between private and NHS patients. Private patients completed their staging tests within 9 days (range 126) of endoscopy and started definitive treatment within 10 days (range 2–59) of the last staging test. 26 of the 40 patients (65%) operated on in the private sector survived 5 years which was more than the 39% of NHS patients who survived 5 years (P  = 0.0084). Conclusion Treatment for oesophago-gastric cancer is evolving. Patients with oesophago-gastric cancer treated in the private sector have better long-term survival than NHS patients which might be related to their shorter treatment pathway. Further studies will elucidate the changes in treatment required to improve survival for all UK patients with oesophago-gastric cancer. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

We present a Monte Carlo simulation study of suspensions of hard ellipsoids of revolution. Based on the spatial fluctuations of the orientational order, we have computed the Frank elastic constants for prolate and oblate ellipsoids and compared them to the affine transformation model. The affine transformation model predicts the right order of magnitude of the twist and bend constant but not of the splay constant. In addition, we report the observation of a stable nematic phase at an aspect ratio as low as 2.5. [ABSTRACT FROM AUTHOR]

Abstract Background The HL7 Clinical Document Architecture (CDA) constrains the HL7 Reference Information model (RIM) to specify the format of HL7-compliant clinical documents, dubbed CDA documents. The use of clinical terminologies such as SNOMED CT® further improves interoperability as they provide a shared understanding of concepts used in clinical documents. However, despite the use of the RIM and of shared terminologies such as SNOMED CT®, gaps remain as to how to use both the RIM and SNOMED CT® in HL7 clinical documents. The HL7 implementation guide on Using SNOMED CT in HL7 Version 3 is an effort to close this gap. It is, however, a human-readable document that is not suited for automatic processing. As such, health care professionals designing clinical documents need to ensure validity of documents manually. Results We represent the CDA using the Ontology Web Language OWL and further use the OWL version of SNOMED CT® to enable the translation of CDA documents to so-called OWL ontologies. We formalize a subset of the constraints in the implementation guide on Using SNOMED CT in HL7 Version 3 as OWL Integrity Constraints and show that we can automatically validate CDA documents using OWL reasoners such as Pellet. Finally, we evaluate our approach via a prototype implementation that plugs in the Open Health Workbench. Conclusions We present a methodology to automatically check the validity of CDA documents which make reference to SNOMED CT® terminology. The methodology relies on semantic technologies such as OWL. As such it removes the burden from IT health care professionals of having to manually implement such guidelines in systems that use HL7 Version 3 documents.

Hypertension and/or aging impose stress on the heart with consecutive cardiac hypertrophy, inflammation and fibrosis, processes that lead to heart failure. Our group has previously shown that non-structural matrix proteins such as TSP-2 and SPARC are critical during hypertension, fibrosis, and age-related cardiac dysfunction. Osteoglycin (OGN) is a class III member of the small leucine rich proteoglycans, and was recently identified as a marker of increased left ventricular mass in a study using genomics in recombinant inbred hypertensive rat strains. Its precise biological role in cardiac remodeling, however, remains unclear. We hypothesize that OGN will influence cardiac hypertrophy and fibrosis and hence is critical in the cardiac response during hypertension and aging.We show in young adult mice (3 months old) that hypertension-induced pressure overload of the heart causes two phases of cardiac fibrosis, following 28 days of angiotensin-II (AngII) infusion. The first phase develops between days 3 to 7 after the AngII-treatment and consists of diffuse interstitially deposited loose fibers. During the second wave of fibrosis, which starts at 14 days, these loose fibers transition into more localized scars of denser collagens. Interestingly, the expression of OGN mRNA also shows a biphasic response, significantly decreasing prior to each phase of fibrosis, at day 1 (96% decrease, p=0.002) and day 14 (84% decrease, p=0.004) respectively. Moreover, hypertension causes exaggerated cardiac fibrosis (7.54±1.58 vs. 3.65±0.62 %, p=0.04) and increased heart weight to body weight ratios (6.39±0.31 vs. 5.42±0.17 mg/g, p=0.01) in young adult OGN null mice when compared to WT littermates, but no differences in the amount of infiltrating leukocytes (31.48±9.82 vs. 36.32±18.75 cells/mm2), after 28 days of AngII infusion. In addition, aging results in decreased cardiac function, as measured by ejection fraction, in 18 months versus 3 months old OGN null mice (42.65±2.74 vs. 58.05±1.37 %, p=0.0001), which is absent in WT mice (51.01±3.11 vs. 53.01±1.67 %, p=0.62). Furthermore, a follow-up study in WT and OGN null mice showed a decrease in stroke volume over time in the OGN null mice (39.30±2.90 μl at 6 months, 35.54±1.95 μl at 12 months and 31.13±1.29 μl at 18 months, p=0.04 between 6 and 18 months) but not in the WT mice (41.61±2.02 μl at 6 months, 39.04±1.95 μl at 12 months and 41.04±3.05 μl at 18 months). Collectively, these data suggest that OGN regulates cardiac fibrosis during pressure overload and is therefore important in the remodeling response to hypertension and aging. [ABSTRACT FROM AUTHOR]

Purpose: Despite major advances in the treatment of cardiovascular diseases, heart failure (HF) remains one of the top causes of death world-wide. The implications of microRNAs in this process are well accepted but still only incompletely understood. The microRNAs 221-3p and 222-3p are processed from a common precursor and share the same seed sequence and thus form the microRNA-221/222 family (miR-221/222). Both microRNAs were found to be involved in myoblast differentiation and are upregulated after aortic banding in mice. We therefore hypothesized that the miR-221/222 family is involved in the pathophysiology of cardiac hypertrophy and failure upon pressure overload.Methods and results: In a genome wide screen for microRNAs regulated in human dilated cardiomyopathy, we found miR-222 levels to be significantly decreased (p<0.01). MiR-221/222 were also downregulated in neonatal rat cardiomyocytes (nRCMs) upon stimulation with the pro-hypertrophic compound phenylephrine (PE) (p<0.05). Interestingly, the overexpression of these miRs in nRCMs using mimics significantly blunted the induction of the hypertrophy markers Bnp and skeletal alpha actin (Acta1) in nRCMs upon stimulation with PE.To investigate the role of miR-221/222 in pressure overload-induced heart failure, we simultaneously injected anti-miR-221 and anti-miR-222 antisense oligonucleotides (ASOs) or scrambled control oligonucleotides (SCOs) in male C57BL/6 mice 3 days before implanting angiotensin II-filled osmotic minipumps (AngII, 2.5 mg/(kg d)). After 4 weeks, we assessed cardiac function and histology as well as molecular changes in the left ventricle. Surprisingly, we did not find an effect of miR-221/222 inhibition on overall cardiac hypertrophy after AngII infusion (HW/TL: 8.04 vs 7.92 mg/mm, p>0.05). However, interstitial fibrosis was significantly increased upon AngII stimulation in mice that received miR-221/222 ASOs as compared to SCOs (6.1 vs 3.7% LV area, p<0.05). On the mRNA level, these mice also showed a 2.9-fold higher induction of Anp upon AngII stimulation (p~0.10), in line with anti-hypertrophic effects of miR-221/222 mimics shown in vitro.Conclusions: Taken together, our results indicate a protective effect of the microRNA-221/222 family in the stressed heart. Inhibition of miR-221/222 prior to pressure overload in mice led to increased fibrosis indicating adverse remodeling. In vitro, a direct effect of miR-221/222 overexpression on the hypertrophic response of nRCMs could be shown. Further experiments will aim at identifying the function of the miR-221/222 family both in cardiac fibroblast and cardiomyocytes. [ABSTRACT FROM PUBLISHER]

Cardiac hypertrophy and consequent contractile dysfunction continue to burden Western society. Cardiomyocyte cyclic AMP (cAMP) and calcium are driving forces behind cardiomyocyte contraction. Distortion of their balance may induce HF, but specific therapies aiming at restoring physiological cAMP/calcium signaling are lacking.We recently identified microRNA-139 (miR-139) to be downregulated in failing human hearts. MiR-139 resides in the phosphodiesterase gene PDE2A and is predicted to target several phosphodiesterase messengers. In view of the central role of phosphodiesterases in controlling cardiac cAMP and calcium signaling, we hypothesized that miR-139 may affect HF progression by fine-tuning cAMP and calcium balances.Adeno-associated virus serotype 9 (AAV9), either empty control or expressing pre-miR-139, was administered to male C57Bl/6J mice. After allowing transgene expression for 3 weeks, mice were subjected to sham treatment or 4 weeks of pressure overload by subcutaneous Angiotensin II infusion (AngII, 2,5 mg/(kg·d). MiR-139 overexpression mildly aggravated HF development upon AngII with echocardiographically measured fractional shortening decreasing by 24±7% in AAV9-control AngII and by 46±5% in AAV9-pre-miR-139 AngII (n>11/group; p=0.14). In AAV9-control mice, AngII infusion led to concentric hypertrophy with an increased relative wall thickness (RWT) of 35±6%, whereas mice overexpressing miR-139 showed a rather eccentric form of hypertrophy with an increased RWT of 14±7% (p<0.05). The fraction of unphosphorylated cardiac troponin I (cTnI), a substrate of the cAMP dependent protein kinase A (PKA), tended to increase upon AngII infusion only in mice overexpressing miR-139 (n=4/group; p=0.11), indicating a reduced relaxation rate due to increased calcium sensitivity, a feature commonly observed in HF. Complimentary to these data, in vivo knockdown of mir-139 by cholesterol-tagged antagomiRs (20mg/kg) on three consecutive days before start of AngII infusion dampened the development of pressure overload-induced cardiac hypertrophy (increase in HW/TL: ctrl: 48±10%, n=4; antagomiR: 25±7%, n=7; p=0.16).In conclusion, cardiac downregulation of miR-139 upon pressure overload is a protective response to preserve cardiac function. AAV9-mediated overexpression of miR-139 promotes cardiac dilation and predisposes to HF. Upcoming experiments will aim at defining the molecular mechanism by which miR-139/phosphodiesterase signaling affects cardiac pathophysiology. [ABSTRACT FROM PUBLISHER]

The article presents an abstract of research paper on chronic dilated cardiomyopathy submitted at the 5th European Workshop on Immune-Mediated Inflammatory Diseases held at Barcelona, Spain, on December 1-3, 2010.

An abstract of the article "Matrix metalloproteinases-1 and -9, new biomarkers of human cardiac allograft rejection," by D. Vanhoutte and colleagues is presented.

An abstract of the article "Thrombospondin-2 guards against aging-related cardiomyopathy by increasing beta 1-integrin mediated signaling," by M. Swinnen and colleagues is presented.

An abstract of the study "Increased Expression of Syndecan-1 Protects Against Cardiac Dilatation and Dysfunction After Myocardial Infarction," by D. Vanhoutte and colleagues is presented.

An abstract of the study "Inhibition of urokinase and matrix metalloproteinases prevents left ventricular hypertrophy and cardiac failure during hypertension," by S. Heymans and colleagues is presented.

An abstract of the article "u-PA-inactivation or TIMP-1-overexpression prevents cardiac injury and dysfunction during acute viral myocarditis in mice," by S. Heymans et al., is presented.

• A model mixture representative of the plastic waste was established. • Pyrolysis of virgin and polymer mixtures was investigated. • The decomposition process is accelerated with polymer mixtures. • The amount of aromatics is higher than expected for PP/ PE and model mixture. Recovery of plastic waste is becoming crucial since the amount of such waste increases continuously. The objective of this study is to investigate the potential of the pyrolysis technique for the recovery of plastic waste. In that frame, the influence of temperature (550°C or 600°C) on the pyrolysis of pure polypropylene (PP), polyethylene (PE), polystyrene (PS) and polyethylene terephthalate (PET) was first studied. It is shown that whatever the type of polymer, aromatic compounds are mainly formed and could reach 55wt.-% of the oil fraction for PP and 31wt.-% for PE at 550°C. In a second step, a PP/PE mixture and a model mixture representative of the packaging plastic waste stream were pyrolyzed to investigate the influence of a combination of polymers on the proportions and composition of the different fractions. The pyrolysis of the polymer mixtures shows that, even if the aromatic compounds formed are similar to those obtained for the virgin polymers, the proportion of aromatic compounds is much more important than when the polymers are pyrolyzed alone. Indeed, mixing PE with PP at a 50/50 ratio does not affect the amount of liquid, gas and solid fractions but leads to the formation of a higher quantity of xylene (39 wt-%) at 550°C. The combination of the plastics in the model mixture has also led to a decrease of the amount of waxy compounds. Furthermore, it was shown that a higher amount of aromatics than expected was formed. As a conclusion, this study demonstrates that pyrolysis is an effective technique to recover plastic waste as aromatic compounds for the petroleum industry. In the specific conditions used in this study (proposed model mixture and pyrolysis conditions), it will favor the idea that sorting is not needed to recover plastic waste through pyrolysis since aromatics formation is favored when the stream is composed of a mixture of polymers. [ABSTRACT FROM AUTHOR]

Gene therapy has recently become a reality in the treatment of cardiovascular diseases. Strategies to modulate gene expression using antisense oligonucleotides or small interfering RNA are proving to be safe and effective in the clinic. Adeno-associated viral vector-based gene delivery and CRISPR-Cas9-based genome editing have emerged as efficient strategies for gene delivery and repair in humans. Overall, gene therapy holds the promise not only of expanding current treatment options, but also of intervening in previously untackled causal disease mechanisms with little side effects. This scientific statement provides a comprehensive overview of the various modalities of gene therapy used to treat heart failure and some of its risk factors, and their application in the clinical setting. It discusses specifically the possibilities of gene therapy for hereditary heart diseases and (non)-genetic heart failure. Furthermore, it addresses safety and clinical trial design issues and challenges for future regulatory strategies., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL., (© 2024. The Author(s).)