bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Presentation No. 64 Elevated soluble glycoprotein VI, a specific predictor of bleeding risk in patients with chronic coronary syndromes undergoing percutaneous coronary intervention
Authors: Lahu* Shqipdona , Adler* Kristin , Ndrepepa Gjin , Mayer Katharina , Hein-Rothweiler Ralph , Bernlochner Isabell , Laugwitz Karl-Ludwig , Kastrati Adnan , Gawaz Meinrad , Massberg Steffen , Münch Götz
Published: October 2022

Background

Whether plasma levels of soluble glycoprotein VI (sGPVI) are able to predict ischemic or bleeding risk in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI) is not known. The objective of this study was to answer this question.

Material and methods

The present study included 317 patients out of 334 patients of the ISAR-PLASTER trial (randomized trial of 2 doses of revacept vs. placebo), who underwent PCI for CCS and had baseline plasma sGPVI levels available. Patients were categorized into three groups according to tertiles of sGPVI: low (n = 106; sGPVI ≤ 9.5 ng/ml), intermediate (n = 106; sGPVI ≤ 16.2 ng/ml) and high tertile of sGPVI (n = 105; sGPVI ≥ 16.5 ng/ml). The composite of death and myocardial injury (MI) at 48 hours after randomization served as a measure of ischemic risk, and Bleeding Academic Research Consortium (BARC) type 1 to 5 bleeding at 30 days as a measure of bleeding risk.

Results and conclusions

Baseline plasma levels of sGPVI (before PCI and revacept administration) correlated with bleeding (bleeding incidence among low, intermediate and high sGPVI tertile: 11.8%, 13.6%, and 25.8%, respectively; P = 0.005), but not with ischemic events (incidence of death/MI among low, intermediate and high sGPVI tertile: 25.0%, 21.9%, and 26.9%, respectively; P = 0.70). Revacept did not interact with these associations. Elevated plasma sGPVI levels are associated with an increased risk of bleeding but not ischemic complications after PCI in patients with CCS.

Funding

German Center for Cardiovascular Research, Deutsches Herzzentrum München, Federal Ministry of Education and Research, and advanceCOR.
Oral Presentation No. 67 Thrombotic Events in COVID-19 Patients Admitted at Chinese General Hospital and Medical Center
Authors: Santos Joel , Beltran Jenny
Published: October 2022

Background

Thrombosis is among the most prominent and concerning complications associated with COVID-19. These thrombotic events have been associated in progression of ARDS and morbidity and mortality.

Methodology

Retrospective cohort study of 203 patients ≥ 18 years old with confirmed COVID-19 admitted on tertiary referal hospital from January to December 2021. All thrombotic events were established by clinical signs and symptoms, ultrasonography and CT scan.

Results and conclusions

Sixty five (32%) patients out of 203 developed thrombotic complications. The most common thrombotic event was pulmonary embolism (36%), followed by myocardial infarction (28%), cerebrovascular infarct (27%), DVT (25%), acute limb ischemia (7%) and lastly, mesenteric ischemia (6%). There were significant differences in demographic and clinical profile among COVID-19 patients with and without thrombotic events. Thrombosis was more commonly seen in advanced age (≥ 75 years, 49.2% vs. 23.9%; RR2.06, CI1.4–3.03), severe infection (severe, 24.6% vs. 19.6%; RR1.2, CI0.8–1.9 and critical and 47.7% vs. 10.1%; RR3.2, CI2.2–4.6, respectively), ICU admission (20% vs. 3.6%; RR2.6, CI1.8–3.7). Other complications were acute respiratory syndrome (83% vs. 43.5%; RR3.8, CI2.1–6.9), acute kidney injury (50.8% vs. 19.6%; RR2.46, CI1.68–3.6), major bleeding (9.2% vs. 0%; RR2.07, CI1.83–2.34), clinically relevant non-major bleeding (30.8% vs. 10.1%; RR2.21, CI1.52–3.22), hospitalization > 21 days (29.2% vs. 13%; RR1.85, CI1.24–2,76), and all-cause mortality (60% vs. 3.6%; RR5.42, CI3.76–7.82). Patients who developed thrombosis had prolonged duration of immobilization, higher Padua prediction and CURB 65 scores, with wall motion abnormality in 2D-echocardiography, elevated D-dimer and pro-BNP, reduced oxygen saturation an often received invasive and non-invasive ventilation and hemoperfusion. Majority of patients was given thromboprophylaxis in both groups; hence a significant difference was not found. An institutional thromboprophylaxis protocol is needed in managing COVID-19 patients at risk for thrombotic events.
Poster No. 027 Clinical, echocardiographic, analytic and anatomical parameters: which are the main prognostic factors in hospitalized patients with acute pulmonary embolism?
Authors: Duarte Fabiana , Inês Barradas M , Oliveira Luís , Dos Santos Inês Coutinho , Machado Carina , Dourado Raquel , Martins Dinis
Published: October 2022

Background

Acute pulmonary embolism (PE) is a life-threatening disease and an early diagnosis and herapy are crucial. Several parameters for risk stratification have been evaluated and it's important to assess their impact on clinical practice.

Objective

We assessed four different parameters (clinical, echocardiographic, analytical and anatomical imaging parameters) - PESI class; PESI-Echo score; lactate and troponin I values and central or peripheral thrombi location. We determined a composite outcome of adverse events: shock, acute ventilatory failure, severe bleeding events or in-hospital mortality.

Methods

Retrospective single center analysis including 131 patients admitted for PE.

Results

Mean age of 67.6 ± 15.3 years-old and 71% patients were female. Eighty patients (63.4%) had arterial hypertension, 27.4% had a recent hospitalization or surgery and 16% an active neoplasm disease. According to the PESI classification, 29.8% of the patients were in class V, 26.7% in class III and 17.6% in class II. This classification had a weak positive correlation with the outcome (P < 0.001; r = 0.37) as PESI-Echo score (p 0.018; r = 0.36). The majority (72.2%) of the in-hospital adverse events occurred in PESI class V patients. Analytic parameters determined at hospital admission had a good discriminative power to predict the outcome, mainly lactate value (AUC 0.864; P < 0.001). PESI-Echo score presented the best discriminative power (AUC 1.0), followed by PESI class (AUC 0.925) and lactate (AUC 0.856). The cut-off value for PESI-Echo was 211.

Conclusion

The association of clinical and echocardiographic parameters was superior as a predictor of adverse events when compared with their isolated use.
Poster No. 054 Genetic variation in the TCF21 gene is associated with the severity of coronary artery disease
Authors: Sá Débora , Mendonça M I , Santos M , Temtem M , Sousa A C , Rodrigues M , Henriques E , Freitas S , Borges S , Guerra G , Freitas A I , Ornelas I , Drumond A , Palma Dos Reis R
Published: October 2022

Introduction

In vitro studies demonstrated that targeted deletion of the transcription factor encoding gene TCF21, was associated with vascular smooth muscle cell disruption. Recent research showed that TCF21 expression contribute to fibrous cap formation, preventing heart attacks.

Purpose

Analyse the TCF21 rs12190287 gene and evaluate its association with atherosclerosis severity measured according to the coronary angiogram patients´ data. Methods: Prospective study with 1,639 coronary artery disease (CAD) patients (mean age 53.4 ± 7.8 years). Two age groups (< 55 and > 55 years) were stratified and analyzed. TCF21 rs12190287 G > C was genotyped in all patients. The severity of CAD was graded according to the number of obstructed coronary arteries with at least 70% narrowed lumen. Chi-squared tests and multivariate logistic regression models were analysed.

Results

The CC genotype was associated with > 70% obstructive lesions (vascular disease rate, 48.1%). Contrariwise, the GG wild genotype was associated with less severe obstructive disease (19.5%) (P = 0.003). When we stratified the TCF21 genotypes per age group (55 years), the CC genotype in the younger group had more obstructed disease (47.4%) when compared with GG (18.8%) (P = 0.012), but this effect was not significant in the older group. Multivariate analysis (logistic regression) showed that the CC genotype had a high risk of multivessel coronary disease (OR = 2.88; P = 0.001) than GG.

Conclusion

This work shows that the TCF21 wild genotype protects against CAD severity. In contrast, the CC genotype is associated with an increased risk of CAD severity.
Oral Presentation No. 114 Small-bore aspiration thrombectomy versus catheter-directed thrombolysis in intermediate-high risk acute Pulmonary Embolism
Authors: Martinho Mariana , Calé Rita , Pereira Ana Rita , Ferreira Filipa , Alegria Sofia , Morgado Gonçalo , Martins Cristina , Ferreira Melanie , Gomes Ana , Judas Tiago , Gonzalez Filipe , Lohmann Corinna , Repolho Débora , Santos Pedro , Pereira Ernesto , Loureiro Maria José , Pereira Hélder
Published: October 2022

Introduction

Catheter-directed thrombolysis (CDT) and mechanical thrombectomy (MT) are treatment options in intermediate-high risk pulmonary embolism (IHRPE).

Purpose

Compare the efficacy and safety of CDT and MT in IHRPE.

Methods

Retrospective single-centre study of consecutive IHRPE patients (pts) since 2018, treated with CDT (5Fr Cragg-McNamara device) or MT (Indigo MT system, Penumbra 8Fr). Clinical success at 48h was defined as survival and haemodynamic (HD) stabilization, oxygenation improvement or decrease in pulmonary hypertension (PH)/right heart strain. MACE during follow-up (FUP) was a composite endpoint of cardiovascular mortality, PE recurrence, chronic thromboembolic PH and heart failure hospitalization. Safety endpoint was defined as Major bleeding (BARC3).

Results

Of 25 pts, 60% were submitted to MT and 40% to CDT. Age (68.6 ± 15.6 vs. 62.7 ± 16.4, P = 0.381), Charlson Comorbidity Index (4.2 ± 1.9 vs. 2.9 ± 2.0, P = 0.121) and PESI score (103.2 ± 40.6 vs. 119.8 ± 46.2, P = 0.410) were similar. MT had increased fluoroscopy time (43.0 ± 19.1 vs. 10.1 ± 6.2 min, P < 0.001) and procedure time (115 ± 63 vs. 45 ± 18 min, P = 0.009). Success at 48 h was similar (80% MT vs. 90% CDT; P = 0.626). Severe adverse events related with the technique happened in 2 pts in MT (1 death, 1 macroembolization) and 1pt in CDT developed HD instability. Haemoglobin fall was higher in MT (1.8 ± 1.3 vs. 0.7 ± 0.8 g/dL, P = 0.018), but BARC3 and transfusion were identical. In-hospital mortality was 8% (2 pts in MT, P = 0.229). Mean FUP was 229 ± 147days, with higher MACE in MT (40% vs. 0%, P = 0.051).

Conclusions

Despite similar efficacy at short-term, adverse events related to the procedure seemed higher in MT group. CDT was less time consuming.
Poster No. 115 Switch the risk: from PDE5i to Riociguat in real world pulmonary hypertension
Authors: Martinho Mariana , Alegria Sofia , Ferreira Filipa , Calé Rita , Repolho Débora , Pereira Ana Rita , Briosa Alexandra , Santos João Grade , Ferreira Bárbara , Cunha Diogo Santos , Baltazar Oliveira , Ilchyshyn Nazar , Luz João Mirinha , Loureiro Maria José , Pereira Hélder
Published: October 2022

Introduction

Switching from phosphodiesterase-5 inhibitors (PDE5i) to Riociguat is associated with increased efficacy in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Objective

To show clinical efficacy of replacing PDE5i to Riociguat in a portuguese PH-dedicated centre.

Methods

Retrospective single-centre study of PAH and inoperable/persistent/recurrent CTEPH patients (pts) who switched vasodilator therapy. Parameters were stratified according to the 2022 PH guidelines and stratification as low/intermediate/high-risk PH followed the COMPERA registry, before switching, at 3–6 months of follow-up (FUP) and until the last clinical evaluation, balloon pulmonary angioplasty (BPA), heart transplant or death.

Results

Of 13 pts, 75.0% had CTEPH (4 pts had persistent disease after surgical endarterectomy), 16.7% had PAH and 1pt had mixed PAH/CTEPH. Mean age was 56.2 ± 16.3years and 83.3% were females. Mean time until switch was 33.5 ± 25.5 months. Previous therapy was: 33.3% Sildenafil, 41.7% Sildenafil/Bosentan and 25% Sildenafil/Bosentan/prostanoid. Before switching, 66.7% had intermediate and 33.3% low-risk PH; at a FUP of 4.4 ± 1.7 months, 8.3% had intermediate and 91.7% low-risk PH. There was a significant benefit in the COMPERA risk (1.50[1.33;1.62] vs. 1.22[1.09;1.40], P = 0.011). Long-term FUP was performed in 8 pts at 48.2 ± 35.6 months (death 1pt, transplant 1pt, BPA 3 pts). Medical treatment was Riociguat in 33.3%, Riociguat and Bosentan in 58.3%, and 1pt with Riociguat, Bosentan and Treprostinil. Clinical benefit was significant at long-term FUP when compared to the initial evaluation (1.22[1.09;1.40], P = 0.011), but not to the first FUP.

Conclusion

This study corroborates previous evidence regarding the vasodilator switch and also suggests that the treatment goal is maintained throughout long-term FUP.
Poster No. 116 Hemodynamic characteristics associated with partial thrombosis of the false lumen in patients with chronic aortic dissection of the descending aorta: a 4D flow CMR study
Authors: Muñoz Aroa Ruiz , Guala Andrea , Dux-Santoy Lydia , Teixidó-Turà Gisela , Garrido-Oliver Juan , Garcia-Duran Ana , Valente Filipa , Galian-Gay Laura , Gutierrez Laura , Cuellar-Calabria Hug , Johnson Kevin , Wieven Oliver , Ferreira-Gonzalez Ignacio , Evangelista Arturo , Rodriguez-Palomares Jose
Published: October 2022

Background

Partial thrombosis of the false lumen (FL) in patients with chronic aortic dissection (AD) of the descending aorta has been associated with faster aortic dilation. Four-dimensional phase-contrast cardiovascular magnetic resonance (4D flow CMR) studies analyzing flow dynamics and biomechanics in the FL and their relationship with partial thrombosis are lacking. This study aimed to compare FL flow dynamics and biomechanics between patients with a patent and partially thrombosed FL.

Materials and methods

Patients with a chronic, patent (no thrombus) or partially thrombosed FL in the descending aorta after an AD underwent an imaging follow-up including a magnetic resonance angiography (MRA) and a 4D flow CMR study. FL thrombosis was quantified as the ratio of thrombus volume and FL volume on MRA. FL flow dynamics was assessed in terms of forward flow, wall shear stress (WSS), maximum kinetic energy (KE) and acceleration, and flow stasis on 4D flow CMR. Aortic stiffness in the FL was quantified using pulse wave velocity (PWV).

Results and conclusions

Sixty-five patients with a complete imaging protocol were included in the study (patency in 34 patients, partial thrombosis in 31). Partial thrombosis of the FL was associated with a reduction in the amount and energy of flow in the FL (reduced forward systolic flow, KE and acceleration), and a more stagnated flow in the FL (increased flow stasis). Axial WSS showed a tendency to be lower in the partial thrombosis group compared to the patency group, while PWV were similar in both of them.

Funding

IJC2018-037349-I.
Poster No. 133 Local TGF-beta sequestration by fibrillin-1 regulates vascular wall homeostasis in the thoracic aorta
Authors: de Backer Julie , de Leeuw Violette , Van Impe Mathias , Vanhomwegen Marine , Logghe Gerlinde , Oblinado Margie , Stampanoni Marco , Segers Patrick , Mosquera Laura Muino , Sakai Lynn , Sips Patrick
Published: October 2022

Introduction

Marfan syndrome (MFS) is caused by a defect in fibrillin-1, which binds TGF-beta via interaction with latent TGF-beta binding proteins (LTBPs). The role of TGF-beta in MFS is controversial.

Objectives

use dedicated mouse models for MFS, with defects interfering with TGF-beta binding and function, to gain insights into the role of TGF-beta signaling in aneurysm formation and dissection.

Material & methods

Mice lacking the binding site for LTBPs (Fbn1H1Δ/+ and Fbn1H1Δ/H1Δ), mice with a truncated fibrillin-1 (Fbn1GT-8/+), and mice with a combination (Fbn1GT-8/H1Δ) were subjected to cardiac ultrasound and ex vivo synchrotron X-ray imaging.

Results

Only Fbn1GT-8/H1Δ mice showed increased mortality (aortic rupture) starting at 4–5 months, whereas all other mice had a normal life span. Aortic root dilatation occurred both in Fbn1GT-8/+ and Fbn1GT-8/H1Δ mice at 6 months, but not in Fbn1H1D/+ or Fbn1H1Δ/H1Δ mice. Significant elastin fragmentation was observed in the thoracic aortic wall of Fbn1GT-8/+ mice, and to a larger extent in Fbn1GT-8/H1Δ mice. Surprisingly, localized elastin fragmentation was also found in the ascending aorta of Fbn1H1Δ/+ and Fbn1H1Δ/H1Δ mice, despite a lack of aortic aneurysm formation. Moreover, Fbn1H1Δ/H1Δ mice displayed more severe aortic wall damage.

Conclusion

Our data suggest that loss of LTBP binding to fibrillin-1 leads to the development of localized aortic microdissections in the absence of aortic aneurysm, and exacerbates the aortic wall morphology abnormalities in mice with truncated fibrillin-1. We therefore hypothesize that local TGF-beta sequestration is required to maintain aortic homeostasis.
Poster No. 134 Zebrafish as a tool to study cardiovascular effects caused by fibrillin impairment
Authors: de Backer Julie , de Rycke Karo , Caboor Lisa , Vermassen Petra , Sips Patrick
Published: October 2022

Introduction

Marfan syndrome (MFS) is the most common type of fibrillinopathy with a high predisposition to develop TAAD. A thorough understanding of the underlying mechanisms is still lacking, indicating a particular need for more flexible in vivo models to address this knowledge gap.

Objectives

We aimed to generate a relevant zebrafish model to gain insight into the molecular mechanisms relating fibrillin defects to the cardiovascular system.

Methods

The CRISPR/Cas9 system was used to systematically target the three different fibrillin genes (fbn1, fbn2a and fbn2b) in Tg(kdrl:GFP) reporter zebrafish. Time-lapse fluorescent microscopy was used to evaluate the cardiovascular phenotype.

Results

zebrafish lacking fbn1 and/or fbn2a do not show any cardiovascular phenotype during early-stage development. On the other hand, approximately 50% of homozygous fbn2b mutant (fbn2b-/-) zebrafish embryo's show a severe phenotype characterized by endocardial detachment, leading to vascular embolism and premature mortality at 7–9 dpf. Interestingly, the remaining fbn2b-/- zebrafish survive until adulthood, but during larval stages already develop a dilation of the bulbus arteriosus. The caudal vein of all fbn2b-/- embryos also develops abnormally as a cavernous structure lacking vessel integrity. This phenotype is resolved in embryos retaining normal blood flow and aggravated upon pharmacological inhibition of blood flow during development.

Conclusion

These data indicate that fbn2b-/- zebrafish model recapitulates cardiovascular complications, and can be considered as a relevant model to study the mechanisms underlying MFS pathogenesis. Our preliminary data suggest that there is an interplay between fibrillin deficiency and biomechanical signaling in the regulation of cardiovascular development.
Poster No. 139 Direct Oral Anticoagulant Use in the Treatment of Venous Thromboembolism Associated with Cancer
Authors: Carmo Francisca , Cabral Joana Martins , Magalhães Luísa
Published: October 2022

Venous thromboembolism (VTE) is a common cause of death and complications in patients with cancer. Choosing an anticoagulant is challenging because these patients are at high risk of recurrent VTE and bleeding. Major guidelines recommended the use of low-molecular-weight heparin (LMWH), but recent studies recommend consideration of direct anticoagulants (DOACs) in selected patients. However, their clinical use is limited by the increased risk of bleeding and interaction with other drugs.

Retrospective study, including patients followed since 2015 in VTE consultation, with cancer-associated VTE. Patients with an ECOG Performance Status Scale of 4 and with contraindications for anticoagulation were excluded. We reported the incidence of recurrent VTE and haemorrhage within the first year after anticoagulation. In this study, we compared the efficacy and safety of the use of DOACs versus LMWH in patients with cancer-associated VTE.

91 patients were included, 55% male, median age of 70 years and most frequent ECOG Performance Status Scale of 0 (44%). 65% of the patients were treated with DOACs. The most common cancers included: colorectal (26%), genitourinary (25%), haematological (10%) and upper gastrointestinal (9%). Were reported 6 recurrent VTE events (4 pulmonary embolisms, 2 deep vein thrombosis) and 6 minor bleeding events, without any major or fatal event. The occurrence of recurrent thromboembolic events or bleeding was not significantly different between patients treated with LMWH or DOACs.

In this real-world observational study, we confirm the efficacy and safety of the use of DOACs in the treatment of VTE associated with cancer in selected patients.
Poster No. 140 Major cardiovascular events in high cardiovascular risk patients submitted to non-cardiac surgery and its clinical determinants
Authors: Carvalho Mariana Ferreira , Gonçalves Carolina , Cabral Margarida , Fernandes Sara Lopes , Carvalho Rita Ribeiro , Guardado Jorge , Antunes Alexandre , Morais João
Published: October 2022

Introduction

Pre-operative cardiovascular assessment of patients with high ischaemic risk is fundamental to give the best perioperative management. Morbi-mortality is mainly due to patient-related risk and surgery-related risk. However, the risk scores are very heterogeneous and derived from non-cardiac populations, making them less accurate.

Purpose

The study aims to characterize a cohort of patients with high ischemic risk who underwent non-cardiac surgery and to identify predictors of perioperative major adverse cardiovascular events (MACE) defined by urgent revascularization, myocardial infarction (MI) and/or cardiac death, thromboembolism and acute limb ischemia.

Methods

A single-center retrospective observational analysis between January 2015 and August 2022 evaluated 356 patients. Eligibility criteria included: patients with high cardiovascular risk with previous diagnosis of cardiac disease, planned to be submitted to high-risk non-cardiac surgery, and perioperative follow-up at our center.

Results

A total of 356 patients with high cardiovascular risk undergoing NCS were eligible in the cohort. Perioperative MACE occurred in 4.5% of the patients. Predictors of MACE during perioperative period were older age (P < 0.001), chronic pulmonary disease (P = 0.031), coronary artery disease (CAD) (P = 0.011) and valvular heart disease (P = 0.039). Diabetes and hypertension exhibited a neutral impact in these patients.

Conclusions

These results highlight the increased thrombotic risk inherent to major surgery in patients with high risk cardiovascular disease. Older age, previous diagnosis of chronic pulmonary disease, coronary artery disease, and valvular heart disease are predictors of MACE in patients submitted to non-cardiac surgery, providing incremental value for predicting these events. More studies are needed to further caracterize this population.x
Clinical Case 26—Is it possible to live with thrombosed left ventricular assist device (LVAD)?
Authors: Dračina Nina , Golubović Miodrag , Zdravković Ranko , Redžek Aleksandar , Todić Mirko , Preveden Andrej
Published: October 2022

LVAD HeartWare was implanted in a 63-year-old patient with end-stage dilated cardiomyopathy. The postoperative course was complicated by massive gastrointestinal (GI) bleeding that required surgical exploration of the GI tract.

For the next 1.5 years, the patient has significantly improved functional capacity with proper LVAD function. A month before the incident, an alarm indicating a pump malfunction was recorded. The patient presents with congestive symptoms and an altered sound of LVAD. Laboratory indicates seven times elevated LDH values, low HGB and INR 3.03. Thrombophilia tests were negative. Echo examination does not indicate pump thrombosis, but the pump parameters show increased energy consumption (>6 W) and increased flow (>7 L/min). A diagnosis of LVAD thrombosis was made.

Fibrinolytic therapy was contraindicated because of a history of GI bleeding, so a continuous infusion of heparin was started. Despite this, the patient's clinical condition deteriorates, and a decision was made to discontinue the LVAD, to prevent further hemolysis that led to acute kidney injury (AKI). The procedure was performed without endangering the patient.

Massive hemolysis, however, leads to the progressive development of AKI requiring CVVHDF. Global respiratory insufficiency develops and mechanical ventilation was started. After six days of intensive treatment, the patient recovered and was discharged home with a thrombosed pump.

For the next 2.5 years, the patient was in satisfactory condition during follow-ups, the pump was not explanted.

Even sophisticated medical devices carry with them risks for the patient's life despite adequate management.

Treatment of LVAD thrombosis depends on patient characteristics and pump-related factors.
NanoSPECT imaging reveals the uptake of 123I-labelled oxidized low-density lipoprotein in the brown adipose tissue of mice via CD36
Authors: Hosomi Kento , Kawashima Hidekazu , Nakano Atsushi , Kakino Akemi , Okamatsu-Ogura Yuko , Yamashita Yuki , Sasaoka Mai , Masuda Daisaku , Yamashita Shizuya , Chen Chu-Huang , Yuzuriha Shunsuke , Hosoda Hiroshi , Iida Hidehiro , Sawamura Tatsuya
Published: October 2022

Aims

The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-effects, we used 123I-labelled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT.

Methods and results

We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anaesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering β3-agonist. Furthermore, exposing mice to cold stress at 4°C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labelled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labelled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analysed the expression of known oxLDL receptors (e.g. SR-A, CD36, and LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT.

Conclusion

We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation.
Parenthood and the gender division of labour across the income distribution: the relative importance of relative earnings
Authors: Dunatchik Allison
Published: October 2022

This study employs a gendered relative resource approach to examine whether the importance of relative resources varies by couples’ household income in shaping changes in the gender division of labour after first birth. Scholarship has long argued that the gender division of labour within different-sex couples is influenced by partners’ relative resources. However, couples face class-based constraints that may alter the relevance of relative resources in shaping changes in gender divisions of labour following the transition to parenthood. This study compares couples’ paid work and housework before and up to four years after first birth, using 28 waves of the British Household Panel Survey and the UK Household Longitudinal Study (N = 1,606 couples). I find that the effect of relative resources on changes in couple’s paid work and housework behaviour after first birth varies substantially by household income. Among higher-income couples, women’s paid work and housework time changes less among those with high relative earnings and more among those with low relative earnings, while men’s time allocation varies little after first birth. In contrast, among low-income couples, women’s paid work time and share decreases most after first among female breadwinners while their male partners’ paid work time increases substantially. These findings reflect the greater constraints that low-income parents face in reconciling work and family and highlight the need for greater attention to class interactions in the process of gender specialization in both research and work-family policy.
Restrictive cardiomyopathy: definition and diagnosis
Authors: Rapezzi Claudio , Aimo Alberto , Barison Andrea , Emdin Michele , Porcari Aldostefano , Linhart Ales , Keren Andre , Merlo Marco , Sinagra Gianfranco
Published: October 2022

Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.
Modelling of fluid pressure migration in a pressure sensitive fault zone subject to cyclic injection and implications for injection-induced seismicity
Authors: Ji Yinlin , Zhang Wei , Hofmann Hannes , Chen Yuedu , Kluge Christian , Zang Arno , Zimmermann Günter
Published: October 2022

Fault zones often serve as the major fluid pathways in a variety of geo-energy systems, such as deep geothermal systems. However, injection-induced instability of faults can sometimes lead to large-magnitude earthquakes. Cyclic injection has thus been proposed as an alternative injection protocol to better manage and mitigate the associated seismic risks. The risks of injection-induced seismicity depend primarily on the extent and magnitude of the fluid pressure perturbation. When fluid is injected into a fault zone, the local fault permeability will be enhanced, which in turn promotes the migration of fluid along the fault. This nonlinear process is further complicated during cyclic injection via alternating the injection pressure. In this study, both numerical and analytical modelling are conducted to investigate cyclic fluid injection into a fault zone with pressure sensitive permeability, in which the local fault permeability changes as a function of the local effective stress. The match with laboratory-scale experimental and field-scale analytical results of cyclic fluid injection verifies the accuracy of the numerical model. The parametric study reveals that the injection pressure attenuation, quantified by the amplitude ratio and phase shift, is enhanced by a lower initial fault permeability, a smaller stress sensitivity coefficient and a shorter period of pressure cycle (i.e. a higher frequency). Besides, the amplitude of the pressure cycle has a negligible effect on the injection pressure attenuation. We also discuss the implications of our results for the less amenable far-field seismic hazard and post shut-in seismicity.
4. Criteria For Protection
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter examines the criteria used to determine whether a work is to be protected by copyright. More specifically, it considers the requirements for copyright protection: the work must be recorded in a material form; must be ‘original’; should be sufficiently connected to the UK to qualify for protection under UK law; and should not be excluded from protection on public policy grounds. There is discussion of the traditional British conception of originality, harmonization of ‘originality’ in Europe, analysis of differences between British and European standards on originality, and the issue of whether the UK can—and does—protect non-original works. The chapter concludes by focusing on subject matter excluded from copyright protection.
29. Copyright Protection for Designs
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter deals with the conditions under which copyright law might protect designs as well as the limitations on the term of design protection. It first considers the subsistence of copyright in designs via two routes: either directly, by protecting the form and decoration of articles as artistic works (particularly sculptures, engravings, or works of artistic craftsmanship), or indirectly, by protecting the author of a preliminary document on which a design is based. It then discusses the limitation on protection afforded by design documents in section 51 of the Copyright, Designs and Patents Act 1988.
30. Design Right
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter focuses on the unregistered Design Right as a means of protecting designs in the United Kingdom under Part III of the Copyright, Designs and Patents Act 1988. It begins by considering the subsistence of the Design Right, with emphasis on the requirement that there be a ‘design’ and exclusions to design protection by the unregistered design right. The chapter then discusses issues of ownership, duration, and infringement as well as the defences that are available in cases of infringement of unregistered designs.
32. Passing Off
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter focuses on the tort of passing off as a legal regime for the protection of trade marks. It considers three elements that are required in order to succeed in an action for passing off: the claimant has ‘goodwill’; the defendant made a ‘misrepresentation’ that is likely to deceive the public; and the misrepresentation damages the goodwill of the claimant. It also surveys the law in relation to goodwill. This chapter discusses manifestations of goodwill and describes goodwill associated with packaging, get-up, and trade dress as well as advertising style. It concludes by analysing the scope and ownership of goodwill, together with goodwill as a form of property.
33. Misrepresentation
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter considers one element of the action of passing off with respect to trade marks: the requirement that there be a misrepresentation. It first describes the type of conduct that amounts to misrepresentation and the consequences that flow from that conduct, as well as the types of suggestion that are actionable. It then discusses the requirement that a statement must be likely to cause confusion in order to qualify as a misrepresentation. In addition, the chapter explains how passing off action can be brought not only against a person who carries out the misrepresentation, but also against anyone who provides the means for the misrepresentation to occur (such as by providing instruments of deception).
49. Civil and Criminal Remedies
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter deals with civil and criminal remedies that are available where intellectual property rights are violated. It first considers the civil relief that is available before a trial takes place, namely, interim injunctions and prevention of imports. It then outlines the civil remedies that are available at full trial: final injunction, delivery up or destruction, the awarding of damages, the account of profits, and publicity orders. Finally, the chapter examines the various criminal remedies that intellectual property right holders may avail.
Celebrating 25 Years of Varicella Vaccination Coverage for Children and Adolescents in the United States: A Success Story
Authors: Elam-Evans Laurie D , Valier Madeleine R , Fredua Benjamin , Zell Elizabeth , Murthy Bhavini P , Sterrett Natalie , Harris LaTreace Q , Leung Jessica , Singleton James A , Marin Mona
Published: October 2022

Tracking vaccination coverage is a critical component of monitoring a vaccine program. Three different surveillance systems were used to examine trends in varicella vaccination coverage during the United States vaccination program: National Immunization Survey–Child, National Immunization Survey–Teen, and immunization information systems (IISs). The relationship of these trends to school requirements and disease decline was also examined. Among children aged 19–35 months, ≥1 dose of varicella vaccine increased from 16.0% in 1996 to 89.2% by the end of the 1-dose program in 2006, stabilizing around at least 90.0% thereafter. The uptake of the second dose was rapid after the 2007 recommendation. Two-dose coverage among children aged 7 years at 6 high-performing IIS sites increased from 2.6%–5.5% in 2006 to 86.0%–100.0% in 2020. Among adolescents aged 13–17 years, ≥2-dose coverage increased from 4.1% in 2006 to 91.9% in 2020. The proportion of adolescents with history of varicella disease declined from 69.9% in 2006 to 8.4% in 2020. In 2006, 92% of states and the District of Columbia (DC) had 1-dose daycare or school entry requirements; 88% of states and DC had 2-dose school entry requirements in the 2020–2021 school year. The successes in attaining and maintaining high vaccine coverage were paramount in the dramatic reduction of the varicella burden in the United States over the 25 years of the vaccination program, but opportunities remain to further increase coverage and decrease varicella morbidity and mortality.
A novel technique of STEM observation of TEM section using LVSEM and application of pathological diagnosis of renal biopsy
Authors: Nagumo Tasuku , Sakaue Mari , Wakatsuki Mone , Inoue Yuriko , Mukai Shumpei , Yamochi Toshiko , Takaki Takashi
Published: October 2022

The usefulness of the transmission electron microscope (TEM) for pathological diagnosis is apparent. However, high operating costs and other disadvantages have limited the ability to maintain and operate a TEM. In recent years, a general-purpose benchtop low-vacuum scanning electron microscope (LVSEM), which is inexpensive and easy to operate, has been developed and is expected to be applied in electron microscopic pathological diagnosis. To date, we have previously observed TEM ultrathin sections of Immunoglobulin A (IgA) nephropathy with a benchtop LVSEM using an ultra variable-pressure detector (UVD) and a newly developed holder for observing scanning transmission electron microscope (STEM) images (UVD-STEM holder) and compared the images with those obtained with typical TEM observations. We reported the results in the 53rd Annual Meeting of the Japanese Society for Clinical Molecular Morphology and the 64th Symposium of The Japanese Society of Microscopy and discussed the validity of the methods in the pathological diagnosis of IgA nephropathy and other renal diseases. As a result, we demonstrated the potential for pathological diagnosis using benchtop LVSEM. In this study, we similarly examined typical kidney diseases such as membranous nephropathy, lupus nephritis and amyloidosis. We could obtain sufficient data for the pathological diagnosis of IgA nephropathy, membranous nephropathy and lupus nephritis. However, it is difficult to detect amyloid fibres that are characteristic of amyloidosis. The development of this method is expected to expand the possibilities for pathological diagnosis using electron microscopy, including its application to other diseases.
Bayesian reconstruction of dark matter distribution from peculiar velocities: accounting for inhomogeneous Malmquist bias
Authors: Boruah Supranta S , Lavaux Guilhem , Hudson Michael J
Published: October 2022

We present a Bayesian velocity field reconstruction algorithm that performs the reconstruction of the mass density field using only peculiar velocity data. Our method consistently accounts for the inhomogeneous Malmquist (IHM) bias using analytical integration along the line of sight. By testing our method on a simulation, we show that our method gives an unbiased reconstruction of the velocity field. We show that not accounting for the IHM bias can lead to significant biases in the Bayesian reconstructions. We applied our method to a peculiar velocity data set consisting of the SFI++ and 2MTF Tully–Fisher catalogues and the A2 supernovae compilation, thus obtaining a novel velocity reconstruction in the local Universe. Our velocity reconstructions have a cosmological power spectrum consistent with the theoretical expectation. Furthermore, we obtain a full description of the uncertainties on reconstruction through samples of the posterior distribution. We validate our velocity reconstruction of the local Universe by comparing it to an independent reconstruction using the 2M++ galaxy catalogue, obtaining good agreement between the two reconstructions. Using Bayesian model comparison, we find that our velocity model performs better than the adaptive kernel smoothed velocity with the same peculiar velocity data. However, our velocity model does not perform as well as the velocity reconstruction from the 2M++ galaxy catalogue, due to the sparse and noisy nature of the peculiar velocity tracer samples. The method presented here provides a way to include peculiar velocity data in initial condition reconstruction frameworks.
Design of programmable post-translational switch control platform for on-demand protein secretion in mammalian cells
Authors: Mansouri Maysam , Ray Preetam Guha , Franko Nik , Xue Shuai , Fussenegger Martin
Published: October 2022

The development of novel strategies to program cellular behaviors is a central goal in synthetic biology, and post-translational control mediated by engineered protein circuits is a particularly attractive approach to achieve rapid protein secretion on demand. We have developed a programmable protease-mediated post-translational switch (POSH) control platform composed of a chimeric protein unit that consists of a protein of interest fused via a transmembrane domain to a cleavable ER-retention signal, together with two cytosolic inducer-sensitive split protease components. The protease components combine in the presence of the specific inducer to generate active protease, which cleaves the ER-retention signal, releasing the transmembrane-domain-linked protein for trafficking to the trans-Golgi region. A furin site placed downstream of the protein ensures cleavage and subsequent secretion of the desired protein. We show that stimuli ranging from plant-derived, clinically compatible chemicals to remotely controllable inducers such as light and electrostimulation can program protein secretion in various POSH-engineered designer mammalian cells. As proof-of-concept, an all-in-one POSH control plasmid encoding insulin and abscisic acid-activatable split protease units was hydrodynamically transfected into the liver of type-1 diabetic mice. Induction with abscisic acid attenuated glycemic excursions in glucose-tolerance tests. Increased blood levels of insulin were maintained for 12 days.
TNF or EGFR inhibition equally block AKI-to-CKD transition: opportunities for etanercept treatment
Authors: Abdelmageed Mai M , Kefaloyianni Eirini , Arthanarisami Akshayakeerthi , Komaru Yohei , Atkinson Jeffrey J , Herrlich Andreas
Published: October 2022

Background

Inflammation is a key driver of the transition of acute kidney injury to progressive fibrosis and chronic kidney disease (AKI-to-CKD transition). Blocking a-disintegrin-and-metalloprotease-17 (ADAM17)-dependent ectodomain shedding, in particular of epidermal growth factor receptor (EGFR) ligands and of the type 1 inflammatory cytokine tumor necrosis factor (TNF), reduces pro-inflammatory and pro-fibrotic responses after ischemic AKI or unilateral ureteral obstruction (UUO), a classical fibrosis model. Metalloprotease or EGFR inhibition show significant undesirable side effects in humans. In retrospective studies anti-TNF biologics reduce the incidence and progression of CKD in humans. Whether TNF has a role in AKI-to-CKD transition and how TNF inhibition compares to EGFR inhibition is largely unknown.

Methods

Mice were subjected to bilateral renal ischemia-reperfusion injury or unilateral ureteral obstruction. Kidneys were analyzed by histology, immunohistochemistry, qPCR, western blot, mass cytometry, scRNA sequencing, and cytokine profiling.

Results

Here we show that TNF or EGFR inhibition reduce AKI-to-CKD transition and fibrosis equally by about 25%, while combination has no additional effect. EGFR inhibition reduced kidney TNF expression by about 50% largely by reducing accumulation of TNF expressing immune cells in the kidney early after AKI, while TNF inhibition did not affect EGFR activation or immune cell accumulation. Using scRNAseq data we show that TNF is predominantly expressed by immune cells in AKI but not in proximal tubule cells (PTC), and PTC-TNF knockout did not affect AKI-to-CKD transition in UUO. Thus, the anti-inflammatory and anti-fibrotic effects of the anti-TNF biologic etanercept in AKI-to-CKD transition rely on blocking TNF that is released from immune cells recruited or accumulating in response to PTC-EGFR signals.

Conclusion

Short-term anti-TNF biologics during or after AKI could be helpful in the prevention of AKI-to-CKD transition.