Percutaneous septal ablation for left mid-ventricular obstructive hypertrophic cardiomyopathy: a case report

BACKGROUND: Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHC) is a rare type of cardiomyopathy. The diagnosis is based on the hourglass appearance on the left ventriculogram and the presence of pressure gradient between apical and basal chamber of the ventriculum on the hemodynamic assessment. CASE PRESENTATION: The present case represents successful percutaneous treatment with septal ablation to patient with MVOHC associated with systolic anterior motion of the mitral valve and obstruction at both the mid-ventricular and outflow levels. CONCLUSION: Alcohol septal ablation has been proposed as less invasive alternatives to surgery in patients with MVOHC

Investigating 3R in vivo approaches for bio-distribution and efficacy evaluation of nucleic acid nanocarriers: studies on peptide-mimicking ionizable lipid

Formulations based on ionizable amino-lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre-clinical translation. This is further exacerbated by limited access to mammalian models. The present work proposes to close this gap by investigating in vivo nucleic acid delivery within simpler models, but which still offers physiologically complex environments and also adheres to the 3R guidelines (replace/reduce/refine) to improve animal experiments. The efficacy of OH4:DOPE as a delivery system for nucleic acids is demonstrated using in vivo approaches. It is shown that the formulation is able to transfect complex tissues using the chicken chorioallantoic membrane model. The efficacy of DNA and mRNA lipoplexes is tested extensively in the zebra fish (Danio rerio) embryo which allows the screening of biodistribution and transfection efficiency. Effective transfection of blood vessel endothelial cells is seen, especially in the endocardium. Both model systems allow an efficacy screening according to the 3R guidelines bypassing the in vitro-in vivo gap. Pilot studies in mice are performed to correlate the efficacy of in vivo transfection.Drug Delivery Technolog

Presence of factors that activate platelet aggregation in mitral stenotic patients' plasma

BACKGROUND: Although the association between mitral stenosis (MS) and increased coagulation activity is well recognized, it is unclear whether enhanced coagulation remains localized in the left atrium or whether this represents a systemic problem. To assess systemic coagulation parameters and changes in platelet aggregation, we measured fibrinogen levels and performed in vitro platelet function tests in plasma obtained from mitral stenotic patients' and from healthy control subjects' peripheral venous blood. METHODS: Sixteen newly diagnosed patients with rheumatic MS (Group P) and 16 healthy subjects (Group N) were enrolled in the study. Platelet-equalized plasma samples were evaluated to determine in vitro platelet function, using adenosine diphosphate (ADP), collagen and epinephrine in an automated aggregometer. In vitro platelet function tests in group N were performed twice, with and without plasma obtained from group P. RESULTS: There were no significant differences between the groups with respect to demographic variables. Peripheral venous fibrinogen levels in Group P were not significantly different from those in Group N. Adenosine diphosphate, epinephrine and collagen-induced platelet aggregation ratios were significantly higher in Group P than in Group N. When plasma obtained from Group P was added to Group N subjects' platelets, ADP and collagen-induced, but not epinephrine-induced, aggregation ratios were significantly increased compared to baseline levels in Group N. CONCLUSION: Platelet aggregation is increased in patients with MS, while fibrinogen levels remain similar to controls. We conclude that mitral stenotic patients exhibit increased systemic coagulation activity and that plasma extracted from these patients may contain some transferable factors that activate platelet aggregation

The origins and spread of domestic horses from the Western Eurasian steppes

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).Descriptive and Comparative Linguistic

The origins and spread of domestic horses from the Western Eurasian steppes

Domestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 bc. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture

The Origins and Spread of Domestic Horses from the Western Eurasian Steppes

Domestication of horses fundamentally transformed long-range mobility and warfare1. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling2–4 at Botai, Central Asia around 3500 bc3. Other longstanding candidate regions for horse domestication, such as Iberia5 and Anatolia6, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association7 between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc8,9 driving the spread of Indo-European languages10. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture11,12. © 2021, The Author(s).We thank all members of the AGES group at CAGT. We are grateful for the Museum of the Institute of Plant and Animal Ecology (UB RAS, Ekaterinburg) for providing specimens. The work by G. Boeskorov is done on state assignment of DPMGI SB RAS. This project was supported by the University Paul Sabatier IDEX Chaire d’Excellence (OURASI); Villum Funden miGENEPI research programme; the CNRS ‘Programme de Recherche Conjoint’ (PRC); the CNRS International Research Project (IRP AMADEUS); the France Génomique Appel à Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); IB10131 and IB18060, both funded by Junta de Extremadura (Spain) and European Regional Development Fund; Czech Academy of Sciences (RVO:67985912); the Zoological Institute ZIN RAS (АААА-А19-119032590102-7); and King Saud University Researchers Supporting Project (NSRSP–2020/2). The research was carried out with the financial support of the Russian Foundation for Basic Research (19-59-15001 and 20-04-00213), the Russian Science Foundation (16-18-10265, 20-78-10151, and 21-18-00457), the Government of the Russian Federation (FENU-2020-0021), the Estonian Research Council (PRG29), the Estonian Ministry of Education and Research (PRG1209), the Hungarian Scientific Research Fund (Project NF 104792), the Hungarian Academy of Sciences (Momentum Mobility Research Project of the Institute of Archaeology, Research Centre for the Humanities); and the Polish National Science Centre (2013/11/B/HS3/03822). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (grant agreement 797449). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements 681605, 716732 and 834616)

Vascular endothelial functions, carotid intima-media thickness, and soluble CD40 ligand levels in dipper and nondipper essential hypertensive patients

PubMed ID: 18347767Objective: The lack of nocturnal decline in blood pressure (BP) is associated with an increase in cardiovascular events. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. The purpose of this study was to examine the relationship between vascular endothelial functions, carotid intima-media thickness (cIMT), plasma sCD40L levels and circadian BP profile in patients with essential hypertension. Material and methods: The study population consisted of 81 essential hypertensive out-patients. BP dipping was defined as a night-to-day systolic and diastolic decrease ?10%. Forty-seven dipper and 34 nondipper patients were compared. High sensitivity C-reactive protein (hs-CRP), sCD40L and urinary albumin were measured. Brachial artery flow-mediated dilatation (FMD) and cIMT was compared between the groups. Results: sCD40L level (3.28 ± 2.08 and 2.30 ± 1.99 ng/ml, respectively, P = 0.036) and urinary albumin concentration (36.7 ± 20.1 and 23 ± 29.7 mg/l, respectively, P < 0.0001) were higher in nondippers than in dippers. Serum hs-CRP levels were not significantly different. FMD was found higher in dippers than nondippers (11.8 ± 3.9% and 6.6 ± 2.2%, respectively, P < 0.0001). The average cIMT was significantly higher in nondippers than dippers (0.928 ± 0.060 Vs. 0.734 ± 0.134 mm; P < 0.0001). Conclusions: Nondipper patern has an additional negative effect on endothelial functions in hypertensive patients. Nondippers have enhanced sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage. © 2008 Springer-Verlag

Femoral arterial thrombosis after cardiac catheterization in infancy: impact of Doppler ultrasound for diagnosis

Femoral arterial thrombosis (FAT) is a nonnegligible complication after cardiac catheterization (CC) in infancy. The aim of this study was to evaluate the impact of Doppler ultrasound (US) for diagnostic work-up after catheterization. We compared standard follow-up (FU) without Doppler US by relying on clinical signs of FAT with advanced FU using Doppler US of the femoral vessels. Between January and December 2009, we evaluated the rate of FAT in infants <12 months of age using a multicenter, prospective observational survey. We analysed 171 patients [mean age 4.1 ± 3.3 (SD) months; mean body weight 5.3 ± 1.8 kg] from 6 participating centres. The mean duration of catheter studies was 57.7 ± 38.0 min. The overall rate of FAT based on clinical diagnosis was 4.7% and was comparable in both groups [3.4% undergoing standard FU vs. 7.4% undergoing advanced FU (p = 0.15)]. However, the overall rate of thrombosis as screened by Doppler US was greater at 7.1 %, especially in patients after advanced FU [18.5% advanced vs. standard FU 1.7% (p < 0.01)]. In conclusion, FAT remains a relevant and underestimated complication after catheterization in young infants when relying only on clinical signs of FAT. Therefore, to start effective treatment as soon as possible, we recommend Doppler US to be performed the day after CC