Nanoplastics causes extensive congenital malformations during embryonic development by passively targeting neural crest cells.

Nanomaterials are widespread in the human environment as pollutants, and are being actively developed for use in human medicine. We have investigated how the size and dose of polystyrene nanoparticles affects malformations in chicken embryos, and have characterized the mechanisms by which they interfere with normal development. We find that nanoplastics can cross the embryonic gut wall. When injected into the vitelline vein, nanoplastics become distributed in the circulation to multiple organs. We find that the exposure of embryos to polystyrene nanoparticles produces malformations that are far more serious and extensive than has been previously reported. These malformations include major congenital heart defects that impair cardiac function. We show that the mechanism of toxicity is the selective binding of polystyrene nanoplastics nanoparticles to neural crest cells, leading to the death and impaired migration of those cells. Consistent with our new model, most of the malformations seen in this study are in organs that depend for their normal development on neural crest cells. These results are a matter of concern given the large and growing burden of nanoplastics in the environment. Our findings suggest that nanoplastics may pose a health risk to the developing embryo.

Asymmetry and Heterogeneity: Part and Parcel in Cardiac Autonomic Innervation and Function.

The cardiac autonomic nervous system (cANS) regulates cardiac adaptation to different demands. The heart is an asymmetrical organ, and in the selection of adequate treatment of cardiac diseases it may be relevant to take into account that the cANS also has sidedness as well as regional differences in anatomical, functional, and molecular characteristics. The left and right ventricles respond differently to adrenergic stimulation. Isoforms of nitric oxide synthase, which plays an important role in parasympathetic function, are also distributed asymmetrically across the heart. Treatment of cardiac disease heavily relies on affecting left-sided heart targets which are thought to apply to the right ventricle as well. Functional studies of the right ventricle have often been neglected. In addition, many principles have only been investigated in animals and not in humans. Anatomical and functional heterogeneity of the cANS in human tissue or subjects is highly valuable for understanding left- and right-sided cardiac pathology and for identifying novel treatment targets and modalities. Within this perspective, we aim to provide an overview and synthesis of anatomical and functional heterogeneity of the cANS in tissue or subjects, focusing on the human heart.

Initial report on distribution of ß3-adrenoceptor in the human female urethra.

INTRODUCTION: Past research has demonstrated that the urethral tonus is mainly under sympathetic control. Since 5 years, a beta 3-adrenoceptor (ADRB3) agonist is available in the treatment of overactive bladder syndrome. The presence of ADRB3 within the human urethra has not been demonstrated to date. Presence of ADRB3 in the urethra could influence urethral tonus. The aim of this study is to investigate the presence of ADRB3 in the human female urethra. MATERIAL AND METHODS: We performed anatomical studies in five female specimens. Three specimens were obtained from the body donation program, two from female patients with muscle-invasive bladder cancer, where radical resection of bladder and urethra was performed. The urethra up till the bladder neck was separated from the rest of the bladder and freshly obtained for this study. For demonstrating ADRB3 expression, we used rabbit polyclonal anti-human ADRB3 LS-A4198. RESULTS: Expression of ADBR3 was demonstrated in the epithelial layer of all urethral parts, except at the level of the meatus. The level of ADRB3 expression was highest in the mid urethra. There was no direct contact between ADRB3 and nerve tissue. ADRB3 expression was also demonstrated in the stratified muscle layer at the level of the external urethral sphincter. CONCLUSIONS: This is the first study to demonstrate the expression of ADRB3 in the human female urethra. There is an absence of a direct connection between ADRB3 and nerve tissue.

Whole human heart histology to validate electroanatomical voltage mapping in patients with non-ischaemic cardiomyopathy and ventricular tachycardia.

Aims: Electroanatomical voltage mapping (EAVM) is an important diagnostic tool for fibrosis identification and risk stratification in non-ischaemic cardiomyopathy (NICM); currently, distinct cut-offs are applied. We aimed to evaluate the performance of EAVM to detect fibrosis by integration with whole heart histology and to identify the fibrosis pattern in NICM patients with ventricular tachycardias (VTs). Methods and results: Eight patients with NICM and VT underwent EAVM prior to death or heart transplantation. EAVM data was projected onto slices of the entire heart. Pattern, architecture, and amount of fibrosis were assessed in transmural biopsies corresponding to EAVM sites. Fibrosis pattern in NICM biopsies (n = 507) was highly variable and not limited to mid-wall/sub-epicardium. Fibrosis architecture was rarely compact, but typically patchy and/or diffuse. In NICM, biopsies without abnormal fibrosis unipolar voltage (UV) and bipolar voltage (BV) showed a linear association with wall thickness (WT). The amount of viable myocardium showed a linear association with both UV and BV. Accordingly, any cut-off to delineate fibrosis performed poorly. An equation was generated calculating the amount of fibrosis at any location, given WT and UV or BV. Conclusion: Considering the linear relationships between WT, amount of fibrosis and both UV and BV, the search for any distinct voltage cut-off to identify fibrosis in NICM is futile. The amount of fibrosis can be calculated, if WT and voltages are known. Fibrosis pattern and architecture are different from ischaemic cardiomyopathy and findings on ischaemic substrates may not be applicable to NICM.

Echocardiographic assessment of embryonic and fetal mouse heart development: a focus on haemodynamics and morphology.

BACKGROUND: Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. METHODS: A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n = 105). RESULTS: Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. CONCLUSION: High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts.

Changing intracellular compartmentalization of beta-galactosidase in the ROSA26 reporter mouse during embryonic development: a light- and electron-microscopic study.

The beta-geo (LacZ) reporter gene encodes for beta-galactosidase (beta-gal) in all cells of the ROSA26 mouse during embryonic development. As such, beta-gal activity constitutes an excellent marker for in situ labeling of expressing cells. However, the intracellular distribution of beta-gal differs between cells, and changes during embryonic development. Therefore, we studied LacZ-encoded beta-gal using light and electron microscopy in the heart, lung, liver, and small intestine on days 13 and 16 of gestation, and the kidney on day 16 of gestation in ROSA26 mice. The Bluo-gal method was carried out under standardized conditions, including fixation, washing, and incubation procedures. Intracellular beta-gal staining is encountered in a combination of membranous compartments, including the nuclear envelope, the endoplasmic reticulum, and the plasma membrane. Its exact localization depends on the cell type and is regulated during development. Therefore, one must take the compartmental transition of intracellular beta-gal staining into consideration when interpreting results obtained from experiments using ROSA26 mice.

Anatomy of the arcus tendineus fasciae pelvis in females.

Because of its proximity to the urethra, the anterior part of the arcus tendineus fasciae pelvis (ATFP) may be used in urethrosuspension procedures for urinary stress incontinence. In this study, 10 embalmed female cadaver hemipelves were dissected and their gross anatomy described. In females, the ATFP is a condensation of the endopelvic fascia. The anterior attachment of the ATFP is to the caudal inner surface of the body of the pubic bone at a site averaging 4 mm lateral to the pubic symphysis and covering an average area of 53 mm(2). Posteriorly, it attaches to the medial surface of the ischial spine. In nine of the 10 hemipelves the first anterior centimeters of the ATFP have a clear lateral fixation either to the lateral part of the levator ani muscle (n = 1), to the fascia covering the obturator internus muscle (n = 7), or to the obturator membrane (n = 1). Medially from the ATFP derives a 2-3-cm long flat fibrous attachment to the posterolateral aspect of the urethra. In eight unembalmed cadavers, the ATFP gave way at a pulling force of 8.2 kg (range = 3.5-11.5 kg). The ATFP resists caudal movement of the proximal anterior vaginal wall and the urethra in the upright posture and, therefore, may be suitable for urethrosuspension procedures.