Abstract
Background
Accurate imaging differentiation of various cardiac masses is pivotal due to differences in clinical management and treatment. The most common primary cardiac tumor is cardiac ...myxoma (CM), which is typically located in the left atrium attached to the interatrial septum. Although benign, serious clinical manifestations may occur and surgical treatment of CM is warranted in most cases. Echocardiography is the most common imaging modality, with a reported sensitivity of 90–96%, however accurate diagnosis can be challenging due to the heterogeneous morphological presentation of CM.
Purpose
The aim of this study was to determine the utility of echocardiography in CM diagnosis.
Methods
We retrospectively analyzed the echocardiographic and pathohistological findings of all consecutive patients admitted to our cardiology department for possible CM between 2005 and 2020.
Results
During the 15-year period, 73 patients were admitted for diagnostic evaluation of a possible CM. Subsequently, 54 patients (74%) were diagnosed with CM or another non-myxomal (NM) cardiac tumor, while in others cardiac masses of other etiologies (thrombus, infective endocarditis, etc.) were diagnosed (Figure 1). All but one patient with CM or NM cardiac tumor were treated surgically at our institution and pathohistological specimens were obtained from the resected tumor. There was a significant female preponderance (n=34, 63%) and the mean age at the time of surgery was 64±14 years. Based on the preoperative echocardiographic findings, 45 (85%) tumors were diagnosed as CM and 8 as NM cardiac tumors (Figure 1). Evaluation of pathohistological specimens revealed CM in 39 of 53 (74%) operated patients. Patohistiologically, a NM cardiac tumor was diagnosed in 7 patients who were preoperatively classified as CM. The sensitivity and specificity of preoperative echocardiography for the detection of CM were 97% and 50%, respectively (Figure 1). The echocardiographic characteristics of pathohistologically confirmed CM were compared to cases of NM cardiac tumors. The comparison between the two groups revealed statistically significant differences in localization and tumor size. All NM cardiac tumors were located in an atypical position and 72% of CM were found in a typical position within the left atrium (p<0.001). NM cardiac tumors were also significantly smaller than CM (25.1±12.6 mm vs. 37.5±18.5 mm, p=0.029).
Conclusion
Our single-center study confirms the excellent sensitivity of echocardiography for CM diagnosis. The specificity of echocardiography was modest, thus caution is warranted due to a wide differential diagnosis of CM. The diagnosis of CM seems to be less likely with atypical tumor location and small tumor size. Other non-invasive imaging modalities such as cardiac computed tomography or magnetic resonance imaging should be considered in such cases.
Funding Acknowledgement
Type of funding sources: None. Figure 1. Flow chart showing the number of patients diagnosed with CM on preoperative echocardiography.
Abstract
Funding Acknowledgements
Type of funding sources: None.
Background
Myocardial fibrosis is a known prognostic factor in patients with systemic right ventricle (SRV). In these patients fixed ...myocardial perfusion defects are a common finding and are thought to represent areas of myocardial infarction and fibrosis. However, no study has yet correlated myocardial perfusion imaging findings with cardiac magnetic resonance (CMR) imaging, which is the imaging gold standard for detecting myocardial fibrosis.
Purpose
Our aim was to evaluate whether fixed myocardial perfusion defects in adult patients with SRV represent myocardial fibrosis.
Methods
Patients with SRV followed at our outpatient clinic for congenital heart disease were prospectively included. Myocardial perfusion was evaluated with a two-day stress/rest single-photon emission computed tomography (SPECT) protocol, focal myocardial fibrosis with late gadolinium enhancement (LGE) and diffuse myocardial fibrosis with T1 mapping by CMR. The 12-segment model of the right ventricle was used to report segments with myocardial perfusion defects and fibrosis (Figure 1).
Results
Fifteen patients with SRV (12 patients with transposition of the great arteries following atrial switch procedure and 3 patients with congenitally corrected transposition of the great arteries; 4 (26.7%) females; mean age 34.6 ± 10.0 years) were included. Myocardial perfusion defects were present in 14 patients (93%), with predominate fixed perfusion defects (73%) and less common reversible perfusion defects (27%). Fixed myocardial perfusion defects were most frequent in anterior RV segments (figure 1), with multiple segments affected in 11 patients (median number of affected segments – 2 segments). CMR was possible in 11 (73%) patients, others had a permanent pacemaker. LGE indicating focal myocardial fibrosis was detected in only 1 (9%) patient, while increased T1 values indicating diffuse myocardial fibrosis were present in 7 (64%) patients. There was no matching between areas of fixed myocardial perfusion defects and focal myocardial fibrosis in individual patients.
Conclusions
In our study, fixed myocardial perfusion defects detected on SPECT in patients with SRV did not represent areas of focal myocardial fibrosis on CMR. Other causes than scar may explain the frequently reported fixed perfusion defects, such as SRV anatomy with anterior position of the outflow tract and aorta, SRV morphology with variable degree of wall thickness and hypertrophy that influences tracer accumulation and image quality, or difficulties due to complex image acquisition and interpretation. To improve the diagnostic accuracy, the use of fused imaging modalities (SPECT-CT or PET-CT) is recommended in patients with SRV.
Figure 1. Bull`s eye 12-segment plots of the right ventricle (RV) representing the number of segments with fixed myocardial perfusion defects detected by SPECT (1A) and LGE by CMR (1B) in patients with SRV. ANT – anterior, FW – free wall, INF – inferior, SEP – septal wall of RV.
Abstract Figure.
To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS ...and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
The structural diversity and tunability of the capsid proteins (CPs) of various icosahedral and rod-shaped viruses have been well studied and exploited in the development of smart hybrid ...nanoparticles. However, the potential of CPs of the wide-spread flexuous filamentous plant viruses remains to be explored. Here, we show that we can control the shape, size, RNA encapsidation ability, symmetry, stability and surface functionalization of nanoparticles through structure-based design of CP from potato virus Y (PVY). We provide high-resolution insight into CP-based self-assemblies, ranging from large polymorphic or monomorphic filaments to smaller annular, cubic or spherical particles. Furthermore, we show that we can prevent CP self-assembly in bacteria by fusion with a cleavable protein, enabling controlled nanoparticle formation in vitro. Understanding the remarkable structural diversity of PVY CP not only provides possibilities for the production of biodegradable nanoparticles, but may also advance future studies of CP's polymorphism in a biological context.
Kinked-stepped, high Miller index surfaces of metal crystals are chiral and, therefore, exhibit enantiospecific properties. Previous temperature-programmed desorption (TPD) spectra have shown that ...the desorption energies of R-3-methylcyclohexanone (R-3-MCHO) on the chiral Cu(643)R and Cu(643)S surfaces are enantiospecific (J. Am. Chem. Soc. 2002, 124, 2384). Here, a comparison of the TPD spectra from Cu(111), Cu(221), Cu(533), Cu(653)R&S, and Cu(643)R&S surfaces reveals that the enantiospecific desorption occurs from the chiral kink sites on the Cu(643) surfaces. Titration of the chiral kink sites with I atoms confirms this assignment of desorption features in the TPD spectra. Finally, the enantiospecific difference in the desorption energies of R- and S-3-MCHO has been used as the basis for demonstration of an enantioselective, kinetic separation of racemic 3-MCHO into its purified components during adsorption and desorption on the Cu(643)R&S surfaces.
Abstract
Pore-forming toxins are an important component of the venom of many animals. Actinoporins are potent cytolysins that were first detected in the venom of sea anemones; however, they are ...occasionally found in animals other than cnidarians and are expanded in a few predatory gastropods. Here, we report the presence of 27 unique actinoporin-like genes with monophyletic origin in Mytilus galloprovincialis, which we have termed mytiporins. These mytiporins exhibited a remarkable level of molecular diversity and gene presence–absence variation, which warranted further studies aimed at elucidating their functional role. We structurally and functionally characterized mytiporin-1 and found significant differences from the archetypal actinoporin fragaceatoxin C. Mytiporin-1 showed weaker permeabilization activity, no specificity towards sphingomyelin, and weak activity in model lipid systems with negatively charged lipids. In contrast to fragaceatoxin C, which forms octameric pores, functional mytiporin-1 pores on negatively charged lipid membranes were hexameric. Similar hexameric pores were observed for coluporin-26 from Cumia reticulata and a conoporin from Conus andremenezi. This indicates that also other molluscan actinoporin-like proteins differ from fragaceatoxin C. Although the functional role of mytiporins in the context of molluscan physiology remains to be elucidated, the lineage-specific gene family expansion event that characterizes mytiporins indicates that strong selective forces acted on their molecular diversification. Given the tissue distribution of mytiporins, this process may have broadened the taxonomic breadth of their biological targets, which would have important implications for digestive processes or mucosal immunity.
Aims
This report presents the clinical course, neuropathology and ultrastructure of neuronal tau inclusions of four Slovene relatives with P364S MAPT mutation.
Methods
The clinical history of three ...out of four P364S MAPT mutation carriers was taken. After formalin fixation, thorough sampling of the central nervous system was followed by paraffin embedding, H&E, Gallyas, Bielschowsky and immunostaining with AT8, anti‐3R, anti‐4R tau, anti‐amyloid‐β, anti‐TDP43 and anti‐alpha‐synuclein antibodies. The distribution and density of different types of neuronal tau inclusions were semiquantitatively assessed. In addition, the ultrastructure of neuronal tau inclusions was analysed.
Results
Macroscopic examination of the brains was unremarkable. Microscopically, neuronal tau inclusions of almost all known types were widespread and distributed fairly uniformly in all cases. Pick bodies and swollen neurones were found in only one family member. Mutant tau was composed of 3R and 4R isoforms, with a slight predominance of 3R tau. Composite neuronal tau inclusion (CNTI), found in all four relatives, was a hallmark of the P364S MAPT mutation. CNTI showed compartmental differences in H&E and Gallyas staining, tau isoforms immunolabelling and ultrastructure, displaying fuzzy fibrils in the core and paired twisted tubules at the periphery.
Conclusions
P364S MAPT mutation is characterized clinically by a variable combination of frontotemporal dementia, parkinsonism and motor neurone disease of short duration, and neuropathologically by a widespread uniform distribution of all known neuronal tau inclusions in one family member. Two‐compartment CNTI is a unique characteristic of the P364S MAPT mutation.
Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European ...marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).
Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.
Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.
Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.
Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Whilst the act of sniffing can provide us with an indirect method to study the central mechanisms of respiratory control, functional neuroimaging now provides us with a tool to directly ...visualise the activity of the human brain during this voluntary action using functional magnetic resonance imaging (fMRI). We performed fMRI during sniffing in 11 healthy volunteers where all subjects executed single, brisk sniffs of around 60% of their maximum sniff pressure at intervals of approximately every 20 s. Simultaneous nasal pressure and chest movements were also measured during the task and a statistical parametric map of activation correlating with the sniff manoeuvre was calculated. A bilateral cortical and subcortical sensorimotor network was activated. The activations were localised within the primary sensorimotor cortex, lateral premotor cortex, supplementary motor area, anterior cingulate, insula, basal ganglia, thalami, mesencephalon, upper pons, cerebellar vermis, piriform cortex, entorhinal cortex and parahippocampal gyrus. The activated brain areas identified, i.e. the cortical and subcortical respiratory network, are similar to those described in other neuroimaging studies of voluntary inspiration. Sniffing is a component of olfactory processing and activations of the olfaction-related cortical areas were also observed in our study. The results of our study show that event-related fMRI can be successfully used to study sniffing. This provides a novel approach to our study of the central neural control of respiration.
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