Quantitative Approach to Fragmented QRS in Arrhythmogenic Cardiomyopathy: From Disease towards Asymptomatic Carriers of Pathogenic Variants

Fragmented QRS complexes (fQRS) are common in patients with arrhythmogenic cardiomyopathy (ACM). A new method of fQRS quantification may aid early disease detection in pathogenic variant carriers and assessment of prognosis in patients with early stage ACM. Patients with definite ACM (n = 221, 66%), carriers of a pathogenic ACM-associated variant without a definite ACM diagnosis (n = 57, 17%) and control subjects (n = 58, 17%) were included. Quantitative fQRS (Q-fQRS) was defined as the total amount of deflections in the QRS complex in all 12 electrocardiography (ECG) leads. Q-fQRS was scored by a single observer and reproducibility was determined by three independent observers. Q-fQRS count was feasible with acceptable intra- and inter-observer agreement. Q-fQRS count is significantly higher in patients with definite ACM (54 ± 15) and pathogenic variant carriers (55 ± 10) compared to controls (35 ± 5) (p < 0.001). In patients with ACM, Q-fQRS was not associated with sustained ventricular arrhythmia (p = 0.701) at baseline or during follow-up (p = 0.335). Both definite ACM patients and pathogenic variant carriers not fulfilling ACM diagnosis have a higher Q-fQRS than controls. This may indicate that increased Q-fQRS is an early sign of disease penetrance. In concealed and early stages of ACM the role of Q-fQRS for risk stratification is limited.

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The Role of MicroRNAs in Arrhythmogenic Cardiomyopathy: Biomarkers or Innocent Bystanders of Disease Progression?

International Journal of Molecular Sciences ◽

10.3390/ijms21176434 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6434

Author(s):

Maria Bueno Marinas ◽

Rudy Celeghin ◽

Marco Cason ◽

Gaetano Thiene ◽

Cristina Basso ◽

...

Keyword(s):

Gene Expression Regulation ◽

Phenotypic Variability ◽

Incomplete Penetrance ◽

Primary Role ◽

Arrhythmogenic Cardiomyopathy ◽

Small Noncoding Rnas ◽

Early Disease Detection ◽

Pathogenic Variants ◽

Fatty Replacement ◽

Genes Encoding

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease characterized by a progressive fibro-fatty replacement of the working myocardium and by life-threatening arrhythmias and risk of sudden cardiac death. Pathogenic variants are identified in nearly 50% of affected patients mostly in genes encoding for desmosomal proteins. AC incomplete penetrance and phenotypic variability advocate that other factors than genetics may modulate the disease, such as microRNAs (miRNAs). MiRNAs are small noncoding RNAs with a primary role in gene expression regulation and network of cellular processes. The implication of miRNAs in AC pathogenesis and their role as biomarkers for early disease detection or differential diagnosis has been the objective of multiple studies employing diverse designs and methodologies to detect miRNAs and measure their expression levels. Here we summarize experiments, evidence, and flaws of the different studies and hitherto knowledge of the implication of miRNAs in AC pathogenesis and diagnosis.

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Environmental technology: Fluidised-bed steam dryers — latest developments and practical experience

Sugar Industry ◽

10.36961/si17160 ◽

2016 ◽

pp. 86-90

Author(s):

Gerald Caspers ◽

Klaus Nammert ◽

Holger Fersterra ◽

Hartmut Hafemann

Keyword(s):

Data Acquisition ◽

Early Stage ◽

Practical Experience ◽

Great Depth ◽

Fluidised Bed ◽

Operating Data ◽

Beet Pulp ◽

Improved Design ◽

Distribution Plate ◽

And Control

Fluidised-bed steam dryers have been in use for industrial-scale drying of pressed beet pulp for more than 20 years. This highly energy-efficient process can be considered to be state of the art in the industry. Scientific laboratory and pilot-plant testing have provided the basis for a detailed description of the principles of fluidisation and drying in superheated water vapour. Advances in production data acquisition, in particular regarding the options for the real-time presentation and evaluation of high-resolution operating data (Industry 4.0), have opened up new potentials for optimisation of the drying process in fluidised-bed steam dryers. By analysing and interpreting sequences of events, or simultaneous events, it is now possible to analyse process behaviour in great depth. This allows malfunctions to be avoided by improved design or, assisted by suitable measuring and control systems, to be detected at an early stage. Failures can then be prevented altogether by initiating automated countermeasures. On the basis of more recent insights gained from the analysis of faults and disruptions using modern operating data acquisition, BMA’s fluidised-bed steam dryer (WVT) has been subjected to fundamental technological and technical improvements, so it now meets today’s demands for efficiency and reliability. Modifications include the product inlet, the distribution plate and several other parts, in addition to the known and patented PPS (Plug Protection System; EP 2457649 B1), and the patented rotary weir (EP 2146167 B1).

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Interactive effects between travel behaviour and COVID-19: a questionnaire study

Transportation Safety and Environment ◽

10.1093/tse/tdab003 ◽

2021 ◽

Author(s):

Jinbao Zhang ◽

Jaeyoung Lee

Keyword(s):

Early Stage ◽

Travel Behaviour ◽

Interactive Effects ◽

Factors Affecting ◽

Individual Level ◽

Passenger Volume ◽

Spatial Autoregressive ◽

Railway Passenger ◽

The Individual ◽

And Control

Abstract This study has two main objectives: (i) to analyse the effect of travel characteristics on the spreading of disease, and (ii) to determine the effect of COVID-19 on travel behaviour at the individual level. First, the study analyses the effect of passenger volume and the proportions of different modes of travel on the spread of COVID-19 in the early stage. The developed spatial autoregressive model shows that total passenger volume and proportions of air and railway passenger volumes are positively associated with the cumulative confirmed cases. Second, a questionnaire is analysed to determine changes in travel behaviour after COVID-19. The results indicate that the number of total trips considerably decreased. Public transport usage decreased by 20.5%, while private car usage increased by 6.4%. Then the factors affecting the changes in travel behaviour are analysed by logit models. The findings reveal significant factors, including gender, occupation and travel restriction. It is expected that the findings from this study would be helpful for management and control of traffic during a pandemic.

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Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome

Genetics in Medicine ◽

10.1038/s41436-020-01078-6 ◽

2021 ◽

Author(s):

Pauline Arnaud ◽

Hélène Morel ◽

Olivier Milleron ◽

Laurent Gouya ◽

Christine Francannet ◽

...

Keyword(s):

Marfan Syndrome ◽

Somatic Mosaicism ◽

Variant Calling ◽

Copy Number Variations ◽

Pathogenic Variant ◽

Single Nucleotide Variants ◽

Bioinformatics Analyses ◽

Single Nucleotide ◽

Fbn1 Gene ◽

Pathogenic Variants

Abstract Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. Results These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. Conclusion This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.

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Macular vessel density and foveal avascular zone parameters in patients after acute primary angle closure determined by OCT angiography

Scientific Reports ◽

10.1038/s41598-020-73223-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kangcheng Liu ◽

Huizhuo Xu ◽

Haibo Jiang ◽

Hua Wang ◽

Pingbao Wang ◽

...

Keyword(s):

Early Stage ◽

Normal Subjects ◽

Vessel Density ◽

Foveal Avascular Zone ◽

Angle Closure ◽

Acute Primary Angle Closure ◽

Primary Angle Closure ◽

Circularity Index ◽

Avascular Zone ◽

And Control

Abstract This study analyzed the optical coherence tomography angiography (OCTA) macular parameters in primary angle-closure glaucoma (PACG) patients after acute primary angle closure (APAC) episodes. Thirty-three patients with 33 APAC eyes and 33 primary angle closure suspect (PACS) eyes and 33 age-matched normal subjects (controls) were enrolled. Macular vessel density (VD) in central, inner, outer and full regions and foveal avascular zone (FAZ) parameters (area, perimeter and circularity index) were compared between APAC, PACS, and control eyes. For resolved APAC eyes, the VD in each macular region was significantly lower than that in control eyes, with less central and inner macular VD than PACS eyes. The central macular VD was significantly lower in PACS eyes than in controls. There was no difference in FAZ area and perimeter between APAC, PACS, and control eyes. FAZ circularity was highest in control eyes, followed by PACS eyes, and lowest in APAC eyes. The AUC, sensitivity and specificity of FAZ circularity were 0.944, 93.9% and 84.8%, respectively, in APAC eyes and 0.881, 84.8% and 81.8%, respectively, in PACS eyes. Therefore, FAZ circularity had the best discrimination capability for detecting both APAC and PACS eyes. Macular assessment with OCTA could provide an accurate early-stage diagnostic tool for PACG.

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Supporting Co-Design of Physical and Control Architectures of Mechatronic Systems

Volume 2: 31st Computers and Information in Engineering Conference, Parts A and B ◽

10.1115/detc2011-48200 ◽

2011 ◽

Author(s):

Andre´s A. Alvarez Cabrera ◽

Hitoshi Komoto ◽

Tetsuo Tomiyama

Keyword(s):

Control Structure ◽

Mutual Influence ◽

Early Stage ◽

Physical Structure ◽

Mechatronic Systems ◽

Design Problems ◽

Software And Hardware ◽

Design Integration ◽

And Control ◽

Recent Tendency

There is a rather recent tendency to define the physical structure and the control structure of a system concurrently when designing the architecture of a product, i.e., to perform codesign. We argue that co-design can only be enabled when the mutual influence between physical system and control is made evident to the designer at an early stage. Though the idea of design integration is not new, to the best of our knowledge, there is no computer tooling that explicitly supports this activity by enabling co-design as stated before. In this paper the authors propose a method for co-design of physical and control architectures as a better approach to design mechatronic systems, allowing to exploit the synergy between software and hardware and detecting certain design problems at an early stage of design. The proposed approach is supported by a set of tools and demonstrated through an example case.

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Antisettici e controllo della carica batterica nelle ulcere venose/Antiseptics and control of bacterial load in venous ulcers

Italian Journal of Wound Care ◽

10.4081/ijwc.2018.21 ◽

2018 ◽

Vol 2 (2) ◽

Author(s):

Giuseppe Nebbioso ◽

Ciro Falasconi ◽

Viviana Nebbioso ◽

Francesco Petrella

Keyword(s):

Tissue Repair ◽

Chronic Wound ◽

Early Stage ◽

Bacterial Load ◽

Repair Process ◽

Local Infection ◽

Bacterial Burden ◽

Venous Ulcers ◽

Systemic Antibiotic Therapy ◽

And Control

L’insorgenza di infezione su una lesione cutanea cronica determina un arresto del processo di riparazione tessutale e impone l’instaurazione di una terapia antibiotica sistemica che, in una fase iniziale, sarà empirica e, dunque, non scevra di insuccessi. L’utilizzo di antimicrobici con ridotto potere citotossoco/istiolesivo può essere considerata, in molti casi, una valida alternativa per il controllo della carica batterica e dell’infezione locale. L’associazione di antimicrobici a base di poliesanide biguanide, betaina e cadexomero iodico, in molti casi, permette di controllare/ridurre la carica batterica e l’infezione locale fungendo da starter per la ripresa del processo di riparazione tessutale. The onset of infection on a skin ulcer (chronic wound) leads to a halt in the tissue repair process and requires a systemic antibiotic therapy which, at an early stage, will be empirical and, therefore, not free from setbacks. The use of antimicrobials with reduced cytotoxic/histiolesive power can be considered, in many cases, a valid alternative for bacterial burden and local infection control. The combination of antimicrobials based on polystyrene biguanide, betaine and iodine cadexomer, in many cases, allows to control/reduce the bacterial burden and local infection by acting as a starter for the resumption of the tissue repair process.

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Whole-Exome Sequencing Identifies Pathogenic Variants in TJP1 Gene Associated With Arrhythmogenic Cardiomyopathy

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.118.002123 ◽

2018 ◽

Vol 11 (10) ◽

Cited By ~ 19

Author(s):

Marzia De Bortoli ◽

Alex V. Postma ◽

Giulia Poloni ◽

Martina Calore ◽

Giovanni Minervini ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Arrhythmogenic Cardiomyopathy ◽

Pathogenic Variants ◽

Whole Exome

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Clinical and molecular characterization of patients fulfilling Chompret criteria for Li-Fraumeni syndrome in Southern Brazil

PLoS ONE ◽

10.1371/journal.pone.0251639 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0251639

Author(s):

Camila Matzenbacher Bittar ◽

Yasminne Marinho de Araújo Rocha ◽

Igor Araujo Vieira ◽

Clévia Rosset ◽

Tiago Finger Andreis ◽

...

Keyword(s):

Soft Tissue Sarcomas ◽

Pathogenic Variant ◽

Southern Brazil ◽

Premenopausal Breast Cancer ◽

Li Fraumeni Syndrome ◽

Cancer Predisposition Syndrome ◽

Pathogenic Variants ◽

Li Fraumeni ◽

Group B ◽

Adrenocortical Carcinomas

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis. Information on TP53 germline pathogenic variant (PV) prevalence when using Chompret criteria in South America and especially in Brazil is scarce. Therefore, the aim of this study was to characterize patients that fulfilled these specific criteria in southern Brazil, a region known for its high population frequency of a founder TP53 variant c.1010G>A (p.Arg337His), as known as R337H. TP53 germline testing of 191 cancer-affected and independent probands with LFS phenotype identified a heterozygous pathogenic/likely pathogenic variant in 26 (13.6%) probands, both in the DNA binding domain (group A) and in the oligomerization domain (group B) of the gene. Of the 26 carriers, 18 (69.23%) were R337H heterozygotes. Median age at diagnosis of the first tumor in groups A and B differed significantly in this cohort: 22 and 2 years, respectively (P = 0.009). The present study shows the clinical heterogeneity of LFS, highlights particularities of the R337H variant and underscores the need for larger collaborative studies to better define LFS prevalence, clinical spectrum and penetrance of different germline TP53 pathogenic variants.

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A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype

BioMed Research International ◽

10.1155/2021/6661860 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Lulu Yan ◽

Ru Shen ◽

Zongfu Cao ◽

Chunxiao Han ◽

Yuxin Zhang ◽

...

Keyword(s):

De Novo ◽

Genetic Disorder ◽

Neurodevelopmental Disorder ◽

Three Dimensional ◽

Missense Variant ◽

Pathogenic Variant ◽

Dimensional Structure ◽

Chinese Family ◽

Speech Impairment ◽

Pathogenic Variants

PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the PPP2R5D gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the PPP2R5D gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of PPP2R5D associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.

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