Congenital Muscular Dystrophies and Myopathies: An Overview and Update

2017 ◽  
Vol 48 (04) ◽  
pp. 247-261 ◽  
Author(s):  
Janbernd Kirschner ◽  
Carsten Bönnemann ◽  
David Schorling
Keyword(s):  
Genetic Background ◽  
Wide Spectrum ◽  
Clinical Care ◽  
Genetic Diagnosis ◽  
Muscular Dystrophies ◽  
Congenital Myopathies ◽  
Clinical Phenotypes ◽  
Recent Advances ◽  
The Right ◽  
Therapeutic Considerations

AbstractWith continuous deciphering of the genetic background of congenital muscular dystrophies and congenital myopathies, some of the historic classifications based on clinical phenotypes or histopathological similarities have become blurred. With a growing number of associated genes, the general understanding of these disorders is shifting to a more genotype-based classification. Furthermore, establishing of the right genetic diagnosis involves new aspects of clinical care and therapeutic considerations for gene-specific phenotypes and pathology. In this review, we give an overview of the wide spectrum of clinical phenotypes of congenital muscular dystrophies and congenital myopathies, outline diagnostic considerations, and summarize recent advances in research for selected diseases.

Recent Advances in Therapeutic Applications of Bisbenzimidazoles

2020 ◽  
Vol 16 (4) ◽  
pp. 454-486 ◽  
Author(s):  
Smita Verma ◽  
Vishnuvardh Ravichandiran ◽  
Nihar Ranjan ◽  
Swaran J.S. Flora
Keyword(s):  
Heterocyclic Compounds ◽  
Wide Spectrum ◽  
Dna Recognition ◽  
Present Review ◽  
Pharmacological Activities ◽  
Structural Motifs ◽  
Therapeutic Applications ◽  
The Past ◽  
Recent Advances

Nitrogen-containing heterocycles are one of the most common structural motifs in approximately 80% of the marketed drugs. Of these, benzimidazoles analogues are known to elicit a wide spectrum of pharmaceutical activities such as anticancer, antibacterial, antiparasitic, antiviral, antifungal as well as chemosensor effect. Based on the benzimidazole core fused heterocyclic compounds, crescent-shaped bisbenzimidazoles were developed which provided an early breakthrough in the sequence-specific DNA recognition. Over the years, a number of functional variations in the bisbenzimidazole core have led to the emergence of their unique properties and established them as versatile ligands against several classes of pathogens. The present review provides an overview of diverse pharmacological activities of the bisbenzimidazole analogues in the past decade with a brief account of its development through the years.

scholarly journals Role of CMR Imaging in Diagnostics and Evaluation of Cardiac Involvement in Muscle Dystrophies

2021 ◽  
Author(s):  
Edyta Blaszczyk ◽  
Jan Gröschel ◽  
Jeanette Schulz-Menger
Keyword(s):  
Clinical Care ◽  
Fatty Infiltration ◽  
Severe Heart Failure ◽  
Diffuse Fibrosis ◽  
Muscular Dystrophies ◽  
Invasive Technique ◽  
Myocardial Tissue ◽  
Therapeutic Decisions ◽  
Cardiovascular Evaluation ◽  
Unique Capability

Abstract Purpose of Review This review aims to outline the utility of cardiac magnetic resonance (CMR) in patients with different types of muscular dystrophies for the assessment of myocardial involvement, risk stratification and in guiding therapeutic decisions. Recent Findings In patients suffering from muscular dystrophies (MD), even mild initial dysfunction may lead to severe heart failure over a time course of years. CMR plays an increasing role in the diagnosis and clinical care of these patients, mostly due to its unique capability to precisely characterize subclinical and progressive changes in cardiac geometry, function in order to differentiate myocardial injury it allows the identification of inflammation, focal and diffuse fibrosis as well as fatty infiltration. CMR may provide additional information in addition to the physical examination, laboratory tests, ECG, and echocardiography. Summary Further trials are needed to investigate the potential impact of CMR on the therapeutic decision-making as well as the assessment of long-term prognosis in different forms of muscular dystrophies. In addition to the basic cardiovascular evaluation, CMR can provide a robust, non-invasive technique for the evaluation of subclinical myocardial tissue injury like fat infiltration and focal and diffuse fibrosis. Furthermore, CMR has a unique capability to detect the progression of myocardial tissue damage in patients with a preserved systolic function.

scholarly journals Challenges and Controversies in the Genetic Diagnosis of Hereditary Spastic Paraplegia

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Lydia Saputra ◽  
Kishore Raj Kumar
Keyword(s):  
Genetic Diagnosis ◽  
Spastic Paraplegia ◽  
Limb Weakness ◽  
Hereditary Spastic Paraplegias ◽  
Gene Testing ◽  
Testing Strategies ◽  
Whole Exome ◽  
The Right ◽  
Gene Panels ◽  
High Degree

Abstract Purpose of Review The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP. Recent Findings There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments. Summary Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis.

scholarly journals Enabling Technologies for Improved Data Management: Hardware

2001 ◽  
Vol 9 (1) ◽  
pp. 11-25
Author(s):  
Kerstin van Dam-Kleese ◽  
Michael Hopewell
Keyword(s):  
Data Management ◽  
Scientific Community ◽  
Wide Spectrum ◽  
Work Force ◽  
Working Environment ◽  
Computational Techniques ◽  
Enabling Technologies ◽  
New Challenges ◽  
The Uk ◽  
The Right

The most valuable assets in every scientific community are the expert work force and the research results/data produced. The last decade has seen new experimental and computational techniques developing at an ever-faster pace, encouraging the production of ever-larger quantities of data in ever-shorter time spans. Concurrently the traditional scientific working environment has changed beyond recognition. Today scientists can use a wide spectrum of experimental, computational and analytical facilities, often widely distributed over the UK and Europe. In this environment new challenges are posed for the Management of Data every day, but are we ready to tackle them? Do we know exactly what the challenges are? Is the right technology available and is it applied where necessary? This part of enabling technologies investigates current hardware techniques and their functionalities and provides a comparison between various products.

scholarly journals A Mini Review: Recent Advances in Surface Modification of Porous Silicon

Materials ◽  
2018 ◽  
Vol 11 (12) ◽  
pp. 2557 ◽  
Author(s):  
Seo Lee ◽  
Jae Kang ◽  
Dokyoung Kim
Keyword(s):  
Surface Modification ◽  
Porous Silicon ◽  
Wide Spectrum ◽  
Basic Research ◽  
Recent Advances ◽  
Developed Surface ◽  
The Many ◽  
Insight Into ◽  
Biomedical Fields

Porous silicon has been utilized within a wide spectrum of industries, as well as being used in basic research for engineering and biomedical fields. Recently, surface modification methods have been constantly coming under the spotlight, mostly in regard to maximizing its purpose of use. Within this review, we will introduce porous silicon, the experimentation preparatory methods, the properties of the surface of porous silicon, and both more conventional as well as newly developed surface modification methods that have assisted in attempting to overcome the many drawbacks we see in the existing methods. The main aim of this review is to highlight and give useful insight into improving the properties of porous silicon, and create a focused description of the surface modification methods.

Is GRADE the Right Choice for Clinical Practice Guidelines Developed by the American Academy of Otolaryngology–Head and Neck Surgery Foundation?

2019 ◽  
Vol 161 (1) ◽  
pp. 3-5
Author(s):  
Andrés M. Bur ◽  
Richard M. Rosenfeld
Keyword(s):  
Clinical Practice ◽  
American Academy ◽  
Head And Neck ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Current Knowledge ◽  
Clinical Care ◽  
Neck Surgery ◽  
Head And Neck Surgery ◽  
The Right

Clinical practice guidelines (CPGs), developed to inform clinicians, patients, and policy makers about what constitutes optimal clinical care, are one way of increasing implementation of evidence into clinical practice. Many factors must be considered by multidisciplinary guideline panels, including strength of available evidence, limitations of current knowledge, risks/benefits of interventions, patient values, and limited resources. Grading of Recommendations Assessment, Development and Evaluation (GRADE) is a framework for summarizing evidence that has been endorsed by many national and international organizations for developing CPGs. But is GRADE the right choice for CPGs developed by the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF)? In this commentary, we will introduce GRADE, discuss its strengths and limitations, and address the question of what potential benefits GRADE might offer beyond existing methodology used by the AAO-HNSF in developing CPGs.

scholarly journals Pain Assessment: Subjectivity, Objectivity, and the Use of Neurotechnology Part One: Practical and Ethical Issues

2010 ◽  
Vol 4;13 (4;7) ◽  
pp. 305-315 ◽  
Author(s):  
James Giordano
Keyword(s):  
Pain Assessment ◽  
Subjective Experience ◽  
Ethical Issues ◽  
Social Issues ◽  
Clinical Care ◽  
Pain Syndrome ◽  
Objective Evaluation ◽  
Pain Patient ◽  
Key Words Pain ◽  
The Right

The pain clinician is confronted with the formidable task of objectifying the subjective phenomenon of pain so as to determine the right treatments for both the pain syndrome and the patient in whom the pathology is expressed. However, the experience of pain — and its expression — remains enigmatic. Can currently available evaluative tools, questionnaires, and scales actually provide adequately objective information about the experiential dimensions of pain? Can, or will, current and future iterations of biotechnology — whether used singularly or in combination (with other technologies as well as observational-behavioral methods) — afford objective validation of pain? And what of the clinical, ethical, legal and social issues that arise in and from the use — and potential misuse — of these approaches? Subsequent trajectories of clinical care depend upon the findings gained through the use of these techniques and their inappropriate employment – or misinterpretation of the results they provide — can lead to misdiagnoses and incorrect treatment. This essay is the first of a two-part series that explicates how the intellectual tasks of knowing about pain and the assessment of its experience and expression in the pain patient are constituent to the moral responsibility of pain medicine. Herein, we discuss the problem of pain and its expression, and those methods, techniques, and technologies available to bridge the gap between subjective experience and objective evaluation. We address how these assessment approaches are fundamental to apprehend both pain as an objective, neurological event, and its impact upon the subjective experience, existence, and expectations of the person in pain. In this way, we argue that the right use of technology — together with inter-subjectivity, compassion, and insight — can sustain the good of pain care as both a therapeutic and moral enterprise. Key words: pain, assessment, neurotechnology, biotechnology, neuroethics, medicine

scholarly journals Rare variants in the genetic background modulate the expressivity of neurodevelopmental disorders

2018 ◽  
Author(s):  
Lucilla Pizzo ◽  
Matthew Jensen ◽  
Andrew Polyak ◽  
Jill A. Rosenfeld ◽  
Katrin Mannik ◽  
...  
Keyword(s):  
Family History ◽  
Genetic Background ◽  
Rare Variants ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Clinical Information ◽  
Disease Genes ◽  
Complete Evaluation ◽  
Rare Cnvs ◽  
Complex Disorders

AbstractPurposeTo assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations.MethodsWe analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated mutations.ResultsThe number of rare secondary mutations in functionally intolerant genes (second-hits) correlated with the expressivity of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in probands with autism carrying gene-disruptive mutations (n=184, p=0.03) compared to their carrier family members. Probands with 16p12.1 deletion and a strong family history presented more severe clinical features (p=0.04) and higher burden of second-hits compared to those with mild/no family history (p=0.001). The number of secondary variants also correlated with the severity of cognitive impairment in probands carrying pathogenic rare CNVs (n=53) or de novo mutations in disease genes (n=290), and negatively correlated with head size among 80 probands with 16p11.2 deletion. These second-hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for genes affecting cellular and developmental processes.ConclusionAccurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate gene mutation is identified.

scholarly journals Latest Advances in Cardiac CT

2020 ◽  
Vol 15 ◽  
Author(s):  
Thomas D Heseltine ◽  
Scott W Murray ◽  
Balazs Ruzsics ◽  
Michael Fisher
Keyword(s):  
Machine Learning ◽  
Fractional Flow Reserve ◽  
Cardiac Ct ◽  
Disease Risk ◽  
Clinical Care ◽  
Plaque Burden ◽  
Extensive Literature ◽  
Fractional Flow ◽  
Flow Reserve ◽  
Recent Advances

Recent rapid technological advancements in cardiac CT have improved image quality and reduced radiation exposure to patients. Furthermore, key insights from large cohort trials have helped delineate cardiovascular disease risk as a function of overall coronary plaque burden and the morphological appearance of individual plaques. The advent of CT-derived fractional flow reserve promises to establish an anatomical and functional test within one modality. Recent data examining the short-term impact of CT-derived fractional flow reserve on downstream care and clinical outcomes have been published. In addition, machine learning is a concept that is being increasingly applied to diagnostic medicine. Over the coming decade, machine learning will begin to be integrated into cardiac CT, and will potentially make a tangible difference to how this modality evolves. The authors have performed an extensive literature review and comprehensive analysis of the recent advances in cardiac CT. They review how recent advances currently impact on clinical care and potential future directions for this imaging modality.

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