scholarly journals A generic assay for the identification of splicing variants that induce nonsense-mediated decay in Pompe disease

2020 ◽  
Author(s):  
Atze J. Bergsma ◽  
Stijn L. M. in ’t Groen ◽  
Fabio Catalano ◽  
Manjiro Yamanaka ◽  
Satoru Takahashi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Pompe Disease ◽  
Treatment Options ◽  
Genetic Diseases ◽  
Mrna Degradation ◽  
Aberrant Splicing ◽  
Monogenic Disorder ◽  
Nonsense Mediated Decay ◽  
Splicing Variants ◽  
The Common

Abstract DNA variants affecting mRNA expression and processing in genetic diseases are often missed or poorly characterized. We previously reported a generic assay to identify variants that affect mRNA expression and splicing in Pompe disease, a monogenic disorder caused by deficiency of acid α-glucosidase (GAA). However, this assay could miss mRNA that is subjected to degradation. Here, we inhibited mRNA degradation using cycloheximide and performed unbiased splicing analysis of all GAA exons using exon flanking RT-PCR and exon internal RT-qPCR. In four patients that were suspected of harboring splicing variants but for which aberrant splicing could not be detected in normally growing cells, we detected a total of 10 novel splicing events in cells treated with cycloheximide. In addition, we found that sequences of GAA introns 6 and 12 were naturally included in a subset of transcripts from patients and healthy controls, indicating inefficient canonical splicing. Identification of aberrant splicing caused by the common Asian variant c.546G>T allowed the development of an antisense oligonucleotide that promoted canonical GAA pre-mRNA splicing and elevated GAA enzymatic activity. Our results indicate that this extended generic splicing assay allows the detection of aberrant splicing in cases of mRNA degradation to enable functional analysis of unknown splicing variants and the development of targeted treatment options.

An Overview of Dementias

2012 ◽  
Vol 21 (3) ◽  
pp. 75-84
Author(s):  
Venkata Vijaya K. Dalai ◽  
Jason E. Childress ◽  
Paul E Schulz
Keyword(s):  
Clinical Presentation ◽  
Treatment Options ◽  
Current Treatment ◽  
Great Variability ◽  
Health Concern ◽  
Public Health Concern ◽  
Life Threatening ◽  
The Common ◽  
Neurodegenerative Dementias ◽  
Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

An overview of proximal suspensory ligament desmitis

UK-Vet Equine ◽  
2019 ◽  
Vol 3 (5) ◽  
pp. 175-181
Author(s):  
Jonathan Anderson
Keyword(s):  
Treatment Options ◽  
Poor Performance ◽  
Diagnostic Techniques ◽  
Common Cause ◽  
Suspensory Ligament ◽  
The Common ◽  
Hindlimb Lameness

Proximal suspensory disease is a common cause of both forelimb and hindlimb lameness and poor performance in the horse. The following article describes the common presentations, diagnostic techniques and treatment options for the condition in both the forelimbs and the hindlimbs.

Heart failure in an elderly population

2001 ◽  
Vol 11 (4) ◽  
pp. 311-321
Author(s):  
DN Carmichael ◽  
Michael Lye
Keyword(s):  
Heart Failure ◽  
Treatment Options ◽  
Clinical Syndrome ◽  
Point Of View ◽  
Diagnostic Challenge ◽  
The Common ◽  
Characteristic Features ◽  
The Many ◽  
Neuroendocrine Activation ◽  
Symptoms And Signs

Heart failure has been defined in many ways and definitions change over time. The multiplicity of definitions reflect the paucity of our understanding of the primary underlying physiology of heart failure and the many diseases for which heart failure is the common end-point. Fundamentally, heart failure represents a failure of the heart to meet the body’s requirement for blood supply for whatever reason. It is thus a clinical syndrome with characteristic features – not a single disease in its own right. The syndrome includes symptoms and signs of organ underperfusion, fluid retention and neuroendocrine activation. The syndrome arises from a range of possible causes of which ischaemic heart disease is the commonest. From the point of view of a clinician, the underlying pathology will determine treatment options and prognosis. The extensive range of possible aetiologies present a diagnostic challenge both to correctly identify the syndrome amongst all other causes of dyspnoea and to identify the aetiology, allowing optimization of treatment.

Vanishing tumour of the internal auditory meatus

2008 ◽  
Vol 123 (5) ◽  
pp. 563-565 ◽  
Author(s):  
A Jain ◽  
M Ablett ◽  
P Wardrop
Keyword(s):  
World Literature ◽  
Cerebellopontine Angle ◽  
Renal Carcinoma ◽  
Treatment Options ◽  
Internal Auditory Meatus ◽  
Radiological Investigation ◽  
Urological Symptoms ◽  
History Of ◽  
The Common ◽  
Rare Report

AbstractObjectives:We report a very rare case of prostatic metastasis in the internal auditory meatus, which disappeared with treatment.Case report:An elderly man presented with a history of hearing loss, dizzy spells and, more recently, facial palsy. He also complained simultaneously of urological symptoms, which on investigation revealed advanced, metastatic prostate cancer. Radiological investigation, in the form of magnetic resonance imaging, revealed an internal auditory meatus mass which resembled an acoustic neuroma. The patient was treated with hormone injections.Tumours of the internal auditory meatus and cerebellopontine angle are mostly primary. Rarely, metastatic deposits have been described in this region, from squamous cell carcinoma, malignant melanoma, malignant parotid oncocytoma, renal carcinoma, and lung and thyroid primaries.Conclusion:To our knowledge, this is a very rare report in the world literature of prostatic metastasis to the internal auditory meatus. We discuss the common presenting features, investigations and treatment options for metastatic prostatic tumours of the internal auditory meatus and cerebellopontine angle.

Abstract 316: A Potential Mechanism Involving mTOR For The Expression Of CTGF In Agonist-stimulated Adult Cardiomyocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kamala P Sundararaj ◽  
Sundaravadivel Balasubramanian ◽  
Dorea Pleasant ◽  
Dhandapani Kuppuswamy
Keyword(s):  
Mrna Expression ◽  
Wound Repair ◽  
Cardiac Fibrosis ◽  
Interstitial Fibrosis ◽  
Treatment Options ◽  
Tissue Growth ◽  
Dependent Manner ◽  
Potential Mechanism ◽  
Wall Stiffness ◽  
Wide Range

Cardiac hypertrophy ensues as a response to multiple stimuli, such as mechanical stress, neurohumoral activation, growth factors and cytokines. Connective Tissue Growth Factor (CTGF), a potent fibrogenic cytokine, regulates a wide range of biological functions including ECM deposition, wound repair, angiogenesis, migration, differentiation, survival and proliferation. While CTGF overexpression in fibroblasts has been shown to be responsible for fibrosis in various organs, controversy exists about the source of CTGF. Since interstitial fibrosis contributes to ventricular wall stiffness and impairs diastolic function, understating how key factors such as CTGF are expressed and released for the genesis of fibrosis in the hypertrophying heart is important to develop new treatment options. To this end, we explored the signaling pathway(s) involved in the phenylephrine (PE), a hypertrophic agonist, induced expression of CTGF by cardiomyocytes (CMs). Since mammalian target of rapamycin (mTOR) is reported to regulate PE-induced hypertrophic signaling, we hypothesize that mTOR plays a role in PE induced CTGF expression in CMs. To test if CMs produce CTGF, we treated adult feline CMs with phenylephrine. PE stimulated CTGF mRNA expression in a dose and time dependent manner. mTOR forms two distinct complexes, mTORC1 and mTORC2. Whereas both complexes are sensitive to a pharmacological inhibitor Torin1, only mTORC1 is sensitive to Rapamycin inhibition. Our results indicate that PE stimulated CTGF expression could be substantially enhanced by torin1 pretreatment of CMs. Moreover, shRNA mediated silencing of Rictor in CMs, one of the components of mTORC2, significantly augmented the PE induced CTGF mRNA expression. But mTORC1 inhibition using Rapamycin or activation of its downstream target S6K1 using Rapamycin resistant S6K1 adenovirus had no impact in PE -stimulated CTGF expression. The same trend was also observed in the level of secreted CTGF. In conclusion, these results strongly indicate that mTORC2 plays a repressive role in CTGF mRNA expression in adult CMs, and that the loss of such repression in PO myocardium might be a potential mechanism for the onset of cardiac fibrosis in hypertrophying myocardium.

scholarly journals Superficial venous insufficiency from the infernal to the endothermal

2014 ◽  
Vol 96 (1) ◽  
pp. 5-10 ◽  
Author(s):  
D Carradice
Keyword(s):  
Gold Standard ◽  
Venous Insufficiency ◽  
Varicose Veins ◽  
Treatment Options ◽  
Resource Limitation ◽  
Skin Damage ◽  
The Common ◽  
Modern Treatment ◽  
The Cost ◽  
Superficial Venous Insufficiency

This review presents the common diseases associated with superficial venous insufficiency of the leg. These include varicose veins, swelling, skin damage and ulceration. The benefits and rationale behind treatment are discussed, followed by the historical advances from ancient mortality and prayer to the modern endovenous revolution. Finally, an overview of modern treatment options will discuss the evidence supporting the gold standard of endothermal ablation and the cost effectiveness of treatment at this time of challenging resource limitation.

scholarly journals Diagnostics and Treatment of Cervical Causes of Infertility

2019 ◽  
Vol 12 (1) ◽  
pp. 33-39
Author(s):  
Aleksandar K. Kunev
Keyword(s):  
Intrauterine Insemination ◽  
Treatment Options ◽  
Cervical Canal ◽  
Male Factor ◽  
Gynaecological Examination ◽  
The Common ◽  
Common Problems ◽  
Cervical Diseases ◽  
And Function ◽  
Methods Of Treatment

Summary Nowadays, infertility is a problem that affects an increasing number of people. The causes of infertility in a couple may be due to a variety of factors – female, male or unexplained. One of the common problems associated with infertility in women is related to uterine cervical diseases. The cervix is an essential part of the sperm passage, so various disorders in the cervix structure and function may be the cause of infertility. The study aimed to identify the leading cervical causes of female infertility, methods of treatment and their success. The most common problems of cervical origin are cervical polyps and stenosis of the cervical canal. They are easily diagnosed with a routine gynaecological examination and ultrasound examination. Polyps are removed through polypectomy, and after that, a natural pregnancy can be achieved. In the case of stenosis of the cervical canal, there are two treatment options – dilation or intrauterine insemination (IUI). In younger patients and lack of male factor in the couple, dilation is performed. Dilation is mechanical with classic Hegar dilatiors or with synthetic hygroscopic dilatiors (Dilapan). If, in addition to the stenosis of the cervical canal in a woman, there is a male factor, treatment with IUI is preferred. Methods for cervical factor treatment vary in their success rate but are generally characterised by good results.

scholarly journals Migraine

2021 ◽  
Vol 9 (12) ◽  
pp. 1407-1427
Author(s):  
Mr. Ghene Mauli Ganesh
Keyword(s):  
Chronic Migraine ◽  
Medication Overuse ◽  
Treatment Options ◽  
Preventive Treatment ◽  
Primary Headaches ◽  
Brain Disorder ◽  
Current State ◽  
The Common ◽  
Chronic Headaches ◽  
Migrainous Headache

Abstract: Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine.

Sign in / Sign up

Export Citation Format

Share Document