Abstract Background Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may ...enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. Objectives This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. Methods In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. Results In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). Conclusions Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.
Implantation of a device to narrow the coronary sinus and increase myocardial venous pressure was compared with a sham procedure in patients with refractory angina. The proportion of patients with ...improvement at 6 months was significantly greater with the device.
A growing number of patients with severe and diffuse obstructive coronary artery disease who are not candidates for revascularization have debilitating angina despite medical therapy.
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The worldwide prevalence of refractory angina is increasing, and new therapeutic options are needed.
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An endoluminal, balloon-expandable, stainless steel, hourglass-shaped device designed for percutaneous implantation in the coronary sinus (Reducer, Neovasc) creates a focal narrowing that leads to increased pressure in the coronary sinus, which may relieve angina (Figure 1). A nonrandomized first-in-human study involving 15 patients with refractory angina who were treated with the device showed significant improvement with respect to angina class. . . .
Stable angina pectoris affects 2–4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1–2 % and 3 %, respectively. Heart rate (HR) is ...linearly related to myocardial oxygen consumption and coronary blood flow, both at rest and during stress. HR reduction is a key target for the prevention of ischemia/angina and is an important mechanism of action of drugs which are recommended as first line therapy for the treatment of angina in clinical guidelines. However, many patients are often unable to tolerate the doses of beta blocker or non-dihydropyridine calcium antagonists required to achieve the desired symptom control. The selective pacemaker current inhibitor ivabradine was developed as a drug for the management of patients with angina pectoris, through its ability to reduce HR specifically. The available data suggest that ivabradine is a well-tolerated and effective anti-anginal agent and it is recommended as a second-line agent for relief of angina in guidelines. However, recent clinical trials of ivabradine have failed to show prognostic benefit and have raised potential concerns about safety. This article will review the available evidence base for the current role of ivabradine in the management of patients with symptomatic angina pectoris in the context of stable coronary artery disease.
Biopiracy as “a silent disease” is hardly detectable because it does not leave traces frequently. The corporate hijacking of food is the most important health hazard in this era; giant commercial ...enterprises are using intellectual property rights to patent indigenous medicinal plants, seeds, genetic resources, and traditional medicines. The new era of biotechnology relies on the genes of living organisms as raw materials. The “Gene Rush” has thus become similar to that of the old “Gold Rush.” Sri Lanka has been spotted in the top 34 biodiversity hotspots globally. Moreover, localized in the tropics, human generations in Sri Lanka have utilized the array of plant species for herbal treatments and treatment of diseases. Sri Lanka after its 30-year civil war is moving towards a solid growth and conservation of the environment which is a major component in a sustainable development where the conservation of biodiversity plays a significant role. In this paper, we present an overview of typical cases of global biopiracy, bioprospecting via introduction of cost-effective deoxyribonucleic acid (DNA) fingerprinting and international protocol with Private-Public-People Partnership concept as excellent forms of utilization of natural resources. We propose certain perspectives as scientists towards abolishing biopiracy and also to foster the fair utilization of natural resources; since the economy of most developing countries is agriculture based, the gross domestic product of the developing countries could be increased by enhanced bioprospecting via introduction of cost-effective DNA fingerprinting technologies and thus not being a pray of corporate hijacking.“Biopiracy is biological theft; illegal collection of indigenous plants by corporations who patent them for their own use” (Vandana Shiva).
Sri Lanka is a rapidly aging country, where dementia prevalence will increase significantly in the future. Thus, inexpensive and sensitive cognitive screening tools are crucial.
To assess the ...reliability, validity, and diagnostic accuracy of the Sinhalese version of the Addenbrooke's Cognitive Examination-Revised (ACE-R s).
The ACE-R was translated into Sinhala with cultural and linguistic adaptations and administered, together with the Sinhala version of the Montreal Cognitive Assessment (MoCA), to 99 patients with dementia and 93 gender-matched controls.
The ACE-R s cutoff score for dementia was 80 (sensitivity 91.9%, specificity 76.3%). The areas under the curve for the ACE-R s, Mini-Mental State Examination (MMSE) and MoCA were 0.90, 0.86, and 0.86, respectively. The -ACE-R s had good interrater reliability (intraclass correlation = 0.94), test-retest reliability (intraclass correlation = 0.99), and internal consistency (Cronbach's α = 0.8442).
The ACE-R s is sensitive, specific and reliable to detect dementia in persons aged ≥50 years in a Sinhala-speaking population and its diagnostic accuracy is superior to previously validated tools (MMSE and MoCA).
The phenotype of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients is determined by the type of DMD gene variation, its location, effect on reading frame, and its size. ...The primary objective of this investigation was to determine the frequency and distribution of DMD gene variants (deletions/duplications) in Sri Lanka through the utilization of a combined approach involving multiplex polymerase chain reaction (mPCR) followed by Multiplex Ligation Dependent Probe Amplification (MLPA) and compare to the international literature. The current consensus is that MLPA is a labor efficient yet expensive technique for identifying deletions and duplications in the DMD gene.
Genetic analysis was performed in a cohort of 236 clinically suspected pediatric and adult myopathy patients in Sri Lanka, using mPCR and MLPA. A comparative analysis was conducted between our findings and literature data.
In the entire patient cohort (n = 236), mPCR solely was able to identify deletions in the DMD gene in 131/236 patients (DMD-120, BMD-11). In the same cohort, MLPA confirmed deletions in 149/236 patients DMD-138, BMD -11. These findings suggest that mPCR has a detection rate of 95% (131/138) among all patients who received a diagnosis. The distal and proximal deletion hotspots for DMD were exons 45-55 and 6-15. Exon 45-60 identified as a novel in-frame variation hotspot. Exon 45-59 was a hotspot for BMD deletions. Comparisons with the international literature show significant variations observed in deletion and duplication frequencies in DMD gene across different populations.
DMD gene deletions and duplications are concentrated in exons 45-55 and 2-20 respectively, which match global variation hotspots. Disparities in deletion and duplication frequencies were observed when comparing our data to other Asian and Western populations. Identified a 95% deletion detection rate for mPCR, making it a viable initial molecular diagnostic approach for low-resource countries where MLPA could be used to evaluate negative mPCR cases and cases with ambiguous mutation borders. Our findings may have important implications in the early identification of DMD with limited resources in Sri Lanka and to develop tailored molecular diagnostic algorithms that are regional and population specific and easily implemented in resource limited settings.
Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a ...corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, “standing on one leg R”, “standing on one leg L”, and “walk”, declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial.
Neuroimmune diseases are a group of disorders that occur due to the dysregulation of both the nervous and immune systems, and these illnesses impact tens of millions of people worldwide. However, ...patients who suffer from these debilitating conditions have very few FDA-approved treatment options. Neuroimmune crosstalk is important for controlling the immune system both centrally and peripherally to maintain tissue homeostasis. This review aims to provide readers with information on how natural products modulate neuroimmune crosstalk and the therapeutic implications of natural products, including curcumin, epigallocatechin-3-gallate (EGCG), ginkgo special extract, ashwagandha, Centella asiatica, Bacopa monnieri, ginseng, and cannabis to mitigate the progression of neuroimmune diseases, such as Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, depression, and anxiety disorders. The majority of the natural products based clinical studies mentioned in this study have yielded positive results. To achieve the expected results from natural products based clinical studies, researchers should focus on enhancing bioavailability and determining the synergistic mechanisms of herbal compounds and extracts, which will lead to the discovery of more effective phytomedicines while averting the probable negative effects of natural product extracts. Therefore, future studies developing nutraceuticals to mitigate neuroimmune diseases that incorporate phytochemicals to produce synergistic effects must analyse efficacy, bioavailability, gut-brain axis function safety, chemical modifications, and encapsulation with nanoparticles.
A biobank in Sri Lanka that links East and West Wijekoon, Nalaka; Gonawala, Lakmal; Wijesinghe, Printha ...
Lancet neurology,
December 2020, 2020-12-00, 20201201, Letnik:
19, Številka:
12
Journal Article
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