Non-Coding RNA-Mediated Gene Regulation in Cardiovascular Disorders: Current Insights and Future Directions.

Cardiovascular diseases (CVDs) pose a significant burden on global health. Developing effective diagnostic, therapeutic, and prognostic indicators for CVDs is critical. This narrative review explores the role of select non-coding RNAs (ncRNAs) and provides an in-depth exploration of the roles of miRNAs, lncRNAs, and circRNAs in different aspects of CVDs, offering insights into their mechanisms and potential clinical implications. The review also sheds light on the diverse functions of ncRNAs, including their modulation of gene expression, epigenetic modifications, and signaling pathways. It comprehensively analyzes the interplay between ncRNAs and cardiovascular health, paving the way for potential novel interventions. Finally, the review provides insights into the methodologies used to investigate ncRNA-mediated gene regulation in CVDs, as well as the implications and challenges associated with translating ncRNA research into clinical applications. Considering the broader implications, this research opens avenues for interdisciplinary collaborations, enhancing our understanding of CVDs across scientific disciplines.

A Comprehensive Review of Neuronal Changes in Diabetics.

There has been an exponential rise in diabetes mellitus (DM) cases on a global scale. Diabetes affects almost every system of the body, and the nervous system is no exception. Although the brain is dependent on glucose, providing it with the energy required for optimal functionality, glucose also plays a key role in the regulation of oxidative stress, cell death, among others, which furthermore contribute to the pathophysiology of neurological disorders. The variety of biochemical processes engaged in this process is only matched by the multitude of clinical consequences resulting from it. The wide-ranging effects on the central and peripheral nervous system include, but are not limited to axonopathies, neurodegenerative diseases, neurovascular diseases, and general cognitive impairment. All language search was conducted on MEDLINE, COCHRANE, EMBASE, and GOOGLE SCHOLAR till September 2021. The following search strings and Medical Subject Headings (MeSH terms) were used: "Diabetes Mellitus," "CNS," "Diabetic Neuropathy," and "Insulin." We explored the literature on diabetic neuropathy, covering its epidemiology, pathophysiology with the respective molecular pathways, clinical consequences with a special focus on the central nervous system and finally, measures to prevent and treat neuronal changes. Diabetes is slowly becoming an epidemic, rapidly increasing the clinical burden on account of its wide-ranging complications. This review focuses on the neuronal changes occurring in diabetes such as the impact of hyperglycemia on brain function and structure, its association with various neurological disorders, and a few diabetes-induced peripheral neuropathic changes. It is an attempt to summarize the relevant literature about neuronal consequences of DM as treatment options available today are mostly focused on achieving better glycemic control; further research on novel treatment options to prevent or delay the progression of neuronal changes is still needed.

Impact of Vitamin D Supplementation on Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease affecting a large number of people every year. The exact causal factor for this disease is unclear, but it commonly affects middle-aged women, with known triggers like stress, childbirth, infections, poor diet, lack of sleep, etc. Many epidemiological studies have indicated that various genetic abnormalities are also critical drivers of the onset of MS. The major risk factors of MS identified include hypovitaminosis D while environmental protective factors include allele HLA DRB1 1501, obesity, Epstein-Barr virus infection, sexual hormones, and smoking. Our article explores the correlation between the deficiency of vitamin D and the onset and progression of MS. The study uses a systematic review methodology by researching and reviewing scholarly articles exploring the topic. We conducted online searches of literature on Google Scholar and PubMed using the keywords "vitamin D deficiency" and "multiple sclerosis" and accessed the relevant secondary literature sources for review. The variables under study included vitamin D insufficiency as the dependent variable while MS was the independent variable. Causal variables included environmental, genetic, and protective factors. We hypothesized that there is indeed a correlation between vitamin D deficiency and MS. The findings from our review indicate a strong correlation between the insufficiency of vitamin D and the onset and progression of MS. These results are essential in devising interventions to accomplish primary and secondary prevention of MS, as well as integrating vitamin D supplementation in current treatment protocols for MS.

Pathogenesis of Ventricular Arrhythmias and Its Effect on Long-Term Prognosis in Patients With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TTC), also known as broken heart syndrome, stress cardiomyopathy (SCM), or apical ballooning syndrome, is a non-ischemic cardiac disease with an initial clinical presentation that is very similar to acute coronary syndrome (ACS). Ventricular arrhythmias (VAs) contribute significantly to an increase in the rates of death in patients with TTC, especially during the acute phase, in which patients with TTC are more susceptible to develop life-threatening arrhythmias (LTA) such as ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes (TdP), and sudden cardiac death (SCD). However, the pathophysiology of TTC and how VA occurs are still a mystery. We aim to review previous literature and discuss the possible mechanisms of VA in TTC patients. VA usually complicates the acute phase of the disease and worsens the long-term prognosis. Alterations of repolarization (negative T wave, prolonged QTc) indicate a high risk of arrhythmic events (TdP, VT, VF, and SCD). Catecholamine effect on myocardial cells and myocardial edema can create a substrate for the development of VA. Some of the most commonly proposed mechanisms for the development of VA in patients with TTC are coronary vasospasm, myocardial stunning due to catecholamines, re-entry, and triggered activity. Further prospective studies, including a more significant number of patients, are required to understand the disease's pathophysiology better and improve LTA management in patients with TTC.

Myasthenia Gravis and its Association With Thyroid Diseases.

Myasthenia gravis (MG) is a rare autoimmune neuromuscular junction disorder, and thyroid disorder is a disorder involving the thyroid receptor, of which Graves' disease (GD) is the most common autoimmune thyroid disorder, in which antibodies develop against thyroid receptors. Both may have similar clinical features. In myasthenia gravis, autoimmune antibodies develop against postsynaptic neuromuscular junction disrupting the neuromuscular transmission, resulting in fluctuating muscle weakness and fatigue. It is a disease of young women and older men. The two pathologies may coexist in a patient or can precede one another. Graves' disease (GD) among thyroid diseases is most often associated with MG.  Similarities in clinical features lead to difficulty in distinguishing MG and GD. Despite the standard treatment of myasthenia gravis, including steroids, acetylcholinesterases, rituximab, immunosuppressants, and thymectomy, there is still an increased number of relapses and myasthenia crisis. Eculizumab and plasmapheresis are the two new treatment options for MG, with supporting evidence of marked improvement in recent studies. Myasthenia gravis and Graves' disease have a see-saw relationship. Treating one pathology may worsen the other, so physicians should always consider MG as a differential in patients of hyperthyroidism presenting with new symptoms of fatigue or respiratory failure or neuromuscular weakness. In this comprehensive review article, we tried to establish an association between myasthenia gravis and Graves' disease (GD) by exploring currently available literature from PubMed. However, more studies need to be done to establish an association between pathologies.

The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis.

As a worldwide aging population is on the rise, osteoporosis (OS) is becoming a global health burden. Therefore, many researchers and health authorities are looking into the potential prevention and treatment of OS. Although previously regarded as two separate pathological processes, diabetes (DM) and OS are now regarded as two conditions that can occur together. It is now believed that OS can develop as a complication of DM. This relationship is further evidenced through a reduction in bone mineral density in type-1 diabetes with a resulting increased risk of fracture. Although bone mineral density in type-2 diabetes mellitus is normal or increased, there is also increased fragility due to decreased bone quality. These abnormal bone qualities tend to occur through the production of reduced bone microvasculature and advanced glycation end product, AGE. Interestingly, one of the most common treatments for DM, metformin (MF), shows a promising result on the protection of diabetes and non-diabetes related bone turnover. It is believed that MF modulates its effect through the adenosine monophosphate-activated protein kinase (AMPK) pathway. Recent data regarded AMPK as a vital mediator of homeostasis. It is involved not only in glucose metabolism but also in osteogenesis. AMPK can directly influence the production of mature and good quality bone by decreasing osteoclasts, increasing osteoblast formation, and enhancing bone mineral deposition. As an activator of AMPK, MF also upregulates osteogenesis. Furthermore, MF can influence osteogenesis through a non-AMPK pathway, such as the fructose 1-6 phosphatase pathway, by reducing glucose levels. While already recognized as a safe and effective treatment for DM, this article discusses whether MF can be used for the prevention and treatment of OS.

Opsoclonus Myoclonus Syndrome: A Rare Manifestation of Dengue Infection in a Child.

Opsoclonus myoclonus syndrome (OMS) is an inflammatory neurological disorder, which is characterized by chaotic uncontrolled movements of the eyes and involuntary jerk-like movements of the body. Different modalities of treatment have been described in medical literature to treat OMS. Immunomodulatory treatment with either steroids or intravenous immunoglobulin has been considered. Our case was a 14-year-old boy who presented with fever, mild confusion, without any seizures or focal deficits. On examination, he had opsoclonus in his eyes and had cortical myoclonus in his hands and body. On evaluation, he had low platelets, normal metabolic workup, normal brain imaging, and cerebrospinal fluid showed lymphocytic pleocytosis. He was managed conservatively and had spontaneous improvement in opsoclonus myoclonus by 5th day of his illness and complete recovery in 2 weeks. Although dengue is primarily considered hematotropic virus, it can involve nervous system as well and manifest with OMS.

Equitable utilisation of Indian community based health insurance scheme among its rural membership: cluster randomised controlled trial.

OBJECTIVE: To evaluate alternative strategies for improving the uptake of benefits of a community based health insurance scheme by its poorest members. DESIGN: Prospective cluster randomised controlled trial. SETTING: Self Employed Women's Association (SEWA) community based health insurance scheme in rural India. Participants 713 claimants at baseline (2003) and 1440 claimants two years later among scheme members in 16 rural sub-districts. INTERVENTIONS: After sales service with supportive supervision, prospective reimbursement, both packages, and neither package, randomised by sub-district. MAIN OUTCOME MEASURES: The primary outcome was socioeconomic status of claimants relative to members living in the same sub-district. Secondary outcomes were enrolment rates in SEWA Insurance, mean socioeconomic status of the insured population relative to the general rural population, and rate of claim submission. RESULTS: Between 2003 and 2005, the mean socioeconomic status of SEWA Insurance members (relative to the rural population of Gujarat) increased significantly. Rates of claims also increased significantly, on average by 21.6 per 1000 members (P<0.001). However, differences between the intervention groups and the standard scheme were not significant. No systematic effect of time or interventions on the socioeconomic status of claimants relative to members in the same sub-district was found. CONCLUSIONS: Neither intervention was sufficient to ensure that the poorer members in each sub-district were able to enjoy the greater share of the scheme benefits. Claim submission increased as a result of interventions that seem to have strengthened awareness of and trust in a community based health insurance scheme. Trial registration Clinical trials NCT00421629.

Helping members of a community-based health insurance scheme access quality inpatient care through development of a preferred provider system in rural Gujarat.

We describe and analyse the experience of piloting a preferred provider system (PPS) for rural members of Vimo SEWA, a fixed-indemnity, community-based health insurance (CBHI) scheme run by the Self-Employed Women's Association (SEWA). The objectives of the PPS were (i) to facilitate access to hospitalization by providing financial benefits at the time of service utilization; (ii) to shift the burden of compiling a claim away from members and towards Vimo SEWA staff; and (iii) to direct members to inpatient facilities of acceptable quality. The PPS was launched between August and October 2004, in 8 subdistricts covering 15,000 insured. The impact of the scheme was analysed using data from a household survey of claimants and qualitative data from in-depth interviews and focus group discussions. The PPS appears to have been successful in terms of two of the three primary objectives--it has transferred much of the burden of compiling a health Insurance claim onto Vimo SEWA staff, and it has directed members to inpatient facilities with acceptable levels of technical quality (defined in terms of structural Indicators). However, even under the PPS, user fees pose a financial barrier, as the insured have to mobilize funds to cover the costs of medicines, supplies, registration fee, etc. before receipt of cash payment from Vimo SEWA. Other barriers to the success of the PPS were the geographic Inaccessibility of some of the selected hospitals, lack of awareness about the PPS among members and a variety of administrative problems. This pilot project provides useful lessons relating to strategic purchasing by CBHI schemes and, more broadly, managed care in India. In particular, the pragmatic approach taken to assessing hospitals and identifying preferred providers is likely to be useful elsewhere.