Survey on Prevalence of Vegadharana as a Risk Factor for Cardiac Disorders- An Observational Pilot Study

The present era, which is a reflection of changing major driving forces such as social, economic and cultural due to globalization, urbanization and population ageing. By this change, there is raise in the prevalence of certain non-communicable diseases. Cardiac disorders are among such which stands first in increasing mortality rate about 31% globally. Now a day, the prevalence rate is increasing due to behavioral risk factors like tobacco use, unhealthy diet, obesity, physical inactivity, alcohol and smoking. People are also at higher risk of these disorders with the presence of high risk of one or more already established disease conditions like Hyperlipidemia, Hypertension, Diabetes mellitus etc. Indians are being affected by high rates of these major risk factors which are striking for cardiac disorders at an earlier age almost 33% earlier than other demographical regions. Considering all these many organizations like MRFIT, American Heart association, National Lipid organization etc. are conducting various trials since four decades to establish the appropriate relation with risk factors to plan the better lines of management. Ayurveda explains about the concept of Dharaneeya and Adharaneeya vegas, where in Acharyas emphasize that many of the systemic diseases are caused by the forceful suppression of natural urges. Among 13 Dharaneeya vegas 9 are found to be the risk factors in causing various cardiac disorders. With this regard to explore and to assess the prevalence of Vegadharana as risk factor for cardiac disorders, an attempt has made as a pilot survey study on 40 cardiac patients. Aim: To understand the Prevalence and epidemiology of Vegadharana in Cardiac disorders. To observe the Co-relation between Vegadharana and Cardiac disorders. Methodology: It is a Pilot observational study done by using a survey strategy. The questionnaire method in an electronic format was used to collect the data. Descriptive statistics and Co-relation Co-efficient was used to analyze the data obtained. Result: In this Pilot study, the sum of the prevalence of Vegadharana was observed it was found that the frequency of Vegadharana was more in cardiac individuals, especially the category of few times and sometimes with n value=76 and 64 respectively. Conclusion: With the above data, it can be concluded that; Vegadharana has an impact on the expectancy of Cardiac disorders. The data also revealed the co-relation of Vegadharana in permutation which are signifying as higher risk factors in causing cardiac disorders.

Fractional-order COVID-19 pandemic outbreak: Modeling and stability analysis

Today, the entire world is witnessing an enormous upsurge in coronavirus pandemic (COVID-19 pandemic). Confronting such acute infectious disease, which has taken multiple victims around the world, requires all specialists in all fields to devote their efforts to seek effective treatment or even control its disseminate. In the light of this aspect, this work proposes two new fractional-order versions for one of the recently extended forms of the SEIR model. These two versions, which are established in view of two fractional-order differential operators, namely, the Caputo and the Caputo–Fabrizio operators, are numerically solved based on the Generalized Euler Method (GEM) that considers Caputo sense, and the Adams–Bashforth Method (ABM) that considers Caputo–Fabrizio sense. Several numerical results reveal the impact of the fractional-order values on the two established disease models, and the continuation of the COVID-19 pandemic outbreak to this moment. In the meantime, some novel results related to the stability analysis and the basic reproductive number are addressed for the proposed fractional-order Caputo COVID-19 model. For declining the total of individuals infected by such pandemic, a new compartment is added to the proposed model, namely the disease prevention compartment that includes the use of face masks, gloves and sterilizers. In view of such modification, it is turned out that the performed addition to the fractional-order Caputo COVID-19 model yields a significant improvement in reducing the risk of COVID-19 spreading.

NMR Studies of Tau Protein in Tauopathies

Tauopathies, including Alzheimer’s disease (AD), are the most troublesome of all age-related chronic conditions, as there are no well-established disease-modifying therapies for their prevention and treatment. Spatio-temporal distribution of tau protein pathology correlates with cognitive decline and severity of the disease, therefore, tau protein has become an appealing target for therapy. Current knowledge of the pathological effects and significance of specific species in the tau aggregation pathway is incomplete although more and more structural and mechanistic insights are being gained using biophysical techniques. Here, we review the application of NMR to structural studies of various tau forms that appear in its aggregation process, focusing on results obtained from solid-state NMR. Furthermore, we discuss implications from these studies and their prospective contribution to the development of new tauopathy therapies.

ACPA-IgG variable domain glycosylation increases before the onset of rheumatoid arthritis and stabilizes thereafter; a cross-sectional study encompassing over 1500 samples

Objective: The autoimmune response in rheumatoid arthritis (RA) is marked by anti-citrullinated protein antibodies (ACPA). A remarkable feature of ACPA-IgG is the abundant expression of N-linked glycans in the variable domain. Nonetheless, the presence of ACPA variable domain glycans (VDG) across disease stages and its response to therapy is poorly described. To understand its dynamics, we investigated the abundance of ACPA-IgG VDG in 1574 samples from individuals in different clinical disease stages. Methods: Using liquid chromatography, we analyzed ACPA-IgG VDG profiles of 7 different cohorts from Japan, Canada, the Netherlands and Sweden. We assessed 184 healthy, 228 pre-symptomatic, 277 arthralgia, 305 patients at RA-onset and 117 RA-patients 4, 8 and 12 months after disease onset. Additionally, we measured VDG of 234 samples from RA-patients that did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. Results: Our data show that ACPA-IgG VDG significantly increases (p<0.0001) towards disease-onset and associates with ACPA-levels and epitope spreading pre-diagnosis. A slight increase in VDG was observed in established RA and a moderate influence of treatment. Individuals who later achieved DFR displayed reduced ACPA-IgG VDG already at RA-onset. Conclusion: The abundance of ACPA-IgG VDG rises towards RA-onset and correlates with maturation of the ACPA-response. Although, ACPA-IgG VDG levels are rather stable in established disease, a lower degree at RA-onset correlates with DFR. Even though the underlying biological mechanisms are still elusive, our data support the concept that VDG relates to an expansion of the ACPA-response pre-disease and contributes to disease-development.

Bi-allelic loss-of-function variants in KIF21A cause severe fetal akinesia with arthrogryposis multiplex

BackgroundFetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.MethodsWe performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature.ResultsWe identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the kinesin family member 21A gene (KIF21A) was found.ConclusionOur study underlines the broad locus heterogeneity of FA with well-established and atypical genotype–phenotype associations. We describe KIF21A as a new factor implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia and facial dysmorphisms. This hypothesis is further corroborated by a recent report on overlapping phenotypes observed in Kif21a null piglets.

Effect of Early and Delayed Commencement of Paricalcitol in Combination with Enalapril on the Progression of Experimental Polycystic Kidney Disease

Vitamin D secosteroids are intranuclear regulators of cellular growth and suppress the renin-angiotensin system. The aim of this study was to test the hypothesis that the vitamin D receptor agonist, paricalcitol (PC), either alone or with enalapril (E) (an angiotensin-converting enzyme inhibitor), reduces the progression of polycystic kidney disease. Preventative treatment of Lewis polycystic kidney (LPK) and Lewis control rats with PC (0.2 μg/kg i.p. 5 days/week) or vehicle from postnatal weeks 3 to 10 did not alter kidney enlargement. To evaluate the efficacy in established disease, LPK rats received either PC (0.8 μg/kg i.p; 3 days/week), vehicle, E (50 mg/L in water) or the combination of PC + E from weeks 10 to 20. In established disease, PC also did not alter the progression of kidney enlargement, kidney cyst growth or decline in renal function in LPK rats. Moreover, the higher dose of PC was associated with increased serum calcium and weight loss. However, in established disease, the combination of PC + E reduced systolic blood pressure and heart-body weight ratio compared to vehicle and E alone (p < 0.05). In conclusion, the combination of PC + E attenuated cardiovascular disease but caused hypercalcaemia and did not alter kidney cyst growth in LPK rats.

Intracystic papillary neoplasm of the gallbladder concomitant with xanthogranulomatous cholecystitis: a case report

Background The intracystic papillary neoplasm (ICPN) is a newly established disease concept. It has been regarded as a preinvasive neoplastic lesion, similar to intraductal papillary mucinous neoplasm of the pancreas. Limited information is available on the clinical and imaging features of ICPN. Case presentation A 65-year-old woman was referred to our hospital for assessment of a gallbladder tumor. Contrast-enhanced computed tomography showed a papillary tumor in the fundus of the gallbladder with irregular thickening of the gallbladder wall that spread into the cystic duct. The boundary between the tumor and liver was unclear. The patient was diagnosed with gallbladder cancer with liver invasion. We performed extended cholecystectomy with liver bed resection after confirming the absence of cancer cells in the resection margin of the cystic duct. After pathological examination, the tumor was diagnosed as an ICPN with xanthogranulomatous cholecystitis. The patient was discharged on postoperative day 8 with no complications. Conclusions We have described a rare case of ICPN concomitant with xanthogranulomatous cholecystitis. Clinicians should include ICPN as a differential diagnosis in patients with a papillary or polypoid tumor in the gallbladder.

miR-20a Overexpression in Adipose-Derived Mesenchymal Stem Cells Promotes Therapeutic Efficacy in Murine Lupus Nephritis by Regulating Autophagy

Objective. Lupus nephritis is the most common and severe complication of systemic lupus erythematosus. The aim of our study was to investigate the efficacy of miR-20a overexpressing adipose-derived stem cell (ADSC) transplantation in murine lupus nephritis (LN) and explore potential molecular mechanisms. Methods. Mouse ADSCs were transfected with a miR-20a lentiviral vector to obtain miR-20a overexpression ADSCs (miR-20a-ADSCs). We first observed the influence of miR-20a on ADSC viability and apoptosis in vitro. B6.MRL/lpr mice were administered ADSC/miR-20a-ADSC intravenously every week from age 30 to 33 weeks, and the lupus and normal control groups received PBS on the same schedule. Results. miR-20a expression increased in miR-20a-ADSC-derived exosomes, and miR-20a overexpression promoted ADSC proliferation and inhibited apoptosis. Compared with ADSCs, miR-20a-ADSC treatment significantly improved serologic and histologic abnormalities, as evidenced by reduced serum creatinine, anti-dsDNA antibody, 24 h urine protein levels, nephritis scores, and C3/IgG deposits. Furthermore, miR-20a-ADSC treatment resulted in downregulated Akt, mTOR, and p62 expression and upregulated miR-20a, Beclin 1, and LC3 II/I expression compared with ADSC treatment. After treatment with miR-20a-ADSC, a significant increase in the number of autophagosomes within podocytes was observed, along with upregulated expression of podocin and nephrin, compared with the ADSC group. Conclusions. miR-20a-ADSC transplantation prevents the development of lupus nephritis and significantly ameliorates already-established disease, and its mechanism is related to autophagy by targeting the miR-20a-regulated mTOR pathway.

Infant leukaemia – faithful models, cell of origin and the niche

ABSTRACT For patients and their families, the diagnosis of infant leukaemia is devastating. This disease has not seen the improvements in outcomes experienced with other paediatric leukaemias and it is becoming ever more apparent that infant leukaemia is a distinct biological entity. Insights into some of the distinguishing features of infant leukaemia, such as a single mutation – the MLL-gene rearrangement, the biology of disease aggressiveness and lineage plasticity, and the high incidence of central nervous system involvement, are likely to be gained from understanding the interactions between leukaemic cells and their environment or niche. The origins of infant leukaemia lie in the embryonic haematopoietic system, which is characterised by shifting locations and dynamic changes in the microenvironment. Understanding this foetal or embryonic context is integral to understanding infant leukaemia development. Owing to its rarity and prenatal origins, developing accurate modelling systems for further investigation of infant leukaemia is essential. In this Review, we discuss how available in vitro, ex vivo and in vivo infant leukaemia models contribute to our current understanding of the leukaemia niche in embryonic development, established disease and specialised non-haematopoietic niches. The mechanistic insights provided by accurate models will help identify viable novel therapeutic options.