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Introduction: Previous studies suggest that crimping causes permanent structural damage to the leaflet tissues of transcatheter heart valves (THV). However, this damage is not yet known to facilitate calcification process. Hypothesis: Our hypothesis is to test whether crimp-induced damage promotes valvular calcification. Methods: Self-expandable THVs with Glutaraldehye-fixed bovine pericardial leaflets was used. The valves were divided into two groups; crimped and uncrimped, and each group was split into two to be exposed either to a calcifying solution or to a control -normal phosphate buffered saline- solution. For the crimped group, the valves were carefully crimped with a standard crimper at 14Fr and held crimped for 20 minutes. The calcifying solution contains ionic concentrations corresponding to normal human plasma. All groups were maintained at pH 7.5, 37°C, on an orbital shaker at 400 rpm for 7 weeks. At the end, each tissue sample was individually embedded, sectioned and stained for calcium stain (Von Kossa), Verhoff’s Van Geison (VVG) stain for elastin and collagen stain (trichrome III). Results: Fig 1A show the normal bovine pericardium with arranged collagen layers in blue whereas intermittent striations are seen across the collagen fibers in the crimped group (Fig 1B). VVG stains show similar results with continuous elastin fibers (black) in the uncrimped group (Fig 1C) versus fragmented elastin fibers in the crimped group (Fig 1D). Of most significance are the results from the von kossa stains where crimped samples in saline show minimal hydroxyapatite deposition (Fig 1E) while crimped samples in calcifying buffer show brown deposits of hydroxyapatite along the crimped regions (Fig 1F). No hydroxyapatite deposition was observed in uncrimped group exposed to calcifying solution. Conclusions: Our results indicate that severe structural changes due to crimping are associated with greater levels of calcium deposition along the crimped sites.

Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given., Author(s): Agnes Trautmann [sup.1] , Marina Vivarelli [sup.2] , Susan Samuel [sup.3] , Debbie Gipson [sup.4] , Aditi Sinha [sup.5] , Franz Schaefer [sup.1] , Ng Kar Hui [sup.6] , [...]

The extracellular matrix of the atrioventricular (AV) valves' leaflets has a key role in the ability of these valves to properly remodel in response to constantly varying physiological loads. While the loading on mitral and tricuspid valves is significantly different, no information is available on how collagen fibers change their orientation in response to these loads. This study delineates the effect of physiological loading on AV valves' leaflets microstructures using Second Harmonic Generation (SHG) microscopy. Fresh natural porcine tricuspid and mitral valves' leaflets (n = 12/valve type) were cut and prepared for the experiments. Histology and immunohistochemistry were performed to compare the microstructural differences between the valves. The specimens were imaged live during the relaxed, loading, and unloading phases using SHG microscopy. The images were analyzed with Fourier decomposition to mathematically seek changes in collagen fiber orientation. Despite the similarities in both AV valves as seen in the histology and immunohistochemistry data, the microstructural arrangement, especially the collagen fiber distribution and orientation in the stress-free condition, were found to be different. Uniaxial loading was dependent on the arrangement of the fibers in their relaxed mode, which led the fibers to reorient in-line with the load throughout the depth of the mitral leaflet but only to reorient in-line with the load in deeper layers of the tricuspid leaflet. Biaxial loading arranged the fibers in between the two principal axes of the stresses independently from their relaxed states. Unlike previous findings, this study concludes that the AV valves' three-dimensional extracellular fiber arrangement is significantly different in their stress-free and uniaxially loaded states; however, fiber rearrangement in response to the biaxial loading remains similar.

Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality. [ABSTRACT FROM AUTHOR]

Background While patients with frequently relapsing nephrotic syndrome (FRNS) are initially treated with long-term alternate-day prednisolone, relapses and adverse effects are common. In an open-label randomized controlled trial, we compared the efficacy of therapy with low-dose daily to standard alternate-day prednisolone in reducing relapse rates over 12-month follow-up. Methods Consecutive patients, aged 2-18 years, with FRNS were included. Following therapy of relapse, prednisolone was tapered to 0.75 mg/kg on alternate days. Stratifying for steroid dependence, patients were randomly assigned to prednisolone at 0.2-0.3 mg/kg daily or 0.5-0.7 mg/kg alternate day for 12 months. Relapses were treated with daily prednisolone, followed by return to intervention. Primary outcome was the incidence of relapses. Proportion with therapy failure ([greater than or equal to] 2 relapses in any 6 months or significant steroid toxicity) and sustained remission, cumulative prednisolone intake and adverse events were evaluated. Results Patients receiving daily prednisolone (n = 30) showed significantly fewer relapses than those on alternate-day therapy (n = 31) (0.55 relapses/person-year versus 1.94 relapses/person-year; incidence rate ratio 0.28; 95% CI 0.15, 0.52). Daily therapy was associated with higher rates of sustained remission at 6 months (73.3 versus 48.4%) and 1 year (60 versus 31.6%; log rank p = 0.013), lower rates of treatment failure at 6 months (3.3 versus 32.8%) and 1 year (6.7 versus 57.4%; p < 0.0001), and lower prednisolone use (0.27 ± 0.07 versus 0.39 ± 0.19 mg/kg/day; p = 0.003). Three and two patients need to receive the study intervention to enable sustained remission and prevent treatment failure, respectively. Conclusions In patients with FRNS, daily administration of low-dose prednisolone is more effective than standard-dose alternate day therapy in lowering relapse rates, sustaining remission, and enabling steroid sparing., Author(s): Menka Yadav [sup.1] , Aditi Sinha [sup.1] , Priyanka Khandelwal [sup.1] , Pankaj Hari [sup.1] , Arvind Bagga [sup.1] Author Affiliations: (Aff1) 0000 0004 1767 6103, grid.413618.9, Division of [...]

Background Dyslipidemia is an important cardiovascular risk factor in steroid-resistant nephrotic syndrome (SRNS). Efficacy of statins for treatment of hyperlipidemia in children with SRNS is unclear. Methods This prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial enrolled 30 patients with SRNS, aged 5-18 years, with serum low-density lipoprotein cholesterol (LDL-C) levels between 130 and 300 mg/dl, to receive a fixed dose of atorvastatin (n = 15, 10 mg/d) or placebo (n = 15) by block randomization in a 1:1 ratio. Primary outcome was change in serum LDL-C at 12 months. Change in levels of other lipid fractions, carotid intima-media thickness (cIMT), flow-mediated dilation (FMD) of the brachial artery, and adverse events were also evaluated. Results At the end of 12 months, atorvastatin was not superior to placebo in reducing plasma LDL-C levels, median percentage reduction 15.8% and 9.5% respectively, in atorvastatin and placebo arms (n = 14 in each; P = 0.40). Apolipoprotein B levels significantly declined with atorvastatin in modified intention-to-treat analysis (P = 0.01) but not in the per-protocol analysis. There was no significant effect on other lipid fractions, cIMT and FMD. Adverse events were similar between groups. Change in serum albumin was negatively associated with change in serum LDL-C, very low-density lipoprotein cholesterol, total cholesterol, triglyceride, and apolipoprotein B (P < 0.001), irrespective of receiving atorvastatin, age, gender, body mass index, and serum creatinine. Conclusions Atorvastatin, administered at a fixed daily dose of 10 mg, was not beneficial in lowering lipid levels in children with SRNS; rise in serum albumin was associated with improvement in dyslipidemia., Author(s): Pankaj Hari [sup.1] , Priyanka Khandelwal [sup.1] , Amit Satpathy [sup.1] , Smriti Hari [sup.1] , Ranjeet Thergaonkar [sup.1] , R Lakshmy [sup.2] , Aditi Sinha [sup.1] , Arvind [...]

This article explores the option of restructuring a corporate debtor through sale as a going concern in liquidation, as opposed to the corporate insolvency resolution process. Although the existing insolvency law in India treats liquidation as a matter of last resort, this article argues that if sale as a going concern in liquidation entails a higher realisation for the creditors, it should be viewed as an equally viable and beneficial option for restructuring. However, this would necessitate overhauling the existing insolvency regime to allow the stakeholders to assess and select the best option for themselves and the corporate debtor. [ABSTRACT FROM AUTHOR]

Byline: Priyanka. Madaan, Prashant. Jauhari, Shruthi. Michael, Aditi. Sinha, Biswaroop. Chakrabarty, Sheffali. Gulati Sir, Pediatric arterial ischemic stroke (AIS) is relatively uncommon and often under-recognized. It comprises 5%-10% of all [...]