Evaluation of the Role of Merromoside from Ipomoea aquatica Forsskal Hydroalcoholic Extract in the Downregulation of ROS Species in Overcoming MDR in Breast Cancer

Purpose: The medicinal plant Ipomoea aquatica belonging to convulvulaceae family is an effective natural herb for treatment of various ailments and possesses effective anticancer activity. The aim of the work is to characterize a secondary metabolite merromoside (a resin glycoside) for anti-breast cancer activity through down regulation of ROS species. Methods: The Extract of the whole plant has been prepared by maceration method using 50%v/v ethanol in distilled water to get a hydroalcoholic extract. The phytochemical evaluation reveals that the active secondary metabolite was isolated by using column chromatographic technique. The isolated compound was evaluated for its anticancer properties through invitro method such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on Michigan Cancer Foundation-7 Cell lines. The purity and structural characterization were done by high-performance thin layer chromatography, Fourier Transform Infrared Spectroscopy, Proton and13C Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography–Mass Spectrometry. Results: The isolated compound (W04) from the derived extract showed Rf value of 0.79 that showed IC50 of 182.8μg/ml. The chemical structure of W04 has been confirmed as [4,5-dihydroxy-6-[5-hydroxy-2-methyl-4-(2-methylpropanoyloxy)-6-[(24,25,26-trihydroxy-5,23-dimethyl-9-oxo-19-pentyl-2,4,8,20,22-pentaoxatricyclo[19.2.2.13,7]hexacosan-6-yl)oxy]oxan-3-yl]oxy-2-methyloxan-3-yl] 2-methyl propanoate with the molecular weight of 979.15268. The isolated compound merromoside from hydroalcoholic extract of Ipomoea aquatica has been evaluated for anti-breast cancer properties. The down regulation of ROS species will prevent reverse signalling and angiogenesis. This indicates that merromoside will overcome MDR in breast cancer especially DOX-resistant.     

Spectrally‐selective measurements of reversible and irreversible transverse relaxation rates from single spin‐echo PRESS acquisitions in muscle

The goal of this study was to test a new formalism for extracting reversible and irreversible transverse relaxation rates from resonances within typical proton muscle spectra using only a single spin echo as acquired with routine single‐voxel, point‐resolved echo spectroscopy (PRESS) acquisitions. Single‐voxel, non‐water‐suppressed PRESS acquisitions within the calf muscles of four healthy subjects were performed at 1.5 T using six echo times ranging from 30 to 576 ms. Novel transverse relaxation analyses of water, choline, creatine, and lipid resonances were performed based upon the disparate relaxation sensitivities of the left versus the right sides of spectroscopically sampled spin echoes. Irreversible and reversible transverse relaxation rates R₂ and R₂′ were extracted for water, metabolites, and lipids using echo times of 288 ms and longer. The R₂ values so obtained were compared with more conventional “gold standard” Hahn values, R_2Hahn, evaluated from the echo‐time dependence of spectral peak areas generated from right‐side sampling alone. Water resonances displayed biexponential Hahn signal decays, consistent with observations of decreasing R₂ values with increasing echo time via the new approach. Choline and creatine resonances displayed monoexponential echo‐time decays, with R_2Hahn values in reasonable agreement with R₂ values obtained from the single‐echo analyses at the longer echo times. Lipid methylene and methyl R₂ values extracted from the new approach were also in reasonable accord with R_2Hahn values. Further validation of the technique was provided through PRESS acquisitions on a water phantom to which various levels of gadolinium were added in order to manipulate transverse relaxation rates, yielding excellent agreement between water‐resonance R_2Hahn and single‐echo R₂ values. In summary, this work demonstrates the feasibility of measuring reversible and irreversible transverse relaxation rates for individual spectral peaks from single‐echo PRESS acquisitions, enabling a reduction in overall scan time relative to the use of multiple acquisitions with varying echo time.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

An unusual ECG pattern in restrictive cardimyopathy

Restrictive cardiomyopathy is the least common type of primary cardiomyopathies. Electrocardiographic recording is abnormal in 99% of patients with RCM. Biatrial enlargement, obliquely elevated ST segment with notched or biphasic late peaking T waves are considered characteristic ECG finding. Significant ST depression with T inversion mimicking subendocardial ischemia has also been reported in patients with RCM and is even suggested as a predictor of sudden cardiac death. We noted a similar ECG pattern in a 16 yr girl with Idiopathic restrictive cardiomyopathy. Coronaries were normal, stress perfusion imaging did not show any perfusion defect. This diffuse resting ST depression with T inversion in precordial & inferior leads along with ST elevation in aVR was persistent for more than six months.     

Assessment of backward walking unmasks mobility impairments in post-stroke community ambulators

Background: While over half of stroke survivors recover the ability to walk without assistance, deficits persist in the performance of walking adaptations necessary for safe home and community mobility. One such adaptation is the ability to walk or step backward. Post-stroke rehabilitation rarely includes backward walking (BW) assessment and BW deficits have not been quantified in post-stroke community ambulators.

Objective: To quantify spatiotemporal and kinematic BW characteristics in post-stroke community ambulators and compare their performance to controls.

Methods: Individuals post-stroke (n = 15, 60.1 ± 12.9 years, forward speed: 1.13 ± 0.23 m/s) and healthy adults (n = 12, 61.2 ± 16.2 years, forward speed: 1.40 ± 0.13 m/s) performed forward walking (FW) and BW during a single session. Step characteristics and peak lower extremity joint angles were extracted using 3D motion analysis and analyzed with mixed-method ANOVAs (group, walking condition).

Results: The stroke group demonstrated greater reductions in speed, step length and cadence and a greater increase in double-support time during BW compared to FW (p < .01). Compared to FW, the post-stroke group demonstrated greater reductions in hip extension and knee flexion during BW (p < .05). The control group demonstrated decreased plantarflexion and increased dorsiflexion during BW, but these increases were attenuated in the post-stroke group (p < .05).

Conclusions: Assessment of BW can unmask post-stroke walking impairments not detected during typical FW. BW impairments may contribute to the mobility difficulties reported by adults post-stroke. Therefore, BW should be assessed when determining readiness for home and community ambulation.     

Lumbar Lipomeningomyelocele Associated with Multiple Café au Lait Spots: A Case Report

We report on a child with several café au lait spots in association with a lumbar lipomeningomyelocele as an apparently new association. Cutaneous markers, the identification of which plays a crucial role in the early diagnosis and management of spinal malformations, can accompany occult spinal dysraphism. Herein we report a case of lumbar lipomeningomyelocele associated with an overlying café au lait spot that served as a marker of occult spinal dysraphism. The patient also had segmental café au lait spots on the face, making the association unique.     

Chest radiography in acute aortic syndrome: pearls and pitfalls

Acute aortic syndrome is a group of life-threatening diseases of the thoracic aorta that usually present to the emergency department. It includes aortic dissection, aortic intramural hematoma, and penetrating aortic ulcer. Rare aortic pathologies of aorto-esophageal fistula and mycotic aneurysm may also be included in this list. All these conditions require urgent treatment with complex clinical care and management. Most patients who present with chest pain are evaluated with a chest radiograph in the emergency department. It is important that maximum diagnostic information is extracted from the chest radiograph as certain signs on the chest radiograph are extremely useful in pointing towards the diagnosis of acute aortic syndrome.     

Evaluation of cardiac signals using discrete wavelet transform with MATLAB graphical user interface

Aim

To process the electrocardiogram (ECG) signals using MATLAB-based graphical user interface (GUI) and to classify the signals based on heart rate.

Method

The subject condition was identified using R-peak detection based on discrete wavelet transform followed by a Bayes classifier that classifies the ECG signals. The GUI was designed to display the ECG signal plot.

Results

Obtained from MIT database 18 patients had normal heart rate and 9 patients had abnormal heart rate; 14.81% of the patients suffered from tachycardia and 18.52% of the patients have bradycardia.

Conclusion

The proposed GUI display was found useful to analyze the digitized ECG signal by a non-technical user and may help in diagnostics. Further improvement can be done by employing field programmable gate array for the real time processing of cardiac signals.     

Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient

WDR45 gene‐associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta‐propeller protein‐associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6‐year‐old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood.