MOLECULAR DOCKING AND SCREENING OF DRUGS FOR 6LU7 PROTEASE INHIBITOR AS A POTENTIAL TARGET FOR COVID-19

Objective: The aim of present investigation is docking of various existing antiviral, anti-tubercular and anti-malarial drugs on 6LU7 receptor of SARS-CoV-2 in the treatment of COVID-19. Methods: In this study, the structure of coronavirus binding protein and ligands for various drugs were collected from the protein data bank and pub chem. Molecular docking was carried out using Schrodinger 9.0 software. In molecular docking study, 19 different drugs of various categories like antiviral, anti-malarial and anti-tubercular were investigated for analyzing binding to 6LU7 receptors of COVID-19. Results: The docking result showed a high affinity of zanamivir, montelukast, ramdesvir, ritonavir, cobicistat and favipravir to the 6LU7 receptor of novel coronavirus. Thus the combination of these drugs may be useful in preventing further infection and can be used as a potential target for further in vitro and in vivo studies of SARS-CoV-2. Conclusion: Treatment of COVID-19 has been challenge due to the non-availability of effective drug therapy. In this study, we reported drugs for targeting 6LU7 Mpro/3Clpro protein, which showed prominent effects as potential inhibitors of COVID-19 Mpro

A validated RP-HPLC method for simultaneous determination of Hydrochlorothiazide and Losartan Potassium in pharmaceutical formulation

A new, simple and sensitive reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed for the separation and quantification of Hydrochlorothiazide (HCTZ) and Losartan Potassium (LOS) in tablet dosage form. The determination was carried out using GRACE C18 [4.6 x 250 mm] column as a stationary phase and mobile phase comprised of Acetonitrile: Phosphate Buffer(50 : 50) pH 3.1 in proportion of 50:50(v/v); the pH of phosphate buffer adjusted to (3.1) using orthophosphoric acid. The flow rate was maintained at 1.0ml/min and the eluent was monitored at 226nm.The retention time of MET and VILD were 4.250 min and 8.300 min respectively. The method was validated in terms of linearity, precision, accuracy, specificity and robustness. The method was linear and for precision studies; RSD for HCTZ and LOS were 0.02 and 0.04 respectively. The percentage recoveries for both drugs from their tablets were 100.80 and 99.76 respectivel

A Comprehensive Corpus Callosum Segmentation Tool for Detecting Callosal Abnormalities and Genetic Associations from Multi Contrast MRIs

Structural alterations of the midsagittal corpus callosum (midCC) have been associated with a wide range of brain disorders. The midCC is visible on most MRI contrasts and in many acquisitions with a limited field-of-view. Here, we present an automated tool for segmenting and assessing the shape of the midCC from T1w, T2w, and FLAIR images. We train a UNet on images from multiple public datasets to obtain midCC segmentations. A quality control algorithm is also built-in, trained on the midCC shape features. We calculate intraclass correlations (ICC) and average Dice scores in a test-retest dataset to assess segmentation reliability. We test our segmentation on poor quality and partial brain scans. We highlight the biological significance of our extracted features using data from over 40,000 individuals from the UK Biobank; we classify clinically defined shape abnormalities and perform genetic analyses

Grzybiczy tętniak rzekomy tętnicy płucnej u pacjentki z historią ubytku przegrody międzykomorowej. Opis przypadku i przegląd piśmiennictwa

Tętniaki są rzadko zlokalizowane w tętnicy płucnej. Częstszą jest lokalizacja wewnątrzczaszkowa, aorta lub inne naczynia krwionośne. Tętniak tętnicy płucnej może być spowodowany zakażeniem takimi bakteriami, jak Staphylococcus, Streptococcus, Mycobacteria, Treponema pallidum, rzadziej grzybami. W pracy przedstawiono opis przypadku 7-letniej pacjentki, u której wystąpiły dwa prawostronne, przywnękowe tętniaki rzekome pochodzenia grzybiczego. Pacjentka była wcześniej leczona z powodu ubytku przegrody międzykomorowej. Grzybicze tętniaki rzekome tętnicy płucnej występują rzadko, a ich diagnostyka jest trudna. Jeśli u chorego przez dłuższy czas utrzymują się gorączka i kaszel, a zagęszczenie w obrębie miąższu płuc nie odpowiada na antybiotykoterapię, zaleca się wykonanie tomografii komputerowej klatki piersiowej z kontrastem. Można podejrzewać, że „krucha masa przyczepiona do łaty ubytku przegrody międzykomorowej” była punktem wyjścia dla rozwoju infekcyjnego zapalenia wsierdzia oraz powstania grzybiczego materiału zatorowego w tętnicach płucnych. Leczony wcześniej ubytek przegrody międzykomorowej mógł się w ten sposób przyczynić do rozwoju grzybiczego zapalenia wsierdzia.Tętniaki są rzadko zlokalizowane w tętnicy płucnej. Częstszą jest lokalizacja wewnątrzczaszkowa, aorta lub inne naczynia krwionośne. Tętniak tętnicy płucnej może być spowodowany zakażeniem takimi bakteriami, jak Staphylococcus, Streptococcus, Mycobacteria, Treponema pallidum, rzadziej grzybami. W pracy przedstawiono opis przypadku 7-letniej pacjentki, u której wystąpiły dwa prawostronne, przywnękowe tętniaki rzekome pochodzenia grzybiczego. Pacjentka była wcześniej leczona z powodu ubytku przegrody międzykomorowej. Grzybicze tętniaki rzekome tętnicy płucnej występują rzadko, a ich diagnostyka jest trudna. Jeśli u chorego przez dłuższy czas utrzymują się gorączka i kaszel, a zagęszczenie w obrębie miąższu płuc nie odpowiada na antybiotykoterapię, zaleca się wykonanie tomografii komputerowej klatki piersiowej z kontrastem. Można podejrzewać, że „krucha masa przyczepiona do łaty ubytku przegrody międzykomorowej” była punktem wyjścia dla rozwoju infekcyjnego zapalenia wsierdzia oraz powstania grzybiczego materiału zatorowego w tętnicach płucnych. Leczony wcześniej ubytek przegrody międzykomorowej mógł się w ten sposób przyczynić do rozwoju grzybiczego zapalenia wsierdzia

Diarrhoea in the critically ill is common, associated with poor outcome, and rarely due to Clostridium difficile

Diarrhoea is common in Intensive Care Unit (ICU) patients, with a reported prevalence of 15-38%. Many factors may cause diarrhoea, including Clostridium difficile, drugs (e.g. laxatives, antibiotics) and enteral feeds. Diarrhoea impacts on patient dignity, increases nursing workload and healthcare costs, and exacerbates morbidity through dermal injury, impaired enteral uptake and subsequent fluid imbalance. We analysed a cohort of 9331 consecutive patients admitted to a mixed general intensive care unit to establish the prevalence of diarrhoea in intensive care unit patients, and its relationship with infective aetiology and clinical outcomes. We provide evidence that diarrhoea is common (12.9% (1207/9331) prevalence) in critically ill patients, independently associated with increased intensive care unit length of stay (mean (standard error) 14.8 (0.26) vs 3.2 (0.09) days, p < 0.001) and mortality (22.0% (265/1207) vs 8.7% (705/8124), p < 0.001; adjusted hazard ratio 1.99 (95% CI 1.70-2.32), p < 0.001) compared to patients without diarrhoea even after adjusting for potential confounding factors, and infrequently caused by infective aetiology (112/1207 (9.2%)) such as Clostridium difficile (97/1048 (9.3%) tested) or virological causes (9/172 (5.7%) tested). Our findings suggest non-infective causes of diarrhoea in ICU predominate and pathophysiology of diarrhoea in critically ill patients warrants further investigation

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME

Measurement, modelling, and closed-loop control of crystal shape distribution: Literature review and future perspectives

Crystal morphology is known to be of great importance to the end-use properties of crystal products, and to affect down-stream processing such as filtration and drying. However, it has been previously regarded as too challenging to achieve automatic closed-loop control. Previous work has focused on controlling the crystal size distribution, where the size of a crystal is often defined as the diameter of a sphere that has the same volume as the crystal. This paper reviews the new advances in morphological population balance models for modelling and simulating the crystal shape distribution (CShD), measuring and estimating crystal facet growth kinetics, and two- and three-dimensional imaging for on-line characterisation of the crystal morphology and CShD. A framework is presented that integrates the various components to achieve the ultimate objective of model-based closed-loop control of the CShD. The knowledge gaps and challenges that require further research are also identified

Feasible products for reaction with separation

Methods to determine feasible products for combined reaction and distillation processes identify its potential advantages over the conventional configuration of reaction followed by distillation. The aim of this dissertation is to develop an approach that determines design targets for combined reaction and separation without equipment specifications. Using this approach, the critical aspect of generation and screening of feasible alternatives in conceptual design is addressed. The generation of feasible alternatives involves development of mathematical models, normally consisting of conservation equations such as the mole balances. A general and systematic method is developed to formulate these mole balances for complex chemistries such as those encountered in the production of many pharmaceuticals, specialty chemicals, pesticides, or monomers. The mole balances are independent of the devices involved in a process. This method not only determines the mole balance constraints on systems with simultaneous reaction and separation, but also it simplifies the task of determining raw materials consumption, wastes generation, and consistency of experimental measurements, all of which are important in the conceptual design of processes. Methods for finding feasible products for combined reaction and separation devices are useful in the generation and screening of alternatives. Systematic methods for batch and continuous systems have been developed. A simple method to determine feasible yields and selectivities for batch reactive distillation devices identifies its potential advantage over the conventional technology. A cross-flow device is used to simplify the determination of feasible products from a continuous counter-current reactive distillation system. A method based on the geometric approach of attainable regions finds feasible product regions for continuous reaction-separation systems, and device configurations that achieve them. The attainable regions approach is based on the fundamental processes and does not assume any device configurations. Useful design targets can therefore be determined without specifying any equipment and allows quick estimation of the process economics. The attainable region (or feasible region) together with the mole balances determine the design targets for combined reaction and separation processes