Computational binding mechanism of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (MurA) with inhibitors fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic aci

Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and about two million deaths are attributable to TB annually. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structural model of Mtb-MurA enzyme has been developed, for the first time, by homology modeling and molecular dynamics simulation techniques. The model provided clear insight in its structure features, i.e. substrate binding pocket, and common docking site. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E.coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structural model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives is showed best interaction compared with other inhibitor, taking in to this we also design a new efficient analogs of T6361 and T6362 which are showed even better interaction with Mtb-MurA than the parental5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing of a more specific inhibitor for Mtb-MurA enzym

Experimental Research on the Effects of Waste Foundry Sand on the Strength and Micro-Structural Properties of Concrete

Now a days, a great distance has to be travelled to find good quality natural river sand. These supplies are also running out very quickly. So, a replacement for river sand is being sought after. Natural river sand is non-renewable and takes millions of years to be produced. By using manufactured sand, natural sand is completely replaced. Lack of research has led to the substitution of leftover waste foundry sand for manufactured sand in concrete. By adding used foundry sand to concrete, it is possible to enhance mechanical properties like compressive strength, fracture toughness, and flexibility. Using tests on cubes, cylinders, and unreinforced beams, the mechanical properties of concrete made with waste foundry sand and manufactured sand as fine aggregate were assessed. Tensile, splitting, and flexural strengths of the concrete were all determined after 7, 14, 28, 56, and 90 days of curing. SEM, EDS, and Thermo Gravimetric Analysis (TGA/DCs) were also used to perform micro structural analyses on the control mixture and mixtures containing 10, 20, 30, 40, and 50% waste foundry sand. The strength differences that occur when fine aggregates are replaced with waste foundry sand in different proportions are better understood, thanks to the micro structural experiments. In order to justify its use as a replacement for fine aggregate in terms of strength and microstructure studies, just the right amount of WFS was added to the concrete. Doi: 10.28991/CEJ-2022-08-10-010 Full Text: PD

CAPABLE CLOUD DATA EXCEEDING MAIN EXPOSURE

This focuses on encrypted data search, which is a vital means of protecting the privacy of file encryption before outsourcing in cloud computing or, in general, on almost all network-based information systems in which servers cannot be totally reliable. We officially demonstrate that our proposed plan is selectively secure against the selected keyword attack. We've created a single, authoritative, scalable search in an encrypted data plan that supports multiple data users and multiple data collaborators. We differentiate between features and keywords in our design. Keywords are the actual content of the files, while the attributes refer to the attributes of the user. In addition, using proxy encryption and slow file encryption techniques, the proposed plan is more relevant to the cloud outsourcing model and is efficient at eliminating the user. Unlike the existing public key search scheme, our plan can achieve scalability and system improvement at the same time. Unlike a search plan with native file encryption, our plan lets you search for approved, adaptable keywords in arbitrarily structured data. The appearance of complexity is a straight line to the amount of attributes within the system versus the number of authorized users. Thus, the one-to-many license mechanism is best suited for any huge system, for example, cloud. Proposed ABKS-UR plan and verification of the results verification mechanism through a real-world dataset and the complexity of an approximation calculation in relation to the conjugation process

A prospective study on the use of anesthetic agents in modern surgical practice at a tertiary care hospital, Karnataka, India

Background: The choice of local anesthetic is based on potency of the agent, onset and duration of anesthesia, and side effects of the drug Objectives of the study were, the study proposes to analysis the pattern, trend, rationality and frequency of use of anesthetic agents in modern surgical procedures.Methods: The study records relevant data obtained from surgical case records of patients from department of General surgery, Obstetrics and Gynecology and Orthopedics during the period December 2014 to May 2015 including first one month of pilot study, at KVGMC, Sullia (D.K), Karnataka.Results: A total of 744 cases were collected and screened according to inclusion and exclusion criteria and finally 348 cases were recorded and critically analysed. Sub-arachnoid block is the most common type of anesthetic procedure (75.28%) performed by the anesthetists. Of 348 cases undergoing anesthesia using local anesthetic agents, 228 cases required only a single agent and 120 cases required a combination anesthetic agents. 206 underwent sub-arachnoid block, 16 epidural block (EPID) and only 2 brachial block. The most commonly used agent for maintainence of general anesthesia is Isoflurane (68%) followed by Halothane (32%) and the combination of skeletal muscle relaxants were Succinylcholine with either Atracurium (39.8%) or Vecuronium (37.16%). Analgesics were the most commonly used adjuvants followed by ondansetron.Conclusions: The study showed that the most common anesthetic procedure performed using local anesthetic agents is SA/SAB block and the most common agent used is bupivacaine which was frequently employed at the dose range of 3-4 ml. There was significant association found between the no. of anesthetic agents used and the type of anesthetic procedure performed and also between the concerned department and the type of anesthetic procedure performed. Thus, the rationality in the usage of relevant anesthetic agents with appropriate adjuvants is evident

High Prevalence of Associated Birth Defects in Congenital Hypothyroidism

Aim. To identify dysmorphic features and cardiac, skeletal, and urogenital anomalies in patients with congenital hypothyroidism. Patients and Methods. Seventeen children with congenital primary hypothyroidism were recruited. Cause for congenital hypothyroidism was established using ultrasound of thyroid and 99mTc radionuclide thyroid scintigraphy. Malformations were identified by clinical examination, echocardiography, X-ray of lumbar spine, and ultrasonography of abdomen. Results. Ten (59%) patients (6 males and 4 females) had congenital malformations. Two had more than one congenital malformation (both spina bifida and ostium secundum atrial septal defect). Five (29%) had cardiac malformations, of whom three had only osteum secundum atrial septal defect (ASD), one had only patent ductus arteriosus (PDA), and one patient had both ASD and PDA. Seven patients (41%) had neural tube defects in the form of spina bifida occulta. Conclusion. Our study indicates the need for routine echocardiography in all patients with congenital hypothyroidism

Proteolytic Activity in the Midgut of Helicoverpa armigera (Noctuidae: Lepidoptera) Larvae Fed on Wild Relatives of Chickpea, Cicer arietinum

Wild relatives of crops are an important source of resistance genes against insect pests. However, it is important to identify the accessions of wild relatives with different mechanisms of resistance to broaden the basis and increase the levels of resistance to insect pests. Therefore, we evaluated 15 accessions of wild relatives of chickpea belonging to seven species and five genotypes of cultivated chickpea for their resistance to pod borer, Helicoverpa armigera, which is the most damaging pest of chickpea. The test genotypes were evaluated for resistance to H. armigera using detached pod assay. Data were also recorded on activity of the digestive enzymes in the midgut of the larvae fed on different wild relatives of chickpea. All the wild chickpea genotypes suffered lower pod damage and weight gained by the third-instar larvae of H. armigera was lower when fed on them compared with the cultivated chickpea. The accessions, IG 69979 (Cicer cuneatum), PI 599066, IG 70006, IG 70018, IG 70022 (Cicer bijugum), IG 599076 (Cicer chrossanicum), and IG 72933, IG 72953 (Cicer reticulatum), showed high levels of resistance to H. armigera. There were significant differences in protease activity in larval gut of H. armigera fed on different wild relatives of chickpea. Total protease, trypsin, and chymotrypsin activities were lowest in larva fed on PI 599066 (C. bijugum) compared with that in the larvae fed IG 69979 (C. cuneatum) and IG 70022 (C. bijugum). Aminopeptidase activity was highest in the larvae fed on IG 70022 (C. bijugum) and IG 599076 (C. chrossanicum), whereas lowest activity was recorded in the larvae fed on ICC 3137 and KAK 2 (susceptible checks). The variation in protease activities may be due to the presence of protease inhibitors in the wild relatives or hyperproduction of enzymes by the larvae as result of protease inhibitor activity of the wild relatives, resulting in low weight gain by larvae. The results suggested that wild relatives of chickpea with diverse mechanisms of resistance can be exploited to increase the levels and diversify the basis of resistance to H. armigera in cultivated chickpea

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

Identifying existing Choosing Wisely recommendations of high relevance and importance to hematology

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE TM relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787–792, 2016. © 2016 Wiley Periodicals, Inc