Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. PATIENTS AND METHODS: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. RESULTS: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. CONCLUSIONS: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.

Mass online training of health care workers during COVID-19: approach, impact, and outcomes for over 10,000 health care providers.

OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

Efficacy of alkyltrimethylammonium bromide for decontaminating salt-cured hides from the red heat causing moderately halophilic bacteria.

Conventionally, animal hide and skin necessitates 95% saturated brine solution (SBS) for its preservation. This salt is primarily derived from different sources including solar-saltern, evaporation ponds, etc., which are laden with different types of halophilic micro-organisms. Previous studies confirmed that the presence of moderately halophilic bacteria caused red heat on cured hide, which adversely affects the leather quality and causes substantial economic losses for leather industries. Thus, this investigation was carried out to examine the effects of different concentrations of alkyltrimethylammonium bromide (ATMB) on selected halophilic-bacteria attributed to the deterioration of hide quality. In nutrient broth solution (NBS), ATMB at 250 and 500 ppm reduced individual halo-bacteria, that is, Halomonas halodenitrificans, Halomonas eurihalina, Alkalibacillus haloalkaliphilus and Salimicrobium album, by averages of 0·64 and 1·90, 1·5 and 2·61, 0·90 and 2·27, 1·65 and 3·36 log CFU per ml respectively in 5 min. ATMB treatment in SBS at 500 ppm for 18 h resulted in a reduction of H. halodenitrificans, H. eurihalina, A. haloalkaliphilus and S. album by averages of 1·9, 1·25, 0·96 and 1·34 log CFU per ml respectively, when compared with the controls. Likewise, 5000 ppm ATMB reduced the cocktail population nearly to zero from that cultivated in SBS for 18 h. SIGNIFICANCE AND IMPACT OF THE STUDY: In this investigation, the inhibition of different halophilic bacteria that causes red heat in salt-preserved hides is described for the first time. The antimicrobial susceptibility test executed via solution procedures for selected halophilic bacterial strains (i.e. resistant to the salt environment) revealed significant efficacy of alkyltrimethylammonium bromide (ATMB). The current study suggests that, chemical compound like ATMB could be utilized to prevent red heat-related damage on salt-cured hides caused by halophilic bacteria, which is a persisting concern of the leather industry.

Deletions of the Idh1, Eco1, Rom2, and Taf10 Genes Differently Control the Hyphal Growth, Drug Tolerance, and Virulence of Candida albicans.

The most recent genome-editing system called CRISPR-Cas9 (clustered regularly interspaced short palindromic repeat system with associated protein 9-nuclease) was employed to delete four non-essential genes (i.e., Caeco1, Caidh1, Carom2, and Cataf10) individually to establish their gene functionality annotations in pathogen Candida albicans. The biological roles of these genes were investigated with respect to the cell wall integrity and biogenesis, calcium/calcineurin pathways, susceptibility of mutants towards temperature, drugs and salts. All the mutants showed increased vulnerability compared to the wild-type background strain towards the cell wall-perturbing agents, (antifungal) drugs and salts. All the mutants also exhibited repressed and defective hyphal growth and smaller colony size than control CA14. The cell cycle of all the mutants decreased enormously except for those with Carom2 deletion. The budding index and budding size also increased for all mutants with altered bud shape. The disposition of the mutants towards cell wall-perturbing enzymes disclosed lower survival and more rapid cell wall lysis events than in wild types. The pathogenicity and virulence of the mutants was checked by adhesion assay, and strains lacking rom2 and eco1 were found to possess the least adhesion capacity, which is synonymous to their decreased pathogenicity and virulence.

Enterotoxin gene profile and molecular epidemiology of Aeromonas species from fish and diverse water sources.

AIMS: This investigation was undertaken to study the prevalence, enterotoxin gene profile and molecular epidemiology of Aeromonads from various sources of water (182) and fish (173). METHODS AND RESULTS: A total of 116 Aeromonas sp. were isolated, of which 48 (26·37%) were from water and 68 (34·62%) were from fish samples collected from retail markets and fish farms. The Aeromonads were recovered from all types of water sources viz. drinking water (13%), surface waters (26%) and fish ponds (69%). The most prevalent species recovered from drinking water was A. hydrophila, from fish ponds it was A. caviae, from surface water sources A. hydrophila and A. caviae were recovered more frequently, and A. hydrophila and A. veronii bv. sobria were isolated predominantly from gills of fish samples. On multiplex PCR analysis for the detection of enterotoxin genes (act, alt, ast), the above mentioned Aeromonas species frequently contained enterotoxin genes, irrespective of their sources. From isolates across all the sources, act (63%) and alt (57%) genes were encountered more frequently than ast (6%). The enterobacterial repetitive intergenic consensus sequences polymerase chain reaction was used for typing of isolates and most of the isolates from water and fish were related, owing to similar ecosystem. CONCLUSION: A wide distribution of enterotoxin genes in Aeromonads from water and fish is a potential public health threat and molecular genotyping can be helpful to study epidemiology of the pathogen. SIGNIFICANCE AND IMPACT OF THE STUDY: A high proportion of isolates recovered from diverse water sources, particularly potable drinking water and fish samples carried one or more enterotoxin genes thereby indicating a potential pathogenic nature of isolates from these sources. The genetic relatedness was detected amongst many isolates recovered from water sources and fish samples indicating circulation of familiar virulent clones in the aquatic environments.

Real-time monitoring of a microbial electrolysis cell using an electrical equivalent circuit model.

Efforts in developing microbial electrolysis cells (MECs) resulted in several novel approaches for wastewater treatment and bioelectrosynthesis. Practical implementation of these approaches necessitates the development of an adequate system for real-time (on-line) monitoring and diagnostics of MEC performance. This study describes a simple MEC equivalent electrical circuit (EEC) model and a parameter estimation procedure, which enable such real-time monitoring. The proposed approach involves MEC voltage and current measurements during its operation with periodic power supply connection/disconnection (on/off operation) followed by parameter estimation using either numerical or analytical solution of the model. The proposed monitoring approach is demonstrated using a membraneless MEC with flow-through porous electrodes. Laboratory tests showed that changes in the influent carbon source concentration and composition significantly affect MEC total internal resistance and capacitance estimated by the model. Fast response of these EEC model parameters to changes in operating conditions enables the development of a model-based approach for real-time monitoring and fault detection.

Towards an electronic national injury surveillance system in Saudi Arabia.

Given the need for a uniform, comprehensive, electronic nationwide surveillance system for injuries in Saudi Arabia, a system was designed with the objectives of establishing an epidemiologic profile of injuries in the country; evaluating injury indicators on an ongoing basis; identifying high-risk groups requiring specific interventions; monitoring and evaluating interventions for effectiveness; and producing reports to assist in planning and resource allocation. A special form for this purpose was designed, modified from validated forms used elsewhere for injury surveillance. This initiative of the Ministry of Health is also expected to help validate data collected by other sectors, such as the Ministry of Interior. This paper reviews the milestones of building the system and aims to prompt a debate within the scientific community, especially within the Eastern Mediterranean Region, about the best way to design injury surveillance systems for the Region in order to fine-tune the proposed system before its full-scale implementation.

A multiplex PCR for detection of enterotoxin genes in Aeromonas species isolated from foods of animal origin and human diarrhoeal samples.

AIMS: The present study describes incidence and enterotoxin gene profile of Aeromonas spp. from human diarrhoeal samples (83) and raw meats (171). METHODS AND RESULTS: The samples were screened for isolation of Aeromonads. Aeromonas spp. contaminated raw meats of all kinds under the study and per cent contamination in chicken, mutton and beef was 14·03, 22·89 and 19·35, respectively. Of the 83 diarrhoeal samples from children, 6 (7·22%) were positive for presence of Aeromonas spp. Seven different species of Aeromonas (Aer. hydrophila, Aer. caviae, Aer. veronii bv sobria, Aer. trota, Aer. schubertii, Aer. jandaei and Aer. allosaccharophila) could be identified from foods and from diarrhoeal samples two species (Aer. caviae and Aer. hydrophila) were encountered. Unique primers were designed, and a multiplex PCR was standardized for detection of three enterotoxin genes (act, alt, ast) in the Aeromonas spp. Of the 39 isolates, 35 (89·74%) carried one or more enterotoxin genes: act, alt and ast genes were detected in 30 (76·92%), 31 (79·48%) and 4 (10·25%) isolates, respectively. The enterotoxin genes from a strain recovered from mutton were sequenced and submitted to GenBank and the accession no.s KC687135, KC633828 and KC687134 were provided for alt, ast and act, respectively, by the GenBank. CONCLUSIONS: The occurrence of enterotoxigenic Aeromonads in raw meats and diarrhoeal samples is a public health concern. SIGNIFICANCE AND IMPACT OF THE STUDY: Given the increasing evidence of involvement of Aeromonads in foodborne outbreaks, the standardization of single-step multiplex PCR will be helpful tool for detection of enterotoxin genes in Aeromonas spp.

Minimizing thermal stress for data center servers through thermal-aware relocation.

A rise in inlet air temperature may lower the rate of heat dissipation from air cooled computing servers. This introduces a thermal stress to these servers. As a result, the poorly cooled active servers will start conducting heat to the neighboring servers and giving rise to hotspot regions of thermal stress, inside the data center. As a result, the physical hardware of these servers may fail, thus causing performance loss, monetary loss, and higher energy consumption for cooling mechanism. In order to minimize these situations, this paper performs the profiling of inlet temperature sensitivity (ITS) and defines the optimum location for each server to minimize the chances of creating a thermal hotspot and thermal stress. Based upon novel ITS analysis, a thermal state monitoring and server relocation algorithm for data centers is being proposed. The contribution of this paper is bringing the peak outlet temperatures of the relocated servers closer to average outlet temperature by over 5 times, lowering the average peak outlet temperature by 3.5% and minimizing the thermal stress.

Sensing of Gunshot Residue components from real sample using Fluorescence Resonance Energy Transfer.

The present work represents a Fluorescence Resonance Energy Transfer (FRET) based sensing method for detecting Gunshot Residue (GSR) components. Two laser dyes Acf and RhB have been used as donor and acceptor respectively in the FRET pair. The real sample was collected after test firing in a forensic science laboratory. On the other hand, a standard GSR solution has been prepared in the laboratory. For the preparation of standard GSR solutions, we used the water solutions of the salts BaCl2, SbCl3, and Pb(NO3)2. The FRET efficiency was measured between Acf and RhB to sense the presence of GSR components (Pb+2, Ba+2, and Sb+3) in both real sample and standard solution by mixing the salts in aqueous solution. It has been observed that the FRET efficiency systematically decreases in the presence of GSR components. To amplify the FRET efficiency of the dye pair, inorganic clay dispersion (laponite) was used. The enhancement in FRET efficiency represents a better sensitivity of the proposed sensor. The current sensor is useful for the quantification of concentrations of the GSR components in a real sample.

Sorafenib for advanced hepatocellular carcinoma (HCC): impact of rationing in the United Kingdom.

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) is dependent upon tumour stage, performance status (PS), severity of underlying liver disease, and the availability of appropriate therapies. The unavailability of sorafenib may have a significantly adverse effect on the prognosis of UK patients with advanced HCC. During the study period, access to sorafenib was at the discretion of local health funding bodies, a process that may delay or deny access to the drug and that remains in place for Wales, Scotland, and Northern Ireland. Here, we attempt to address the impact of this system on patients with advanced HCC in the United Kingdom. METHODS: This is a retrospective study performed in the two largest specialist hepatobiliary oncology units in the United Kingdom. Funding applications were made to local funding bodies for patients with advanced HCC for whom sorafenib was considered appropriate (advanced HCC not suitable for loco-regional therapies, compensated chronic liver disease, PS 0-2). RESULTS: A total of 133 applications were made, of which 57 (43%) were approved and 76 (57%) declined. Demographics and prognostic factors were balanced between the two groups. This cohort had a number of adverse prognostic features: patients were predominantly PS 1-2; the majority had multifocal disease with the largest lesion being >5 cm; and macroscopic vascular invasion, metastases, and AFP >,000 ng ml(-1), were each present in one-third of cases. The median time from application to funding decision was 17 days (range 3-260 days). For the primary 'intention-to-treat' analysis, median overall survival was 4.1 months when funding was declined, and 9.5 months when funding was approved (hazard ratio (HR) 0.48; 95% CI 0.3186-0.7267; P=0.0005). CONCLUSION: These data support the use of sorafenib for patients with advanced HCC as an effective intervention. In the United Kingdom, this applies to a relatively small group of patients, estimated to total ∼800 per year who, unfortunately, do not survive long enough to themselves lobby for the availability of this drug. These data provide a comparison of sorafenib with supportive care and demonstrate the potential detrimental impact on patient outcomes of rationing health-care resources on the basis of cost.

Primary type 3 abomasal ulceration in cattle and buffalo: clinico-biochemical parameters, treatment, and prognostic indicators.

Background: The clinical findings, laboratory alterations, and prognosis of primary type 3 abomasal ulcer (AU3) are poorly reported in the literature. Aims: To describe clinical findings, hemato-biochemical changes, and peritoneal fluid changes in bovines suffering from primary AU3, and to monitor responses to medical treatment and outcomes. Methods: The study included 32 bovines (20 cattle and 12 buffaloes) diagnosed with primary AU3 along with a control group. Results: Common clinical findings were depressed demeanor, anorexia, dehydration, scanty feces, melena, mushy atonic rumen, tachycardia, and tachypnea. Colic was observed in 56.3% of animals. The mean hemoglobin, hematocrit, platelet count, and lymphocyte count were lower (P≤0.05), while WBC and neutrophil count were higher than the values of the control group (P≤0.05). The levels of BHBA, NEFA, glucose, total bilirubin, AST, CK, LDH, BUN, creatinine, and lactate were higher (P≤0.05), while cholesterol, total protein, albumin, sodium, potassium, chloride, and calcium were lower than the values of the control group (P≤0.05). The rumen chloride concentration was increased. The left shift was observed in a higher percentage of nonsurvivors than survivors (P≤0.05). The nonsurvivors had higher levels of bilirubin, CK, LDH, BUN, creatinine, and rumen chloride (P≤0.05), and lower levels of total protein, albumin, and globulin (P≤0.05). Conclusion: Type 3 abomasal ulcers occurred during the various stages of lactation as well as in pregnant animals. The response to medical treatment was fair, long time survival rate was good, and there was no recurrence. There was no effect on fetal survival or milk yield in the subsequent lactation.

Comparative analysis of case screening with varying cough duration and sputum samples for diagnosis of tuberculosis in patients attending the OPD at a tertiary care hospital at Srinagar, India.

RESEARCH QUESTION: Can we minimize cough duration and number of sputum samples in chest symptomatic patients for screening of TB? OBJECTIVE: To evaluate cough of 3 weeks versus 2 weeks duration using two sputum samples versus three samples in chest symptomatic patients attending the OPD. STUDY DESIGN: Hospital-based cross-sectional study. MATERIALS AND METHODS: Outpatients (2810) with H/O cough of 3 weeks and 2 weeks duration were screened by subjecting them to sputum microscopy for tuberculosis using two sputum samples as well as three samples following standard procedure for sputum collection, staining and acid-fast bacillus (AFB) identification. Those on drugs were not included. RESULTS: Using ≥2 weeks cough, sputum positivity rate was 12%, nearly as high as the sputum positivity among patients with ≥3 weeks cough, i.e. 14%. First sputum smear alone on an average could detect 91.8% cases, while the first two sputum smears could detect on an average 96% cases. The study showed that maximum number of cases was diagnosed by only two sputum smears and added diagnostic value of third specimen was small, i.e. 4%.High sputum positivity rate using ≥2 weeks cough with two sputum samples was seen. CONCLUSION: The sensitivity analysis of the study showed that using ≥2 weeks cough with two sputum samples gives almost similar values as ≥3 weeks cough with three sputum samples, but this needs further confirmatory results of culture sensitivity. Hence, using ≥2 weeks cough with two sputum samples as the diagnostic criteria for screening of cough patients for TB should be recommended as one way of improving efficient use of scarce resources.

Diagnosis and management of arterial injuries associated with limb fracture or dislocation.

An arterial injury is a time-critical emergency and, when associated with a fracture or dislocation, its management requires joint specialist input from orthopaedic and vascular or plastic surgeons. Initial management involves haemorrhage control and stabilisation of the patient, reduction and splinting of the limb and careful reassessment. With ongoing vascular compromise, urgent surgery is indicated to restore arterial flow and stabilise the skeleton, and this should be performed at a centre with appropriate expertise. This article provides an evidence-based review of the British Orthopaedic Association Standards for Trauma for the diagnosis and management of arterial injuries associated with extremity fractures and dislocations.

Ultrasonographic assessment of change in omasal position during the last month of gestation and first month of lactation in buffaloes.

INTRODUCTION: This study was aimed to determine the effect of advanced pregnancy on the topography and size of the omasum in 22 healthy Murrah buffaloes. The omasum was scanned 15-20 days before and after parturition, as per the standard procedure. The dorsal and ventral margins of the omasum were identified and marked at each intercostal space (ICS). The dorsal and ventral limits up to the dorsal midline were measured. The omasum was scanned in 6th to 11th ICS during advanced pregnancy and 7th to 11th ICS after the parturition. Irrespective of the pregnancy, the dorsal and ventral margins of the omasum were located farther dorsal and close to the spine in the 6th, 7th and 11th ICS. Except in one buffalo, the omasum was scanned in four consecutive ICS during the advanced pregnancy. After parturition the omasum was scanned in four and five consecutive ICS in 17 and five buffaloes, respectively. The mean dorsal and ventral limits of the omasum increased significantly (P .

INTRODUCTION: Cette étude visait à déterminer l'effet d'une gestation avancée sur la topographie et la taille de l'omasum chez 22 buffles de Murrah en bonne santé. L'omasum a été scanné 15 à 20 jours avant et après la parturition, selon la procédure standard. Les marges dorsale et ventrale de l'omasum ont été identifiées et marquées au niveau de chaque espace intercostal (EIC). Les limites dorsale et ventrale jusqu'à la ligne médiane dorsale ont été mesurées. L'omasum a été scanné du 6ème au 11ème EIC pendant la gestation avancée et du 7ème au 11ème EIC après la mise-bas. Indépendamment de la gestation, les marges dorsale et ventrale de l'omasum étaient situées plus loin dorsalement et plus près de la colonne vertébrale dans les 6ème, 7ème et 11ème EIC. Sauf chez un buffle, l'omasum a été scanné dans quatre EIC consécutifs au cours de la gestation avancée. Après la mise-bas, l'omasum a été scanné dans quatre et cinq EIC consécutifs chez 17 respectivement 5 buffles. Les limites dorsales et ventrales moyennes de l'omasum ont augmenté de manière significative (P.

The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates.

The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Study of resveratrol against bone loss by using in-silico and in-vitro methods.

By applying the in-silico method, resveratrol was docked on those proteins which are responsible for bone loss. The Molecular docking data between the resveratrol and Receptor activator of nuclear factor-kappa-Β ligand [RANKL] receptors proved that resveratrol binds tightly to the receptors, showed the highest binding affinities of -6.9, -7.6, -7.1, -6.9, -6.7, and -7.1 kcal/mol. According to in-vitro data, Resveratrol reduced the osteoclasts after treating Marrow-Derived Macrophages [BMM] with Macrophage colony-stimulating factor [MCSF] 20ng / ml and RANKL 50ng / ml, with different concentrations of resveratrol (2.5, 10 µg / ml) For 7 days, the cells were treated with MCSF (20 ng / ml) and RANKL (40 ng / ml) together with concentrated trimethyl ether and resveratrol (2.5, 10 µg / ml) within 12 hours. Which, not affect cell survival. After fixing osteoclast cells with formaldehyde fixative on glass coverslip followed by incubation with 0.1% Triton X-100 in PBS for 5 min and after that stain with rhodamine phalloidin staining for actin and Hoechst for nuclei. Fluorescence microscopy was performed to see the distribution of filaments actin [F.actin]. Finally, resveratrol reduced the actin ring formation. Resveratrol is the best bioactive compound for drug preparation against bone loss.

QSAR analysis of sodium glucose co-transporter 2 (SGLT2) inhibitors for anti-hyperglycaemic lead development.

QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle and distinguished structural features that are responsible for the inhibitory potency of these compounds against SGLT2, such as less possible number of ring carbons at 8 Å from the lipophilic atoms in the molecule (fringClipo8A) and more possible value for the sum of the partial charges of the lipophilic atoms present within seven bonds from the donor atoms (lipo_don_7Bc). Multivariate GA-MLR (genetic algorithm-multi linear regression) and thorough validation methodology out-turned a statistically robust QSAR model with a very high predictability shown from various statistical parameters. A QSAR model with r2 = 0.83, F = 51.54, Q2LOO = 0.79, Q2LMO = 0.79, CCCcv = 0.88, Q2Fn = 0.76-0.81, r2ext = 0.77, CCCext = 0.85, and with RMSEtr < RMSEcv was proposed. This QSAR model will assist synthetic chemists in the development of the SGLT2 inhibitors as the antidiabetic leads.