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M Ellen Kuenzig,1,2 Therese A Stukel,3,4 Matthew W Carroll,5 Gilaad G Kaplan,6 Anthony R Otley,7 Harminder Singh,8– 10 Alain Bitton,11 Stephen G Fung,12,13 Sarah Spruin,3,14 Stephanie Coward,6 Yunsong Cui,15 Zoann Nugent,8 Anne M Griffiths,1,2,16 David R Mack,12,13,17 Kevan Jacobson,18 Geoffrey C Nguyen,3,4,19 Laura E Targownik,19 Wael El-Matary,20 Charles N Bernstein,8,9 Trevor J B Dummer,21 Jennifer L Jones,15 Lisa M Lix,22 Sanjay K Murthy,14,23– 25 Juan Nicolás Peña-Sánchez,26 Soheila Nasiri,12,13 Eric I Benchimol1– 4,16 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium1SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children (Sickkids), Toronto, Ontario, Canada; 2Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; 3ICES, Toronto, Ontario, Canada; 4Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; 5Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; 6Departments of Medicine & Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 7Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; 8Univeristy of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada; 9Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; 10Research Institute at CancerCare Manitoba, Winnipeg, Manitoba, Canada; 11McGill University Health Centre, Division of Gastroenterology and Hepatology, Montreal, Québec, Canada; 12CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, CHEO, Ottawa, Ontario, Canada; 13CHEO Research Institute, Ottawa, Ontario, Canada; 14Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 15Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 16Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; 17Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada; 18Department of Pediatrics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; 19Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 20Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; 21School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 23Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Division of Gastroenterology, The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada; 25School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; 26Department of Community Health & Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaCorrespondence: Eric I Benchimol, The Hospital for Sick Children Division of Gastroenterology, Hepatology and Nutrition 555 University Avenue, Toronto, ON, M5G 1X8, Canada, Fax +1-416-813-4972, Email eric.benchimol@sickkids.caPurpose: The incidence of childhood-onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes.Patients and Methods: Using population-based deterministically-linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD < 16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed-effects meta-analysis was used to pool results and examine the association between center-level care provision and outcomes.Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had ≥ 1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had ≥ 1 ED visit and there were 1.64 ED visits per person. Between-center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between-center heterogeneity was high for intestinal resection in Crohn’s disease but not colectomy in ulcerative colitis.Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn’s disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary-care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care.Plain Language Summary: Inflammatory bowel disease (IBD) is a chronic health condition of the gastrointestinal system, which is becoming more common in children. They require lifelong treatment and receiving high quality care is important for preventing complications. We determined if outcomes of children with IBD was different across Canada. We also tested if differences in care at diagnosis was related to outcomes. More than three-quarters of children with IBD were treated at pediatric hospitals. Children treated at some hospitals were more likely to be hospitalized and visit the emergency room when compared to children treated at other hospitals. Children with Crohn’s disease (one type of IBD) were more likely to have surgery at some hospitals when compared to children treated at other hospitals. We should improve care to make sure children living with IBD have timely access to high quality specialist care.Keywords: Crohn’s disease, ulcerative colitis, health administrative data, variation in care, health services utilization, surgery

Harjeet Singh,1 Martin F Desimone,2 Shivani Pandya,1,3 Srushti Jasani,1 Noble George,1,3 Mohd Adnan,4 Abdu Aldarhami,5 Abdulrahman S Bazaid,6 Suliman A Alderhami7 1Research and Development Cell, Parul University, Vadodara, Gujarat, 391760, India; 2Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; 3Department of Forensic Science, PIAS, Parul University, Vadodara, Gujarat, 391760, India; 4Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia; 5Department of Medical Microbiology, Qunfudah Faculty of Medicine, Umm Al-Qura University, Al-Qunfudah, 28814, Saudi Arabia; 6Department of Medical Laboratory Science, College of Applied Medical Sciences, University of Hail, Hail, 55476, Saudi Arabia; 7Chemistry Department, Faculty of Science and Arts in Almakhwah, Al-Baha University, Al-Baha, Saudi ArabiaCorrespondence: Shivani Pandya, Department of Forensic Science, PIAS, Parul University, Vadodara, Gujarat, 391760, India, Email shivpan02@gmail.com Abdu Aldarhami, Department of Medical Microbiology, Qunfudah Faculty of Medicine, Umm Al-Qura University, Al-Qunfudah, 28814, Saudi Arabia, Email ahdarhami@uqu.edu.saBackground: Conventional nanoparticle synthesis methods involve harsh conditions, high costs, and environmental pollution. In this context, researchers are actively searching for sustainable, eco-friendly alternatives to conventional chemical synthesis methods. This has led to the development of green synthesis procedures among which the exploration of the plant-mediated synthesis of nanoparticles experienced a great development. Especially, because plant extracts can work as reducing and stabilizing agents. This opens up new possibilities for cost-effective, environmentally-friendly nanoparticle synthesis with enhanced size uniformity and stability. Moreover, bio-inspired nanoparticles derived from plants exhibit intriguing pharmacological properties, making them highly promising for use in medical applications due to their biocompatibility and nano-dimension.Objective: This study investigates the role of specific phytochemicals, such as phenolic compounds, terpenoids, and proteins, in plant-mediated nanoparticle synthesis together with their influence on particle size, stability, and properties. Additionally, we highlight the potential applications of these bio-derived nanoparticles, particularly with regard to drug delivery, disease management, agriculture, bioremediation, and application in other industries.Methodology: Extensive research on scientific databases identified green synthesis methods, specifically plant-mediated synthesis, with a focus on understanding the contributions of phytochemicals like phenolic compounds, terpenoids, and proteins. The database search covered the field’s development over the past 15 years.Results: Insights gained from this exploration highlight plant-mediated green synthesis for cost-effective nanoparticle production with significant pharmacological properties. Utilizing renewable biological resources and controlling nanoparticle characteristics through biomolecule interactions offer promising avenues for future research and applications.Conclusion: This review delves into the scientific intricacies of plant-mediated synthesis of nanoparticles, highlighting the advantages of this approach over the traditional chemical synthesis methods. The study showcases the immense potential of green synthesis for medical and other applications, aiming to inspire further research in this exciting area and promote a more sustainable future.Keywords: nanomaterials, biocompatibility, medicinal plants, surface functionalization, green synthesis, biomedical application

Thomas Hedman,1 James Yu,2 Harwant Singh,3 Timothy Deer4 1F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA; 2Sydney Spine and Pain, Waratah Private Hospital, Hurstville, New South Wales, Australia; 3Spine and Joint Centre, Pantai Hospital, Kuala Lumpur, Malaysia; 4The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Thomas Hedman, Tel +1 512 818-8468, Email tomhedman@alum.mit.eduBackground: Genipin is a polymer-forming collagen bonding substance that can be dissolved in a buffered carrier and injected into disc annulus tissues. Therapeutic benefit is derived from the mechanical support provided by a large number of genipin polymers attached to collagen fibers in a degraded disc.Study Design/Setting: IRB-approved prospective, multi-site, single-arm, 12-month feasibility studies were undertaken in two countries to evaluate the safety and efficacy of the genipin-based implant for treating discogenic chronic low back pain (CLBP).Patient Sample: Twenty CLBP patients with symptomatic discs at one or two levels were enrolled in the study.Outcome Measures: The primary safety endpoint was serious adverse events at 1 month, and the primary efficacy endpoint was reduction of pain and disability at 3 months. Secondary efficacy endpoints included reduction of pain and disability at 2 weeks, 1 month, 6 months, and 12 months; reduction of flexion–extension instability; increase in segmental lordosis and rotation; and patient satisfaction.Methods: Fluoroscopic image-guidance was used to deliver two posterolateral injections of buffered genipin to each symptomatic disc. Flexion–extension radiographs were used to quantify joint kinematics at three time-points.Results: Clinically meaningful improvements in pain and disability scores were reported in 80% or more of patients from 2 weeks to 1 year post-treatment. For the more severely unstable joints, treatment significantly reduced the instability score from a pre-treatment level of 2.4 standard deviations above the mean for an asymptomatic population to the asymptomatic mean at the 3-month follow-up.Conclusion: These initial clinical data demonstrate the safety and efficacy of a genipin-based collagen tethering device capable of improving spinal joint stability while successfully addressing CLBP. This work merits additional randomized clinical studies.Keywords: disc disease, lumbar spine, collagen, degenerative disc disease

We describe a population of the acanthocephalan Corynosoma australe Johnston, 1937 (Polymorphidae) from a California sea lion Zalophus californianus (Lesson, 1828) in California using novel scanning electron microscopy (SEM) images, Energy Dispersive x-ray analysis (EDXA), and molecular analysis for the first time. The taxonomic history of C. australe is replete with accounts using only line drawings some of which proved erroneous. The distribution of ventral spines on the female trunk has been the primary distinction between C. australe and Corynosoma obtuscens Lincicome, 1943, its junior synonym; being continuous in the latter but discontinuous posteriorly in the former species. The distribution of ventral spines is invariably discontinuous in males. Our redescription and SEM images help to resolve this issue further validating the synonymy. Morphological variability has been documented between our California population and others from various host species in California, South Australia, South Shetlands, and the Argentinian coast. Our SEM images document features not previously detectable in line drawings, erroneously reported or missed in previous accounts. The EDXA spectra show high levels of calcium and phosphorous and low levels of sulfur characteristic of C. australe. EDXA for other species of Corynosoma Lühe, 1904 provide support for the diagnostic distinction of C. australe. EDXA spectra were shown to be species specific and have diagnostic value in the taxonomy of the Acanthocephala. Our molecular analysis used amplification of 18S of ribosomal DNA and cytochrome c oxidase 1 (Cox1) gene. Phylogenetic analyses for Cox1 gene revealed a close relationship between Corynosoma hannae Zdzitowiecki, 1984 and C. australe. The phylogenetic trees confirmed that the isolates belonged to C. australe. The haplotype network inferred by Cox1 with C. australe sequences revealed that haplotypes clearly separated from each other and formed clusters related to samples from the Northern Hemisphere (the USA and Mexico), and the second from the Southern Hemisphere (Argentina, Brazil and Peru).

Harpreet Singh,1 Liam Wilson,2 Tom Tencer,3 Jinender Kumar3 1Health Economics & Market Access (HEMA), Amaris Consulting Ltd, Toronto, ON, Canada; 2Health Economics & Market Access (HEMA), Amaris Consulting Ltd, Shanghai, People’s Republic of China; 3Bristol Myers Squibb, Princeton, NJ, USACorrespondence: Jinender Kumar, Global HEOR, Bristol Myers Squibb, 100 Nassau Park Blvd &num;300, Princeton, NJ, 08540, USA, Tel +1-609-302-7630, Email Jinender.Kumar@bms.comBackground: Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching.Objective: We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib.Methods: We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017− 2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching.Results: In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20– 95% (1.8– 36 months), clinical remission rates were 10– 94% (1.8– 36 months), colectomy rates were 0– 33% (12– 38 months), and adverse event rates were 0– 18%. Treatment switching rates in 21 studies were 4– 70% over 3– 62 months, with switch due to loss of response rates of 4– 35% over 12– 62 months (7 studies). Up to 35% of patients underwent colectomy 12− 120 weeks after switching, and 13– 38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching.Conclusion: Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.Keywords: ulcerative colitis, real-world evidence, systematic literature review, biologic therapies, tofacitinib

Gaurav Pande,1 Manjunath Hatti,1 Mohit Kumar Rai,2 Praveer Rai,1 Kamlesh Kumar,1 Krishna VP,1 Abhimanyu Nehra,1 Sudeep Kumar,3 Smarak Ranjan Rout,3 Sourav Kumar Mishra,3 Dinesh Kumar,4 Umesh Kumar,4 Prabhaker Mishra,5 Abdul Majeed,1 Vivek Anand Saraswat,1,&ast; Kritika Singh,2 Harshit Singh,2 Durga Prasanna Misra,2 Vikas Agarwal2,&ast; 1Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 2Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 3Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 4Department of Advanced Spectroscopy and Imaging, Center of Biomedical Research, Lucknow, India; 5Biostatistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India&ast;These authors contributed equally to this workCorrespondence: Vikas Agarwal, Unit III, Clinical Immunology and Rheumatology, SGPGIMS, Raebareli Road, Lucknow, India, Tel +918004904390, Fax +91522268812, Email vikasagr@yahoo.comBackground and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival.Methods: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium > 80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated.Results: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = < 0.001). All those who were unable to reach urine sodium > 80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations.Conclusion: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.Graphical Abstract: Keywords: urine sodium, hemodynamics, renal artery resistive index, cytokines, neutrophil extracellular traps

Acharya Balkrishna,1– 3 Siva Kumar Solleti,1,&ast; Hoshiyar Singh,1,&ast; Rani Singh,1 Niti Sharma,1 Anurag Varshney1,2,4 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India; 2Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Haridwar, Uttarakhand, India; 3Patanjali UK Trust, Glasgow, UK; 4Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, India&ast;These authors contributed equally to this workCorrespondence: Anurag VarshneyDrug Discovery and Development, Patanjali Research Institute, NH-58, Near Bahadrabad, Haridwar, 249405, UttraKhand, IndiaTel +91 1334-244107 x7458Fax +91 1334 244805Email anurag@prft.co.inPurpose: Asthma is a heterogeneous airway inflammatory disease with limited therapeutic options. Traditional medicine is extensively used for treating various ailments including asthma. Sahastraputi-Abhrak-Bhasma (SPAB) is a biotite-calx based Indian medicine.Methods: We have tested for the anti-inflammatory and anti-asthmatic properties of SPAB, using a mouse model of ovalbumin-induced allergic asthma in-vivo and cell-based assays in-vitro. Histological analysis, qPCR and ELISA were performed to assess the pathology. SEM, EDX and XRD-analysis were performed to characterize the SPAB particles.Results: SEM, EDX and XRD-analysis identified the presence of SPAB particle of 100 nm–∼ 1μm diameter and contains annite-1M, aluminium silicate, kyanite, aluminium oxide, magnesium silicate, and maghemite in the samples. Ova-challenge resulted in severe inflammatory responses, airway remodelling and increased oxidative burden in lungs. Importantly, prophylactic treatment with SPAB significantly attenuated allergen induced leukocyte infiltration specifically eosinophils, lymphocytes, macrophages and neutrophils in BALF. Ova-induced mucus hypersecretion, peri-bronchial collagen deposition, inflammatory cell infiltration and bronchial epithelial thickening were significantly abrogated upon SPAB treatment. qPCR and ELISA analysis identified that allergen induced increases in IL-5, IL-13, IL-33, IFN-γ and IL-1β cytokines mRNA in whole lungs and the levels of IL-6, IL-1β and TNF-α proteins in BALF were significantly attenuated upon oral SPAB treatment. SPAB restored allergen induced decreases in anti-oxidant markers in lungs. In-vitro, SPAB attenuated the secretion of IL-6, and TNF-α from human bronchial epithelial cells and modestly inhibited NF-kB/AP-1 pathway in HEK cells.Conclusion: Taken together, our results experimentally validated the prophylactic ameliorative potential of the Indian classical medicine Sahastraputi-Abhrak-Bhasma against asthma associated airway inflammation.Keywords: Sahastraputi-Abhrak-Bhasma, asthma, physicochemical analysis, lung inflammation, cytokine, mica-medicine

Acharya Balkrishna,1,2 Subarna Pokhrel,1 Hoshiyar Singh,1 Monali Joshi,1 Vallabh Prakash Mulay,1 Swati Haldar,1 Anurag Varshney1,2 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, 249405, Uttarakhand, India; 2Department of Allied and Applied Sciences, University of Patanjali, Haridwar, 249405, Uttarakhand, IndiaCorrespondence: Anurag Varshney; Swati HaldarDrug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar, 249405, Uttarakhand, IndiaTel +91-1334-244107, Ext. 7458; +91-1334-244107, Ext. 7481Fax +91-1334-244805Email anurag@prft.co.in; swati.haldar@prft.inPurpose: SARS-CoV-2 engages human ACE2 through its spike (S) protein receptor binding domain (RBD) to enter the host cell. Recent computational studies have reported that withanone and withaferin A, phytochemicals found in Withania somnifera, target viral main protease (MPro) and host transmembrane TMPRSS2, and glucose related protein 78 (GRP78), respectively, implicating their potential as viral entry inhibitors. Absence of specific treatment against SARS-CoV-2 infection has encouraged exploration of phytochemicals as potential antivirals.Aim: This study aimed at in silico exploration, along with in vitro and in vivo validation of antiviral efficacy of the phytochemical withanone.Methods: Through molecular docking, molecular dynamic (MD) simulation and electrostatic energy calculation the plausible biochemical interactions between withanone and the ACE2-RBD complex were investigated. These in silico observations were biochemically validated by ELISA-based assays. Withanone-enriched extract from W. somnifera was tested for its ability to ameliorate clinically relevant pathological features, modelled in humanized zebrafish through SARS-CoV-2 recombinant spike (S) protein induction.Results: Withanone bound efficiently at the interacting interface of the ACE2-RBD complex and destabilized it energetically. The electrostatic component of binding free energies of the complex was significantly decreased. The two intrachain salt bridge interactions (K31-E35) and the interchain long-range ion-pair (K31-E484), at the ACE2-RBD interface were completely abolished by withanone, in the 50 ns simulation. In vitro binding assay experimentally validated that withanone efficiently inhibited (IC50=0.33 ng/mL) the interaction between ACE2 and RBD, in a dose-dependent manner. A withanone-enriched extract, without any co-extracted withaferin A, was prepared from W. somnifera leaves. This enriched extract was found to be efficient in ameliorating human-like pathological responses induced in humanized zebrafish by SARS-CoV-2 recombinant spike (S) protein.Conclusion: In conclusion, this study provided experimental validation for computational insight into the potential of withanone as a potent inhibitor of SARS-CoV-2 coronavirus entry into the host cells.Keywords: ACE2-RBD complex, Withania somnifera, withanone, docking and MD simulation, ELISA, SARS-CoV-2 S-protein, humanized zebrafish model

Acharya Balkrishna,1,2 Swati Haldar,1 Hoshiyar Singh,1 Partha Roy,3 Anurag Varshney1,2 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, 249405, Uttarakhand, India; 2Department of Allied and Applied Sciences, University of Patanjali, Haridwar, 249405, Uttarakhand, India; 3Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, IndiaCorrespondence: Anurag VarshneyDrug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar, 249405, Uttarakhand, IndiaTel +91-1334-244107, Ext.: 7458Fax +91-1334-244805Email anurag@prft.co.inPurpose: Coronil is a tri-herbal formulation containing extracts from Withania somnifera, Tinospora cordifolia, and Ocimum sanctum. Recently, it was shown that Coronil rescued humanized zebrafish from SARS-CoV-2 induced pathologies. Based on reported computational studies on the phytochemicals present in Coronil, it could be a potential inhibitor of SARS-CoV-2 entry into the host cell and associated cytokines’ production.Methods: Through an ELISA-based biochemical assay, effects of Coronil on interaction between ACE-2 and different mutants of viral spike (S) protein, crucial for viral invasion of host cell, were evaluated. Additionally, using recombinant pseudoviruses having SARS-CoV-2 spike (S) protein in their envelopes and firefly luciferase reporter in their genomes, effects of Coronil on virus entry into human alveolar epithelial cells were evaluated through luciferase assay. UHPLC profiled Coronil also modulated S-protein mediated production of pro-inflammatory cytokines in A549 cells, like interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), as evaluated through RT-qPCR and ELISA.Results: Coronil effectively inhibited the interaction of ACE-2 not only with the wild-type S protein (SWT) but also with its currently prevalent and more infectious variant (SD614G) and another mutant (SW436R) with significantly higher affinity toward ACE-2. Treatment with Coronil significantly reduced the increased levels of IL-6, IL-1β, and TNF-α in A549 cells incubated with different S-protein variants in a dose-dependent manner. Likewise, it also prevented the SARS-CoV-2 S-protein pseudotyped vesicular stomatitis virus (VSVppSARS-2S) mediated cytokine response in these cells by reducing entry of pseudoviruses into host cells.Conclusion: Coronil prevented SARS-CoV-2 S-protein mediated viral entry into A549 cells by inhibiting spike protein-ACE-2 interactions. SARS-CoV-2 S protein induced inflammatory cytokine response in these cells was also moderated by Coronil.Keywords: Coronil, SARS-CoV-2, pseudovirus, spike protein, ACE-2, pro-inflammatory cytokines

Harjit Singh,1 Gerard A Kennedy,1– 3 Ieva Stupans1 1The School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia; 2School of Science, Psychology and Sport, Federation University, Melbourne, VIC, Australia; 3Institute for Breathing and Sleep, Austin Health, Melbourne, VIC, AustraliaCorrespondence: Harjit SinghThe School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC 3083, AustraliaEmail s3200840@student.rmit.edu.auObjective: The purpose of this review was to evaluate the modalities (e.g., face-to-face, telephone or electronic) of pharmacist health coaching providing the greatest improvement in patient outcomes, to enable a more comprehensive evaluation to be done and quality decision-making around health coaching modalities to be undertaken by pharmacists.Methods: This systematic review followed the PRISMA guidelines. CINHAL, EMBASE, PubMed, PsychINFO and SCOPUS were searched (2000– 2019). Included articles were reviewed for the modality used to health coach, the training provided, and the outcomes.Results: Twelve papers met the eligibility criteria. A majority of studies included involved a combination of modalities of pharmacist health coaching. Four papers referred to face-to-face sessions, and one study used telephone coaching. In each paper, coaching led to an improvement in clinical and non-clinical health outcomes.Conclusion: The training provided to health coaches varied and in some cases was not reported. Inconsistencies in reports led to difficulties when comparing study outcomes. Therefore, conclusions about the modality providing the greatest improvement in patient outcomes and the most pragmatic health coaching modality are not possible. Studies that document the training, the modality, the outcomes and the cost benefits of coaching by pharmacists are warranted to enable a more comprehensive evaluation to be done and quality decision-making around health coaching modalities to be undertaken by pharmacists.Keywords: health, coaching, pharmacy, modalities

Suresh Sadhasivam,1 Kalpna Garkhal,1 Himanshi Singh,1 Vishal Yadav,1 Suresh Chawrai,1 Mukesh Ramnane,2 Shilpi Jain,1 Kabir Sardana,3 Shamik Ghosh1 1Vyome Therapeutics Limited, New Delhi 110092, India; 2MS Clinical Research Pvt. Ltd, Ulsoor, Bangalore 560008, India; 3Department of Dermatology, Dr RML Hospital and PGIMER, New Delhi 110001, IndiaCorrespondence: Shamik GhoshVyome Therapeutics Limited, 465 Ground Floor, Patparganj Industrial Area, New Delhi 110092, IndiaEmail shamik.ghosh@vyometx.comKabir SardanaDepartment of Dermatology, Dr. RML Hospital and PGIMER, New Delhi 110001, IndiaEmail article.sardana@gmail.comBackground: Uninhibited proliferation of Malassezia spp., enhanced sebaceous gland activity and individual sensitivity are three prime etiological factors behind dandruff. For many dandruff sufferers, existing anti-dandruff products start yielding unsatisfactory results after a few cycles of use. This observation made us explore the physical and biological environment of the host and exploit the specific type of lipid dependence of Malassezia spp. for their survival. A shampoo formulation (product code VB-3222) was developed to address the shortcomings of existing therapy.Purpose: Evaluating efficacy of VB-3222 in comparison to marketed products through in vitro assays and subsequently demonstrating its advantages in a clinical study.Methods: VB-3222 was developed with a derivative of medium chain fatty acid (MCFA) and zinc pyrithione and compared against marketed comparators by in vitro time kill assay. Subsequently, VB-3222 shampoo was tested in a 21-day clinical trial on 25 moderate dandruff subjects to evaluate local safety and efficacy.Results: VB-3222 in all in vitro cases demonstrated significantly better fungicidal activity than its marketed comparators. In the clinical trial, VB-3222 was well tolerated in all subjects and imparted consistent reduction of the ASFS (adherent scalp flaking score) and the pruritus score. At days 7 and 21, 55% and 90% reduction in the ASFS in comparison to treatment initiation and 50% and 95.5% reduction in the pruritus score were observed.Conclusion: The increased efficacy of VB-3222 over comparator products in vitro, and the dramatic reduction (> 90%) in ASFS and pruritis in subjects within 21 days of use with excellent tolerability and sensorial profile, positions VB-3222 as the new generation treatment for adherent dandruff.Clinical Trial Registration No: CTRI/2018/05/013567.Keywords: anti-dandruff shampoo, Malassezia spp., potentiator, dandruff, seborrheic dermatitis

The aim of the present study was to determine copro-prevalence of gastrointestinal parasites and their associated potential risk factors in pigs of Punjab (India). A total of 839 faecal samples were collected from pigs of all age group and sex from different agro-climatic zones of Punjab covering all seasons and subjected to qualitative and quantitative examination. Among the samples examined, 28.4 % were positive for gastrointestinal parasites and their respective prevalences were Ascaris suum (11.1 %), coccidia (9.41 %), Trichuris suis (6.43 %), Balantidium coli (4.5 %), amphistome (3.33 %), strongyle (2.14 %) and Ascarops strongylina (1.78 %). Upon sporulation of coccidian positive samples, 8 species of Eimeria were recorded (Eimeria polita, E. spinosa, E. scabra, E. perminuta, E. suis, E. debliecki, E. neodebliecki and E. porci). Among the various risk factors analysed, season, agro-climatic zones and managemental practices had a signifi cant (p

Two species of digenetic trematodes of the genus Pleurogenoides viz., P. cyanophlyctiShinad & Prasadan (2018a) and P. euphlyctiShinad & Prasadan (2018b) have been described from India. Information regarding the molecular data of various species of the genus Pleurogenoides Travassos, 1921 is virtually lacking. This study addresses the application of molecular markers to validate the phylogenetic position of P. cyanophlycti and P. euphlycti. In the present study, two species P. cyanophlycti and P. euphlycti were collected between January 2016 to October 2017, infecting the freshwater frogs inhabiting the Western Ghats, India. In the present study, the two species were identifi ed morphologically and by PCR amplification of the 28S ribosomal RNA gene. Phylogenetic tree results clearly demonstrate that both P. cyanophlycti and P. euphlycti belongs to the family Pleurogenidae Looss, 1899. Based on these results, we presented and discussed the phylogenetic relationships of P. cyanophlycti and P. euphlycti within family Pleurogenidae from India. Phylogenetic analyses showed that P. cyanophlycti and P. euphlycti cluster according to their vertebrate host and revealed an important congruence between the phylogenetic trees of Pleurogenoides and of their vertebrate hosts. P. cyanophlycti and P. euphlycti clearly constitute a separate, sister branch with other species of the genera, Pleurogenoides, Pleurogenes (=Candidotrema), Prosotocus and Brandesia. The present study firstly provides important information about the molecular study and phylogenetic analysis of P. cyanophlycti and P. euphlycti. This study will also serve as a baseline for Pleurogenoides species identifi cation for further studies.

A new nematode species, Heliconema monopteri n. sp. (Physalopteridae), is described from the stomach and intestine of the freshwater fish Monopterus cuchia (Hamilton) (Synbranchidae) in Bijnor district, Uttar Pradesh, India. It is mainly characterized by the lengths of spicules (468 – 510 µm and 186 – 225 µm), the postequatorial vulva without elevated lips, the presence of pseudolabial lateroterminal depressions and by the number and arrangement of caudal papillae. This is the first representative of the genus reported from a synbranchiform fish. Another new congeneric species, Heliconema pisodonophidis n. sp. is established based on a re-examination of nematodes previously reported as H. longissimum (Ortlepp, 1922) from Pisodonophis boro (Hamilton) (Ophichthidae) in Thailand; ovoviviparity in this species is a unique feature among all physalopterids. Heliconema hamiltonii Bilqees et Khanum, 1970 is designated as a species dubia and the nematodes previously reported as H. longissimum from Mastacembelus armatus (Lacépède) in India are considered to belong to H. kherai Gupta et Duggal, 1989. A key to species of Heliconema Travassos, 1919 is provided.

Introduction: Olecranon osteotomy is well described approach for complex intra-articular distal humeral fractures. In this study, we investigated the usefulness and complications of olecranon osteotomy approach for such fractures. We hypothesise that outcome is comparable in young adults and middle age group and also functional outcome is independent of fracture subtype following surgical fixation. Materials and Methods: Between December 2012 and September 2015, twenty-four adult patients (male: 15, female: 9) having mean age of 41.4 years with closed intra-articular fracture (AO-13C) were surgically managed using olecranon osteotomy approach and were followed-up for a mean of 28.5 months (range: 22-35 months). Functional outcome was measured using Mayo Elbow Performance Score (MEPS) and complications were observed. Statistical analysis was done using Student t-test and Kruskal Wallis test. Results: All fractures united by the end of three months. Mean elbow flexion achieved was 123°, mean extension lag was 9° and mean active arc of motion was 114°. Mean MEPS was 87 (excellent: 8, good: 14, fair: 1 and poor: 1). Post-operative transient ulnar nerve palsy was noted in two cases, heterotopic ossification (HO) was in one case, infection in two cases, implant prominence in five and elbow stiffness in three cases. Motion arc was higher in young adults and MEPS was comparable in both age group. Functional outcome was also dependent on fracture subtype. Conclusion: The olecranon osteotomy approach for distal humerus fractures had good functional outcome with fewer complications. Joint congruity and fixation could easily be assessed intraoperatively.

Eric I Benchimol,1–5 M Ellen Kuenzig,1,2,5 Charles N Bernstein,6,7 Geoffrey C Nguyen,5,8 Astrid Guttmann,5,9 Jennifer L Jones,10 Beth K Potter,4 Laura E Targownik,6,7 Christina A Catley,5 Zoann J Nugent,6,11 Divine Tanyingoh,12,13 Nassim Mojaverian,5 Fox E Underwood,12,13 Shabnaz Siddiq,1,2 Anthony R Otley,14 Alain Bitton,15 Matthew W Carroll,16 Jennifer C deBruyn,17 Trevor JB Dummer,18 Wael El-Matary,19 Anne M Griffiths,9 Kevan Jacobson,20,21 Desmond Leddin,10 Lisa M Lix,22 David R Mack,1–3 Sanjay K Murthy,4,23 Juan Nicolás Peña-Sánchez,24 Harminder Singh,6,7 Gilaad G Kaplan12,13 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium 1Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 2Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 3Department of Pediatrics, University of Ottawa, Ottawa, Canada; 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 5ICES, Toronto, Canada; 6University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada; 7Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; 8Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Canada; 9Department of Paediatrics, University of Toronto, Toronto, Canada; 10Department of Medicine, Dalhousie University, Halifax, Canada; 11CancerCare Manitoba, Winnipeg, Canada; 12Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 13Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 14Department of Pediatrics, Dalhousie University, Halifax, Canada; 15Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; 16Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada; 17Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada; 18School of Population and Public Health, University of British Columbia, British Columbia, Canada; 19Department of Pediatrics, University of Manitoba, Winnipeg, Canada; 20Department of Pediatrics, The University of British Columbia, British Columbia, Canada; 21Child and Family Research Institute, The University of British Columbia, British Columbia, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada; 23The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada Background and aims: Canada’s large geographic area and low population density pose challenges in access to specialized health care for remote and rural residents. We compared health services use, surgical rate, and specialist gastroenterologist care in rural and urban inflammatory bowel disease (IBD) patients in Canada.Methods: We used validated algorithms that were applied to population-based health administrative data to identify all people living with the following three Canadian provinces: Alberta, Manitoba, and Ontario (ON). We compared rural residents with urban residents for time to diagnosis, hospitalizations, outpatient visits, emergency department (ED) use, surgical rate, and gastroenterologist care. Multivariable regression compared the outcomes in rural/urban patients, controlling for confounders. Provincial results were meta-analyzed using random-effects models to produce overall estimates.Results: A total of 36,656 urban and 5,223 rural residents with incident IBD were included. Outpatient physician visit rate was similar in rural and urban patients. IBD-specific and IBD-related hospitalization rates were higher in rural patients (incidence rate ratio [IRR] 1.17, 95% CI 1.02–1.34, and IRR 1.27, 95% CI 1.04–1.56, respectively). The rate of ED visits in ON were similarly elevated for rural patients (IRR 1.53, 95% CI 1.42–1.65, and IRR 1.33, 95% CI 1.25–1.40). There were no differences in surgical rates or prediagnosis lag time between rural and urban patients. Rural patients had fewer IBD-specific gastroenterologist visits (IRR 0.79, 95% CI 0.73–0.84) and a smaller proportion of their IBD-specific care was provided by gastroenterologists (28.3% vs 55.2%, P65 years (33.0% vs 59.2%, P

David K Simson,1 Swarupa Mitra,2 Parveen Ahlawat,2 Upasna Saxena,2 Manoj Kumar Sharma,2 Sheh Rawat,2 Harpreet Singh,1 Babita Bansal,1 Lalitha Kameshwari Sripathi,1 Aditi Tanwar2 1Department of Radiation Oncology, Action Cancer Hospital, New Delhi, India; 2Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India Aims and objectives: The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. Materials and methods: All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Results: Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. Conclusion: IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy. Keywords: IMRT, rectal cancer, chemoradiation, neoadjuvant, response

Manjunath Siddaiah-Subramanya,1,2 Harveen Singh,3 Kor Woi Tiang1,2 1Department of Surgery, Logan Hospital, 2Department of Medicine, Griffith University, 3Department of Gastroenterology, Lady Cilento Children’s Hospital, Brisbane, QLD, Australia Objectives: Medical student involvement in research has been declining over the years. We reviewed the factors that hinder participation in research with a focus on developing countries. Methods: Literature search was performed using PubMed, MEDLINE and Cochrane Library. Peer-reviewed articles published between 1995 and 2017 were screened for relevance to identify key factors affecting medical student involvement in research with a particular focus on developing world. Analytical review is presented here in this article in relation to commonly reported aspects related to research during medical school. Results: This search revealed varied contributing factors that hinder students’ growth and interest in research. It commonly highlighted few aspects in relation to research during medical school, and they were “variability in research uptake among students and issues related to them, their knowledge and attitude toward research and organizational input and its influence on students”. Conclusion: While early introduction to research by inculcating a mindset aimed at research has been proposed, it has not been seen in practice during either the medical school or beyond to an extent that was expected. It appears that developing countries, while they share some of the reasons with developed countries, have their own set of difficulties, which are influenced by culture, beliefs and priorities. Keywords: developing country, developed country, medical student, undergraduate, research

Ibrahim Hussain, Mubashar Ameen, Hamdip Singh University of Nottingham, Faculty of Medicine and Health Sciences, Medical School, Queen’s Medical Center, Nottingham NG7 2UH, EnglandCorrespondence: Ibrahim HussainUniversity of Nottingham, Faculty of Medicine and Health Sciences, Medical School, Queen’s Medical Center, Nottingham NG7 2UH, EnglandEmail ibrahim_250@hotmail.co.uk The paper on the use of peer assessments in the training of medical students to obtain and provide quality feedback, by Lerchenfeldt and Taylor,1 was read with great interest. The authors provided an intriguing insight into the current use of peer assessments and how they could be better incorporated into the curriculum. We, as final year medical students, believe that there are other factors which should also be considered. View the original paper by Lerchenfeldt and Taylor

Yi Ni Koh,1,2 Shu Fen Ho,2 Letchumanan Pathma,3 Harvinder Singh,3 Embong Zunaina1 1Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; 2Department of Ophthalmology, 3Department of Otorhinolaryngology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia Abstract: There are various causes that can lead to compressive optic neuropathy. We present here orbital apex cyst as an unusual cause of compressive optic neuropathy in a 49-year-old male. He presented with 2 weeks painless loss of vision in the left eye with left-sided headache. He had had left functional endoscopic sinus surgery for left nasal polyps 4 years earlier. Magnetic resonance imaging of brain and orbit revealed a left discrete orbital nodule, possibly orbital cyst or mucocele, which was compressing on the left optic nerve. Left eye vision improved markedly from hand movement to 6/36 pinhole 6/18 after initiation of intravenous dexamethasone. A subsequent endoscopic endonasal left optic nerve decompression found the orbital nodule lesion to be an orbital cyst. Marsupialization was performed instead of excision, as the cyst ruptured intraoperatively. Postoperative vision improved to 6/7.5 with normal optic nerve function postoperatively. Possible cause of orbital apex cyst is discussed. Keywords: orbital cyst, compressive optic neuropathy, functional endoscopic sinus surgery

Dharmendra K Yadav,1 Surendra Kumar,2 Saloni,1 Harpreet Singh,3 Mi-hyun Kim,1 Praveen Sharma,4 Sanjeev Misra,4 Feroz Khan5 1Department of Pharmacy, College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, Republic of Korea; 2Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Babu Banarasi Das Northern India Institute of Technology, Lucknow, 3Department of Bioinformatics, Indian Council of Medical Research, New Delhi, 4Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 5Metabolic & Structural Biology Department, CSIR– Central Institute of Medicinal & Aromatic Plant, Lucknow, India Abstract: Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian traditional practice of medicine. Withanolides are steroidal lactones (highly oxygenated C-28 phytochemicals) and have been reported to exhibit immunomodulatory, anticancer and other activities. In the present study, a quantitative structure activity relationship (QSAR) model was developed by a forward stepwise multiple linear regression method to predict the activity of withanolide analogs against human breast cancer. The most effective QSAR model for anticancer activity against the SK-Br-3 cell showed the best correlation with activity (r2=0.93 and rCV2 =0.90). Similarly, cross-validation regression coefficient (rCV2=0.85) of the best QSAR model against the MCF7/BUS cells showed a high correlation (r2=0.91). In particular, compounds CID_73621, CID_435144, CID_301751 and CID_3372729 have a marked antiproliferative activity against the MCF7/BUS cells, while 2,3-dihydrowithaferin A-3-beta-O-sulfate, withanolide 5, withanolide A, withaferin A, CID_10413139, CID_11294368, CID_53477765, CID_135887, CID_301751 and CID_3372729 have a high activity against the Sk-Br-3 cells compared to standard drugs 5-fluorouracil (5-FU) and camptothecin. Molecular docking was performed to study the binding conformations and different bonding behaviors, in order to reveal the plausible mechanism of action behind higher accumulation of active withanolide analogs with β-tubulin. The results of the present study may help in the designing of lead compound with improved activity. Keywords: ADMET, breast cancer, QSAR, molecular docking, withanolides

Priyanka Singh,1,2 Yeon Ju Kim,1 Hina Singh,1 Sungeun Ahn,1 Verónica Castro-Aceituno,1 Deok Chun Yang1,2 1Department of Oriental Medicine Biotechnology, Ginseng Bank, 2Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Republic of Korea Abstract: The present study investigates a simple and convenient one-step procedure for the preparation of bovine serum albumin (BSA)-Rh2 nanoparticles (NPs) at room temperature. In this work, ginsenoside Rh2 was entrapped within the BSA protein to form BSA-Rh2 NPs to enhance the aqueous solubility, stability, and therapeutic efficacy of Rh2. The physiochemical characterization by high-performance liquid chromatography, nuclear magnetic resonance, Fourier transform infrared spectroscopy, field emission transmission electron microscopy, dynamic light scattering, and thermogravimetric analysis confirmed that the prepared BSA-Rh2 NPs were spherical, highly monodispersed, and stable in aqueous systems. In addition, the stability of NPs in terms of different time intervals, pHs, and temperatures (20°C–700°C) was analyzed. The results obtained with different pHs showed that the synthesized BSA-Rh2 NPs were stable in the physiological buffer (pH 7.4) for up to 8 days, but degraded under acidic conditions (pH 5.0) representing the pH inside tumor cells. Furthermore, comparative analysis of the water solubility of BSA-Rh2 NPs and standard Rh2 showed that the BSA nanocarrier enhanced the water solubility of Rh2. Moreover, in vitro cytotoxicity assays including cell viability assays and morphological analyses revealed that Rh2-entrapped BSA NPs, unlike the free Rh2, demonstrated better in vitro cell viability in HaCaT skin cell lines and that BSA enhanced the anticancer effect of Rh2 in A549 lung cell and HT29 colon cancer cell lines. Additionally, anti-inflammatory assay of BSA-Rh2 NPs and standard Rh2 performed using RAW264.7 cells revealed decreased lipopolysaccharide-induced nitric oxide production by BSA-Rh2 NPs. Collectively, the present study suggests that BSA can significantly enhance the therapeutic behavior of Rh2 by improving its solubility and stability in aqueous systems, and hence, BSA-Rh2 NPs may potentially be used as a ginsenoside delivery vehicle in cancer and inflammatory cell lines. Keywords: bovine serum albumin, ginsenoside Rh2, solubility, stability, cancer, inflammation

Two species of Thaparocleidus Jain (1952a) were found harboring W. attu from the Ganga River at two localities, Meerut and Farrukhabad, Uttar Pradesh, India, during the period of 2013-2015. Morphology and morphometric study of specimens identified as Thaparocleidus gomtius (Jain, 1952a) Lim, 1996 and T. sudhakari (Gusev, 1976) Lim, 1996. Molecular analyses using the 18S rRNA gene confirmed the validity of T. gomtius and T. sudhakari and demonstrated that both the species clustered with other Thaparocleidus species from different geographical regions. We aim at reassessing the taxonomy and establishing the phylogenetic relationships among these two redescribed species with other representatives of the genus Thaparocleidus.

The nematode, Procamallanus spiculogubernaculus Agarwal, 1958 was found from the Stinging catfish, Heteropneustes fossilis (Bloch, 1794) from Ghazipur, Delhi, India. Morphological characterization, including scanning electron microscope observation supplemented with DNA sequences is provided. Specimens recently found are characterized by the presence of an unlined buccal capsule having a small basal ring, esophagus muscular and glandular, vulva position is slightly post-equatorial, tail conical, long, and ending in three digit-like processes, phasmids present at about mid-length and cloaca located at the posterior end. In this study the species P. spiculogubernaculus is validated on the basis of molecular data after 47 years from its original description. In the scanning electron microscope examination, the topology of mouth and sensory pits in anterior portion, while the phasmids and digit like processes in posterior portion is clearly observed. Molecular data of the 18S ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were analyzed. Molecular phylogenetic analyses supported the validity of Procamallanus spiculogubernaculus and confirmed the paraphyletic status of the members of Procamallanus, Spirocamallanus, Camallanus and Paracamallanus. Taxonomic status of members of the family Camallanidae are briefly discussed along with the results of the systematic evaluation of P. spiculogubernaculus based on molecular data.

Three species of digenetic trematodes are redescribed based on specimens collected from the intestine of freshwater fishes of Hastinapur and Meerut (U.P.), India: Allocreadium handiai (Pande, 1937) Madhavi, 1980 (Allocreadioidea: Allocreadiidae) from Mystus tengara (Hamilton, 1822) (Siluri-formes: Bagridae), Genarchopsis goppoOzaki, 1925 (Hemiuroidea: Derogenidae) and Phyllodistomum chauhaniMotwani & Srivastava, 1961 (Plagiorchioidea: Gorgoderidae) from Channa punctata (Bloch, 1793) (Perciformes: Channidae). The three species were subjected to morphological, morphometric and molecular analyses. The morphological study revealed that A. handiai, G. goppo and P. chauhani can be distinguished by their congeners on the basis of their morphology. Partial nucleotide sequences of the 28S ribosomal RNA gene were obtained from the three trematode species and deposited in the GenBank. A phylogenetic reconstruction based on the 28S rRNA gene placed the three studied species within their respective families and their validity is discussed. For the first time molecular data of newly collected material of these species from India were used for confirmation of their validity and to assess their phylogenetic relationships.

This study was conducted to examine the effects of feed restriction on production performance as well as traits relating to egg and carcass yield in Potchefstroom Koekoek dual purpose chicken bred under Ethiopian conditions. A total of 240 one-day-old dual purpose Koekoek chicks were randomly distributed into 12 experimental pens, representing 4 feeding treatments to evaluate the performance of chicks on body weight and age at onset of laying eggs (AOLE), egg quality, and carcass parameters. Treatments were control (unrestricted feed), R7-28 (restricted feed at 7, 10, 13, 16, 19, 22, 25 and 28 days of age), R35-56 (restricted feed at 35, 38, 41, 44, 47, 50, 53 and 56 days of age) and R63-84 (restricted feed at 63, 66, 69, 72, 75, 78, 81 and 84 days of age) groups. The results showed a significant difference between the control and R63-84 group's birds in both daily and total feed consumption (P < 0.05). There was a significant (P < 0.05) difference in body weight at the end of the starter period, where R63-84 group's birds had a heavier body weight and body weight gain than R7-28 and R35-56 groups' birds, but not control birds. Yolk diameter was significantly lower in R35-56 group than R7-28 and R63-84 groups (P < 0.05). Feed restriction also did not affect slaughter and dressed weight, but the eviscerated weight was significantly lower in R35-56 and R63-84 groups than control (P < 0.05). Feed restriction was associated with production costs of the treatments, and the feeding regime of R63-84 group significantly decreased the amount of feed consumed by birds (P < 0.05). Thus, feed restriction during 63 to 84 days of age (R63-84 group) can be useful because of improving the production profitability of rearing chicks without affecting the AOLE, body weight at AOLE, egg weight, and carcass parameters.

No abstract available. Article truncated after 150 words. A 68 year old man with a past medical history significant only for mild hyperlipidemia and distant cigar smoking presented to this primary physician’s office with a chief complaint of left sided shoulder pain for more than 6 months duration. His only other complaint was a hacking morning cough that was attributed to GERD after resolution with omperazole therapy. He was without any other complaints such as weight loss, fevers, chills, night sweats, shortness of breath, or dyspnea on exertion. His physical exam was without any abnormality. An initial radiograph of the rileft shoudler was obtained which was without any obvious bony abnormality but demonstrated numerous potential pulmonary nodules (Figure 1). He was then referred to pulmonology for further assessment. A chest CT scan peformed with contrast again demonstrated numerous pulmonary nodules with thick walled central cavitations throughout the lung parenchyma bilaterally (Figures 2 & 3). Additional testing performed included …

Priyanka Singh,1 Yeon Ju Kim,2 Hina Singh,1 Chao Wang,2 Kyu Hyon Hwang,3 Mohamed El-Agamy Farh,1 Deok Chun Yang1,2 1Department of Oriental Medicinal Material and Processing, 2Graduate School of Biotechnology and Ginseng Bank, College of Life Sciences, Kyung Hee University, Yongin, 3Gyeonggi-Do Agricultural Research & Extension Services, Gyeonggi, Republic of Korea Abstract: In the present study, the strain Brevibacterium frigoritolerans DC2 was explored for the efficient and extracellular synthesis of silver nanoparticles. These biosynthesized silver nanoparticles were characterized by ultraviolet-visible spectrophotometry, which detected the formation of silver nanoparticles in the reaction mixture and showed a maximum absorbance at 420 nm. In addition, field emission transmission electron microscopy revealed the spherical shape of the nanoparticles. The dynamic light scattering results indicated the average particle size of the product was 97 nm with a 0.191 polydispersity index. Furthermore, the product was analyzed by energy dispersive X-ray spectroscopy, X-ray diffraction, and elemental mapping, which displayed the presence of elemental silver in the product. Moreover, on a medical platform, the product was checked against pathogenic microorganisms including Vibrio parahaemolyticus, Salmonella enterica, Bacillus anthracis, Bacillus cereus, Escherichia coli, and Candida albicans. The nanoparticles demonstrated antimicrobial activity against all of these pathogenic microorganisms. Additionally, the silver nanoparticles were evaluated for their combined effects with the commercial antibiotics lincomycin, oleandomycin, vancomycin, novobiocin, penicillin G, and rifampicin against these pathogenic microorganisms. These results indicated that the combination of antibiotics with biosynthesized silver nanoparticles enhanced the antimicrobial effects of antibiotics. Therefore, the current study is a demonstration of an efficient biological synthesis of silver nanoparticles by B. frigoritolerans DC2 and its effect on the enhancement of the antmicrobial efficacy of well-known commercial antibiotics. Keywords: Brevibacterium frigoritolerans, biosynthesis, silver nanoparticles, antimicrobial activity, synergistic effect

La-Mg alloys of different compositions were prepared by electrolysis of LaCl3-MgCl2-KCl melts. Different phases of La-Mg alloys were characterized by X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). Energy dispersive spectrometry (EDS) and Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) analyses showed that chemical compositions of La-Mg alloys were consistent with phase structures of XRD pattern, and magnesium content in the alloy could be controlled by electrolysis parameters. The effects of various process parameters such as concentration of magnesium chloride in the bath, temperature of electrolysis and cathode current density on the current efficiency have been investigated. A maximum current efficiency of 85% and yield of 80% was obtained from the bath at 12.5A/cm2 current density at an operating temp 850°C.

Lomas Tomar,1,2 Charu Tyagi,1,3 Manoj Kumar,2 Pradeep Kumar,1 Harpal Singh,2 Yahya E Choonara,1 Viness Pillay11University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, Johannesburg, Gauteng, South Africa; 2Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India; 3VSPG College, Chaudhary Charan Singh University, Meerut, IndiaAbstract: Poly(ethylene glycol) (PEG) and polylactic acid (PLA)-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90–140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH2-PEGDA-NH2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various concentrations of polymers with respect to each other. Incorporation of insulin within the polymeric matrix was modeled using Connolly molecular surfaces. The computational results corroborated the experimental and analytical data. The ability to control blood glucose levels effectively coupled with the nontoxic behavior of the nanoparticles indicates that these nanoparticles are a potential candidate for insulin delivery.Keywords: parenteral delivery, insulin, nanoparticles, poly(lactide-ethylene glycol) diblock copolymer, molecular mechanics energy relationship

Manoj Kumar,1 Gurpal Singh,1 Vikas Arora,2 Sujeet Mewar,3 Uma Sharma,3 NR Jagannathan,3 Sameer Sapra,2 Amit K Dinda,4 Surender Kharbanda,5 Harpal Singh11Center for Biomedical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India; 2Department of Chemistry, Indian Institute of Technology, Delhi Hauz Khas, New Delhi-110016, India; 3Department Of NMR, All India Institute of Medical Sciences, Ansari Nagar New Delhi-110029, India; 4Department Of Pathology, All India Institute of Medical Sciences, Ansari Nagar New Delhi-110029, India; 5Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAAbstract: The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8–10 nm), and relatively high T2 relaxivity (R2 = 222L · mmol-1 · sec-l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer.Keywords: superparamagnetic iron oxide nanoparticles (SPION), cellular internalization, magnetic resonance imaging (MRI), cancer-cell targeting ligand

Idiopathic Thrombocytopenic Purpura (ITP) is a blood disorder characterized by an abnormal decrease in the number of platelets in the blood. Acute thrombocytopenic purpura is most commonly seen in young children, with a sudden onset, following a viral illness, vaccination or an insect bite. The report is a rare case of ITP, which was triggered by a honey-bee bite and caused continuous intermittent bleeding from the gingival sulcular region of the maxillary left permanent first molar, and ecchymotic spots on the forehead, scalp, and lower limbs. A complete hemogram revealed severe thrombocytopenia with platelet count as low as 15,000/mm3. The patient was immediately hospitalized and administered platelet replacement and medication. With this report, the authors, as dentists, emphasize the significance of recognition, early diagnosis, and referral of such patients with bleeding disorders to specialized centers, for prompt treatment.