Displaying all 13 publications

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  1. Verma DK, Gupta D, Lal SK
    Viruses, 2018 11 18;10(11).
    PMID: 30453689 DOI: 10.3390/v10110650
    Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV.
  2. Gupta D, Singh A, Somvanshi P, Singh A, Khan AU
    ACS Omega, 2020 Apr 28;5(16):9356-9365.
    PMID: 32363287 DOI: 10.1021/acsomega.0c00356
    The manifestation of class D β-lactamases in the community raises significant concern as they can hydrolyze carbapenem antibiotics. Hence, it is exceptionally alluring to design novel inhibitors. Structure-based virtual screening using docking programs and molecular dynamics simulations was employed to identify two novel non-β-lactam compounds that possess the ability to block different OXA variants. Furthermore, the presence of a nonpolar aliphatic amino acid, valine, near the active site serine, was identified in all OXA variants that can be accounted to block the catalytic activity of OXA enzymes.
  3. Huggins JE, Guger C, Ziat M, Zander TO, Taylor D, Tangermann M, et al.
    PMID: 29152523 DOI: 10.1080/2326263X.2016.1275488
    The Sixth International Brain-Computer Interface (BCI) Meeting was held 30 May-3 June 2016 at the Asilomar Conference Grounds, Pacific Grove, California, USA. The conference included 28 workshops covering topics in BCI and brain-machine interface research. Topics included BCI for specific populations or applications, advancing BCI research through use of specific signals or technological advances, and translational and commercial issues to bring both implanted and non-invasive BCIs to market. BCI research is growing and expanding in the breadth of its applications, the depth of knowledge it can produce, and the practical benefit it can provide both for those with physical impairments and the general public. Here we provide summaries of each workshop, illustrating the breadth and depth of BCI research and highlighting important issues and calls for action to support future research and development.
  4. Clark D, Joannides A, Ibrahim Abdallah O, Olufemi Adeleye A, Hafid Bajamal A, Bashford T, et al.
    PMID: 32211566 DOI: 10.1016/j.isjp.2020.02.001
    Introduction: Traumatic brain injury (TBI) accounts for a significant amount of death and disability worldwide and the majority of this burden affects individuals in low-and-middle income countries. Despite this, considerable geographical differences have been reported in the care of TBI patients. On this background, we aim to provide a comprehensive international picture of the epidemiological characteristics, management and outcomes of patients undergoing emergency surgery for traumatic brain injury (TBI) worldwide.

    Methods and analysis: The Global Neurotrauma Outcomes Study (GNOS) is a multi-centre, international, prospective observational cohort study. Any unit performing emergency surgery for TBI worldwide will be eligible to participate. All TBI patients who receive emergency surgery in any given consecutive 30-day period beginning between 1st of November 2018 and 31st of December 2019 in a given participating unit will be included. Data will be collected via a secure online platform in anonymised form. The primary outcome measures for the study will be 14-day mortality (or survival to hospital discharge, whichever comes first). Final day of data collection for the primary outcome measure is February 13th. Secondary outcome measures include return to theatre and surgical site infection.

    Ethics and dissemination: This project will not affect clinical practice and has been classified as clinical audit following research ethics review. Access to source data will be made available to collaborators through national or international anonymised datasets on request and after review of the scientific validity of the proposed analysis by the central study team.

  5. Bordone MP, Salman MM, Titus HE, Amini E, Andersen JV, Chakraborti B, et al.
    J Neurochem, 2019 10;151(2):139-165.
    PMID: 31318452 DOI: 10.1111/jnc.14829
    The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.
  6. Joannides A, Korhonen TK, Clark D, Gnanakumar S, Venturini S, Mohan M, et al.
    NIHR Open Res, 2023;3:34.
    PMID: 37881453 DOI: 10.3310/nihropenres.13377.1
    BACKGROUND: The epidemiology of traumatic brain injury (TBI) is unclear - it is estimated to affect 27-69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment.

    OBJECTIVE: The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research.

    DESIGN: Multi-centre, international, registry-based, prospective cohort study.

    SUBJECTS: Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence.

    METHODS: All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol.

    DATA: Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

  7. Joannides AJ, Korhonen TK, Clark D, Gnanakumar S, Venturini S, Mohan M, et al.
    Neurosurgery, 2024 Feb 01;94(2):278-288.
    PMID: 37747225 DOI: 10.1227/neu.0000000000002661
    BACKGROUND AND OBJECTIVES: Global disparity exists in the demographics, pathology, management, and outcomes of surgically treated traumatic brain injury (TBI). However, the factors underlying these differences, including intervention effectiveness, remain unclear. Establishing a more accurate global picture of the burden of TBI represents a challenging task requiring systematic and ongoing data collection of patients with TBI across all management modalities. The objective of this study was to establish a global registry that would enable local service benchmarking against a global standard, identification of unmet need in TBI management, and its evidence-based prioritization in policymaking.

    METHODS: The registry was developed in an iterative consensus-based manner by a panel of neurotrauma professionals. Proposed registry objectives, structure, and data points were established in 2 international multidisciplinary neurotrauma meetings, after which a survey consisting of the same data points was circulated within the global neurotrauma community. The survey results were disseminated in a final meeting to reach a consensus on the most pertinent registry variables.

    RESULTS: A total of 156 professionals from 53 countries, including both high-income countries and low- and middle-income countries, responded to the survey. The final consensus-based registry includes patients with TBI who required neurosurgical admission, a neurosurgical procedure, or a critical care admission. The data set comprised clinically pertinent information on demographics, injury characteristics, imaging, treatments, and short-term outcomes. Based on the consensus, the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry was established.

    CONCLUSION: The GEO-TBI registry will enable high-quality data collection, clinical auditing, and research activity, and it is supported by the World Federation of Neurosurgical Societies and the National Institute of Health Research Global Health Program. The GEO-TBI registry ( https://geotbi.org ) is now open for participant site recruitment. Any center involved in TBI management is welcome to join the collaboration to access the registry.

  8. Rosenthal VD, Bat-Erdene I, Gupta D, Belkebir S, Rajhans P, Zand F, et al.
    Infect Control Hosp Epidemiol, 2020 05;41(5):553-563.
    PMID: 32183925 DOI: 10.1017/ice.2020.20
    BACKGROUND: Short-term peripheral venous catheter-related bloodstream infection (PVCR-BSI) rates have not been systematically studied in resource-limited countries, and data on their incidence by number of device days are not available.

    METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013, to May 31, 2019, in 727 intensive care units (ICUs), by members of the International Nosocomial Infection Control Consortium (INICC), from 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific regions. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.

    RESULTS: We followed 149,609 ICU patients for 731,135 bed days and 743,508 short-term peripheral venous catheter (PVC) days. We identified 1,789 PVCR-BSIs for an overall rate of 2.41 per 1,000 PVC days. Mortality in patients with PVC but without PVCR-BSI was 6.67%, and mortality was 18% in patients with PVC and PVCR-BSI. The length of stay of patients with PVC but without PVCR-BSI was 4.83 days, and the length of stay was 9.85 days in patients with PVC and PVCR-BSI. Among these infections, the microorganism profile showed 58% gram-negative bacteria: Escherichia coli (16%), Klebsiella spp (11%), Pseudomonas aeruginosa (6%), Enterobacter spp (4%), and others (20%) including Serratia marcescens. Staphylococcus aureus were the predominant gram-positive bacteria (12%).

    CONCLUSIONS: PVCR-BSI rates in INICC ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs in resource-limited countries.

  9. Rosenthal VD, Bat-Erdene I, Gupta D, Belkebir S, Rajhans P, Zand F, et al.
    Am J Infect Control, 2020 04;48(4):423-432.
    PMID: 31676155 DOI: 10.1016/j.ajic.2019.08.023
    BACKGROUND: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2012 to December 2017 in 523 intensive care units (ICUs) in 45 countries from Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific.

    METHODS: During the 6-year study period, prospective data from 532,483 ICU patients hospitalized in 242 hospitals, for an aggregate of 2,197,304 patient days, were collected through the INICC Surveillance Online System (ISOS). The Centers for Disease Control and Prevention-National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI) were applied.

    RESULTS: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the medical-surgical ICUs, the pooled central line-associated bloodstream infection rate was higher (5.05 vs 0.8 per 1,000 central line-days); the ventilator-associated pneumonia rate was also higher (14.1 vs 0.9 per 1,000 ventilator-days,), as well as the rate of catheter-associated urinary tract infection (5.1 vs 1.7 per 1,000 catheter-days). From blood cultures samples, frequencies of resistance, such as of Pseudomonas aeruginosa to piperacillin-tazobactam (33.0% vs 18.3%), were also higher.

    CONCLUSIONS: Despite a significant trend toward the reduction in INICC ICUs, DA-HAI rates are still much higher compared with CDC-NHSN's ICUs representing the developed world. It is INICC's main goal to provide basic and cost-effective resources, through the INICC Surveillance Online System to tackle the burden of DA-HAIs effectively.

  10. Rosenthal VD, Bat-Erdene I, Gupta D, Rajhans P, Myatra SN, Muralidharan S, et al.
    J Vasc Access, 2021 Jan;22(1):34-41.
    PMID: 32406328 DOI: 10.1177/1129729820917259
    BACKGROUND: Short-term peripheral venous catheter-associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter-associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available.

    METHODS: Prospective, surveillance study on peripheral venous catheter-associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.

    RESULTS: We followed 83,295 intensive care unit patients for 369,371 bed-days and 376,492 peripheral venous catheter-days. We identified 999 peripheral venous catheter-associated bloodstream infections, amounting to a rate of 2.65/1000 peripheral venous catheter-days. Mortality in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.53% and 12.21% in patients with peripheral venous catheter-associated bloodstream infections. The mean length of stay in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.40 days and 7.11 days in patients with peripheral venous catheter and peripheral venous catheter-associated bloodstream infections. The microorganism profile showed 67.1% were Gram-negative bacteria: Escherichia coli (22.9%), Klebsiella spp (10.7%), Pseudomonas aeruginosa (5.3%), Enterobacter spp. (4.5%), and others (23.7%). The predominant Gram-positive bacteria were Staphylococcus aureus (11.4%).

    CONCLUSIONS: Infection prevention programs must be implemented to reduce the incidence of peripheral venous catheter-associated bloodstream infections.

  11. Reid MJA, Arinaminpathy N, Bloom A, Bloom BR, Boehme C, Chaisson R, et al.
    Lancet, 2019 Mar 30;393(10178):1331-1384.
    PMID: 30904263 DOI: 10.1016/S0140-6736(19)30024-8
  12. Rosenthal VD, Duszynska W, Ider BE, Gurskis V, Al-Ruzzieh MA, Myatra SN, et al.
    Am J Infect Control, 2021 Oct;49(10):1267-1274.
    PMID: 33901588 DOI: 10.1016/j.ajic.2021.04.077
    BACKGROUND: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific.

    METHODS: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied.

    RESULTS: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases.

    CONCLUSIONS: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.

  13. Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
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