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2.
J Hosp Infect ; 121: 39-48, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1966846

ABSTRACT

BACKGROUND: Registered nurses perform numerous functions critical to the success of antimicrobial stewardship, but only 63% of pre-registration nursing programmes include any teaching about stewardship. Updated nursing standards indicate that nurses require antimicrobial stewardship knowledge and skills. AIM: To explore the delivery of key antimicrobial stewardship competencies within updated pre-registration nursing programmes. METHODS: This study had a cross-sectional survey design. Data were collected between March and June 2021. FINDINGS: Lecturers from 35 UK universities responsible for teaching antimicrobial stewardship participated in this study. The provision of antimicrobial stewardship teaching and learning was inconsistent across programmes, with competencies in infection prevention and control, patient-centred care and interprofessional collaborative practice taking precedent over competencies pertaining to the use, management and monitoring of antimicrobials. Online learning and teaching surrounding hand hygiene, personal protective equipment and immunization theory was reported to have increased during the pandemic. Only a small number of respondents reported that students shared taught learning with other healthcare professional groups. CONCLUSION: There is a need to ensure consistency in antimicrobial stewardship across programmes, and greater knowledge pertaining to the use, management and monitoring of antimicrobials should be included. Programmes need to adopt teaching strategies and methods that allow nurses to develop interprofessional skills in order to practice collaboratively.


Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , Education, Nursing , Anti-Infective Agents/therapeutic use , Cross-Sectional Studies , Education, Nursing/methods , Humans , United Kingdom
3.
J Am Acad Dermatol ; 2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1966655
4.
Bull Acad Natl Med ; 206(1): 1-2, 2022 Jan.
Article in French | MEDLINE | ID: covidwho-1966364
6.
Wiley Interdiscip Rev Nanomed Nanobiotechnol ; 14(1): e1759, 2022 01.
Article in English | MEDLINE | ID: covidwho-1966114

ABSTRACT

Natural lipid molecules are an essential part of life as they constitute the membrane of cells and organelle. In most of these cases, the hydrophobicity of natural lipids is contributed by alkyl chains. Although natural lipids with a nonfatty acid hydrophobic backbone are quite rare, steroids and isoprenoids have been strong candidates as part of a lipid. Over the years, these natural molecules (steroid and isoprenoids) have been used to make either lipid-based nanoparticle or functionalize in such a way that it could form nano assembly alone for therapeutic delivery. Here we mainly focus on the synthetic functionalized version of these natural molecules which forms cationic liposomal nanoparticles (LipoNPs). These cationic LipoNPs were further used to deliver various negatively charged genetic materials in the form of pDNA, siRNA, mRNA (nucleic acids), and so on. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures.


Subject(s)
Nanoparticles , Terpenes , Gene Transfer Techniques , RNA, Messenger , RNA, Small Interfering , Steroids
7.
Clin Infect Dis ; 73(6): e1405-e1407, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1965686
8.
Gastroenterology ; 163(2): 531-532, 2022 Aug.
Article | MEDLINE | ID: covidwho-1967638
9.
RSC Adv ; 12(30): 19579-19589, 2022 Jun 29.
Article in English | MEDLINE | ID: covidwho-1967637

ABSTRACT

A novel series of fused pyrazolo[5',1':2,3]imidazo[1,5-c]quinazolin-6(5H)-ones were synthesized and their affinity against the COVID-19 main protease was investigated using molecular docking study and compared to that of some used standard clinical drugs. These compounds were obtained in good to excellent yields from 63 to 91% in the presence of 30 mol% catalyst in ethanol at reflux for 2 h through an efficient one-pot three-component reaction including an intramolecular rearrangement and a cyclization through intramolecular nucleophilic reaction. The results of in silico studies showed that electronegativity, resonance effects, hydrophobic interaction, halogen and hydrogen bonding had significant effects on the performance of these compounds as an inhibitor ligand. Also, these results indicated the proper affinity of these compounds against the COVID-19 main protease with excellent binding energies (especially 4r = -8.77, 4q = -8.73 and 4m = -8.63) in comparison to remdesivir, chloroquine, hydroxychloroquine, molnupiravir and nirmatrelvir drugs.

10.
Commun Med (Lond) ; 2: 96, 2022.
Article in English | MEDLINE | ID: covidwho-1967635

ABSTRACT

Background: An estimated 8 million people die every year due to tobacco use. The COVID-19 pandemic has increased the health consequences of smoking, which is a leading risk factor for more severe COVID-19 symptoms, hospitalization, and death. The pandemic has also led to reductions in physical activity, increases in stress and declines in mental well-being, all factors commonly associated with triggering higher tobacco use. Methods: Using a longitudinal data set of purchasing behavior from 2019-2020 among a national sample of the Danish population (n = 4042), we estimate changes in tobacco use during the COVID-19 pandemic. Our analysis compares tobacco purchases prior to the pandemic to purchases during the pandemic, at the individual level. We also examine effects within subgroups based on smoking behavior in 2019 prior to the pandemic. We estimate effects for smokers and non-smokers and, within smokers, for occasional smokers and regular smokers. Results: We find large, sustained decreases in tobacco purchases during COVID-19. We estimate that weekly tobacco purchase rates decline by 24% and average quantities decline by 12% during the period spanning the onset of the pandemic in March 2020 through the end of the year. The declines are driven by regular smokers with little change in behavior among nonsmokers and increases in purchases among occasional smokers. Among regular smokers, purchase rates decline by about 30%, tobacco purchases decline by about 20% and quitting rates increase by about 10 percentage points. Conclusions: Our results suggest that the COVID-19 pandemic could lead to sustained reductions in smoking.

11.
Commun Biol ; 5(1): 764, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967632

ABSTRACT

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and their downstream targets across time. While interactions between these molecular clocks are necessary for proper homeostasis, these features remain undefined. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. We found that 53.4% (8120) of baboon genes are oscillating body-wide. Additionally, two basic network modes were observed at the systems level: daytime and nighttime mode. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. A substantial number of diseases only form significant disease modules at either daytime or nighttime. In addition, a majority of SARS-CoV-2-related genes and modules are rhythmically expressed, which have significant network proximities with circadian regulators. Our data suggest that synchronization amongst circadian gene networks is necessary for proper homeostatic functions and circadian regulators have close interactions with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Gene Regulatory Networks , Animals , COVID-19/genetics , Circadian Rhythm/genetics , Mammals/genetics , Primates/genetics , SARS-CoV-2
12.
Commun Biol ; 5(1): 766, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967631

ABSTRACT

Studying the antibody response to SARS-CoV-2 informs on how the human immune system can respond to antigenic variants as well as other SARS-related viruses. Here, we structurally identified a YYDRxG motif encoded by IGHD3-22 in CDR H3 that facilitates antibody targeting to a functionally conserved epitope on the SARS-CoV-2 receptor binding domain. A computational search for a YYDRxG pattern in publicly available sequences uncovered 100 such antibodies, many of which can neutralize SARS-CoV-2 variants and SARS-CoV. Thus, the YYDRxG motif represents a common convergent solution for the human humoral immune system to target sarbecoviruses including the Omicron variant. These findings suggest an epitope-targeting strategy to identify potent and broadly neutralizing antibodies for design of pan-sarbecovirus vaccines and antibody therapeutics.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Epitopes/genetics , Humans , Membrane Glycoproteins/metabolism , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolism
13.
Sci Rep ; 12(1): 13146, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967629

ABSTRACT

The main protease (Mpro) of SARS-CoV-2 has been recognized as an attractive drug target because of its central role in viral replication. Our previous preliminary molecular docking studies showed that theaflavin 3-gallate (a natural bioactive molecule derived from theaflavin and found in high abundance in black tea) exhibited better docking scores than repurposed drugs (Atazanavir, Darunavir, Lopinavir). In this study, conventional and steered MD-simulations analyses revealed stronger interactions of theaflavin 3-gallate with the active site residues of Mpro than theaflavin and a standard molecule GC373 (a known inhibitor of Mpro and novel broad-spectrum anti-viral agent). Theaflavin 3-gallate inhibited Mpro protein of SARS-CoV-2 with an IC50 value of 18.48 ± 1.29 µM. Treatment of SARS-CoV-2 (Indian/a3i clade/2020 isolate) with 200 µM of theaflavin 3-gallate in vitro using Vero cells and quantifying viral transcripts demonstrated reduction of viral count by 75% (viral particles reduced from Log106.7 to Log106.1). Overall, our findings suggest that theaflavin 3-gallate effectively targets the Mpro thus limiting the replication of the SARS-CoV-2 virus in vitro.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biflavonoids , COVID-19/drug therapy , Catechin , Chlorocebus aethiops , Coronavirus 3C Proteases , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Vero Cells
14.
Sci Rep ; 12(1): 13207, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967628

ABSTRACT

Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in > 70 countries. Yet there is a shortage of data on this vaccine's performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in Kazakhstan. COVID-19-free participants (n = 82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays. We observed that most of the reported adverse events were mild-to-moderate injection site or systemic reactions, no severe or potentially life-threatening conditions were reported, and dose 1 appeared to be more reactogenic than dose 2. The seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization was 83% post-dose 1, increasing to 98% post-dose 2, with the largest relative increase observed in participants without prior COVID-19 exposure. Dose 1 boosted nasal S-IgG and S-IgA, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count. Overall, Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal. Thus, adjustments to the current vaccine dosing regimen are necessary to optimize immunization efficacy and cost-effectiveness. While Sputnik-V reactogenicity is similar to that of other COVID-19 vaccines, the induced alterations to the GRO/platelet axis warrant investigation of the vaccine's effects on systemic immunology.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Immunoglobulin A , Immunoglobulin G , Mucous Membrane , Prospective Studies , SARS-CoV-2
15.
Sci Rep ; 12(1): 13118, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967627

ABSTRACT

The pandemic caused by severe acute respiratory Coronavirus-2 (SARS-CoV-2) has been ongoing for over two years, and treatment for COVID-19, other than monoclonal antibodies, is urgently required. Accordingly, we have investigated the inhibitors of SARS-CoV-2 protein targets by high-throughput virtual screening using a marine natural products database. Considering the calculated molecular properties and availability of the compounds, (+)-usnic acid was selected as a suitable hit. In the in vitro antiviral assay of (+)-usnic acid by the immunofluorescence method, IC50 was 7.99 µM, which is similar to that of remdesivir used as a positive control. The generalized Born and surface area continuum solvation (MM/GBSA) method was performed to find the potent target of (+)-usnic acid, and the Mpro protein showed the most prominent value, -52.05 kcal/mol, among other SARS-CoV-2 protein targets. Thereafter, RMSD and protein-ligand interactions were profiled using molecular dynamics (MD) simulations. Sodium usnate (NaU) improved in vitro assay results with an IC50 of 5.33 µM and a selectivity index (SI) of 9.38. Additionally, when (+)-usnic acid was assayed against SARS-CoV-2 variants, it showed enhanced efficacy toward beta variants with an IC50 of 2.92 µM and SI of 11.1. We report the in vitro anti-SARS-CoV-2 efficacy of (+)-usnic acid in this study and propose that it has the potential to be developed as a COVID-19 treatment if its in vivo efficacy has been confirmed.


Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , Benzofurans , COVID-19/drug therapy , Coronavirus 3C Proteases , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/pharmacology , SARS-CoV-2 , Salts
16.
Sci Rep ; 12(1): 12998, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967626

ABSTRACT

To investigate whether diurnal changes in noninvasive ocular surface parameters and subjective symptoms occur in healthy subjects wearing face mask who were analyzed before and after 8 h of continuous use. In this prospective cross-sectional study, healthy volunteers attending the same workplace environment underwent a noninvasive ocular surface workup by means of Keratograph 5 M (Oculus, Wetzlar, Germany) in the same day at 2 different time points: (i) in the early morning before wearing face mask (T0); (ii) after 8 h of continuous face mask use (T1). Noninvasive break-up time (NIBUT), tear meniscus height (TMH), ocular redness and meibomian gland dropout were measured. All subjects were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire before and after 8 h of face mask wearing. Data from 20 healthy subjects (10 males and 10 females, mean age 25.1 ± 3.9 years) were included. Mean value of TMH decreased significantly from 0.29 ± 0.07 at T0 to 0.23 ± 0.07 mm at T1 (P < 0.001); conversely, mean values of NIBUT, redness score and meibomian gland dropout did not change significantly after continuous face mask wearing (always P > 0.532). Concerning ocular discomfort symptoms, mean value of OSDI score worsened significantly at T1 compared to T0 (from 12.9 ± 12.6 to 19.4 ± 12.0; P = 0.017). Continuous face mask wearing for 8 h led to decreased TMH associated with the onset of ocular discomfort symptoms in young healthy subjects.


Subject(s)
COVID-19 , Dry Eye Syndromes , Adult , Cross-Sectional Studies , Dry Eye Syndromes/diagnosis , Female , Healthy Volunteers , Humans , Male , Masks/adverse effects , Meibomian Glands , Pandemics , Prospective Studies , Tears , Young Adult
17.
Sci Rep ; 12(1): 13123, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967625

ABSTRACT

Fatigue, attentional deficits and cognitive fluctuations are the most characterizing symptoms of neurological involvement in Post COVID-19 syndrome (PCS). As the intraindividual variability (IIV) in cognitive performances has been recognized as a hallmark of brain-related disorders associated with cognitive deficits, it could be an interesting measure to elucidate the mechanisms subtending both the attentive impairment and the cognitive fluctuations in these patients. By referring to IIV analysis of Reaction Times (RTs), the present study aims to define the attentive impairment and its relation to fluctuations and fatigue, in patients suffering from Post COVID-19 neurological symptoms. 74 patients were enrolled. They underwent an extensive clinical and neuropsychological assessments, as well as computerized Sustained Attention and Stroop tasks. For studying IIV, RTs distributions of performances in computerized tasks were fitted with ex-Gaussian distribution, for obtaining the τ values. Finally, the Resting Motor Threshold (RMT) was also collected to estimate cortical excitability. 29 healthy volunteers served as controls. Patients showed poorer scores in Montreal Cognitive Assessment and higher RMT, in comparison with controls. In Sustained Attention Task, Mean, µ, σ and τ values were significantly higher in PCS patients (p value = < 0.0001; 0.001; 0.018 and < 0.0001, respectively). Repeated measures ANOVA comparing the RTs mean in Stroop task within-subject and between-subjects revealed significant condition and group effect (p < 0.0001 both) and significant interaction (p = 0.005), indicating worst performances in patients. The mean of the derived interference value was significantly higher in PCS patients than in controls (p = 0.036). Patients suffering from PCS show deficits in attention, both in the sustained and executive components. Both high RTs means and high IIV subtend these deficits and could explain the often-complained cognitive fluctuations in this population.


Subject(s)
COVID-19 , COVID-19/complications , Cognition , Fatigue , Humans , Neuropsychological Tests , Reaction Time
18.
Sci Rep ; 12(1): 13069, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967624

ABSTRACT

Reverse transcription quantitative PCR (RT-qPCR) assays are gold standard in diagnosing SARS-CoV-2 infection and play a major role in viral subtyping for rapid detection and monitoring of important mutations, containing the spread of new virus variants. We wanted to compare RT-qPCR melting curve analysis assays to Sanger Sequencing for detection of variants within the SARS-CoV-2 spike glycoprotein and examined their sensitivity and specificity. Samples positive for SARS-CoV-2 (n = 663 + 82) were subtyped using both Sanger sequencing and five RT-qPCR melting curve analysis assays specific for the mutations N501Y, P681H, E484K, K417N/T, and N439K. The results of the two methods were compared. The training cohort and the clinical validation cohort showed equally, or significantly better sensitivity of the assays compared to the Sanger sequencing. The agreement of the Sanger sequencing and the assays ranged from 92.6 to 100% for the training cohort and 99.4-100% for the clinical validation. The sensitivity, specificity, and turn-around time of the RT-qPCR melting curve analysis assays are well-suited for clinical monitoring of VOCs, making the assays an important tool in contact tracing and risk stratification. Furthermore, the assays were able to indicate the presence of new mutations in the complementary sequence to the mutation-specific probes.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/genetics , Humans , Mutation , Reverse Transcription , SARS-CoV-2/genetics , Sensitivity and Specificity
19.
Sci Rep ; 12(1): 12988, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967623

ABSTRACT

The long-term impact of COVID-19 among those with mild infections is not well characterized. Among 81 adults who completed online assessments at 3- and 12-months following infection, quality of life scores did not significantly improve over time. Among 62 subjects who also completed telephone interviews, respiratory symptoms or exercise limitation were reported by 42% at a median follow-up of 387 days (IQR 251-402 days). Those with persistent respiratory symptoms scored lower on the EQ-5D visual analog score compared to those without. Persistent respiratory symptoms were associated with a lower likelihood of full-time employment at 1 year (aOR 0.09, 95%CI 0.01-0.91; P = 0.041). In an adjusted linear regression, persistent respiratory symptoms (P = 0.037) and female sex (P = 0.016) were both independent risks for increased visits to a primary care provider. This cohort study demonstrates that respiratory symptoms are frequent at 1 year following COVID-19 and more importantly, are associated with negative impacts on employment, quality of life, and health care utilization. Further research is needed to determine the pathophysiology and risk factors for persistent symptoms as well as optimal management strategies to improve the level of functioning and quality of life.


Subject(s)
COVID-19 , Quality of Life , Adult , Cohort Studies , Female , Humans , Outpatients , Patient Acceptance of Health Care , Prospective Studies
20.
Sci Rep ; 12(1): 13095, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967622

ABSTRACT

This study evaluates the use of the Global Pharma Health Fund (GPHF) Minilab for medicine quality screening by 16 faith-based drug supply organizations located in 13 low- and middle-income countries. The study period included the year before the COVID-19 pandemic (2019) and the first year of the pandemic (2020). In total 1,919 medicine samples were screened using the GPHF Minilab, and samples showing serious quality deficiencies were subjected to compendial analysis in fully equipped laboratories. Thirty-four (1.8%) of the samples were found not to contain the declared active pharmaceutical ingredient (API), or less than 50% of the declared API, or undeclared APIs, and probably represented falsified products. Fifty-four (2.8%) of the samples were reported as substandard, although the true number of substandard medicines may have been higher due to the limited sensitivity of the GPHF Minilab. The number of probably falsified products increased during the COVID-19 pandemic, especially due to falsified preparations of chloroquine; chloroquine had been incorrectly advocated as treatment for COVID-19. The reports from this project resulted in four international WHO Medical Product Alerts and several national alerts. Within this project, the costs for GPHF Minilab analysis resulted as 25.85 € per sample. Medicine quality screening with the GPHF Minilab is a cost-effective way to contribute to the global surveillance for substandard and falsified medical products.


Subject(s)
COVID-19 , Counterfeit Drugs , Faith-Based Organizations , Financial Management , COVID-19/drug therapy , COVID-19/epidemiology , Chloroquine , Counterfeit Drugs/analysis , Developing Countries , Humans , Pandemics
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