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1.
Jundishapur Journal of Microbiology ; 15(5), 2022.
Article in English | CAB Abstracts | ID: covidwho-20236086

ABSTRACT

Background: Clostridium spp. spores are resistant to many factors, including alcohol-based disinfectants. The presence of clostridial spores in a hospital environment may lead to infection outbreaks among patients and health care workers. Background: This study is aimed to detect clostridial spores in the aurology hospital using C diff Banana BrothTM and assess the antibiotic sensitivity and toxinotypes of isolates. Methods: After diagnosing COVID-19 in medical staff and closing an 86-bed urology hospital in 2020 for H2O2 fogging, 58 swabs from the hospital environment were inoculated to C diff Banana BrothTM, incubated at 37 degrees C for 14 days, checked daily, and positive broths were sub-cultured anaerobically for 48 h at 37 degrees C. After identification, multiplex PCR (mPCR) was performed for Clostridium perfringens, C. difficile toxin genes, and minimum inhibitory concentration (MIC) determination. Results: In this study, 16 out of 58 (~ 28%) strains of Clostridium spp. were cultured: 11 - C. perfringens, 2 - C. baratii, and 1 each of C. paraputrificum, C. difficile, and C. clostridioforme. 11 C. perfringens were positive for the cpa, 7 - the cpb2, 2 - cpiA, and 1 - cpb toxin genes. All isolates were sensitive to metronidazole, vancomycin, moxifloxacin, penicillin/tazobactam, and rifampicin. Two out of the 11 C. perfringens strains were resistant to erythromycin and clindamycin. Conclusions: Regardless of the performed H2O2 fogging, antibiotic-resistant, toxigenic strains of C. perfringens (69%) obtained from the urology hospital environment were cultured using C diff Banana BrothTM, indicating the need to develop the necessary sanitary and epidemiological procedures in this hospital.

2.
CNS Spectrums Conference: Neuroscience Education Institute Congress, NEI ; 28(2), 2022.
Article in English | EMBASE | ID: covidwho-20232426

ABSTRACT

The proceedings contain 96 papers. The topics discussed include: practical pharmacotherapy for opioid use disorder in the age of fentanyl;can COVID-19 cause acute psychosis in pediatric patients? a case report;a survey of bullying experiences in a child and adolescent psychiatric clinic population;acute emergence of suicidal thoughts following Lemborexant initiation: an adverse reaction case report;assessing the unmet clinical need and opportunity for digital therapeutic intervention in schizophrenia: perspective from people with schizophrenia;rapid antidepressant effects and MADRS item improvements with AXS-05 (DEXTROMETHORPHAN-BUPROPION), an oral NMDA receptor antagonist in major depressive disorder: results from two randomized double-blind, controlled trials;targeting lncRNA NEAT1 impedes Alzheimers disease progression via MicroRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways;and impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA receptor antagonist, on Anhedonic symptoms in major depressive disorder.

3.
Biomolecules ; 13(5)2023 05 11.
Article in English | MEDLINE | ID: covidwho-20239134

ABSTRACT

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer's disease (AD) and DM, promote healthy aging, facilitate clearance of ß-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.


Subject(s)
Alzheimer Disease , COVID-19 , Diabetes Mellitus , Metabolic Diseases , Neurodegenerative Diseases , Humans , AMP-Activated Protein Kinases/metabolism , Post-Acute COVID-19 Syndrome , TOR Serine-Threonine Kinases/metabolism , Alzheimer Disease/metabolism , Neurodegenerative Diseases/metabolism , Brain/metabolism
4.
Cell Mol Life Sci ; 80(6): 151, 2023 May 17.
Article in English | MEDLINE | ID: covidwho-2325328

ABSTRACT

Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has membranolytic activity against various bacterial species, while the HBA(111-142) fibrils aggregated bacteria to promote their phagocytotic clearance. Further, HBA(111-142) fibrils selectively inhibited measles and herpes viruses (HSV-1, HSV-2, HCMV), but not SARS-CoV-2, ZIKV and IAV. HBA(111-142) is released from its precursor by ubiquitous aspartic proteases under acidic conditions characteristic at sites of infection and inflammation. Thus, HBA(111-142) is an amyloidogenic AMP that may specifically be generated from a highly abundant precursor during bacterial or viral infection and may play an important role in innate antimicrobial immune responses.


Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , Humans , Peptides , Amyloid/chemistry , Anti-Bacterial Agents/pharmacology , Hemoglobins
5.
6th Local Scientific Conference-The 3rd Scientific International, ICCEPS 2021 ; 2414, 2023.
Article in English | Scopus | ID: covidwho-2250714

ABSTRACT

In this paper, we will use the ordinary differential equations for the SIR model as a non-linear system with the Runge-Kutta numerical method of the 6th order and 7th order to generate default values for (susceptible people, infected people and recovered from disease) for epidemic disease COVID-19 by giving it the initial values for a population in a particular country. The MATLAB program was used to solve the two problems (6th & 7th order) and obtain the results.Through this work we notice the difference between the results of the two methods and the solution period as well as the estimated error value for the solution in each problem and the comparison between results and solutions for both methods and shown in a table for clarity.We also used the binary test (0-1) to know the behavior of the disease in terms of chaos and the results indicated that this disease(covid-19) is chaotic and irregular and by using the MATLAB program we obtained the figures and results and that illustrate its chaotic behavior (kcorr 6th =0.9212) and (kcorr 7th = 0.9560),as well as, the figures that illustrate the system's workflow in this paper. © 2023 American Institute of Physics Inc.. All rights reserved.

6.
J Med Virol ; 95(2): e28584, 2023 02.
Article in English | MEDLINE | ID: covidwho-2260437

ABSTRACT

Novel adjuvants are highly desired to improve immune responses of SARS-CoV-2 vaccines. This work reports the potential of the stimulator of interferon genes (STING) agonist adjuvant, the cyclic di-adenosine monophosphate (c-di-AMP), in a SARS-CoV-2 vaccine based on the receptor binding domain (RBD). Here, mice immunized with two doses of monomeric RBD adjuvanted with c-di-AMP intramuscularly were found to exhibit stronger immune responses compared to mice vaccinated with RBD adjuvanted with aluminum hydroxide (Al(OH)3 ) or without adjuvant. After two immunizations, consistent enhancements in the magnitude of RBD-specific immunoglobulin G (IgG) antibody response were observed by RBD + c-di-AMP (mean: 15360) compared to RBD + Al(OH)3 (mean: 3280) and RBD alone (n.d.). Analysis of IgG subtypes indicated a predominantly Th1-biased immune response (IgG2c, mean: 14480; IgG2b, mean: 1040, IgG1, mean: 470) in mice vaccinated with RBD + c-di-AMP compared to a Th2-biased response in those vaccinated with RBD + Al(OH)3 (IgG2c, mean: 60; IgG2b: n.d.; IgG1, mean: 16660). In addition, the RBD + c-di-AMP group showed better neutralizing antibody responses as determined by pseudovirus neutralization assay and by plaque reduction neutralization assay with SARS-CoV-2 wild type. Moreover, the RBD + c-di-AMP vaccine promoted interferon-γ secretion of spleen cell cultures after RBD stimulation. Furthermore, evaluation of IgG-antibody titers in aged mice showed that di-AMP was able to improve RBD-immunogenicity at old age after 3 doses (mean: 4000). These data suggest that c-di-AMP improves immune responses of a SARS-CoV-2 vaccine based on RBD, and would be considered a promising option for future COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Animals , Mice , Humans , SARS-CoV-2 , Adjuvants, Immunologic , Immunity, Cellular , Antibodies, Neutralizing , Adjuvants, Pharmaceutic , Immunoglobulin G , Adenosine Monophosphate , Antibodies, Viral , Spike Glycoprotein, Coronavirus , Immunity, Humoral
7.
Int J Pharm X ; 5: 100174, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-2258117

ABSTRACT

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

8.
Int J Pept Res Ther ; 29(1): 5, 2023.
Article in English | MEDLINE | ID: covidwho-2270528

ABSTRACT

In spite of existing cases of severe viral infections with a high mortality rate, there are not enough antiviral drugs and vaccines available for the prevention and treatment of such diseases. In addition, the increasing reports of the emergence of viral epidemics highlight, the need for novel molecules with antiviral potential. Antimicrobial peptides (AMPs) with antiviral activity or antiviral peptides (AVPs) have turned into a research hotspot and already show tremendous potential to become pharmaceutically available antiviral medicines. AMPs, a diverse group of bioactive peptides act as a part of our first line of defense against pathogen inactivation. Although most of the currently reported AMPs are either antibacterial or antifungal peptides, the number of antiviral peptides is gradually increasing. Some of the AMPs that are shown as effective antivirals have been deployed against viruses such as influenza A virus, severe acute respiratory syndrome coronavirus (SARS-CoV), HIV, HSV, West Nile Virus (WNV), and other viruses. This review offers an overview of AVPs that have been approved within the past few years and will set out a few of the most essential patents and their usage within the context mentioned above during 2000-2020. Moreover, the present study will explain some of the progress in antiviral drugs based on peptides and peptide-related antivirals.

9.
Immunol Med ; 46(2): 97-107, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2264176

ABSTRACT

A 61-year-old man with no previous record of autoimmune disease developed fever, polyarthralgia, purpura, and urticaria-like rash 2 weeks after the first dose of the Moderna mRNA-1273 vaccine, and symptoms deteriorated following the second dose. He presented reduced erythrocyte and platelet counts, hyperferritinemia, high sIL-2R levels, and severe hypocomplementemia. We diagnosed hypocomplementemic urticarial vasculitis (HUVS), and his symptoms as well as laboratory findings improved following treatment with mPSL 1000 mg/day for 3 days and PSL 40 mg/day. Twelve weeks following treatment initiation, the patient relapsed with fever, sore throat, pancytopenia, and hyperferritinemia when the PSL dose was reduced to 12.5 mg/day. Bone marrow biopsy and MRI presented fatty marrow and hemophagocytosis. The patient's blood cells started recovering using ATG + CsA + EPAG therapy for hemophagocytic lymphohistiocytosis (HLH). This is the first case report of HUVS and HLH following SARS-CoV-2 mRNA vaccination. It is presumed that SARS-CoV-2 mRNA vaccine can induce the excessive production of certain types of cytokines, such as TNF-α, IL-1, IL-4, IL-5, IL-6, and IL-17 as a consequence of IL-6 Amplification (IL-6 Amp). SARS-CoV-2 mRNA-vaccines can cause disruption of immune homeostasis in healthy individuals. An extremely rare disease of HUVS complicated by HLH can be developed as a consequence.


Subject(s)
COVID-19 , Hyperferritinemia , Lymphohistiocytosis, Hemophagocytic , Urticaria , Vasculitis , Male , Humans , Middle Aged , Lymphohistiocytosis, Hemophagocytic/etiology , SARS-CoV-2 , COVID-19 Vaccines/adverse effects , Interleukin-6 , 2019-nCoV Vaccine mRNA-1273 , Hyperferritinemia/complications , COVID-19/complications , Urticaria/etiology , Urticaria/diagnosis , Urticaria/drug therapy , Fever/complications , Vaccination , Vasculitis/diagnosis , Vasculitis/pathology , RNA, Messenger
10.
American Journal of the Medical Sciences ; 365(Supplement 1):S407-S408, 2023.
Article in English | EMBASE | ID: covidwho-2229073

ABSTRACT

Case Report: Purpose: Milrinone is an inodilator that is used in the treatment of cardiogenic dysfunction and shock. It causes increased cardiac output by stimulating myocardial contractility, enhancing cardiac relaxation, and reducing afterload via phosphodiesterase III inhibition, preventing cyclic adenosine monophosphate (cAMP) degradation. Increased cAMP concentrations are known to inhibit platelet aggregation. Veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal treatment option for inotrope-refractory cardiogenic shock and is often used in conjunction with inodilators. Often, patients supported on ECMO require systemic anticoagulation to prevent clotting complications. Therefore, thromboelastography (TEG) with platelet mapping is used to help gauge a patient's clotting status and gives clinicians information about the degree of platelet inhibition present. We present the case of two patients, both supported on VA-ECMO, who developed platelet inhibition with clinically significant bleeding while on milrinone, requiring the cessation of the milrinone infusion. Cases: First, we present an adult female in her fourth decade of life who required VA-ECMO for Covid-19 ARDS and cardiogenic shock. TEG platelet mapping was obtained for clinically significant bleeding from her trachea and gastrointestinal tract. Ten days after starting milrinone, adenosine-5'-diphosphate (ADP) inhibition was elevated at 67.4% and arachidonic acid (AA) inhibition normal at 1.8%. Twenty days after starting milrinone, ADP inhibition was 93.3% and AA inhibition was 76.4%. Milrinone discontinued and repeat TEG platelet mapping (10 days after discontinuation) showed ADP inhibition of 76.8% and AA inhibition of 0%. Her lowest ADP inhibition was 41.9%, approximately 1 month after milrinone discontinuation. Milrinone again attempted and ADP inhibition was 87.9% and AA inhibition 89.2% within 24 hours of initiation. No data available for platelet inhibition prior to starting milrinone. Next, we present a 9 year old female with acute myeloid leukemia who required VA-ECMO for septic shock. Initial TEG platelet mapping, obtained 2 days after milrinone initiation, showed ADP inhibition of 43.6% and AA inhibition of 98.7%. Two days after discontinuation of milrinone, her ADP inhibition was 19.6% but AA inhibition remained elevated at 91.9%. However, after 4 days off milrinone, her ADP inhibition was normal at 15.5% and AA inhibition mildly elevated at 33.6%. No data available for platelet inhibition prior to starting milrinone. Conclusion(s): Milrinone is a known platelet inhibitor due to increased intracellular cAMP concentrations. For patients on ECMO and milrinone, care should be given to the degree of platelet inhibition and potential risk of clinically significant bleeding. Further studies are needed to further investigate the correlation between milrinone, platelet inhibition, and clinically significant bleeding in ECMO patients. Copyright © 2023 Southern Society for Clinical Investigation.

11.
Technological Forecasting and Social Change ; 188, 2023.
Article in English | Web of Science | ID: covidwho-2227939

ABSTRACT

Communicating the familiness of the firm allows family businesses to leverage a strategic resource: the idiosyncratic characteristics of the family firms. Drawing on the ontological perspective of the nature of family firm, this study investigates the effect of family firms' characteristics on consumers' willingness to pay (WTP) for family firms' products in an online environment. The study presents a novel context of analysis investigating the mediating effect of frequency of purchase and peer-to-peer online reviews in the digital channel. Results offer support for a direct effect of the family firms' characteristics on consumers' WTP and validate the total effect of mediation of frequency of purchase and peer-to-peer online reviews. The findings provide intriguing implications for practitioners. Defining the antecedents of consumers' WTP for family firms in the online channel shall be helpful for managers to create more efficient communication and marketing campaigns, with the effect of deploying more customer-centric revenue management techniques.

12.
7th International Conference on Advanced Production and Industrial Engineering, ICAPIE 2022 ; 27:565-570, 2022.
Article in English | Scopus | ID: covidwho-2198468

ABSTRACT

The pandemic that started in 2019 in Wuhan caused a vast number of deaths worldwide due to the absence of effective therapy against SARS-CoV-2. The present study investigates the interaction of AMP with viral protein and host receptors. We screened plant-derived antimicrobial peptides (AMP) from the docking web server with the help of PDB ID. We selected five anti-microbial peptides based on their antiviral and physiological activities. The interaction of anti-microbial peptide and Mpro was analyzed using the HADDOCK web server. The results revealed that the minimum Z-score was obtained by the 6LU7-1N4N complex followed by 6LU7-1GPS docked complex. The docking results showed the interaction potency of AMP with 6LU7. The dynamic simulation study of 100ns was performed to check the stability of the docked complexes of AMP and 6LU7. From the stable and positive results of dynamics studies, we can conclude that these selected AMPs have immense potential to be used as therapeutic agents for the treatment of disease. © 2022 The authors and IOS Press.

13.
Comunicacio-Revista De Recerca I D Analisi ; 39(2):89-108, 2022.
Article in English | Web of Science | ID: covidwho-2198245

ABSTRACT

In response to the Covid-19 pandemic, the media have used historical precedents and artistic representations to interpret the situation. Within this framework, and given its proximity and the abundance of testimonies, the 1918 influenza pandemic has been an ineluctable reference episode, with numerous parallels exploited by the media. This study analyzes how the Catalan press has treated this precedent, focusing the analysis on the literary testimonies of the 1918 influenza pandemic cited in the harshest period of the Covid-19 crisis. From a primarily Catalan viewpoint, an interpretation is made of the factors that have led the media to choose certain specific testimonies - mainly Josep Pla's The grey notebook - and not to take into account others that are also valuable. Likewise, considerations are made about the future and the mechanisms that determine the media's use of literature for the construction of the collective memory of traumatic episodes such as the Covid-19 pandemic.

14.
Biocell ; 46(Supplement 4):5, 2022.
Article in English | EMBASE | ID: covidwho-2167881

ABSTRACT

Infectious diseases show a great impact on public health and productivity, particularly in low-income countries. Proper diagnosis access can make a great difference in reducing both human and economic losses. Currently, there is a vacancy in diagnostic methods adapted to the field possibilities of the user, the beneficiary, and the system in which they are immersed (infrastructure, equipment, etc.). Ten years ago, we have started to work to develop and transfer tests -and associated know-how- for the detection of infectious agents (in human, veterinary, and plant health), which were fast, affordable, and simple to use in any field conditions. The first development done by this group arose from the call of FITS CHAGAS, FONARSEC-National Agency for Scientific and Technological Promotion (today "Agencia I+D+i"), to develop a simplified molecular diagnostic test for vertical Chagas. The grant required us, as CONICET researchers, to form a Public-Private Partnership Consortium (CAPP) with companies. The two signatory companies were national SMEs. That developed kit, namely Chagas NeoKit, has shown adequate sensitivity and specificity, but also has resulted very easy to perform, from a blood sample in the liquid state, from purified DNA, or directly from a dry blood drop on a card from the Neonatal Screening Program (PPN). It only requires the use of a simple thermal device, since the reaction is based on a loop-mediated isothermal amplification (LAMP), and no pipettes, centrifuges, or other laboratory equipment are necessary. This kit has been the 1st ARGENTINE MOLECULAR DETECTION REAGENT APPROVED by ANMAT (Resol. 1-47-3110-1994/17-5). This experience has been the beginning of a great learning process to turn a molecular reaction into a tangible good, adding capabilities from the scientific, health, and industrial systems. The work team grew and received other funds from the Agency that allowed us to increase and consolidate this knowledge, systematizing it in a technological platform where the LAMP technique is combined with tools focused on simplifying both the processing of the sample. as well as the reading out method, to obtain effective, robust, fast and simple to apply kits to detect different infectious agents. With the advent of the pandemic, the NEOKIT COVID-19 was developed and clinically and analytically validated (with 2 presentations: TecnoAMI and Plus), in record time, obtaining the approval of ANMAT in May 2020. This pandemic scenario has driven the installation of production capacities of approx. 1 million reactions/month and generated more than 10 job positions. Currently, in addition to accompanying the production process of the kit for COVID-19, work is being done on the development of kits for the detection of other infections, including vertical syphilis, dengue, zika, and chikungunya, among others. This is an example of the convergence of researchers from CONICET, the Pablo Cassara Foundation, and the Pablo Cassara SRL Laboratory, accompanied by state policies of the MINCyT, for transforming science and technology into diagnostic kits.

15.
Vaccines (Basel) ; 11(1)2023 Jan 10.
Article in English | MEDLINE | ID: covidwho-2200937

ABSTRACT

BACKGROUND: A pilot study was performed at a low-income emergency care clinic to assess the humoral immune response to the Johnson & Johnson (J&J) COVID-19 vaccine (Ad26.COV2.S) to better understand how to evaluate the COVID-19 health status of its Hispanic patient population following vaccination. METHODS: This study used the Clungene® SARS-CoV-2 IgG/IgM Rapid Test Cassette to determine the presence of binding antibodies resulting from the J&J COVID-19 vaccine. The Clungene test principle is based on the receptor-binding domain (RBD) of the spike protein. Antibodies targeting the spike protein are considered an appropriate measure of humoral response from spike-based vaccines. RESULTS: The study confirmed previous research that antibodies wane over time, and results are consistent with reported vaccine efficacy. There was a statistically significant relationship between the humoral immune response and demographic and health status variables. CONCLUSIONS: COVID-19 negative patients can be easily and efficiently monitored to determine the success and durability of COVID-19 vaccines in low-income minority populations. The use of simple low-cost spike targeted COVID-19 antibody lateral flow devices may serve as a useful adjunct to assist community-based physicians on the COVID-19 health status of its patients. Further research is needed to confirm the utility of this approach.

16.
Viruses ; 15(2)2023 01 23.
Article in English | MEDLINE | ID: covidwho-2200910

ABSTRACT

The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections.


Subject(s)
COVID-19 , Influenza A virus , Influenza, Human , Humans , Antiviral Agents/pharmacology , Chlorocebus aethiops , Influenza, Human/drug therapy , Pandemics , RNA, Viral , SARS-CoV-2 , Virus Replication
17.
Biology (Basel) ; 11(12)2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2123513

ABSTRACT

Throughout the pandemic, individuals 65 years and older have contributed most COVID-19 related deaths. To best formulate effective vaccination and other prevention policies to protect older adults, large scale observational studies of these higher risk individuals are needed. We conducted a Vaccine Effectiveness (VE) study during the B.1.617.2 Delta variant phase of the pandemic in July and August 2021 in a cohort of 17 million Medicare beneficiaries of which 5.7 million were fully vaccinated. We found that individuals fully vaccinated with the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines in January 2021 had 2.5 times higher breakthrough infections and hospitalizations than those fully vaccinated in March 2021, consistent with waning of vaccine-induced immunity. Measuring VE weekly, we found that VE against hospitalization, and even more so against infection, increased from July 2021 through August 2021, suggesting that in addition to the protective role of vaccination, increased masking or social distancing might have contributed to the unexpected increase in VE. Ongoing monitoring of Medicare beneficiaries should be a priority as new variants continue to emerge, and the VE of the new bivalent vaccines remains to be established. This could be accomplished with a large Medicare claims database and the analytics platform used for this study.

18.
BMJ Open ; 12(11): e065930, 2022 11 15.
Article in English | MEDLINE | ID: covidwho-2119468

ABSTRACT

INTRODUCTION: Interprofessional education is a relatively new addition to health professional education curricula in the Arab world. To understand current practice in this area, a scoping review will enable reporting of essential elements for the implementation of interprofessional education. The objective of this scoping review is to report on the implementation components, including presage, process and product, of interprofessional education in prelicensure health professions education programmes in the Arab world. METHODS AND ANALYSIS: A comprehensive and systematic search for literature will be conducted using eight electronic databases from their inception to September 2022. A presearch was devised in PubMed, Scopus and CINAHL using a combination of terms related to population, context and concept. The Covidence Systematic Review tool will be used for blind screening, selection and conflict resolution. Data will be presented in tabular format and as a narrative synthesis and will include elements that support the implementation of interprofessional education. This review will be presented according to the Joanna Briggs Institute methodology.Studies conducted with students and/or faculty in prelicensure health professions education programmes will be included. The concept to be explored is interprofessional education. The context is the region commonly known as the Arab world, which includes 18 countries, sharing many common social and cultural traditions and where Arabic is the first language.Excluded will be studies conducted on collaborative practice of health professionals and postlicensure interprofessional education. ETHICS AND DISSEMINATION: No ethical approval was required. Findings will be disseminated in conference presentations and peer-reviewed articles.


Subject(s)
Arab World , Health Personnel , Interprofessional Education , Humans , Curriculum , Health Occupations , Health Personnel/education , Research Design
19.
BMJ Open ; 12(11): e061360, 2022 11 14.
Article in English | MEDLINE | ID: covidwho-2119452

ABSTRACT

INTRODUCTION: This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment. METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48. ETHICS AND DISSEMINATION: The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: jRCTs071200011.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipidemias , Humans , Adult , Apolipoprotein B-48 , Pandemics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Japan , Prospective Studies , Eicosapentaenoic Acid , Treatment Outcome , Esters , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
20.
BMJ Open ; 12(11): e064105, 2022 11 11.
Article in English | MEDLINE | ID: covidwho-2119445

ABSTRACT

OBJECTIVES: To examine whether the use of process mapping and a multidisciplinary Delphi can identify potential contributors to perioperative risk. We hypothesised that this approach may identify factors not represented in common perioperative risk tools and give insights of use to future research in this area. DESIGN: Multidisciplinary, modified Delphi study. SETTING: Two centres (one tertiary, one secondary) in the UK during 2020 amidst coronavirus pressures. PARTICIPANTS: 91 stakeholders from 23 professional groups involved in the perioperative care of older patients. Key stakeholder groups were identified via process mapping of local perioperative care pathways. RESULTS: Response rate ranged from 51% in round 1 to 19% in round 3. After round 1, free text suggestions from the panel were combined with variables identified from perioperative risk scores. This yielded a total of 410 variables that were voted on in subsequent rounds. Including new suggestions from round two, 468/519 (90%) of the statements presented to the panel reached a consensus decision by the end of round 3. Identified risk factors included patient-level factors (such as ethnicity and socioeconomic status), and organisational or process factors related to the individual hospital (such as policies, staffing and organisational culture). 66/160 (41%) of the new suggestions did not feature in systematic reviews of perioperative risk scores or key process indicators. No factor categorised as 'organisational' is currently present in any perioperative risk score. CONCLUSIONS: Through process mapping and a modified Delphi we gained insights into additional factors that may contribute to perioperative risk. Many were absent from currently used risk stratification scores. These results enable an appreciation of the contextual limitations of currently used risk tools and could support future research into the generation of more holistic data sets for the development of perioperative risk assessment tools.


Subject(s)
Hospitals , Perioperative Care , Humans , Delphi Technique , Systematic Reviews as Topic , Consensus , Perioperative Care/methods
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