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1.
International Journal of Applied Pharmaceutics ; 15(3):1-11, 2023.
Article in English | EMBASE | ID: covidwho-20242785

ABSTRACT

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

2.
Pigment & Resin Technology ; 52(4):490-501, 2023.
Article in English | ProQuest Central | ID: covidwho-20242763

ABSTRACT

PurposeThis study aims to focus on the preparation and characterization of the silver nanowire (AgNWs), as well as their application as antimicrobial and antivirus activities either with incorporation on the waterborne coating formulation or on their own.Design/methodology/approachPrepared AgNWs are characterized by different analytical instruments, such as ultraviolet-visible spectroscope, scanning electron microscope and X-ray diffraction spectrometer. All the paint formulation's physical and mechanical qualities were tested using American Society for Testing and Materials, a worldwide standard test procedure. The biological activities of the prepared AgNWs and the waterborne coating based on AgNWs were investigated. And, their effects on pathogenic bacteria, antioxidants, antiviral activity and cytotoxicity were also investigated.FindingsThe obtained results of the physical and mechanical characteristics of the paint formulation demonstrated the formulations' greatest performance, as well as giving good scrub resistance and film durability. In the antimicrobial activity, the paint did not have any activity against bacterial pathogen, whereas the AgNWs and AgNWs with paint have similar activity against bacterial pathogen with inhibition zone range from 10 to 14 mm. The development of antioxidant and cytotoxicity activity of the paint incorporated with AgNWs were also observed. The cytopathic effects of herpes simplex virus type 1 (HSV-1) were reduced in all three investigated modes of action when compared to the positive control group (HSV-1-infected cells), suggesting that these compounds have promising antiviral activity against a wide range of viruses, including DNA and RNA viruses.Originality/valueThe new waterborne coating based on nanoparticles has the potential to be promising in the manufacturing and development of paints, allowing them to function to prevent the spread of microbial infection, which is exactly what the world requires at this time.

3.
Kliniceskaa Mikrobiologia i Antimikrobnaa Himioterapia ; 24(4):295-302, 2022.
Article in Russian | EMBASE | ID: covidwho-20242710

ABSTRACT

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

4.
Journal of Biological Chemistry ; 299(3 Supplement):S136, 2023.
Article in English | EMBASE | ID: covidwho-20242023

ABSTRACT

According to the World Health Organization, Tuberculosis (TB) is the second leading cause of death by a single infectious disease behind COVID-19. Despite a century of effort, the current TB vaccine does not effectively prevent pulmonary TB, promote herd immunity, or prevent transmission. Therefore, we seek to develop a genetic prophylaxis for TB. We have determined D-cycloserine to be the optimal target for this approach due to its relatively short six-enzyme biosynthetic pathway. D-CS is a second-line antibiotic for TB that inhibits bacterial cell wall synthesis. The first committed step towards D-CS synthesis is catalyzed by the L-serine-O-acetyltransferase (DcsE) which converts L-serine and acetyl-CoA to O-acetyl-L-serine (L-OAS). To test if the D-CS pathway could be an effective prophylaxis for TB in human cells, we endeavored to express DcsE in human cells and test its functionality. We overexpressed DcsE tagged with FLAG and GFP in A549 lung cancer cells as determined using fluorescence microscopy. We observed that purified DcsE catalyzed the synthesis of L-OAS as observed by HPLC-MS. Therefore, DcsE synthesized in human cells is a functional enzyme capable of converting L-serine and acetyl-CoA to L-OAS demonstrating the first step towards DCS production in human cells.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

5.
Asian Journal of Pharmaceutical and Clinical Research ; 16(5):153-156, 2023.
Article in English | EMBASE | ID: covidwho-20241523

ABSTRACT

Objectives: Globally, cataract and glaucoma are the predominant causes of blindness. Screening glaucoma in patients referred for cataract surgery is a convenient tool for detecting glaucoma cases in rural population. The COVID period has adversely affected eye care as the routine screening and follow-ups at hospital were substantially reduced owing to pandemic restrictions. We aim to study the impact of COVID on detection of glaucoma in patients with cataract. Method(s): It was a retrospective study conducted to compare the prevalence of glaucoma in rural patients presenting with cataract pre- and post-COVID. Details of 975 consecutive patients each were taken prior to March 2020 (pre-COVID) and after October 2021 (post-COVID) from hospital database and patient case files. Result(s): The prevalence of glaucoma was higher during the pre-COVID time (3.8%) as compared to pre-COVID (3.8%), but the result was not statistically significant. In both the groups, primary open-angle glaucoma was the pre-dominant form of glaucoma, with prevalence being 1.5% and 2.2% in the pre-COVID and post-COVID groups, respectively. The mean intraocular pressure and mean VCDR values were higher in the post-COVID group as compared to the pre-COVID group, and the result was statistically significant. Conclusion(s): This was the first study to compare the prevalence of glaucoma in patients with cataract in rural population in the pre-COVID and post-COVID periods. In the aftermath of the pandemic, the present study emphasizes the role of screening and follow-ups in glaucoma management to prevent irreversible loss of vision.Copyright © 2023 The Authors.

6.
American Journal of Clinical Pathology, suppl 1 ; 158, 2022.
Article in English | ProQuest Central | ID: covidwho-20241384

ABSTRACT

Introduction/Objective Kidney injury has now become one of the known complications following COVID-19 infection and vaccination. Only few cases of minimal change disease following administration of COVID-19 vaccination and infection have been reported. This study was to highlight incidence of minimal change disease following COVID-19 infection or vaccination. Methods/Case Report Case 1:15 year-old female with past medical history of asthma and hypercholesterolemia presented for evaluation of periorbital edema, nephrotic-range proteinuria, hypoalbuminemia, elevated serum creatinine, elevated blood pressures, and hematuria after COVID-19 infection. Renal biopsy after 1 week of infection showed unremarkable glomeruli and negative immunofluorescent stains in glomeruli, and 20-30% fusion of foot processes. The biopsy was consistent with a minimal change disease with features of natural remission (her nephrotic-range proteinuria resolved soon after). Case 2: 18 year-old female with no significant past medical history presented with a chief complaint of generalized swelling, which started around the same time she received her 1st dose of Pfizer COVID vaccine (the 2nd dose 2 months later). She had a nephrotic range proteinuria and hypoalbuminemia, but normal level of serum creatinine. A renal biopsy after 4 months of vaccination showed unremarkable glomeruli by light microscopy, negative immunofluorescent study, but diffuse effacement of foot processes involving more than 80% of the examined loops by electron microscopy. This biopsy findings were consistent with a minimal change disease. Both patients did not receive any treatment before the renal biopsies. Results (if a Case Study enter NA) NA Conclusion Minimal change disease can be a rare complication following COVID-19 infection or Pfizer COVID-19 vaccination, raising a question if there are similar antigens induced by the infection or by the vaccination that trigger the minimal change disease. Further studies are needed to determine the incidence and pathophysiology of minimal change disease either post COVID-19 vaccines or following COVID-19 infections.

7.
International Journal of Applied Pharmaceutics ; 15(Special Issue 1):51-55, 2023.
Article in English | EMBASE | ID: covidwho-20240315

ABSTRACT

Objective: To design an optimal formulation for quercetin and vitamin C nano-phytosome. Method(s): Nano-phytosomes are prepared by the thin layer hydration technique using a 2-level-5-factor design experimental. A total of 32 experimental formulas were used for data analysis. The ratio of quercetin: soy lecithin (X1), the ratio of quercetin: cholesterol (X2), stirring speed (X3), stirring temperature (X4), and stirring time (X5) were used as independent factors, while globule size as a dependent factor. Data analysis was carried out by Design Expert12 application. Characterization of the optimal formula included physicochemical evaluation, globule size analysis, zeta potential, polydispersity index, entrapment efficiency, Transition Electron Microscopy (TEM) analysis, and FTIR analysis. Result(s): The optimal formula consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, at temperature 51.73 degreeC which produced 59.26 nm average globule size, PDI value 0.66;zeta potential value-35.93+/-0.95 mV and average SPAN value 0.61. This formulation showed entrapment efficiency of quercetin 91.69+/-0.18 % and vitamin C 90.82+/-0.13 %. The TEM and FITR analysis showed the morphological of the globules and interactions between the drugs, soy lecithin, and cholesterol to form nano-phytosomes. Conclusion(s): The conditions to obtain the optimal formula for quercetin vitamin C nano-phytosome consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, and at temperature 51.73 degreeC.Copyright © 2023 The Authors.

8.
Proceedings of SPIE - The International Society for Optical Engineering ; 12611, 2023.
Article in English | Scopus | ID: covidwho-20238796

ABSTRACT

The 6XS6 is the structure of the SARS-CoV-2 spike protein. The physiological role of the spike protein is relative to the respiratory syndrome coronavirus and has a stronger infect on the human body than the ancestor virus. The purification of the 6XS6 is in the homo sapiens cell by the affinity chromatography, PBS supplemented and Size Exclusion chromatography. At last, using the Cryo-Electron Microscopy to see the structure. This paper is using the D614G mutation to illustrate the structure of the 6XS6. The N-terminal domain and C-terminal domain of the 6XS6 protein are ALA27 and VAL1137. Furthermore, the mutation doesn't have the hydrogen bond because the Asp614 is substituted by the Gly614, and the molecule that interacts with the Ala 647 may occur. While the 6XS6 structure has lots of non-covalent and disulfide bonds. Comparing the structure of the 6XS6 and 6VXX, both are glycoproteins, have three monomers, have two subunits, and have the same category of expression and classification. The different conformations of the two structures can affect the binding ability with the ACE2. This paper can help the researchers to further understand the structure and function of the 6XS6 which can be used in future experiments. © 2023 SPIE.

9.
Cytotherapy ; 25(6 Supplement):S109, 2023.
Article in English | EMBASE | ID: covidwho-20236255

ABSTRACT

Background & Aim: Liposomes are spherical-shaped vesicles composed of one or more lipid bilayers. The ability of liposomes to encapsulate hydro- or lipophilic drugs allowed these vesicles to become a useful drug delivery system. Natural cell membranes, such as Bioxome, have newly emerged as new source of materials for molecular delivery systems. Bioxome are biocompatible and GMP-compliant liposome-like membrane that can be produced from more than 200 cell types. Bioxome self-assemble, with in-process self-loading capacity and can be loaded with a variety of therapeutic compounds. Once close to the target tissue, Bioxome naturally fuse with the cell membrane and release the inner compound. Orgenesis is interested in evaluating the potential of Bioxome as new drug delivery system for treatment of several diseases, including skin repair, local tumour or COVID19. Methods, Results & Conclusion(s): Bioxome were obtained from adipose- derived Mesenchymal Stem Cells, with a process of organic- solvent lipid extraction, followed by lyophilization and sonication assemblage. During the sonication process, Bioxome were charged or not with several cargos. Size distribution of empty Bioxome was detected by Particle Size Analyzer (NanoSight). Electron Microscopy (EM) was performed to assess Bioxome morphology. Lipid content was evaluated by electrospray ionization system. Dose response in vitro test on human lung fibroblasts treated or not with Bioxome encapsulating a specific cargo (API) against COVID19 were performed. NanoSight analysis showed that nanoparticle size in Bioxome samples ranged between 170+/-50 nm, with a concentration ranging between 109-1010+/-106 particles/mL. EM clearly showed the double phospholipid layers that composes the Bioxome. Stability study demonstrated that Bioxome are stable in size and concentration up to 90 days at +4Cdegree or even at RT. No change in size between encapsulated Bioxome with small size (~340 Da) cargo vs empty Bioxome was observed up to 30 days storage. Lipidomic analysis approach revealed that the yield of lipids and their composition are satisfactory for a therapeutic product using Bioxome. Lastly, in the in vitro model of COVID19, Bioxome encapsulating API effectively saved cells from death (20x vs untreated cells) and at lower doses of API than these of non-encapsulated cargo (0.005 microM vs 0.1 microM). Bioxome seems to be an excellent candidate for liposome mimetic tool as drug delivery system for targeting specific organs and diseases treatment.Copyright © 2023 International Society for Cell & Gene Therapy

10.
Journal of Geoscience Education ; 2023.
Article in English | Scopus | ID: covidwho-20235258

ABSTRACT

A virtual microscope resource was created when face-to-face labs were halted due to the COVID-19 pandemic in March 2020 to replicate the learning goals of an introductory petrology course on microscopy. This virtual microscope resource utilized images and videos of thin sections, as well as 3D rock models to allow students to complete labs online. It also incorporated directed questioning and feedback as would be provided by demonstrators (teaching assistants) in a face-to-face lab. Insights obtained from student reflective questionnaires (n = 75) were used to adapt the online resource so that it could be used in conjunction with the face-to-face lab, thus becoming a blended lab resource in the subsequent year. These reflective questionnaires were utilized again to provide feedback on the revised version of the resource for blended learning. Findings showed that students in the blended learning cohort rated the quality of the available online material higher than the previous students. The blended learning cohort appreciated the immediate feedback from the resource, as well as its ability to provide remote access to lab materials. They also gained confidence by being able to review the material multiple times online. We conclude that blended resources are a useful tool in introductory petrology which we hope to see become more commonplace in the future. © 2023 National Association of Geoscience Teachers.

11.
Retina-Vitreus ; 32(1):70-73, 2023.
Article in English | EMBASE | ID: covidwho-20234405

ABSTRACT

A 40-year-old male patient, an office worker, is a hospital staff. He applied with the complaint of sudden onset of blurred vision in the right eye. He stated that he had the first dose of inactivated covid vaccine (sinovac) 4 days ago in his story. In his examination, his vision was 0.5 in the right eye, 1.0 in the left eye, and his intraocular pressure was in both eyes. It was at the level of 15 mmHg. Biomicroscopically, the anterior segment looked natural. CSC was diagnosed in the FFA and OCT examinations.Treatment with oral acetazolamide (2x250 mg), topical nepafanac (4x1) was started. On the 13th day of the treatment, there was insufficient improvement in clinical findings, and oral acetazolamide was used. The dose was reduced (2x125 mg), oral epleronone (50 mg) was added. On the 70th day of the treatment, the vision in the right eye increased to full level in the control examination and it was observed that the retina returned to its normal appearance in the OCT examination.Copyright © 2023 Gazi Eye Foundation. All rights reserved.

12.
Fresenius Environmental Bulletin ; 32(5):2146, 2023.
Article in English | ProQuest Central | ID: covidwho-20233781

ABSTRACT

Determination of the filtration efficiency (even to nanosize) of several textiles was carried out during emergency time at the beginning of the COVID-19 pandemic lockdown in order to perform a fast screening of materials candidate for facial masks. At this purpose, a double strategy was adopted in Milan: scanning electron microscopy investigation and a classical filtration test of ambient aerosol. The latter was used in order to mimic as much as possible the capability to filter ambient aerosol that might contain COVID-19. The two methods were compared to investigate their capability to identify only textiles characterized by a filtration efficiency higher than 90% (thus candidate for facial mask production). Results showed filtration efficiency above 90% for promising candidate textiles as well as poor filtration capabilities (below 60%) of other textiles, enabling a fast screening of the materials from different Italian factories.

13.
Bio Protoc ; 11(16): e4128, 2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-20239621

ABSTRACT

Analyzing cellular structures and the relative location of molecules is essential for addressing biological questions. Super-resolution microscopy techniques that bypass the light diffraction limit have become increasingly popular to study cellular molecule dynamics in situ. However, the application of super-resolution imaging techniques to detect small RNAs (sRNAs) is limited by the choice of proper fluorophores, autofluorescence of samples, and failure to multiplex. Here, we describe an sRNA-PAINT protocol for the detection of sRNAs at nanometer resolution. The method combines the specificity of locked nucleic acid probes and the low background, precise quantitation, and multiplexable characteristics of DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT). Using this method, we successfully located sRNA targets that are important for development in maize anthers at sub-20 nm resolution and quantitated their exact copy numbers. Graphic abstract: Multiplexed sRNA-PAINT. Multiple Vetting and Analysis of RNA for In Situ Hybridization (VARNISH) probes with different docking strands (i.e., a, b, …) will be hybridized to samples. The first probe will be imaged with the a* imager. The a* imager will be washed off with buffer C, and then the sample will be imaged with b* imager. The wash and image steps can be repeated sequentially for multiplexing.

14.
Molecules ; 28(11)2023 May 26.
Article in English | MEDLINE | ID: covidwho-20243101

ABSTRACT

Nowadays, due to a higher resistance to drugs, antibiotics, and antiviral medicaments, new ways of fighting pathogens are intensively studied. The alternatives for synthesized compositions are natural products, most of which have been known in natural medicine for a long time. One of the best-known and intensively investigated groups are essential oils (EOs) and their compositions. However, it is worth noting that the method of application can play a second crucial part in the effectiveness of the antimicrobial activity. EOs possess various natural compounds which exhibit antimicrobial activity. One of the compositions which is based on the five main ingredients of eucalyptus, cinnamon, clove, rosemary, and lemon is named "five thieves' oil" (Polish name: olejek pieciu zlodziei) (5TO) and is used in natural medicine. In this study, we focused on the droplet size distribution of 5TO during the nebulization process, evaluated by the microscopic droplet size analysis (MDSA) method. Furthermore, viscosity studies, as well as UV-Vis of the 5TO suspensions in medical solvents such as physiological salt and hyaluronic acid, were presented, along with measurements of refractive index, turbidity, pH, contact angle, and surface tension. Additional studies on the biological activity of 5TO solutions were made on the P. aeruginosa strain NFT3. This study opens a way for the possible use of 5TO solutions or emulsion systems for active antimicrobial applications, i.e., for surface spraying.


Subject(s)
Anti-Infective Agents , Eucalyptus , Oils, Volatile , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antiviral Agents , Pseudomonas aeruginosa
15.
J Biomol Struct Dyn ; : 1-13, 2022 May 31.
Article in English | MEDLINE | ID: covidwho-20243817

ABSTRACT

Achillea millefolium (Yarrow) is a herbaceous plant of Greek origin noted to treat pneumonia, common cold, cough, and other respiratory disorders. The flowers and leaves are the core part used to prepare herbal tea that gains the world's recognition as medicinal tea. Coronavirus disease is spreading across the globe, and numerous approaches are lodged to treat virus-induced lung inflammation. Here, we used the network pharmacology, metabolite analysis, docking and molecular simulation and MM-PBSA analysis to comprehend the biochemical basis of the health-boosting impact of Yarrow tea. Next, we performed the microscopic and dynamic light scattering (DLS) analysis of yarrow-treated ChAdOx1 nCoV-19 to evaluate the virucidal activity of the Yarrow. The present study investigates the druggability, metabolites and potential interaction of the title tea with genes associated with Covid-19-induced pathogenesis. Towards this, 1022 gene hits were obtained, 30 are mutually shared. Network Pharmacology and microarray gene expression analysis find the connection of PTGS2 in relieving the virus-induced inflammation. Yarrow constituents Luteolin may inhibit or down-regulate the Cyclooxygenase II (PTGS2), a plausible mechanism underlying the Yarrow's anti-inflammatory actions. Further, the Yarrow's virucidal activity was assessed towards Transmission Electron Microscopic (TEM). The Yarrow treated SARS-nCoV-2 cell exhibits the disintegration of the virus membrane. This work provides a scientific basis for further elucidating the mechanism underlying Achillea millefolium's antiviral and anti-inflammatory properties.

16.
Ultrastruct Pathol ; : 1-6, 2023 Jun 12.
Article in English | MEDLINE | ID: covidwho-20241445

ABSTRACT

Recent studies indicate that cilia impairment, accompanied by the axonema loss and the basal body misorientation, is a common pathological feature of SARS-CoV-2-infected bronchial epithelial cells. However, these data were obtained using either cultured cells, or animal models, while in human postmortem material, cilia impairment has not been described yet. Here, we present direct observation of cilia impairment in SARS-CoV-2-infected bronchial epithelial cells using transmission electron microscopy of the autopsy material. We were able to observe only single infected cells with cilia impairment in one of twelve examined specimens, while the large number of desquamated bronchial epithelial cells with undisturbed ciliary layer was visible in the bronchial lumens. Thus, it seems that in the lungs of infected patients, the majority of bronchial cells do not die as a direct result of infection, which may explain the rarity of this finding in the autopsy material.

17.
Mol Ther Methods Clin Dev ; 29: 450-459, 2023 Jun 08.
Article in English | MEDLINE | ID: covidwho-20240177

ABSTRACT

Following the recent approval of both siRNA- and mRNA-based therapeutics, nucleic acid therapies are considered a game changer in medicine. Their envisioned widespread use for many therapeutic applications with an array of cellular target sites means that various administration routes will be employed. Concerns exist regarding adverse reactions against the lipid nanoparticles (LNPs) used for mRNA delivery, as PEG coatings on nanoparticles can induce severe antibody-mediated immune reactions, potentially being boosted by the inherently immunogenic nucleic acid cargo. While exhaustive information is available on how physicochemical features of nanoparticles affects immunogenicity, it remains unexplored how the fundamental choice of administration route regulates anti-particle immunity. Here, we directly compared antibody generation against PEGylated mRNA-carrying LNPs administered by the intravenous, intramuscular, or subcutaneous route, using a novel sophisticated assay capable of measuring antibody binding to authentic LNP surfaces with single-particle resolution. Intramuscular injections in mice were found to generate overall low and dose-independent levels of anti-LNP antibodies, while both intravenous and subcutaneous LNP injections generated substantial and highly dose-dependent levels. These findings demonstrate that before LNP-based mRNA medicines can be safely applied to new therapeutic applications, it will be crucial to carefully consider the choice of administration route.

18.
Free Neuropathol ; 22021 Jan.
Article in English | MEDLINE | ID: covidwho-20239279

ABSTRACT

This review highlights ten important advances in the neuromuscular disease field that were first reported in 2020. The overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19, supervillin-deficient myopathy, 19p13.3-linked distal myopathy, vasculitic neuropathy due to eosinophilic granulomatosis with polyangiitis, spinal muscular atrophy, idiopathic inflammatory myopathies, and transthyretin neuropathy/myopathy. In addition, the review highlights several other advances (such as the revised view of the myofibrillar architecture, new insights into molecular and cellular mechanisms of muscle regeneration, and development of new electron microscopy tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.

19.
Free Neuropathol ; 22021 Jan.
Article in English | MEDLINE | ID: covidwho-20234442

ABSTRACT

This article reviews a collection of manuscripts in the field of neurodegenerative disease chosen from what are considered by the author to be among the 10 most important and potentially impactful topics or research trends of 2020 relevant to the field of experimental and diagnostic neuropathology. A deliberate effort was made to provide balance among disease categories covered. The result is a varied selection that includes not just individual papers but also research topics and trends. The association of COVID-19 with longer-term neurological symptoms has launched a research trend fueled by speculation that the SARS-CoV-2 might trigger neurodegenerative changes. The onslaught of transcriptomic studies has begun to give way to proteomics, with three transformative studies published examining glial contributions to Alzheimer disease, cerebral atherosclerosis in cognitive decline, and the complex sequence of post-translational modifications of the tau protein. Plasma biomarkers for Alzheimer disease have continued to make rapid advances, especially around highly sensitive assays capable of detecting different forms of abnormal hyperphosphorylated tau in peripheral blood. Two studies using cryo-electron microscopy showed the power of the approach by continuing to elucidate the diversity of filamentous tau inclusions, and a third study gave the first glimpse of α-synuclein aggregates at near atomic resolution. Another study continued to delineate how different α-synuclein conformers ("strains") target specific brain regions and lead to neurodegeneration. In Huntington's disease, we saw compelling molecular data showing how cells adapt to endoplasmic reticulum stress through the unfolded protein response. Finally, the role of astrocytes in chronic traumatic encephalopathy has emerged as a critical area of interest.

20.
Chinese Journal of Parasitology and Parasitic Diseases ; 40(2):261-265, 2022.
Article in Chinese | EMBASE | ID: covidwho-2324526

ABSTRACT

The epidemiological data were collected from travellers who returned from Guinea on the 23rd of September, 2020 and were diagnosed with malaria at a C OVID -19 quarantine site in Qingdao, Shandong Province. The epidemiological characteristics, diagnosis and treatment of the cases and the epidemiology investigation and the rapid test screening results for other travellers on from the same flight and the interventions in reaction to the imported malaria cases were analyzed. The results showed that 4 out of 231 Guinean returned travellers had developed malaria symptoms, including chills and fever, during the isolation period. Rapid diagnostic test (RDT) indicated Plasmodium falciparum infection. Considering the patients ' travel history, clinical manifestations, and laboratory RDT test results, a confirmed diagnosis of imported P. falciparum malaria was made. The four malaria cases, who are male workers aged 29 to 55, were transferred to Jiaozhou People ' s Hospital for treatment. All four patients were administrated of artemether tablets upon diagnosis. One of the cases experienced severe malaria complications and were administrated with 12 doses (60 mg/dose) of artesunate intravenously for five days. The other three patients were treated with dihydroartemisinin and piperaquine phosphate tablets for one course of 8 tablets in 2 days (40 mg dihydroartemisinin and 320 mg piperaquine phosphate), respectively. Among the 231 returned travellers, 111 (48.1 %) had a history of malaria overseas. There were 23 positive cases detected by RDT, including the four symptomatic cases. The other 19 cases were asymptomatic. One of the asymptomatic cases became symptomatic three months later and was diagnosed as an imported P. malariae infection. Laboratory blood smear microscopic tests at the Jiaozhou City and Qingdao Municipal Center For Disease Control and Prevention showed negative results for the four malaria cases and the 19 RDT positive case. The samples from the four malaria cases were rechecked by the provincial reference laboratory of Shandong Institute of parasitic Disease. The results were negative for malaria infection by microscopic examination but positive for P. falciparum infection by nucleic acid test. It is suggested that during the routine control of COVID-19, the awareness of COVID-19 and malaria should be established among the returned travellers from high malaria-endemic areas. The health education "gate" should be moved forward to improve the treatment compliance for malaria cases and reduce the relapse or recrudescence caused by sub-optimal treatment.Copyright © 2022, Chin J Parasitol Parasit Dis. All rights reserved.

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