Pre-clinical safety evaluation for mRNA-vaccine development in mouse model

Messenger RNA (mRNA) vaccine has emerged as an attractive agent for prevention of infectious disease and anti-cancer therapy. However, there is a fatal risk that the safety evaluation for mRNA vaccine have not been fully studied yet. In this study, we evaluated the safety of four type of COVID-19 S-protein targeting mRNA vaccines with different compositions (C2/ LNP90, C2LNP128, C3LNP90 and C3LNP128). Theses vaccines were intramuscularly injected to 6-wk old male and female ICR mice with twice at an interval of 2 wks. The necropsy was carried out on 2 days or 14 days after secondary injection. The results showed that the body weight was decreased for 2days after the first injection in C2/LNP128 and C3/LNP128-injected mice, but it was almost recovered at 7day post injection (dpi). At 2 dpi after secondary injection, the endpoint blood analysis of demonstrated that C2/LNP128 and C3/LNP128 decreased the number of lymphocytes, monocytes and reticulocytes carrying the abnormal level of liver function indicator such as albumin, AST, ALT and total protein. Additionally, C2/LNP128 decreased the number of platelet and C3LNP128 decreased the number of red blood cells, respectably. Spleen and inguinal lymph node were enlarged in all experimental group. Notably, C2/LNP128 and C3/LNP128 induced severe edema in injection site, femoris muscle. At 14 dpi after secondary injection, the toxicity that was observed at 2 dpi after secondary injection was recovered. These results suggest that the potential side effects of mRNA vaccines must be systematically evaluated with multiple aspect of toxicology.

Establishment of a Mouse Model to Evaluate mRNA Vaccine Safety

FDA granted emergency use authorization (EUA) for the world's first mRNA vaccine, developed by Pfizer-BioNTech, in December 2020. As a result, many vaccinated people were protected from the fatality of COVID-19, but some people suffered from various side effects of the mRNA vaccine. The EUA was immediately decided to control COVID-19 pandemic and the deregulation of preclinical safety assessment for mRNA vaccine was inevitable. In preclinical phase, efficacy assessment of several mRNA vaccine candidates has been performed by using COVID-19 mouse infection model. However, the guideline of safety assessment for mRNA vaccine in mice has not yet been established. Therefore, it is necessary to identify mRNA vaccineinduced toxicity and clinical symptoms. In this study, we evaluated the clinical and serologic changes induced by the intramuscular injection of 4 types of mRNA vaccines (100 mug/head) with different compositions (C2/LNP90, C2LNP128, C3LNP90, and C3LNP128) in 6-wk-old male and female ICR mice. Five mice per group, a total of 25 male and female mice, respectively, were used in this study. mRNA vaccines were injected twice at an interval of 2 wk and necropsy was carried out 2 d after secondary injection. CBC, blood chemistry analysis, and visual evaluation of whole-body tissues were performed. The results showed that the body weight was decreased for 2 d after the first injection in C2/LNP128 and C3/LNP128- injected mice compared to vehicle-injected mice, but it was almost recovered at 14 d postinjection (dpi). The endpoint blood and serum analysis demonstrated that C2/LNP128 and C3/LNP128 decreased the number of lymphocyte, monocyte, and reticulocyte carrying the abnormal level of liver function indicator such as albumin, AST, ALT, and total protein. Additionally, C2/LNP128 decreased the number of platelets and C3LNP128 decreased the number of red blood cells, respectively. Spleen and inguinal lymph nodes were enlarged in all experimental groups compared to the control group. Notably, C2/ LNP128 and C3/LNP128 induced severe edema in the injection site, the femoral muscle, that was significantly enlarged. Although more detailed analyses should be carried out, these results suggest that the safety assessment of mRNA vaccines must be systematically established with multiple aspects of toxicology and laboratory animal medicine.

Secure e-Prescription Management System: Mitigating Blended Threat in IoBE

New information and communication technologies (ICT) are being applied in various industries to upgrade the value of the major service items. Moreover, data collection, storage, processing, and security applications have led to the creation of an interrelated ICT environment in which one industry can directly influence the other. This is called the "internet of blended environments" (IoBE), as it is an interrelated data environment based on internet-ofthings collection activities. In this environment, security incidents may increase as size and interconnectivity of attackable operations grow. Consequently, preemptive responses to combined security threats are needed to securely utilize IoBE across industries. For example, the medical industry has more stringent information protection measures than other industries. Consequently, it has become a major target of attackers, as more clinician-patient interactions occur over the internet owing to COVID-19. Therefore, this study aims to acquire security for IoBE while focusing on the medical industry. Among the various types of medical ICT services, this study analyzes data flow and potential security threats from the e-prescription lifecycle perspective, which is highly utilized, strongly data-centric, and has numerous security issues. Based on our analysis, we propose a secure authentication and data-sharing scheme. © 2023 CRL Publishing. All rights reserved.

Needs For Food, Medicine, and Mental Health Services Among Vulnerable Older Adults During Covid-19 Pandemic

Background: The COVID-19 pandemic has exacerbated multiple barriers to healthcare for vulnerable seniors. They may experience more difficulties in meeting their basic needs for food, medicine, and social support. The objective of the project was to connect with seniors to show our care, to assess food security, medication possession, mental health, and to refer those needing services to appropriate providers. Methods: Using a computer-assisted telephone interview (CATI) approach, we called patients served by our primary care providers from April to December 2020. The CATI assessed their mental health by Personal Health Questionnaire-2 (PHQ2) and General Anxiety Disorder-2 (GAD2). The California Health Place Index (HPI) was used to measure social determinants of health associated with community resources. Descriptive analyses examined the proportion of patients needing follow-up services and being referred to services to address food insecurity (if had <3 days of food), medication needs (if had <30 days of medicine), and mental health services (PHQ2>2 or GAD2>2). Multivariable logistic regression analyses examined demographic and health factors associated with the odds for needing and being referred for follow-up services. Results: Of 1921 respondents, their average age was 76 years (SD11). 52% female and 48% non-female (including male, transgender, and other);74% White, 7% Asian, 7% Hispanic, 3% Black, and 8% other. Medication needs existed among 595 (31%) patients, 196 (10%) faced food insecurity, and 292 (15%) needed mental health services. Regression results suggest, Blacks (OR1.86, p<0.05) had higher odds of being at risk of medication shortage than Whites;Blacks (OR2.30, p<0.05) and Hispanics (OR 2.30, p<0.05) had significantly higher odds of food insecurity than Whites. Higher odds for food insecurity referral were found among non-females (OR7.56, p<0.05) and Blacks (OR10.33, p<0.05). Blacks (OR13.34, p<0.05) and those living in 2nd quartile of HPI (OR2.57, p<0.05) had higher odds for mental health referrals. Conclusions: Significant disparities existed across gender, race, and community resource groups in need for food, medications, and mental health services. Findings underscore the imperatives for health and social services organizations to systematize outreach and follow-up services for vulnerable seniors.

Changes in Shared Bicycle Usage by COVID-19

The Seoul Metropolitan Government is promoting and implementing eco-friendly transportation policies covering the revitalization of public transportation, establishment of green transportation promotion areas, and the expansion of shared-bicycle use. With the prevalence of the COVID-19 pandemic, cities worldwide have been paralyzed by lockdowns, the strict implementation of social-distancing policies, and the shutdown of different industry sectors. People's movement and traffic volume have decreased significantly. The pandemic has forced to people change their travel-related decision-making tendencies. Against this backdrop, this study analysed the changes in shared-bicycle traffic in Seoul during the pandemic. This study analyzed the relationship between social distancing levels and shared bicycle usage using regression analysis. This study conducted an analysis of spatially formed clusters through Moran's I test and hotspot analysis. The results indicate that an important correlation between the spread of COVID-19 and shared bicycle use has been found. When social distancing levels increased by one level, the number of shared bicycle rental per day increased by about 10,000 times. As a result of spatial analysis, changes in shared bicycle usage are spatially forming clusters, and Moran's I test showed statistically significant results with a p-value very close to zero. The study results indicate that under special circumstances, government policy plays an important role in promoting green transportation. The use of green transportation is directly related to falling atmospheric pollution in the city. Such transportation can significantly benefit the environment. The government can produce more effective results by considering local characteristics to revitalize eco-friendly transportation. © 2021, AIDIC Servizi S.r.l.

Rationalization of Network Segregation for Continuity of Financial Services Following COVID-19

As measures for protecting users and ensuring security of electronic financial transactions, such as online banking, financial institutions in South Korea have implemented network segregation policies. However, a revision of such domain-centered standardized network segregation policies has been increasingly requested because of: 1) increased demand for remote work due to changes resulting from COVID-19 pandemic;and 2) the difficulty of applying new technologies of fintech companies based on information and communications technologies (ICTs) such as cloud services. Therefore, in this study, problems of the remote work environment arising from the network segregation policy currently applied to the financial sector in South Korea and those from the application of new ICTs such as fintech technology have been investigated. In addition, internal network protection policies of foreign financial sectors, such as those of the United States, United Kingdom, European Union, and Russia, and internal network protection policies of non-financial sectors, such as control systems, have been analyzed. As measures for the effective improvement of the current network segregation policy, we propose a policy change from domain-based to data-centric network segregation. Furthermore, to resolve threats of hacking at remote work, recently emerging as a global problem due to COVID-19 pandemic, a standard model for remote work system development applicable to financial companies and a reinforced terminal security model are presented, and an alternative control method applicable when network segregation is not applied is proposed.

Intracellular delivery of nuclearlocalization signal suppresses COVID-19 mediatedinflammation by regulating expression ofcytokines/chemokines

The outbreak of coronavirus disease 19 (COVID-19), caused by the recently identified coronavirus named SARS-CoV-2, is leading patients to death (mortality: ∼7%) because of cytokine storm. COVID-19 induces excessivesecretion of proinflammatory cytokines and chemokines accompanied by the disruption of the bronchi and alveoli, which could ultimately develop into permanent lung impairments such as pulmonary fibrosis. To regulate theuncontrolled expression of proinflammatory cytokines/chemokines, improved cell-permeable nuclear import inhibitor(iCP-NI) has been developed by fusing sequence-optimized hydrophobic cell-penetrating peptide (CPP), namelyadvanced macromolecule transduction domain (aMTD) with nuclear localization signal (NLS) of stress responsivetranscription factors (SRTFs: NF-κB, STAT1/3, AP-1, and NFAT). Intracellularly delivered NLS is supposed tosuppress expression of proinflammatory cytokines/chemokines by inhibiting transport of SRTFs from cytoplasm intonucleus. iCP-NI regulated expression of cytokines (TNF-α: -79%, IL-6: -91%, IL-12: -110% and IL-10: +574%) andchemokines (MCP-1: -89%) in bronchoalveolar lavage fluids (BALFs) from RNA virus infection mimetic pneumonitisanimals that were induced with inhalation of RNA structure molecule, poly I:C. iCP-NI also significantly decreasedpulmonary fibrosis (-61%) in bleomycin-induced pulmonary fibrosis animals. Moreover, iCP-NI protected leukocytes(CD3+ T cell: 100%, CD4+/CD3+ T cell: 96%, B220+ B cell: 85%, CD45+ macrophage: 100%) and reducedapoptotic splenocytes (-97%) in staphylococcal enterotoxin B (SEB) and poly I:C-induced acute pneumonitisanimals. These results suggest that iCP-NI has potential as a novel therapeutic measurement for inflammationcaused by various infectious diseases including COVID-19 accompanied with cytokine storm and severe sepsis.