Understanding the experiences of PHC nurses in caring for older patients in the post-fifth wave of the COVID-19 pandemic: an exploratory qualitative study.

Objective: To ensure the best possible care, the perspective of PHC nurse work experience during the COVID-19 pandemic should be considered when developing nursing care protocols for older patients who receive PHC services. Method: This exploratory qualitative study was conducted with 18 nurses working continuously in PHC between the first and fifth waves of the pandemic. Semi-structured thematic interviews were undertaken. Qualitative thematic content analysis was conducted to identify and group the themes that emerged from the discourse. Interviews were transcribed and analyzed using thematic analysis. Results: The first topic describes the nurses' experiences of physical and mental suffering in caring for older patients in response to the pandemic. The second topic covers the experience of reorganizing PHC work. The third topic focuses on the difficulties of caring for older patients. The final topic includes issues of support needs for nurses in PHC work. Conclusion: The experience and understanding of PHC nurses in caring for older people during the COVID pandemic should lead to significant changes in the system of nursing care for geriatric patients and in the cooperative role within geriatric care specialist teams. Drawing on the experience of COVID-19, it is necessary to work on the weak points of PHC exposed by the pandemic in order to improve the quality of care and life for geriatric patients.

Development and assessment of a multiepitope synthetic antigen for the diagnosis of Dengue virus infection.

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.

Lived experiences of women with spontaneous abortion at a district hospital, South Africa.

BACKGROUND:  Spontaneous abortions occur in 12.5% of pregnancies and have a significant impact on the well-being of women. Dissatisfaction with health services is well-documented, but no studies have been conducted in district health services of the Western Cape. The aim was to explore the lived experiences of women presenting with spontaneous abortions to the emergency department at Helderberg Hospital. METHODS:  A descriptive phenomenological qualitative study used criterion-based purposive sampling to identify suitable participants. Data were collected through semi-structured individual interviews. Atlas-ti (version 22) software assisted with data analysis using the framework method. RESULTS:  A total of nine participants were interviewed. There were four main themes: a supportive environment, staff attitudes and behaviour, the impact of time, and sharing of information. The comfort, cleanliness and privacy of the environment were important. COVID-19 had also impacted on this. Showing interest, demonstrating empathy and being nonjudgemental were important, as well as the waiting time for definitive treatment and the time needed to assimilate and accept the diagnosis. In addition, the ability to give relevant information, explain the diagnosis and help patients share in decision-making were key issues. CONCLUSION:  This study highlighted the need for a more person-centred approach and managers should focus on changes to organisational culture through training and clinical governance activities. Attention should be paid to the physical environment, availability of patient information materials and sequential coordination of care with primary care services.Contribution: This study identifies issues that can improve person-centredness and women's satisfaction with care for spontaneous abortion.

Potential Application of Modified mRNA in Cardiac Regeneration.

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

The impact of, and expectations for, lipid nanoparticle technology: From cellular targeting to organelle targeting.

The success of mRNA vaccines against COVID-19 has enhanced the potential of lipid nanoparticles (LNPs) as a system for the delivery of mRNA. In this review, we describe our progress using a lipid library to engineer ionizable lipids and promote LNP technology from the viewpoints of safety, controlled biodistribution, and mRNA vaccines. These advancements in LNP technology are applied to cancer immunology, and a potential nano-DDS is constructed to evaluate immune status that is associated with a cancer-immunity cycle that includes the sub-cycles in tumor microenvironments. We also discuss the importance of the delivery of antigens and adjuvants in enhancing the cancer-immunity cycle. Recent progress in NK cell targeting in cancer immunotherapy is also introduced. Finally, the impact of next-generation DDS technology is explained using the MITO-Porter membrane fusion-based delivery system for the organelle targeting of the mitochondria. We introduce a successful example of the MITO-Porter used in a cell therapeutic strategy to treat cardiomyopathy.

Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein.

Many studies show either the absence, or very low levels of, SARS-CoV-2 viral RNA and/or antigen in the brain of COVID-19 patients. Reports consistently indicate an abortive infection phenomenon in nervous cells despite the fact that they contain the SARS-CoV-2 receptor, ACE2. Dopamine levels in different brain regions are in the range of micromolar to millimolar concentrations. We have shown that sub-micromolar to low micromolar concentrations of dopamine or its precursor (levodopa) time- and dose-dependently inhibit the activity of SARS-CoV-2 main protease (Mpro), which is vital for the viral life cycle, by forming a quinoprotein. Thiol detection coupled with the assessment of Mpro activity suggests that among the 12 cysteinyl thiols, the active site, Cys145-SH, is preferentially conjugated to the quinone derived from the oxidation of dopamine or levodopa. LC-MS/MS analyses show that the Cys145-SH is covalently conjugated by dopamine- or levodopa-o-quinone. These findings help explain why SARS-CoV-2 causes inefficient replication in many nerve cell lines. It is well recognized that inhaled pulmonary drug delivery is the most robust therapy pathway for lung diseases. CVT-301 (orally inhaled levodopa) was approved by the FDA as a drug for Parkinson's patients prior to the outbreak of COVID-19 in 2018. Based on the fact that SARS-CoV-2 causes inefficient replication in the CNS with abundant endogenous Mpro inhibitor in addition to the current finding that levodopa has an Mpro-inhibitory effect somewhat stronger than dopamine, we should urgently investigate the use of CVT-301 as a lung-targeting, COVID-19, Mpro inhibitor.

Temporal shifts in 24 notifiable infectious diseases in China before and during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease transmission dynamics. We analysed the impact of PHSMs on 24 notifiable infectious diseases (NIDs) in the Chinese mainland, using time series models to forecast transmission trends without PHSMs or pandemic. Our findings revealed distinct seasonal patterns in NID incidence, with respiratory diseases showing the greatest response to PHSMs, while bloodborne and sexually transmitted diseases responded more moderately. 8 NIDs were identified as susceptible to PHSMs, including hand, foot, and mouth disease, dengue fever, rubella, scarlet fever, pertussis, mumps, malaria, and Japanese encephalitis. The termination of PHSMs did not cause NIDs resurgence immediately, except for pertussis, which experienced its highest peak in December 2023 since January 2008. Our findings highlight the varied impact of PHSMs on different NIDs and the importance of sustainable, long-term strategies, like vaccine development.

SARS-CoV-2 vaccine breakthrough infection and the evaluation of safety precaution practice before and after vaccination among healthcare workers in South West, Nigeria.

INTRODUCTION: Worldwide, it has been reported that fully vaccinated people still die of COVID-19-associated symptoms, generating public uncertainty about the safety and effectiveness of the vaccines. Hence, this research is aimed at assessing the incidence of COVID-19 breakthrough infection among vaccinated Health Workers and the possible effect of changes in the practice of post-vaccination safety precautions. METHOD: This was a Health facility-based descriptive cross-sectional study. Data were collected using self-administered questionnaires distributed at the participant's work unit across the selected health facilities. The nasopharyngeal specimen was also obtained from the participants and analysed using STANDARD Q COVID-19 Ag Test rapid chromatographic immunoassay for the detection of antigens to SARS-CoV-2. All data were input and analyzed using SPSS version 20. RESULTS: There was a statistically significant relationship between the vaccination status of respondents and the post-vaccination test result (χ2 = 6.816, df = 1, p = 0.009). The incidence of COVID-19 infection among the vaccinated and unvaccinated HCWs was 2% and 8% respectively. 5 of the 15 respondents who tested positive for COVID-19 had been fully vaccinated. However, all 5 of them did not practice safety measures after vaccination. None of the respondents who practised safety measures after vaccination tested positive for COVID-19. The remaining 10 respondents that tested positive for COVID-19 had not been vaccinated though they practised safety precautions. CONCLUSION: Vaccination and the practice of safety precautions will go a long way to preventing future COVID-19 breakthrough infections.

Opportunity and accessibility: an environmental scan of publicly available data repositories to address disparities in healthcare decision-making.

BACKGROUND: Health disparities, starkly exposed and exacerbated by coronavirus disease 2019, pose a significant challenge to healthcare system access and health outcomes. Integrating health inequalities into health technology assessment calls for robust analytical methodologies utilizing disaggregated data to investigate and quantify the scope of these disparities. However, a comprehensive summary of population datasets that can be used for this purpose is lacking. The objective of this review was to identify publicly accessible health inequalities data repositories that are potential resources for healthcare decision-making and future health technology assessment submissions. METHODS: An environmental scan was conducted in June of 2023 of six international organizations (World Health Organization, Organisation for Economic Co-operation and Development, Eurostat, United Nations Inter-agency Group for Child Mortality Estimation, the United Nations Sustainable Development Goals, and World Bank) and 38 Organisation for Economic Co-operation and Development countries. The official websites of 42 jurisdictions, excluding non-English websites and those lacking English translations, were reviewed. Screening and data extraction were performed by two reviewers for each data repository, including health indicators, determinants of health, and health inequality metrics. The results were narratively synthesized. RESULTS: The search identified only a limited number of country-level health inequalities data repositories. The World Health Organization Health Inequality Data Repository emerged as the most comprehensive source of health inequality data. Some country-level data repositories, such as Canada's Health Inequality Data Tool and England's Health Inequality Dashboard, offered rich local insights into determinants of health and numerous health status indicators, including mortality. Data repositories predominantly focused on determinants of health such as age, sex, social deprivation, and geography. CONCLUSION: Interactive interfaces featuring data exploration and visualization options across diverse patient populations can serve as valuable tools to address health disparities. The data they provide may help inform complex analytical methodologies that integrate health inequality considerations into healthcare decision-making. This may include assessing the feasibility of transporting health inequality data across borders.

Examining the immunological responses to COVID-19 vaccination in multiple myeloma patients: a systematic review and meta-analysis.

BACKGROUND: Impaired immune response in multiple myeloma renders the patients vulnerable to infections, such as COVID-19, and may cause worse response to vaccines. Researchers should analyze this issue to enable the planning for special preventive measures, such as increased booster doses. Therefore, this meta-analysis aimed to evaluate the response and efficacy of COVID-19 vaccines in patients with multiple myeloma. METHODS: This meta-analysis followed PRISMA 2020 guidelines, conducting a comprehensive database search using specified keywords. Study selection involved a two-phase title/abstract and full-text screening process. Data extraction was performed by two researchers, and statistical analysis involved meta-analysis, subgroup analysis based on vaccine dosage and study time, random effects meta-regression, and heterogeneity testing using the Q test. RESULTS: The meta-analysis revealed that patients with multiple myeloma (MM) had a lower likelihood of developing detectable antibodies after COVID-19 vaccination compared to healthy controls (Log odds ratio with 95% CI: -3.34 [-4.08, -2.60]). The analysis of antibody response after different doses showed consistent lower seropositivity in MM patients (after first dose: -2.09, [-3.49, -0.69], second: -3.80, 95%CI [-4.71, -3.01], a booster dose: -3.03, [-5.91, -0.15]). However, there was no significant difference in the mean level of anti-S antibodies between MM patients and controls (Cohen's d -0.72, [-1.86, 0.43]). Evaluation of T-cell responses indicated diminished T-cell-mediated immunity in MM patients compared to controls. Seven studies reported clinical response, with breakthrough infections observed in vaccinated MM patients. CONCLUSIONS: These findings highlight the impaired humoral and cellular immune responses in MM patients after COVID-19 vaccination, suggesting the need for further investigation and potential interventions.

Structural and social changes due to the COVID-19 pandemic and their impact on engagement in substance use disorder treatment services: a qualitative study among people with a recent history of injection drug use in Baltimore, Maryland.

BACKGROUND: Substance use disorder treatment and recovery support services are critical for achieving and maintaining recovery. There are limited data on how structural and social changes due to the COVID-19 pandemic impacted individual-level experiences with substance use disorder treatment-related services among community-based samples of people who inject drugs. METHODS: People with a recent history of injection drug use who were enrolled in the community-based AIDS Linked to the IntraVenous Experience study in Baltimore, Maryland participated in a one-time, semi-structured interview between July 2021 and February 2022 about their experiences living through the COVID-19 pandemic (n = 28). An iterative inductive coding process was used to identify themes describing how structural and social changes due to the COVID-19 pandemic affected participants' experiences with substance use disorder treatment-related services. RESULTS: The median age of participants was 54 years (range = 24-73); 10 (36%) participants were female, 16 (57%) were non-Hispanic Black, and 8 (29%) were living with HIV. We identified several structural and social changes due the pandemic that acted as barriers and facilitators to individual-level engagement in treatment with medications for opioid use disorder (MOUD) and recovery support services (e.g., support group meetings). New take-home methadone flexibility policies temporarily facilitated engagement in MOUD treatment, but other pre-existing rigid policies and practices (e.g., zero-tolerance) were counteracting barriers. Changes in the illicit drug market were both a facilitator and barrier to MOUD treatment. Decreased availability and pandemic-related adaptations to in-person services were a barrier to recovery support services. While telehealth expansion facilitated engagement in recovery support group meetings for some participants, other participants faced digital and technological barriers. These changes in service provision also led to diminished perceived quality of both virtual and in-person recovery support group meetings. However, a facilitator of recovery support was increased accessibility of individual service providers (e.g., counselors and Sponsors). CONCLUSIONS: Structural and social changes across several socioecological levels created new barriers and facilitators of individual-level engagement in substance use disorder treatment-related services. Multilevel interventions are needed to improve access to and engagement in high-quality substance use disorder treatment and recovery support services among people who inject drugs.

Development and validation of the Trust in Multidimensional Healthcare Systems Scale (TIMHSS).

CONTEXT: The COVID-19 pandemic has reignited a commitment from the health policy and health services research communities to rebuilding trust in healthcare and created a renewed appetite for measures of trust for system monitoring and evaluation. The aim of the present paper was to develop a multidimensional measure of trust in healthcare that: (1) Is responsive to the conceptual and methodological limitations of existing measures; (2) Can be used to identify systemic explanations for lower levels of trust in equity-deserving populations; (3) Can be used to design and evaluate interventions aiming to (re)build trust. METHODS: We conducted a 2021 review of existing measures of trust in healthcare, 72 qualitative interviews (Aug-Dec 2021; oversampling for equity-deserving populations), an expert review consensus process (Oct 2021), and factor analyses and validation testing based on two waves of survey data (Nov 2021, n = 694; Jan-Feb 2022, n = 740 respectively). FINDINGS: We present the Trust in Multidimensional Healthcare Systems Scale (TIMHSS); a 38-item correlated three-factor measure of trust in doctors, policies, and the system. Measurement of invariance tests suggest that the TIMHSS can also be reliably administered to diverse populations. CONCLUSIONS: This global measure of trust in healthcare can be used to measure trust over time at a population level, or used within specific subpopulations, to inform interventions to (re)build trust. It can also be used within a clinical setting to provide a stronger evidence base for associations between trust and therapeutic outcomes.

Systematic investigation of the material basis, effectiveness and safety of Thesium chinense Turcz. and its preparation Bairui Granules against lung inflammation.

BACKGROUND: Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated. METHODS: Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice. RESULTS: Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-ß). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1ß, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic. CONCLUSIONS: The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.

A high-fidelity DNAzyme-assisted CRISPR/Cas13a system with single-nucleotide resolved specificity.

A CRISPR/Cas system represents an innovative tool for developing a new-generation biosensing and diagnostic strategy. However, the off-target issue (i.e., mistaken cleavage of nucleic acid targets and reporters) remains a great challenge for its practical applications. We hypothesize that this issue can be overcome by taking advantage of the site-specific cleavage ability of RNA-cleaving DNAzymes. To test this idea, we propose a DNAzyme Operation Enhances the Specificity of CRISPR/Cas13a strategy (termed DOES-CRISPR) to overcome the problem of relatively poor specificity that is typical of the traditional CRISPR/Cas13a system. The key to the design is that the partial hybridization of the CRISPR RNA (crRNA) with the cleavage fragment of off-target RNA was not able to activate the collateral cleavage activity of Cas13a. We showed that DOES-CRISPR can significantly improve the specificity of traditional CRISPR/Cas13a-based molecular detection by up to ∼43-fold. The broad utility of the strategy is illustrated through engineering three different systems for the detection of microRNAs (miR-17 and let-7e), CYP2C19*17 gene, SARS-Cov-2 variants (Gamma, Delta, and Omicron) and Omicron subtypes (BQ.1 and XBB.1) with single-nucleotide resolved specificity. Finally, clinical evaluation of this assay using 10 patient blood samples demonstrated a clinical sensitivity of 100% and specificity of 100% for genotyping CYP2C19*17, and analyzing 20 throat swab samples provided a diagnostic sensitivity of 95% and specificity of 100% for Omicron detection, and a clinical sensitivity of 92% and specificity of 100% for XBB.1 detection.

Burnout and Life Satisfaction among Healthcare Workers Related to the COVID-19 Pandemic (Silesia, Poland).

Background: The phenomenon of burnout among healthcare workers during the COVID-19 pandemic is a widespread problem with several negative consequences for the healthcare system. The many stressors of the pandemic have led to an increased development of anxiety and depressive disorders in many healthcare workers. In addition, some manifested symptoms of the so-called postpandemic stress syndrome and the emergence of occupational burnout syndrome, commonly referred to as "COVID-19 burnout." The aim of this study was to assess the burnout and life satisfaction of healthcare workers during the COVID-19 pandemic. Materials and Methods: The study was conducted in 2020-2022 among medical staff working in hospitals in Silesia, Poland. The instruments used to assess life satisfaction and burnout were the Satisfaction with Life Scale (SWLS) and the Maslach Burnout Inventory (MBI), which assesses three dimensions: emotional exhaustion (EE), depersonalisation (DEP), and sense of reduced professional accomplishment (SRPA). Results: The study group included 900 participants. There were 300 physicians (mean age 38 ± 7 years), 300 nurses (mean age 35 ± 6 years), and 300 paramedics (mean age 31 ± 5 years). Life satisfaction as measured by the SWLS was lowest among nurses and paramedics in 2021 and among doctors in 2022. Male respondents and those with fewer years of work had higher levels of life satisfaction. People with more years of work had higher scores in EE and DEP and lower scores in SRPA (p = 0.001). We found a negative correlation between life satisfaction and EE (p = 0.001), DEP (p = 0.001), and SRPA (p = 0.002). Conclusions: The results highlight the need for further research into the causes of burnout among medical professionals and the need for effective interventions to promote well-being and prevent burnout in this group.

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Measles Vaccine Coverage and Disease Outbreaks: A Systematic Review of the Early Impact of COVID-19 in Low and Lower-Middle Income Countries.

Objectives: We aimed to evaluate changes to measles-containing vaccine (MCV) provision and subsequent measles disease cases in low- and lower-middle income countries (LICs, LMICs) in relation to the COVID-19 pandemic. Methods: A systematic search was conducted of MEDLINE, OVID EMBASE and PubMed records. Primary quantitative and qualitative research studies published from January 2020 were included if they reported on COVID-19 impact on MCV provision and/or measles outbreak rates within LICs and LMICs. Results: 45 studies were included. The change in MCV1 vaccination coverage in national and international regions ranged -13% to +44.4% from pre-COVID time periods. In local regions, the median MCV1 and overall EPI rate changed by -23.3% and -28.5% respectively. Median MCV2 rate was disproportionally impacted in local areas during COVID-interruption time-periods (-48.2%) with ongoing disruption in early-recovery time-periods (-17.7%). 8.9% of studies reported on vaccination status of confirmed measles cases; from these, 71%-91% had received no MCV dose. Conclusion: MCV vaccination coverage experienced ongoing disruption during the recovery periods after initial COVID-19 disruption. Vaccination in local area datasets notably experienced longer-term disruption compared to nationally reported figures.

Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development.

Modified nucleosides are integral to modern drug development, serving as crucial building blocks for creating safer, more potent, and more precisely targeted therapeutic interventions. Nucleobase modifications often confer antiviral and anti-cancer activity as monomers. When incorporated into nucleic acid oligomers, they increase stability against degradation by enzymes, enhancing the drugs' lifespan within the body. Moreover, modification strategies can mitigate potential toxic effects and reduce immunogenicity, making drugs safer and better tolerated. Particularly, N1-methylpseudouridine modification improved the efficacy of the mRNA coding for spike protein of COVID-19. This became a crucial step for developing COVID-19 vaccine applied during the 2020 pandemic. This makes N1-methylpseudouridine, and its "parent" analogue pseudouridine, potent nucleotide analogues for future RNA therapy and vaccine development. This review focuses on the structure and properties of pseudouridine and N1-methylpseudouridine. RNA has a greater structural versatility, different conformation, and chemical reactivity than DNA. Watson-Crick pairing is not strictly followed by RNA that has more unusual base pairs and base-triplets. This requires detailed structural studies and structure-activity relationship analyses for RNA, also when modifications are incorporated. Recent successes in this direction are revised in this review. We describe recent successes with using pseudouridine and N1-methylpseudouridine in mRNA drug candidates. We also highlight remaining challenges that need to be solved to develop new mRNA vaccines and therapies.

Susceptibility and transmissibility of SARS-CoV-2 variants in transgenic mice expressing the cat angiotensin-converting enzyme 2 (ACE-2) receptor.

The emergence of SARS-CoV-2 in 2019 and its rapid spread throughout the world has caused the largest pandemic of our modern era. The zoonotic origin of this pathogen highlights the importance of the One Health concept and the need for a coordinated response to this kind of threats. Since its emergence, the virus has caused >7 million deaths worldwide. However, the animal source for human outbreaks remains unknown. The ability of the virus to jump between hosts is facilitated by the presence of the virus receptor, the highly conserved angiotensin-converting enzyme 2 (ACE2), found in various mammals. Positivity for SARS-CoV-2 has been reported in various species, including domestic animals and livestock, but their potential role in bridging viral transmission to humans is still unknown. Additionally, the virus has evolved over the pandemic, resulting in variants with different impacts on human health. Therefore, suitable animal models are crucial to evaluate the susceptibility of different mammalian species to this pathogen and the adaptability of different variants. In this work, we established a transgenic mouse model that expresses the feline ACE2 protein receptor (cACE2) under the human cytokeratin 18 (K18) gene promoter's control, enabling high expression in epithelial cells, which the virus targets. Using this model, we assessed the susceptibility, pathogenicity, and transmission of SARS-CoV-2 variants. Our results show that the sole expression of the cACE2 receptor in these mice makes them susceptible to SARS-CoV-2 variants from the initial pandemic wave but does not enhance susceptibility to omicron variants. Furthermore, we demonstrated efficient contact transmission of SARS-CoV-2 between transgenic mice that express either the feline or the human ACE2 receptor.

Exploring social media influences on vaccine decision-making in parents: a netnography.

Background: Immunization is one of the most significant health initiatives of recent times. Despite this, vaccine hesitancy is increasing and was listed as one of the top 10 threats to global health by the World Health Organization in 2019. A major factor associated with vaccine hesitancy is thought to be the viral spread of misinformation by a small but active anti-vaccination movement. Objectives: The purpose of this study was to explore the influences of social media on vaccine decision-making in parents. Design: This study is part of a larger body of research that explored vaccine decision-making in parents. Other methods included were an online survey and semi-structured interviews. This study investigated the influence of cyberculture on parents in an online environment. Method: This study employed netnography, a form of qualitative inquiry with its roots in ethnography as methodology and a purpose-designed Facebook page as the means of exploring a purpose-designed online community with a particular focus on the culture, belief systems and influences present. Both manual and computer-assisted thematic analyses were used to analyse the data obtained. Results: Three key themes were identified in this study. These included vaccine safety concerns, the emotional debate and COVID-19-specific issues. The results indicated the presence of strong anti-vaccination sentiment combined with an 'infodemic' of conspiracy theories, misinformation and vitriol with the potential to negatively impact parents seeking immunization information. Conclusion: Given the popularity and accessibility of social media and the ready access to misinformation present online, it is evident that parental vaccine decision-making may be impacted adversely. Therefore, it is important that healthcare professionals are aware of this and provide adequate and timely education prior to parents seeking information on social media.

Exploring the influence of social media on vaccine decision-making in parents: a netnography This research explored the impact of Facebook interactions on the vaccine decision-making of parents.