How to manage comorbidities in people with dementia: A scoping review.

BACKGROUND: People with dementia experience a high prevalence of comorbidities that seriously affect patient outcomes. The aim of this study was to map the evidence and components related to comorbidity management, including interventions to facilitate and support the practice of management. METHODS: A scoping review was conducted. In June 2022, PubMed, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The National Institute of Health and Care Excellence (NICE), Open grey, and the Cochrane Library were searched to identify relevant literature. The inclusion criteria were outlined to identify studies on comorbidity management in people with dementia. RESULTS: We found 43 items that met the inclusion criteria. The majority of the studies were published since 2010. Most research focused on medication management, health care service use and provision, and comorbidity-related monitoring and management; there were a small number of studies that involved decision-making. Only 6 studies developed interventions to support dementia care, which included comorbidity management. Studies involving the comorbidity management process were mainly based on qualitative methods, which make it difficult to quantify the impact of these processes on comorbidity management. CONCLUSIONS: Given the serious impact of dementia on managing comorbidities, there is a need to develop systematic interventions targeting the management of comorbidities.

How tablets/applications enhance social connections and social support in people with dementia: A qualitative systematic review.

The 2020 Lancet issue identified social isolation as one of 12 modifiable risk factors for dementia and revealed that enhanced social connections and social support can effectively reduce the incidence of social isolation. During the COVID-19 pandemic, technology attracted an increasing amount of attention, and it is necessary to synthesize ideas from existing evidence. First, we explored how people with dementia experienced changes in social connection and social support due to tablet/app use. Second, we explored the attitudes of people with dementia towards tablets and mobile applications. Third, we explored the feasibility of using tablets and mobile applications to enhance social connection and social support among people with dementia. We systematically searched the PubMed, Web of Science, Cochrane Library, Embase, CINAHL, CNKI, WanFang, and VIP databases. Two reviewers independently screened the titles and abstracts of studies, extracted the data and performed critical appraisals of each included study. The data synthesis was conducted using thematic analysis. A total of nine studies were included. Eight studies used mobile applications via tablets, and one study collected textual data from Twitter for analysis. Four themes were synthesized: (1) change from the perspective of caregivers; (2) growth of nonsingle aspects; (3) emotional feeling of belonging; and (4) feasibility of using digital technology. Tablet- and mobile application-based interventions can enhance both online and offline social connections and provide multiple types of social support among people with dementia. People with dementia have positive attitudes towards tablets and mobile applications. Overall, it is feasible for people with dementia to use technology.

Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine. However, emerging SARS-CoV-2 variants of concern (VOCs), such as the delta variant, have escaped mutations against vaccine-induced neutralizing antibodies. This suggests that modified vaccines accommodating VOCs need to be developed promptly. Here, we first modified the current DNA vaccine to enhance antigenicity. Compared with the parental DNA vaccine, the modified version (GP∆-DNA vaccine) induced rapid antibody production. Next, we updated the GP∆-DNA vaccine to spike glycoprotein of the delta variant (GP∆-delta DNA vaccine) and compared the efficacy of different injection routes, namely intramuscular injection using a needle and syringe and intradermal injection using a pyro-drive jet injector (PJI). We found that the levels of neutralizing antibodies induced by the intradermal PJI injection were higher than intramuscular injection. Furthermore, the PJI-injected GP∆-delta DNA vaccine effectively protected human angiotensin-converting enzyme 2 (hACE2) knock-in mice from delta-variant infection. These results indicate that the improved DNA vaccine was effective against emerging VOCs and was a potential DNA vaccine platform for future VOCs or global pandemics.

Phase I Study to Assess the Safety and Immunogenicity of an Intradermal COVID-19 DNA Vaccine Administered Using a Pyro-Drive Jet Injector in Healthy Adults.

We conducted a nonrandomized, open-label phase I study to assess the safety and immunogenicity of an intradermal coronavirus disease 2019 (COVID-19) DNA vaccine (AG0302-COVID-19) administered using a pyro-drive jet injector at Osaka University Hospital between Yanagida November 2020 and December 2021. Twenty healthy volunteers, male or female, were enrolled in the low-dose (0.2 mg) or high-dose (0.4 mg) groups and administered AG0302-COVID19 twice at a 2-week interval. There were no adverse events that led to discontinuation of the study drug vaccination schedule. A serious adverse event (disc protrusion) was reported in one patient in the high-dose group, but the individual recovered, and the adverse event was not causally related to the study drug. In the analysis of the humoral immune response, the geometric mean titer (GMT) of serum anti-SARS-CoV-2 spike glycoprotein-specific antibody was low in both the low-dose and high-dose groups (246.2 (95% CI 176.2 to 344.1, 348.2 (95% CI 181.3 to 668.9)) at the 8 weeks after first vaccination. Regarding the analysis of the cellular immune, the number of IFN-γ-producing cells responsive to the SARS-CoV-2 spike glycoprotein increased with individual differences after the first dose and was sustained for several months. Overall, no notable safety issues were observed with the intradermal inoculations of AG0302-COVID19. Regarding immunogenicity, a cellular immune response was observed in some subjects after AG0302-COVID19 intradermal inoculation, but no significant antibody production was observed.

Immune response induced in rodents by anti-CoVid19 plasmid DNA vaccine via pyro-drive jet injector inoculation.

There is an urgent need to stop the coronavirus disease 2019 (COVID-19) pandemic through the development of efficient and safe vaccination methods. Over the short term, plasmid DNA vaccines can be developed as they are molecularly stable, thus facilitating easy transport and storage. pVAX1-SARS-CoV2-co was designed for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) S protein. The antibodies produced led to immunoreactions against the S protein, an anti-receptor-binding-domain, and a neutralizing action of the pVAX1-SARS-CoV2-co, as previously confirmed. To promote the efficacy of the pVAX1-SARS-CoV2-co vaccine a pyro-drive jet injector (PJI) was used. An intradermally adjusted PJI demonstrated that the pVAX1-SARS-CoV2-co vaccine injection caused a high production of anti-S protein antibodies, triggered immunoreactions, and neutralized the actions against SARS-CoV-2. A high-dose pVAX1-SARS-CoV2-co intradermal injection using PJI did not cause any serious disorders in the rat model. A viral challenge confirmed that intradermally immunized mice were potently protected from COVID-19. A pVAX1-SARS-CoV2-co intradermal injection using PJI is a safe and promising vaccination method for overcoming the COVID-19 pandemic.

Preclinical study of a DNA vaccine targeting SARS-CoV-2.

To fight against the worldwide COVID-19 pandemic, the development of an effective and safe vaccine against SARS-CoV-2 is required. As potential pandemic vaccines, DNA/RNA vaccines, viral vector vaccines and protein-based vaccines have been rapidly developed to prevent pandemic spread worldwide. In this study, we designed plasmid DNA vaccine targeting the SARS-CoV-2 Spike glycoprotein (S protein) as pandemic vaccine, and the humoral, cellular, and functional immune responses were characterized to support proceeding to initial human clinical trials. After intramuscular injection of DNA vaccine encoding S protein with alum adjuvant (three times at 2-week intervals), the humoral immunoreaction, as assessed by anti-S protein or anti-receptor-binding domain (RBD) antibody titers, and the cellular immunoreaction, as assessed by antigen-induced IFNγ expression, were up-regulated. In IgG subclass analysis, IgG2b was induced as the main subclass. Based on these analyses, DNA vaccine with alum adjuvant preferentially induced Th1-type T cell polarization. We confirmed the neutralizing action of DNA vaccine-induced antibodies by a binding assay of RBD recombinant protein with angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, and neutralization assays using pseudo-virus, and live SARS-CoV-2. Further B cell epitope mapping analysis using a peptide array showed that most vaccine-induced antibodies recognized the S2 and RBD subunits. Finally, DNA vaccine protected hamsters from SARS-CoV-2 infection. In conclusion, DNA vaccine targeting the spike glycoprotein of SARS-CoV-2 might be an effective and safe approach to combat the COVID-19 pandemic.

Computational Methods to Study Human Transcript Variants in COVID-19 Infected Lung Cancer Cells.

Microbes and viruses are known to alter host transcriptomes by means of infection. In light of recent challenges posed by the COVID-19 pandemic, a deeper understanding of the disease at the transcriptome level is needed. However, research about transcriptome reprogramming by post-transcriptional regulation is very limited. In this study, computational methods developed by our lab were applied to RNA-seq data to detect transcript variants (i.e., alternative splicing (AS) and alternative polyadenylation (APA) events). The RNA-seq data were obtained from a publicly available source, and they consist of mock-treated and SARS-CoV-2 infected (COVID-19) lung alveolar (A549) cells. Data analysis results show that more AS events are found in SARS-CoV-2 infected cells than in mock-treated cells, whereas fewer APA events are detected in SARS-CoV-2 infected cells. A combination of conventional differential gene expression analysis and transcript variants analysis revealed that most of the genes with transcript variants are not differentially expressed. This indicates that no strong correlation exists between differential gene expression and the AS/APA events in the mock-treated or SARS-CoV-2 infected samples. These genes with transcript variants can be applied as another layer of molecular signatures for COVID-19 studies. In addition, the transcript variants are enriched in important biological pathways that were not detected in the studies that only focused on differential gene expression analysis. Therefore, the pathways may lead to new molecular mechanisms of SARS-CoV-2 pathogenesis.

Pulmonary function of patients with 2019 novel coronavirus induced-pneumonia: a retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the pulmonary function of patients with 2019 novel coronavirus (COVID-19)-induced pneumonia. METHODS: A retrospective analysis of 137 patients with COVID-19-induced pneumonia who were discharged from the Enze Hospital, Taizhou Enze Medical Center (Group) from January 31 2020 to March 11 2020 was conducted. Follow-up occurred 2 weeks after hospital discharge, during which patients underwent a pulmonary function test. RESULTS: Of the 137 patients who underwent a pulmonary function test 2 weeks after discharge, 51.8% were male, and the mean age was 47 years. Only 19.7% of the patients were identified as having severe COVID-19-induced pneumonia. The pulmonary function tests showed that for a small number of patients the forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC)/% values were <70%, and the mean forced inspiratory volume (IVC) and FVC values were 2.4±0.7 and 3.2±0.8 L, respectively. In severe cases, 88.9% of patients had an IVC <80% of the predicted value, and 55.6% of patients had an FVC <80% of the predicted value. The proportion of patients with maximum expiratory flow rate at 25%, 50% and 75% of the vital capacity (MEF25, MEF50, and MEF75) values <70% were 55.6%, 40.7%, and 25.9%, respectively. In the non-severe group, 79.1% of patients had an IVC <80% of the predicted value, and 16.4% of patients had an FVC <80% of the predicted value. The mean MEF25, MEF50, and MEF75 <70% values were 57.3%, 30%, and 13.6%, respectively. CONCLUSIONS: Our results demonstrated that the pulmonary function of patients with COVID-19-induced pneumonia predominantly manifested as restrictive ventilation disorder and small airway obstruction, which was increased in critically ill patients.

Focus on Characteristics of COVID-19 with the Special Reference to the Impact of COVID-19 on the Urogenital System.

Coronavirus disease 2019 (COVID-19) is a new infectious disease that first emerged in December 2019. It has infected more than 4,890,000 people in more than 200 countries. This virus can cause progressive respiratory symptoms and severe diseases such as organ failure and death. The complete genomic sequence of SARS-CoV-2 was determined after the virus's identification, and the sequence analysis showed that SARS-CoV-2 strains are genetically similar to SARS-CoV. Angiotensin converting enzyme II is an entry receptor for SARS-CoV-2, which is highly expressed in the kidney, so some patients had symptoms of kidney damage. Here we reviewed the current progress of COVID-19 and its urogenital manifestations. In this rapidly moving field, this review was comprehensive as of May 30, 2020.