Contact-number-driven virus evolution: A multi-level modeling framework for the evolution of acute or persistent RNA virus infection.

Viruses evolve in infected host populations, and host population dynamics affect viral evolution. RNA viruses with a short duration of infection and a high peak viral load, such as SARS-CoV-2, are maintained in human populations. By contrast, RNA viruses characterized by a long infection duration and a low peak viral load (e.g., borna disease virus) can be maintained in nonhuman populations, and the process of the evolution of persistent viruses has rarely been explored. Here, using a multi-level modeling approach including both individual-level virus infection dynamics and population-scale transmission, we consider virus evolution based on the host environment, specifically, the effect of the contact history of infected hosts. We found that, with a highly dense contact history, viruses with a high virus production rate but low accuracy are likely to be optimal, resulting in a short infectious period with a high peak viral load. In contrast, with a low-density contact history, viral evolution is toward low virus production but high accuracy, resulting in long infection durations with low peak viral load. Our study sheds light on the origin of persistent viruses and why acute viral infections but not persistent virus infection tends to prevail in human society.

Information and Communication Technology Use for Alleviation of Disability Onset in Socially Isolated Older Adults: A Longitudinal Cohort Study.

INTRODUCTION: Delaying the onset of disability is important for maintaining independence and quality of life in community-dwelling older adults. Given that social isolation is a significant risk factor for disability, effective means associated with social isolation are needed to alleviate disability. Although information and communication technology (ICT) may be a reasonable measure considering the recent social contexts due to the coronavirus disease 2019 pandemic, further insights are required. This study aimed to investigate whether ICT use can alleviate the onset of disability in community-dwelling older adults with and without social isolation. METHODS: This longitudinal cohort study on 4,346 community-dwelling independent Japanese older adults (mean age, 73.5 ± 5.3 years) was conducted between 2017 and 2018. Participants were classified into four groups based on social isolation (the condition where two or more of the following measures were met: domestic isolation, less social contact, and social disengagement) and ICT users (those who had recently used a computer or a smartphone) and followed up to assess disability incidence for 24 months after baseline assessments. Cox proportional-hazards regression models were used to identify the effect of social isolation and ICT use on the risk of disability onset by adjusting for age, sex, education history, number of medications, eye disease, level of annual income, Mini-Mental State Examination, Geriatric Depression Scale 15, and gait speed. RESULTS: The group comprised nonsocial isolation and ICT users (44.7%), social isolation and ICT users (5.4%), nonsocial isolation and ICT nonusers (41.7%), and social isolation and ICT nonusers (8.2%). At the follow-up, 2.2%, 2.4%, 5.5%, and 12.4% of the participants in the above order developed disability (p < 0.01). Cox regression models revealed a significantly higher risk of disability onset in the social isolation and ICT nonusers group than in the social isolation and ICT users group (HR = 2.939; 95% confidence interval (CI) 1.029-8.397; p = 0.044). In the subgroup analysis stratified by social isolation, ICT use significantly reduced the risk of disability onset in the socially isolated group (HR = 0.320; 95% CI 0.109-0.943; p = 0.039), although the same association was not observed in the nonsocially isolated group (HR = 0.845; 95% CI 0.565-1.264; p = 0.411). CONCLUSION: ICT use can alleviate the onset of disability in socially isolated older adults in a community setting. Considering ICT-applied methods for alleviating disability is beneficial for older adults in social isolation.

Singing Is a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Case-Control Study of Karaoke-Related Coronavirus Disease 2019 Outbreaks in 2 Cities in Hokkaido, Japan, Linked by Whole Genome Analysis.

Background: Singing in an indoor space may increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a case-control study of karaoke-related coronavirus disease 2019 (COVID-19) outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke. Methods: Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by reverse-transcription polymerase chain reaction between 16 May and 3 July 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ORs of key variables adjusted for each other were also estimated (aOR). Results: We identified 81 cases, the majority of whom were active elderly individuals (median age, 75 years). Six cases died (case fatality ratio, 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited ≧2 karaoke bars. A genome analysis conducted in 30 cases showed 6 types of isolates within 4 single-nucleotide variation difference. The case-control study revealed that singing (aOR, 11.0 [95% CI, 1.2-101.0]), not wearing a mask (aOR, 3.7 [95% CI, 1.2-11.2]), and additional hour spent per visit (aOR, 1.7 [95% CI, 1.1-2.7]) were associated with COVID-19 infection. Conclusions: A karaoke-related COVID-19 outbreak that occurred in 2 different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.

Singing Is a Risk Factor for SARS-CoV-2 Infection: A Case-control Study of Karaoke-related COVID-19 Outbreaks in Two Cities in Hokkaido, Japan, Linked by Whole Genome Analysis

Background Singing in an indoor space may increase the risk of SARS-CoV-2 infection. We conducted a case-control study of karaoke-related COVID-19 outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke. Methods Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by RT-PCR between May 16 and July 3, 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratio (OR) and confidence interval (CI) were calculated. ORs were adjusted by variables with significantly high odds ratio (aOR). Results We identified 81 cases, the majority of whom were active elderly individuals (median age: 75 years). Six cases died (case fatality ratio: 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited more than two karaoke bars. A genome analysis conducted in 30 cases showed six types of isolates within four single-nucleotide variations difference. The case-control study revealed that singing (aOR 11.0, 95% CI, 1.2-101.0), not wearing a mask (aOR 3.7, 95% CI 1.2-11.2) and time spent per visit (aOR 1.7, 95% CI 1.1-2.7) were associated with COVID-19 infection. Conclusions A karaoke-related COVID-19 outbreak that occurred in two different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.

Core belief disruption amid the COVID-19 pandemic in Japanese adults

Due to the rapid spread of the novel coronavirus disease (COVID-19) worldwide, most people have been forced to alter their lifestyles. This situation may affect the mental health of individuals through the disruption of core beliefs about humans, the world, and the self. Therefore, in this study, an online survey of Japanese adults was conducted to investigate the associations between subjective achievement and the burden of cooperation in preventive measures, disruption of core beliefs, and psychological distress. The results showed that pandemic-induced disruption of core beliefs occurred at a relatively low level in the general population of Japan. In addition, the achievement and psychological burden of preventive measures, reduced income due to the pandemic, and stressfulness of the pandemic were significantly associated with the level of the disruption of core beliefs. Moreover, the greater the disruption of core beliefs, the greater the psychological distress. These findings indicate that the violation of fundamental assumptions about life are an important factor determining mental health during a pandemic.

First-in-human clinical trial of transplantation of iPSC-derived NS/PCs in subacute complete spinal cord injury: Study protocol.

INTRODUCTION: Our group has conducted extensive basic and preclinical studies of the use of human induced pluripotent cell (iPSC)-derived neural stem/progenitor cell (hiPSC-NS/PC) grafts in models of spinal cord injury (SCI). Evidence from animal experiments suggests this approach is safe and effective. We are preparing to initiate a first-in-human clinical study of hiPSC-NS/PC transplantation in subacute SCI. SETTING: NS/PCs were prepared at a Good Manufacturing Practice-grade cell processing facility at Osaka National Hospital using a clinical-grade integration-free hiPSC line established by the iPSC Stock Project organized by the Kyoto University Center for iPS Cell Research and Application. After performing all quality checks, the long-term safety and efficacy of cells were confirmed using immunodeficient mouse models. METHODS: The forthcoming clinical study uses an open-label, single-arm design. The initial follow-up period is 1 year. The primary objective is to assess the safety of hiPSC-NS/PC transplantation in patients with subacute SCI. The secondary objective is to obtain preliminary evidence of its impact on neurological function and quality-of-life outcomes. Four patients with C3/4-Th10 level, complete subacute (within 24 days post-injury) SCI will be recruited. After obtaining consent, cryopreserved cells will be thawed and prepared following a multi-step process including treatment with a γ-secretase inhibitor to promote cell differentiation. A total of 2 × 106 cells will be transplanted into the injured spinal cord parenchyma 14-28 days post-injury. Patients will also receive transient immunosuppression. This study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000035074; Japan Registry of Clinical Trials [jRCT] number, jRCTa031190228). DISCUSSION/CONCLUSION: We plan to start recruiting a patient as soon as the COVID-19 epidemic subsides. The primary focus of this clinical study is safety, and the number of transplanted cells may be too low to confirm efficacy. After confirming safety, a dose-escalation study is planned.