clusion The prevalence of primary aldosteronism is high and largely unrecognized. Beyond this categorical definition of primary aldosteronism, there is a prevalent continuum of renin-independent aldosterone production that parallels the severity of hypertension. These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of “essential” hypertension. Primary funding source National Institutes of Health.Background A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Methods We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by eny. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. Funding National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.Astroglial complexity and pleomorphism have increased significantly with hominid evolution. This suggests a potential association between glial evolution and the development of human cognition, as well as between glial evolution and the advent of human-selective neurodegenerative and neuropsychiatric disorders.Background The concept of prefrailty lacks clarity. Often, prefrailty is defined in relation to frailty and less often as a distinct concept. VEGFR inhibitor Theoretical evidence for prefrailty is minimal unlike frailty, which has been examined for decades although consensus about how to measure frailty has not been achieved. Objective The aim of this study was to conduct a concept analysis of prefrailty to provide greater understanding of this phenomenon in the context of older adults. Design Rodgers and Knafl’s evolutionary concept analysis approach. Data sources The literature search for the concept analysis was conducted as follows three databases (MEDLINE, CINAHL, and Abstracts in Social Gerontology databases) were searched using carefully selected search terms; and grey literature was not included. Review methods In phase one, we used the search strategy and search terms to narrow the search for relevant articles. We selected articles that met the following inclusion criteria (1) how prefrailty was conceptualized; (2) of frailty. Surrogate and related terms (noted in the literature) that had shared attributes with prefrailty were increased vulnerability, transitional stage, dynamic process, progressive process with latent phase, and physical frailty. Conclusions As a result of conducting this concept analysis, we found that prefrailty was defined as a clinically silent process that predisposes individuals to frailty. Prefrailty, as a concept, was derived from the Fried’s operational definition for frailty. Attributes, antecedents, consequences, and related terms will help clinicians consider how prefrailty presents in older adults separate from frailty. Further research is needed to build upon our understanding from this concept analysis. Tweetable Abstract Prefrailty is unclear as a concept – Research on sociodemographic characteristics of older adults living with frailty will help clarify.Cellular senescence is mainly characterized as a stable proliferation arrest and a senescence associated secretory phenotype (SASP). Senescence is triggered by diverse stimuli such as telomere shortening, oxidative stress, oncogene activation and DNA damage, and consequently contributes to multiple physiology and pathology outcomes, including embryonic development, wound healing and tumor suppression as well as aging or age-associated diseases. Interestingly, therapeutic clearance of senescent cells in tissues has recently been demonstrated to be beneficial for extending a healthy lifespan and for improving numerous age-related disorders. However the molecular mechanisms of senescence regulation remain partially understood. Theoretically, senescence is tightly regulated by a vast number of molecules, among which the p16 and p53 pathways are the most classical. In addition, intracellular cellular calcium signaling has emerged as a key regulator of senescence. In the last few decades, a growing number of studies have demonstrated that microRNAs (miRNAs, small non-coding RNAs) are strongly implicated in controlling senescence, especially at the transcriptional and post-transcriptional levels. In this review we will discuss the involvement of miRNAs in modulating senescence through the major p16, p53, SASP and calcium signaling pathways, thus aiming to reveal the mechanisms of how miRNAs regulate cellular senescence.Objectives To detect possible SARS-CoV-2 RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with COVID-19. Methods Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. Results Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of Continuous Positive Airway Pressure (CPAP) helmets. All transport media were inoculated onto susceptible cells, however, none induced a cytopathic effect on day 7 of culture. Conclusions Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real life conditions suggest that it might be less extensive than hitherto recognized.