Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota.

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19

Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset

Mariana G Figueiro, Barbara Plitnick, Mark S Rea Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA Abstract: Circadian rhythm disturbances parallel the increased prevalence of sleep disorders in older adults. Light therapies that specifically target regulation of the circadian system in principle could be used to treat sleep disorders in this population. Current recommendations for light treatment require the patients to sit in front of a bright light box for at least 1 hour daily, perhaps limiting their willingness to comply. Light applied through closed eyelids during sleep might not only be efficacious for changing circadian phase but also lead to better compliance because patients would receive light treatment while sleeping. Reported here are the results of two studies investigating the impact of a train of 480 nm (blue) light pulses presented to the retina through closed eyelids on melatonin suppression (laboratory study) and on delaying circadian phase (field study). Both studies employed a sleep mask that provided narrowband blue light pulses of 2-second duration every 30 seconds from arrays of light-emitting diodes. The results of the laboratory study demonstrated that the blue light pulses significantly suppressed melatonin by an amount similar to that previously shown in the same protocol at half the frequency (ie, one 2-second pulse every minute for 1 hour). The results of the field study demonstrated that blue light pulses given early in the sleep episode significantly delayed circadian phase in older adults; these results are the first to demonstrate the efficacy and practicality of light treatment by a sleep mask aimed at adjusting circadian phase in a home setting. Keywords: circadian phase, dim light melatonin onset, light through closed eyelids, blue light, slee

Effects of red light on sleep inertia

Mariana G Figueiro,1 Levent Sahin,1 Charles Roohan,1 Michael Kalsher,2 Barbara Plitnick,1 Mark S Rea11Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; 2Department of Cognitive Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USAIntroduction: Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia.Methods: Thirty participants (18 females, 12 males; mean age=30.4 years [SD 13.7]) completed this crossover, within-subjects, counterbalanced design study. Self-reported measures of sleepiness and objective measures of auditory performance and cortisol levels were collected on 3 Friday nights over the course of 3 consecutive weeks.Results: Performance improved significantly during the 30-min data collection period in all experimental conditions. Subjective sleepiness also decreased significantly with time awake in all experimental conditions. As hypothesized, performance of some tasks was significantly better in the red light mask condition than in the dim light condition. Performance scores in the red light goggles condition improved significantly after a few minutes of wearing the light goggles.Discussion: The results show that saturated red light delivered through closed eyelids at levels that do not suppress melatonin can be used to mitigate sleep inertia upon waking.Keywords: sleep inertia, cognitive performance, alertness, red light, closed eyelid

Lipoteichoic Acid Inhibits Interleukin-2 (IL-2) Function by Direct Binding to IL-2

Lipoteichoic acid (LTA) is associated with the cell envelope of most gram-positive bacteria. Although previously thought to act mainly as a virulence factor by virtue of its adhesive nature, evidence is now provided that LTA can also suppress the function of interleukin-2 (IL-2), an autocrine growth factor for T cells. LTA from four separate bacterial strains lowered the levels of detectable IL-2 during a peripheral blood mononuclear cell response to the antigen tetanus toxoid (TT). T-cell proliferation in response to TT was similarly inhibited by LTA. In contrast, levels of detectable gamma interferon increased. In addition, LTA inhibited IL-2 detection by enzyme-linked immunosorbent assay (ELISA) and blocked the proliferative response of an IL-2-dependent T-cell line to soluble IL-2. Further studies using ELISA demonstrated that LTA blocks IL-2 detection and function by binding directly to IL-2. Flow cytometric analysis revealed that IL-2 binding to T cells is inhibited in the presence of purified LTA but not LTA plus anti-LTA monoclonal antibody. In summary, these studies demonstrate a novel effect of LTA on the immune response through direct binding to IL-2 and inhibition of IL-2 function. Importantly, gram-positive organisms from which LTA is obtained not only play an important role in the pathology of diseases such as bacterial endocarditis, septic shock, acute respiratory distress syndrome, and multiple organ failure but also comprise a significant portion of commensal populations within the human host. Inhibition of IL-2 function by LTA may represent yet another mechanism by which gram-positive bacteria dampen the host immune response and facilitate survival. Thus, LTA provides a potential target for therapeutic intervention when gram-positive organisms are involved

Challenges and approaches for the development of safer immunomodulatory biologics

Immunomodulatory biologics are a class of agents that render their therapeutic effect via modulating or harnessing immune responses. Despite their therapeutic efficacy in complex conditions including cancer and autoimmune diseases, there is a growing concern about their unwanted adverse events including infections, malignancy, cytokine release syndromes, anaphylaxis, hypersensitivity and immunogenicity. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the key approaches to understand, predict and mitigate adverse events associated with their use