Sick and tired: how molecular regulators of human sleep schedules and duration impact immune function.

Why do we need to sleep? What regulates when we sleep? And what dictates the number of hours we require? These are often viewed as three separate biological questions. Here, we propose they share molecular etiologies, whereby regulators of sleep schedules and sleep duration also govern the physiological purposes of sleep. To support our hypothesis, we review Mendelian human genetic variants sufficient to advance sleep-wake onset (PER2) and shorten sleep length (DEC2), and evaluate their emerging roles in immune responses that may rely on a sound night of slumber

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19

IntroductionThere remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19.MethodsBlood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured.ResultsDifferences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis.DiscussionElevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage

Evaluation of a point of care lateral flow assay for antibody detection following SARS CoV-2 mRNA vaccine series

BackgroundBreakthrough cases of SARS-CoV-2 infection correlate with decreased antibody immunity following mRNA vaccination. Measuring kinetics of vaccine efficacy using traditional laboratory approaches is more expensive and can be impractical. In this study, we evaluated the diagnostic performance of a validated COVID-19 point-of-care lateral flow assay (LFA) kit in detecting post-vaccination antibody response.MethodsWe conducted a prospective cohort study of whole blood and plasma samples to evaluate the performance of a LFA in detecting SARS-CoV-2-specific antibodies following mRNA vaccination compared to enzyme-linked immunosorbent assays (ELISAs). Health care workers at 2 tertiary centers who completed an initial BNT162b2 (n = 103) or mRNA-1273 (n = 35) vaccine series were enrolled between June and August of 2021. We performed an exploratory analysis to correlate band strength and antibody concentration of LFAs and ELISAs respectively.ResultsWhen compared to the ELISA, LFA results showed similar test positivity for plasma samples (P = 0.55), but not for whole blood samples (P < 0.001). For whole blood samples on the LFA, antibody detection differed between BNT162b2 (68.9%, 95% CI: 59.1%-77.7%) and mRNA-1273 (100%, 95% CI: 90.0%-100%, P < 0.001) vaccines. Higher plasma antibody concentrations correlated with greater LFA sensitivity. Samples with thick LFA bands had higher antibody concentrations compared to samples having faint LFA bands (81.8 arbitrary unit [AU]/mL vs. 57.1 AU/mL, P < 0.01).ConclusionsThe performance of a LFA in detecting SARS-CoV-2 antibodies was significantly better when plasma samples were used. The strength of label bands on the LFA may correlate with antibody concentration and could be a useful point-of-care monitoring tool for post-vaccine antibody status

Sleep and Anesthesia - Common mechanisms of action.

Appropriate sleep hygiene is crucial for repair in states of disease and injury and in restoring function especially in the central nervous and immune systems. Anesthetics have different action targets and ultimately different consequences. The effects of anesthetics on circadian rhythm possibly also lead to immune deregulation. α2-adrenergic agonists converge on sleep pathways within the brainstem and are associated with changes in neuronal activity similar to those seen in deeper stages of NREM sleep. Thoughtful attention must be made in selecting an anesthetic agent that best mimics natural sleep. Future studies will further elucidate the benefits of dexmedetomidine as a good anesthetic/sedative candidate. © 2013 Elsevier Inc

Sleep and Anesthesia - Common mechanisms of action.

Appropriate sleep hygiene is crucial for repair in states of disease and injury and in restoring function especially in the central nervous and immune systems. Anesthetics have different action targets and ultimately different consequences. The effects of anesthetics on circadian rhythm possibly also lead to immune deregulation. α -adrenergic agonists converge on sleep pathways within the brainstem and are associated with changes in neuronal activity similar to those seen in deeper stages of NREM sleep. Thoughtful attention must be made in selecting an anesthetic agent that best mimics natural sleep. Future studies will further elucidate the benefits of dexmedetomidine as a good anesthetic/sedative candidate. © 2013 Elsevier Inc.

Pneumococcal serotypes associated with invasive disease in under five children in India & implications for vaccine policy

Background & objectives: Streptococcus pneumoniae is a major cause of morbidity and mortality especially in children less than five years, particularly in India. We present data on S.pneumoniae infections in children less than five years age group, with response to its serotype distribution, antibiotic resistance profile and available vaccines expected coverage. Methods: Children aged less than five, who were suspected for invasive pneumococcal disease were included in the study and their sterile body fluids were investigated for the presence of S. pneumoniae. Invasive S. pneumoniae isolates from sterile body fluids were identified by bile solubility and optochin susceptibility test. Pneumococcal serotyping was performed with co-agglutination technique and reconfirmed with multiplex PCR. Results: The most common pneumococcal serotypes causing invasive infections in children less than five years of age were 14, 19F, 5, 6A and 6B. Of the 114 S. pneumoniae isolates studied, 110 (96.4%) were non-susceptible to co-trimoxazole and 30 per cent were non-susceptible to erythromycin, 5.2 per cent of the isolates were non-susceptible to penicillin and only 0.8 per cent was non-susceptible to cefotaxime. Interpretation & conclusions: Our results indicate that PCV-10 can protect against 64 per cent of serotypes causing invasive pneumococcal infections. Use of PCV-13 in this region can provide increase in protection upto 74.6 per cent against serotypes causing invasive pneumococcal infections. Incorporating PCV-13 in the Universal Immunization Programme may provide incremental protection against IPD serotypes in the southern region of the country

Real-time Dynamic Hydraulic Model for Potable Water Loss Reduction

AbstractSouth Africa is a water scarce country with limited water resources and steadily growing water demand. Unacceptably high water losses and non-revenue water threaten our water resource security as well as the financial viability of municipal water service provision. Traditional approaches of solving water loss problems are not enough to make a significant improvement; for this, new approaches involving increased automation and monitoring are needed. Furthermore, the sensory and automation ICT-overlay required for the WDN can itself be a cause of technical problems that also need to be solved before water utilities will implement these techniques. This paper propose a real-time dynamic hydraulic model (DHM) based control system connected to near real-time sensing and actuation capability on the WDN as an effective approach to implementing an efficient, reliable and adaptive WDN. This is in contrast to current design and operation of most WDNs that rely on steady-state hydraulic models which have inherent limitations with respect to reliability and efficiency