Background

Breakthrough 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.

Methods

We 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.

Results

When 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).

Conclusions

The 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.

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.

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.

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.

Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by designer drugs (DREADD) chemogenetic approach. With injection of adeno-associated virus into the orexin-Cre transgenic mouse brain, we expressed the DREADD receptor hM3Dq specifically in orexin neurons and applied the hM3Dq ligand clozapine to activate orexin neurons. We monitored orexin neuronal activities by c-Fos staining and whole-cell patch-clamp recording and examined the consequence of orexin neuronal activation via EEG recording. Our results revealed that the orexin-DREADD mice with activated orexin neurons emerged from anesthesia with significantly shorter latency than the control mice. As an indication of reduced pain sensitivity, these orexin-DREADD mice took longer to respond to the 55 °C thermal stimuli in the hot plate test and exhibited significantly less frequent licking of the formalin-injected paw in the formalin test. Our study suggests that approaches to activate the orexin system can be beneficial in postoperative recovery.

Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by designer drugs (DREADD) chemogenetic approach. With injection of adeno-associated virus into the orexin-Cre transgenic mouse brain, we expressed the DREADD receptor hM3Dq specifically in orexin neurons and applied the hM3Dq ligand clozapine to activate orexin neurons. We monitored orexin neuronal activities by c-Fos staining and whole-cell patch-clamp recording and examined the consequence of orexin neuronal activation via EEG recording. Our results revealed that the orexin-DREADD mice with activated orexin neurons emerged from anesthesia with significantly shorter latency than the control mice. As an indication of reduced pain sensitivity, these orexin-DREADD mice took longer to respond to the 55 °C thermal stimuli in the hot plate test and exhibited significantly less frequent licking of the formalin-injected paw in the formalin test. Our study suggests that approaches to activate the orexin system can be beneficial in postoperative recovery.

Many components of the circadian molecular clock are conserved from flies to mammals; however, the role of mammalian Timeless remains ambiguous. Here, we report a mutation in the human TIMELESS (hTIM) gene that causes familial advanced sleep phase (FASP). Tim CRISPR mutant mice exhibit FASP with altered photic entrainment but normal circadian period. We demonstrate that the mutation prevents TIM accumulation in the nucleus and has altered affinity for CRY2, leading to destabilization of PER/CRY complex and a shortened period in nonmature mouse embryonic fibroblasts (MEFs). We conclude that TIM, when excluded from the nucleus, can destabilize the negative regulators of the circadian clock, alter light entrainment, and cause FASP.

Veteran access to sleep medicine is of paramount importance to the Veterans Health Administration (VA). To increase access, VA has created community referral policies and programs, as well as telehealth programs. In 2017, the Office of Rural Health (ORH) funded a TeleSleep initiative focused on reaching rural Veterans with unmet sleep needs. ORH provided 3-6 years of funding to help 19 hubs support 98 spoke sites serving rural Veterans. As ORH funding concluded, each hub identified its path to sustainment. This case study follows one TeleSleep hub in VAs western geographic region as it transitioned from ORH funding sustainment as a regional Sleep Clinical Resource Hub. This case study describes the real-world process of adaptation in care delivery strategies. One key area of adaptation revolved around whether to deliver care via the patients home facility or the providers home facility. In early 2021, the TeleSleep team implemented an innovative provider transfer model, where temporary reinforcements from the TeleSleep hub increased the workforce capacity of spoke sites, similar to the concept of locum tenens. In this provider transfer model, TeleSleep clinicians scheduled, documented, and billed for each encounter at the Veterans home facility. Positioning TeleSleep clinicians as local providers facilitated communication and referrals and promoted continuity and quality of care for Veterans in their home facility. This provider transfer model reduced the administrative burden of providers and schedulers and supported patient-side-only documentation of care. While this mirrors current locum tenens practice, transferring providers did not fit VAs financial model as implemented by the western regions Sleep Clinical Resource Hub. Therefore, in December 2021, VA aligned TeleSleep with VAs preferred practice of patient rather than provider transfers. In the patient transfer model, providers schedule and document in both the provider and patient electronic health records, and bill in the providers facility. However, reflecting on this period of innovation, TeleSleep team members concluded that the provider transfer model could improve patient safety and care coordination while reducing the administrative burden of frontline clinicians. Further research and development are needed to align the provider transfer model with VAs financial model.

Background

The mechanisms of aberrant circulating platelet behavior following injury remain unclear. Platelets retain megakaryocyte immature ribonucleic acid (RNA) splicing and protein synthesis machinery to alter their functions based on physiologic signals. We sought to identify fluctuating platelet-specific RNA transcripts in cell-free plasma (CFP) from traumatic brain injury (TBI) patients as proof-of-concept for using RNA sequencing to improve our understanding of postinjury platelet behavior. We hypothesized that we could identify differential expression of activated platelet-specific spliced RNA transcripts from CFP of patients with isolated severe fatal TBI (fTBI) compared with minimally injured trauma controls (t-controls), filtered by healthy control (h-control) data sets.

Methods

High-read depth RNA sequencing was applied to CFP from 10 patients with fTBI (Abbreviated Injury Scale [AIS] for head ≥3, AIS for all other categories <3, and expired) and five t-controls (Injury Severity Score ≤1, and survived). A publicly available CFP RNA sequencing data set from 23 h-controls was used to determine the relative steady state of splice-form RNA transcripts discoverable in CFP. Activated platelet-specific spliced RNA transcripts were derived from studies of ex vivo platelet activation and identified by splice junction presence greater than 1.5-fold or less than 0.67-fold ex vivo nonactivated platelet-specific RNA transcripts.

Results

Forty-two differentially spliced activated platelet-specific RNA transcripts in 34 genes were altered in CFP from fTBI patients (both upregulated and downregulated).

Conclusion

We have discovered differentially expressed activated platelet-specific spliced RNA transcripts present in CFP from isolated severe fTBI patients that are upregulated or downregulated compared with minimally injured trauma controls. This proof-of-concept suggests that a pool of immature platelet RNAs undergo splicing events after injury for presumed modulation of platelet protein products involved in platelet function. This validates our exploration of injury-induced platelet RNA transcript modulation as an upstream "liquid biopsy" to identify novel postinjury platelet biology and treatment targets for aberrant platelet behavior.

Level of evidence

Diagnostic tests, level V.