Evaluation of "Test to Return" after COVID-19 Diagnosis in a Massachusetts Public School District.

BACKGROUND: Per Centers for Disease Control and Prevention guidance, students with COVID-19 may end isolation after 5 days if symptoms are improving; some individuals may still be contagious. Rapid antigen testing identifies possibly infectious virus. We report on a test-to-return (TTR) program in a Massachusetts school district to inform policy decisions about return to school after COVID-19. METHODS: During the 2021-2022 Omicron BA.1 surge, students with COVID-19 could return on day 6-10 if they met symptom criteria and had a negative rapid test; students with positive rapid tests and those who declined TTR remained isolated until day 11. TTR positivity rates were compared by grade level, vaccination status, symptom status, and day of infection. RESULTS: 31.4% of students had a positive TTR rapid test; there were no differences by grade or vaccination status. Ever-symptomatic students were more likely to have a positive rapid test (75/174 [43.1%] vs 18/104 [17.3%]). For ever-symptomatic students, TTR positivity decreased by day of infection. CONCLUSIONS: A substantial proportion of students may still be contagious 6 days after onset of COVID-19 infection. TTR programs may increase or reduce missed school days, depending on when return is otherwise allowed (day 6 or 11). The impact of TTR programs on school-associated transmission remains unknown.

Medical student education in sleep and its disorders is still meagre 20 years on: A cross-sectional survey of UK undergraduate medical education.

Sleep is a pillar of health, alongside adequate nutrition and exercise. Problems with sleep are common and often treatable. Twenty years ago, UK medical school education on sleep disorders had a median teaching time of 15 min; we investigate whether education on sleep disorders has improved. This is a cross-sectional survey, including time spent on teaching sleep medicine, subtopics covered and forms of assessment. Thirty-four medical degree courses in the UK were investigated via a questionnaire. We excluded responses not concerned with general undergraduate education (i.e. optional modules). Twenty-five (74%) medical schools responded. Time spent teaching undergraduates sleep medicine was: median, 1.5 hr; mode, <1 hr; mean, 3.2 hr (SD = 2.6). Only two schools had a syllabus or core module (8%) and five (22%) were involved in sleep disorders research. Despite the above, half of the respondents thought provision was sufficient. Free-text comments had recurring themes: sleep medicine is subsumed into other specialties, obstructive sleep apnea dominates teaching, knowledge of sleep disorders is optional, and there is inertia regarding change. A substantial minority of respondents were enthusiastic about improving provision. In conclusion, little has changed over 20 years: sleep medicine is neglected despite agreement on its importance for general health. Sleep research is the exception rather than the rule. Obstacles to change include views that "sleep is not a core topic" or "the curriculum is too crowded". However, there is enthusiasm for improvement. We recommend establishment of a sleep medicine curriculum. Without better teaching, doctors will remain ill-equipped to recognize and treat these common conditions.

Incorporation of three endocytosed varicella-zoster virus glycoproteins, gE, gH, and gB, into the virion envelope.

The cytoplasmic tails of all three major varicella-zoster virus (VZV) glycoproteins, gE, gH, and gB, harbor functional tyrosine-based endocytosis motifs that mediate internalization. The aim of the present study was to examine whether endocytosis from the plasma membrane is a cellular route by which VZV glycoproteins are delivered to the final envelopment compartment. In this study, we demonstrated that internalization of the glycoproteins occurred in the first 24 h postinfection but was reduced later in infection. Using surface biotinylation of VZV-infected cells followed by a glutathione cleavage assay, we showed that endocytosis was independent of antibody binding to gE, gH, and gB. Subsequently, with this assay, we demonstrated that biotinylated gE, gH, and gB retrieved from the cell surface were incorporated into nascent virus particles isolated after density gradient sedimentation. To confirm and extend this finding, we repeated the above sedimentation step and specifically detected envelopes decorated with Streptavidin-conjugated gold beads on a majority of complete virions through examination by transmission electron microscopy. In addition, a gE-gI complex and a gE-gH complex were found on the virions. Therefore, the above studies established that VZV subsumed a postendocytosis trafficking pathway as one mechanism by which to deliver viral glycoproteins to the site of virion assembly in the cytoplasm. Furthermore, since a recombinant VZV genome lacking only endocytosis-competent gE cannot replicate, these results supported the conclusion that the endocytosis-envelopment pathway is an essential component of the VZV life cycle.

Comparison of varicella-zoster virus ORF47 protein kinase and casein kinase II and their substrates.

ORF47, a serine/threonine protein kinase encoded by varicella-zoster virus (VZV), has often been compared to the ubiquitous cellular kinase, casein kinase II (CKII). However, no direct comparison of the two protein kinases has been carried out. Herein, we show that the ORF47 kinase was resistant to heparin, while CKII activity is profoundly inhibited by the acidic molecule in vitro. ORF47 required the presence of polyamines (aliphatic, positively-charged molecules) for in vitro activity. When polyamines were depleted from MeWo cells prior to VZV infection by pretreatment with D,L-alpha-difluoromethylornithine, VZV replication was reduced by 80%. Finally, the substrate specificity of the ORF47 kinase was defined using an in vitro assay. The ORF47 kinase phosphorylated maltose-binding protein, the mouse IgG2A heavy chain, the rabbit IgG heavy chain, casein, VZV ORF62, and VZV ORF63. The ORF47 kinase failed to phosphorylate an ORF62 truncation mutant, glutathione-S-transferase, or VZV gB. In contrast, CKII weakly phosphorylated VZV gB in vitro. By analyzing the sequences of these substrates, the minimal ORF47 consensus sequence was deduced to be the following motif: S/T-X-D/E-D/E, with a marked preference for additional acidic amino acids in the -1 and +1 position.