Key Points
Question
Based on the current understanding of the associations between school disruption and decreased educational attainment and between decreased educational attainment and lower life expectancy, is it possible to estimate the association between school closure during the coronavirus disease 2019 pandemic and decreased life expectancy of publicly educated primary school–aged children in the United States?
Findings
This decision analytical model found that missed instruction during 2020 could be associated with an estimated 5.53 million years of life lost. This loss in life expectancy was likely to be greater than would have been observed if leaving primary schools open had led to an expansion of the first wave of the pandemic.
Meaning
These findings suggest that the decision to close US public primary schools in the early months of 2020 may be associated with a decrease in life expectancy for US children.
Although nicotinic agonists can modulate sensory transmission, particularly nociceptive signaling, remarkably little is known about the functional expression of nicotinic acetylcholine receptors (nAChRs) on primary sensory neurons. We have utilized molecular and electrophysiological techniques to characterize the functional diversity of nAChR expression on mammalian dorsal root ganglion (DRG) neurons. RT-PCR analysis of subunit mRNA in DRG tissue revealed the presence of nAChR subunits alpha2-7 and beta2-beta4. Using whole cell patch-clamp recording and rapid application of nicotinic agonists, four pharmacologically distinct categories of nicotinic responses were identified in cultured DRG neurons. Capacitance measurements were used to divide neurons into populations of large and small cells, and the prevalence of nicotinic responses was compared between groups. Category I (alpha7-like) responses were seen in 77% of large neurons and 32% of small neurons and were antagonized by 10 nM methyllycaconitine citrate (MLA) or or 50 nM alpha-bungarotoxin (alpha-BTX). Category II (alpha3beta4-like) responses were seen in 16% of large neurons and 9% of small neurons and were antagonized by 20 microM mecamylamine but not 10 nM MLA or 1 microM DHbetaE. Category II responses had a higher sensitivity to cytisine than nicotine. Two other types of responses were identified in a much smaller percentage of neurons and were classified as either category III (alpha4beta2-like) or category IV (subtype unknown) responses. Both the alpha7-like and alpha3beta4-like responses could be desensitized by prolonged applications of the analgesic epibatidine.
Recombinant human parainfluenza virus type 1 (HPIV1) and mutants containing point and deletion (Delta) mutations in the P/C gene (r-CDelta10-15HNT553A, r-CR84G, r-CF170S and r-CDelta170), which have previously been evaluated as HPIV1 vaccine candidates, were evaluated for their effect on the type I interferon (IFN) response in vitro. HPIV1 wt infection inhibited the IFN response by inhibiting IFN regulatory factor-3 (IRF-3) activation and IFN production in A549 cells and IFN signaling in Vero cells. In contrast, r-CR84G, r-CF170S and r-CDelta170 were defective for inhibition of IRF-3 activation and IFN production and r-CF170S and r-CDelta170 did not inhibit IFN signaling. Thus, HPIV1 antagonizes the IFN response at both the level of induction and signaling, and antagonism at both levels was disrupted by mutations in the P/C gene. Because CF170S affects C and not P, the anti-IFN function can be attributed to the C proteins. These data, in the context of previous in vivo studies, suggest that the loss of antagonism of the IFN response at both the level of induction and signaling, observed with the P/C mutants, r-CF170S and r-CDelta170, was necessary for significant attenuation in African green monkeys (AGMs).
Globally, pneumonia is the leading cause of death in children <5 years of age. Hypoxemia, a frequent complication of pneumonia, is a risk factor for death. To better understand the availability of oxygen and pulse oximetry, barriers to use and provider perceptions and practices regarding their role in childhood pneumonia, we conducted a survey using a convenience sampling strategy targeting clinicians working in resource-limited countries. Most respondents were physicians from public district and provincial hospitals with access to oxygen and pulse oximetry; however, reported therapeutic use for childhood pneumonia was low. Common barriers included insufficient supply, competition for use, lack of policies, guidelines and training and perceived high cost. Despite the frequency of hypoxemia, the inaccuracy of clinical predictors, the poor outcome hypoxemia portends and the effectiveness of pulse oximetry and oxygen in childhood pneumonia, our data indicate that these tools may be underused in resource-limited settings.
Introduction Distinguishing pulmonary edema due to acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) from hydrostatic or cardiogenic edema is challenging in critically ill patients. B-type natriuretic peptide (BNP) can effectively identify congestive heart failure in the emergency room setting but, despite increasing use, its diagnostic utility has not been validated in the intensive care unit (ICU).
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