Association of social vulnerability index and masking adherence among children enrolled in COVID-19 community research partnership study.

BACKGROUND: Individuals with high social vulnerability index (SVI) have poorer outcomes with COVID-19. Masking reduces transmission of COVID-19 among children, but how SVI plays a role in masking behavior is unknown. We aimed to measure the association of SVI with masking adherence among children during the COVID-19 pandemic. METHODS: We conducted a multi-site, prospective syndromic surveillance study among children aged 2 - 17 years in the Southeastern United States by daily electronic surveys which solicited symptoms of COVID-19-like illness, infection with or exposure to SARS-CoV-2, masking habits, and any receipt of COVID-19 vaccines. Parents/guardians submitted surveys for their children; adolescents 13 years and older could opt to submit their own surveys. Multivariable and univariate linear models were used to measure the associations of different predictors such as SVI with masking adherence. RESULTS: One thousand four hundred sixty-one children from 6 states and 55 counties predominately from North and South Carolina were included in the analysis. Most children in the cohort were 5 - 11 years old, non-Hispanic White, from urban counties, and with low-moderate SVI. Overall masking adherence decreased over time, and older children had higher masking adherence throughout the study period compared with younger children. Children who resided in urban counties had greater masking adherence throughout the study period than those who resided in suburban or rural counties. Masking adherence was higher among children with both low and medium SVI than those with high SVI. CONCLUSIONS: Despite being at risk for more severe outcomes with COVID-19, children with high SVI had lower levels of masking adherence compared to those with low SVI. Our findings highlight opportunities for improved and targeted messaging in these vulnerable communities.

Characterisation of infection-induced SARS-CoV-2 seroprevalence amongst children and adolescents in North Carolina.

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2-17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0-22.0) in May 2021 to 54.1% (95% CrI 46.7-61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12-17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection.

Feasibility of At-Home Virological and Serological Testing for SARS-CoV-2 in Children.

Longitudinal virological and serological surveillance is essential for understanding severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) transmission among children but requires increased test capacity. We assessed the uptake of serial at-home testing in children (2-17 years) via mailed SARS-CoV-2 antibody and molecular tests. Completion rates demonstrated the feasibility and sustainability of at-home testing across age groups.

Diagnostic potential of the diffusion tensor tractography with fractional anisotropy in the diagnosis and treatment of cervical spondylotic and posttraumatic myelopathy.

BACKGROUND: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI)-based methodology widely used for the evaluation of microstructural integrity of the central nervous system (CNS), particularly of brain white matter fibers and bundles. METHODS: The most common parameters evaluated in a DTI study are the fractional anisotropy (FA) and mean diffusivity (MD). Combining FA and MD analyses is commonly used in the evaluation of various types of brain pathologies, such as brain tumors, where a combined analysis allows an accurate tumor characterization. RESULTS: Recent studies have shown that FA and MD could be of value in non-oncologic spinal pathology. In this regard, it has been demonstrated that DTI can provide new insights into the diagnosis and prognosis of cervical spondylotic myelopathy and cervical spinal cord injury. CONCLUSIONS: Further studies are needed to assess the role of DTI in such a new clinical scenario.

Effect of N-arachidonoyl-l-serine on human cerebromicrovascular endothelium.

N-arachidonoyl-l-serine (ARA-S) is an endogenous lipid, chemically related to the endocannabinoid, N-arachidonoyl ethanolamine (i.e., anandamide) and with similar physiologic and pathophysiologic functions. Reports indicate that ARA-S possesses vasoactive and neuroprotective properties resembling those of cannabinoids. However, in contrast to cannabinoids, ARA-S binds weakly to its known classical receptors, CB1 and CB2, and is therefore considered to be a 'cannabinoid-like' substance. The originally described ARA-S induced-endothelial-dependent vasorelaxation was not abrogated by CB1, CB2 receptor antagonists or TRPV1 competitive inhibitor. The present report demonstrates that ARA-S enhances the fluorescence staining of both cannabinoid receptors (CB1 and CB2) in human brain endothelial cells (HBEC). This reaction is specific since it was reduced by respective selective receptor antagonist (SR141716A and SR141728A). ARA-S alone or in the presence of ET-1 was shown to alter the cytoskeleton (actin). Both ARA-S stimulated phosphorylation of various kinases (MAPK, Akt, JNK and c-JUN) and alteration of cytoskeleton are mediated via CB1, CB2 and TRPV1 receptors. The findings also showed the involvement of Rho/Rock and PI3/Akt/NO pathways in the ARA-S-induced phosphorylation of kinases and actin reorganization in HBEC. All of the above mentioned ARA-S-induced effects were reduced by the treatment with LY294002 (inhibitor of PI3/Akt kinase), except MAPK kinase. In addition, MAPK, JNK, c-JUN phosphorylation were inhibited by H1152 (inhibitor of Rho/ROCK kinase), except Akt kinase. Furthermore, PI3/Akt pathway was inhibited by pretreatment with l-NAME (inhibitor of NOS). The findings suggest that ARA-S is a modulator of Rho kinase and may play a critical role in the regulation of its activity and subsequent effects on the cytoskeleton and its role in supporting essential cell functions like vasodilation, proliferation and movement.

Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, D-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented. Mammalian hibernation provides a valuable model of tolerance to ischemic stress. Herein, we demonstrate that marked reductions in the phosphorylation of ribosomal protein S6 (rpS6), extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinase p44/42 (p44/42MAPK) and ribosomal protein S6 kinase (S6K) occur within the brains of both hibernating squirrels and rats, which have undergone an ischemic preconditioning paradigm. We therefore propose that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning, via a suppression of protein synthesis and/or energy consumption.

Poly(ADP-ribose) polymerase-1 and its cleavage products differentially modulate cellular protection through NF-kappaB-dependent signaling.

Poly(ADP-ribose) polymerase-1 (PARP-1) and its cleavage products regulate cell viability and NF-kappaB activity when expressed in neurons. PARP-1 cleavage generates a 24 kDa (PARP-1(24)) and an 89 kDa fragment (PARP-1(89)). Compared to WT (PARP-1WT), the expression of an uncleavable PARP-1 (PARP-1(UNCL)) or of PARP-1(24) conferred protection from oxygen/glucose deprivation (OGD) or OGD/restoration of oxygen and glucose (ROG) damage in vitro, whereas expression of PARP-1(89) was cytotoxic. Viability experiments were performed in SH-SY5Y, a human neuroblastoma cell line, as well as in rat primary cortical neurons. Following OGD, the higher viability in the presence of PARP-1UNCL or PARP-1(24) was not accompanied with decreased formation of poly(ADP-riboses) or higher NAD levels. PARP-1 is a known cofactor for NF-kappaB, hence we investigated whether PARP-1 cleavage influences the inflammatory response. All PARP-1 constructs mimicked PARP-1WT in regard to induction of NF-kappaB translocation into the nucleus and its increased activation during ischemic challenge. However, expression of PARP-1(89) construct induced significantly higher NF-kB activity than PARP-1WT; and the same was true for NF-kappaB-dependent iNOS promoter binding activity. At a protein level, PARP-1UNCL and PARP-1(24) decreased iNOS (and lower levels of iNOS transcript) and COX-2, and increased Bcl-xL The increased levels of NF-kB and iNOS transcriptional activities, seen with cytotoxic PARP-189, were accompanied by higher protein expression of COX-2 and iNOS (and higher levels of INOS transcript) and lower protein expression of Bcl-xL Taken together, these findings suggest that PARP-1 cleavage products may regulate cellular viability and inflammatory responses in opposing ways during in vitro models of "ischemia".

SUMOylation participates in induction of ischemic tolerance.

Ground squirrels in hibernation torpor have been shown to have striking increases in global SUMOylation on tissue immunoblots. Here, we find evidence that global SUMOylation is also involved in ischemic tolerance in primary cortical neuronal cultures (from rats and mice) and SHSY5Y human neuroblastoma cells. Cultured cortical neurons preconditioned by sublethal oxygen/glucose deprivation (OGD) were less vulnerable to severe OGD than non-preconditioned neurons. Preconditioned neurons maintained elevated SUMO-1 conjugation levels (and, to a lesser extent those of SUMO-2/3) on western blots in contrast to non-preconditioned cells. Further, cortical neurons and SHSY5Y cells in which transfected SUMO-1 or SUMO-2 were over-expressed showed increased survival after severe OGD. In contrast, cell cultures subjected to depletion of endogenous SUMO-1 protein by RNAi had reduced survival after exposure to this form of in vitro ischemia and an attenuated protective response to preconditioning. These findings suggest that maintenance of a globally elevated SUMO-1 (and maybe SUMO-2/3) conjugation level as revealed by immunoblot assays is a component of ischemic tolerance.

Reduced insulin-induced phosphatidylinositol-3-kinase activation in peripheral blood mononuclear leucocytes from patients with Alzheimer's disease.

The epidemiological finding of an increased risk of dementia in patients with diabetes mellitus has raised the hypothesis that a dysfunction of the insulin receptors plays a role in the pathogenesis of Alzheimer's disease (AD). A possible link is suggested by the evidence that the insulin-stimulated phosphatidylinositol-3-kinase (PI-3-K)/phospho-Akt pathway negatively controls the glycogen synthase kinase-3beta. The activation of this enzyme mediates the hyperphosphorylation of the tau protein, a relevant step in the formation of the neurofibrillary tangles associated with AD. We hypothesized that the neurodegeneration associated with AD is related to an impairment of the intracellular signalling stimulated by insulin receptors. To test this hypothesis we assessed the PI-3-K/phospho-Akt pathway following in-vitro challenge with insulin in peripheral blood mononuclear cells from subjects with AD (n = 20) and controls (n = 20). We found that the stimulation of PI-3-K is blunted in patients with AD with respect to control. The reduction did not correlate with the extent of cognitive decline or with scores at neuropsychological tests exploring attention, memory, language or visuospatial abilities. The study supports the hypothesis that an impaired control of glycogen synthase kinase-3beta activity by insulin receptor-mediated signalling plays a role in the pathogenesis of AD, facilitating tau protein phosphorylation and neurofibrillary tangle formation.

Protection by apomorphine in two independent models of acute inhibition of oxidative metabolism in rodents.

Apomorphine was administered by continuous infusion in the mouse following acute inhibition of oxidative metabolism induced by systemic administration of MPTP, and in the gerbil following transient occlusion of the carotid arteries. The dosage employed was comparable to the one used in the treatment of severe on-off fluctuations in Parkinson's disease. The results show that apomorphine significantly diminishes the striatal lesion caused by MPTP and the size of the infarct associated with the transient global ischemia. These data suggest that apomorphine is neuroprotective, probably by means of an antioxidant effect, at doses that are clinically used. The finding may be relevant to brain ischemia as well to chronic neurodegeneration.