Camposkorsgaard0338

Respiratory Syncytial virus (RSV) is a major threat to many vulnerable populations. There are currently no approved vaccines, and RSV remains a high unmet global medical need. Here we describe the employment of a novel synthetic DNA-encoded antibody technology platform to develop and deliver an engineered human DNA-encoded monoclonal antibody (dMAbTM) targeting the fusion protein (F) of RSV as a new approach to prevention or therapy of at risk populations. In in vivo models, a single administration of synthetic DNA-encoding the single-chain fragment variable-constant fragment (scFv-Fc) RSV-F dMAb resulted in robust and durable circulating levels of a functional antibody systemically and in mucosal tissue. In cotton rats, which are the gold-standard animals to model RSV infection, we observed sustained scFv-Fc RSV-F dMAb in the sera and lung-lavage samples, demonstrating the potential for both long-lasting immunity to RSV and effective biodistribution. The scFv-Fc RSV-F dMAb harbored in the sera exhibited RSV antigen-specific binding and potent viral neutralizing activity. Importantly, in vivo delivery of synthetic DNA-encoding, the scFv-Fc RSV-F dMAb protected animals against viral challenge. Our findings support the significance of dMAbs as a potential platform technology for durable protection against RSV disease.This study examined core belief violation and meaning making as mechanisms mediating the relationship between adherence to social isolation policies for mitigating coronavirus transmission and reduced coronavirus anxiety (CA). Adherence to social isolation policies (social distancing, sheltering in place, and cessation of long-distance travel), use of nonsocial precautionary measures (handwashing, wearing a mask), core belief violation, meaning made of the COVID pandemic, and CA were assessed in a sample of 408 North Americans. Process analysis revealed that adhering to social isolation policies predicted lower levels of CA and that this effect was largely mediated by conservation of core beliefs (e.g., in predictability, control, and self-agency) and ability to make meaning of the pandemic. see more In contrast, exclusive reliance on nonsocial protections such as handwashing and mask wearing was associated with high levels of CA. These results suggest that social isolation policies support the integrity of adherents' meaning systems, thereby mitigating distress, which carries useful implications for both policy and psychological intervention.Objectives Although hearing has been shown to interact with sleep, the underlying mechanisms for the interaction remain largely unclear. In the absence of knowledge about the neural pathways that are associated with hearing-sleep interaction, this study aimed to examine whether the auditory radiation, the final portion of the auditory pathway from the cochlea to the cerebral cortex, shows association with sleep duration. Methods Using Diffusion Tensor Imaging (DTI) data from enhanced Nathan Kline Institute-Rockland Sample (NKI-RS), we isolated the white matter tracts between the medial geniculate nucleus of the thalamus and Heschl's gyrus in each individual subject (N = 465) using probabilistic tractography. As a measure of the white matter microstructure integrity, the mean fractional anisotropy (FA) of the whole auditory radiation was examined and tested for an association with sleep length in the Pittsburgh Sleep Assessment Index. Results A significant inverse-U shaped association was found between the auditory radiation FA and sleep duration. Discussion It is suggested that the auditory radiations are a part of the pathway mediating the sleep-hearing interaction. Although the current study does not resolve the causal relationship between hearing and sleep, it would be the first evidence that the auditory radiation is associated with sleep duration.Objective Recent publications on Coronavirus Disease-2019 (COVID-19) report that diabetic people with or without co-morbidities are at higher risk of developing severe and/or fatal illnesses. Method and result We report the first case of a 60-year-old man with a 27-year history of type 1 diabetes mellitus, infected by SARS-CoV-2 presenting with an euglycaemic ketoacidosis and an acute respiratory distress syndrome. Conclusion This case report reminds us of the importance of adjusting more recent glucose-lowering drugs, including sodium-glucose cotransporter 2 inhibitors, in the overall management of type 1 diabetic individuals during the ongoing COVID-19 outbreak. Abbreviations COVID-19 Coronavirus disease 2019 (SARS-CoV-2) virus, T1DM Type 1 diabetes mellitus, T2DM Type 2 diabetes mellitus, SGLT2i Sodium-glucose cotransporter 2 inhibitor, DKA diabetic ketoacidosis, euDKA euglycaemic diabetic ketoacidosis.Effective therapies are urgently needed for COVID-19. Here we describe the identification of a new stable human immunoglobulin G1 heavy-chain variable (VH) domain scaffold that was used for the construction of a large library, lCAT6, of engineered human VHs. This library was panned against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. Two VH domains (VH ab6 and VH m397) were selected and fused to Fc for increased half-life in circulation. The VH-Fc ab6 and m397 specifically neutralized SARS-CoV-2 with high potencies (50% neutralization at 0.35 µg/ml and 1.5 µg/ml, respectively) as measured by two independent replication-competent virus neutralization assays. Ab6 and m397 competed with ACE2 for binding to RBD, suggesting a competitive mechanism of virus neutralization. These VH domains may have potential applications for prophylaxis and therapy of COVID-19 alone or in combination, as well as for diagnosis and as tools for research.Objective Amnestic mild cognitive impairment (MCI) is a known risk factor for conversion to Alzheimer's disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, research on predictors of rate of decline has been considerably less extensive. The present study sought to more systematically and comprehensively examine predictors of rate of cognitive decline in a longitudinal sample of individuals with MCI, including age, genetic vulnerability, baseline cognitive performance, and baseline neuropsychiatric severity.Method Participants with single or multi-domain amnestic MCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years).Results Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures compared to non-carriers. Older individuals did not decline more rapidly in dementia severity. Participants with lower executive functions composite scores and greater memory impairment severity at baseline predicted faster decline on dementia severity measures.