Everyday life experiences of Chinese community-dwelling oldest old who live alone at home.

PURPOSE: Older adults aged ≥ 80 years living alone at home are more likely to experience challenges. Daily life experiences regarding living alone are still limited in the Asian context. This study explored the everyday life experiences of older Chinese residents living alone at home. Research questions included: (1) How do Chinese community-dwelling old people describe everyday life experiences related to living alone? (2) What kind of difficulties and needs do Chinese community-dwelling older people living alone face in everyday lives? (3) How do Chinese community-dwelling older people cope with challenges faced in their everyday lives related to living alone? METHODS: This was qualitative descriptive research. Purposive sampling was adopted to recruit 13 participants aged 80-92 years of age from communities and one hospital. Semi-structured interviews were conducted to collect data which was analysed by conventional content analysis. RESULTS: Three themes were identified: theme 1-difficulty in finding a sense of belonging, theme 2-striving to maintain independence, theme 3-hard to gain a sense of control. CONCLUSIONS: This study provided novel insights into understanding the difficulties and needs of Chinese older people living alone at home. Three key challenges and associated strategies they used to cope with in daily lives were presented.

Pan-neutralizing, germline-encoded antibodies against SARS-CoV-2: Addressing the long-term problem of escape variants.

Despite the initially reported high efficacy of vaccines directed against ancestral SARS-CoV-2, repeated infections in both unvaccinated and vaccinated populations remain a major global health challenge. Because of mutation-mediated immune escape by variants-of-concern (VOC), approved neutralizing antibodies (neutAbs) effective against the original strains have been rendered non-protective. Identification and characterization of mutation-independent pan-neutralizing antibody responses are therefore essential for controlling the pandemic. Here, we characterize and discuss the origins of SARS-CoV-2 neutAbs, arising from either natural infection or following vaccination. In our study, neutAbs in COVID-19 patients were detected using the combination of two lateral flow immunoassay (LFIA) tests, corroborated by plaque reduction neutralization testing (PRNT). A point-of-care neutAb LFIA, NeutraXpress™, was validated using serum samples from historical pre-COVID-19 negative controls, patients infected with other respiratory pathogens, and PCR-confirmed COVID-19 patients. Surprisingly, potent neutAb activity was mainly noted in patients generating both IgM and IgG against the Spike receptor-binding domain (RBD), in contrast to samples possessing anti-RBD IgG alone. We propose that low-affinity, high-avidity, germline-encoded natural IgM and subsequent generation of class-switched IgG may have an underappreciated role in cross-protection, potentially offsetting immune escape by SARS-CoV-2 variants. We suggest Reverse Vaccinology 3.0 to further exploit this innate-like defense mechanism. Our proposition has potential implications for immunogen design, and provides strategies to elicit pan-neutAbs from natural B1-like cells. Refinements in future immunization protocols might further boost long-term cross-protection, even at the mucosal level, against clinical manifestations of COVID-19.

Longitudinal waning of mRNA vaccine-induced neutralizing antibodies against SARS-CoV-2 detected by an LFIA rapid test.

Although mRNA vaccines against SARS-CoV-2 were highly efficacious against severe illness and hospitalization, they seem to be less effective in preventing infection months after vaccination, especially with the Delta variant. Breakthrough infections might be due to higher infectivity of the variants, relaxed protective measures by the general public in "COVID-19 fatigue", and/or waning immunity post-vaccination. Determining the neutralizing antibody levels in a longitudinal manner may address this issue, but technical complexity of classic assays precludes easy detection and quick answers. We developed a lateral flow immunoassay NeutraXpress™ (commercial name of the test kit by Antagen Diagnostics, Inc.) and tested fingertip blood samples of subjects receiving either Moderna or Pfizer vaccines at various time points. With this device, we confirmed the reported clinical findings that mRNA vaccine-induced neutralizing antibodies quickly wane after 3-6 months. Thus, using rapid tests to monitor neutralizing antibody status could help identify individuals at risk, prevent breakthrough infections, and guide social behavior to curtail the spread of COVID-19.

Bone Morphogenetic Protein-2 Promotes Osteoclasts-mediated Osteolysis via Smad1 and p65 Signaling Pathways.

STUDY DESIGN: An in vitro biological study. OBJECTIVE: The aim of this study was to explore the role of bone morphogenetic protein-2 (BMP-2) in the regulation of osteoclast-mediated osteolysis, and the possible mechanism involving BMP-2 and nuclear factor-kappa B (NF-κB) signaling pathways. SUMMARY OF BACKGROUND DATA: Recombinant human BMP-2 (rhBMP-2) has been approved as a therapeutic agent in spinal fusion and bone defect repair. However, its efficacy and clinical application are limited by associated complications including osteoclast-mediated bone resorption. The mechanism of BMP-2-induced osteolysis remains unknown. METHODS: Bone marrow-derived macrophages (BMMs) were isolated from C57BL/6J mice and cultured with macrophage colony-stimulating factor (M-CSF) and receptor activator for nuclear factor-κB Ligand (RANKL) to induce osteoclast differentiation. An in vitro bone resorption assay was performed by co-culturing BMMs and bone slides. The expression of BMP canonical and NF-κB signaling factors and their interaction during signal transduction were quantitated by reverse transcription polymerase chain reaction, Western blot analysis, confocal microscopy, and co-immunoprecipitation. RESULTS: BMP-2 enhanced osteoclast-mediated bone resorption via inducing osteoclast differentiation in a concentration-dependent manner. In addition, a high concentration of BMP-2 significant upregulated phosphorylation of BMP signaling factors p-Smad1/5/8 and NF-κB downstream factor p65, and promoted the degeneration of IκBα. In addition, BMP-2 induced osteoclast differentiation through coupling between BMP receptor II and RANK. CONCLUSION: High concentrations of BMP-2 enhanced osteoclast-mediated bone resorption by promoting RANKL-induced pre-osteoclast differentiation, probably by mediating the cross-talk between BMP canonical and NF-κB signaling pathways.Level of Evidence: N/A.

Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aß1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway.

Inflammatory damage aggravates the progression of Alzheimer's disease (AD) and the mechanism of inflammatory damage may provide a new therapeutic window for the treatment of AD. Toll-like receptor 4 (TLR4)-mediated signaling can regulate the inflammatory process. However, changes in TLR4 signaling pathway induced by beta-amyloid (Aß) have not been well characterized in brain, especially in the hippocampus. In the present study, we explored the changes of TLR4 signaling pathway induced by Aß in the hippocampus and the role of atorvastatin in modulating this signal pathway and neurotoxicity induced by Aß. Experimental AD rats were induced by intrahippocampal injection of Aß1-42, and the rats were treated with atorvastatin by oral gavage from 3 weeks before to 6 days after injections of Aß1-42. To determine the spatial learning and memory ability of rats in the AD models, Morris water maze (MWM) was performed. The expression of the glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule-1 (Iba-1), TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), and nuclear transcription factor (NF)-κB (NF-κB) protein in the hippocampus was detected by immunohistochemistry and Western blot. Compared to the control group, increased expression of TLR4, TRAF6, and NF-κB was observed in the hippocampus at 7 days post-injection of Aß (P < 0.01). Furthermore, atorvastatin treatment significantly ameliorated cognitive deficits of rats, attenuated microglia and astrocyte activation, inhibited apoptosis, and down-regulated the expression of TLR4, TRAF6, and NF-κB, both at the mRNA and protein levels (P < 0.01). TLR4 signaling pathway is thus actively involved in Aß-induced neuroinflammation and atorvastatin treatment can exert the therapeutic benefits for AD via the TLR4 signaling pathway.