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Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern- triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation., Introduction Macrophages play a pivotal role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis (RA), with broad proinflammatory, destructive, and remodeling capabilities (1, 2). Similar to other [...]

Aim: To evaluate nurses' workload during the coronavirus disease 2019 (COVID‐19) pandemic and to identify their perception of medical serviced robots (MSRs) that may help with or replace the tasks of nurses in negative‐pressure isolated wards and general wards. Design: Cross‐sectional survey. Methods: A researcher‐made questionnaire was applied that assessed nurses' current workload and their attitudes towards and perceptions of MSRs. A visual analogue scale (VAS) from 1 to 10 was used to assess workload. Perceptions evaluated on a 5‐point Likert scale ranging from one point for 'strongly disagree' to five points for 'strongly agree'. A higher VAS score indicated a higher workload. On the other hands, a higher Likert score indicated a more positive perception and three points was neutral. The questionnaire was conducted on 150 nurses in negative‐pressure isolated wards for the management of COVID‐19 and 150 nurses in general wards. Quota sampling technique was used as sampling technique. Data analysis was performed through independent t‐tests, chi‐square tests and two‐tailed tests. The p‐value <0.05 was interpreted to statistically significant. Results: Two hundred eighty‐two participants responded and 142 belonged to the negative‐pressure isolated ward. The overall response rate was 94%, and 94.7% in the negative isolated ward. The mean score ± standard deviation for nursing‐related psychological stress at the current work site was 7.18 ± 1.58 points, and the mean score for physical workload was 7.65 ± 1.48. The need for MSRs was rated as 3.66 ± 0.86 out of 5. Overall, a positive attitude towards MSRs was confirmed, with no difference between ward groups. The overall ratings were 3.14 ± 1.15 for perceived availability and 3.26 ± 1.13 for perceived efficiency. Both nurse groups perceived that MSRs were most available and efficient for monitoring and measurements. Nurses in negative‐pressure isolated wards perceived MSRs more positively than did nurses in general wards regarding setting of alarms (p = 0.003) and delivery of medical devices/materials (p = 0.013). Based on these results, functional development of MSRs associated with monitoring, measurements, setting of alarms and delivery should be prioritized. No patient or public contribution. [ABSTRACT FROM AUTHOR]

In 2009, Lyubashevsky proposed a lattice-based signature scheme using the Schnorr-like identification and the Fiat-Shamir heuristic and proved its security under the collision resistance of a generalized compact knapsack function. However, their security analysis requires the witness indistinguishability property, leading to significant inefficiency and an increase of sizes of public key and signature. To overcome the efficiency issue associated with the WI property, we introduce a new lattice-based assumption, called the target-modified one-wayness problem of the GCK function and show its reduction to well-known lattice-based problems. Additionally, we present a simple and efficient GCK-based signature scheme, GCKSign, whose security is based on the Module GCK-TMO problem in the random oracle model. GCKSign is a natural extension of Lyubashevsky's scheme in a module setting, but achieves considerable efficiency gains due to eliminating the witness indistinguishability property. As a result, GCKSign achieves approximately 3.4 times shorter signature size and 2.4 times shorter public key size at the same security level. [ABSTRACT FROM AUTHOR]

Recent advances in robotics technology and artificial intelligence (AI) have sparked increased interest in humanoid robots that resemble humans and social robots capable of interacting socially. Alongside this trend, a new field of robot research called human-robot interaction (HRI) is gaining prominence. The aim of this review paper is to introduce the fundamental concepts of HRI and social robots, examine their current applications in the medical field, and discuss the current and future prospects of HRI and social robots in spinal care. HRI is an interdisciplinary field where robotics, AI, social sciences, design, and various disciplines collaborate organically to develop robots that successfully interact with humans as the ultimate goal. While social robots are not yet widely deployed in clinical environments, ongoing HRI research encompasses various areas such as nursing and caregiving support, social and emotional assistance, rehabilitation and cognitive enhancement for the elderly, medical information provision and education, as well as patient monitoring and data collection. Although still in its early stages, research related to spinal care includes studies on robotic support for rehabilitation exercises, assistance in gait training, and questionnaire-based assessments for spinal pain. Future applications of social robots in spinal care will require diverse HRI research efforts and active involvement from spinal specialists. [ABSTRACT FROM AUTHOR]

A number of single nucleotide polymorphisms (SNPs) within the mprF open reading frame (ORF) have been associated with daptomycin-resistance (DAP-R) in Staphylococcus aureus. Such SNPs have been found throughout the mprF ORF, although there are clearly preferred hot spots within this gene frequently linked to DAP-R phenotype. These mprF SNPs are often correlated with a gain-in-function phenotype, either in terms of increased production (synthase activity) and/or enhanced translocation (translocase activity) of lysyl-phosphatidylglycerol (L-PG) within its cell membrane. However, it is unclear if multiple hot spot mprF SNPs can accumulate within mprF ORFs and cause additive elevations of DAP minimum inhibitory concentrations (MICs). In this study, we used a previously well-characterized plasmid complementation system in S. aureus Newman ΔmprF mutant to express: (1) single point-mutated forms of mprF ORFs cloned from two DAP-R S. aureus strains (mprFS295L or mprFT345A) and (2) dual point-mutated forms of mprF ORFs simultaneously harboring SNPs in the central bifunctional domain and synthase domain in MprF, respectively (mprFS295L+L826F or mprFT345A+L826F). The current study revealed that, although individual hot spot point mutations within mprF ORF can recapitulate signature DAP-R-associated phenotypes (i.e., increased DAP MICs, enhanced surface positive charge, and increased L-PG synthesis), accumulation of such hot spot point mutations paradoxically caused reduction in these latter three metrics.