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Although vaccine administration by microneedles has been demonstrated, delivery reliability issues have prevented their implementation. Through an ex vivo porcine skin experiment, we show visual evidence indicating that detachable dissolvable microneedles (DDMN) can deposit cargo into the dermis with insignificant loss of cargo to the stratum corneum. Using ovalbumin (OVA), a model antigen vaccine, as a cargo, the ex vivo experiments yielded a delivery efficiency of 86.08 ± 4.16 %. At room temperature, OVA could be stabilized for up to 35 days in DDMN made from hyaluronic acid and trehalose. The DDMN matrix could improve the denaturation temperature of the OVA from around 70–120 °C to over 150 °C, as demonstrated by differential scanning calorimetric analysis. In vivo delivery of OVA antigen into the mice's skin via DDMN elicited 10 times higher specific antibody responses compared to conventional intramuscular injection. We envision DDMN as an effective, precise dosing, intradermal vaccine delivery system that may require no cold-chain, offers a dose-sparing effect, and can be administered easily.

Falls are a serious problem for older adults, leading to adverse injuries and decreased quality of life. Balance impairment is a key factor in falls. The Otago Exercise Program (OEP) is a promising intervention for preventing falls, thereby improving balance and gait. Previous studies reported improved effects on balance using the OEP conducted in a group setting, and recommended additional walking. Walking is a feasible exercise that benefits both fall-related physical and physiological functions. This study aims to investigate the effects of a modified-Otago Exercise Program (modified-OEP) on four components of actual balance (static, dynamic, proactive, and reactive balance) and perceived balance in healthy older adults, by conducting the modified-OEP in a groupsetting, and including additional walking in one session to gain better efficacy. Participants aged 60–85 years old were randomly assigned to the modified-OEP group or the control group (CT). The modified-OEP consisted of 60 min sessions made up of 30 min of OEP and 30 min of walking, three times a week for 12 weeks, while no intervention was assigned to the control group. The modified-OEP group showed significant improvement in the four components of actual balance and in perceived balance. Furthermore, the modified-OEP group outperformed the control group in all parameters except for dynamic balance, after 12 weeks. The present study highlights the beneficial effects of a modified-OEP on all balance components. Additionally, this study is the first to demonstrate the measurement of all actual balance components as well as perceived balance.

Carbon Storage Regulator A (CsrA) is a well-characterized post-transcriptional global regulator that plays a critical role in response to environmental changes in many bacteria. CsrA has been reported to regulate several metabolic pathways, motility, biofilm formation, and virulence-associated genes. The role of csrA in Leptospira spp., which are able to survive in different environmental niches and infect a wide variety of reservoir hosts, has not been characterized. To investigate the role of csrA as a gene regulator in Leptospira, we generated a L. biflexa csrA deletion mutant (ΔcsrA) and csrA overexpressing Leptospira strains. The ΔcsrA L. biflexa displayed poor growth under starvation conditions. RNA sequencing revealed that in rich medium only a few genes, including the gene encoding the flagellar filament protein FlaB3, were differentially expressed in the ΔcsrA mutant. In contrast, 575 transcripts were differentially expressed when csrA was overexpressed in L. biflexa. Electrophoretic mobility shift assay (EMSA) confirmed the RNA-seq data in the ΔcsrA mutant, showing direct binding of recombinant CsrA to flaB3 mRNA. In the pathogen L. interrogans, we were not able to generate a csrA mutant. We therefore decided to overexpress csrA in L. interrogans. In contrast to the overexpressing strain of L. biflexa, the overexpressing L. interrogans strain had poor motility on soft agar. The overexpressing strain of L. interrogans also showed significant upregulation of the flagellin flaB1, flaB2, and flaB4. The interaction of L. interrogans rCsrA and flaB4 was confirmed by EMSA. Our results demonstrated that CsrA may function as a global regulator in Leptospira spp. under certain conditions that cause csrA overexpression. Interestingly, the mechanisms of action and gene targets of CsrA may be different between non-pathogenic and pathogenic Leptospira strains.