Assessing eating ability and mealtime behaviors of persons living with dementia: A systematic review of instruments.

This systematic review aimed to describe the characteristics of instruments that assess eating ability and/or mealtime behaviors in persons living with dementia, and evaluate their psychometric properties. Five databases were searched for relevant records between 1/1/1980 and 5/25/2023. Records included instruments assessing eating ability and/or mealtime behaviors of people with dementia. The psychometric quality of the instruments was evaluated using the Psychometric Assessment for Self-report and Observational Tools (PAT). 45 eligible instruments were identified from 115 records. While 38 instruments were scored as having low psychometric quality, 7 had moderate quality. Edinburgh Feeding Evaluation in Dementia (EdFED), Mealtime Difficulty Scale for older adults with Dementia (MDSD), and Dementia Hyperphagic Behavior Scale (DHBS) were scored as having the highest quality (total PAT score = 9). Further refinement of existing instruments and additional psychometric testing in larger, diverse samples will improve pragmatic use in dementia mealtime care research and practice.

ACE mRNA (Additional Chimeric Element incorporated IVT mRNA) for Enhancing Protein Expression by Modulating Immunogenicity.

The development of in vitro transcribed mRNA (IVT mRNA)-based therapeutics/vaccines depends on the management of IVT mRNA immunogenicity. IVT mRNA, which is used for intracellular protein translation, often triggers unwanted immune responses, interfering with protein expression and leading to reduced therapeutic efficacy. Currently, the predominant approach for mitigating immune responses involves the incorporation of costly chemically modified nucleotides like pseudouridine (Ψ) or N1-methylpseudouridine (m1Ψ) into IVT mRNA, raising concerns about expense and the potential misincorporation of amino acids into chemically modified codon sequences. Here, an Additional Chimeric Element incorporated mRNA (ACE mRNA), a novel approach incorporating two segments within a single IVT mRNA structure, is introduced. The first segment retains conventional IVT mRNA components prepared with unmodified nucleotides, while the second, comprised of RNA/DNA chimeric elements, aims to modulate immunogenicity. Notably, ACE mRNA demonstrates a noteworthy reduction in immunogenicity of unmodified IVT mRNA, concurrently demonstrating enhanced protein expression efficiency. The reduced immune responses are based on the ability of RNA/DNA chimeric elements to restrict retinoic acid-inducible gene I (RIG-I) and stimulator of interferon genes (STING)-mediated immune activation. The developed ACE mRNA shows great potential in modulating the immunogenicity of IVT mRNA without the need for chemically modified nucleotides, thereby advancing the safety and efficacy of mRNA-based therapeutics/vaccines.

Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy.

Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue-specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor-targeting peptides into the LNPs; the programmed death ligand 1 (PD-L1) binding peptides are conjugated to PEGylated lipids via a copper-free click reaction, and directly incorporated into the LNP composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD-L1 proteins, which leads to the uptake of LNPs into PD-L1 overexpressing cancer cells both in vitro and in vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, mRNA encoding phosphatase and tensin homolog (PTEN) is delivered via Pep LNPs to PTEN-deficient triple-negative breast cancers (TNBCs). Pep LNPs loaded with PTEN mRNA specifically promotes autophagy-mediated immunogenic cell death in 4T1 tumors, resulting in effective anticancer immune responses. This study highlights the potential of tumor-targeted LNPs for mRNA-based cancer therapy.

The Relationship Between Rejection of Care Behaviors and Pain and Delirium Severity in Hospital Dementia Care.

Background and Objectives: Rejection of care is common in hospitalized persons living with dementia. However, distinguishing between rejection of care behaviors related to care practices or other causes, such as pain or delirium, is challenging. The purpose of this study is to further understand the relationship between rejection of care and pain and delirium in hospitalized patients with dementia by identifying which rejection of care behaviors are associated with pain and delirium. Research Design and Methods: Care encounters between hospitalized patients with dementia (n = 16) and nursing staff (n = 53) were observed on 88 separate occasions across 35 days. Rejection of care was measured using the 13 behaviors from the Resistiveness to Care Scale. Pain and delirium severity were measured using a variety of scales including the Pain Assessment in Advanced Dementia Scale, Checklist of Nonverbal Pain Indicators, and numeric rating scale for pain severity and the Confusion Assessment Method-Severity short form and Delirium Observation Screening Scale for delirium severity. Linear mixed modeling was used to determine the relationship between rejection of care behaviors and pain and delirium severity for each measure. Results: About 48.9% of the observations included rejection of care, 49.9% included a patient in pain, and 12.5% included a patient with delirium. Cry, push away, scream/yell, and turn away indicated a higher pain severity across pain measures. No rejection of care behaviors were found to indicate delirium severity. Discussion and Implications: Certain rejection of care behaviors may be helpful in identifying pain in hospitalized patients with dementia, suggesting that caregivers should be cognizant of pain when these rejection of care behaviors are present. However, in this sample rejection of care behaviors was not found to be useful for identifying delirium severity in hospital dementia care.

Chewing and Swallowing Abilities of Persons Living With Dementia: A Systematic Review of Psychometric Properties of Instruments.

Background and Objectives: It is critical to use validated instruments to diagnose and manage chewing and swallowing problems of persons living with dementia. The study aimed to synthesize the characteristics and psychometric quality of instruments that assess the chewing and swallowing abilities of persons living with dementia. Research Design and Methods: The systematic review was used to conduct this study. We searched 5 electric databases for records published from January 1, 1980, to July 8, 2022. Records were eligible if they included any instrument to assess chewing ability or swallowing ability in the dementia population. Eight characteristics of eligible instruments were extracted from the records: (1) development process, (2) operationalized concept/construct, (3) sample and setting, (4) administration method, (5) items, (6) scoring format/interpretation, (7) reliability, and (8) validity. The psychometric assessment for self-report and observational tool was used to evaluate 12 psychometric properties of eligible instruments. Results: In total, 11,074 records were reviewed. Thirty-five eligible instruments, including observational tools, self-report questionnaires, and physiological instruments, were identified from 60 records. All 8 instruments assessing chewing ability were evaluated as having low psychometric quality, and only 3 out of 27 instruments assessing swallowing ability were evaluated as having moderate psychometric quality. Fifteen instruments were tested for only 1 type of psychometric property, limiting the overall evaluation of psychometric evidence. Discussion and Implications: The study findings inform the use and adaptation of appropriate instruments for practice and research. All existing instruments warrant further validation in larger samples to expand use in diverse care settings. This review described and evaluated current instruments measuring chewing and swallowing abilities and potential use in research and clinical practice to plan for and evaluate the effectiveness of mealtime and oral care practice and reduce health-related negative outcomes of persons living with dementia.

Curcumin inhibits human cancer cell growth and migration through downregulation of SVCT2.

Curcumin is a natural polyphenol that is extracted from the rhizomes of the turmeric plant (Curcuma longa), a member of the ginger family. It has been used for centuries in traditional Indian and Chinese medicine for its medicinal properties, including anti-inflammatory, antioxidant and antitumor effects. SVCT2 (Solute Carrier Family 23 Member 2, also known as SLC23A2) is a protein that plays a role in the transport of Vitamin C (Ascorbic Acid) into cells. SVCT2 plays an important role in tumor progression and metastasis, however, the molecular mechanisms of curcumin on SVCT2 have not been studied to date. Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner. We found that curcumin reduced the expression of SVCT2 in cancer cells with a wild type p53, but not in those with a mutant type of p53. SVCT2 downregulation also reduced the MMP2 activity. Taken together, our results indicate that curcumin inhibited human cancer cell growth and migration by regulating SVCT2 through a downregulating p53. These findings provide new insights into the molecular mechanisms of curcumin's anticancer effects and potential therapeutic strategies for the treatment of metastatic migration.

Development of mRNA Vaccines/Therapeutics and Their Delivery System.

The rapid development of mRNA vaccines has contributed to the management of the current coronavirus disease 2019 (COVID-19) pandemic, suggesting that this technology may be used to manage future outbreaks of infectious diseases. Because the antigens targeted by mRNA vaccines can be easily altered by simply changing the sequence present in the coding region of mRNA structures, it is more appropriate to develop vaccines, especially during rapidly developing outbreaks of infectious diseases. In addition to allowing rapid development, mRNA vaccines have great potential in inducing successful antigen-specific immunity by expressing target antigens in cells and simultaneously triggering immune responses. Indeed, the two COVID-19 mRNA vaccines approved by the U.S. Food and Drug Administration have shown significant efficacy in preventing infections. The ability of mRNAs to produce target proteins that are defective in specific diseases has enabled the development of options to treat intractable diseases. Clinical applications of mRNA vaccines/therapeutics require strategies to safely deliver the RNA molecules into targeted cells. The present review summarizes current knowledge about mRNA vaccines/ therapeutics, their clinical applications, and their delivery strategies.

Association between Dental Caries and Handgrip Strength: In a Population-Based Study in Korea (KNHANES 2016-2018).

This study aimed to verify the relationship between handgrip strength and oral health using data from the Korea National Health and Nutrition Examination Survey, representing Korean adults. Data from the seventh survey (2016−2018) conducted by the Korea Centers for Disease Control and Prevention were utilized, and 10,607 final study participants were recruited according to the selection and exclusion criteria. A complex sample logistic regression analysis was performed to confirm the relationship between handgrip strength and dental caries according to the sex of the study participants. On analyzing the correlation in men, "C1 (DMFT: 11−32)," when compared to "C4 (DMFT: 0−3)," in Model 1 without adjustment for potential confounders, was 2.92 (95% confidence interval [CI]: 2.15−3.97) times more likely to be associated with lower handgrip strength, and a statistically significant result was detected (p < 0.001). Additionally, significant odds ratios (ORs) were confirmed for all adjusted models. In women, the ORs in Model 1 without adjustment for potential confounders were 1.41 times (95% CI: 1.14−1.75) and demonstrated a significant result; however, the results were not significant in all adjusted models 2−4. Resultantly, a significant association was detected between dental caries and handgrip strength in Korean adults.

mRNA vaccines: the most recent clinical applications of synthetic mRNA.

Synthetic mRNA has been considered as an emerging biotherapeutic agent for the past decades. Recently, the SARS-CoV-2 pandemic has led to the first clinical use of synthetic mRNA. mRNA vaccines showed far surpassing influences on the public as compared to other vaccine platforms such as viral vector vaccines and recombinant protein vaccines. It allowed rapid development and production of vaccines that have never been achieved in history. Synthetic mRNA, called in vitro transcribed (IVT) mRNA, is the key component of mRNA vaccines. It has several advantages over conventional gene-expressing systems such as plasmid DNA and viral vectors. It can translate proteins in the cytoplasm by structurally resembling natural mRNA and exhibit various protein expression patterns depending on how it is engineered. Another advantage is that synthetic mRNA enables fast, scalable, and cost-effective production. Therefore, starting with the mRNA vaccine, synthetic mRNA is now in the spotlight as a promising new drug development agent. In this review, we will summarize the latest IVT mRNA technology such as new mRNA structures or large-scale production. In addition, the nature of the innate immunogenicity of IVT mRNA will be discussed along with its roles in the development of vaccines. Finally, the principles of the mRNA vaccine and the future direction of synthetic mRNA will be provided.

Microneedle systems for delivering nucleic acid drugs.

Background: Nucleic acid-based gene therapy is a promising technology that has been used in various applications such as novel vaccination platforms for infectious/cancer diseases and cellular reprogramming because of its fast, specific, and effective properties. Despite its potential, the parenteral nucleic acid drug formulation exhibits instability and low efficacy due to various barriers, such as stability concerns related to its liquid state formulation, skin barriers, and endogenous nuclease degradation. As promising alternatives, many attempts have been made to perform nucleic acid delivery using a microneedle system. With its minimal invasiveness, microneedle can deliver nucleic acid drugs with enhanced efficacy and improved stability. Area covered: This review describes nucleic acid medicines' current state and features and their delivery systems utilizing non-viral vectors and physical delivery systems. In addition, different types of microneedle delivery systems and their properties are briefly reviewed. Furthermore, recent advances of microneedle-based nucleic acid drugs, including featured vaccination applications, are described. Expert opinion: Nucleic acid drugs have shown significant potential beyond the limitation of conventional small molecules, and the current COVID-19 pandemic highlights the importance of nucleic acid therapies as a novel vaccination platform. Microneedle-mediated nucleic acid drug delivery is a potential platform for less invasive nucleic acid drug delivery. Microneedle system can show enhanced efficacy, stability, and improved patient convenience through self-administration with less pain.

An Online International Collaborative Learning Program During the COVID-19 Pandemic for Nursing Students: Mixed Methods Study.

BACKGROUND: Given the limitations imposed by the COVID-19 pandemic, a better understanding of how nursing programs around the globe have implemented distance education methods and related initiatives to provide international collaborative learning opportunities as well as complementary aspects of practical education would be constructive for nursing students. It is expected that international collaboratives through web-based communication will continue to be increasingly utilized after the pandemic; therefore, it is time to discuss the effects and direction of these developments. OBJECTIVE: We aimed to examine the impact of an online international collaborative learning program on prelicensure nursing students' international and global competencies in South Korea. METHODS: We conducted a mixed methods study (web-based surveys and focus group interviews). A total of 15 students participated in the study. The surveys were used to examine changes in participants' global leadership competencies, and the focus group interviews were used to evaluate the program's effectiveness and to identify opportunities for improvement. The online international collaborative program consisted of 7 synchronous web-based classroom sessions. Each session ran for 60 to 90 minutes. Faculty experts and nurses working in the United States discussed various topics with students, such as nursing education in the United States and evidence-based teaching and learning. The students gave presentations on the South Korean nursing education system. Data were analyzed with descriptive statistics, the Mann-Whitney U test, and content analysis methods. RESULTS: Participants reported improvement in their global leadership competencies. Four main categories emerged from analysis of the focus interviews: (1) realistic applicability, (2) clarification, (3) expansion of perspectives, and (4) initiative. CONCLUSIONS: The online international collaborative learning program had a positive impact on the development of students' international competencies. The findings support the further development of international exchange programs through web-based meetings in the postpandemic era.

Protein-RNA interaction guided chemical modification of Dicer substrate RNA nanostructures for superior in vivo gene silencing.

Dicer substrate RNA is an alternative gene silencing agent to canonical siRNA. Enhanced in vitro gene silencing can be achieved with RNA substrates by facilitating Ago2 loading of dsRNA after Dicer processing. However, the in vivo use of Dicer substrate RNA has been hindered by its instability and immunogenicity in the body due to the lack of proper chemical modification in the structure. Here, we report a universal chemical modification approach for Dicer substrate RNA nanostructures by optimizing protein-RNA interactions in the RNAi pathway. Proteins involved in the RNAi pathway were utilized for evaluating their recognition and binding of substrate RNA. It was found that conventional chemical modifications could severely affect the binding and processing of substrate RNA, consequently reducing RNAi activity. Protein-RNA interaction guided chemical modification was introduced to RNA nanostructures, and their gene silencing activity was assessed. The optimized RNA nanostructures showed excellent binding and processability with RNA binding proteins and offered the enhancement of in vivo EC50 up to 1/8 of its native form.

Eating Difficulties among Older Adults with Dementia in Long-Term Care Facilities: A Scoping Review.

This paper reports a scoping review of the literature on eating difficulties among older adults with dementia in long-term care facilities to identify key concepts, methods of measuring outcomes, interventions, and related factors. A scoping review was performed using the bibliographic databases PubMed, CINAHL, PsycINFO, and Cochrane Library. A combination of keywords and subject headings related to eating or feeding difficulties was used. Inclusion criteria were limited to materials published in English. A total of 1070 references were retrieved, of which 39 articles were selected after applying the inclusion and exclusion criteria. Articles that met the criteria were published between 1987 and 2020. "Eating disabilities" have been defined as problems related to choosing food and/or the ability to get food to one's mouth, chew, and swallow. Interventions for eating difficulties described in the literature include spaced retrieval training, Montessori training, and feeding skill training. Intrapersonal, interpersonal, and environmental factors related to eating difficulties were identified. This scoping review will provide direct care workers, nursing educators, and administrators with an overview of eating performance and a broad understanding of eating difficulties for older adults with dementia in long-term care facilities.

Antibody-siRNA conjugates (ARCs) using multifunctional peptide as a tumor enzyme cleavable linker mediated effective intracellular delivery of siRNA.

The tissue-specific targeted delivery and efficient cellular uptake of siRNAs are the main obstacles to their clinical application. Antibody-siRNA-conjugates (ARCs) can deliver siRNA by exploiting the targeting property of antibodies like antibody-drug conjugates (ADCs). However, the effective conjugation of antibodies and siRNAs and the release of siRNAs specifically at target sites have posed challenges to the development of ARCs. In this study, the successful conjugation of antibodies and siRNAs was achieved using a multifunctional peptide as a linker, composed of a cell-penetrating peptide (CPP) and a substrate peptide (SP), which is highly expressed in solid tumors. The resulting antibody-multifunctional peptide (SP-CPP)-siRNA system delivered the siRNA to target tumor cells by the specific binding of the antibody. Once the enzymes on the tumor cell surface hydrolyzed the substrate peptide linker, siRNA-CPP was released from ARCs. The released siRNA-CPP entered the targeted cells via the cellular penetrating ability of CPP, resulting in improved siRNA-mediated gene silencing efficiency, verified both in vitro and in vivo. After intravenous administration, the designed ARCs achieved approximately 66.7% EGFP (Enhanced Green Fluorescent Protein) downregulation efficiency in nude mice xenografted with the HCT116-EGFP tumor model. The proposed system provides a prospective choice for ARC production and the safe and efficient delivery of siRNAs.

Examination of the Educational Needs of Home Visit Nurses: A Cross-Sectional Descriptive Study.

This study aimed to identify educational needs and determine priorities in nursing care for home visit nurses providing services within the national long-term care insurance system in South Korea. This cross-sectional descriptive study assessed the educational needs of 92 home visit nurses. Participants' characteristics were analyzed using percentages, averages, and standard deviations. Educational needs were calculated for participants' current and required competency levels, utilizing the paired t-test, Borich's educational needs formula, and the locus for focus model. Four main categories were identified as top priorities: (1) health assessment, (2) cognitive function care, (3) disease management, and (4) medication management. The study's findings could support the development of appropriate and responsive education and training programs for home-visit nurses-as it reflects the actual needs of this group.

Feasibility of a Mobile Meal Assistance Program for Direct Care Workers in Long-Term Care Facilities in South Korea.

PURPOSE: The purpose of this study was to assess the feasibility and examine the preliminary effectiveness of a mobile application-based meal assistant training program (APP) for use by direct care workers (CAs) assisting residents with dementia in long-term care facilities in South Korea. METHODS: We adopted a mixed methods research design, which included a pre- and post-intervention study and focus group interviews for the feasibility assessment. Participants included 23 dyads of older adults with dementia and their CAs from a long-term care facility in South Korea. Upon completion of the APP intervention, focused group interviews were conducted with six CAs and five nurses. RESULTS: The results of paired t-tests showed that the effects of the APP intervention on the older adults with dementia and their CAs were not significant; however, the results of the focused group interviews support the potential usefulness of the APP for CAs. CONCLUSION: The APP may be applicable to long-term care workers who need meal assistant skills education.

Combined hybrid structure of siRNA tailed IVT mRNA (ChriST mRNA) for enhancing DC maturation and subsequent anticancer T cell immunity.

RNA therapeutics have received much attention in the development of anti-cancer therapies. Among them, synthetic mRNA (IVT mRNA) was investigated for cancer immunotherapy due to its abilities to express tumor associated antigens with stimulation of immune responses in dendritic cells (DCs). Despite of its great potential, several hurdles were remained such as insufficient immune stimulation and DC maturation. In this study, we aimed to present a novel IVT mRNA that can simultaneously express tumor associated antigens while suppress STAT3 proteins. Combined functions of siRNA and IVT mRNA were investigated and the hybrid structure of siRNA tailed mRNA (ChriST mRNA) was developed. We prepared the ChriST mRNA by employing polyA tail structures with RNAi sequences at the 3' end of mRNA. Complementary strands were annealed to form duplex siRNA structure to induce STAT3 gene silencing. In addition, a hybrid structure of DNA/RNA was introduced into the ChriST mRNA between polyA tail and RNAi sequences. It was expected that DNA/RNA duplex would be readily cleaved by RNase H in the intracellular environment. After the cleavage, ChriST mRNA was fully functionalized in cells and exhibited enhanced tumor specific DC maturation.

Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells.

As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.

Adjuvant incorporated lipid nanoparticles for enhanced mRNA-mediated cancer immunotherapy.

For mRNA mediated cancer immunotherapy, Pam3 was incorporated as an adjuvant within lipid nanoparticles (LNPs) with OVA mRNA. The developed Pam3 incorporated LNPs showed successful expression of tumor antigens with enhanced immune stimulation. We demonstrated that the synergies of Pam3 LNPs could greatly improve the efficacy of tumor prevention by mRNA vaccines.

The cutting-edge technologies of siRNA delivery and their application in clinical trials.

siRNA therapeutics allows precise regulation of disease specific gene expression to treat various diseases. Although gene silencing approaches using siRNA therapeutics shows some promising results in the treatment of gene-related diseases, the practical applications has been limited by problems such as inefficient in vivo delivery to target cells and nonspecific immune responses after systemic or local administration. To overcome these issues, various in vivo delivery platforms have been introduced. Here we provide an overview for three different platform technologies for the in vivo delivery of therapeutic siRNAs (siRNA-GalNAc conjugate, SAMiRNA technology, and LNP-based delivery method) and their applications in the treatment of various diseases. In addition, a brief introduction to some rare diseases and mechanisms of siRNA therapeutics-mediated treatment is described.