Impact of malnutrition evaluated by the mini nutritional assessment on the prognosis of acute hospitalized older adults.

Background: Malnutrition is prevalent among hospitalized older patients. Therefore, this study aimed to investigate the association between nutritional status [assessed using the Mini Nutritional Assessment (MNA) and serum albumin levels] and adverse outcomes in hospitalized older patients. We also aimed to compare the predictive utility of our findings. Methods: This retrospective cohort study was conducted between January 2016 and June 2020. In total, 808 older patients (aged ≥ 65 years, mean age 82.8 ± 6.70 years, 45.9% male) admitted to the acute geriatric unit were included in our sample. Comprehensive geriatric assessments, including the MNA, were performed. Malnutrition and risk of malnutrition were defined as MNA < 17, albumin < 3.5 g/dL and 17 ≤ MNA ≤ 24, 3.5 g/dL ≤ albumin < 3.9 g/dL, respectively. The primary outcome was that patients could not be discharged to their own homes. The secondary outcomes were overall all-cause mortality, 3-month all-cause mortality, and incidence of geriatric syndrome, including delirium, falls, and newly developed or worsening pressure sores during hospitalization. Results: Poor nutritional status was associated with older age; female sex; admission from the emergency room; high risk of pressure sores and falls; lower physical and cognitive function; higher depressive score; and lower serum albumin, protein, cholesterol, and hemoglobin levels. In the fully adjusted model, malnutrition assessed using the MNA predicted discharge to nursing homes or long-term care hospitals [odds ratio (OR) 5.822, 95% confidence interval (CI): 2.092-16.199, P = 0.001], geriatric syndrome (OR 2.069, 95% CI: 1.007-4.249, P = 0.048), and 3-month mortality (OR 3.519, 95% CI: 1.254-9.872, P = 0.017). However, malnutrition assessed using albumin levels could only predict 3-month mortality (OR 3.848, 95% CI: 1.465-10.105, P = 0.006). The MNA predicted 3-month mortality with higher precision than serum albumin levels (P = 0.034) when comparing the areas under the receiver operating characteristic curve. Conclusion: Nutritional risk measured by the MNA was an independent predictor of various negative outcomes in hospitalized older patients. Poor nutritional status assessed by serum albumin levels, the most widely used biochemical marker, could predict mortality, but not the development of geriatric syndrome or discharge location reflecting functional status.

Aged Microglia in Neurodegenerative Diseases: Microglia Lifespan and Culture Methods.

Microglia have been recognized as macrophages of the central nervous system (CNS) that are regarded as a culprit of neuroinflammation in neurodegenerative diseases. Thus, microglia have been considered as a cell that should be suppressed for maintaining a homeostatic CNS environment. However, microglia ontogeny, fate, heterogeneity, and their function in health and disease have been defined better with advances in single-cell and imaging technologies, and how to maintain homeostatic microglial function has become an emerging issue for targeting neurodegenerative diseases. Microglia are long-lived cells of yolk sac origin and have limited repopulating capacity. So, microglial perturbation in their lifespan is associated with not only neurodevelopmental disorders but also neurodegenerative diseases with aging. Considering that microglia are long-lived cells and may lose their functional capacity as they age, we can expect that aged microglia contribute to various neurodegenerative diseases. Thus, understanding microglial development and aging may represent an opportunity for clarifying CNS disease mechanisms and developing novel therapies.

Metal-Mediated Protein Assembly Using a Genetically Incorporated Metal-Chelating Amino Acid.

Many natural proteins function in oligomeric forms, which are critical for their sophisticated functions. The construction of protein assemblies has great potential for biosensors, enzyme catalysis, and biomedical applications. In designing protein assemblies, a critical process is to create protein-protein interaction (PPI) networks at defined sites of a target protein. Although a few methods are available for this purpose, most of them are dependent on existing PPIs of natural proteins to some extent. In this report, a metal-chelating amino acid, 2,2'-bipyridylalanine (BPA), was genetically introduced into defined sites of a monomeric protein and used to form protein oligomers. Depending on the number of BPAs introduced into the protein and the species of metal ions (Ni2+ and Cu2+), dimers or oligomers with different oligomerization patterns were formed by complexation with a metal ion. Oligomer sizes could also be controlled by incorporating two BPAs at different locations with varied angles to the center of the protein. When three BPAs were introduced, the monomeric protein formed a large complex with Ni2+. In addition, when Cu2+ was used for complex formation with the protein containing two BPAs, a linear complex was formed. The method proposed in this report is technically simple and generally applicable to various proteins with interesting functions. Therefore, this method would be useful for the design and construction of functional protein assemblies.

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic ß-Cells.

To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic ß-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 µM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of ß-cells.

Korean Consumers' Recognition of Risks Depending on the Provision of Safety Information for Chemical Products.

After the 2011 "Oxy accident" involving deaths from humidifier disinfectants, Korean consumers' anxiety about chemical products has risen. To provide timely, appropriate information to consumers, we must understand their risk recognition and explore methods of safety information provision. We investigated Korean consumers' level of risk perception for chemical products depending on the provision of safety information and other factors. We conducted an online survey for 10 days with 600 adult Korean consumer participants and analyzed seven factors: catastrophic potential, controllability, familiarity, fear, scientific knowledge, and risk for future generations. Our results showed that married women over 30 perceived chemical products as higher risk, but when information was provided on how to use products safely, catastrophic potential, controllability, fear, scientific knowledge, as well as risk perception, increased significantly. When only risk diagnosis information was provided, catastrophic potential, fear, and risk for future generations remained static, but familiarity had a negative effect (R^2 = 0.586). Age and scientific knowledge affected the recognition of risk when safe risk management methods were provided (R^2 = 0.587). Risk controllability did not have any effect on risk perception. These results suggest that providing information about avoiding or dealing with risks has a positive effect on consumers' risk perception.

Impact of a delirium prevention project among older hospitalized patients who underwent orthopedic surgery: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common clinical syndrome with significant negative outcomes. Thus, we aimed to evaluate the feasibility and effectiveness of a delirium screening tool and multidisciplinary delirium prevention project. METHODS: A retrospective cohort study was conducted at a single teaching center in Korea. A cohort of patients who underwent a delirium prevention program using a simple delirium screening tool from December 2018 to February 2019 (intervention group, N = 275) was compared with the cohort from the year before implementation of the delirium prevention program (December 2017 to February 2018) (control group, N = 274). Patients aged ≥65 years who were admitted to orthopedic wards and underwent surgery were included. The incidence rates of delirium before and after implementation of the delirium prevention program, effectiveness of the delirium screening tool, change in the knowledge score of nurses, and length of hospital stay were assessed. RESULTS: The sensitivity and specificity of the screening tool for the incidence of POD were 94.1 and 72.7%, respectively. The incidence rates of POD were 10.2% (control group) and 6.2% (intervention group). The odds ratio for the risk reduction effect of the project related to the incidence of POD was 0.316 (95% confidence interval: 0.125-0.800, p = 0.015) after adjustment for possible confounders. The delirium knowledge test score increased from 40.52 to 43.24 out of 49 total points (p < 0.001). The median length of hospital stay in the intervention and control groups was 6.0 (interquartile range, 4-9) and 7.0 (interquartile range, 4-10) days, respectively (p = 0.062). CONCLUSION: The screening tool successfully identified patients at a high risk of POD at admission. The POD prevention project was feasible to implement, effective in preventing delirium, and improved knowledge regarding delirium among the medical staff. TRIAL REGISTRATION: None.

The Korean version of the FRAIL scale: clinical feasibility and validity of assessing the frailty status of Korean elderly.

BACKGROUND/AIMS: The fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale is a screening tool for frailty status using a simple 5-item questionnaire. The aim of this study was to evaluate the clinical feasibility and validity of the Korean version of the FRAIL (K-FRAIL) scale. METHODS: Questionnaire items were translated and administered to 103 patients aged ≥ 65 years who underwent a comprehensive geriatric assessment at the Seoul National University Bundang Hospital. In this cross-sectional study, the K-FRAIL scale was compared with the domains and the multidimensional frailty index of the comprehensive geriatric assessment. We also assessed the time required to complete the scale. RESULTS: The participants' mean age was 76.8 years (standard deviation [SD], 6.1), and 55 (53.4%) were males. The mean overall frailty index was 0.19 (SD, 0.17). For K-FRAIL-robust, prefrail, and frail patients, the mean frailty indices were 0.09, 0.18, and 0.34, respectively (p for trend < 0.001). A higher degree of impairment in the K-FRAIL scale was associated with worse nutritional status, poor physical performance, functional dependence, and polypharmacy. The number of items with impairment in the K-FRAIL scale was positively associated with the frailty index (B = 3.73, p < 0.001). The K-FRAIL scale could differentiate vulnerability from robustness with a sensitivity of 0.90 and a specificity of 0.33. Of all patients, 75 (72.8%) completed the K-FRAIL scale within < 3 minutes. CONCLUSIONS: The K-FRAIL scale is correlated with the frailty index and is a simple tool to screen for frailty in a clinical setting.

Nutritional intake of pregnant women with gestational diabetes or type 2 diabetes mellitus.

Adequate intake of nutrients by pregnant women diagnosed with gestational diabetes mellitus (GDM) or type 2 diabetes (T2DM) is very important for appropriate weight gain and maintenance of normoglycemia without ketonuria. The aim of this study was to investigate the nutritional intake of pregnant women with GDM or T2DM who had not been provided with nutritional education regarding blood glucose management. Between June 2008 and May 2010, 125 pregnant women who had been diagnosed with GDM or T2DM and had not received any nutrition education regarding glycemic control and proper diet during pregnancy were interviewed to collect data regarding background characteristics, health-related behaviors, and course of pregnancy and instructed to record their dietary intake using a 24-hour recall method for one day. Using the collected data, the index of nutritional quality, nutrient adequacy ratio, and mean adequacy ratio values of the subjects were calculated. Analysis of the values indicated that the majority of the subjects did not meet recommended intake levels for most micronutrients and consumed an undesirable ratio of macronutrients, specifically a higher percentage of total carbohydrates than the current recommendation level. The GDM and T2DM groups obtained 56.6% and 63.6%, respectively (p = 0.012), of their calories by carbohydrate intake, which exceeded the recommended levels (125.8% in GDM groups, 141.3% in T2DM groups).

[Development and validation of the Korean Nursing Delirium Scale].

PURPOSE: The aims of this study were to develop and test the validity of the Korean Nursing Delirium Scale (Nu-DESC) for older patients in hospital. METHODS: The Korean Nu-DESC was developed based on the Nu-DESC (Gaudreau, 2005), and revised according to nursing records related to signs and symptoms of older patients with delirium (n=361) and the results of a pilot study (n=42) in one general hospital. To test the validity of the Korean Nu-DESC, 75 older patients whom nurses suspected of delirium from 731 older patients from 12 nursing units were assessed by bedside nurses using the Korean Nu-DESC. A Receiver Operating Characteristic Curve of the Korean Nu-DESC was constructed with an accompanying Area Under the Curve (AUC). RESULTS: Specific examples such as irritable, kidding, sleeping tendency, which were observed by bedside nurses in Korea, were identified in the five features of signs and symptoms of delirium in the instrument. The Korean Nu-DESC was psycho-metrically valid and had a sensitivity and specificity of .81-.76 and .97-.73, respectively. The AUC were .89, .74. CONCLUSION: Results of this study indicate that the Korean Nu-DESC is well-suited for widespread clinical use in busy inpatients settings and shows promise as a research instrument.

Colon-targeted cell-permeable NFκB inhibitory peptide is orally active against experimental colitis.

For the purpose of development of orally active peptide therapeutics targeting NFκB for treatment of inflammatory bowel disease (IBD), two major barriers in oral delivery of therapeutic peptides, metabolic lability and tissue impermeability, were circumvented by introduction of a colon-targeted delivery system and cell permeable peptides (CPP) to NFκB inhibitory peptides (NIP). Suppression of NFκB activation was compared following treatment with various CPP conjugated NIPs (CPP-NIP). The most potent CPP-NIP was loaded in a capsule coated with a colon specific polymer, which was administered orally to colitic rats. The anti-inflammatory activity of the colon-targeted CPP-NIP was evaluated by measuring inflammatory indices in the inflamed colonic tissue. For confirmation of the local action of the CPP-NIP, the same experiment was done after rectal administration. Tissue permeability of the CPP-NIP was examined microscopically and spectrophotometrically using FITC-labeled CPP-NIP (CPP-NIP-FITC). NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury, which was in parallel with decrease in MPO activity and the levels of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC was detected at much greater level in the inflamed tissue than was NBD-FITC. Taken together, introduction of cell permeability and colon targetability to NIP may be a feasible strategy for an orally active peptide therapy for treatment of IBD.

Production and characterization of monoclonal antibodies to mesenchymal stem cells derived from human bone marrow.

The bone marrow (BM) serves as a reservoir for different classes of stem cells. In addition to haematopoietic stem cells, bone marrow contains a population of mesenchymal stem cells (MSCs). These cells have a multilineage differentiation capacity and are able to generate progenitors with restricted developmental potential, which include fibroblasts, osteoblasts, adipocytes, and chondrocytes. Characteristic markers have been reported for expanded MSCs, but none of these markers are specific for MSCs. Thus, the objective of this study was to produce monoclonal antibodies against MSCs. MSCs derived from human bone marrow were cultured, expanded, and immunized into mice, and spleen cells subsequently harvested were used to generate hybridoma cell lines secreting antibodies against MSCs. Hybridoma culture supernatants were screened for antibodies against MSCs by enzyme-linked immunosorbent assay (ELISA), and 33 positive clones were then screened against cell suspensions of MSCs by immunofluorescence staining and flow cytometry. Ten clones were positive in immunofluorescence staining. Among these, three hybridoma cell lines, namely, YS08, YS14, and YS18 were found to be reactive with MSC by flow cytometry, but non-reactive with human tumor cell lines and hematopoietic stem cells. YS08 and YS14 showed specific bands in Western blotting. In conclusion, we developed three monoclonal antibodies, YS08, YS14, and YS18, that recognize human MSC cell surface antigen.

Upregulation of receptor activator of nuclear factor-kappaB ligand expression in the thymic subcapsular, paraseptal, perivascular, and medullary epithelial cells during thymus regeneration.

The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL; also termed TRANCE/OPGL/ODF/TNFSF11), a new member of the tumor-necrosis factor (TNF) superfamily, was identified as a key cytokine involved in the differentiation of the immune system and the regulation of immunity as well as in bone metabolism. In particular, RANKL-deficient mice showed defects in the early differentiation of T lymphocytes, suggesting that RANKL is a novel regulator of early thymocyte development. Here, we describe the expression of RANKL during regeneration following acute involution induced by cyclophosphamide in the rat thymus. The present study demonstrates the presence and upregulated expression of the RANKL in thymic subcapsular, paraseptal, perivascular, and medullary epithelial cells during thymus regeneration. Our results suggest that the RANKL expressed in these thymic epithelial cells plays a role in the development of T cells during thymic regeneration.