Effectiveness and Safety of the Korean Medicine Senior Health Promotion Program Using Herbal Medicine and Acupuncture for Mild Cognitive Impairment: A Retrospective Study of 500 Patients in Seoul, Korea.

BACKGROUND: The management of mild cognitive impairment (MCI) is becoming increasingly important. The Korean Medicine Senior Health Promotion Program (KSHPP) was developed in 2016, and it has been in use to date. This study aimed to assess the effectiveness of KSHPP using herbal medicine and acupuncture for treating MCI and the safety of herbal medicine using liver and renal function tests. METHODS: We retrospectively reviewed the medical records of the participants with MCI. We assessed the Korean version of the Montreal Cognitive Assessment (MoCA-K), the Mini-Mental State Examination-Dementia Screening (MMSE-DS), and the Geriatric Depression Scale Short Form-Korea version (GDSSF-K) scores before and after KSHPP to determine its effectiveness. To evaluate its safety, the liver and renal function tests were conducted before and after herbal treatment. RESULTS: We enrolled 1002 participants, and 500 participants satisfied the inclusion criteria. Of 500 patients, 364 (72.8%) were depressed and 136 (27.2%) were not. The mean MoCA-K score significantly increased by 2.77 for the entire sample and 3.22 for the depressed sample (all P < 0.0001). The mean MMSE-DS score significantly increased by 2.19 for the entire sample and 2.51 for the depressed sample (all P < 0.0001); the mean GDSSF-K score significantly decreased by 1.73 for the entire sample and 2.68 for the depressed sample (all P < 0.0001). CONCLUSIONS: Our findings suggest that Korean medicine interventions can improve cognitive function and depression symptoms in patients with MCI. In addition, the results of the liver and renal function tests were analyzed as surrogate outcomes to assess the safety of herbal medicine. Based on these results, we expect that Korean medicine interventions can promote the cognitive and mental health of seniors. However, as there were several study limitations, particularly study design, practice effect, and short follow-up, these results must be interpreted with caution. We need a further long-term study with a rigorous design to retain confidence in the effectiveness and safety of KSHPP.

Effects of a low-FODMAP enteral formula on diarrhea on patients in the intensive care unit.

BACKGROUND/OBJECTIVES: A dietary restriction on the intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has been reported to be effective in the treatment of gastrointestinal (GI) tract complications. Enteral nutrition (EN) is widely used for patients who cannot obtain their nutritional requirements orally, but many studies have reported EN complications, especially diarrhea, in up to 50% of patients. SUBJECTS/METHODS: We performed a single-center, non-randomized, controlled trial to determine the effects of a low-FODMAP enteral formula on GI complications in patients in intensive care units (ICUs). Patients in the ICU who needed EN (n = 66) were alternately assigned to the low-FODMAP group (n = 33) or the high-FODMAP group (n = 33). RESULTS: Anthropometric and biochemical parameters were measured, and stool assessment was performed using King's Stool Chart. We excluded patients who received laxatives, GI motility agents, proton pump inhibitors, antifungal agents, and antibiotics other than ß-lactams. There were no differences in GI symptoms during 7 days of intervention, including bowel sound, abdominal distension, and vomiting between the 2 groups. However, diarrhea was more frequent in the high-FODMAP group (7/33 patients) than the low-FODMAP group (1/33 patients) (P = 0.044). CONCLUSIONS: Our results suggest that a low-FODMAP enteral formula may be a practical therapeutic approach for patients who exhibit enteral formula complications. Our study warrants further randomized clinical trials and multicenter trials. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005660.

Aspects of Health-Related Factors and Nutritional Care Needs by Survival Stage among Female Cancer Patients in South Korea.

PURPOSE: This study examined diet-related problems and needs associated with nutritional care according to survival stage in Korean female cancer survivors. METHODS: 186 outpatients (breast or gynecologic cancer survivors) recruited. Subjects were classified as (1) extended stage (ES, 2-5 years from diagnosis) and (2) long-term stage (LS, ≥5 years from diagnosis). Eating habits, changes in health related factors, nutritional needs, and quality of life were investigated. RESULTS: 43% of ES survivors had diet-related problems (p = .031); ES group reported dyspepsia and LS group reported anorexia/nausea as the major problem. Half of ES survivors had taste change, decreasing amount of intake, and reduced quality of life (p < .05). The LS group had a greater preference for sweet tastes than the ES group. According to their diagnosis, ES survivors with breast cancer gained weight (27.1%), whereas ES survivors with gynecologic cancer lost their body weight (34.5%) significantly. LS breast cancer patients showed great food preference for vegetables, whereas those with gynecologic cancer showed an increased preference for fish, meat and grain. Approximately 90% of survivors demanded nutritional care regarding restricted foods, preventing recurrence, particularly in ES survivors (p < .01). Moreover, main factors for nutritional care needs were body weight control for breast cancer and food environment for gynecologic cancer. CONCLUSION: Survivors have different aspects of diet-related problems by survival stage as dyspepsia in ES and anorexia in LS. ES stage had changes in dietary patterns and their food consumption have decreased. Most of survivors have demanded nutritional care regardless of survival stage. These features of each stage should be considered to improve their health.

Effects of ionization on the toxicity of silver nanoparticles to Japanese medaka (Oryzias latipes) embryos.

Increase in the use of manufactured nanomaterials (NMs) has led to concerns about the environmental impacts. Especially, hazard of metal-based NMs is more severe due to ions released from surface by water quality parameters and physicochemical properties after entering into the water environment. However, little is known about the effects of ionization on the toxicity of metal-based NMs in the water environment. To address this question, we prepared the suspensions of silver nanoparticles (AgNP) at 25 µg L(-1) containing different concentrations of Ag(+) (5, 10, 20, 45, and 75% Ag(+) to total Ag), and evaluated their toxicity to Japanese medaka (Oryzias latipes) embryos. Higher Ag(+) ratios in the AgNP suspension, suggesting the lower number of particles, led to the higher adverse effects on embryos and sac-fries. In addition, histopathology analysis revealed that AgNPs penetrated through chorion of eggs and skin membrane, and were distributed into the tissues. The results imply that the ionization could decrease the toxicity of metal-based NMs in the water environment.

Synthesis of mono-dispersed nano-scale fullerene (C60) crystals.

Fullerene (C60), which has a unique molecular structure, was used in the preparation of crystalline organic nano-crystals. Fullerene was dissolved in toluene and this fullerene solution was mixed with water drastically. During this process, fullerene transferred from toluene to water phase. The significantly different solubility of fullerene in a toluene/water solvent system played an important role in the self-assembly of single fullerene nano-crystals, as it is called drowning-out crystallization. In addition, pH of water was controlled to carry out the interfacial transference of fullerene. An optical spectrum analysis showed that the fullerene was transferred by a hydrolysis reaction from toluene to water, depending on the pH and toluene involved in the crystal structure. During the interfacial transference, the growth of nano-scale fullerene occurred at pH > 7. Importantly, fullerene nanocrystals were formed with a mono-dispersed square structure on a nano-scale (104 nm average size and 1.03 +/- 0.24 aspect ratio) at pH 10.

Bacterial cytotoxicity of the silver nanoparticle related to physicochemical metrics and agglomeration properties.

Silver particles are used in various consumer products due to their positive effects, which include sterilization and antibacterial properties. However, it has been reported that silver nanoparticles (AgNPs) have strongly acute toxic effects on various cells. Therefore, the cytotoxicity of AgNPs was investigated, using Escherichia coli as a model organism, from the standpoint of three key metrics (ionic ratio, size, and agglomeration) that are the most relevant physicochemical properties. The findings indicated that cytotoxicity is depressed by the agglomeration of AgNPs. The order of toxic sensitivity was as follows: total Ag concentration > ionic ratio > size, the order of which was inversely related to the extent of agglomeration.

Gliosis in the amygdala following myocardial infarction in the rat.

We observed gliosis with cell death in the rat amygdala 3 and 14 days after myocardial infarction (MI). Cresyl violet-positive neurons had condensed cytoplasm, and Fluoro-Jade B-positive cells were detected in the amygdala 14 days, not 3 days, after MI. Only a few glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes and ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive microglia showed activated form; hypertrophied cytoplasm, and highly ramified and retracted processes of astrocytes and microglia in the amygdala at 3 days after MI, respectively. At 14 days after MI, many astrocytes and most of microglia showed activated forms. These results suggest that MI may induce neuronal death and reactive gliosis in the amygdala.

Phosphorylated extracellular signal-regulated kinase 1/2 immunoreactivity and its protein levels in the gerbil hippocampus during normal aging.

Phosphorylated extracellular signal-regulated kinase (pERK) mediates neuronal synaptic plasticity, long-term potentiation, and learning and memory in the hippocampus. In this study, we examined pERK1/2 immunoreactivity and its protein level in the gerbil hippocampus at various ages. In the postnatal month 1 (PM 1) group, very weak pERK1/2 immunoreactivity was detected in the hippocampus. In the CA1 region, pERK1/2 immunoreactivity was considerably increased in the stratum pyramidale in the PM 6 group. Thereafter, pERK1/2 immunoreactivity was decreased. In the CA2/3 region, pERK1/2 immunoreactivity increased in an age-dependent manner until PM 12. Thereafter, numbers of pERK1/2-immunoreactive neurons were decreased. However, in the mossy fiber zone, pERK1/2 immunostaining became stronger with age. In the dentate gyrus, a few pERK1/2-immunoreactive cells were observed until PM 12. In the PM 18 and 24 groups, numbers of pERK1/2-immunoreactive cells were increased, especially in the polymorphic layer. In Western blot analysis, pERK1/2 level in the gerbil hippocampus was increased with age. These results indicate that total pERK1/2 levels are increased in the hippocampus with age. However pERK1/2 immunoreactivity in subregions of the gerbil hippocampus was changed with different pattern during normal aging.

Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles.

Toxicity of nanoparticles depends on many factors including size, shape, chemical composition, surface area, surface charge, and others. In this study, we compared the toxicity of different sized-silver nanoparticles (AgNPs) which are being widely used in consumer products due to its unique antimicrobial activity. When mice were treated with AgNPs 1mg/kg for 14 days by oral administration, small-sized AgNPs (22nm, 42nm, and 71nm) were distributed to the organs including brain, lung, liver, kidney, and testis while large-sized AgNPs (323nm) were not detected in those tissues. The levels of TGF-ß in serum were also significantly increased in the treated group of small-sized AgNPs but not in large-sized AgNPs. In addition, B cell distribution was increased in small-sized AgNPs but not in large-sized-AgNPs by the phenotype analysis. However, body weight or in the ratio of organ/body weight were not different between the control group and all the AgNPs-treated groups. The repeated-dose toxicity of AgNPs (42nm) was also investigated in mice by oral administration for 28 days. By the administration of AgNPs (0.25mg/kg, 0.50mg/kg, 1.00mg/kg), adverse impacts on liver and kidney were observed in a high dose-treated group (1.00mg/kg), when determined by blood chemistry and histipathological analysis. Cytokines including IL-1, IL-6, IL-4, IL-10, IL-12, and TGF-ß were also increased in a dose-dependent manner by repeated oral administration. In addition, B cell distribution in lymphocyte and IgE production were increased. Based on these results, it is suggested that repeated oral administration of nano-sized AgNPs may cause organ toxicity and inflammatory responses in mice.

Pregnancy inhibits cell proliferation and neuroblast differentiation without neuronal damage in the hippocampal dentate gyrus in C57BL/6N mice.

Neural changes occur in the dam during gestation, and brain size has been shown to decrease across pregnancy in humans as well as rodents. In this study, we monitored neuronal damage, cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) at age-matched virgin control (17- to 18-week-old), gestation day (GD) 14.5, 16.5 and 18.5 (17- to 18-week-old dams), using NeuN for mature neurons, terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL) and Fluoro-Jade B (F-J B) for neuronal death, Ki67 for cell proliferation and doublecortin (DCX) for neuroblast differentiation in C57BL/6 mice. There were no significant differences in NeuN-immunoreactive ((+)) neurons between the age-matched control and gestating groups. TUNEL or F-J B positive neurons were rarely detected in the DG in all the groups. Ki67(+) cell proliferation was significantly decreased in the subgranular zone of the dentate gyrus (SZDG) at GD16.5. In addition, DCX(+) neuroblasts with/without tertiary dendrites were decreased in the SZDG with gestation by GD16.5. However, in the GD18.5 group, the number of Ki67(+) nuclei and DCX(+) neuroblasts with/without tertiary dendrites was slightly increased compared to that observed at GD16.5. DCX protein levels were low at GD16.5, and thereafter slightly increased. These results suggest that cell proliferation and neuroblast differentiation in DG of the hippocampus is decreased during gestation.

Evaluation of the toxic impact of silver nanoparticles on Japanese medaka (Oryzias latipes).

The increased use of nano-sized metallic materials is likely to result in the release of these particles into the environment. It is, however, unclear if these materials are harmful to aquatic animals. Furthermore, because the dissolution of such nanomaterials will occur, it is probable that some of the adverse effects resulting will result from the dissolved metal species. In this study, therefore, we investigated the health and environmental impact of silver nanoparticles (Ag-NPs) on Japanese Medaka by studying changes in the expression of stress-related genes using real time RT-PCR analysis and compared these results with those of Medaka exposed to soluble silver ions. The stress-related genes selected here were metallothionein, HSP 70, GST, p53, CYP 1A and the transferrin gene. The expression levels of each gene were determined using two different Ag-NPs dosages and were quantified by measuring the mRNA concentrations in liver extracts with the Taqman-based Real-Time PCR method. The results suggest that these two silver forms have distinguishable toxic fingerprints between them. While the Ag-NPs led to cellular and DNA damage, as well as carcinogenic and oxidative stresses, genes related with metal detoxification/metabolism regulation and radical scavenging action were also induced. In contrast, the ionic silver led to an induction of inflammatory response and metallic detoxification processes in the liver of the exposed fish, but resulted in a lower overall stress response when compared with the Ag-NPs.