Mid-Term Strategic Plan for the Public Health and Medical Care Cooperation in the Korean Peninsula.

As extensive as the concept of and the resources required for 'Health for Korean Unification' are, and due to the limited access to information on the state of health and medical care in North Korea, discussion on 'Health for Korean Unification' has tended to be intermittent and lacked concrete action plans. In this article, we specifically distinguished areas of cooperation and selected five executable agenda that meet the goals of international development cooperation: 1) Health security; 2) Easing the burden of major diseases; 3) Resilient healthcare system; 4) R&D cooperation; 5) Sustainable cooperation system. Then we provided corresponding strategic priorities and operative directions, in consideration of future military and political sanctions against North Korea. The strategies we outline are sustainable, preemptive for problems that might affect lives of South and North Korean citizens, and satisfy the unmet needs of the North Korean health system. Throughout the process, we utilized a special platform, the 'Korean Peninsula Healthcare Cooperation Platform,' designed to enable continual communication across sectors engaged in public health and medical care. By doing so, we take the first step to actually carry out the 'Health for Korean Unification,' which tended to have remained on the discussion agenda.

Analysis of Changes in Antibiotic Use Patterns in Korean Hospitals during the COVID-19 Pandemic.

With the onset of the coronavirus disease 2019 (COVID-19) pandemic, changes in patient care and antibiotic use have occurred in hospitals. The data of the National Health Insurance System's claims of inpatients from all hospitals in Korea between January 2019 and December 2020 were obtained from the Health Insurance Review & Assessment Service and analyzed. The trend in the use of all antibacterial agents in both hospitals declined for the total number of COVID-19 patients at the bottom 10% and those in the top 10%. Specifically, a decreasing trend in the use of broad-spectrum antibacterial agents predominantly prescribed for community-acquired cases and narrow-spectrum beta-lactam agents were observed in both hospitals. In the aftermath of the COVID-19 pandemic, the total use of antibacterial agents has gradually decreased among patients with pneumonia and those with severe COVID-19. In contrast, its use has increased gradually among those with mild to moderate COVID-19. A decreasing trend in overall antibiotic use was observed during the COVID-19 pandemic, and an increasing trend in antibiotic use was observed in patients with mild to moderate COVID-19 in Korean hospitals.

Effect of Human Amniotic Epithelial Stem Cell Transplantation on Preterm Premature Rupture of Fetal Membrane Using the Amniotic Pore Culture Technique in vitro.

OBJECTIVES: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro. DESIGN: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes. MATERIALS: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study. SETTINGS: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control. METHODS: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05. RESULTS: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 µm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 µm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8). LIMITATIONS: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested. CONCLUSIONS: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine.

Quantitative Evaluation of the Economic Impact of Antimicrobial Resistance on the Treatment of Community-Acquired Acute Pyelonephritis in Korea.

BACKGROUND: The proportion of antimicrobial-resistant Enterobacteriales as a causative pathogen of community-acquired acute pyelonephritis (APN) has been increasing. The aim of this study was to quantitatively evaluate the impact of antimicrobial resistance on medical costs and length of hospital stay for the treatment of APN. MATERIALS AND METHODS: A single-center retrospective cohort study was conducted between January 2018 and December 2019. All hospitalized patients aged ≥19 years who were diagnosed with community-acquired APN were recruited, and those diagnosed with Enterobacteriales as a causative pathogen were included. Log-linear regression analysis was performed to determine the risk factors for medical costs and length of hospital stay. RESULTS: A total of 241 patients participated in this study. Of these, 75 (31.1%) and 87 (36.1%) had extended-spectrum beta-lactamase (ESBL)-producing pathogens and ciprofloxacin-resistant pathogens as the causative pathogen, respectively. Based on the log-linear regression model, ESBL-producing Enterobacteriales is a causative pathogen that is, on average, 27.0%, or United States Dollar (USD) 1,211 (P = 0.026) more expensive than non-ESBL-producing Enterobacteriales. A patient who is a year older would incur USD 23 (P = 0.040) more, those having any structural problems in the urinary tract would incur USD 1,231 (P = 0.015) more, and those with a unit increase in the Pitt bacteremia score would incur USD 767 (P <0.001) more, with all other variables constant. Having a case in which ESBL-producing Enterobacteriales is a causative pathogen would explain staying 22.0% longer or 2 more days (P = 0.050) in the hospital than non-ESBL-producing Enterobacteriales. A patient who is 10 years older would, on average, would have to stay for half a day longer (P = 0.045). Any structural problems in the urinary tract explain a longer stay (2.4 days longer; P = 0.032), and moving from 0 to 5 on the Pitt bacteremia score would explain four more days (P = 0.038) in the hospital. CONCLUSION: Patients with community-acquired APN with ESBL-producing Enterobacteriale as the causative pathogen would incur, on average, 27.0% higher medical costs and 22.0% longer hospitalization days than patients detected with non-ESBL-producing pathogens.

Nose-to-brain delivery of hyaluronate - FG loop peptide conjugate for non-invasive hypoxic-ischemic encephalopathy therapy.

The intranasal drug administration has attracted great interest as a non-invasive route allowing targeted delivery of drugs directly to the brain. However, one of the main issues in nasal drug administration is mucociliary clearance. Hyaluronate (HA) has been widely used as a mucoadhesive excipient for ocular, rectal, and vaginal delivery. Here, FG loop peptide (FGL) was conjugated to HA for improving enzymatic stability and delivery efficiency from the nose to the brain. The successful conjugation of FGL to aldehyde modified HA was confirmed by gel permeation chromatography (GPC) and 1H nuclear magnetic resonance (NMR). The outstanding enzymatic stability of HA-FGL conjugate was also corroborated by the GPC. The HA-FGL conjugate showed enhanced binding affinity onto nasal epithelial cells. In addition, in vivo nose-to-brain delivery of HA-FGL conjugate could be visualized by using an IVIS imaging system and fluorescence microscopy. Finally, in vivo therapeutic effect of HA-FGL conjugate was successfully confirmed by histological analysis, transferase-mediated uridine 5-triphosphate-biotin nick end-labeling (TUNEL) assay, immunofluorescent staining, transmission electron microscopy (TEM), and rotarod tests in hypoxic-ischemic encephalopathy model animals.

Synergistic effects of hyaluronate - epidermal growth factor conjugate patch on chronic wound healing.

The proteolytic microenvironment in the wound area reduces the stability and the half-life of growth factors in vivo, making difficult the topical delivery of growth factors. Here, epidermal growth factor (EGF) was conjugated to hyaluronate (HA) to improve the long-term stability against enzymatic degradation and the therapeutic effect by enhancing the biological interaction with HA receptors on skin cells. After the synthesis of HA-EGF conjugates, they were incorporated into a patch-type formulation for the facile topical application and sustained release of EGF. According to ELISA, the HA-EGF conjugates showed a long-term stability compared with native EGF. Furthermore, HA-EGF conjugates appeared to interact with skin cells through two types of HA and EGF receptors, resulting in a synergistically improved healing effect. Taken together, we could confirm the feasibility of HA-EGF conjugates for the transdermal treatment of chronic wounds.

Bioimaging of botulinum toxin and hyaluronate hydrogels using zwitterionic near-infrared fluorophores.

BACKGROUND: The injection of botulinum toxin (BTX) to reduce facial wrinkles is one of the most frequently performed plastic surgery procedures. The biocompatible hydrogels are injected with BTX for effective tissue augmentation. However, it is difficult to determine the interval of injection for effective tissue augmentation. METHOD: BTX and hyaluronate (HA) hydrogels were labeled with zwitterionic (ZW) near-infrared (NIR) fluorophores and visualized for 3 weeks after injection to BALB/c nude mice. RESULTS: BTX-ZW conjugates and diaminohexane (DAH)-HA-ZW hydrogels were successfully prepared by the conventional EDC/NHS chemistry. Using the NIR fluorescence imaging, we confirmed that approximately 10% of BTX-ZW conjugates and 50% of DAH-HA-ZW hydrogels remained 3 weeks post-injection. CONCLUSION: This bioimaging technique using invisible NIR fluorescence light can be exploited for various biomedical applications.

Targeted systemic mesenchymal stem cell delivery using hyaluronate - wheat germ agglutinin conjugate.

A variety of receptors for hyaluronate (HA), a natural linear polysaccharide, were found in the body, which have been exploited as target sites for HA-based drug delivery systems. In this work, mesenchymal stem cells (MSCs) were surface-modified with HA - wheat germ agglutinin (WGA) conjugate for targeted systemic delivery of MSCs to the liver. WGA was conjugated to HA by coupling reaction between aldehyde-modified HA and amine group of WGA. The conjugation of WGA to HA was corroborated by gel permeation chromatography (GPC) and the successful surface modification of MSCs with HA-WGA conjugate was confirmed by confocal microscopy. The synthesized HA-WGA conjugate could be incorporated onto the cellular membrane by agglutinating the cell-associated carbohydrates. Fluorescent imaging for in vivo biodistribution visualized the targeted delivery of the HA-WGA/MSC complex to the liver after intravenous injection. This new strategy for targeted delivery of MSCs using HA-WGA conjugate might be successfully exploited for various regenerative medicines including cell therapy.

Obesity and Hypertension among School-going Adolescents in Peru.

BACKGROUND: Adolescent obesity and hypertension are global public health issues. The burden of adolescent obesity and hypertension in Peru is unclear. The aim of this study was to determine the prevalence of obesity and hypertension and their relationship among school-attending adolescents and to assess the need for health-promoting school programs in the study area. METHODS: A cross-sectional school-based survey was conducted in a randomly selected sample of 952 secondary school adolescents from 11 schools in Lima or Callao, Peru, in 2014. Weight, height, and blood pressure (BP) were measured and categorized. Obesity was defined as ≥ 95(th) percentile in body mass index (BMI) for age and sex. Hypertension was defined as average systolic blood pressure and/or diastolic blood pressure ≥95(th) percentile in BP for sex, age, and height. Chi-square test and univariate logistic regressions were used at a 5% significance level to determine the relationship between BMI and BP category. RESULTS: The mean age of subjects was 14.6 years; 46.4% were boys and 53.6% were girls. The prevalence of overweight and obesity was 20.2% and 9.5% overall, 17.4% and 11.1% for boys, and 22.5% and 8.0% for girls, respectively. The prevalence of hypertension was 26.7% overall, 34.8% for boys, and 19.6% for girls. In both sexes, BMI was strongly associated with BP (p < 0.01). CONCLUSION: The prevalence of obesity and hypertension observed in the study area is relatively high. Overweight and obesity are strongly associated with BP status among adolescents. Health-promoting school programs may reduce the burdens of obesity and hypertension among school-going adolescents.

Hyaluronate-gold nanoparticle/tocilizumab complex for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory immune disease causing the inflammation of synovial membrane and the articular cartilage destruction. In this work, hyaluronate-gold nanoparticle/Tocilizumab (HA-AuNP/TCZ) complex was prepared for the treatment of RA. AuNP was used as a drug carrier with antiangiogenic effect. TCZ is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and used as an immunosuppressive drug by interfering IL-6 in the pathogenesis of RA. HA is known to have cartilage-protective and lubricant effects. HA was modified with cystamine via reductive amination, which was reduced with dithiothreitol (DTT) to prepare end-group thiolated HA (HA-SH). AuNP was chemically modified with HA-SH and physically modified with TCZ. The formation of HA-AuNP/TCZ complex was corroborated by UV-vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The therapeutic effect of HA-AuNP/TCZ complex on RA was confirmed in collagen-induced arthritis (CIA) model mice by ELISA, histological, and Western blot analyses.

Repression of TNF-alpha-induced IL-8 expression by the glucocorticoid receptor-beta involves inhibition of histone H4 acetylation.

Increased expression of a number of proinflammatory genes, including IL-8, is associated with inflammatory conditions such as asthma. Glucocorticoid receptor (GR)beta, one of the GR isoforms, has been suggested to be upregulated in asthma associated with glucocorticoid insensitivity and to work as a dominant negative inhibitor of wild type GRalpha. However, recent data suggest that GRbeta is not a dominant negative inhibitor of GRalpha in the transrepressive process and has its own functional role. We investigated the functional role of GRbeta expression in the suppressive effect of glucocorticoids on tumor necrosis factor (TNF)-alpha-induced IL-8 release in an airway epithelial cell line. GRbeta expression was induced by treatment of epithelial cells with either dexamethasone or TNF-alpha. GRbeta was able to inhibit glucocorticoid-induced transcriptional activation mediated by binding to glucocorticoid response elements (GREs). The suppressive effect of dexamethasone on TNF-alpha-induced IL-8 transcription was not affected by GRbeta overexpression, rather GRbeta had its own weak suppressive activity on TNF-alpha-induced IL-8 expression. Overall histone deacetylase activity and histone acetyltransferase activity were not changed by GRbeta overexpression, but TNF-alpha-induced histone H4 acetylation at the IL-8 promoter was decreased with GRbeta overexpression. This study suggests that GRbeta overexpression does not affect glucocorticoid-induced suppression of IL-8 expression in airway epithelial cells and GRbeta induces its own histone deacetylase activity around IL-8 promoter site.