Developing a Mobile App for Monitoring Medical Record Changes Using Blockchain: Development and Usability Study.

BACKGROUND: Although we are living in an era of transparency, medical documents are often still difficult to access. Blockchain technology allows records to be both immutable and transparent. OBJECTIVE: Using blockchain technology, the aim of this study was to develop a medical document monitoring system that informs patients of changes to their medical documents. We then examined whether patients can effectively verify the monitoring of their primary care clinical medical records in a system based on blockchain technology. METHODS: We enrolled participants who visited two primary care clinics in Korea. Three substudies were performed: (1) a survey of the recognition of blockchain medical records changes and the digital literacy of participants; (2) an observational study on participants using the blockchain-based mobile alert app; and (3) a usability survey study. The participants' medical documents were profiled with HL7 Fast Healthcare Interoperability Resources, hashed, and transacted to the blockchain. The app checked the changes in the documents by querying the blockchain. RESULTS: A total of 70 participants were enrolled in this study. Considering their recognition of changes to their medical records, participants tended to not allow these changes. Participants also generally expressed a desire for a medical record monitoring system. Concerning digital literacy, most questions were answered with "good," indicating fair digital literacy. In the second survey, only 44 participants-those who logged into the app more than once and used the app for more than 28 days-were included in the analysis to determine whether they exhibited usage patterns. The app was accessed a mean of 5.1 (SD 2.6) times for 33.6 (SD 10.0) days. The mean System Usability Scale score was 63.21 (SD 25.06), which indicated satisfactory usability. CONCLUSIONS: Patients showed great interest in a blockchain-based system to monitor changes in their medical records. The blockchain system is useful for informing patients of changes in their records via the app without uploading the medical record itself to the network. This ensures the transparency of medical records as well as patient empowerment.

Is Blockchain Technology Suitable for Managing Personal Health Records? Mixed-Methods Study to Test Feasibility.

BACKGROUND: There are many perspectives on the advantages of introducing blockchain in the medical field, but there are no published feasibility studies regarding the storage, propagation, and management of personal health records (PHRs) using blockchain technology. OBJECTIVE: The purpose of this study was to investigate the usefulness of blockchains in the medical field in relation to transactions with and propagation of PHRs in a private blockchain. METHODS: We constructed a private blockchain network using Ethereum version 1.8.4 and conducted verification using the de-identified PHRs of 300 patients. The private blockchain network consisted of one hospital node and 300 patient nodes. In order to verify the effectiveness of blockchain-based PHR management, PHRs at a time were loaded in a transaction between the hospital and patient nodes and propagated to the whole network. We obtained and analyzed the time and gas required for data transaction and propagation on the blockchain network. For reproducibility, these processes were repeated 100 times. RESULTS: Of 300 patient records, 74 (24.7%) were not loaded in the private blockchain due to the data block size of the transaction block. The remaining 226 individual health records were classified into groups A (80 patients with outpatient visit data less than 1 year old), B (84 patients with outpatient data from between 1 and 3 years before data collection), and C (62 patients with outpatient data 3 to 5 years old). With respect to mean transaction time in the blockchain, C (128.7 seconds) had the shortest time, followed by A (132.2 seconds) and then B (159.0 seconds). The mean propagation times for groups A, B, and C were 1494.2 seconds, 2138.9 seconds, and 4111.4 seconds, respectively; mean file sizes were 5.6 KB, 18.6 KB, and 45.38 KB, respectively. The mean gas consumption values were 1,900,767; 4,224,341; and 4,112,784 for groups A, B, and C, respectively. CONCLUSIONS: This study confirms that it is possible to exchange PHR data in a private blockchain network. However, to develop a blockchain-based PHR platform that can be used in practice, many improvements are required, including reductions in data size, improved personal information protection, and reduced operating costs.

The Free Radical Scavenger NecroX-7 Attenuates Acute Graft-versus-Host Disease via Reciprocal Regulation of Th1/Regulatory T Cells and Inhibition of HMGB1 Release.

Graft-versus-host disease (GVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation. Despite the prominent role of the adaptive immune system, the importance of controlling the innate immune system in the pathogenesis of GVHD has recently been rediscovered. High-mobility group box 1 (HMGB1) is a crucial damage-associated molecular pattern signal that functions as a potent innate immune mediator in GVHD. In the present study, we investigated treatment of experimental GVHD through HMGB1 blockade using the compound cyclopentylamino carboxymethylthiazolylindole (NecroX)-7. Treated animals significantly attenuated GVHD-related mortality and inhibited severe tissue damage. These protective effects correlated with the decrease in HMGB1 expression and lower levels of reactive oxidative stress. Additionally, NecroX-7 inhibited the HMGB1-induced release of TNF and IL-6, as well as the expression of TLR-4 and receptor for advanced glycation end products. We also observed increased regulatory T cell numbers, which may be associated with regulation of differentiation signals independent of HMGB1. Taken together, these data indicate that NecroX-7 protects mice against lethal GVHD by reciprocal regulation of regulatory T/Th1 cells, attenuating systemic HMGB1 accumulation and inhibiting HMGB1-mediated inflammatory response. Our results indicate the possibility of a new use for a clinical drug that is effective for the treatment of GVHD.

ROS Production and ERK Activity Are Involved in the Effects of d-ß-Hydroxybutyrate and Metformin in a Glucose Deficient Condition.

Hypoglycemia, a complication of insulin or sulfonylurea therapy in diabetic patients, leads to brain damage. Furthermore, glucose replenishment following hypoglycemic coma induces neuronal cell death. In this study, we investigated the molecular mechanism underlying glucose deficiency-induced cytotoxicity and the protective effect of d-ß-hydroxybutyrate (D-BHB) using SH-SY5Y cells. The cytotoxic mechanism of metformin under glucose deficiency was also examined. Cell viability under 1 mM glucose (glucose deficiency) was significantly decreased which was accompanied by increased production of reactive oxygen species (ROS) and decreased phosphorylation of extracellular signal-regulated kinase (ERK) and glycogen synthase 3 (GSK3ß). ROS inhibitor reversed the glucose deficiency-induced cytotoxicity and restored the reduced phosphorylation of ERK and GSK3ß. While metformin did not alter cell viability in normal glucose media, it further increased cell death and ROS production under glucose deficiency. However, D-BHB reversed cytotoxicity, ROS production, and the decrease in phosphorylation of ERK and GSK3ß induced by the glucose deficiency. ERK inhibitor reversed the D-BHB-induced increase in cell viability under glucose deficiency, whereas GSK3ß inhibitor did not restore glucose deficiency-induced cytotoxicity. Finally, the protective effect of D-BHB against glucose deficiency was confirmed in primary neuronal cells. We demonstrate that glucose deficiency-induced cytotoxicity is mediated by ERK inhibition through ROS production, which is attenuated by D-BHB and intensified by metformin.

Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters.

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of 1,000 µM. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and IL-1ß, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of TNF-α, IL-6, and IL-1ß. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

Therapeutic potential of low-dose IL-2 in a chronic GVHD patient by in vivo expansion of regulatory T cells.

Chronic graft-versus-host disease (cGVHD) is a common complication following allogeneic hematopoietic stem cell transplantation (HSCT), which is characterized by autoimmune like inflammatory responses and reduced levels of regulatory T cells (Tregs). Recently, the use of low-dose IL-2 has been reported to selectively increase Tregs and therefore facilitate immune regulation and promote clinical improvements in cGVHD patients. In this report, we describe the case of a cGVHD patient who was treated with daily low-dose IL-2 therapy. Our observations demonstrate that low-dose IL-2 could induce significant expansion of Tregs in vivo leading to improved Treg/Th17 ratios. The patient showed moderate clinical benefits suggesting that multiple factors may be involved in the immunological responses. Therefore, while the therapeutic potential of low-dose IL-2 is promising, strategic approaches may be needed to induce a clinically significant and sustained Treg effect.

Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans.

OBJECTIVES: One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. METHODS: One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. RESULTS: Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P < 0.05). The ATI showed a higher correlation than EI with FEF25-75%, RV and RV/TLC, and was comparable to Exp -856 and the E/I ratio of MLD. The ATI of emphysema and hyperinflated areas on CT showed better correlation than the normal lung area with PFT parameters. CONCLUSIONS: Detailed analysis of density change at inspiration and expiration CT of COPD can provide new insights into pulmonary functional impairment in each lung area. KEY POINTS: • COPD patients show significant air trapping in the lung. • The air trapping index is a comparable parameter to other CT indices. • Air trapping of emphysema and hyperinflated lung areas relates to functional loss. • The emphysema area changes more, with less air trapping than other areas.

Percutaneous biliary covered stent insertion in patients with malignant duodenobiliary obstruction.

BACKGROUND: Although the use of polytetrafluoroethylene (PTFE)-covered biliary stents has proven to be feasible for the treatment of benign and malignant biliary disease, less is known regarding the outcomes of percutaneous placement of a covered stent in patients with malignant duodenobiliary obstruction. PURPOSE: To investigate the technical and clinical efficacy of the percutaneous placement of a PTFE-covered biliary stent in patients with malignant duodenobiliary obstruction. MATERIAL AND METHODS: From April 2007 to September 2012, the medical records of 45 consecutive patients with malignant duodenobiliary obstruction were retrospectively reviewed. All percutaneous biliary stent deployment was performed using PTFE-covered stents, whereas duodenal stent insertion was performed either fluoroscopically or endoscopically using covered or uncovered stents. RESULTS: Biliary stent deployment was technically successful in all patients. None of the stents migrated after deployment. Procedure-related minor complications, including self-limiting hemobilia, occurred in three (7%) patients. Successful internal drainage was achieved in 39 (87%) of the 45 patients. The median survival time after biliary stent placement was 62 days (95% confidence interval, 8-116 days), and the cumulative stent patency rates at 1, 3, 6, and 12 months were 96%, 92%, 75%, and 38%, respectively. The causes of biliary stent dysfunction included stent occlusion caused by a subsequently inserted duodenal stent (n = 7), food impaction (n = 3), and sludge incrustation (n = 1). One patient developed acute cholecystitis 131 days after biliary stent placement and underwent percutaneous transhepatic gallbladder drainage. CONCLUSION: Percutaneous insertion of a PTFE-covered stent is a safe and effective method for palliative treatment of patients with malignant duodenobiliary obstruction. If possible, subsequent biliary stent insertion is preferable in order to prevent possible biliary stent dysfunction caused by subsequent insertion of a duodenal stent.

Age- and gender-specific estimates of cumulative CT dose over 5 years using real radiation dose tracking data in children.

BACKGROUND: It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. OBJECTIVE: To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. MATERIALS AND METHODS: Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. RESULTS: Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. CONCLUSION: Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children.

Atresia of the bilateral pulmonary veins: a rare and dismal anomaly identified on cardiac CT.

BACKGROUND: Imaging findings of bilateral pulmonary vein atresia have not been described. OBJECTIVE: To describe cardiac CT findings and clinical outcomes of bilateral pulmonary vein atresia. MATERIALS AND METHODS: Three newborns with bilateral pulmonary vein atresia were encountered at our institution during a period of 8 years. We evaluated prenatal echocardiographic findings, clinical presentations, postnatal echocardiographic findings, chest radiographic findings, cardiac CT findings and clinical outcomes. RESULTS: All newborns presented immediately after birth with severe cyanosis, respiratory distress and acidosis that were unresponsive to medical management. Prenatal and postnatal echocardiographic studies and chest radiography were misleading, inconclusive or nonspecific in making the diagnosis in these children; however cardiac CT clearly demonstrated atresia of the bilateral pulmonary veins with multiple small mediastinal collateral veins and pulmonary edema. Surgical treatments were not feasible for this anomaly. Their clinical outcomes were universally dismal and all infants died within 3 days. CONCLUSION: Cardiac CT provides an accurate diagnosis of bilateral pulmonary vein atresia and leads to prompt treatment decision in these children.

Development of 5-Fluorouracil/pH-Responsive Adjuvant-Embedded Extracellular Vesicles for Targeting αvß3 Integrin Receptors in Tumors.

To selectively target and treat murine melanoma B16BL6 tumors expressing αvß3 integrin receptors, we engineered tumor-specific functional extracellular vesicles (EVs) tailored for the targeted delivery of antitumor drugs. This objective was achieved through the incorporation of a pH-responsive adjuvant, cyclic arginine-glycine-aspartic acid peptide (cRGD, serving as a tumor-targeting ligand), and 5-fluorouracil (5-FU, employed as a model antitumor drug). The pH-responsive adjuvant, essential for modulating drug release, was synthesized by chemically conjugating 3-(diethylamino)propylamine (DEAP) to deoxycholic acid (DOCA, a lipophilic substance capable of integrating into EVs' membranes), denoted as DEAP-DOCA. The DOCA, preactivated using N-(2-aminoethyl)maleimide (AEM), was chemically coupled with the thiol group of the cRGD-DOCA through the thiol-maleimide click reaction, resulting in the formation of cRGD-DOCA. Subsequently, DEAP-DOCA, cRGD-DOCA, and 5-FU were efficiently incorporated into EVs using a sonication method. The resulting tumor-targeting EVs, expressing cRGD ligands, demonstrated enhanced in vitro/in vivo cellular uptake specifically for B16BL6 tumors expressing αvß3 integrin receptors. The ionization characteristics of the DEAP in DEAP-DOCA induced destabilization of the EVs membrane at pH 6.5 through protonation of the DEAP substance, thereby expediting 5-FU release. Consequently, an improvement in the in vivo antitumor efficacy was observed for B16BL6 tumors. Based on these comprehensive in vitro/in vivo findings, we anticipate that this EV system holds substantial promise as an exceptionally effective platform for antitumor therapeutic delivery.

A novel kit for enrichment of fecal helminth eggs.

We developed a new concentration kit, called the ParaEgg (PE), for easy detection trematode eggs from fecal samples in endemic areas of clonorchiasis and metagonimiasis in Korea. To create a standard of detection efficiency, 120 fecal samples were examined using the water-ether concentration method (WECM). The PE kit and Mini ParaSep (PS) kit were used to compare the detection sensitivity of 100 egg-positive and 20 egg-negative samples in WECM. Additionally, stool samples, which were intentionally spiked with 10, 20, and 30 Clonorchis sinensis eggs, were evaluated to assess the sensitivity in lowinfection cases. The PE and PS kits showed detection rates of 100% and 92%, respectively, from 100 egg-positive samples in WECM. Meanwhile, eggs were detected in 3 (PE) and 2 (PS) out of 20 egg-negative samples in WECM. The PE kit detected the highest number of eggs per gram of feces (727 on average), followed by the WECM (524) and PS kit (432). In fecal samples that were intentionally spiked with 10, 20, and 30 C. sinensis eggs, PE only detected eggs 2 out of 5 samples in 10 eggs spiked (40%), and the detection rates were 80% and 100%, respectively. The PE kit enabled a more accurate identification of trematode eggs because of the clearance of small fecal debris in the microscopic field. In conclusion, the PE kit is obviously helpful to detect and identify trematode eggs in stool examinations especially in endemic areas of clonorchiasis and metagonimiasis.

A blockchain-based healthcare data marketplace: prototype and demonstration.

Objectives: This study aimed to develop healthcare data marketplace using blockchain-based B2C model that ensures the transaction of healthcare data among individuals, companies, and marketplaces. Materials and methods: We designed an architecture for the healthcare data marketplace using blockchain. A healthcare data marketplace was developed using Panacea, MySQL 8.0, JavaScript library, and Node.js. We evaluated the performance of the data marketplace system in 3 scenarios. Results: We developed mobile and web applications for healthcare data marketplace. The transaction data queries were executed fully within about 1-2 s, and approximately 9.5 healthcare data queries were processed per minute in each demonstration scenario. Discussion: Blockchain-based healthcare data marketplaces have shown compliance performance in the process of data collection and will provide a meaningful role in analyzing healthcare data. Conclusion: The healthcare data marketplace developed in this project can iron out time and place limitations and create a framework for gathering and analyzing fragmented healthcare data.

Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy.

In this study, we fabricated γ-cyclodextrin (γCD)-based nanoparticles (NPs) for dual antitumor therapy. First, γCD (the backbone biopolymer) was chemically conjugated with low-molecular-weight hyaluronic acid (HA; a tumoral CD44 receptor-targeting molecule) and 3-(diethylamino)propylamine (DEAP; a pH-responsive molecule), termed as γCD-(DEAP/HA). The obtained γCD-(DEAP/HA) self-assembled in aqueous solution, producing the γCD-(DEAP/HA) NPs. These NPs efficiently entrapped paclitaxel (PTX; an antitumor drug) and triiron dodecacarbonyl (FeCO; an endogenous cytotoxic gas molecule) via hydrophobic interactions between PTX and FeCO with the unprotonated DEAP molecules in γCD-(DEAP/HA) and a possible host-guest interaction in the γCD rings. The release of PTX and FeCO from the NPs resulted from particle destabilization at endosomal pH, probably owing to the protonation of DEAP in the NPs. In vitro studies using MCF-7 tumor cells demonstrated that these NPs were efficiently internalized by the cells expressing CD44 receptors and enhanced PTX/FeCO-mediated tumor cell apoptosis. Importantly, local light irradiation of FeCO stimulated the generation of cytotoxic CO, resulting in highly improved tumor cell death. We expect that these NPs have potential as dual-modal therapeutic candidates with enhanced antitumor activity in response to acidic pH and local light irradiation.

Seroprevalence of Varicella-Zoster Virus and Measles among Healthcare Workers in a Tertiary Medical Center in Korea.

Measles and varicella still occur in the general population despite the widespread vaccination against them, and healthcare workers (HCWs) are still at risk of exposure to these diseases. Here, we evaluated the seroprevalence of measles and varicella-zoster virus (VZV) in HCWs and the trend of seroprevalence according to age, birth year, and occupational group. The serostatuses of measles and VZV of HCWs during new employee medical examinations between October 2015 and October 2021 were included. Thereafter, the trends of seroprevalence according to age, birth year, and occupational groups were evaluated. Overall, 2070 and 1827 HCWs were evaluated for VZV and measles serostatus, respectively. The seroprevalences of VZV and measles were 91% (1884/2070) and 70% (1284/1827), respectively. Younger HCWs had a significantly lower seroprevalence of measles (p = 0.02, age) and VZV (p = 0.003, birth year and p < 0.001, age). The seroprevalence of measles and VZV was significantly higher among doctors and nursing assistants than among nurses and other HCWs (p < 0.001 in both). In conclusion, the seroprevalence of measles and VZV significantly decreased in younger HCWs. Additionally, monitoring the serostatus of measles and VZV and the immunization of susceptible HCWs are required to prepare and control infectious diseases in healthcare facilities.

The effectiveness of Paxlovid treatment in long-term care facilities in South Korea during the outbreak of the Omicron variant of SARS-CoV-2.

OBJECTIVES: On November 5, 2021, Pfizer Inc. announced Paxlovid (nirmatrelvir +ritonavir) asa treatment method that could reduce the risk of hospitalization or death for patients withconfirmed coronavirus disease 2019 (COVID-19). METHODS: From February 6, 2022 to April 2, 2022, the incidence of COVID-19 and the effectsof treatment with Paxlovid were analyzed in 2,241 patients and workers at 5 long-term carefacilities during the outbreak of the Omicron variant of severe acute respiratory syndromecoronavirus 2 in South Korea. RESULTS: The rate of severe illness or death in the group given Paxlovid was 51% lower thanthat of the non-Paxlovid group (adjusted risk ratio [aRR], 0.49; 95% confidence interval [CI],0.24-0.98). Compared to unvaccinated patients, patients who had completed 3 doses of thevaccine had a 71% reduced rate of severe illness or death (aRR, 0.29; 95% CI, 0.13-0.64) and a65% reduced death rate (aRR, 0.35; 95% CI, 0.15-0.79). CONCLUSION: Patients given Paxlovid showed a lower rate of severe illness or death and alower fatality rate than those who did not receive Paxlovid. Patients who received 3 dosesof the vaccine had a lower rate of severe illness or death and a lower fatality rate than theunvaccinated group.

Developing a Mobile App for Patients to Monitor Medical Record Changes Using Blockchain.

According to recent revisions to medical laws in Korea, changes to electronic medical records are to be documented. To do so, however, a transparent system with which to store original documents and changes thereto is needed. The transparency and immutability of blockchain records are the key characters of blockchain technology. Employing these characteristics, we developed an application with which to monitor changes of medical records using blockchain.

Alendronate/cRGD-Decorated Ultrafine Hyaluronate Dot Targeting Bone Metastasis.

In this study, we report the hyaluronate dot (dHA) with multiligand targeting ability and a photosensitizing antitumor model drug for treating metastatic bone tumors. Here, the dHA was chemically conjugated with alendronate (ALN, as a specific ligand to bone), cyclic arginine-glycine-aspartic acid (cRGD, as a specific ligand to tumor integrin αvß3), and photosensitizing chlorin e6 (Ce6, for photodynamic tumor therapy), denoted as (ALN/cRGD)@dHA-Ce6. These dots thus prepared (≈10 nm in diameter) enabled extensive cellular interactions such as hyaluronate (HA)-mediated CD44 receptor binding, ALN-mediated bone targeting, and cRGD-mediated tumor integrin αvß3 binding, thus improving their tumor targeting efficiency, especially for metastasized MDA-MB-231 tumors. As a result, these dots improved the tumor targeting efficiency and tumor cell permeability in a metastatic in vivo tumor model. Indeed, we demonstrated that (ALN/cRGD)@dHA-Ce6 considerably increased photodynamic tumor ablation, the extent of which is superior to that of the tumor ablation of dot systems with single or double ligands. These results indicate that dHA with multiligand can provide an effective treatment strategy for metastatic bone tumors.

Predicting risk of type 2 diabetes mellitus in Korean adults aged 40-69 by integrating clinical and genetic factors.

AIMS: The purpose of our investigation was to identify the genetic and clinical risk factors of type 2 diabetes mellitus (T2DM) and to predict the incidence of T2DM in Korean adults aged 40-69 at follow-up intervals of 5, 7, and 10years. METHODS: Korean Genome and Epidemiology Study (KoGES) cohort data (n=10,030) were used to develop T2DM prediction models. Both clinical-only and integrated (clinical factors+genetic factors) models were derived using the Cox proportional hazards model. Internal validation was performed to evaluate the prediction capabilities of the clinical and integrated models. RESULTS: The clinical model included 10 selected clinical risk factors. The selected SNPs for the integrated model were rs9311835 in PTPRG, rs10975266 in RIC1, rs11057302 in TMED2, rs17154562 in ADAM12, and rs8038172 in CGNL1. For the clinical model, validated c-indices with time points of 5, 7, and 10 years were 0.744, 0.732, and 0.732, respectively. Slightly higher validated c-indices were observed for the integrated model at 0.747, 0.736, and 0.738, respectively. The p-values of the survival net reclassification improvement (NRI) for the SNP point-based score were statistically significant. CONCLUSIONS: Clinical and integrated models can be effectively used to predict the incidence of T2DM in Koreans.

Detection of thioredoxin-1 using ultra-sensitive ELISA with enzyme-encapsulated human serum albumin nanoparticle.

Many methods for early diagnosis of the disease use biomarker tests, which measure indicators of biological state in body fluids or blood. However, a limitation of these methods is their low sensitivity to biomarkers. In this study, human serum albumin (HSA) based nanoparticles capable of encapsulating excess horseradish peroxidase (HRP) are synthesized and applied to the development of enzyme-linked immunosorbent assay (ELISA) kit with ultra-high sensitivity. The size of the nanoparticles and the amount of encapsulated enzyme are controlled by varying the synthesis conditions of pH and protein concentration, and the surface of the nanoparticles is modified with protein A (proA) to immobilize antibodies to the nanoparticles by self-assembly. Using the synthesized nanoparticles, the biomarker of breast cancer, thioredoxin-1, can be measured in the range of 10 fM to 100 pM by direct sandwich ELISA, which is 105 times more sensitive than conventional methods.