Analysis of Military-Civilian Patient Handoff at Vista Forge Multi-Agency Nuclear Disaster Exercise 2022.

INTRODUCTION: The leadership of Vista Forge 2022 requested evaluation of the handoff process between military assets and civilian emergency medical services (EMS) providers by the Beth Israel Deaconess Fellowship in Disaster Medicine (BIDMF). Vista Forge was a multi-agency military-civilian full-scale disaster exercise coordinated by the U.S. Military. The exercise, held in Atlanta, Georgia, simulated response to a nuclear bomb in an urban setting by military and civilian disaster teams. MATERIALS AND METHODS: BIDMF had several two-person teams who monitored handoff procedures between military assets after decontamination and civilian emergency medical services providers during the exercise evaluation. RESULTS: A verbal handoff between military and civilian entities was usually not done. Triage tags placed on mannequins before decontamination remained attached to the bodies and were sent with them to civilian hospitals. Triage tags were generic military forms without specific radiation or chemical exposure information. Not all decontamination groups had the same medical capabilities, and in a disaster it is unclear how these teams would manage medical emergencies. CONCLUSIONS: Future studies should develop a standardized handoff procedure to be used in mass casualty situations, and trial it in future multi-agency disaster exercises. Radiation specific triage tags should be considered.

Pulmonary abnormality screening on chest x-rays from different machine specifications: a generalized AI-based image manipulation pipeline.

BACKGROUND: Chest x-ray is commonly used for pulmonary abnormality screening. However, since the image characteristics of x-rays highly depend on the machine specifications, an artificial intelligence (AI) model developed for specific equipment usually fails when clinically applied to various machines. To overcome this problem, we propose an image manipulation pipeline. METHODS: A total of 15,010 chest x-rays from systems with different generators/detectors were retrospectively collected from five institutions from May 2020 to February 2021. We developed an AI model to classify pulmonary abnormalities using x-rays from a single system. Then, we externally tested its performance on chest x-rays from various machine specifications. We compared the area under the receiver operating characteristics curve (AUC) of AI models developed using conventional image processing pipelines (histogram equalization [HE], contrast-limited histogram equalization [CLAHE], and unsharp masking [UM] with common data augmentations) with that of the proposed manipulation pipeline (XM-pipeline). RESULTS: The XM-pipeline model showed the highest performance for all the datasets of different machine specifications, such as chest x-rays acquired from a computed radiography system (n = 356, AUC 0.944 for XM-pipeline versus 0.917 for HE, 0.705 for CLAHE, 0.544 for UM, p [Formula: see text] 0.001, for all) and from a mobile x-ray generator (n = 204, AUC 0.949 for XM-pipeline versus 0.933 for HE, p = 0.042, 0.932 for CLAHE (p = 0.009), 0.925 for UM (p = 0.001). CONCLUSIONS: Applying the XM-pipeline to AI training increased the diagnostic performance of the AI model on the chest x-rays of different machine configurations. RELEVANCE STATEMENT: The proposed training pipeline would successfully promote a wide application of the AI model for abnormality screening when chest x-rays are acquired using various x-ray machines. KEY POINTS: • AI models developed using x-rays of a specific machine suffer from generalization. • We proposed a new image processing pipeline to address the generalization problem. • AI models were tested using multicenter external x-ray datasets of various machines. • AI with our pipeline achieved the highest diagnostic performance than conventional methods.

A Descriptive Analysis of the Use of Chemical, Biological, Radiological, and Nuclear Weapons by Violent Non-State Actors and the Modern-Day Environment of Threat.

INTRODUCTION: The use of chemical, biological, radiation, and nuclear (CBRN) weapons is not new, and though rare, it is an issue of concern around the world due to their ability to cause large-scale mass-casualty events and their potential threat to global stability. The purpose of this study is to explore the use of CBRN weapons by non-state actors through analysis of the Violent Non-State Actor (VNSA) CBRN Event database, and aims to better inform health care systems of the potential risks and consequences of such events. METHODS: Data collection was performed using a retrospective database search through the VNSA CBRN Event database. RESULTS: A total of 565 events were recorded. Five hundred and five (505) events (89.4%) involved single agents while 60 events (10.6%) involved multiple agents. Fatalities numbered 965 for chemical agents, 19 for biological agents, and none for radiological and nuclear events. Injuries numbered 7,540 for chemical agents, 59 for biological agents, 50 for radiological events, and none for nuclear attacks. Fatality and injury per attack was 2.22 and 17.37, respectively, for chemical event agents and 0.15 and 0.48, respectively, for biological event agents. CONCLUSION: Violent Non-State Actors were responsible for 565 unique events around the world involving the use of CBRN weapons from 1990-2020. The United States (118), Russia (49), and Iraq (43) accounted for the top three countries where these events occurred. While CBRN events remain relatively rare, technological advances have the potential to facilitate the use of such weapons as part of a hybrid warfare strategy with significant repercussions for civilian health and health care systems.

Improved inference for doubly robust estimators of heterogeneous treatment effects.

We propose a doubly robust approach to characterizing treatment effect heterogeneity in observational studies. We develop a frequentist inferential procedure that utilizes posterior distributions for both the propensity score and outcome regression models to provide valid inference on the conditional average treatment effect even when high-dimensional or nonparametric models are used. We show that our approach leads to conservative inference in finite samples or under model misspecification and provides a consistent variance estimator when both models are correctly specified. In simulations, we illustrate the utility of these results in difficult settings such as high-dimensional covariate spaces or highly flexible models for the propensity score and outcome regression. Lastly, we analyze environmental exposure data from NHANES to identify how the effects of these exposures vary by subject-level characteristics.

Terrorism-Related Attacks in East Asia from 1970 through 2020.

AIM: This study aims to analyze and describe terrorism-related attacks in East Asia from 1970 through 2020. BACKGROUND: East Asia consists of South Korea, North Korea, Singapore, Hong Kong, China, Japan, Taiwan, and Macao. According to the Global Terrorism Index (GTI) 2022, the impact of terrorism in East Asia is very low. However, the assassination of former Japanese Prime Minister Shinzo Abe on July 8, 2022 demonstrates that East Asia is not safe from terrorist attacks. This descriptive analysis of terrorist attacks in East Asia will help first responders, Emergency Medical Services (EMS), hospital-based medical providers, and policymakers establish a more refined hazard vulnerability assessment (HVA) framework and develop a Counter-Terrorism Medicine (CTM) mitigation, preparedness, response, and recovery plan. METHODS: This is a descriptive observational study drawing data from the Global Terrorism Database (GTD) from January 1, 1970 through December 31, 2020. Epidemiology outcomes included primary weapon type, primary target type, the country where the incident occurred, and the number of total deaths and injured collected. Data from 2021 were not yet available at the time of this study. Results were exported into an Excel spreadsheet (Microsoft Corp.; Redmond, Washington USA) for analysis. RESULTS: There were 779 terrorism-related events in East Asia from 1970 through 2020. In total, the attacks resulted in 1,123 deaths and 9,061 persons injured. The greatest number of attacks (371; 47.63%) occurred in Japan and the second most occurred in China (268; 34.4%). Explosives were the most used primary weapon type (308; 39.54%) in the region, followed by incendiary devices (260; 33.38%). Terrorist attacks drastically diminished from their peak of 92 in 1990, but there were additional peaks of 88 in 1996, 18 in 2000, 20 in 2008, and 36 attacks in 2014. CONCLUSIONS: A total of 779 terrorist attacks occurred from 1970 through 2020 in East Asia, resulting in 1,123 deaths and 9,061 injuries. Of those, 82.03% attacks occurred in Japan and China. Terrorist attacks drastically diminished since their peak in 1996, but there is an overall uptrend in attacks since 1999.

Analysis of Factors Contributing to the Occurrence of Systemic Toxicity in Patients with Hydrofluoric Acid Skin Exposure Injury: An Individual Participant Data Meta-Analysis of 125 Clinical Cases from 1979 to 2020.

The purpose of this study is to analyze the factors contributing to the occurrence of systemic toxicity in patients injured after skin exposure to hydrofluoric acid (HFA) and to present guidelines for active treatment intervention based on this analysis. Data were acquired from EMBASE, PubMed, and Cochrane library for individual participant data (IPD) meta-analysis. Key searching terms included calcium gluconate (CAG), hydrofluoric acid, and case. This research consisted of case studies published between 1979 and 2020. Systemic toxicity was set as the main outcome. Data sets from 50 case studies (N = 125 participants) were analyzed. Multivariate binary logistic regression analyses of IPD found significant association effect of the total body surface area (TBSA) burned, indicating systemic toxicity [Regression coefficient estimate, 0.82; SE, 0.41; Odds ratio, 2.28; [95% confidence interval, 1.03-5.06], and p = 0.0424]. The optimal cutoff point (sensitivity; specificity) of the receiver operating characteristic curve of the total body surface area (TBSA) burned for contributing occurrence of systemic toxicity was 2.38(0.875; 0.959). IPD meta-analysis indicates that existing evidence supports the positive proportional association of the TBSA burned for systemic toxicity. If the TBSA burned (%) in patients exposed to hydrofluoric acid is greater than 2.38, early aggressive treatment intervention, including decontamination and various CAG application, should be recommended as the guideline.

Comparative Analysis of Hydrogen Fluoride-Exposed Patients Based on Major Burn Criteria After the 2012 Gumi City Chemical Leak Disaster.

This study conducted to analyze and compare the epidemiological and clinical characteristics of hydrogen fluoride-exposed patients based on major burn criteria for the appropriate emergency department (ED) response to a mass casualty chemical spill. This retrospective cross-sectional study included the records of patients (n = 199) who visited the ED of Gumi City University Hospital from September 27, 2012, to October 20, 2012. Subjects were included in the major burn group (MBG) if they presented with wounds that required referral to a burn center according to the American Burn Association guidelines or in the nonmajor burn group (NMBG) if not. Males were predominant in both the MBG (n = 55, 48 males) and NMBG (n = 144, 84 males; P < .05). The most prevalent timeline for visiting the ED was the phase which included 9-32 hours post-leak of hydrogen fluoride, including 45 patients (81.8%) in the MBG and 122 patients (84.7%) in the NMBG (P < .001). The respiratory tract was the site of greatest damage in patients in both the MBG and NMBG (n = 47, 85.5% vs n = 142, 98.6%, P < .001). Regarding dispositions, all patients in the NMBG were discharged (n = 144, 100%); however, eight patients (14.5%) in the MBG underwent other dispositions (discharge against medical advice, five patients; admission, one patient; death, two patients, P < .05). Patient outcomes after major chemical contamination events should be characterized in future studies to maximize the quality of patient care.

Operation and management of a community treatment center using telemedicine for foreign patients with mild COVID-19 symptoms.

ABSTRACT: South Korean studies on coronavirus disease-2019 (COVID-19) treatment have described the use of community treatment centers (CTCs), which combine elements of the home and hospital, to isolate and treat mild COVID-19 patients. While the number of South Koreans diagnosed with COVID-19 cases has varied greatly by season, the number of confirmed cases in foreign nationals has shown no seasonality, with an average of around 25 to 30 per day. For foreign patients, accommodation arrangements and travel routes may be difficult; they may also have difficulty accessing medical care, so require careful management.We discuss our experience in operating and managing a CTC for foreign COVID-19 patients arriving in South Korea with mild symptoms. We also propose guidelines for efficient use of resources with respect to treating these patients in CTCs.We present the clinical findings of patients treated at the CTC between 7 October and 22 November 2020, and make some recommendations. We quarantined and treated foreign patients with mild symptoms of COVID-19 at the Ansan CTC. Discharge is determined based on clinical symptoms rather than polymerase chain reaction results. Medical and administrative staff use building A, while building B is used for isolating patients. Medical rounds are in the form of twice-daily video calls. Three kinds of foods with medication are served according to the patient's country of origin.In total, 315 patients were admitted to the Ansan CTC between 7 October and 22 November 2020; 145 of them were discharged from the CTC and 26 were transferred to other hospitals.To utilize medical resources efficiently during the pandemic, it is desirable to reserve CTCs exclusively for foreign patients.

Evaluating the Effectiveness of the Chemical-Mass Casualty Incident Response Education Module (C-MCIREM): A Pilot Simulation Study With a Before and After Design.

Background With the occurrence of a number of major disasters around the world, there is growing interest in chemical disaster medicine. In South Korea, there is a training program for mass casualty incidents (MCI) and backup by legal regulations by the Framework Act on the Management of Disasters and Safety. However, there is no program focusing on chemical disasters. Thus, the authors newly created a program, the Chemical-Mass Casualty Incident Response Education Module (C-MCIREM) in September 2019. This was a pilot study to verify the educational effect of the program. Method A pre/post study was conducted of a chemical MCI training program based on simulation. A total of 25 representative and qualified participants were recruited from fire departments, administrative staff of public health centers, and healthcare workers of hospitals in the Gyeonggi-do province of South Korea. They participated in a one-day training program. A knowledge test and confidence survey were provided to participants just before training, and again immediately following the training online. The authors compared improvements of pre/post-test results. In the tabletop drill exercise, quantified qualitative analyses were used to measure the educational effect on the participants. Results In the knowledge test, the mean (standard deviation) scores for all 25 participants at baseline and after training were 41.72 (15.186) and 77.96 (11.227), respectively (p < 0.001). In the confidence survey for chemical MCI response for all 25 participants, all the sub-items concerning personal protective equipment selection, antidote selection, antidote stockpiling and passing on knowledge to colleagues, zone setup and decontamination, and chemical triage were improved compared to the baseline score (p < 0.001). The tabletop exercise represented a prehospital setting and had 11 participants. The self-efficacy qualitative survey showed pre- and post-exercise scores of 64/100 and 84/100 respectively. For a hospital setting exercise, it had 14 participants. The survey showed pre/post-exercise scores of 26/100 and 73/100 respectively. Twenty-two (88%) participants responded to the final satisfaction survey, and their overall mean scores regarding willingness to recommend this training program to others, overall satisfaction with theoretical education, overall satisfaction with tabletop drill simulation, and opinion about whether policymakers need this training were all over 8 out of 10 respectively. Conclusion C-MCIREM, the newly created chemical MCI program, provided effective education to the selected 25 participants among Korean chemical MCI responders in terms of both knowledge and practice at a single pilot trial. Participants were highly satisfied with the educational material and their confidence in disaster preparedness was clearly improved. In order to prove the universal educational effect of this C-MCIREM in the future, more education is needed.

Lessons learned from reviewing a hospital's disaster response to the hydrofluoric acid leak in Gumi city in 2012.

BACKGROUND: This study analyzed the characteristics of hydrogen fluoride-exposed patients (HFEPs) treated in the emergency department (ED) of a local university hospital, and reviewed the hospital's disaster response according to space, staff, supplies, and systems (4Ss). METHODS: This retrospective observational chart review and descriptive study included 199 HFEPs among 2588 total ED patients who visited a local university emergency medical center for treatment between September 27, 2012 and October 20, 2012, following a hydrofluoric acid leak at the Hube Globe factory in Gumi City, Republic of Korea. Descriptive results concerning the 4Ss were obtained by interviewing ED specialist staff physicians on duty during the study period. In accordance with American Burn Association criteria, patients requiring burn center referral were assigned to the major burn group (MBG) as severe condition. RESULTS: During the acute phase (within 8 h after leak initiation), there were 43 patients in the ED, which was staffed with 3 doctors and 3 nurses, without 4S resources. Of these 43 patients, there were 8 HFEPs (100%) in the MBG and 0 in the non-MBG (NMBG). During the subacute phase (24 h after the acute phase), there were 262 patients in the ED including 167 HFEPs, of whom 45 (26.95%) were in the MBG and 122 (73.05%) were in the NMBG. The ED was then staffed with 6 doctors (3 on day shift and 3 on night shift) and 10 nurses (3 on day shift, 4 on evening shift, and 3 on night shift), and no 4S resources were available. Throughout the study period, no 4Ss were available. First, there was no expansion of ED space or secured disaster reserve beds. Second, there was no increase in manpower with duty time adjustments or duty relocation for ED working personnel. Third, there was no logistics reinforcement (e.g., antidote or personal protective equipment). Fourth, there were no disaster-related measures for the administration department, decontamination zone setup, safety diagnostic testing, or designated disaster triage implementation. CONCLUSIONS: The hospital's disaster response was insufficient for all aspects of the 4Ss. Detailed guidance concerning a hospital disaster management plan is required.

Helicobacter pylori-targeting multiligand photosensitizer for effective antibacterial endoscopic photodynamic therapy.

Helicobacter pylori (H. pylori) infection is closely associated with the development of gastric inflammatory diseases and cancer. However, the continued abuse and misuse of antibiotics has accelerated the spread of antibiotic-resistant strains, which poses a tremendous challenge for antibiotic-based H. pylori treatment. In this study, a H. pylori-targeting photodynamic therapy (PDT) system is proposed that multiple 3'-sialyllactose (3SL)-conjugated, poly-l-lysine-based photosensitizer (p3SLP). p3SLP facilitates H. pylori-targeting PDT via the specific interaction between 3SL and sialic acid-binding adhesin (SabA) in the H. pylori membrane. p3SLP can be orally administered to H. pylori infected mice and irradiated using an endoscopic laser system. The gastrointestinal pathological analysis of the H. pylori-infected mice demonstrated significant H. pylori specific antibacterial effects of PDT without side effects to normal tissue. In addition, an anti-inflammatory response was observed at the site of infection after p3SLP treatment. Consequently, this study demonstrates the superior efficacy of anti-H. pylori PDT with p3SLP in H. pylori-infected mice, and this approach shows great potential for replacing antibiotic-based therapy.

Facile Hydrothermal Synthesis of an Iodine-Doped Computed Tomography Contrast Agent Using Insoluble Triiodobenzene.

Carbonized iodine-doped particles (CIPs) were developed to overcome the disadvantages of computed tomography (CT) contrast agents, such as high osmolality and the radiodensity dilution of monomolecular contrast agents and low solubility and high toxicity of polymeric contrast agents. The CIPs were synthesized via a hydrothermal synthesis for 8 h using ATIPA (5-amino-2,4,6-triiodoisophthalic acid), glycerol, and tromethamine in the presence of D.W. (deionized water)-insoluble ATIPA converted into CIPs through a hydrothermal synthesis, showing high solubility and low osmotic pressure. The in vitro contrast effect determined for the resulting CIPs demonstrated a 57.6% enhancement compared to iohexol, and the osmotic pressure of the resulting CIPs was lower than that of iohexol. In addition, the CIPs demonstrated no dilution-induced contrast decrease in plasma and, therefore, demonstrated high contrast strength in vivo. Cytotoxicity tests, hemolysis assays, and histological analyses were conducted to verify the biocompatibility of the CIP product; however, no toxicity was observed. Furthermore, the CIP demonstrated a much higher contrast effect than iohexol at low concentrations. These results indicate that the CIP we have produced may be used as an effective blood pool agent for CT imaging.

Anthocyanin-fucoidan nanocomplex for preventing carcinogen induced cancer: Enhanced absorption and stability.

Anthocyanins, commonly extracted from aronia, exhibit excellent in antioxidant activity and anti-cancer activity. However, anthocyanins are not only easily oxidized in water but also rapidly disappear from the body, thus requiring a large amount of administration. To solve these limitations, we selected fucoidan, an anionic polymer, to produce an anthocyanin-fucoidan nanocomplex (AFNC) with enhanced absorption and chemical stability by ionic bonding and π-π stacking between anthocyanins. In vitro, AFNC showed increased cell permeability absorption and plasma chemical stability than free anthocyanins. AFNC suppressed the epithelial mesenchymal transition (EMT) signal including IκBα/NF-κB signaling pathway and the release of pro-inflammatory cytokines. In vivo, AFNC exhibited 3.24-fold higher bioavailability than free anthocyanin in rats. AFNC effectively suppressed the generation of carcinogenesis in the 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) well-known tumorigenesis model. These results could be used to extend the applications of anthocyanins in anti-cancer treatment and in health care foods, and various pharmaceutical industries.

Drive-Through Screening Center for COVID-19: a Safe and Efficient Screening System against Massive Community Outbreak.

As the coronavirus disease 2019 (COVID-19) outbreak is ongoing, the number of individuals to be tested for COVID-19 is rapidly increasing. For safe and efficient screening for COVID-19, drive-through (DT) screening centers have been designed and implemented in Korea. Herein, we present the overall concept, advantages, and limitations of the COVID-19 DT screening centers. The steps of the DT centers include registration, examination, specimen collection, and instructions. The entire service takes about 10 minutes for one testee without leaving his or her cars. Increased testing capacity over 100 tests per day and prevention of cross-infection between testees in the waiting space are the major advantages, while protection of staff from the outdoor atmosphere is challenging. It could be implemented in other countries to cope with the global COVID-19 outbreak and transformed according to their own situations.

Cancer-Targetable pH-Sensitive Zinc-Based Immunomodulators Combined with Photodynamic Therapy for in Situ Vaccination.

A cancer vaccine is a promising immunotherapy modality, but the heterogenicity of tumors and substantial time and costs required in tumor-associated antigen (TAA) screening have hindered the development of an individualized vaccine. Herein, we propose in situ vaccination using cancer-targetable pH-sensitive zinc-based immunomodulators (CZIs) to elicit antitumor immune response against TAAs of patients' tumors without the ex vivo identification processes. In the tumor microenvironment, CZIs promote the release of large amounts of TAAs and exposure of calreticulin on the cell surface via immunogenic cell death through the combined effect of excess zinc ions and photodynamic therapy (PDT). With these properties, CZIs potentiate antitumor immunity and inhibit tumor growth as well as lung metastasis in CT26 tumor-bearing mice. This nanoplatform may suggest an alternative therapeutic strategy to overcoming the limitations of existing cancer vaccines and may broaden the application of nanoparticles for cancer immunotherapy.

Can We Predict Good Survival Outcomes by Classifying Initial and Re-Arrest Rhythm Change Patterns in Out-of-Hospital Cardiac Arrest Settings?

Objective The purpose of this study was to investigate whether a change in prehospital arrest rhythms could allow medical personnel to predict survival outcomes in patients who achieved a return of spontaneous circulation (ROSC) in the setting of out-of-hospital cardiac arrest (OHCA). Methods The design of this study was retrospective, multi-regional, observational, and cross-sectional with a determining period between August 2015 and July 2016. Cardiac arrest rhythms were defined as a shockable rhythm (S), which refers to ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT), and non-shockable rhythm (NS), which refers to pulseless electrical activity or asystole. Survival to admission, survival to discharge, and good cerebral performance category (CPC) (CPC 1 or 2) were defined as good survival outcomes. Results A total of 163 subjects were classified into four groups according to the rhythm change pattern: NS→NS (98), S→S (27), S→NS (23), and NS→S (15). NS→NS pattern was used as the reference in logistic regression analysis. In the case of survival to hospital admission, the odds ratio (OR) (95% CI) of the S→S pattern was the highest [12.63 (3.56-44.85), p: <0.001 by no correction] and [7.29 (1.96-27.10), p = 0.003 with adjusting]. In the case of survival to hospital discharge, the OR (95% CI) of the S→S pattern was the highest [37.14 (11.71-117.78), p: <0.001 by no correction] and [13.85 (3.69-51.97), p: <0.001 with adjusting]. In the case of good CPC (CPC 1 or 2) at discharge, the OR (95% CI) of the S→S pattern was the highest [96 (19.14-481.60), p: <0.001 by no correction] and [149.69 (19.51-1148.48), p: <0.001 with adjusting]. Conclusions The S→S group showed the highest correlation with survival to hospital admission, survival to hospital discharge, and good CPC (CPC 1 or 2) at discharge compared to the NS→NS group. Verifying changes in initial cardiac arrest rhythm and prehospital re-arrest (RA) rhythm patterns after prehospital ROSC can help us predict good survival outcomes in the OHCA setting.

In situ vaccination with biocompatibility controllable immuno-sensitizer inducing antitumor immunity.

Anticancer immunotherapy is emerging as a promising tumor treatment that can replace the conventional tumor treatment such as surgery, radiation and chemo drug, but its therapeutic effect against solid tumor is limited due to the tumor microenvironment (TME). Herein, to overcome this limitation, the biocompatibility controllable immuno-sensitizer (BCI) based on polyethylene imine that can be applied to solid tumors is developed. BCI accumulates in the tumors by EPR effect and induces in situ tumor destruction that convert tumors into antigen source by biocompatibility change through surface charge switching in response to the acidic TME. Generated tumor antigens promote the maturation of dendritic cells and recruitment of cytotoxic T cells in tumors. Results from in vitro and in vivo experiments reveal that the BCI effectively induces tumor destruction and antitumor immune response. In consequence, the synergic effect of in situ tumor destruction and antitumor immune response induced by BCI's biocompatibility conversion remarkably enhances immunotherapeutic effect. This study may provide a way to improve immunotherapeutic effect on solid tumors by demonstrating the therapeutic effect of BCI against solid tumor and suggest a platform to control the toxicity of cationic polymer for the its extended biomedical application.

Gene expression profiling of chondrogenic differentiation by dexamethasone-conjugated polyethyleneimine with SOX trio genes in stem cells.

BACKGROUND: During differentiation of stem cells, it is recognized that molecular mechanisms of transcription factors manage stem cells towards the intended lineage. In this study, using microarray-based technology, gene expression profiling was examined during the process of chondrogenic differentiation of human mesenchymal stem cells (hMSCs). To induce chondrogenic differentiation of hMSCs, the cationic polymer polyethyleneimine (PEI) was coupled with the synthetic glucocorticoid dexamethasone (DEX). DEX/PEI could be polyplexed with anionic plasmid DNAs (pDNAs) harboring the chondrogenesis-inducing factors SOX5, SOX6, and SOX9. These are named differentiation-inducing nanoparticles (DI-NPs). METHODS: A DI-NP system for inducing chondrogenic differentiation was designed and characterized by dynamic light scattering and scanning electron microscopy (SEM). Chondrogenic induction of hMSCs was evaluated using various tools such as reverse-transcription polymerase chain reaction (RT-PCR), Western blotting, confocal fluorescent microscopy, and immunohistochemistry analysis. The gene expression profiling of DI-NP-treated hMSCs was performed by microarray analysis. RESULTS: The hMSCs were more efficiently transfected with pDNAs using DI-NPs than using PEI. Moreover, microarray analysis demonstrated the gene expression profiling of hMSCs transfected with DI-NPs. Chondrogenic factors including SOX9, collagen type II (COLII), Aggrecan, and cartilage oligometric matrix protein (COMP) were upregulated while osteogenic factors including collagen type I (COLI) was downregulated. Chondrogenesis-induced hMSCs were better differentiated as assessed by RT-PCR, Western blotting analyses, and immunohistochemistry. CONCLUSION: DI-NPs are good gene delivery carriers and induce chondrogenic differentiation of hMSCs. Additionally, comprehensive examination of the gene expression was attempted to identify specific genes related to differentiation by microarray analysis.

Should Let Them Go? Study on the Emergency Department Discharge of Patients Who Attempted Suicide.

OBJECTIVE: The purpose of this study was to analyze the characteristics and factors of voluntary discharged patients after suicide attempt and analyze the effectiveness of follow-up measures. METHODS: Total 504 adult patients aged 14 years and over, who visited a local emergency medical center from September 1, 2013 to December 31, 2015 were enrolled and retrospectively reviewed. We analyzed the relationship with voluntary discharge group (VDG) among basic characteristics, suicidal attempt variables, outcome variables related to suicide attempts, and treatment related variables comparing with normal discharge group (NDG). RESULTS: Of the total 504 suicide attempts, three hundred eleven (61.7%) patients were VDG and 193 (38.2%) were NDG. The proportion of patients who completed the community service linkage were 18.7% (36/193) in NDG, compared with 7.7% (24/311) in VDG (p<0.05). In addition, the ratio of the patients who visited psychiatric outpatient department in NDG were 57.0% (110/193), more than four times as likely as 14.5% (45/311) in VDG (p<0.05). CONCLUSION: Over sixty percent of suicide attempters discharged against medical advice. Further various aspects of national supportive measures including strengthening case management service should be considered.

Combination of chemotherapy and photodynamic therapy for cancer treatment with sonoporation effects.

To overcome the limitations of single therapy, chemotherapy has been studied to be combined with photodynamic therapy. However, nanomedicine combining anticancer drug and photosensitizer still cannot address the insufficiency of drug delivery and the off-targeting effect. To address drug delivery issue, we have developed a doxorubicin encapsulating human serum albumin nanoparticles/chlorin e6 encapsulating microbubbles (DOX-NPs/Ce6-MBs) complex system. Microbubbles enable ultrasound-triggered local delivery via sonoporation for maximizing the drug delivery to a target site. In both in vitro and in vivo experiments, the developed DOX-NPs/Ce6-MBs drug delivery complex could be confirmed to transfer drugs deeply and effectively into cancerous tumors through the following three steps; (1) the local release of nanoparticles due to the cavitation of DOX-NPs/Ce6-MBs; (2) the enhanced extravasation of DOX-NPs and Ce6-liposome/micelle due to the sonoporation phenomenon; (3) the improved penetration of extravasated nanomedicines into the deep tumor region due to the mechanical energy of ultrasound. As a result, the developed DOX-NPs/Ce6-MBs complex with ultrasound irradiation showed increased therapeutic effects compared to the case where no ultrasound irradiation was applied. The DOX-NPs/Ce6-MBs was concluded from this study to be the optimal drug delivery system for external-stimuli local combination (chemotherapy + PDT) therapy.