Fatal Primary Amebic Meningoencephalitis due to Naegleria fowleri: The First Imported Case in Korea

Primary amebic meningoencephalitis (PAM) is a rare, but almost always fatal, central nervous system infection caused by Naegleria fowleri, which are thermophilic free-living amoeba. Here, we report the first case of PAM detected in South Korea, probably imported from Thailand. Despite antimicrobial treatment for N. fowleri infection with a combination of intravenous liposomal amphotericin B, fluconazole, azithromycin, and oral rifampin, the patient died 13 days after the onset of symptoms. Clinicians in South Korea treating severe meningoencephalitis, especially in individuals returning from tropical areas, are encouraged to include PAM in the differential diagnoses, given the accelerated global warming and increased overseas trips.

The Impact of Referral to Mental Health Services on Suicide Death Risk in Adolescent Suicide Survivors

Objectives@#This study aims to examine the effect of adolescent suicide survivors’ experience on suicide death risk, and the effect of referral to mental health services (hereafter referral) in this regard. @*Methods@#This study used the data of 878 suicide-deceased and suicide-attempted adolescents aged 8–19 years, managed by the Suicide and School Mental Health Institute from 2016 to 2018. @*Results@#Regression analysis for main effects showed that although suicide experience had no direct effect on suicide death, non-referral status was associated with a greater risk of death by suicide. While the “non-suicide survivor with non-referral” and “suicide survivor with non-referral” groups showed 1.87 [adjusted odds ratio=1.87, 95% confidence interval (CI)=1.21–2.89] and 4.59 (adjusted odds ratio= 4.59, 95% CI=2.02–10.42) times higher odds of suicide death, respectively, the “suicide survivor with referral” group showed no difference compared to the “non-suicide survivor with referral” group. @*Conclusion@#From these findings, there is a need to strengthen referral to mental health services and apply complicated grief treatment to improve the mental health of adolescent suicide survivors.

Characteristics of First Visit Pediatric Patients with Suicidal Ideation and Behavior: An 8-Year Retrospective Chart Review

Objectives@#Our study aimed to analyze the demographic and clinical characteristics of children and adolescents during their first visit to psychiatric outpatient departments for the management of suicidal ideation and behavior, and to compare the changes before and in 2012 or later. @*Methods@#This multicenter study was conducted at five university hospitals in a metropolitan area in South Korea. Medical records of patients aged 6–18 years were retrospectively reviewed from January 2009 to December 2016. Patients were analyzed by classifying them into suicidal and non-suicidal groups based on their visit to the hospital for management of suicidal ideation or suicide attempt and other mental problems, respectively. @*Results@#There were differences in the year of visit, diagnosis, education level, and referral sources between patients in the suicidal and non-suicidal groups. Multiple regression analysis was conducted based on the sex, education level, referral by school, and diagnosis of depression in patients in the suicidal group, which revealed significant association. @*Conclusion@#Suicide-related problems were significantly associated with the sex, education level, referral by school, and a diagnosis of depression in the patients. A well-connected referral system would be necessary for professional mental health management of high-risk children and adolescents.

Molecular Prevalence and Genotypes of Cryptosporidium parvum and Giardia duodenalis in Patients with Acute Diarrhea in Korea, 2013–2016

Cryptosporidium parvum and Giardia duodenalis are the main diarrhea-causing parasitic pathogens; however, their prevalence in Korea is unknown. Here, we conducted a survey to determine the prevalence and genotype distribution of these 2 pathogens causing acute diarrhea in 8,571 patients hospitalized in 17 Regional Institute of Health Environment sites in Korea, during 2013–2016. C. parvum and G. duodenalis were detected and genotyped by nested PCR, and the isolate were molecularly characterized by sequencing the glycoprotein 60 (Gp60) and β-giardin genes, respectively. The overall prevalence of C. parvum and G. duodenalis was 0.37% (n=32) and 0.55% (n=47), respectively, and both pathogens were more prevalent in children under 9 years old. Molecular epidemiological analysis showed that the C. parvum isolates belonged to the IIa family and were subtyped as IIaA13G2R1, IIaA14G2R1, IIaA15G2R1, and IIaA18G3R1. Analysis of the β-giardin gene fragment from G. duodenalis showed that all positive strains belong to assemblage A. This is the first report on the molecular epidemiology and subtyping of C. parvum and G. duodenalis in such a large number of diarrheal patients in Korea. These results highlight the need for continuous monitoring of these zoonotic pathogens and provide a basis for implementing control and prevention strategies. Further, the results might be useful for epidemiological investigation of the source of outbreak.

Serological and Molecular Detection of Toxoplasma gondii and Babesia microti in the Blood of Rescued Wild Animals in Gangwon-do (Province), Korea

Infections of Toxoplasma gondii and Babesia microti are reported in many wild animals worldwide, but information on their incidence and molecular detection in Korean wild fields is limited. In this study, the prevalence of T. gondii and B. microti infection in blood samples of 5 animal species (37 Chinese water deer, 23 raccoon dogs, 6 roe deer, 1 wild boar, and 3 Eurasian badgers) was examined during 2008–2009 in Gangwon-do (Province), the Republic of Korea (=Korea) by using serological and molecular tests. The overall seropositivity of T. gondii was 8.6% (6/70); 10.8% in Chinese water deer, 4.3% in raccoon dogs, and 16.7% in roe deer. PCR revealed only 1 case of T. gondii infection in Chinese water deer, and phylogenic analysis showed that the positive isolate was practically identical to the highly pathogenetic strain type I. In B. microti PCR, the positive rate was 5.7% (4/70), including 2 Chinese water deer and 2 Eurasian badgers. Phylogenetic analysis results of 18S rRNA and the β-tubulin gene showed that all positive isolates were US-type B. microti. To our knowledge, this is the first report of B. microti detected in Chinese water deer and Eurasian badger from Korea. These results indicate a potentially high prevalence of T. gondii and B. microti in wild animals of Gangwon-do, Korea. Furthermore, Chinese water deer might act as a reservoir for parasite infections of domestic animals.

Preclinical development of a humanized neutralizing antibody targeting HGF

Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation in vitro and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the in vitro and in vivo data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.

Follow-up Study of Patients Previously Diagnosed with Lymphatic Filariasis in Korea

OBJECTIVES: Korea was an endemic area for lymphatic filariasis (LF), caused by the nematode parasite Brugia malayi, until the 1970s. The World Health Organization recognized Korea as LF-free in June 2008. However, it is necessary to confirm that patients that have had LF in the past still test negative, to prevent the re-emergence of LF in Korea. METHODS: We followed up a total of 83 patients who had been diagnosed with LF between 2002 and 2010 in endemic LF areas. RESULTS: Fifty-two of the 83 subjects were negative for LF, whereas 31 subjects had re-located to a different city or province, were dead, or were unaccounted for. Most subjects with negative test results still exhibited edema in the legs or the arms, and some complained of redness and swelling in the legs or ankle joints. However, we found that these symptoms were due to diseases other than LF. CONCLUSION: In this follow-up study, we did not find any evidence indicating the potential re-emergence of LF in Korea.

Anthropometric Analysis of Facial Foramina in Korean Population: A Three-Dimensional Computed Tomographic Study

BACKGROUND: Position of the facial foramina is important for regional block and for various maxillofacial surgical procedures. In this study, we report on anthropometry and morphology of these foramina using three-dimensional computed tomography (3D-CT) data. METHODS: A retrospective review was performed for all patients who have undergone 3D-CT scan of the facial skeleton for reasons other than fracture or deformity of the facial skeleton. Anthropometry of the supraorbital, infraorbital, and mental foramina (SOF, IOF, MF) were described in relation to facial midline, inferior orbital margin, and inferior mandibular margin (FM, IOM, IMM). This data was analyzed according to sex and age. Additionally, infraorbital and mental foramen were classified into 5 positions based on the anatomic relationships to the nearest perpendicular dentition. RESULTS: The review identified 137 patients meeting study criteria. Supraorbital foramina was more often in the shape of a foramen (62%) than that of a notch (38%). The supraorbital, infraorbital, and mental foramina were located 33.7 mm, 37.1 mm, and 33.7 mm away from the midline. The mean vertical distance between IOF and IOM was 13.4 mm. The mean distance between MF and IMM was 21.0 mm. The IOF and MF most commonly coincided with upper and lower second premolar dentition, respectively. Between the sex, the distance between MF and IMM was significantly higher for males than for female. In a correlation analysis, SOF-FM, IOF-FM and MF-FM values were significantly increased with age, but IOF-IOM values were significantly decreased with age. CONCLUSION: In the current study, we have reported anthropometric data concerning facial foramina in the Korean population, using a large-scale data analysis of three-dimensional computed tomography of facial skeletons. The correlations made respect to patient sex and age will provide help to operating surgeons when considering nerve blocks and periosteal dissections around the facial foramina.

Non-Melanocytic Benign Tumors of the Face: A Retrospective Study

BACKGROUND: Although plastic surgeons daily encounter various facial tumors in the field, reports limited on face are scarce. In our study, we want to provide basic epidemiologic data to help clinicians to decide the proper management for their patients. METHODS: We retrospectively reviewed the medical records of patients including age and gender, location and size of the tumor, histopathologic result, recurrence, type of anesthesia and any associated disorders who had undergone a surgical removal of their facial tumors and received the histopathologic report in the same institution between January 2009 and October 2012. RESULTS: One hundred eighty-nine patients with 203 non-melanocytic benign tumors were included. The most frequent site of tumors was the central subunit of the forehead, followed by the lateral subunit of the cheek and the auricular unit. Of 36 different histopathologic results, the epidermal cyst was most frequent, followed by lipoma, pilomatricoma and osteoma. Statistical analysis showed that males were dominant in the epidermal cyst and lipoma groups. While, females were dominant in the osteoma and pilomatricoma groups. No associations were found between lesions and other diseases. CONCLUSIONS: Our study is the at most specific and concentrated study on non-melanocytic benign tumors of the face. We expect the epidemiologic data of our study may help plastic surgeons who are confronted with so many facial lesions in the field to decide on the most proper management for their patients.

Toxoplasma gondii Infection Suppresses House Dust Mite Extract-Induced Atopic Dermatitis in NC/Nga Mice

PURPOSE: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects humans and animals via congenital or postnatal routes, and it is found worldwide. Modulation of the immune system by parasite infection is proposed to suppress allergic inflammation. Growing evidences have shown that interleukin (IL)-10-producing regulatory B cells (B(regs)) and CD4+CD25+FoxP3+ regulatory T cells (T(regs)) induced by parasite infection play a critical role in allergic or autoimmune diseases because these cells regulate negatively cellular immune responses and inflammation. Currently, the role of IL-10-producing regulatory B cells in host immune response during T. gondii infection is unknown. In this study, we investigate whether T. gondii infection can suppress the development of unrelated atopic dermatitis (AD)-like lesions. METHODS: AD is a chronically relapsing inflammatory skin disease accompanied by severe itching; for this, we used NC/Nga mice, a well-known experimental model of systemic AD. Repeated exposure to Dermatophagoides farinae crude extract (DfE), known as a major environmental allergen, evokes AD-like skin lesions in NC/Nga mice under specific pathogen-free conditions. NC/Nga mice were intraperitoneally infected with 10 cysts of T. gondii. RESULTS: T. gondii infection significantly ameliorated AD-like skin lesions in NC/Nga mice. The subpopulation of B(regs) and T(regs) in the AD mice was expanded in the course of T. gondii infection. In addition, T. gondii infection inhibited Th2 and enhanced Th1 immune response in the DfE-treated AD mice. CONCLUSIONS: We have experimentally demonstrated for the first time that T. gondii infection ameliorated AD-like skin lesions in a mouse model of AD. Our study could in part explain the mechanisms of how parasite infection prevents the development of allergic disorder. Therefore, these immunemechanisms induced by T. gondii infection may be beneficial for the host in terms of reduced risk of allergic immune reactions.

Molecular Detection and Seroprevalence of Babesia microti among Stock Farmers in Khutul City, Selenge Province, Mongolia

Babesiosis is an emerging tick-borne disease in humans worldwide; however, little is known about the frequency of infection or prevalence of this disease in other parts of the world, excluding North America. In this study, we aimed to investigate Babesia microti infection frequency in a human population in Mongolia. One hundred blood samples were collected from stock farmers living in Khutul city of Selenge province, Mongolia. The sera and DNA from blood samples were evaluated for the presence of B. microti infection by using indirect fluorescent antibody (IFA) tests and PCR. The positive detection rates obtained using the IFA tests and PCR assays were 7% and 3%, respectively. This study is the first to detect of B. microti infections based on antibody seroprevalence or PCR assays for the presence of B. microti DNA in a Mongolian population.

Seroprevalence of Toxoplasma gondii and Bartonella henselase infection in stray cats of the Daejeon City, Korea / 대한수의학회지

In this study, the seroprevalence of Toxoplasma (T.) gondii and Bartonella (B.) henselae infection among stray cats in Daejeon City, Korea was surveyed. A total of seven samples were positive (7/118, 5.93%) for T. gondii including three samples from female cats (3/58, 5.2%) and four samples from male cats (4/60, 6.7%). There was no significant difference between the genders. A total 22 samples (22/118, 18.6%) were positive for B. henselae; nine were from females and 13 were from males. There was no significant difference between genders. Nineteen samples had a titer of 1 : 50, two samples had a titer of 1 : 100, and one sample had a titer of 1 : 200. The present study is the first to use serological tests to analyze B. henselae prevalence among stray cats in Korea.

Prevalence of Toxoplasma gondii Infection in Household Cats in Korea and Risk Factors

Several epidemiological surveys have reported the prevalence of Toxoplasma gondii infection in stray cats in Korea, but little information is available on T. gondii infection in household cats. The aim of the present study was to assess the prevalence and risk factors of T. gondii infection among household cats reared in Seoul, Korea. A total of 474 blood samples were collected from clinically healthy household cats. All samples were tested using ELISA and PCR. The risk factor analysis was based on a questionnaire filled out by the owners. The overall positive rate for ELISA and PCR assays was 2.2% (10/437) and 2.1% (10/474), respectively. With regard to the origin of cats, the positive rates among cats adopted from the animal shelter and veterinary clinic for stray cats were significantly different (P<0.05). Our study demonstrated that the positive rate of T. gondii infection in household cats was low and that this low prevalence was assumed to be associated with keeping the cats indoors and restriction of eating raw food and uncooked meat. Therefore, we suggest that the owners check the origin of the cats prior to adoption to prevent infection of other animals, including humans.

Characterization of H460R, a Radioresistant Human Lung Cancer Cell Line, and Involvement of Syntrophin Beta 2 (SNTB2) in Radioresistance

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and gamma-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

Detection of Ocular Toxoplasma gondii Infection in Chronic Irregular Recurrent Uveitis by PCR

Toxoplasma gondii is a zoonotic parasite resulting in human infections and one of the infectious pathogens leading to uveitis and retinochoroiditis. The present study was performed to assess T. gondii infection in 20 ocular patients with chronic irregular recurrent uveitis (20 aqueous humor and 20 peripheral blood samples) using PCR. All samples were analyzed by nested PCR targeting a specific B1 gene of T. gondii. The PCR-positive rate was 25% (5/20), including 5% (1) in blood samples, 25% (5) in aqueous humor samples, and 5% (1) in both sample types. A molecular screening test for T. gondii infection in ocular patients with common clinical findings of an unclear retinal margin and an inflammatory membrane over the retina, as seen by fundus examination, may be helpful for early diagnosis and treatment.

Prevalence of Enterobius vermicularis among Preschool Children in Muan-gun, Jeollanam-do, Korea

We assessed the prevalence of Enterobius vermicularis infection and changes in the egg positive rate (EPR) over 1-year time, using the adhesive cellophane-tape perianal swab method in 2,347 preschool children in Muan-gun, Jeollanam-do, Republic of Korea in 2008 and 2009. The overall EPR for E. vermicularis was 4.1% in 2008 and 4.5% in 2009. A study population of 389 children was repeatedly examined for 2 years. Within this group, the EPR in 2009 was twice higher than in 2008, and the EPR of the group of 5-7-year-old children was significantly higher than that of other age groups. Moreover, in the group of 5-7-year-old children in 2009, the rates of positive and negative conversion were significantly higher and lower, respectively, than in other age groups. Conclusively, enterobiasis was prevalent during 2008-2009 among preschool children in Muan-gun, Jeollanam-do, and the increased EPR in 2009 was due to an increase in newly acquired infections among 5-7-year-old children.

Scalp Free Flap Reconstruction Using Anterolateral Thigh Flap Pedicle for Interposition Artery and Vein Grafts

We experienced satisfactory outcomes by synchronously transplanting an artery and vein using an anterolateral thigh flap pedicle between the vascular pedicle and recipient vessel of a flap for scalp reconstruction. A 45-year-old man developed a subdural hemorrhage due to a fall injury. In this patient, the right temporal cranium was missing and the patient had 4x3 cm and 6x5 cm scalp defects. We planned a scalp reconstruction using a latissimus dorsi free flap. Intraoperatively, there was a severe injury to the right superficial temporal vessel because of previous neurosurgical operations. A 15 cm long pedicle defect was needed to reach the recipient facial vessels. For the vascular graft, the descending branch of the lateral circumflex femoral artery and two venae comitantes were harvested. The flap survived well and the skin graft was successful with no notable complications. When an interposition graft is needed in the reconstruction of the head and neck region for which mobility is mandatory to a greater extent, a sufficient length of graft from an anterolateral flap pedicle could easily be harvested. Thus, this could contribute to not only resolving the disadvantages of a venous graft but also to successfully performing a vascular anastomosis.

Comparison of Egg Positive Rates of Enterobius vermicularis among Preschool Children in Three Korean Localities

This survey was performed to investigate and compare egg positive rates (EPRs) of Enterobius vermicularis among preschool children in 3 Korean localities (Chuncheon-si, Inje-gun, and Paju-si) in 2008. A total of 7,048 preschool children were examined. Overall, the total EPR was 4.0%; the EPR was the highest in Chuncheon-si (5.6%), followed by Inje-gun (4.5%) and Paju-si (3.4%). The EPR of boys (4.9%) was higher than that of girls (3.1%). The EPR significantly increased with age, with the highest observed in 5~7-year-olds. These findings demonstrate that E. vermicularis infection is widely prevalent among preschool children in Chuncheon-si, Inje-gun, and Paju-si, Republic of Korea.

Comparative Efficacy for Dressing Methods of Iodine on Infected Full Thickness Skin Wound in the Mouse

PURPOSE: Iodine has been used for the prevention or management of wound infection as a topical agent. Although iodine was widely used mainly by Betadine(R) and cadexomer iodine, there was no comparative study on the efficacies of dressing methods of iodine. And also it's wound healing effect was not yet clear. The purpose of this study is to compare antibacterial effects and wound healing effects associated with various dressing methods of iodine on infected full thickness skin defect in the mouse. METHODS: One full thickness skin defects in the mice (n=60) were developed on the back and left open for twenty-four hours. Sixty mice were divided into four groups : group S(dressing with Betadine(R) soaking, n=15), group T (dressing with Betadine(R) topping, n=15), group I(dressing with Iodosorb(R), n=15), group G(control group, dressing with dry gauze, n=15). The size of the wound defects and the grades of wound healing were evaluated in 4, 7, 10 days, and antibacterial effect was evaluated with restricted zone in Mueller Hinton agar by disk diffusion method. RESULTS: After the wound was left open for twenty-four hours, many Staphylococcus aureus were cultured. The wound defect size was decreased in order of Betadine(R) soaking, Iodosorb(R), Betadine(R) topping and gauze dressing group in all days, but difference among experimental groups was not statistically significant. The grade score of wound healing was increased in order of Betadine(R) soaking, Iodosorb(R), Betadine(R) topping and gauze dressing group, and the difference was statistically significant. Antibacterial effect for S. aureus was increased in order of Iodosorb(R), Betadine(R) soaking, Betadine(R) topping and gauze dressing group, and the difference was statistically significant. CONCLUSION: Selection of the effective dressing method of iodine for infected wounds remains a controversial decision. According to this study, Iodosorb(R) may be most effective method for antibacterial effect and Betadine(R) soaking may be most effective method for infected wound healing. However, further study is necessary to evaluate the clinical efficacy of dressing methods of iodine and to search for the mechanisms that explain their effects.

The Wound Healing Effect of PDRN(polydeoxyribonucleotide) Material on Full Thickness Skin Defect in the Mouse

PURPOSE: Many topical agents had been used for burn or wound treatment. An awareness of topical agents on various aspects of wound healing permits the clinician to choose the most appropriate material to advantageously control the wound process and final results. Although polydeoxyribonucleotide(PDRN) was used as a tissue repair stimulating agent in a number of human diseases, such as ulcers and burns, its wound healing effects were largely unreported. We aimed to compare the wound-healing effects of PDRN and common dressing materials on full-thickness skin defect in the mouse. METHODS: Full-thickness skin defects were made on the back of mice(N=60). The mice were divided into the following 4 groups according to the dressing used for the wounds: group O(Polydeoxyribonucleotide cream), group I (Polydeoxyribonucleotide solution), group M(Medifoam(R)), and group G(dry gauze, control group). We analyzed the gross findings, wound sizes and histological findings for the groups. RESULTS: The rate of wound size was decreased in order of group I, group O, group M and group G. The histological findings revealed that the I group showed more reepithelialization and granulation tissue formation and less inflammatory cell infiltration than the other materials. The grade score of wound healing was increased in order of group I, group O, group M and group G. CONCLUSION: PDRN applicated wound dressings can be used for treating a full-thickness skin defect wounds. Considering its superior efficacy in comparison to the efficacies of other wound dressings, PDRN soaked gauze dressing should be preferentially used for the treatment of full-thickness skin wounds.