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PURPOSE: To determine the genomic feature of novel spotted fever-causing Rickettsia koreansis strain CNH17-7, which is different from R. japonica that is a causative agent for Japanese spotted fever (JSF), and to perform its comparative genomic analysis. METHODS: Whole genome sequencing (WGS) was performed on R. koreansis strain CNH17-7 by using the Illumina Miseq system. After WGS, assembly and annotation were done by SPAdes. Then, its genomic features were compared with 19 different Rickettsia species. Based on the average nucleotide identity (ANI) value, an unweighted pair group method with an arithmetic mean (UPGMA) dendrogram was generated. Following the dendrogram analysis, pan-and core-genome analysis was performed. Then additional comparative analyses with two genetically closest Rickettsia species were conducted based on gene repertoire. RESULTS: R. koreansis strain CNH17-7 has a chromosome consisting of 1,392,633 bp with GC content of 32.4%. The ANI-derived UPGMA showed that R. koreansis strain CNH17-7 is genetically close to R. japonica YH and R. heilongjiangensis 054 but is distinctively differentiated. The ANI value of R. koreansis strain CNH17-7 to R. japonica YH and R. heilongjiangensis 054 are 98.14% and 98.04% respectively, indicating R. koreansis strain CNH17-7 is sufficient to be classified as a new species. Other than ANI, R. koreansis strain CNH17-7 also contains novel CDS and its COG functional category proportion which is distinct compared to R. japonica YH and R. heilongjiangensis 054. CONCLUSION: We have revealed genomic features of the novel R. koreansis strain CNH17-7. Hence, we propose R. koreansis strain CNH17-7 as new Rickettsia species.
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The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.
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Cancer cells use multiple mechanisms to evade the effects of glutamine metabolism inhibitors. The pathways that govern responses to alterations in glutamine availability within the tumor may represent therapeutic targets for combinatorial strategies with these inhibitors. Here, we showed that targeting glutamine utilization stimulated Yes-associated protein (YAP) signaling in cancer cells by reducing cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent phosphorylation of large tumor suppressor (LATS). Elevated YAP activation induced extracellular matrix (ECM) deposition by increasing secretion of connective tissue growth factor (CTGF) that promoted production of fibronectin and collagen by surrounding fibroblasts. Consequently, inhibiting YAP synergized with inhibition of glutamine utilization to effectively suppress tumor growth in vivo, along with a concurrent decrease in ECM deposition. Blocking ECM remodeling also augmented the tumor suppressive effects of the glutamine utilization inhibitor. Collectively, these data reveal mechanisms by which targeting glutamine utilization increases ECM accumulation and identify potential strategies to reduce ECM levels and increase the efficacy of glutamine metabolism inhibitors.
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Vaccines aim to efficiently and specifically activate the immune system via a cascade of antigen uptake, processing, and presentation by antigen-presenting cells (APCs) to CD4 and CD8 T cells, which in turn drive humoral and cellular immune responses. The specific formulation of vaccine carriers can not only shield the antigens from premature sequestering before reaching APCs but also favorably promote intracellular antigen presentation and processing. This study compares two different acid-degradable polymeric nanoparticles that are capable of encapsulating a moderately immunogenic antigen, GFP, at nearly full efficacy via electrostatic interactions or molecular affinity between His tag and Ni-NTA-conjugated monomners. This resulted in GFP-encapsulating NPs composed of ketal monomers and crosslinkers (KMX/GFP NPs) and NTA-conjugated ketal monomers and crosslinkers (NKMX/GFP NPs), respectively. Encapsulated GFP was found to be released more rapidly from NKMX/GFP NPs (electrostatic encapsulation) than from KMX/GFP NPs (affinity-driven encapsulation). In vivo vaccination studies demonstrated that while repeated injections of either NP formulation resulted in poorer generation of anti-GFP antibodies than injections of the GFP antigen itself, sequential injections of NPs and GFP as prime and booster vaccines, respectively, restored the humoral response. We proposed that NPs primarily assist APCs in antigen presentation by T cells, and B cells need to be further stimulated by free protein antigens to produce antibodies. The findings of this study suggest that the immune response can be modulated by varying the chemistry of vaccine carriers and the sequences of vaccination with free antigens and antigen-encapsulating NPs.
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Antígenos , Nanopartículas , Polímeros , Nanopartículas/química , Animales , Polímeros/química , Ratones , Antígenos/inmunología , Antígenos/química , Vacunación , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/inmunología , Femenino , Ratones Endogámicos C57BL , Tamaño de la Partícula , Vacunas/inmunología , Vacunas/química , Vacunas/administración & dosificaciónRESUMEN
145 fungal isolates were obtained from three sampling sites situated within the Nam River basin, located in the southern region of South Korea. Through ITS sequence analysis, the fungal isolates were identified to comprise 55 species of ascomycetes and 11 species of basidiomycetes. The 55 species of ascomycetes exclusively belong to the phylum Pezizomycotina, comprising 33 species of Dothideomycetes, 6 species of Eurotiomycetes, and 16 species of Sordariomycetes. Regarding their plant pathogenicity, an investigation into the fungi's ability to penetrate solid media revealed Nigrospora chinensis as displaying the highest growth, followed by Pseudopestalotiopsis theae, various Curvularia species, Diaporthe species, and Alternaria alternata. Further research associating this penetration ability with fungal pathogenicity is deemed necessary. Among the 10 fungal species exhibiting penetration abilities, an examination of their capability to degrade biological polymers revealed that two strains of D. phaseolorum displayed exceptional polymer degradation. These strains exhibited remarkable abilities in decomposing malachite green and crystal violet, both recalcitrant dyes. This study underscores the potential utilization of fungal diversity in freshwater environments as a foundational approach to address freshwater pollution issues.
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Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl-coenzyme A. Adenosine 5'-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5'-triphosphate-citrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.
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Background: The density of tumor-associated macrophages in the tumor microenvironment of anaplastic thyroid cancer (ATC) is associated with poor prognosis. However, the crosstalk between macrophages and ATC cells is poorly understood. This study aimed to examine the impact of macrophages on cancer cell phenotypes. We found a new mediator between M2 macrophages and ATC cells through proteomics analysis. Methods: The role of macrophages in proliferation, migration, and invasion of ATC cells was evaluated using coculture assay and conditioned medium (CM). Secretory factors in the CM from single or coculture were identified using liquid chromatography-tandem mass spectrometry proteomics analysis. We evaluated the role of the secretory factor in proliferation, migration, and invasion of cancer cells. In vivo xenograft model was used to evaluate the effect of the factor. Results: M2 macrophages significantly increased the proliferation, migration, and invasion of ATC cells, whereas M1 macrophages decreased the proliferation, migration, and invasion of ATC cells. Based on proteomic analysis of CM, we identify carboxypeptidase A4 (CPA4) as a mediator of the crosstalk between macrophages and ATC cells. CPA4 was only detected in the coculture media of M2 macrophage/8505C, and its expression in cancer cells increased by M2 macrophage. The expression of CPA4 protein was significantly higher in human thyroid cancers, particularly in ATCs, than normal and benign tissues. A bioinformatics analysis of public data revealed that CPA4 expression was associated with poor prognosis and dedifferentiation of thyroid cancer. Knockdown of CPA4 suppressed proliferation, colony formation, migration, and invasion of ATC cells, consistent with the decrease of STAT3, ERK, and AKT/mTOR phosphorylation and epithelial-mesenchymal transition (EMT) marker expression. In addition, the increased expression of CPA4 in cancer cells by M2 macrophage stimulation induced the polarization of macrophages to the M2 phenotype, which formed a positive feedback loop. Xenograft tumors did not develop after CPA4 knockdown. Conclusions: Our data suggest that CPA4 stimulates the progression of thyroid cancer by mediating between M2 macrophages and ATC cells. CPA4 can be a new therapeutic target for the treatment of patients with ATC.
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XRD diffraction and IR absorption were investigated for raw loess powder and heat-treated loess powder. Raw loess retains its useful minerals, but loses their beneficial properties when calcined at 850 °C and 1050 °C. To utilize the useful minerals, loess balls were made using a low-temperature wet-drying method. The radiant energy and transmittance were measured for the loess balls. Far-infrared ray (FIR) emitted from loess bio-balls is selectively absorbed as higher vibrational energy by water molecules. FIR can raise the body's core temperature, thereby improving blood flow through the body's thermoregulatory mechanism. In an exploratory study with 40 participants, when the set temperature of the loess ball mat was increased from 25 °C to 50 °C, blood flow increased by 39.01%, from 37.48 mL/min to 52.11 mL/min, in the left middle finger; in addition, it increased by 39.62%, from 37.15 mL/min to 51.87 mL/min, in the right middle finger. The FIR emitted from loess balls can be widely applied, in various forms, to diseases related to blood flow, such as cold hands and feet, diabetic foot, muscle pain, and menstrual pain.
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mRNAs continually change their protein partners throughout their lifetimes, yet our understanding of mRNA-protein complex (mRNP) remodeling is limited by a lack of temporal data. Here, we present time-resolved mRNA interactome data by performing pulse metabolic labeling with photoactivatable ribonucleoside in human cells, UVA crosslinking, poly(A)+ RNA isolation, and mass spectrometry. This longitudinal approach allowed the quantification of over 700 RNA binding proteins (RBPs) across ten time points. Overall, the sequential order of mRNA binding aligns well with known functions, subcellular locations, and molecular interactions. However, we also observed RBPs with unexpected dynamics: the transcription-export (TREX) complex recruited posttranscriptionally after nuclear export factor 1 (NXF1) binding, challenging the current view of transcription-coupled mRNA export, and stress granule proteins prevalent in aged mRNPs, indicating roles in late stages of the mRNA life cycle. To systematically identify mRBPs with unknown functions, we employed machine learning to compare mRNA binding dynamics with Gene Ontology (GO) annotations. Our data can be explored at chronology.rna.snu.ac.kr.
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ARN Mensajero , Proteínas de Unión al ARN , Humanos , ARN Mensajero/metabolismo , ARN Mensajero/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Unión Proteica , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Células HeLa , Factores de Tiempo , Aprendizaje AutomáticoRESUMEN
Tumor-associated macrophages (TAMs) are vital contributors to the growth, metastasis, and therapeutic resistance of various cancers, including hepatocellular carcinoma (HCC). However, the exact phenotype of TAMs and the mechanisms underlying their modulation for therapeutic purposes have not been determined. Here, we present compelling evidence that glutamine-derived aspartate in TAMs stimulates spermidine production through the polyamine synthesis pathway, thereby increasing the translation efficiency of HIF-1α via eIF5A hypusination. Consequently, augmented translation of HIF-1α drives TAMs to undergo an increase glycolysis and acquire a metabolic phenotype distinct from that of M2 macrophages. Finally, eIF5A levels in tumor stromal lesions were greater than those in nontumor stromal lesions. Additionally, a higher degree of tumor stromal eIF5A hypusination was significantly associated with a more advanced tumor stage. Taken together, these data highlight the potential of inhibiting hypusinated eIF5A by targeting glutamine metabolism in TAMs, thereby opening a promising avenue for the development of novel therapeutic approaches for HCC.
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Ácido Aspártico , Carcinoma Hepatocelular , Factor 5A Eucariótico de Iniciación de Traducción , Glutamina , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Hepáticas , Factores de Iniciación de Péptidos , Proteínas de Unión al ARN , Macrófagos Asociados a Tumores , Factores de Iniciación de Péptidos/metabolismo , Factores de Iniciación de Péptidos/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Humanos , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Glutamina/metabolismo , Ácido Aspártico/metabolismo , Ácido Aspártico/análogos & derivados , Biosíntesis de Proteínas , Animales , Línea Celular Tumoral , Ratones , Glucólisis , Lisina/análogos & derivadosRESUMEN
Cell death is crucial for maintaining tissue balance and responding to diseases. However, under pathological conditions, the surge in dying cells results in an overwhelming presence of cell debris and the release of danger signals. In the liver, this gives rise to hepatic inflammation and hepatocellular cell death, which are key factors in various liver diseases caused by viruses, toxins, metabolic issues, or autoimmune factors. Both clinical and in vivo studies strongly affirm that hepatocyte death serves as a catalyst in the progression of liver disease. This advancement is characterized by successive stages of inflammation, fibrosis, and cirrhosis, culminating in a higher risk of tumor development. In this review, we explore pivotal forms of cell death, including apoptosis, pyroptosis, and necroptosis, examining their roles in both acute and chronic liver conditions, including liver cancer. Furthermore, we discuss the significance of cell death in liver surgery and ischemia-reperfusion injury. Our objective is to illuminate the molecular mechanisms governing cell death in liver diseases, as this understanding is crucial for identifying therapeutic opportunities aimed at modulating cell death pathways.
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Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.
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Células Endoteliales , Células Madre Pluripotentes Inducidas , Humanos , Diferenciación Celular , Miocitos Cardíacos , Ingeniería de Tejidos/métodosRESUMEN
OBJECTIVES: Prior research into the factors linked to mental health of caregivers of older adults have largely focused on individual- or household-level characteristics, but neighborhood supports and stressors may also matter for caregiver mental health. The current study fills this knowledge gap by examining the association of neighborhood social cohesion and disorder and depressive symptoms among spousal caregivers. METHOD: We used data from the 2006 to 2016 waves of the Health and Retirement Study, which include 2,322 spousal caregivers. Negative binomial regression models were estimated to examine the association of perceived neighborhood social cohesion and disorder with depressive symptoms. RESULTS: A higher level of perceived neighborhood social cohesion was associated with fewer depressive symptoms (b = -0.06, 95% CI: -0.10, -0.02). On the other hand, greater perceived neighborhood disorder was associated with more symptoms (b = 0.04, 95% CI: 0.01, 0.08). The association of perceived social cohesion with depressive symptoms remained even after controlling for perceived disorder, but neighborhood disorder was no longer associated with depressive symptoms after accounting for reported neighborhood social cohesion. CONCLUSIONS: This study suggests neighborhood supports and stressors matter for caregiver well-being. Neighborhood-based social support may be particularly important for caregivers as they navigate the challenges caregiving for an aging spouse can bring. Future studies should determine if enhancing positive characteristics of the neighborhood promotes well-being of spousal caregivers.
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Cuidadores , Depresión , Humanos , Anciano , Depresión/epidemiología , Depresión/psicología , Cohesión Social , Apoyo Social , Salud Mental , Características de la ResidenciaRESUMEN
BACKGROUND: Recently, a new cryotherapy device that precisely controls skin temperature was developed. Precision cryotherapy (PC) can be a safe and alternative treatment modality for immune-related skin diseases that are difficult to treat by conventional cryotherapy because of serious adverse events. OBJECTIVE: To evaluate the efficacy and safety of PC in scalp seborrheic dermatitis (SD). METHODS: A single-arm, prospective trial was designed. Twenty-four patients with SD underwent 3 PC interventions 2 weeks apart. At the baseline, Week 6, and Week 8, overall improvements in Physician Global Assessment (PGA) and clinical severity scores were assessed. At each visit, the erythema index (EI) and transepidermal water loss were evaluated. The patients scored 9 subjective symptoms using a visual analog scale (VAS). RESULTS: The itch VAS score decreased by 50.4% at Week 8. Blinded investigators reported improvement of PGA scores from 2.86 ± 0.62 to 1.66 ± 0.61 and clinical severity scores from 4.55 ± 1.30 to 2.45 ± 1.37. The average EI decreased by 19.6% at Week 8 ( p < .05). CONCLUSION: This study not only demonstrated the efficacy and safety of PC in scalp SD but it also revealed insights for PC being a promising treatment modality in immune-related skin diseases.
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Dermatitis Seborreica , Humanos , Dermatitis Seborreica/terapia , Dermatitis Seborreica/inducido químicamente , Dermatitis Seborreica/diagnóstico , Antifúngicos/uso terapéutico , Cuero Cabelludo , Estudios Prospectivos , Resultado del Tratamiento , Eritema/tratamiento farmacológico , Crioterapia/efectos adversosRESUMEN
Low-grade myofibroblastic sarcoma (LGMS) is a rare spindle cell tumor with indolent course. Due to rarity and low-grade histologic features of LGMS, accurate diagnosis is challenging. We report a 63-year-old female patient with a three-month history of a 3.1 cm×2.5 cm sized, firm, skin-colored, painless, protruding left back mass. Initial excisional biopsy was performed and the mass was diagnosed as nodular fasciitis. After 18 months after excision, the mass recurred with pain and grew larger. Considering the clinical manifestations, diagnostic impression was changed as dermatofibrosarcoma protuberans not nodular fasciitis. Second wide excision was performed and the histopathology revealed proliferative atypical spindle cells with moderate nuclear atypia and a distinctive whorling pattern, which is suggestive of low-grade sarcoma. Additional computed tomography and positron emission tomography revealed no metastasis and suspicious residual viable malignant tissue. To remove suspicious residual tumor, third wide excision were performed and the diagnosis confirmed as LGMS. A microscopically clear resection was achieved with deep and lateral safety margin 0.6 cm each. Despite of postoperative radiotherapy with 35 times, recurrence of the tumor and lung metastasis was found after 7 months later. LGMS rarely metastasizes and occurs most commonly in the head and neck region. Thus, we report a rare case of LGMS on back which repeated localized recurrence and regional lung metastasis occurred despite wide excision and adjuvant radiotherapy.
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Ganglioside GM3 is a simple monosialoganglioside (NeuAc-Gal-Glc-ceramide) that modulates cell adhesion, proliferation, and differentiation. Previously, we reported isolation of GM3-binding vascular endothelial growth factor receptor and transforming growth factor-ß receptor by the T7 phage display method (Chung et al., 2009; Kim et al., 2013). To further identify novel proteins interacting with GM3, we extended the T7 phage display method in this study. After T7 phage display biopanning combined with immobilized biotin-labeled 3'-sialyllactose prepared on a streptavidin-coated microplate, we isolated 100 candidate sequences from the human lung cDNA library. The most frequently detected clones from the blast analysis were the human nucleolar and coiled-body phosphoprotein 1 (NOLC1) sequences. We initially identified NOLC1 as a molecule that possibly binds to GM3 and confirmed this binding ability using the glutathione S-transferase fusion protein. Herein, we report another GM3-interacting protein, NOLC1, that can be isolated by the T7 phage display method. These results are expected to be helpful for elucidating the functional roles of ganglioside GM3 with NOLC1. When human breast cancer MCF-7 cells were examined for subcellular localization of NOLC1, immunofluorescence of NOLC1 was observed in the intracellular region. In addition, NOLC1 expression was increased in the nucleolus after treatment with the anticancer drug doxorubicin. GM3 and NOLC1 levels in the doxorubicin-treated MCF-7 cells were correlated, indicating possible associations between GM3 and NOLC1. Therefore, direct interactions between carbohydrates and cellular proteins can pave the path for new signaling phenomena in biology.
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Bacteriófago T7 , Neoplasias de la Mama , Humanos , Femenino , Bacteriófago T7/genética , Factor A de Crecimiento Endotelial Vascular , Gangliósido G(M3) , Células MCF-7 , Neoplasias de la Mama/genética , Doxorrubicina , Proteínas Nucleares/metabolismo , FosfoproteínasRESUMEN
Despite recent progress in medical and endovascular therapy, the prognosis for patients with critical limb ischemia (CLI) remains poor. In response, various stem cells and growth factors have been assessed for use in therapeutic neovascularization and limb salvage in CLI patients. However, the clinical outcomes of cell-based therapeutic angiogenesis have not provided the promised benefits, reinforcing the need for novel cell-based therapeutic angiogenic strategies to cure untreatable CLI. In the present study, we investigated genetically engineered mesenchymal stem cells (MSCs) derived from human bone marrow that continuously secrete stromal-derived factor-1α (SDF1α-eMSCs) and demonstrated that intramuscular injection of SDF1α-eMSCs can provide long-term paracrine effects in limb ischemia and effectively contribute to vascular regeneration as well as skeletal muscle repair through increased phosphorylation of ERK and Akt within the SDF1α/CXCR4 axis. These results provide compelling evidence that genetically engineered MSCs with SDF-1α can be an effective strategy for successful limb salvage in limb ischemia.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Humanos , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/farmacología , Miembro Posterior/irrigación sanguínea , Isquemia/terapia , Isquemia/metabolismo , Células Madre Mesenquimatosas/metabolismo , Músculo Esquelético/metabolismo , Neovascularización FisiológicaRESUMEN
Fixed drug eruption (FDE) is a well-defined hyperpigmented patch that recurs in a fixed location each time a particular drug is taken. Common causative agents of FDE are non-steroidal anti-inflammatory drugs, non-narcotic analgesics, sedatives, anticonvulsants, sulfonamides, and tetracycline. We report a 33-year-old male who presented with a recurrent, localized, brownish-to-erythematous macule and papules on the peri-philtrum area two hours after taking valacyclovir. Three episodes of valacyclovir ingestion for treatment of Herpes simplex virus infection provoked a similar skin rash at the same site. Histopathology results showed vacuolar degeneration in the basal layer of the epidermis, pigmentary incontinence, and perivascular inflammatory cell infiltration in the papillary dermis. Although patch test and skin prick test showed negative responses to acyclovir and valacyclovir, an intradermal test showed a positive reaction only to valacyclovir. The oral provocation test to acyclovir and valacyclovir showed a positive reaction only to valacyclovir. Through drug history, histopathological examination, patch test, intradermal test, and oral provocation test, we established a final diagnosis of FDE due to valacyclovir without cross-reactivity to acyclovir. To find alternative therapeutic drugs, we suggest diagnostic tests with not only the suspected drugs, but also other drugs in the same class.
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The genus Bryaxis Kugelann (Goniaceritae: Bythinini) is the most species-rich genus of the subfamily Pselaphinae and is mainly distributed in the Palearctic region. Although previous studies have documented 14 species in the Korean Peninsula, the true diversity, ecology, and immature stages of the genus are still inadequately known. In this study, five new Korean species are described: B.grandinodussp. nov., B.uljinensissp. nov., B.fabaiformissp. nov., B.girinensissp. nov., and B.nemorosussp. nov. Illustrations of the habitus and other morphological details, and a distribution map are provided. In addition, Bryaxisleechanyoungi Nomura & Lee, 1993 is proposed as a new synonym of B.mahunkai Löbl, 1975 based on the original description and illustrations of diagnostic characters.