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

Sorafenib is an inhibitor of receptor tyrosine kinases and the rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathway that is approved for the treatment of patients with metastatic hepatocellular carcinoma (HCC) and renal cell carcinoma. Sorafenib is known to have various cutaneous adverse effects, including hand-foot reaction, facial and scalp eruption, xerosis, and alopecia1.A 56-year-old man presented with non-painful, nonpruritic psoriasiform lesions that has been present for approximately 1 month (Fig. 1A∼E). Six months prior to presentation, he had been prescribed sorafenib at a daily dosage of 600∼800 mg after diagnosis of HCC with distant metastasis to the lung. A punch biopsy showed psoriasiform dermatitis (Fig. 1F, G). The skin lesions improved gradually after discontinuing sorafenib. However, at 1 month after discontinuation of sorafenib, considering the dose-dependent adverse effect of the medication, the patient resumed sorafenib at 400 mg daily after an oncology consultation. The lesions recurred beginning at 1 week after restarting sorafenib. A clinical diagnosis of sorafenib-associated psoriasiform drug eruption was made. The sorafenib treatment was maintained at 400 mg daily in conjunction with concurrent phototherapy and topical and intralesional corticosteroids for thick erythematous plaques, and intermittent systemic corticosteroid treatment when the cutaneous eruptions flared up.After approximately 2 years of sorafenib treatment, the patient presented with new crusting lesions without any other systemic adverse reactions. Multiple papules and plaques with central hyperkeratotic and crusted papules were present (Fig. 2A∼D). Punch biopsy showed a ‘perforating phenomenon’ (PP) (Fig. 2E∼G). The brownish hyperkeratotic crusts occurred consistently in prolonged psoriasiform plaques and resolved over time (Fig. 2A∼D). The psoriasiform eruptions and delayed-onset PP persisted with continuing sorafenib use (Fig. 2H). Along with a dose-decrease of sorafenib at 400mg daily, he was treated with systemic and topical corticosteroids, intralesional triamcinolone injection and narrowband ultraviolet B therapy. However, the patient showed recurrent cutaneous lesions aggravation upon tapering the dosage of corticosteroid.The psoriasiform lesions improved and then worsened with sorafenib dose change, and the PP featured hyperkeratotic crusts within multiple, long-lasting psoriasiform plaques. This phenomenon might have occurred to eliminate connective tissue or inflammatory material2 and differs from the appearance of transepidermal elimination in previously reported sorafenib-associated acquired perforating dermatosis cases3,4. Transepidermal elimination is a similar process to wound healing2, and considering that our patient had no history of diabetes, renal insufficiency, and trauma, our case might have exhibited the perforating and resolving phenomenon in response to the abnormal psoriasiform drug eruption.The RAS/MAPK cascade that is inhibited by sorafenib could be activated paradoxically; due to its role in antiangiogenesis, this activation results in epidermal disruption. The reduction and suppression of the hepatocyte growth factor-enhanced expression of matrix metalloproteinase induced by sorefenib could influence homeostasis of dermal elastic fibres, resulting in their disruption5. A few cases of psoriasiform drug eruption and PP after administration of sorafenib and other various tyrosine kinase inhibitors have been reported.The PP could represent a manifestation of the resolution of inflammation whereby the psoriasiform hyperplasia and the proliferated dermal tissue might be eliminated via a trans-epidermal route.

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.

The positive rate of Clonorchis sinensis is the highest among intestinal parasites in the Republic of Korea (Korea). More than 1.2 million people were at risk of C. sinensis infection in Korea in 2012. An intensive control program is being implemented for residents of the 5 major river basins to reduce helminthic infections, including C. sinensis infection. This study evaluated the continuous intensive control program for parasitic diseases including clonorchiasis in areas near the 5 major river basins in Korea over the past 10 years (2011-2020). A total of 335,020 fecal samples (one sample per resident) prepared by the modified sedimentation technic were microscopically examined. Those who expelled helminth eggs were treated with anthelmintics through local health centers and re-examined 3 months later. The overall positive rate of helminths egg was 7.1%. The annual positive rates were dramatically decreased from 14.4% (2011) to 5.9% (2020). The egg positive rate was highest in C. sinensis (5.3%), followed by heterophyid flukes (1.5%) and Trichuris trichiura (0.2%). The prevalence of C. sinensis was significantly higher in males (7.6%) than in females (3.7%), and the highest in the 50–59 years (7.0%) age group. Our results are beneficial to establish prevention and control policies against helminthiases including clonorchiasis in endemic areas in this country.

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

Background: Foreign bodies may be embedded or left behind in the oral cavity during oral surgical procedure. The loss of instruments such as impression material, surgical gauze, and broken injection needles are commonly reported in the dental field. These complications are generally symptomatic and show signs of inflammation, pain, and purulent discharge. Accidental breakage of suture needles is a rare but potentially dangerous event.Case presentation: In this report, we present one case of lost suture needle during the procedure of flap operation at local dental clinic and its successful removal under local/general anesthesia administration via CBCT with a help of two reference needles to localize the 6-0 nylon needle and consulting with the clinician. Conclusion CT scanning taken while mouth-closing may not be accurate with regard to real location measurement performed while mouth-opening. If so, other up-to-date radiographic devices and methods to retrieve a needle are recommended.

Simultaneous quantification of multiple marker compounds in herbal medicine by high performance liquid chromatography (HPLC) analysis is still a challenge due to the complexity in various parameters to be considered and co-existing multi-components. As a case study, a reliable HPLC method for simultaneous quantification of paeoniflorin from Paeoniae Radix and decursin from Angelicae Gigantis Radix in various commercial herbal medicine was developed based on analytical quality by design (AQbD) strategy. As a first step, risk assessment was performed to select the critical method parameters (CMPs) which were decided as organic mobile phase ratio and column oven temperature. In order to evaluate the effect of the CMPs on critical method attributes (CMAs) of peak resolution and tailing, central composite design (CCD) was employed. The final chromatographic conditions were optimized as follows: column- C 18 , 4.6 × 250 mm, 5 μm particle size; mobile phase- A: acetonitrile, B: 0.1% acetic acid water; detection wavelength- 235 nm for paeoniflorin, 325 nm for decursin; column oven temperature- 25 o C; flow rate- 1.0 mL/min; gradient mobile phase system as Time (min) : % A, 0:14, 25:14, 30:50, 60:50, 61:100, 65:100, 66:14, 75:14. The method was successfully validated according to the International Conference on Harmonization (ICH) guidelines and piloted for ten commercial herbal medicines.

BACKGROUND: Cyclosporine (CS) is widely used to treat various skin diseases. Gastrointestinal (GI) discomfort is the most common adverse effect of orally administered CS for dermatologic indications. However, few studies on CS-associated adverse GI events have been conducted. OBJECTIVE: In this study, we aimed to describe the major features of adverse GI events associated with CS therapy using a validated symptom questionnaire, and to investigate the factors contributing to their development. We also evaluated the effectiveness of three empirical GI medications in relieving adverse GI events. METHODS: This study consisted of 2 phases. Phase I was a prospective observational cohort study to investigate the characteristics of CS-associated adverse GI events in 942 consecutive patients treated with CS. Phase II was a randomized controlled trial to evaluate the efficacy of three different classes of GI medications. RESULTS: CS-associated adverse GI events occurred in 119 patients (12.6%). GI complications were more common in female patients (p=0.04), patients with a history of GI disorders (p=0.02), and patients whose initial CS doses were greater than 3 mg/kg/day (p=0.05). In patients treated with any one of the three GI medications, the mean Gastrointestinal Symptom Rating Scale scores significantly decreased (p<0.001). CONCLUSION This study demonstrated that adverse GI events are common during early CS treatment, especially in women, patients receiving high doses of CS, and those with a history of GI disorders. Our results suggest that new-onset CS-associated GI side effects can be effectively managed with the addition of GI medications.