Stimuli-Responsive Adaptive Nanotoxin to Directly Penetrate the Cellular Membrane by Molecular Folding and Unfolding.

Biological nanomachines, including proteins and nucleic acids whose function is activated by conformational changes, are involved in every biological process, in which their dynamic and responsive behaviors are controlled by supramolecular recognition. The development of artificial nanomachines that mimic the biological functions for potential application as therapeutics is emerging; however, it is still limited to the lower hierarchical level of the molecular components. In this work, we report a synthetic machinery nanostructure in which actuatable molecular components are integrated into a hierarchical nanomaterial in response to external stimuli to regulate biological functions. Two nanometers core-sized gold nanoparticles are covered with ligand layers as actuatable components, whose folding/unfolding motional response to the cellular environment enables the direct penetration of the nanoparticles across the cellular membrane to disrupt intracellular organelles. Furthermore, the pH-responsive conformational movements of the molecular components can induce the apoptosis of cancer cells. This strategy based on the mechanical motion of molecular components on a hierarchical nanocluster would be useful to design biomimetic nanotoxins.

Pure laparoscopic donor right hepatectomy: perspectives in manipulating a flexible scope.

BACKGROUND: Interest in pure laparoscopic donor hepatectomy (PLDH) is increasing worldwide with the donor's cosmetic demands and improvements in surgical techniques. Efficient manipulation of flexible scope is mandatory for successful PLDH, especially in right hepatectomy which requires more mobilization. This study provides guidelines on how to manipulate optimally a flexible scope. METHODS: Data from 158 donors who underwent pure laparoscopic donor right hepatectomy (PLDRH) between November 2015 and December 2017 were retrospectively reviewed. RESULTS: None of the donors required transfusion, conversion to open hepatectomy, or experienced any irreversible disabilities or mortalities. Three types of laparoscopic view provided by the flexible scope, which are bird's eye view, low angle view, and lateral view, were applied to each step of the procedure. CONCLUSIONS: PLDRH can be successfully performed with maximizing visibility given by the tips and pitfalls in manipulating the flexible scope.

Transnasal Endoscopic Resection of a Pleomorphic Adenoma Originate From Nasal Floor.

A 81-year-old female presented to our hospital frequent epistaxis. Nasal endoscopy showed a mass obstructing nasal cavity completely and occupying middle meatus. Magnetic resonance imaging was performed, an about 4.8 × 4 × 4.2 cm sized heterogeneous T2 high signal intensity and T1 enhancing mass mainly involving right nasal cavity with invasion of right hard palate with bony destruction. Therefore, the authors planned to do endoscopic mass excision, under general anesthesia for diagnosis and treatment. The authors removed the mass from lateral nasal wall, nasal roof, nasal septum, medial maxillary wall by piece-meal. Margins of mass were clear except the nasal floor. So, the authors did frozen biopsy to confirm the clear margin in nasal floor. Endoscopy enables better visualization of tumor margins, facilitating complete removal and avoiding excessive resection and following up using good visualization.

Low dose of mycophenolate mofetil is enough in desensitized kidney transplantation using rituximab.

BACKGROUND: Rituximab is widely used in kidney transplantation. However, it is not clear whether the conventional doses of maintenance immunosuppressant in rituximab-treated kidney transplantation (KT) are appropriate. In our previous study, decreasing mycophenolate mofetil (MMF) dose due to infection did not increase the incidence of rejection or graft failure. Based on these experiences, we developed a new protocol with a lower dose of MMF and studied its clinical outcomes in rituximab-treated KT. METHODS: We enrolled all patients who underwent ABO-incompatible or human leukocyte antigen (HLA)-sensitized living donor KT with the new immunosuppressant protocol after preconditioning with rituximab, but without splenectomy from November 2011 to May 2013. Seventy-two patients (group 1) were consecutively enrolled in this study and followed until November 2013. Patients from our previous study served as control groups. Sixty-seven patients received KT using rituximab with a conventional dose of MMF (group 2), and 87 patients received ABO compatible KT without need for rituximab (group 3). Clinical outcomes, including rejection, infection, and graft survival, were compared between the groups. The χ (2) test and Fisher's exact test were used for categorical variables, the Student's t-test and Mann-Whitney U test were used for continuous variables, and a log-rank test was used for mortality analysis. RESULTS: Doses of postoperative MMF (g/day) were lower in group 1 than in the other groups (1.03 ± 0.19, 1.48 ± 0.34 and 1.48 ± 0.32 g/day at 1 week, p < 0.001). Infectious complications occurred more often in groups with conventional MMF doses (group 2 and 3) than in group 1 (16.7 vs. 37.3 %, p = 0.007 and 16.7 vs. 34.5 %, p = 0.012, respectively). Notably, group 1 showed a lower incidence of cytomegalovirus infection than group 2. However, reduction in MMF dose did not increase the incidence of acute rejection (4.2, 4.5 and 10.3 %). Only one graft failure occurred in group 2 due to vessel kinking after operation. There were no significant differences in the incidence of malignancy and mortality between groups. CONCLUSIONS: A low MMF dose reduces infection without increasing rejection or graft loss and it may be appropriate to reduce the dose of MMF for rituximab-treated KT patients.

Single-Walled Carbon Nanotube-Guided Topical Skin Delivery of Tyrosinase to Prevent Photoinduced Damage.

When the skin is exposed to ultraviolet radiation (UV), it leads to the degradation of the extracellular matrix (ECM) and results in inflammation. Subsequently, melanocytes are triggered to induce tyrosinase-mediated melanin synthesis, protecting the skin. Here, we introduce a proactive approach to protect the skin from photodamage via the topical delivery of Streptomyces avermitilis-derived tyrosinase (SaTy) using single-walled carbon nanotube (SWNT). Utilizing a reverse electrodialysis (RED) battery, we facilitated the delivery of SaTy-SWNT complexes up to depths of approximately 300 µm, as analyzed by using confocal Raman microscopy. When applied to ex vivo porcine skin and in vivo albino mouse skin, SaTy-SWNT synthesized melanin, resulting in 4-fold greater UV/vis absorption at 475 nm than in mice without SaTy-SWNT. The synthesized melanin efficiently absorbed UV light and alleviated skin inflammation. In addition, the densification of dermal collagen, achieved through SaTy-mediated cross-linking, reduced photoinduced wrinkles by 66.3% in the affected area. Our findings suggest that SWNT-mediated topical protein delivery holds promise in tissue engineering applications.

Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis.

Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (-637.5 kJ mol-1) than for adenosine diphosphate (ADP) (-578.2 kJ mol-1). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP-ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.

Effects of Using Perineal Underwear on Discomfort and Shame in Angiography Patients.

The purpose of this study is to develop and apply a type of perineal underwear that protects the patient's physical privacy and to examine its effects on perineal discomfort and shame. This study collected primary data from 44 patients who visited Kyung Hee University hospital in Seoul city and were admitted to the neurosurgery ward to undergo angiography between 7 August 2017, and 30 April 2018. In this quasi-experimental study with a nonequivalent control group posttest-only design, participants were divided into an experimental group (n = 22) and a control group (n = 22). The control group used conventional protection, which involved wearing padding around the perineum, while the experimental group wore the perineal underwear developed in this study. The underwear group showed a significantly lower degree of shame (Z = -5.39, p < 0.001) and perineal discomfort (Z = -5.88, p < 0.001) than the padding group. In the padding group, women felt significantly more shame than men did (Z = -2.48, p = 0.013). The use of the perineal underwear developed in this study significantly reduced the degree of shame and perineal discomfort in patients undergoing angiography. Such perineal underwear could also be useful for protecting patients' privacy during perineal examinations.

Nonshaved Ear Surgery: Effect of Hair on Surgical Site Infection of the Middle Ear/Mastoid Surgery and Patients' Preference for the Hair Removal.

BACKGROUND AND OBJECTIVES: This study aimed 1) to compare the rates of surgical site infection (SSI) between two groups with and without preoperative hair shaving, 2) to compare the bacterial colonization just before the skin incision between them, and 3) to evaluate people's preference for the hair shaving. SUBJECTS AND METHODS: The retrospective study enrolled cases in which middle ear and mastoid surgery was performed with as well as without hair removal. Main measurement outcomes were the SSI rate within 3 months following the surgery, bacterial culture results obtained from the incision area just before the skin incision, and questionnaire to evaluate the preference for hair shaving from patients with chronic suppurative otitis media but without experience with the ear surgery. RESULTS: This study did not show any difference in the rates of SSI and bacterial colonization between two groups with and without preoperative hair shaving. Most patients without experience with the ear surgery chose the nonshaved ear surgery, even though the questionnaire presented a comment as follow; "Your hair will always grow back as the growth speed of about 1.25 cm per month." CONCLUSIONS: There is no evidence showing that preoperative shaving of the surgical site is helpful for the SSI than no hair removal. Nonshaved middle ear and mastoid surgery via postauricular approach appears to be preferable. Contrary to doctors' popular belief, the hair shaving can cause psychological discomfort, especially for women. Now is the time to keep the balance between the professional's perspective and the patients' preferences.

Biodegradation of endocrine-disrupting bisphenol A by white rot fungus Irpex lacteus.

Biodegradation of endocrine-disrupting bisphenol A was investigated with several white rot fungi (Irpex lacteus, Trametes versicolor, Ganoderma lucidum, Polyporellus brumalis, Pleurotus eryngii, Schizophyllum commune) isolated in Korea and two transformants of T versicolor (strains MrP 1 and MrP 13). I. lacteus degraded 99.4% of 50 mg/l bisphenol A in 3 h incubation and 100% in 12 h incubation. which was the highest degradation rate among the fungal strains tested. T. versicolor degraded 98.2% of 50 mg/l bisphenol A in 12 h incubation. Unexpectedly, the transformant of the Mn-repressed peroxidase gene of T. versicolor, strain MrP 1, degraded 76.5% of 50 mg/l bisphenol A in 12 h incubation, which was a lower degradation rate than wild-type T. versicolor. The removal of bisphenol A by I. lacteus occurred mainly by biodegradation rather than adsorption. Optimum carbon sources for biodegradation of bisphenol A by I. lacteus were glucose and starch, and optimum nitrogen sources were yeast extract and tryptone in a minimal salts medium; however, bisphenol A degradation was higher in nutrient-rich YMG medium than that in a minimal salts medium. The initial degradation of endocrine disruptors was accompanied by the activities of manganese peroxidase and laccase in the culture

TiO2 Nanowire Networks Prepared by Titanium Corrosion and Their Application to Bendable Dye-Sensitized Solar Cells.

TiO2 nanowire networks were prepared, using the corrosion of Ti foils in alkaline (potassium hydroxide, KOH) solution at different temperatures, and then a further ion-exchange process. The prepared nanostructures were characterized by field emission scanning electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The wet corroded foils were utilized as the photoanodes of bendable dye-sensitized solar cells (DSSCs), which exhibited a power conversion efficiency of 1.11% under back illumination.

Temple syndrome: A patient with maternal hetero-UPD14, mixed iso- and hetero-disomy detected by SNP microarray typing of patient-father duos.

Temple syndrome (TS, MIM 616222) is an imprinting disorder involving genes within the imprinted region of chromosome 14q32. TS is a genetically complex disorder, which is associated with maternal uniparental disomy of chromosome 14 (UPD14), paternal deletions on chromosome 14, or loss of methylation at the intergenic differentially methylated region (IG-DMR). Here, we describe the case of a patient with maternal hetero-UPD14, mixed iso-/hetero-disomy mechanism identified by a single nucleotide polymorphism (SNP) array analysis of patient-father duos study. The phenotype of our case is similarities to Prader-Willi syndrome (PWS) during infancy and to Russell-Silver syndrome (RSS) during childhood. This SNP array appears to be an effective initial screening tool for patients with nonspecific clinical features suggestive of chromosomal disorders.

Clinical Analysis of Paper Patch Myringoplasty in Patients with Tympanic Membrane Perforations.

OBJECTIVE: The aims of our study were to evaluate the outcome of office-based paper patch grafting in tympanic membrane (TM) perforation regardless of the disease duration or etiology and to compare the clinical factors influencing the successful closure of perforation between the success and failure groups of paper patch myringoplasty. MATERIALS AND METHODS: This is a retrospective study of 114 patients that underwent paper patch myringoplasty in an outpatient setting (success group, 83 cases; failure group, 31 cases). Thirteen clinical factors with potential impact on the healing status of the TM were investigated: gender, age, laterality, etiology, duration of perforation, tinnitus, hearing loss, otorrhea, size and location of perforation, status of contralateral ear, ipsilateral findings of computed tomography, and duration of complete healing. The follow-up period was at least 1 year. RESULTS: The total success rate of paper patch grafting was 72.8%. The mean age of the failure group was significantly more higher than that of the success group. Significant differences in the etiology as well as in the history of otorrhea were found between the success and failure groups. There were no significant differences for any of the other factors between chronic and non-chronic perforations. CONCLUSION: The predictors of successful outcome were patient's age, etiology of perforation, and history of otorrhea. Clinicians can attempt paper patch myringoplasty first in younger patients, traumatic TM perforation cases, and in patients with no history of otorrhea. Paper patch grafting can also be considered before formal surgical myringoplasty in the case of small, dry, chronic TM perforations.

Risk Factors for Graft Failure and Death following Geriatric Renal Transplantation.

BACKGROUND: Population aging is a major health concern in Asian countries and it has affected the age distribution of patients with end-stage renal disease (ESRD). As a consequence, the need for kidney transplantation in the geriatric population has increased, but the shortage of donors is an obstacle for geriatric renal transplantation. The aim of this study was to evaluate risk factors for graft failure and death in geriatric renal transplantation. METHODS: Kidney transplantations performed in a tertiary hospital in South Korea from May 1995 to December 2014 were retrospectively reviewed. Recipients younger than 60 years of age or who underwent other organ transplantations were excluded. The Kaplan-Meier method was used to assess patient and graft survival. A Cox regression analysis was used to evaluate risk factors for graft failure and patient death. RESULTS: A total of 229 kidney transplantation patients were included. Graft survival at 1, 5, and 10 years were 93.2%, 82.9%, and 61.2% respectively. Patient survival at 1, 5, and 10 years were 94.6%, 86.9%, and 68.8%, respectively. According to the Cox multivariate analysis, ABO incompatibility (hazard ratio [HR] 3.91, p < 0.002), DGF (HR 3.544, p < 0.004), CMV infection (HR 2.244, p < 0.011), and HBV infection (HR 6.349, p < 0.015) were independent risk factors for graft survival. Recipient age (HR 1.128, p < 0.024), ABO incompatibility (HR 3.014, p < 0.025), CMV infection (HR 2.532, p < 0.010), and the number of HLA mismatches (HR 1.425, p < 0.007) were independent risk factors for patient death. CONCLUSION: Kidney transplantation in the geriatric population showed good clinical outcomes. ABO incompatibility, DGF, CMV infection, and HBV infection were risk factors for graft failure and the recipient age, ABO incompatibility, CMV infection, and the number of HLA mismatches were risk factors for patient death in geriatric renal transplantation.

Usefulness of Tacrolimus without Basiliximab in Well-Matched Living-Donor Renal Transplant Recipients in Korea.

OBJECTIVES: Basiliximab is used alongside tacrolimus-based immunosuppression for routine induction therapy, even for well-matched living-donor renal transplant recipients. Because tacrolimus is a different drug from cyclosporine, this study examined the utility of tacrolimus-based immunosuppression without basiliximab for well-matched living-donor renal transplant recipients. MATERIALS AND METHODS: This prospective study evaluated 36 patients who underwent 1 to 3 human leukocyte antigens mismatched living-donor renal transplants without basiliximab induction therapy between April 2012 and March 2015 (group 1). All transplants were ABO compatible and T-flow negative and were followed until April 2015. Tacrolimus-based triple therapy was used for maintenance immunosuppression. The control group comprised 72 age- and sex-matched patients who underwent 1 to 3 human leukocyte antigens mismatched living-donor renal transplants with basiliximab induction therapy during the same period (group 2). RESULTS: Two patients in group 1 and 12 patients in group 2 had infection,with cytomegalovirus infection and Pneumocystis pneumonia infection occurring only in group 2 and BK virus and urinary tract infection reported in both groups, with a similar incidence. One patient from group 2 had sepsis. Although the incidence of infection tended to be lower in group 1 than in group 2 (5.6% vs 16.7%), the overall incidence of infection was not significantly different (P=.135). In addition, there were no significant differences in incidence of acute rejection between groups 1 and 2 (2.8% vs 4.2%; P=.699). All patients showed stable renal function after treatment. CONCLUSIONS: Tacrolimus-based triple drug maintenance immunosuppression without basiliximab might be an optimal treatment choice for individuals undergoing well-matched living-donor renal transplant.

Isolated Myxoma in the External Auditory Canal of a 10-Year-Old Girl.

Myxoma is a benign connective tissue tumor that is most commonly found in the heart. Because myxoma of the external ear is extremely rare, its diagnosis may be easily delayed or it may be misdiagnosed as another disease. Moreover, because it can be a part of Carney complex (autosomal dominant syndrome), its correct diagnosis is very important. We experienced a 10-year-old girl who had a mass on the posterior surface of the tragus at the entrance of the left ear canal. Fine-needle aspiration revealed mucoid content of the cystic mass, but its cytology did not confirm the diagnosis. The whole mass was surgically removed, and the diagnosis was confirmed as myxoma with a stellate spindle cell proliferation in the hypocellular matrix. Thorough examination failed to determine any presentation of Carney complex, and her final diagnosis was isolated myxoma of the external auditory canal. This is the first reported study regarding myxoma of the external auditory canal in the Korean literature.

Direct exfoliation and dispersion of two-dimensional materials in pure water via temperature control.

The high-volume synthesis of two-dimensional (2D) materials in the form of platelets is desirable for various applications. While water is considered an ideal dispersion medium, due to its abundance and low cost, the hydrophobicity of platelet surfaces has prohibited its widespread use. Here we exfoliate 2D materials directly in pure water without using any chemicals or surfactants. In order to exfoliate and disperse the materials in water, we elevate the temperature of the sonication bath, and introduce energy via the dissipation of sonic waves. Storage stability greater than one month is achieved through the maintenance of high temperatures, and through atomic and molecular level simulations, we further discover that good solubility in water is maintained due to the presence of platelet surface charges as a result of edge functionalization or intrinsic polarity. Finally, we demonstrate inkjet printing on hard and flexible substrates as a potential application of water-dispersed 2D materials.

Both "나" and "な" are yellow: cross-linguistic investigation in search of the determinants of synesthetic color.

Individuals with grapheme-color synesthesia experience "colors" when viewing achromatic letters and digits. Despite the large individual difference in synesthetic association between inducing graphemes and induced colors, the search for the determinants of synesthetic experience has begun. So far, however, research has drawn an inconsistent picture; some studies have shown that graphemes of similar visual shape tend to induce similar synesthetic colors, while others suggested sound as an important factor. Moreover, meaning seems to affect synesthetic color. In the present work, we sought to investigate the determinants of synesthetic color by testing four multilingual grapheme-color synesthetes who experience "colors" upon viewing Korean (hangul), Japanese (katakana and hiragana), and English (Latin alphabet) characters on a standardized color-matching procedure. Results showed that pairs of characters of matched sound tended to induce similar synesthetic colors. This was the case not only between two scripts within the same language (Japanese hiragana and katakana) but also between two different languages (Japanese and Korean). In addition, pairs of characters with similar initial phonemes tended to induce similar colors; this was general across multiple languages. Results also showed that pairs of sequential words in Korean, Japanese, English, and Chinese that have the same meaning tended to elicit similar synesthetic colors. When those pairs of words shared not only meaning but also sound, the similarity of the induced synesthetic colors was even greater. Our work is one of the few initial attempts to examine the influence of visual shape, sound, meaning, and their interaction on synesthetic color induced by characters across multiple languages.

Ameliorative effects of Monascus pilosus-fermented black soybean (Glycine max L. Merrill) on high-fat diet-induced obesity.

The purpose of this study was to examine the antiobesity effects of Monascus pilosus-fermented black soybean (F-BS) in C57BL/6 mice with high-fat diet (HFD)-induced obesity. F-BS (oral, 0.5 and 1.0 g/kg per body weight, twice per day) ameliorated obesity by reducing body and liver weight increases, and regulating blood glucose and cholesterol levels in C57BL/6 mice fed a control or HFD with oral administration of F-BS for 12 weeks. F-BS suppressed the growth of epididymal, retroperitoneal, and perirenal fat pads by preventing increases in the adipocyte size. Moreover, the levels of blood glucose, total cholesterol, and leptin were significantly lowered by F-BS administration in a dose-dependent manner. These results indicated that F-BS is a beneficial food supplement for preventing obesity, controlling blood glucose, and lowering cholesterol. Future research strategies should address the mechanisms that selectively regulate obesity, including hyperglycemia and hypercholesterolemia.

Usefulness of a Helicobacter pylori stool antigen test for diagnosing H. pylori infected C57BL/6 mice.

Among several diagnostic tests, a Helicobacter pylori stool antigen (HpSA) test may offer a useful noninvasive method for diagnosing infection without sacrificing animals. In this study, male C57BL/6 mice (n=6) were infected with H. pylori ATCC 49503 (1×10(8) CFU/mouse) by intragastric inoculation three times at 2-day intervals, and H. pylori infected stool specimens were collected 1, 3, 5, 7, 14, 21 days after infection to assess reliability of the HpSA test. Five of six specimens were positive at 5-21 days after infection, and the sensitivity of the HpSA test was 83.33%. The presence of H. pylori infection was confirmed by the rapid urease test and genomic DNA polymerase chain reaction (PCR), and showed the same results as the HpSA. However, the rapid urease test and genomic DNA PCR are invasive tests and require animal sacrifice to detect H. pylori in gastric biopsy samples. We suggest that an HpSA test kit would be useful and effective for monitoring H. pylori in various laboratory animals, as H. pylori can be easily monitored without sacrificing animals.

Treatment of eggshell with casein phosphopeptide reduces the severity of ovariectomy-induced bone loss.

It has been generally accepted that calcium intake prevents bone loss, and frequent fracture resulted from osteoporosis. However, it is still elusive as to how effective sole calcium intake is in preventing or attenuating the severity of osteoporosis. Here, we demonstrate the effects of eggshell-casein phosphopeptide (ES-CPP), and compared these effects those of calcium supplement, for restoring ovariectomy-mediated bone loss. CPP, synthesized from the hydrolysis of casein (0.5%) using trypsin, was added to the grinded ES and was then administered to the ovariectomized (OVX) rat at 100 mg/kg for 4 weeks. Urine and feces from each group were collected each day, and were used to calculate the apparent calcium absorption rate in a day. After 4 weeks incubation, blood and femoral bones were isolated for the analysis of parameters representing osteoporosis. The apparent calcium absorption rate was significantly increased in the ES-CPP treated groups, in comparison to both the OVX and the commercial calcium supplement (CCS) treated group. Notably, treatment with ES-CPP markedly enhanced the calcium content in femoral bone and the relative weight of femoral bone to body weight, though calcium content in serum was barely changed by treatment with ES-CPP. Parameters of osteoporosis, such as osteocalcin in serum and bone mineral density, were rescued by treatment with ES-CPP, compared to treatment with commercial calcium supplement. This finding strongly suggests the possible use of ES-CPP in preventing or attenuating the severity of postmenopausal osteoporosis.