Efficacy of Asymmetric siRNA Targeting Androgen Receptors for the Treatment of Androgenetic Alopecia.

Asymmetric small interfering RNAs (asiRNAs) that mediate RNA interference have been investigated for therapeutic use in various tissues, including skin tissue. Androgenetic alopecia (AGA) is caused by a combination of genetic factors, resulting in sensitivity to dihydrotestosterone (DHT), which binds to the androgen receptor (AR) to mediate a series of biomolecular changes leading to hair loss. This study aimed to evaluate the therapeutic potential of a cell-penetrating, AR-targeting asiRNA (cp-asiAR) for AGA treatment, which was designed to silence the AR gene. AGA mouse models were developed by stimulation with DHT, and ex vivo human scalp tissues were also used for analysis. Cp-asiAR-mediated changes in mRNA expression and protein levels of AR were assessed along with the examination of phenotypic improvements in mouse model of AGA. We also assessed downstream signaling associated with AR in primary human dermal papilla (DP) cells. Several cp-asiARs were screened for selecting the optimal sequence of AR using cell lines in vitro. A cholesterol-conjugated, chemically modified cp-asiAR candidate was optimized under passive uptake conditions in vitro. Intradermal cp-asiAR injection efficiently reduced mRNA and protein levels corresponding to AR in mouse models. Moreover, cp-asiAR injection promoted hair growth in mouse models with DHT-induced AGA. In ex vivo human hair follicle culture, the proportion of telogen hair decreased, and the mean hair bulb diameter increased in the cp-asiAR-treated group. In isolated primary human DP cells, AR expression was effectively downregulated by cp-asiAR. Furthermore, cp-asiAR attenuated DHT-mediated increases in interleukin-6, transforming growth factor-ß1, and dickkopf-1 levels. No significant toxicity was observed in DP cells after cp-asiAR treatment. Cp-asiAR treatment showed effective downregulation of AR expression and prevention of DHT-mediated alterations in the hair cycle and hair diameter, indicating its potential as a novel therapeutic option for AGA.

Detection of sarcopenic obesity and prediction of long-term survival in patients with gastric cancer using preoperative computed tomography and machine learning.

BACKGROUND: Previous studies evaluating the prognostic value of computed tomography (CT)-derived body composition data have included few patients. Thus, we assessed the prevalence and prognostic value of sarcopenic obesity in a large population of gastric cancer patients using preoperative CT, as nutritional status is a predictor of long-term survival after gastric cancer surgery. METHODS: Preoperative CT images were analyzed for 840 gastric cancer patients who underwent gastrectomy between March 2009 and June 2018. Machine learning algorithms were used to automatically detect the third lumbar (L3) vertebral level and segment the body composition. Visceral fat area and skeletal muscle index at L3 were determined and used to classify patients into obesity, sarcopenia, or sarcopenic obesity groups. RESULTS: Out of 840 patients (mean age = 60.4 years; 526 [62.6%] men), 534 (63.5%) had visceral obesity, 119 (14.2%) had sarcopenia, and 48 (5.7%) patients had sarcopenic obesity. Patients with sarcopenic obesity had a poorer prognosis than those without sarcopenia (hazard ratio [HR] = 3.325; 95% confidence interval [CI] = 1.698-6.508). Multivariate analysis identified sarcopenic obesity as an independent risk factor for increased mortality (HR = 2.608; 95% CI = 1.313-5.179). Other risk factors were greater extent of gastrectomy (HR = 1.928; 95% CI = 1.260-2.950), lower prognostic nutritional index (HR = 0.934; 95% CI = 0.901-0.969), higher neutrophil count (HR = 1.101; 95% CI = 1.031-1.176), lymph node metastasis (HR = 6.291; 95% CI = 3.498-11.314), and R1/2 resection (HR = 4.817; 95% CI = 1.518-9.179). CONCLUSION: Body composition analysis automated by machine learning predicted long-term survival in patients with gastric cancer.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Optimizing the Aspect Ratio of Nanopatterned Mesoporous TiO2 Thin-Film Layer to Improve Energy Conversion Efficiency of Perovskite Solar Cells.

The energy conversion efficiency (ECE) (η), current density (Jsc), open-circuit voltage (Voc), and fill factor (ff) of perovskite solar cells were studied by using the transmittance of a nanopatterned mesoporous TiO2 (mp-TiO2) thin-film layer. To improve the ECE of perovskite solar cells, a mp-TiO2 thin-film layer was prepared to be used as an electron transport layer (ETL) via the nanoimprinting method for nanopatterning, which was controlled by the aspect ratio. The nanopatterned mp-TiO2 thin-film layer had a uniform and well-designed structure, and the diameter of nanopatterning was 280 nm. The aspect ratio was controlled at the depths of 75, 97, 127, and 167 nm, and the perovskite solar cell was fabricated with different depths. The ECE of the perovskite solar cells with the nanopatterned mp-TiO2 thin-film layer was 14.50%, 15.30%, 15.83%, or 14.24%, which is higher than that of a non-nanopatterned mp-TiO2 thin-film layer (14.07%). The enhancement of ECE was attributed to the transmittance of the nanopatterned mp-TiO2 thin-film layer that is due to the improvement of the electron generation. As a result, better electron generation affected the electron density, and Jsc increased the Voc, and ff of perovskite solar cells.

Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.

A Modified Formulation of Sutaehwan Ameliorates Menopausal Anxiety, Depression and Heart Hypertrophy in the VCD-Induced Menopausal Mouse Model.

Sutaehwan (STH) has been used in Korean medicine for the treatment of abortus habitualis such as fetal restlessness in the uterus. Previously, we reported that a modified formulation of STH, Sutaehwan-Gami, has phytoestrogen-like properties in an ovariectomized menopausal rat model. However, the therapeutic effects of STH and the precise mechanisms by which STH affects various menopausal symptoms remain poorly understood. The current study was designed to explore the effects of a modified form of STH on menopausal anxiety, depression and heart hypertrophy and its mechanisms in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal mouse models. VCD-induced menopausal model mice were fed a modified form of STH, which contained water extract of 3 herbs (called STH_KP17001) at a dose of 100 or 300 mg/kg/d or as a positive control, estradiol at a dose of 0.2 mg/kg/d with standard mouse pellets for 13 weeks. The results show that STH_KP17001 significantly restored the VCD-induced weight reduction of uterine and ovary through the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in the uterus and ovary. Moreover, STH_KP17001 showed slight proliferative effects and estrogen receptor α phosphorylation in MCF-7 cells. Treatment with STH_KP17001 reversed VCD-induced anxiety and depression through AMP-activated protein kinase (AMPK) activation and brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex, while improving heart hypertrophy through inactivation of inhibitor of kappaB α (IκBα) in the heart. The results indicate that STH_KP17001 improves menopause-induced anxiety, depression and heart hypertrophy, implying its protective role for the management of menopausal symptoms.

Selection of lethal genes for ingestion RNA interference against western flower thrips, Frankliniella occidentalis, via leaf disc-mediated dsRNA delivery.

The western flower thrips, Frankliniella occidentalis, is a major pest that damages a wide variety of crops and vegetables. Following extensive use of insecticides, it has developed high levels of resistance to almost all groups of insecticides due to its high reproduction rate and short generation time. Therefore, an alternative pest control strategy, such as RNA interference (RNAi)-based control, is essential. To establish an ingestion RNAi-based control, a total of 57 genes involved in various biological processes were selected, and their double-stranded RNAs (dsRNA) were delivered to an insecticide-susceptible strain of F. occidentalis via the leaf disc-feeding method using a bioassay chamber optimized by 3D printing. The mortality of dsRNA-ingested thrips was examined every 24 h until 120 h post-treatment. Of the 57 genes screened, dsRNAs of the Toll-like receptor 6, apolipophorin, coatomer protein subunit epsilon and sorting and assembly machinery component were most lethal when ingested by thrips. The dsRNA-fed thrips showed substantially reduced transcription levels of target genes, demonstrating that the observed mortality was likely due to RNAi. When these genes were tested for ingestion RNAi against an insecticide-resistant strain of F. occidentalis, bioassay results were similar. In conclusion, this study provides the first evidence that ingestion RNAi can be lethal to F. occidentalis, a mesophyll sucking pest, and further suggests that transgenic plants expressing hairpin RNA of these essential genes can be employed to control insecticide-resistant thrips.

Inflammation on spinal magnetic resonance imaging is associated with poor bone quality in patients with ankylosing spondylitis.

Objective: To determine the association between inflammatory lesions on spinal magnetic resonance imaging (MRI) and trabecular bone score (TBS) in patients with ankylosing spondylitis (AS). Methods: Ninety-seven patients with AS underwent spine MRI and dual energy X-ray absorptiometry of the lumbar spine to measure TBS and bone mineral density (BMD). Bone marrow edema (BME) on MRI was considered an inflammatory lesion. The presence, depth (>1 cm), and intensity of BME on MRI were scored for the 1st-4th lumbar spine segments. Inflammatory markers and spinal structural damage scores at the time of MRI examination were recorded. The association between inflammatory activity score on MRI and TBS was evaluated. Results: Among the 97 patients, 52 had BME on spinal MRI (L1-L4). The mean TBS values were 1.38 ± 0.11 and 1.43 ± 0.11 for patients with and without BME, respectively (p = .022). Total inflammatory activity scores on spinal MRI correlated negatively with TBS, but not with BMD. Patients with a TBS value representing a high fracture risk had more deep BME (>1 cm) (p = .048) on MRI. After adjustment for age, symptom duration, and lumbar spinal structural damage, the TBS decreased as inflammation severity on MRI increased (p = .026). Discussion: In AS patients, inflammation on spinal MRI was negatively correlated with TBS. The severity of local bone inflammation in the spine was associated with poor bone quality. These findings suggest that the control of active bone inflammation may be effective for preventing osteoporosis in AS patients.

CF3-Substituted Mollugin 2-(4-Morpholinyl)-ethyl ester as a Potential Anti-inflammatory Agent with Improved Aqueous Solubility and Metabolic Stability.

Although mollugin, the main ingredient of the oriental medicinal herb Rubia cordifolia, has considerable anti-inflammatory effects, it has poor aqueous solubility as well as poor metabolic and plasma stability. To overcome these shortfalls, various mollugin derivatives have been synthesized and evaluated for their ability to inhibit U937 monocyte cell adhesion to HT-29 colonic epithelial cells in TNF-α- or IL-6-induced models of colon inflammation. The 2-(4-morpholinyl)-ethyl ester of CF3-substituted mollugin (compound 15c) showed good water solubility, improved metabolic and plasma stability, and greater inhibitory activity than mesalazine in both the TNF-α- and IL-6-induced colonic epithelial cell adhesion assays, suggesting that 15c is a potential anti-inflammatory agent.

Development of novel tetra- and trinucleotide microsatellite markers for giant grouper Epinephelus lanceolatus using 454 pyrosequencing.

Giant grouper (Epinephelus lanceolatus) is a commercially important species, but its wild population has recently been classified as vulnerable. This species has significant potential for use in aquaculture, though a greater understanding of population genetics is necessary for selective breeding programs to minimize kinship for genetically healthy individuals. High-throughput pyrosequencing of genomic DNA was used to identify and characterize novel tetra- and trinucleotide microsatellite markers in giant grouper from Sabah, Malaysia. In total, of 62,763 sequences containing simple sequence repeats (SSRs) were obtained, and 78 SSR loci were selected to possibly contain tetra- and trinucleotide repeats. Of these loci, 16 had tetra- and 8 had trinucleotide repeats, all of which exhibited polymorphisms within easily genotyped regions. A total of 143 alleles were identified with an average of 5.94 alleles per locus, with mean observed and expected heterozygosities of 0.648 and 0.620, respectively. Among of them, 15 microsatellite markers were identified without null alleles and with Hardy-Weinberg equilibrium. These alleles showed a combined non-exclusion probability of 0.01138. The probability of individual identification (PID) value combined with in descending order 12 microsatellite markers was 0.00008, which strongly suggests that the use of the microsatellite markers developed in this study in various combinations would result in a high resolution method for parentage analysis and individual identification. These markers could be used to establish a broodstock management program for giant grouper and to provide a foundation for genetic studies such as population structure, parentage analysis, and kinship selection.

Rebamipide attenuates 5-Fluorouracil-induced small intestinal mucositis in a mouse model.

5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-ß1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-α levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-ß1, apoptosis, macrophage accumulation, serum TNF-α levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis.

Effect of universal adhesive pretreatments on the bond strength durability of conventional and adhesive resin cements to zirconia ceramic.

PURPOSE: This study aimed to evaluate the effect of pretreatment of three different universal adhesives (Single Bond Universal [SBU], All-Bond Universal [ABU], and Prime&Bond universal [PBU]) on the bonding durability of an adhesive (Panavia F 2.0, PF) and a conventional (Duo-Link, DL) resin cements to air-abraded zirconia. MATERIALS AND METHODS: Rectangular-shaped zirconia specimens were prepared. The chemical composition and surface energy parameters of the materials were studied by Fourier transform infrared spectroscopy and contact angle measurement, respectively. To evaluate resin bonding to the zirconia, all the bonding specimens were immersed in water for 24 h and the specimens to be aged were additionally thermocycled 10000 times before the shear bond strength (SBS) test. RESULTS: The materials showed different surface energy parameters, including the degree of hydrophilicity/hydrophobicity. While the DL/CON (no pretreatment) showed the lowest SBS and a significant decrease in the value after thermocycling (P < .001), the PF/CON obtained a higher SBS value than the DL/CON (P < .001) and no decrease even after thermocycling (P = .839). When the universal adhesives were used with DL, their SBS values were higher than the CON (P < .05), but the trend was adhesive-specific. In conjunction with PF, the PF/SBU produced the highest SBS followed by the PF/ABU (P = .002), showing no significant decrease after thermocycling (P > .05). The initial SBS of the PF/PBU was similar to the PF/CON (P = .999), but the value decreased after thermocycling (P < .001). CONCLUSION: The universal adhesive pretreatment did not necessarily show a synergistic effect on the bonding performance of an adhesive resin cement, whereas the pretreatment was beneficial to bond strength and durability of a conventional resin cement.

Current Status of the Zebrafish Euthanasia and Humane Endpoint in the Republic of Korea and Guideline Suggestion from Nationwide Expert Elicitation: A Model for Other Countries.

Since its introduction as a model organism in the 1980s, the use of zebrafish (Danio rerio) in research has expanded worldwide. Despite its now widespread use in research, guidelines to safeguard the ethical treatment of zebrafish, particularly with regard to euthanasia and humane endpoint practices, remain inadequate. One well-recognized example is the use of excess tricaine methanesulfonate (MS-222) as a means to euthanize zebrafish, regardless of life stage. In this study, through nationwide expert elicitation, we provide a detailed account of zebrafish research practices within the Republic of Korea and the challenges of implementing appropriate methods for euthanasia as a humane endpoint, with many opting for hypothermic shock. We report a local expert consensus for establishing national guidelines to improve zebrafish welfare and good research practice. Suggestions and recommendations for national guidelines were offered. Taken together, our findings raise awareness broadly among zebrafish research practitioners in the field, offer an accurate account of the welfare and treatment of zebrafish in research within the Republic of Korea, and advocate for the development and implementation of national guidelines. As such, our study is useful as a model to adopt the expert elicitation approach to investigate, quantify, and address welfare concerns in zebrafish research, and to establish best practice guidelines.

Molecular analysis of Malassezia pachydermatis isolated from canine skin and ear in Korea.

We investigated Malassezia species and genotypes colonizing dogs, comparing those recovered from the ear canal with those from other anatomical body sites, as well as from diseased and healthy skin. The Malassezia isolates were obtained from four types of skin samples, i.e., diseased ear, diseased skin, healthy ear, and healthy skin. Sequences of the 26S ribosomal DNA region, the intergenic spacer 1 (IGS-1) and the internal transcribed spacer 1 (ITS-1) DNA region were analyzed. These confirmed the presence of Malassezia pachydermatis, which could be separated into three main sequence genotype groups (A, B, C). Genotype A was the most common, only two genotype B isolates were recovered from diseased skin lesion and genotype C was more likely to be isolated from ear samples than from other healthy or diseased-skin sites. The present findings provide the basis for further studies of genotypic diversity in M. pachydermatis, as well as their pathogenic potential.

Combined Effects of Focused Ultrasound and Photodynamic Treatment for Malignant Brain Tumors Using C6 Glioma Rat Model.

PURPOSE: Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect. This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently being used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two. MATERIALS AND METHODS: Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm² using a 0.5-MHz single-element transducer. The 633-nm laser was illuminated at 100 J/cm². Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3. RESULTS: A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group (p<0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG (p<0.001) and Caspase-3 (p<0.001), were observed in the SPDT group compared to other groups in IHC. CONCLUSION: Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM.

Identification and Biological Evaluation of a Potent and Selective JAK1 Inhibitor for the Treatment of Pulmonary Fibrosis.

Janus kinase 1 (JAK1) plays a pivotal role in regulating inflammation and fibrosis via the JAK/STAT signaling pathway, making it a promising target for associated diseases. In this study, we explored the modification of an N-methyl 1H-pyrrolo[2,3-b]pyridine-5-carboxylate core, leading to the identification of 4-(((2S,4S)-1-(4-trifluoromethyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (36b) as a highly potent and selective JAK1 inhibitor. Compound 36b exhibited an impressive IC50 value of 0.044 nM for JAK1 and demonstrated remarkable selectivity of 382-fold, 210-fold, and 1325-fold specificity over JAK2, JAK3, and TYK2, respectively. The kinase panel assays further confirmed its specificity, and cell-based experiments established its efficacy in inhibiting JAK1-STAT phosphorylation in human L-132 or SK-MES-1 cells. Pharmacokinetic studies revealed that compound 36b boasts an oral bioavailability exceeding 36%. In a bleomycin-induced fibrosis mouse model, compound 36b significantly reduced STAT3 phosphorylation, resulting in improvement in body weight and reduced collagen deposition, all achieved without significant side effects.

Highly ordered large-area colloid templates for nanostructured TiO2 thin film gas sensors.

We report a novel process that uses highly ordered colloidal templating to fabricate nanostructured TiO2 thin film gas sensors. An O2 plasma treatment is used to decrease the contact angle of a water droplet on a SiO2/Si substrate from 46 degrees to 3 degrees. The formation of this hydrophilic surface enhances the adhesion of polystyrene microspheres to the substrate during the spin coating of the colloidal solution, leading to a large-area colloid template of closely packed monolayer microspheres on the substrates. Embossed TiO2 thin film gas sensors fabricated through highly ordered colloidal templating using O2 plasma exhibit substantially enhanced gas sensing performance as compared to those without surface treatments prior to colloidal templating.

Pudendal Nerve Terminal Motor Latency Compared by Anorectal Manometry Diagnosing Fecal Incontinence: A Retrospective Study.

OBJECTIVE: The aim of the study was to compare the clinical value of pudendal nerve terminal motor latency in fecal incontinence patients with that of another diagnostic test-anorectal manometry. DESIGN: This study used a cross-sectional design. Medical records of fecal incontinence patients who underwent pudendal nerve terminal motor latency and anorectal manometry testing were reviewed. Greater than 2.4 ms of pudendal nerve terminal motor latency was determined to be abnormal. Anorectal manometry was performed using a station pull-through technique. Mean resting anal pressure, maximal resting anal pressure, mean squeezing anal pressure, and maximal squeezing anal pressure were investigated. For normal and abnormal pudendal nerve terminal motor latency groups, comparative analyses were performed on anorectal manometry results. RESULTS: A total of 31 patients were included. Thirteen patients showed normal pudendal nerve terminal motor latency. For anorectal manometry results, there was no significant difference between normal and abnormal pudendal nerve terminal motor latency groups. Fourteen patients had diabetes mellitus. Subgroup analysis of the 14 diabetic patients showed no significant difference between normal and abnormal pudendal nerve terminal motor latency groups. For 17 nondiabetic patients, there was a significant difference between the groups with positive correlations with mean/maximal resting anal pressures. CONCLUSIONS: Pudendal nerve terminal motor latency significantly correlates with anorectal manometry in fecal incontinence only in nondiabetic patients.

NKT ligand-loaded, antigen-expressing B cells function as long-lasting antigen presenting cells in vivo.

We had previously shown that activated NKT cells licensed B cells to be immunogenic antigen-presenting cells and helped to elicit a wide spectrum of cancer targeted immune responses. In the current study, we sought to verify the safety of αGalCer-loaded, and adenovirus-transduced B cell-based vaccines, together with mechanism of action. Intravenously injected αGalCer-loaded, antigen-expressing B cells rapidly localized in the spleen and directly primed CD8(+) T cells in an antigen-specific manner. The transferred antigen was sustained for at least 30 days. While some injected B cells produced nonspecific IgG, the antigen-specific IgG response was completely dependent on endogenous B cells. The liver was one of the main tissues where injected B cells were retained; however, we could not find the signs of liver toxicity. Our results demonstrate that αGalCer-loaded, antigen-expressing B cells behave as "antigen-presenting" cells that stimulate endogenous antigen-specific T cells and B cells in vivo without significant toxicity.

Crystalline Ge quantum dots embedded in SiO2 matrix synthesized by plasma immersion ion implantation.

A new plasma process, i.e. a combination of plasma immersion ion implantation and deposition (PIII&D) and high power impulse magnetron sputtering (HiPIMS), was developed to implant non-gaseous ions into material surfaces. The new process has the great advantage that thin film deposition and non-gaseous ion implantation can be achieved in a single plasma chamber. In this study, Ge ions were successfully implanted into SiO(2) thin film, which resulted in uniformly and homogeneously distributed crystalline Ge quantum dots (Ge-QDs) embedded in a SiO(2) matrix even without a further annealing process. Broader areas of application of PIII&D technology are envisaged with this newly developed process.