Analysis of an antioxidative defence system of hydrogen peroxide-treated pancreatic islet-derived 1.1B4 cells and siRNA targeting NR4A3-treated cells by microarray.

Pancreatic islet ß-cells weaken under oxidative stress. In this study, human pancreatic islet-derived 1.1B4 cells were exposed to H2O2 and analysed using a human microarray, which revealed that heme oxygenase 1 (HMOX1), glutamate-cysteine ligase, early growth response 1, nuclear receptor subfamily 4 group A member 3 (NR4A3) and jun B proto-oncogene were upregulated, whereas superoxide dismutase 1 and catalase were not. Expression of NR4A3 rapidly increased after H2O2 addition, and the 1.1B4 cells treated with siRNA targeting NR4A3 became sensitive to H2O2; further, HMOX1 expression was strongly inhibited, suggesting that NR4A3 is an oxidative stress-responsive transcription factor that functions through HMOX1 expression in pancreatic islet ß-cells. Expression of cyclin E1 and cyclin-dependent kinase 1 was also inhibited by siRNAs targeting NR4A3.

Morphological redescription of Simulium takahasii (Rubtsov), the first species of the subgenus Wilhelmia Enderlein (Diptera: Simuliidae) recognized in East Asia.

Simulium takahasii (Rubtsov), which was originally described from Japan, and recorded from Korea and China, is the first among the 19 species of the subgenus Wilhelmia Enderlein recorded from East Asia. It is striking in mating, blood-feeding and ovipositing in captivity and in experimentally transmitting Dirofilaria immitis (Leidy) and Brugia pahangi (Buckley & Edeson), and it is a severe biter of cattle and horses, rarely of humans. Nevertheless, updated information about its morphological characteristics was lacking, making comparisons with related species described from China difficult, since species of the subgenus Wilhelmia are almost indistinguishable from one another, in particular, in their female terminalia, male genitalia and most of larval features. In this study, as many morphological characteristics as possible of S. takahasii based on specimens from Japan are redescribed. New information about many features of this species including the length of the female sensory vesicle against the third palpal segment, number of male upper-eye (large) facets, arrangement of the eight pupal gill filaments, presence or absence of tiny dark setae on the dorsum of the larval abdomen and the number of rows and hooklets of the larval posterior circlet will be useful in evaluating the species status of several Wilhelmia species in China including the species regarded as S. takahasii.

Morphological and genetic analyses of Simulium (Gomphostilbia) okinawense Takaoka and S. (G.) tokarense Takaoka (Diptera: Simuliidae) from the Nansei Islands, Japan: redescription and transfer from the S. ceylonicum species-group to the S. asakoae species-group.

Simulium (Gomphostilbia) okinawense Takaoka and S. (G.) tokarense Takaoka, both from the Nansei Islands, Japan, were morphologically reexamined and genetically analysed by using the COI gene sequences. The female, male, pupa and mature larva of the two species are redescribed. Morphological reexamination shows that both species are more similar to species in the S. asakoae species-group than to those in the S. ceylonicum species-group, by having a medium-long female sensory vesicle, yellow tuft hairs (S. (G.) okinawense) or yellow tuft hairs mixed with a few to several dark hairs (S. (G.) tokarense) at the base of the radial vein in the female and male, and medium-long larval postgenal cleft. However, the body of the male ventral plate (viewed ventrally) is parallel-sided (S. (G.) okinawense) or parallelsided or slightly narrowed (S. (G.) tokarense) and not emarginated basally, differing from those of most species in the S. asakoae species-group. Our genetic analysis shows that S. (G.) tokarense is in the S. asakoae species-group, and S. (G.) okinawense formed a separate sister clade with other members of the S. asakoae species-group with high bootstrap support. From the results of morphological and genetic analysis combined, S. (G.) okinawense and S. (G.) tokarense are transferred from the S. ceylonicum species-group to the S. asakoae species-group.

Morphological revision of Simulium (Gomphostilbia) ogatai (Rubtsov) in the S. ceylonicum species-group (Diptera: Simuliidae) from Japan.

Simulium (Gomphostilbia) ogatai (Rubtsov) from Japan, the only Palaearctic species in the S. ceylonicum species-group, is morphologically revised. Its female is described for the first time and its male and pupa are redescribed based on specimens from Gifu, Honshu. It is characterized in the female and male by the base of the radius with a tuft of yellow hairs, in the female by the head slightly wider than the thorax, 5.89 times as wide as the greatest width of the frons, and short sensory vesicle 0.21-0.24 times as long as the third palpal segment; in the male by the number of upper-eye (large) facets in 15 vertical columns and 16 horizontal rows, and hind basitarsus spindle-shaped, enlarged, 3.79 times as long as wide, and 0.83 and 1.00 times as wide as the greatest width of the hind tibia and femur, respectively; and in the pupa by the terminal hooks simple and cone-like, and the cocoon with an anterodorsal projection. Taxonomic notes for this species are given relevant to several related species in the Oriental Region, and its assignment to the S. ceylonicum species-group is confirmed.

Delamination-fretting wear failure evaluation at HAp-Ti-6Al-4V interface of uncemented artificial hip implant.

Present research aims to develop a finite element computational model to examine delamination-fretting wear behaviour that can suitably mimic actual loading conditions at HAp-Ti-6Al-4V interface of uncemented hip implant femoral stem component. A simple finite element contact configuration model based on fretting fatigue experimental arrangement subjected to different mechanical and tribological properties consist of contact pad (bone), HAp coating and Ti-6Al-4V substrate are developed using adaptive wear modelling approach adopting modified Archard wear equation to be examined under static simulation. The developed finite element model is validated and verified with reported literatures. The findings revealed that significant delamination-fretting wear is recorded at contact edge (leading edge) as a result of substantial contact pressure and contact slip driven by stress singularity effect. The delamination-fretting wear behaviour is promoted under higher delamination length, lower normal loading with higher fatigue loading, increased porous (cancellous) and cortical bone elastic modulus with higher cycle number due to significant relative slip amplitude as the result of reduced interface rigidity. Tensile-compressive condition (R=-1) experiences most significant delamination-fretting wear behaviour (8 times higher) compared to stress ratio R=0.1 and R=10.

A male black fly of Simulium (Simulium) iwatense (Shiraki) (Diptera: Simuliidae) with genitalia-like appendages on abdominal segment 8.

A rare non-sex mosaic abnormality represented by genitalia-like appendages on the ventral surface of abdominal segment 8 of a male black fly collected in Hokkaido, Japan, is reported. The appendages consist of a pair of style-like projections each arising from a coxite-like base, inverted-Y shaped ventral plate-like structure, and isolated round structure. This male was morphologically and molecularly identified as an abnormal form of S. (S.) iwatense (Shiraki), the only species in the Simulium (Simulium) ornatum species-group in Japan, although certain morphological characteristics of this male including the reduced number of uppereye (large) facets and elongate cerci are different from those of S. (S.) iwatense.

Gut microbiome alterations in type 1 autoimmune pancreatitis after induction of remission by prednisolone.

Although increasing evidence demonstrates the association between intestinal dysbiosis and pancreatic diseases such as chronic pancreatitis and pancreatic cancer, it remains largely unknown whether intestinal dysbiosis is involved in the immunopathogenesis of autoimmune pancreatitis (AIP). Recently, we found that intestinal dysbiosis mediates experimental AIP via the activation of plasmacytoid dendritic cells (pDCs), which can produce interferon (IFN)-α and interleukin (IL)-33. However, candidate intestinal bacteria, which promote the development of AIP, have not been identified. Fecal samples were obtained from type 1 AIP patients before and after prednisolone (PSL) treatment and subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. Induction of remission by PSL was associated with the complete disappearance of Klebsiella species from feces in two of the three analyzed patients with type 1 AIP. To assess the pathogenicity of Klebsiella species, mild experimental AIP was induced in MRL/MpJ mice by repeated injections of 10 µg of polyinosinic-polycytidylic acid [poly(I:C)], in combination with oral administration of heat-killed Klebsiella pneumoniae. The AIP pathology score was significantly higher in MRL/MpJ mice that received both oral administration of heat-killed K. pneumoniae and intraperitoneal injections of poly(I:C) than in those administered either agent alone. Pancreatic accumulation of pDCs capable of producing large amounts of IFN-α and IL-33 was also significantly higher in mice that received both treatments. These data suggest that intestinal colonization by K. pneumoniae may play an intensifying role in the development of type 1 AIP.

Kimura's disease: effects of age on clinical presentation.

BACKGROUND: Kimura's disease (KD) is known to be dominant among young Asian men, but it can also occur in middle- and advanced-aged people. The clinical characteristics of KD, especially by age, are not well known. AIM: This study was performed to investigate the effects of age on the clinical characteristics of KD. DESIGN: We conducted a case series study. METHODS: All case studies of patients diagnosed with KD were collected via a PubMed search of studies published until August 2018. The data were analyzed by age group. RESULTS: In total, 215 studies were reviewed (238 patients; mean age of 36 years). The male:female ratio was 4:1 overall, 17:1 in patients aged <20 years, 4:1 in patients aged 20-39 years and 2:1 in patients aged ≥40 years (P = 0.01). The percentage of patients with pruritus was 15.4% overall, 3.8% in patients aged <20 years, 15.5% in patients aged 20-39 years and 21.7% in patients aged ≥40 years (P = 0.02). The time to diagnosis was 5.3 years overall, 3.2 years in patients aged <20 years, 4.7 years in patients aged 20-39 years and 7.1 years in patients aged ≥40 years (P < 0.01). CONCLUSIONS: The proportion of female patients affected the incidence of pruritus, and the time to diagnosis increased as the patients' age increased. There were no significant age-related differences in region/race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, immunoglobulin E level, initial treatment, recurrence or outcomes. This may be useful information for the diagnosis of KD.

Improving the Quality of Synthetic FLAIR Images with Deep Learning Using a Conditional Generative Adversarial Network for Pixel-by-Pixel Image Translation.

BACKGROUND AND PURPOSE: Synthetic FLAIR images are of lower quality than conventional FLAIR images. Here, we aimed to improve the synthetic FLAIR image quality using deep learning with pixel-by-pixel translation through conditional generative adversarial network training. MATERIALS AND METHODS: Forty patients with MS were prospectively included and scanned (3T) to acquire synthetic MR imaging and conventional FLAIR images. Synthetic FLAIR images were created with the SyMRI software. Acquired data were divided into 30 training and 10 test datasets. A conditional generative adversarial network was trained to generate improved FLAIR images from raw synthetic MR imaging data using conventional FLAIR images as targets. The peak signal-to-noise ratio, normalized root mean square error, and the Dice index of MS lesion maps were calculated for synthetic and deep learning FLAIR images against conventional FLAIR images, respectively. Lesion conspicuity and the existence of artifacts were visually assessed. RESULTS: The peak signal-to-noise ratio and normalized root mean square error were significantly higher and lower, respectively, in generated-versus-synthetic FLAIR images in aggregate intracranial tissues and all tissue segments (all P < .001). The Dice index of lesion maps and visual lesion conspicuity were comparable between generated and synthetic FLAIR images (P = 1 and .59, respectively). Generated FLAIR images showed fewer granular artifacts (P = .003) and swelling artifacts (in all cases) than synthetic FLAIR images. CONCLUSIONS: Using deep learning, we improved the synthetic FLAIR image quality by generating FLAIR images that have contrast closer to that of conventional FLAIR images and fewer granular and swelling artifacts, while preserving the lesion contrast.

Effective treatment by glycolic acid peeling for cutaneous manifestation of familial generalized acanthosis nigricans caused by FGFR3 mutation.

BACKGROUND: Acanthosis nigricans (AN) can occur as a cutaneous manifestation of genetic diseases, one of which is associated with activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3). OBJECTIVE: We explored familial AN patients with FGFR3 mutations and examined the effectiveness of glycolic acid (GA) peeling in improving their skin manifestations. METHODS: Sanger sequencing was performed for the genomic DNA extracted from leucocytes of the family members involving familial AN. GA peeling was carried out for the two patients of familial AN once every 2 weeks. RESULTS: Heterozygous c.1949A>C (p.K650T) mutation in FGFR3 was identified for the affected family members examined, whereas the wild-type sequence was found for two unaffected individuals. Hyperpigmentation and coarseness of the skin were improved by GA peeling at regular intervals with few adverse effects. CONCLUSION: We diagnosed our cases as familial generalized AN caused by heterozygous c.1949A>C (p.K650T) mutation of FGFR3. We propose that GA peeling is a useful and safe therapeutic option to treat familial AN.

Surface Modifications and Their Effects on Titanium Dental Implants.

This review covers several basic methodologies of surface treatment and their effects on titanium (Ti) implants. The importance of each treatment and its effects will be discussed in detail in order to compare their effectiveness in promoting osseointegration. Published literature for the last 18 years was selected with the use of keywords like titanium dental implant, surface roughness, coating, and osseointegration. Significant surface roughness played an important role in providing effective surface for bone implant contact, cell proliferation, and removal torque, despite having good mechanical properties. Overall, published studies indicated that an acid etched surface-modified and a coating application on commercial pure titanium implant was most preferable in producing the good surface roughness. Thus, a combination of a good surface roughness and mechanical properties of titanium could lead to successful dental implants.

Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma.

PURPOSE: Ipilimumab (IPI), a monoclonal antibody against immune-checkpoint receptor cytotoxic T lymphocyte antigen-4, is designed to enhance antitumor T cell function. IPI 10 mg/kg plus dacarbazine (DTIC) significantly improved overall survival in a phase 3 study involving predominantly Caucasian patients, with an adverse event (AE) profile similar to that of IPI monotherapy. We conducted a single-arm, phase 2 study to evaluate the safety and efficacy of IPI plus DTIC in Japanese patients. METHODS: Previously untreated patients with unresectable stage III or IV melanoma received IPI 10 mg/kg plus DTIC 850 mg/m(2) every 3 weeks for four doses (q3w × 4), followed by DTIC q3w × 4 and then IPI every 12 weeks until disease progression or intolerable toxicity. RESULTS: All 15 treated patients reported drug-related AEs, the most common of which were increases in alanine aminotransferase (n = 12, 80 %) and aspartate aminotransferase (n = 11, 73 %). Treatment-related serious AEs were reported in 11 (73 %) patients. Nine patients (60 %) discontinued treatment due to drug-related toxicities. Immune-related AEs (irAEs) were reported in 14 patients (93 %). The most frequent irAEs were liver (n = 12, 80 %) and skin (n = 10, 67 %) toxicities. Five deaths were reported; all were caused by progressive disease. Efficacy evaluation showed one complete response, one partial response and four patients with stable disease. Best overall response rate was 13 % (2/15), and the disease control rate was 40 % (6/15). The study was terminated early due to frequent, high-grade liver toxicities. CONCLUSIONS: IPI 10 mg/kg plus DTIC 850 mg/m(2) was not considered tolerable in the Japanese patient population. ClinicalTrials.gov identifier: NCT01681212.

A Bayesian approach to person perception.

Here we propose a Bayesian approach to person perception, outlining the theoretical position and a methodological framework for testing the predictions experimentally. We use the term person perception to refer not only to the perception of others' personal attributes such as age and sex but also to the perception of social signals such as direction of gaze and emotional expression. The Bayesian approach provides a formal description of the way in which our perception combines current sensory evidence with prior expectations about the structure of the environment. Such expectations can lead to unconscious biases in our perception that are particularly evident when sensory evidence is uncertain. We illustrate the ideas with reference to our recent studies on gaze perception which show that people have a bias to perceive the gaze of others as directed towards themselves. We also describe a potential application to the study of the perception of a person's sex, in which a bias towards perceiving males is typically observed.

Search for bosonic superweakly interacting massive dark matter particles with the XMASS-I detector.

Bosonic superweakly interacting massive particles (super-WIMPs) are a candidate for warm dark matter. With the absorption of such a boson by a xenon atom, these dark matter candidates would deposit an energy equivalent to their rest mass in the detector. This is the first direct detection experiment exploring the vector super-WIMPs in the mass range between 40 and 120 keV. With the use of 165.9 day of data, no significant excess above background was observed in the fiducial mass of 41 kg. The present limit for the vector super-WIMPs excludes the possibility that such particles constitute all of dark matter. The absence of a signal also provides the most stringent direct constraint on the coupling constant of pseudoscalar super-WIMPs to electrons. The unprecedented sensitivity was achieved exploiting the low background at a level 10(-4) kg-1 keVee-1 day-1 in the detector.

Cytogenetic, crossing and molecular evidence of two cytological forms of Anopheles argyropus and three cytological forms of Anopheles pursati (Diptera: Culicidae) in Thailand.

Nine and 11 isolines of Anopheles argyropus and Anopheles pursati, respectively, were established from individual females collected from cow-baited traps, and the characteristics of metaphase chromosomes were investigated in their F1-progenies. As determined by the different amounts of extra heterochromatin on sex chromosomes, 2 types of X (X1, X2) and Y (Y1,Y2), and 2 types of X (X1, X2) and 3 types of Y (Y1, Y2, Y3) chromosomes were obtained from An. argyropus and An. pursati, respectively. These types of sex chromosomes comprised 2 [Forms A (X1, Y1) and B (X1, X2, Y2)] and 3 [Forms A (X1, X2, Y1), B (X1, X2, Y2) and C (X2, Y3)] karyotypic forms of An. argyropus and An. pursati, respectively. All karyotypic forms acquired from An. pursati are new one that were discovered in this study, of which Forms A, B and C were found generally in Chiang Mai Province, while only 1 isoline of Form B was obtained in Ratchaburi Province. Form A was recovered from An. argyropus only in Ubon Ratchathani Province, whereas Form B from that species was found commonly in both Ubon Rathchathani and Nakhon Si Thammarat Provinces. Crossing experiments among the 2 and 3 isolines representing 2 and 3 karyotypic forms of An. argyropus and An. pursati, respectively, indicated genetic compatibility in yielding viable progenies and synaptic salivary gland polytene chromosomes through F2-generations. The conspecific natures of these karyotypic forms in both species were further supported by very low intraspecific sequence variations (average genetic distance: An. argyropus = 0.003-0.007, An. pursati = 0-0.005) of ribosomal DNA (ITS2) and mitochondrial DNA (COI and COII).