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.

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.

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.

Effects of curcumin supplementation on exercise-induced oxidative stress in humans.

The purpose of this study was to investigate the effects of curcumin supplementation on exercise-induced oxidative stress in humans. 10 male participants, ages 26.8±2.0 years (mean±SE), completed 3 trials in a random order: (1) placebo (control), (2) single (only before exercise) and (3) double (before and immediately after exercise) curcumin supplementation trials. Each participant received oral administration of 90 mg of curcumin or the placebo 2h before exercise and immediately after exercise. Each participant walked or ran at 65% of V˙2max on a treadmill for 60min. Blood samples were collected pre-exercise, immediately after exercise and 2h after exercise. The concentrations of serum derivatives of reactive oxygen metabolites measured immediately after exercise were significantly higher than pre-exercise values in the placebo trial (308.8±12.9 U. CARR, P<0.05), but not in the single (259.9±17.1 U. CARR) or double (273.6±19.7 U. CARR) curcumin supplementation trials. Serum biological antioxidant potential concentrations measured immediately after exercise were significantly elevated in the single and double curcumin supplementation trials compared with pre-exercise values (P<0.05). These findings indicate that curcumin supplementation can attenuate exercise-induced oxidative stress by increasing blood antioxidant capacity.

How do employment types and job stressors relate to occupational injury? A cross-sectional investigation of employees in Japan.

OBJECTIVE: This study investigated whether 1) the risk of occupational injury differs among permanent employees and specific types of temporary workers, 2) the risk of occupational injury differs across different employment types depending on the degree of job stressors. STUDY DESIGN: A cross-sectional study design based on self-report survey data. METHODS: A total of 36,688 full-time workers (28,868 men and 7820 women; average age = 35.4) were surveyed by means of a self-administered questionnaire. Employment types consisted of permanent employment and two forms of temporary employment: direct-hire and temporary work agent (TWA). Job characteristics including job demands, job control, and social support at work were measured. Occupational injury was measured by asking whether the participant had an injury on the job in the past 12 months that required a medical treatment. To investigate the relationships between employment types, job stressors, and occupational injury, hierarchical moderated logistic regression tests were conducted. RESULTS: High job demands (OR = 1.44) and low job control (OR = 1.21) were significantly associated with an increased risk of occupational injury, while controlling for demographic, life style, health, and occupational factors. In addition, direct-hires (OR = 1.85) and temporary agent workers (OR = 3.26) had a higher risk of occupational injury compared with permanent employees. However, the relationship between employment types and the risk of occupational injury depended on the levels of job demands and job control. Specifically, the magnitude of the relationship between job demands and the risk of occupational injury was substantially greater for temporary work agents than for permanent employees when they reported low levels of job control. Such an interaction effect between job demands and job control on the risk of occupational injury was not observed between permanent employees and direct-hire temporary workers. CONCLUSION: The current study indicated that temporary workers might be more vulnerable to occupational injury than permanent employees. High levels of job demands and low levels of job control might also add to temporary workers' risk of occupational injury, particularly for TWAs.

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 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.

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.

Blackfly vectors of zoonotic onchocerciasis in Japan.

Studies of blackfly vectors of Onchocerca dewittei japonica Uni, Bain & Takaoka (Spirurida: Onchocercidae), a parasite of wild boar implicated in the aetiology of zoonotic onchocerciasis in Japan, and six other zoonotic Onchocerca species of this country are reviewed. Molecular identification of infective larvae found in wild-caught female blackflies showed that Simulium bidentatum (Shiraki) (Diptera: Simuliidae) is a natural vector of O. dewittei japonica, and also Onchocerca sp. sensu Fukuda et al., another parasite of wild boar. Inoculation experiments demonstrated that Simulium arakawae Matsumura and four other Simulium species are putative vectors. Similarly, S. arakawae, S. bidentatum and Simulium oitanum (Shiraki) are putative vectors of Onchocerca eberhardi Uni & Bain and Onchocerca skrjabini Rukhlyadev, parasites of sika deer. Morphometric studies of infective larvae indicated that Onchocerca lienalis Stiles, a bovine species, is transmitted by S. arakawae, Simulium daisense (Takahasi) and Simulium kyushuense Takaoka, and that Onchocerca sp. sensu Takaoka & Bain, another bovine species, is transmitted by S. arakawae, S. bidentatum, S. daisense and S. oitanum. Prosimulium sp. (Diptera: Simuliidae) and Simulium japonicum Matsumura are suspected vectors of Onchocerca suzukii Yagi, Bain & Shoho and O. skrjabini [Twinnia japonensis Rubtsov (Diptera: Simuliidae) may also transmit the latter], parasites of Japanese serow, following detection of the parasites' DNA genes in wild-caught blackflies.

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.

Zoonotic onchocerciasis in Hiroshima, Japan, and molecular analysis of a paraffin section of the agent for a reliable identification.

Japan is a country of high specific diversity of Onchocerca with eight species, the adults of two not yet known. Onchocerca dewittei japonica, a common filarial parasite of wild boar, had been proved to be the agent of five zoonotic onchocerciasis in Kyushu island with morphological and molecular studies. The sixth case, at Hiroshima in the main island, was identified to the same Onchocerca species, based on adult characters observed on histological sections. To consolidate the identification, mitochondrial cytochrome c oxidase subunit 1 (CO1) gene analysis was attempted with the formalin-fixed, paraffin-embedded parasite specimen. The sequence (196 bp) of a CO1 gene fragment of the parasite successfully PCR-amplified agreed well with those of O. dewittei japonica registered in GenBank, confirming the morphological identification. Moreover a comparison with the CO1 gene sequences of six other Onchocerca species in GenBank excluded the possibility that Onchocerca sp. from wild boar and Onchocerca sp. type A from cattle in Japan, were the causative agents in this case. Mitochondrial DNA analysis proved to be a valuable tool to support the morphological method for the discrimination of zoonotic Onchocerca species in a histological specimen.

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.

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.

Genetic evidence for the presence of two species of Onchocerca from the wild boar in Japan.

In order to clarify the genetic differences between Onchocerca dewittei japonica, the causative agent of zoonotic onchocerciasis in Japan and a related undescribed Onchocerca sp., both parasitizing wild boar (Sus scrofa) of which the infective larval stages are indistinguishable from each other, we compared the sequences of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene region from four infective larvae (recovered from experimentally infected black flies), one microfilaria, and one adult of O. dewittei japonica, and from one infective larva (recovered from an experimentally infected black fly), one microfilaria, and a pool of several microfilariae of O. sp. The length of the CO1 gene region was 649 bp for all samples but there was a difference of 8.8 to 9.4% in the sequences between the two species although there were intraspecific variations of 0 to 0.5%. The CO1 sequences of O. sp. did not correspond to any of those deposited in the databases. Our study provides evidence that O. dewittei japonica and O. sp. are genetically different from each other.

Molecular identification of infective larvae of three species of Onchocerca found in wild-caught females of Simulium bidentatum in Japan.

Wild female black flies attracted to a man or an idling automobile were collected at Oita, Japan where five cases of zoonotic onchocerciasis had occurred. Among the five Simulium species captured, 2% of Simulium bidentatum, the predominant species, were infected with filarial larvae. There were at least two types of infective larvae, types A and B, based on morphometric observation. Moreover, molecular analysis of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene revealed that types A and B were represented by a single unknown species of Onchocerca and two species, i.e., Onchocerca dewittei japonica from wild boar, the causative agent of zoonotic onchocerciasis in Japan, and an undescribed Onchocerca sp. from wild boar, respectively. Phylogenetic analysis based on the sequences of the mitochondrial 12S ribosomal RNA (12S rRNA) gene also showed that type A is likely to be an unknown species of Onchocerca. Natural infection of black flies with infective larvae of O. dewittei japonica and O. sp. was demonstrated for the first time. The present study strongly suggests that S. bidentatum plays a role as a vector in the transmission of zoonotic onchocerciasis due to O. dewittei japonica in Japan.

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.

Seasonal and diurnal biting activities and zoonotic filarial infections of two Simulium species (Diptera: Simuliidae) in northern Thailand.

Seasonal and daily biting activity patterns, and natural filarial infections of adult black flies attracted to human bait were investigated at Ban Pang Faen, a rural area in Chiang Mai Province in northern Thailand. Collections were carried out twice a month from 0600 to 18-00 hours from January 2005 to February 2006. Among ten Simulium species collected, S. nodosum and S. asakoae were predominant occupying 57.3% and 37.2% of the total 16,553 females, respectively. These two predominant species showed different patterns in seasonal abundance: majority of S. nodosum (86.7%) were collected in hot season (from mid February to mid May), while most of S. asakoae (74.5%) were collected in rainy season (from mid May to mid October). For the daily biting activity, S. nodosum had two patterns: the main one was unimodal with a peak from 17-00 to 18-00, and the other was bimodal and had the major peak from 1600 to 18-00 and the minor one from 07-00 to 09-00. The pattern of S. asakoae was mostly unimodal with a peak from 06-00 to 10-00. The filarial larvae found in S. nodosum and S. asakoae were morphologically different from each other. The short and thick infective larvae found in S. asakoae differed from all known filarial larvae; it is suggested that they might be a bird parasite, Splendidofilariinae or Lemdaninae. The infection of the mammophilic S. nodosum with large Onchocerca type infective larvae was confirmed in this area. Natural filarial infections were found in each month (except December) in either S. nodosum or S. asakoae or in both. Monthly infection rates with all stages of larvae were 0.6-5.0% for S. nodosum, and 1.0-4.0% for S. asakoae. It is suggested that people in this village are exposed to the risk of infection with zoonotic filariae throughout the year.