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Effisayil 1 was a multicentre, randomized, double‐blind, placebo‐controlled study of the anti‐interleukin (IL)‐36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre‐specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline. [ABSTRACT FROM AUTHOR]

Background No easy-to-use fall risk assessment tools have been devised to assess occupational fall risk in older workers. Aims To develop an Occupational Fall Risk Assessment Tool (OFRAT) and report its predictive validity and reliability in older workers. Methods The baseline fall risk assessment was completed by 1113 participants aged ≥60 years who worked ≥4 days/month in Saitama, Japan. Participants were followed up for falls during occupational activities for 1 year, and 30 participants were assessed twice for test–retest reliability. The following assessment measures were summed to form the OFRAT risk score: older age, male sex, history of falls, physical work participation, diabetes, use of medications increasing fall risk, reduced vision, poor hearing, executive dysfunction and slow stepping. The scores were then classified into four grades (0–2 points: very low, 3 points: low, 4 points: moderate and ≥5 points: high). Results During follow-up, 112 participants fell 214 times during work. The negative binomial regression model showed that participants with higher grades had a higher incidence rate ratio [95% confidence interval] for falls than those with very low grades (low: 1.64 [1.08–2.47], moderate: 4.23 [2.82–6.34] and high: 6.12 [3.83–9.76]). The intraclass correlation coefficient for risk score was 0.86 [0.72–0.93], and the weighted kappa coefficient for grade assessment was 0.74 [0.52–0.95]. Conclusions The OFRAT is a valid and reliable tool for estimating the occupational fall risk in older workers. It may assist occupational physicians implement strategies to prevent falls in this group. [ABSTRACT FROM AUTHOR]

Background: The rapid determination of the fatigue limit using temperature second harmonic, which is the temperature variation with twice the frequency of the cyclic load, is attractive in terms of time and cost effectiveness. However, the temperature second harmonic contains non-fatigue-related factors (e.g., internal friction and load second harmonic), in addition to fatigue-related factors (e.g., plastic deformation); therefore, this presents challenges in uniquely determining the fatigue limit. Objective: An experimental procedure for uniquely determining the fatigue limit based on temperature second harmonic measurements is developed. Methods: In the developed procedure, the temperature second harmonic amplitude is accurately measured using the present phase double frequency (2f) lock-in thermography, and the fatigue limit is then uniquely determined based on the generation mechanism of the temperature second harmonic. The present phase 2f lock-in thermography requires only simple post-processing, considering the phase information of both the non-fatigue-related and fatigue-related factors. The fatigue limit estimation accuracies of the developed procedure and four existing methods are quantitatively evaluated in comparison with the actual fatigue limit for heat-treated carbon steel plate specimens subjected to annealing, normalizing, and quenching–tempering. Results: By performing simple post-processing, the present phase 2f lock-in thermography easily eliminates the influence of internal friction and load second harmonic. The developed procedure exhibits the second-best estimation accuracies among all the methods for all the heat-treated specimens. Conclusions: The developed procedure is validated through its reasonable estimation accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Influenza virus infection has significant morbidity and mortality in patients with medical co-morbidities who are also immunosuppressed. The efficacy of the seasonal influenza vaccine has not been well studied in patients receiving chemotherapy. We assessed the efficacy of seasonal influenza vaccine in patients with non-haematological malignancy on active treatment (chemotherapy and targeted therapy).Methods: A prospective single arm, open label study with 53 patients with non-haematological cancers recruited during the 2011 and 2012 influenza seasons. Participants had one dose of 2011/2012 trivalent vaccine containing strains A/California/7/2009(H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 (Fluvax) prior to or in-between treatment cycles. Haemagglutination inhibition antibody (HIA) titres in serum were measured at baseline 3, 6 and 24 weeks. Primary endpoint: seroconversion rate (SCR) at 3 weeks. Secondary endpoints: late SCR at 6 weeks. rate of sustained sero-protection titres (SPR) at 24 weeks. Seroconversion was defined as postvaccination ≥ 4-fold increase in HIA titre and sero-protection defined as a HIA ≥ 1:40.Results: The SCR at 3 weeks were 35%, 30% and 22.5% to the H1N1, H3N2 and B/Bris strains, respectively. There were no new cases of late SC at 6 weeks or 24 weeks. The SPR at 3 weeks were 72.5%, 65% and 40%, respectively, to H1N1, H3N2 and B/Bris. The SPR at 24 weeks to H1N1, H3N2 and B/Bris were 40%, 52.5% and 17.5%, respectively.Conclusions: Patients on various solid tumour treatments achieve sero-protection rate congruent with the general population. The sero-protection HIA titres were not sustained at 24 weeks postvaccination. [ABSTRACT FROM AUTHOR]

Summary: Background: With the increasing use of biological agents for the treatment of psoriasis, the numbers of patients with interstitial lung disease (ILD) associated with biologics have also increased. Many of these cases were associated with tumour necrosis factor (TNF)‐α inhibitors, but cases associated with other families of biologics have also been reported in Japan. Aim: To analyse the background factors of patients who developed ILD, and to discuss better management of biological treatment. Method: We reviewed 246 patients with psoriasis who were treated with biological agents in our department to identify any pulmonary adverse events (AEs). Data on patients who developed ILD were extracted to analyse background factors, clinical type of psoriasis, time to onset of ILD, pre‐existing ILD, smoking habit and prescribed drugs. Results: Pulmonary AEs were seen in 22 cases, of which 11 were diagnosed as drug‐induced ILD. The causative drugs were mainly TNF‐α inhibitors, accounting for eight cases (six treated with infliximab, two with adalimumab). The remaining three cases were associated with secukinumab, ustekinumab and ixekizumab (n = 1 each). Notably, these three cases also had a history of drug‐induced ILD. Conclusion: Patients with a history of drug‐induced ILD seem to be more susceptible to developing another ILD induced by biologics, even if treated with interleukin‐17 inhibitors. Thorough screening of risk factors and evaluation for eligibility, and careful monitoring during treatment are the best solutions to avoid serious pulmonary AE. Early detection and precise diagnosis of pulmonary AEs, especially differentiation from infectious diseases, is essential for managing biological treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Palmoplantar pustulosis (PPP) is a distinct, chronic skin disorder characterized by intraepidermal pustules on the palms and soles. It is hypothesized that microorganisms on the skin might induce the symptoms of PPP via inflammatory cell activation. However, the microbiota has not been studied in detail because of the assumption that the pustules in PPP are sterile. Aim: To elucidate the role of microorganisms in pathogenesis of PPP. Methods: PCR analysis was performed of microbial DNA fragments in the pustules of patients with PPP. The sequence of the D1/D2 LSU 26s rRNA gene and that of the 16S rRNA gene was used for fungal and bacterial DNA detection, respectively. Results: In total, 71 samples were carefully collected from the pustules of patients with PPP. Fungal DNA bands were detected in 68 samples, and fungi including Malassezia spp. were identified in 30 of 71 samples (42.3%). Malassezia restricta was the most frequently encountered fungus (14/71; 19.7%). However, bacterial DNA was not detected by the methods used. Furthermore, identical fungal DNA was not detected in the outer lid of the pustules, suggesting that the fungi detected within the pustule did not derive from contamination via the skin surface. Conclusions: In the present study, we demonstrated for the first time that certain pustules in patients with PPP contain fungal DNA fragments, especially those of Malassezia spp. Our findings provide new insights on the role of skin microbiota in the pathogenesis of PPP. [ABSTRACT FROM AUTHOR]

Background: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24‐ and 52‐week findings of an open‐label, phase 3 trial (UNCOVER‐J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. Objective: To assess the long‐term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. Methods: These subgroup analyses were of a partial population of patients from UNCOVER‐J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment‐emergent adverse events and adverse events of special interest. Results: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. Conclusion: These findings suggest that ixekizumab can be an effective long‐term treatment option for erythrodermic or generalized pustular psoriasis. Linked article: This article is commented on G. Egawa et al., p. 259 in this issue. To view this article visit https://doi.org/10.1111/jdv.15416 [ABSTRACT FROM AUTHOR]

SUMMARY: NTMobile (Network Traversal with Mobility) has been proposed to achieve end‐to‐end encryption communication supporting IP mobility in environments where IPv4/IPv6 networks coexist. However, since NTMobile unconditionally establishes an encrypted User Datagram Protocol (UDP) tunnel between NTMobile‐ready nodes (NTM nodes), a malicious NTM node can attack a target NTM node through the encrypted UDP tunnel without being detected by a firewall. Moreover, since communication with a general server always passes through a relay server (RS), the route becomes redundant even when IP mobility is not needed, and the communication delay increases. In order to solve these problems, this paper proposes an access control function using the name of the correspondent node and a “Route option” that can select whether the RS is used or not. As a result of implementation of the prototype system and evaluation of its performance, it was confirmed that the increase of the start‐up time and that of the overhead at the beginning of the communication were quite small, and there was little influence on practical use. [ABSTRACT FROM AUTHOR]

Summary: A 70‐year‐old man presented to our clinic with a 10‐year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T‐cell receptor (TCR)–Cβ1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis. Anti‐CCR4 monoclonal antibody (mogamulizumab) treatment was started. After seven courses, the CCR4‐positive atypical lymphocytes decreased in the dermis to levels below those seen at the outset of treatment. To our knowledge, there is no previous report of a case of SS managed with vorinostat followed by mogamulizumab demonstrating such a remarkable change in the pathological state following treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Appropriate goal‐oriented treatment strategies are important for optimal treatment outcomes and may prevent under‐treatment. As treatment goals vary by patient, a study to examine treatment goals is more meaningful when patients and their physicians are paired. There has not been any study that examines alignment between paired psoriasis patients and physicians in real‐world clinical practice using skin clearance as a treatment goal indicator. Objectives: To evaluate treatment goal alignment between psoriasis patients and their paired physicians, and to quantitatively identify factors associated with goal misalignment. Methods: The study was a nationwide multicenter cross‐sectional observational study. Subjects were physician‐reported moderate‐to‐severe psoriasis patients with a history of systemic treatments, directly paired with their treating physicians. Subjects completed surveys independently. Treatment goals included seven categories, and patient–physician pairs were grouped as ‘aligned’ or ‘misaligned’ when the answers were the same or different, respectively. Results: A total of 425 pairs (mean response rate, 94.7%) of responses were collected from 54 sites (64.8% general practitioners or clinics; 35.2% university or large hospitals). Treatment goal misalignment was found in 67.9% of the patient–physician pairs. The misalignment was mainly ‘patient predominant’ (60.9%) indicating that patients had higher goals (‘complete clearance’) than physicians. In the multivariate logistic regression analyses, patients’ treatment expectation for ‘complete clearance’ [odds ratio (OR): 1.927; 95% confidential interval (CI): 1.232–3.016] and physician rating of ‘level of understanding on treatment options’ being low (OR: 1.552, 95% CI; 1.082–2.227) were significant factors for treatment goal misalignment. Conclusions: The majority of treatment goal misalignment was found between paired psoriasis patients and their treating physicians in Japan. The most important contributing factors to misalignment were patients’ treatment expectation for ‘complete clearance’ and physicians’ rating of their patients’ ‘level of understanding on treatment options’ being low. [ABSTRACT FROM AUTHOR]

Background Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. Objective To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis and moderate-to-severe non-pustular palmoplantar involvement. Methods In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis [ UNCOVER-1 ( N = 1296), UNCOVER-2 ( N = 1224), UNCOVER-3 ( N = 1346)] were randomized to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160-mg starting dose, or placebo through week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open-label long-term extension ( UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index ( PPASI) ≥8. Results Twenty-eight percent of UNCOVER-1, UNCOVER-2 and UNCOVER-3 patients had baseline palmoplantar involvement ( PPASI ≥0, n = 1092) and 9.1% ( n = 350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and ixekizumab Q2W-treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. Conclusion In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Objectives: To examine the combined association of obesity and low muscle strength with mobility limitation in older adults. Design, setting and participants: This two-year follow-up longitudinal study included pooled data from 283 older community-dwelling Japanese women without mobility limitations who were 65 to 87 years of age (mean age 72.2 ± 5.0 years). Measurements: Muscle strength was measured by hand-grip strength (HGS). The participants were categorized by HGS (high muscle strength: HGS ≥19.6 kg, low muscle strength: HGS <9.6 kg) and body mass index (BMI) (obese: BMI ≥25 kg/m, normal weight: BMI <25 kg/m). The main outcome was mobility limitation, assessed by a self-reported questionnaire (difficulty walking one-half mile or climbing 10 steps without resting). Multivariate logistic regression analysis was performed to determine the combined effect of HGS and BMI on mobility limitation, adjusting for age, exercise habits, medications, and knee pain. Results: During the follow-up period, 82 of 283 participants (29.0%) developed mobility limitation. The adjusted odds ratios (95% confidence interval) for the incidence of mobility limitation were 1.53 (0.86- 2.73) and 2.05 (1.08-3.91) in the obese and low muscle strength groups, respectively. Obesity combined with low muscle strength exhibited a significant and strong association with mobility limitation (odds ratio: 3.88, 1.08-13.91) compared with participants with normal weight and high muscle strength. Conclusion: Among community-dwelling older Japanese women, obesity alone was not associated with the incidence of mobility limitation, but when combined with low muscle weakness, the risk of developing mobility limitation was 3.9-fold greater than for the reference group. [ABSTRACT FROM AUTHOR]

Background: The occurrence of itai-itai disease is thought to be affected by such factors as pregnancy, lactation, hormonal disorders, aging, and calcium deficiency.Aims: To study the influence of years engaged in agriculture and number of pregnancies and deliveries on the mortality of inhabitants of the Jinzu River basin area, which has been an endemic region for itai-itai disease.Methods: From 6,667 participants (3,181 men, 3,486 women; participation rate 93.4%) in the 1967 health survey, 3,639 subjects (1,591 men, 2,048 women) whose years engaged in agriculture were established, and 2,559 women/2,410 women with a known number of pregnancies/deliveries were selected as the target population. These data were confirmed on the basis of self reported replies confirmed afterwards by interview. The survival survey was conducted for 6,127 days from 1 August 1967 to 10 May 1984. Subjects were divided according to three water systems: the Jinzu River, non-Jinzu River, and mixed water system; the influence on mortality of the years engaged in agriculture and the number of pregnancies/deliveries was analysed using a Cox's proportional hazards model according to the water systems.Results: The mean years engaged in agriculture and mean number of pregnancies/deliveries were not different among the three water systems. Cox's hazard ratios of these parameters to mortality were not statistically significant in the any of the water systems.Conclusions: Neither the years engaged in agriculture nor the number of pregnancies/deliveries influenced mortality in subjects living not only in the non-Jinzu River basin but also in the Jinzu River basin using a Cox's proportional hazards model. [ABSTRACT FROM AUTHOR]

In the present case, the mealworm allergy was thought to have resulted from skin sensitization to the allergen in the course of handling mealworms as pet feed. Mealworms ( I Tenebrio molitor i ), the larvae of the Darkling beetle, are commonly bred as food for pets, including herpetiles, guinea pigs and hamsters. [Extracted from the article]

C-type natriuretic peptide (CNP) is a potent stimulator of long bone and vertebral development via endochondral ossification. In the present study, we investigated the effects of CNP on craniofacial skeletogenesis, which consists of both endochondral and membranous ossification. Morphometric analyses of crania from CNP knockout and transgenic mice revealed that CNP stimulates longitudinal growth along the cranial length, but does not regulate cranial width. CNP markedly increased the length of spheno-occipital synchondrosis in fetal murine organ cultures, and the thickness of cultured murine chondrocytes from the spheno-occipital synchondrosis or nasal septum, resulting in the stimulation of longitudinal cranial growth. Mandibular growth includes endochondral and membranous ossification; although CNP stimulated endochondral bone growth of condylar cartilage in cultured fetal murine mandibles, differences in the lengths of the lower jaw between CNP knockout or transgenic mice and wild-type mice were smaller than those observed for the lengths of the upper jaw. These results indicate that CNP primarily stimulates endochondral ossification in the craniofacial region and is crucial for midfacial skeletogenesis. [ABSTRACT FROM PUBLISHER]

Aims/hypothesis: The aim of this study was to understand the role of CXC chemokine receptor 3 (CXCR3), a T-helper 1(Th1) type chemokine receptor, in the pathogenesis of type 1 diabetes. Methods: We observed the incidence of diabetes in Cxcr3 homozygous knockout mice. We compared the expression pattern of various cytokines and chemokines and the frequency of FOXP3 cells in the pancreas and pancreatic lymph nodes from Cxcr3 NOD mice and wild-type NOD mice. In addition, we observed the migration ability of CXCR3CD4 cells to pancreatic islets upon adoptive transfer. Finally, we examined whether Cxcr3 regulatory T cells (Tregs) actually suppressed the onset of diabetes in vivo. Results: Cxcr3 NOD mice developed spontaneous diabetes earlier than did wild-type NOD mice. In Cxcr3 NOD mice, Tregs were more frequent in pancreatic lymph nodes and less frequent in pancreatic islets than in wild-type NOD mice. While transferred CXCR3CD4 cells from wild-type NOD mice did not infiltrate pancreatic islets of NOD-severe combined immunodeficiency (SCID) mice, CXCR3CD4 cells from the same mice migrated into the recipient islets and contained Forkhead box P3 (FOXP3) upon adoptive transfer. Moreover, CD4CD25 cells from wild-type NOD mice suppressed and delayed the onset of diabetes compared with those from Cxcr3 NOD mice in a cyclophosphamide-induced diabetes model system. Conclusions/interpretation: The mechanism of accelerated diabetes onset in Cxcr3 NOD mice was considered to be due to the lack of hybrid Tregs (CXCR3FOXP3CD4 cells), which could effectively migrate into and regulate Th1 inflammation in local lesions under Cxcr3 knockout conditions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the immediate effects of stabilization exercises (SE) and conventional exercises (CE) on static balance. Eleven young male soccer players participated in this study. Using a crossover design, all subjects went through three different procedures, namely, SE, CE, and non-exercise, to compare the immediate effects. They underwent the single-limb standing test with their eyes closed on a foot pressure-recording platform for the static balance test. The result indicated interactions in the total length of the center of pressure (COP) and COP sway speed. Among the three procedures, immediate improvement was only observed after SE. These results showed that static balance improved after SE, but not after the other two procedures. [ABSTRACT FROM AUTHOR]

We used scanning tunneling microscopy to investigate graphene formation on an SiC-on-insulator (SiC-OI) substrate. Annealing of an SiC-OI substrate with an SiC thickness of 1500 nm produced a graphene layer on the SiC surface. When the thickness of the SiC film was 5 nm, a graphene layer was not formed on the SiC surface. However, after annealing a C-covered SiC-OI substrate with an SiC thickness of 5 nm, a graphene layer formed on the SiO2 surface. [ABSTRACT FROM AUTHOR]

Algal blooms in eutrophic water bodies are controlled by inputs of phosphorus (P) as the growth-limiting nutrient. Runoff particulate P associated with soil from fields often predominates among P fractions. Here, an algal bioassay to investigate the potential bioavailability of particulate P in soil collected from a citrus orchard was conducted. Microcystis aeruginosa was cultured in medium containing soil as the sole source of P. The P in the soil was not notably solubilized after autoclaving. Analyses of chlorophyll-a, suspended solids, particulate organic carbon, and particulate organic nitrogen showed that M. aeruginosa could utilize some of the P present in the soil, perhaps that in particulate form, but this form of P was not sufficient to maintain optimum growth. [ABSTRACT FROM AUTHOR]

Objectives: The widespread adoption of 24 h continuous operations in a number of industries has resulted in an increase in shift work, which may influence lipid metabolism because of disturbed circadian rhythms, broken sleep and lifestyle problems. The objective of the present study was to assess the effect of shift work on serum total cholesterol as an index of lipid metabolism. Methods: A 14-year prospective cohort study was conducted in day workers (n = 4079) and alternating shift workers (n = 2807) who received annual health check-ups between 1991 and 2005 in a Japanese steel company. The end-points were either a 20%, 25%, 30%, 35%, 40% or 45% increase in serum total cholesterol during the period of observation, compared with serum total cholesterol at entry to the study. The association between the job schedule type and increase in serum total cholesterol was investigated using multivariate pooled logistic regression analyses. The odds ratios for the effect of shift work were obtained after adjustment for a number of potential confounders. Results: The significant odds ratios of alternating shift work (and 95% confidence intervals) were: ⩾20%, 1.16 (1.07 to 1.26); ⩾25%, 1.16 (1.05 to 1.28); ⩾35%, 1.23 (1.05 to 1.43); ⩾40%, 1.30 (1.07 to 1.58); and ⩾45%, 1.28 (1.01 to 1.63) for serum total cholesterol. Conclusion: Generally the odds ratios of alternating shift work tended to be higher for stricter cut-points of relative increase in serum total cholesterol level. Our study in male Japanese workers revealed that alternating shift work adversely affected lipid metabolism. [ABSTRACT FROM AUTHOR]

Objectives: In our previous functional magnetic resonance imaging (fMRI) study, we determined that there was distinct left hemispheric dominance for lexical-semantic processing without the influence of human voice perception in right-handed healthy subjects. However, the degree of right-handedness in the right-handed subjects ranged from 52 to 100 according to the Edinburgh Handedness Inventory (EHI) score. In the present study, we aimed to clarify the correlation between the degree of right-handedness and language dominance in the fronto-temporo-parietal cortices by examining cerebral activation for lexical-semantic processing.Methods: Twenty-seven normal right-handed healthy subjects were scanned by fMRI while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). Fronto-temporo-parietal activation was observed in the left hemisphere under the SEN - rSEN contrast, which included lexical-semantic processing without the influence of human voice perception. Laterality Index was calculated as LI = (L - R)/(L + R) x 100, L: left, R: right.Results: Laterality Index in the fronto-temporo-parietal cortices did not correlate with the degree of right-handedness in EHI score.Conclusions: The present study indicated that the degree of right-handedness from 52 to 100 in EHI score had no effect on the degree of left hemispheric dominance for lexical-semantic processing in right-handed healthy subjects. [ABSTRACT FROM AUTHOR]

This article discusses a study which determined the effect of cadmium exposure on the post-mortem tissue concentrations of selenium, zinc, copper and iron in heart and aorta. The study also examined the potential correlations between hypertension and altered trace elements concentrations on cadmium-exposed and non-exposed subjects. High exposure to cadmium did not affect the distribution of selenium in heart and aorta. Generally, all trace element concentrations in heart, except cadmium, showed no changes.

In comparison with neutrophil-mediated lung diseases, such as acute respiratory distress syndrome, the involvement of IL-8 in lymphocyte-mediated lung diseases has not been fully investigated. Several reports have shown a slight increase in bronchoalveolar lavage fluid (BALF) IL-8 in patients with hypersensitivity pneumonitis (HP) and sarcoidosis (SAR), but the source of the IL-8 has not been clarified. In the present study, the in vivo production of IL-8 by alveolar macrophages (AMs) is examined in these patients by analyzing the cell-associated IL-8, using the flow cytometric method adopted previously. The IL-8 levels in the epithelial lining fluid (ELF) were also assessed. Initially, slight, but significant, increased levels of ELF IL-8 in HP and SAR were confirmed. Using flow cytometric analysis, a significant increase was found in the cell-associated IL-8 of the freshly isolated AMs in HP, but not in SAR, indicating in vivo production of IL-8 by AMs in HP. The cell-associated IL-8 of the AMs cultured with or without lipopolysaccharide was also analyzed. However, in contrast to previous findings in patients with idiopathic pulmonary fibrosis, no differences were found between SAR and HP patients and control subjects. Based on these findings, it is speculated that ELF IL-8 levels are slightly increased in HP and SAR, and they may contribute to the accumulation of neutrophils and possibly lymphocytes. However, the source of IL-8 may be different and AMs are the candidate source of IL-8 in HP, but not in SAR. The flow cytometric method may be useful in assessing cytokines production by AMs. [ABSTRACT FROM AUTHOR]

We have previously utilized a human bone morphogenetic protein-2 (BMP-2)-expressing recombinant adenoviral vector (AxCAOBMP-2) for osteoinductive gene therapy in rats. However, immunosuppression is essential for osteoinduction by AxCAOBMP-2 and this is one of the major impediments to its clinical use. Injection of AxCAOBMP-2 together with the immunosuppressant FK506 made it possible to markedly reduce the dose of the immunosuppressive agent and still induce ectopic bone reliably. We injected AxCAOBMP-2 and FK506 into the right calf muscle of rats, while the same number of plaque forming units of AxCAOBMP-2 and the same dose of FK506 placebo (vehicle) were injected into the left calf muscle. At 1, 3, 5, 7, 9 days after injection, BMP-2 mRNA expression was significantly higher in the right calf muscle than in the left calf muscle. At 21 days after injection, significantly more ectopic bone was observed in the right calf muscle than in the left calf muscle. These results indicate that coinjection of FK506 significantly promotes osteoinduction. In addition, local injection of FK506 may also make it possible to prevent a decrease of gene expression with other adenoviral vector.Gene Therapy (2004) 11, 439-447. doi:10.1038/sj.gt.3302176 [ABSTRACT FROM AUTHOR]

Pulmonary hemorrhage (PH) is a rare but fatal complication of systemic lupus erythematosus (SLE). We report a patient with SLE and a massive PH who was treated with double-filtration plasmapheresis synchronized with cyclophosphamide pulsed therapy. The patient showed dramatic improvement immediately and was followed for 3 years without recurrence. Prompt treatment during the acute phase of PH with this short-term intensive combination therapy may offer the best chance of success. There are few reports of long-term followup, especially in Japan. [ABSTRACT FROM AUTHOR]

Studies the dose-effect relationship of smoking habits with blood pressure in normotensive men in Japan. Blood pressure measurement; Analysis of covariance; Lifestyle, blood test and physical measurement.

Summary. In neurons, pituitary adenyl cyclase activating peptide (PACAP) stimulates signaling cascades, involving cAMP and calcium. PACAP appears to play a role in up-regulation of tyrosine hydroxylase and dopamine β-hydroxylase via protein kinase C and/or protein kinase A. Furthermore, the PACAP gene (ADCYAP1) is located in chromosome 18p11, where linkage of bipolar disorders and schizophrenia has been reported. In this study, we scanned the coding region of the PACAP gene for mutations in 24 Japanese patients with schizophrenia and 24 Japanese patients with bipolar disorders. No variant in the coding region was found. One polymorphism, INV3-37A/T, in the third intron was detected. Case-control comparisons revealed no significant association between this polymorphism and schizophrenia or bipolar disorders. This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population. [ABSTRACT FROM AUTHOR]

This study endeavours to clarify the effect of alcohol consumption on changes in the blood pressure of Japanese men. The subjects, who were followed from 1990 to 1995, were 2189 male normotensive steelworkers aged from 40 to 54 years in 1990. Drinking habits were represented by two variables: average daily baseline alcohol consumption, and change in alcohol consumption during the observation period, both derived from self-report questionnaires and interviews. Nine other items were analysed as covariates: systolic and diastolic blood pressure, age, body mass index (BMI), salt intake, physical activity, and levels of gamma glutamyl transpeptidase (GTP), uric acid and plasma glucose in 1990. The association between drinking habits and blood pressure was evaluated using ANCOVA. Subjects who had initiated antihypertensive therapy by 1995 were excluded from this dataset. The results of analysis disclosed that both daily alcohol consumption and its change were significantly associated with changes in systolic and diastolic blood pressure during the observation period. J-shaped associations of daily alcohol consumption with adjusted changes in systolic and diastolic blood pressure were found. Positive associations were observed between changes in alcohol consumption and adjusted changes in systolic and diastolic blood pressure. In conclusion, daily alcohol consumption was associated non-linearly with changes in blood pressure and with a threshold effect at 18 ml of ethanol per day in these middle-aged Japanese workers. In addition, increasing alcohol consumption was associated with blood pressure elevation, and decreasing consumption was associated with suppression of blood pressure elevation. [ABSTRACT FROM AUTHOR]