The risk of interstitial lung disease during biological treatment in Japanese patients with psoriasis.

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.

Factor Xa inhibitors for preventing recurrent thrombosis in patients with antiphospholipid syndrome: a longitudinal cohort study.

OBJECTIVE: The objective of this study was to clarify the efficacy and safety of factor Xa inhibitors for antiphospholipid syndrome patients in real world utilization. METHODS: This is a retrospective cohort study comprised of all consecutive patients with antiphospholipid syndrome in our department over a period of 28 years. Patients treated with factor Xa inhibitors were extracted from the cohort. As a control group, patients treated with warfarin were selected from the same cohort with matched age, gender, coexistence of systemic lupus erythematosus, and the presence of antiplatelet therapy, after which we used a propensity score for each of the risk factors as an additional covariate in multivariate Cox proportional hazard regression. The primary endpoint was set as thrombotic and hemorrhagic event-free survival for five years. RESULTS: Among 206 patients with antiphospholipid syndrome, 18 had a history of anti-Xa therapy (five rivaroxaban, 12 edoxaban, one apixaban). Fourteen out of 18 patients on anti-Xa therapy had switched to factor Xa inhibitors from warfarin. Event-free survival was significantly shorter during anti-Xa therapy than that during warfarin therapy (hazard ratio: 12.1, 95% confidence interval: 1.73-248, p = 0.01) ( Figure 1(a) ). Similarly, event-free survival in patients treated with factor Xa inhibitors was significantly shorter compared with controls (hazard ratio: 4.62, 95% confidence interval: 1.54-13.6, p = 0.0075). In the multivariate Cox proportional hazard model, event-free survival in patients with anti-Xa therapy remained significantly shorter (hazard ratio: 11.9, 95% confidence interval: 2.93-56.0, p = 0.0005). CONCLUSIONS: Factor Xa inhibitors may not be recommended for antiphospholipid syndrome.

Room-Temperature Low-Field Colossal Magnetoresistance in Double-Perovskite Manganite.

We have discovered room-temperature low-field colossal magnetoresistance (CMR) in an A-site ordered NdBaMn_{2}O_{6} crystal. The resistance changes more than 2 orders of magnitude at a magnetic field lower than 2 T near 300 K. When the temperature and magnetic field sweep from an insulating (metallic) phase to a metallic (insulating) phase, the insulating (metallic) conduction changes to the metallic (insulating) conduction within 1 K and 0.5 T, respectively. The CMR is ascribed to the melting of the charge and orbital ordering. The entropy change which is estimated from the B-T phase diagram is smaller than what is expected for the charge and orbital ordering. The suppression of the entropy change is attributable to the loss of the short-range ferromagnetic fluctuation of Mn spin moments, which is an important key of the high temperature and low magnetic field CMR effect.

Nonreciprocal Refraction of Light in a Magnetoelectric Material.

In magnetoelectric materials, where the time-reversal and space-inversion symmetries are simultaneously broken, optical properties can differ between the opposite propagation directions of light. We report on an experimental observation of nonreciprocal trajectory of a light ray in magnetoelectric material CuB_{2}O_{4}. The light is refracted in different ways between the opposite propagation directions of light. We find a nonreciprocal refraction at the interface between a matter with macroscopic toroidal moment and vacuum. The resultant nonreciprocal deflection of the light is 0.005 deg, which is quantitatively explained using Fermat's principle.

Correction to: Community knowledge, attitudes and practices related to schistosomiasis and associated healthcare-seeking behaviours in northern Côte d'Ivoire and southern Mauritania.

After publication of this article [1] it came to our attention that Tables 2, 3, 4, 5, 6, 7 were presented incorrectly.

Community knowledge, attitudes and practices related to schistosomiasis and associated healthcare-seeking behaviours in northern Côte d'Ivoire and southern Mauritania.

BACKGROUND: Among parasitic infections, schistosomiasis ranks second after malaria in terms of worldwide morbidity. Despite efforts to contain transmission, more than 230 million people are infected, of which 85% live in Sub-Saharan Africa. While the epidemiologic characteristics of schistosomiasis have been extensively studied across endemic settings, social factors have been paid less attention. The current study assesses community knowledge of schistosomiasis causes, transmission, signs, symptoms and prevention, as well as healthcare-seeking behaviours in two West African settings, with the aim of strengthening schistosomiasis control interventions. METHODS: From August 2014 to June 2015, we conducted two cross-sectional surveys in Korhogo, Côte d'Ivoire and Kaédi, Mauritania. We applied a questionnaire to collect quantitative data at the household level in Korhogo (n = 1456) and Kaédi (n = 1453). Focus group discussions (Korhogo: n = 32, Kaédi: n = 32) and participatory photography (photovoice) (Korhogo: n = 16, Kaédi: n = 16) were conducted within the communities to gather qualitative data. In addition, semi-structured interviews were used to discuss with key informants from control programmes, non-governmental organizations and health districts (Korhogo: n = 8, Kaédi: n = 7). RESULTS: The study demonstrated that schistosomiasis is not well known by the communities; 64.1% claimed to know the causes of the disease, but the reality is different. This knowledge is more from cultural than biomedical source. It was observed that social construction of the disease is different from the biomedical definition. In Korhogo, schistosomiasis was often associated with several other diseases, notably stomach ulcer and gonorrhoea. The populations believe that schistosomiasis is caused by exposure to goat or dog urine in the environment. In Kaédi, schistosomiasis is considered as a disease transmitted by environmenal elements such as sunshine and dirty water. In both settings, the care-seeking pathways were found to be strongly influenced by local customs and self-medication acquired from the informal sector. CONCLUSIONS: This study revealed that knowledge about the aetiology, transmission, symptoms, prevention and treatment of schistosomiasis among the populations in Korhogo and Kaédi is based on their local culture. Deep-rooted habits could therefore pose a significant obstacle to the elimination of schistosomiasis.

Multiple Re-entry Closures After TEVAR for Ruptured Chronic Post-dissection Thoraco-abdominal Aortic Aneurysm.

INTRODUCTION: Although thoracic endovascular aortic repair (TEVAR) has become a promising treatment for complicated acute type B dissection, its role in treating chronic post-dissection thoraco-abdominal aortic aneurysm (TAA) is still limited owing to persistent retrograde flow into the false lumen (FL) through abdominal or iliac re-entry tears. REPORT: A case of chronic post-dissection TAA treatment, in which a dilated descending FL ruptured into the left thorax, is described. The primary entry tear was closed by emergency TEVAR and multiple abdominal re-entries were closed by EVAR. In addition, major re-entries at the detached right renal artery and iliac bifurcation were closed using covered stents. To close re-entries as far as possible, EVAR was carried out using the chimney technique, and additional aortic extenders were placed above the coeliac artery. A few re-entries remained, but complete FL thrombosis of the rupture site was achieved. Follow-up computed tomography showed significant shrinkage of the FL. DISCUSSION: In treating post-dissection TAA, entry closure by TEVAR is sometimes insufficient, owing to persistent retrograde flow into the FL from abdominal or iliac re-entries. Adjunctive techniques are needed to close these distal re-entries to obtain complete FL exclusion, especially in rupture cases. Recently, encouraging results of complete coverage of the thoraco-abdominal aorta with fenestrated or branched endografts have been reported; however, the widespread employment of such techniques appears to be limited owing to technical difficulties. The present method with multiple re-entry closures using off the shelf and immediately available devices is an alternative for the endovascular treatment of post-dissection TAA, especially in the emergency setting.

Involvement of corticotropin-releasing factor and corticotropin-releasing factor 2 receptors in pathogenesis of ischemia/reperfusion-induced enteritis in rats.

We herein investigated, using a corticotropin-releasing factor (CRF) agonist and antagonists, whether CRF plays a role in the pathogenesis of ischemia/reperfusion-induced small intestinal lesions in rats. Under pentobarbital anesthesia, the superior mesenteric artery was clamped (ischemia) for 75 min, followed by reperfusion with removal of the clamp. After a 24-h reperfusion, the area of hemorrhagic lesions that developed in the small intestine was measured. Urocortin I (CRF receptor 1/2 agonist), astressin (CRF receptor 1/2 antagonist), NBI27914 (CRF receptor 1 antagonist), or astressin 2B (CRF receptor 2 antagonist) was administered i.v. twice: 5 min before ischemia and 6 hours after reperfusion. Ischemia/reperfusion caused hemorrhagic lesions in the small intestine in ampicillin- and aminoguanidine-inhibitable manners, accompanied by enterobacterial invasion and the up-regulation of inducible nitric oxide synthase expression and myeloperoxidase activity. The severity of ischemia/reperfusion-induced lesions was significantly reduced by astressin and astressin 2B, but not by NBI27914, with the suppression of bacterial invasion, myeloperoxidase activity, and inducible nitric oxide synthase expression. In contrast, urocortin I markedly aggravated these lesions, and this response was completely abrogated by the co-administration of astressin 2B, but not NBI27914. The gene expression of CRF, CRF receptor 1, and CRF receptor 2 was observed in the small intestine, and remained unchanged following ischemia/reperfusion. These results suggest that ischemia/reperfusion caused hemorrhagic lesions in the small intestine, the pathogenesis of which involved enterobacteria and inducible nitric oxide synthase/nitric oxide. These lesions were aggravated by urocortin I in an astressin 2B-inhibitable manner, but suppressed by astressin in a CRF receptor 2-dependent manner. Endogenous CRF may be involved in the pathogenesis of ischemia/reperfusion-induced enteritis, possibly via the activation of peripheral CRF receptor 2.

An Effective New Cryopreservation Procedure for Pancreatic Islets Using Hollow Fiber Vitrification.

The present study aimed at establishing a new cryopreservation method for mouse pancreatic islets by vitrification using hollow fibers as a container. A unique feature of the hollow fiber vitrification (HFV) method is that this method achieves stable vitrification using a minimum volume of cryoprotectant (CPA) solution, thereby ensuring high viability of the islets. The cytotoxicity, optimum composition, and concentration of the CPAs for vitrifying islets were examined. The viability, functional-integrity of vitrified islets were evaluated in comparison with those vitrified by conventional methods. Insulin secretion was measured in vitro by a static incubation assay and the metabolic functions was tested after transplantation into Streptozotocin-induced diabetic mice. The combination of 15% dimethyl sulfoxide+15% ethylene glycol resulted in the best CPA solution for the HFV of islets. HFV showed the highest viability in comparison to 2 vitrification methods, open pulled straws and vitrification with EDT324 solution. The vitrified islets stably expressed ß-cells markers NeuroD, Pancreatic and duodenal homeobox-1, and MafA. Transplantation of the vitrified islets achieved euglycemia of the host diabetic mice and response to an intraperitoneal glucose tolerance test to a similar extent as non-vitrified transplanted islets. The HFV method allows for efficient long-term cryopreservation of islets.

Data-based prediction of soft tissue changes after orthognathic surgery: clinical assessment of new simulation software.

The aim of the present study was to evaluate the accuracy of a novel simulation software package (OrthoForecast) for predicting the soft tissue profile after orthognathic surgery. The study included 15 patients with facial asymmetry (asymmetry group), 15 with a skeletal class II jaw relationship (class II group), and 15 with a skeletal class III jaw relationship (class III group). Twenty-four feature points were digitized, and the distances between points on the predicted and actual postoperative images were compared. Thirty-seven calibrated evaluators also graded the similarity of the predicted images compared to the actual postoperative photographs. Comparisons between the predicted and actual postoperative images revealed that the mean difference between feature points was 3.1 ± 1.4 mm for the frontal images and 2.9 ± 0.8 mm for the lateral images in the asymmetry group; 2.7 ± 0.9 and 2.1 ± 1.6 mm, respectively, in the class II group; and 1.8 ± 1.2 and 1.7 ± 1.0 mm, respectively, in the class III group. More than half of the evaluators assessed the predicted images as similar to the actual postoperative images in all groups. In conclusion, OrthoForecast can be regarded as useful, accurate, and reliable software to predict soft tissue changes after orthognathic surgery.

One-Way Transparency of Light in Multiferroic CuB(2)O(4).

We experimentally demonstrate one-way transparency of light in multiferroic CuB(2)O(4). The material is rendered transparent for light propagating in one direction, while opaque for light propagating in the opposite direction. The novel transparency results from a destructive interference of the electric dipole and magnetic dipole transitions. The realization of the effect has been accomplished by the application of a high magnetic field and the proper selection of the propagation direction of light in agreement with our quantum mechanical formulation of nonreciprocal directional dichroism.

Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells.

Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress ß-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in ß-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased ß-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited ß-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and ß-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells.

Development of an analytical method for the determination of sterigmatocystin in grains using LCMS after immunoaffinity column purification.

The mycotoxin sterigmatocystin (STC) is produced mainly by some Aspergillus and Penicillium fungi; it naturally contaminates cereals, peanuts, and products derived from these crops, and is both mutagenic and carcinogenic. As an intermediate of aflatoxin (AF) biosynthesis, its structure is similar to that of AF. Although immunoaffinity columns (IACs) are a popular approach to sample clean-up, no IAC is commercially available for STC, but a commercially available IAC for AF shows cross reactivity to STC. We here developed a new method for analyzing STC in grains using such an IAC and liquid chromatography mass spectrometry (LCMS), and validated this method using six different grains. The STC limit of detection (signal-to-noise ratio, S/N = 3) was 2.5 pg (1.0 µg/kg in the product), and the calibration curve was linear in the range of 7.5-375 pg (3.0-150 µg/kg in the product). The within-day recovery of STC from samples spiked with STC at 5.0 and 50 µg/kg was 83.2-102.5% and the RSDr (relative standard deviation of repeatability) of these samples was 1.9-6.5%; the RSDr of STC-pretreated grain samples was 3.1-14.0%. Average recovery of STC from samples spiked with STC in the range of 5.0-100 µg/kg STC was 83.2-102.5%, with an RSDr of 0.24-6.5%; the RSDr of STC-pretreated grain samples was 2.4-14.0%. In an intermediate precision study, the average STC recovery from STC-spiked samples by three analysts was 95.2-107.5%, with RSDRi (intermediate precision) of 4.0-7.1%; the RSDRi of the STC-pretreated samples was 4.8-10.4%. Thus, the proposed method was effective for STC analysis in grains, and holds potential for a novel application of a commercial IAC, intended for AFs, in STC analysis.

Anomalous origin of the right coronary artery from the pulmonary artery: an autopsied sudden death case with severe atherosclerotic disease of the left coronary artery.

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare anomaly. It may contribute to myocardial ischemia or sudden death, although the lesion is usually asymptomatic. We report a sudden death case of a 58-year-old man with ARCAPA coexisting with severe atherosclerotic coronary artery disease. He had been healthy until he complained of chest pain, several days before death, despite the discovery of heart murmur in childhood and suspicion of valvular heart disease. The autopsy revealed not only typical findings of the right coronary anomaly with well-developed collateral circulations but also severe atherosclerotic lesions of the left coronary artery, and ischemic change of the myocardium in the left and right coronary arterial perfusion territory. In addition to the "coronary steal" phenomenon primarily caused by ARCAPA, the reduced flow of both coronary arteries and further increase of "coronary steal" due to atherosclerotic obstructive coronary disease might have contributed to the patient's death.

Magnetization of SrCu2(BO3)2 in ultrahigh magnetic fields up to 118 T.

The magnetization process of the orthogonal-dimer antiferromagnet SrCu2(BO3)2 is investigated in high magnetic fields of up to 118 T. A 1/2 plateau is clearly observed in the field range 84 to 108 T in addition to 1/8, 1/4, and 1/3 plateaus at lower fields. Using a combination of state-of-the-art numerical simulations, the main features of the high-field magnetization, a 1/2 plateau of width 24 T, a 1/3 plateau of width 34 T, and no 2/5 plateau, are shown to agree quantitatively with the Shastry-Sutherland model if the ratio of inter- to intradimer exchange interactions J'/J=0.63. It is further predicted that the intermediate phase between the 1/3 and 1/2 plateaus is not uniform but consists of a 1/3 supersolid followed by a 2/5 supersolid and possibly a domain-wall phase, with a reentrance into the 1/3 supersolid above the 1/2 plateau.