[Autoimmune coagulation factor V/5 deficiency during chronic disseminated intravascular coagulation].

Aortic regurgitation, a thoracoabdominal aortic aneurysm, chronic myeloid leukemia, and chronic kidney disease were all being treated at two hospitals for an 83-year-old man. He was admitted to the Department of Orthopedics at our hospital with a lumbar compression fracture. Later, he experienced melena, for which the Department of Internal Medicine was consulted. Due to the aberrant results of PT-INR (7.1) and a PTT > 200 seconds on a coagulation test, we suspected the presence of an autoimmune coagulation factor deficiency, and prednisolone immunosuppressive therapy medication was started right away. Due to a sharp decline in FV/5 activity, the presence of FV/5 inhibitors, and the presence of anti-FV/5 autoantibodies, a final diagnosis of autoimmune coagulation factor V (FV/5) deficiency was made. After the start of immunosuppressive therapy, the FV/5 inhibitor and anti-FV/5 autoantibodies disappeared, and the FV/5 activity progressively returned to normal. Disseminated intravascular coagulation-which may have been caused by a known aortic aneurysm-worsened while tapering off prednisolone. Due to the patient's advanced age and other problems, the aneurysm was extensive and inappropriate for surgical repair. The coagulation test findings improved gradually upon initiation of warfarin therapy. Herein, the patient had autoimmune FV/5 deficiency, a rare disorder that made diagnosis and therapy difficult because of the patient's several coexisting conditions.

Comparison of the effects of pre-dilution and post-dilution online hemodiafiltration on the levels of inflammatory markers, lymphocytes, and platelets.

Online hemodiafiltration (OL-HDF) is a blood purification therapy based on diffusion and ultrafiltration and is classified into two types according to the mode of addition of the substitution fluid: pre-dilution OL-HDF (pre-HDF) and post-dilution OL-HDF (post-HDF); we previously reported that pre-HDF is more biocompatible. However, we used lower blood and substitution flow rates in that study and may not have accurately simulated the treatment conditions used in Europe. In this study, we compared the biocompatibilities of the treatment conditions of pre-HDF, commonly used in Japan, and post-HDF, commonly used in Europe, to determine the most biocompatible treatment conditions. We compared the biocompatibilities of pre-HDF and post-HDF using high blood flow rates and high substitution fluid volumes, and also compared the results with those of our previous study. We enrolled six stable patients undergoing maintenance dialysis at our clinic for this study. After the patients underwent hemodialysis (HD), post-HDF, and pre-HDF treatment, the biocompatibilities (based on the serum levels of high-sensitivity C-reactive protein, interleukin-6, pentraxin-3, ß-thromboglobulin, and soluble P-selectin, and the results of the lymphocyte blastogenesis test using phytohemagglutinin and concanavalin A as mitogens) and removal performances (removal performance for urea, creatinine, ß2-microglubulin [MG], and α1-MG, and albumin leakage) were determined. There were no significant differences in the biocompatibility parameters evaluated among the three treatment modes. Post-HDF was associated with significantly higher removal rates of ß2-MG than HD. Post-HDF was associated with significantly higher removal rate of α1-MG, and also significantly higher albumin leakage, than HD and pre-HDF.

High accuracy cross-sectional shape analysis by coherent soft x-ray diffraction.

When the scatterer size is less than 100 wavelengths, the effect of diffraction is large. The analysis of diffraction is important for 3D shape measurement. However, in soft x rays, shapes suitable for rigorous diffraction analysis have been limited to ellipses and periodic structures. We have developed a method to expand this to any shape (isolated triangle, rectangle, etc.). Experimentally, we measured the respective widths of the cross section of a column consisting of two layers and showed that the resolution was at least a few wavelengths. For this purpose, we have also developed a fast simulation method with a small memory size.

Therapeutic effect of high-efficiency online hemodiafiltration for recurrent restless legs syndrome in dialysis patients.

Two dialysis patients developed recurrent restless legs syndrome. The clinical courses and the association between the α1-microglobulin removal rate and the therapeutic effects of hemodiafiltration were analyzed. Case 1: a middle-aged woman was switched from predilution online hemodiafiltration to hemodialysis, following which the α1-microglobulin removal rate decreased from 39.1 to 29.9%. A month later, the severe restless legs syndrome occurred. The treatment was then switched to high-efficiency hemodiafiltration and 2 weeks later, these symptoms were resolved. The α1-microglobulin removal rate increased to 41.9%. Her symptoms recurred 5 years later with severity; thus, the hemodiafiltration treatment conditions were changed. Under revised conditions, the α1-microglobulin removal rate was 42.6%, and her symptoms were alleviated. Continuation of high-efficiency hemodiafiltration led to the resolution of the syndrome at 1 month after recurrence. Case 2: a middle-aged man on hemodialysis developed the restless legs syndrome in the second year of treatment. The α1-microglobulin removal rate was 23.8%. After switching to a month-long high-efficiency hemodiafiltration with a removal rate of ≥ 40%, his symptoms were resolved. However, the syndrome recurred after a year with severity. The symptoms were alleviated using various measures. The hemodiafilters were changed, and hemodiafiltration with an α1-microglobulin removal rate of ≥ 40% was continued; 2 months later, his symptoms resolved. High-efficiency online hemodiafiltration is an effective therapeutic strategy for restless legs syndrome in dialysis patients. We found, for the first time, that target removal efficiency is an α1-microglobulin removal rate of 40% or higher.

Evaluation of low-volume post-dilution online hemodiafiltration with Japanese high-performance hemodiafilters.

PURPOSE: To assess the removal performance of low-volume post-hemodiafiltration (HDF) with Japanese hemodiafilters and the removal performance with 20 % reduction in the total dialysate flow rate (Qdtotal). METHODS: Subjects were 8 patients undergoing pre-HDF. Study 1: Post-HDF was performed at a blood flow rate (Qb) of 250 mL/min and a total volume of substitution fluid (Vs) of 12 L/session(s) for 4 hrs using Fineflux-210Seco (FIX), ABH-21PA (ABH), and NVF-21H (NVF). We assessed removal efficiency of small molecular solutes, low-molecular-weight-proteins and the amount of albumin loss. Study 2: Post-HDF was performed at Vs of 12 L/s under G-1, Qdtotal of 500 and Qb of 250 mL/min; G-2, Qdtotal of 400 and Qb of 250 mL/min; and G-3, Qdtotal of 400 and Qb of 300 mL/min. Removal efficiency was compared and analyzed between these conditions. RESULTS: Study 1: The results using FIX, ABH and NVF are shown in order. The Kt/V were 1.8, 1.9 and 1.8. The ß2-Microglobulin (MG) removal rate (RR) (%) were 81.2, 83.1 and 82.8, and the α1-MG RR were 37.4, 40.2 and 38.5, respectively. Study 2: The results in G-1, 2 and 3 are shown in order. The Kt/V and the RR of small solutes, were significantly higher in G-3. The ß2-MG RR (%) were 81.2, 80.1 and 81.0, and the α1-MG RR were 37.4, 37.5 and 38.0, respectively. CONCLUSIONS: Low-volume post-HDF performed at Qb of 250 mL/min with Japanese high-performance hemodiafilters exhibited favorable removal efficiency for all solutes. Even with 20 % reduction in Qdtotal, the removal performance was also favorable.

Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by IL-17-mediated immune responses. p38 is known to be highly activated in the psoriatic epidermis; however, whether p38 is involved in the development of psoriasis is unclear. OBJECTIVE: We sought to demonstrate that activation of p38 mitogen-activated protein kinase is sufficient to induce psoriatic inflammation in mice and that cutaneous p38 activities are the topical therapeutic targets for psoriasis. METHODS: A p38 activator, anisomycin, was applied daily to murine skin. Transcriptomic analyses were performed to evaluate the similarities of the skin responses to those in human psoriasis and the existing animal model. BIRB796, a small-molecule inhibitor targeting p38 activities, was applied to the murine psoriatic models topically or to human psoriatic skin specimens ex vivo. RESULTS: Topical treatment with anisomycin induced key signatures in psoriasis, such as epidermal thickening, neutrophil infiltration, and gene expression of Il1a, Il1b, Il6, Il24, Cxcl1, Il23a, and Il17a, in treated murine skin. These responses were fully abrogated by topical treatment with BIRB796, and were reduced in IL-17A-deficient mice. Transcriptomic analyses demonstrated the similarities of anisomycin-induced dermatitis to human psoriasis and imiquimod-induced murine psoriatic dermatitis. Furthermore, BIRB796 targeting of p38 activities reduced expression of psoriasis-related genes in both human keratinocytes stimulated with recombinant IL-17A in vitro and psoriatic skin specimens ex vivo. CONCLUSION: Therefore our findings suggest that cutaneous p38 activation can be a key event in patients with psoriasis and a potential topical therapeutic target of a small molecule.

Multi-element X-ray movie imaging with a visible-light CMOS camera.

For many years, X-ray movies have been considered a promising tool for exploring and providing insights into chemical reactions. A simultaneous multi-element X-ray movie can further clarify the behavior difference of various elements and help investigate their interactions. The present short communication illustrates how to conduct multi-element X-ray movie imaging in a synchrotron facility solely by placing a micro-pinhole in front of a visible-light complementary metal-oxide semiconductor (CMOS) camera. It has been found that the CMOS camera can resolve X-ray fluorescence spectra when it is specially operated. In this work, a spatial resolution of ∼15 µm was achieved. In the X-ray movie, a movie frame acquisition time of 2 min and a spatial resolution of ∼50 µm were simultaneously achieved. It is clear that the CMOS camera can be a cost-efficient option for many researchers who wish to establish their own setup for visualizing chemical diffusion in various reactions.

Uniaxial Negative Thermal Expansion of Polyvinyl Acetate Thin Film.

The present paper reports some experimental observations of reproducible uniaxial negative thermal expansion (u-NTE) in an amorphous polyvinyl acetate (PVAc) ultrathin film. It has been found that the mechanism of the phenomena is different from latest reports on so-called NTE in crystal or other topological materials. It is known that PVAc exhibits glass transition at around 31 °C. During cooling from the high-temperature side, one can observe the decrease of the thickness by monitoring interference fringes in the X-ray reflectivity curve as a function of temperature. Across the glass transition, however, the thickness starts to increase, instead of reducing. In the heating process, the thickness decreases as long as the temperature is lower than that for glass transition ( Tg). In the present research, such changes in thickness during repeated heating/cooling cycles have been studied systematically. To discuss the mechanism, dependence on film thickness has been investigated as well. It has been found that the present phenomena are well explained as u-NTE, which induces reduction and increase of thickness ( z-direction) just by thermal expansion and shrinking in x- y directions, respectively. This would be caused and enhanced by the growth of a mechanically hard, high-density layer near the interface to the surface of hydrophilic silicon dioxide. The structural change during heating/cooling cycles is discussed in detail.

Current approaches to middle molecule removal: room for innovation.

Aggressive removal of middle molecules or larger low-molecular-weight proteins (LMWPs) has been a growing concern following studies on their harmful effects on the mortality and morbidity of chronic dialysis patients. To remove larger LMWPs and some protein-bound uremic toxins (PBUTs), high- and medium-cutoff (HCOs and MCOs, respectively) membranes, convective therapy and protein adsorptive membranes are available. When we use HCO or MCO membranes for convective therapy, we have to take care to avoid massive albumin leakage during a dialysis session. Convection volume is an important element to increase middle molecule removal; however, a larger convection volume has a risk of larger leakage of albumin. Predilution hemodiafiltration is a useful measurement to increase larger LMWPs without massive albumin leakage. ß2-microglobulin (B2M), α1-microglobulin (A1M) and albumin leakage during a dialysis session are useful parameters for assessing middle-molecule removal. Reduction ratios of B2M >80% and of A1M >35% are favorable to improve severe dialysis-related symptoms. The efficacy of middle molecule removal should be evaluated in comparison with clinical outcomes, mortality, morbidity and the improvement of dialysis-related symptoms. Recently some dialysis-related symptoms such as sleep disturbance, skin itchiness and dialysis hypotension have been recognized as good surrogate makers for mortality. Further studies to evaluate the relationship between middle molecule or PBUTs removal and the improvement of patient symptoms should be performed in well-designed randomized controlled trials.

Cross-sectional particle measurement in the resonance domain on the substrate through scatterometry.

We developed a versatile method for three-dimensional shape measurement where a specific particle can be selected on the substrate and its cross-sectional shape and size can be measured. A non-contact fast measurement is possible for the particle in the resonance domain. We applied rigorous coupled-wave analysis to the particle and calculated the diffraction patterns, comparing the patterns with the experimental results to obtain the size and shape. The shape and position of the focusing spot on the scattering particle was controlled precisely. With this method, the category of the analyzable object is extended to more shapes, such as rectangles and triangles, in addition to a conventional ellipsoid.

Optically Reconfigurable Monolayer of Azobenzene Donor Molecules on Oxide Surfaces.

The structural configuration of molecules assembled at organic-inorganic interfaces within electronic materials strongly influences the functional electronic and vibrational properties relevant to applications ranging from energy storage to photovoltaics. Controlling and characterizing the structural state of an interface and its evolution under external stimuli is crucial both for the fundamental understanding of the factors influenced by molecular structure and for the development of methods for material synthesis. It has been challenging to create complete molecular monolayers that exhibit external reversible control of the structure and electronic configuration. We report a monolayer/inorganic interface consisting of an organic monolayer assembled on an oxide surface, exhibiting structural and electronic reconfiguration under ultraviolet illumination. The molecular monolayer is linked to the surface through a carboxylate link, with the backbone bearing an azobenzene functional group and the head group consisting of a rhenium-bipyridine group. Optical spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy, and X-ray reflectivity show that closely packed monolayers are formed from these molecules via the Langmuir-Blodgett technique. Reversible photoisomerization is observed in solution and in monolayers assembled on Si and quartz substrates. The reconfiguration of these monolayers provides additional means to control excitation and charge transfer processes that are important in applications in catalysis, molecular electronics, and solar energy conversion.

Formation of Ultrathin Liesegang Patterns.

For many years, it has been believed that self-organized periodic ring structures known by the name of Liesegang patterns (LPs) are formed only in quite thick media, typically thicker than at least several micrometers. Actually growing LPs in ultrathin films is extremely difficult because of the drying of film and susceptibility to rapid capillary wetting. The present work reports how we obtain successful LPs in ultrathin films of 65 nm thick. The key parameters are temperature control and the introduction of equilibrium water vapor in the sample environment. Atomic force microscope images clearly showed that the LPs are composed of 300-600 nm laterally coagulated particles. We have also evaluated the densities and thicknesses of the ultrathin films by X-ray reflectivity. During the present research, new patterns, which are different from ordinary LPs, have been discovered for the first time in the outermost part of the whole pattern. Studying LPs in ultrathin films may help to forge a better understanding of the mechanism underlying the intriguing phenomenon. Because of nanoscale scale thicknesses, self-organized periodic structures including so-called LPs will open up new opportunities in nanotechnologies.

Association of Suicidal Ideation with Job Demands and Job Resources: a Large Cross-Sectional Study of Japanese Workers.

PURPOSE: This study aimed to identify the association of suicidal ideation with job demands and job resources among Japanese workers. METHODS: Valid data from questionnaires that were pre-collected from 42,499 workers (34,882 males and 7617 females) were used for multilevel logistic regression analyses. Job demands and job resources were selected as potential predictors of suicidal ideation. Lifestyle variables, support from family and friends, and suffering from depressive or eating disorders were used as covariates. RESULTS: In the employee-level, most job demands and job resources had significant associations with the risk of suicidal ideation in both sexes. High coworker support had a significant negative association with the risk of suicidal ideation in the organization-level, irrespective of their gender. High physical demands and poor physical environment in the organization-level had significant positive associations with increased risk of suicidal ideation only among females. CONCLUSIONS: The risk of suicidal ideation among Japanese workers is associated with job demands and job resources in the employee-level, and coworker support in the organization-level may be important as well.

Interrelationships Between Job Resources, Vigor, Exercise Habit, and Serum Lipids in Japanese Employees: a Multiple Group Path Analysis Using Medical Checkup Data.

BACKGROUND: Physical inactivity is one of the major risk factors for dyslipidemia and coronary heart disease. Job resources have been identified as determinants of employees' vigor and physical activity habits. PURPOSE: Our first purpose was to comprehensively analyze the series of relationships of job resources, through vigor and exercise habit (i.e., one aspect of physical activity), to serum lipid levels in a sample of Japanese employees in a manufacturing company. Our second purpose was to investigate sex differences in these relationships using a multiple-group path analysis. METHODS: Data were collected from 4543 employees (men = 4018, women = 525) during a medical checkup conducted in February and March 2012. Job resources (job control, skill utilization, suitable jobs, and meaningfulness of work), vigor, exercise habit, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured cross-sectionally. RESULTS: Job resources and vigor were positively associated with exercise habit in both sexes. Exercise habit was inversely associated with triglyceride (-0.03 in men and -0.01 in women, ps < 0.05) and LDL-C (-0.07 in both sexes, ps < 0.05). HDL-C was positively associated with exercise habit (0.03 in both sexes, ps < 0.05). There was no significant difference by sex in path coefficients, except for the covariance between suitable jobs and meaningfulness of work. CONCLUSION: Higher levels of job resources were associated with greater vigor, leading to exercise habit, which in turn, improved serum lipid levels. Longitudinal studies are required to demonstrate causality.

Development of a Dehumidification System for a Passive Sampler for Determining 1,3-Butadiene.

The passive sampler is a simple device for collecting gaseous compounds. It is affected by environmental conditions such as relative humidity, but a dehumidification system (DHS) has not been developed for it. We have developed a dehumidification device for the passive sampler for determining 1,3-butadiene. It consists of a passive sampler surrounded by a DHS consisting of a basket filled with granular magnesium perchlorate as the dehumidification agent. The passive sampler consists of a porous polytetrafluoroethylene tube packed with Carboxen 1000 adsorbent. We compared the amounts of water adsorbed on the Carboxen 1000 adsorbent in the presence and in the absence of the DHS; the results showed that the DHS prevented water from entering the sampler. Volatile organic compounds that entered the sampler were collected by the Carboxen 1000 adsorbent. In the case of 1,3-butadiene, much higher amounts were collected by the passive sampler with the DHS than without it. This may be due to interference of adsorption or acceleration of 1,3-butadiene degradation by the water-soluble oxidant on the surface of the Carboxen 1000 adsorbent.

Independent recognition of Staphylococcus aureus by two receptors for phagocytosis in Drosophila.

Integrin ßν, one of two ß subunits of Drosophila integrin, acts as a receptor in the phagocytosis of apoptotic cells. We here examined the involvement of this receptor in defense against infection by Staphylococcus aureus. Flies lacking integrin ßν died earlier than control flies upon a septic but not oral infection with this bacterium. A loss of integrin ßν reduced the phagocytosis of S. aureus and increased bacterial growth in flies. In contrast, the level of mRNA of an antimicrobial peptide produced upon infection was unchanged in integrin ßν-lacking flies. The simultaneous loss of integrin ßν and Draper, another receptor involved in the phagocytosis of S. aureus, brought about a further decrease in the level of phagocytosis and accelerated death of flies compared with the loss of either receptor alone. A strain of S. aureus lacking lipoteichoic acid, a cell wall component serving as a ligand for Draper, was susceptible to integrin ßν-mediated phagocytosis. In contrast, a S. aureus mutant strain that produces small amounts of peptidoglycan was less efficiently phagocytosed by larval hemocytes, and a loss of integrin ßν in hemocytes reduced a difference in the susceptibility to phagocytosis between parental and mutant strains. Furthermore, a series of experiments revealed the binding of integrin ßν to peptidoglycan of S. aureus. Taken together, these results suggested that Draper and integrin ßν cooperate in the phagocytic elimination of S. aureus by recognizing distinct cell wall components, and that this dual recognition system is necessary for the host organism to survive infection.

The genetic and antigenic diversity of avian influenza viruses isolated from domestic ducks, muscovy ducks, and chickens in northern and southern Vietnam, 2010-2012.

To estimate the prevalence of avian influenza virus infection in Vietnam, surveillance was conducted in domestic and wild birds from households, live-bird markets, slaughtering sites, and bird sanctuaries in Vietnam between October 2010 and October 2012. Of the 4,550 samples collected, 226 influenza A virus isolates were obtained from domestic ducks, muscovy ducks, and chickens. Of these, 25 and 22 H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from apparently healthy domestic ducks in live-bird markets and slaughtering sites in northern and southern Vietnam, respectively. The HA genes of H5 viruses isolated from birds in northern Vietnam phylogenetically belonged to the genetic clade 2.3.2.1 and those in southern Vietnam belonged to the genetic clade 1.1. In addition, 39 H3, 12 H4, 1 H5, 93 H6, 2 H7, 18 H9, 3 H10, and 11 H11 viruses were isolated. Phylogenetic and antigenic analyses of the H6 and H9 viruses revealed that they were closely related to the isolates obtained from domestic poultry in China. Phylogenetic analyses of internal gene segments of these isolates revealed that these viruses were circulating in both domestic and wild birds in Asia and reassortment events had occurred frequently. Therefore, it will be important to continue the surveillance and strict controls over the movement and trade of poultry and poultry products in order to eradicate H5N1 HPAIV from Asia.

Efficient and accurate homologous recombination in hESCs and hiPSCs using helper-dependent adenoviral vectors.

Low efficiencies of gene targeting via homologous recombination (HR) have limited basic research and applications using human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Here, we show highly and equally efficient gene knockout and knock-in at both transcriptionally active (HPRT1, KU80, LIG1, LIG3) and inactive (HB9) loci in these cells using high-capacity helper-dependent adenoviral vectors (HDAdVs). Without the necessity of introducing artificial DNA double-strand breaks, 7-81% of drug-resistant colonies were gene-targeted by accurate HR, which were not accompanied with additional ectopic integrations. Even at the motor neuron-specific HB9 locus, the enhanced green fluorescent protein (EGFP) gene was accurately knocked in in 23-57% of drug-resistant colonies. In these clones, induced differentiation into the HB9-positive motor neuron correlated with EGFP expression. Furthermore, HDAdV infection had no detectable adverse effects on the undifferentiated state and pluripotency of hESCs and hiPSCs. These results suggest that HDAdV is one of the best methods for efficient and accurate gene targeting in hESCs and hiPSCs and might be especially useful for therapeutic applications.