The relationship between socio-demographic factors, health status, treatment type, and employment outcome in patients with inflammatory bowel disease in Japan.

BACKGROUND: Inflammatory Bowel Disease (IBD) constitutes a huge burden for patients and studies show that IBD patients have difficulties remaining in employment. Because there is no data about the unemployment of IBD patients in Japan. METHODS: We surveyed a representative sample of 1068 Japanese IBD patients regarding their employment status. RESULTS: We found that the labor force participation rate is lower and unemployment higher for patients with IBD compared to the general population. Factors associated with unemployment in the IBD sample are older age, female gender, and the prevalence of depression. DISCUSSION: IBD constitutes a high burden for patients in Japan regarding employment outcome.

Retrospective evaluation of the effect of carotid artery stenosis on cerebral oxygen saturation during off-pump coronary artery bypasses grafting in adult patients.

BACKGROUND: It is unknown whether cerebral oxygenation in patients with carotid artery stenosis (CAS) undergoing off-pump coronary artery bypass grafting (CABG) differs from that in patients without CAS. Thus, the effect of the presence of CAS ≥ 50 % on cerebral oxygenation during off-pump CABG in adult patients was evaluated retrospectively. METHODS: Eleven patients with CAS ≥ 50% and 14 patients without CAS ≥ 50% were enrolled. Regional cerebral tissue oxygen saturation (rSO2) was quantified using near-infrared spectroscopy. Mean arterial pressure, cardiac index, central venous pressure (CVP), and rSO2 at specific points were collected, and significant changes in each parameter were detected using repeated analysis of variance. Mean rSO2 and minimum rSO2 during anastomosis were analyzed by one-way analysis of variance. Multiple logistic regression analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI) for cerebral desaturation (a decrease in rSO2 ≥ 10% from preoperative value). RESULTS: Two patients with CAS ≥ 50% who received complete carotid artery stenting preoperatively were excluded from the analyses. In both patients with and without CAS, a decrease in rSO2 and cardiac index and an increase in CVP were observed during anastomosis. Mean (SD) maximum decrease in rSO2 from preoperative value was 9.2 (12.7) % on the left side and 8.1 (11.7) % on the right side in patients with CAS ≥ 50%, and 13.5 (11.3) % on the left side and 16.1 (9.8) % on the right side in patients without CAS ≥ 50% (p = 0.316). Neurological complications were not identified in both patients with and without CAS ≥ 50%. In multiple logistic regression analysis, CAS ≥ 50% was not associated with an increased risk of cerebral desaturation (OR 0.160, 95% CI 0.036-0.707, p = 0.016), and rSO2 decreased with decreasing cardiac index < 2.0 l/min/m(2) (OR 3.287, 95 % CI 2.218-5.076, p < 0.001). CONCLUSIONS: CAS ≥ 50% was not an independent risk factor of cerebral desaturation during off-pump CABG. Our results suggest that maintaining cardiac output can prevent a decrease in cerebral oxygenation in both patients with and without CAS ≥ 50%.

Hypoxic condition promotes differentiation and mineralization of dental pulp cells in vivo.

AIM: To investigate the behaviour of dental pulp cells under hypoxic conditions in vivo using an experimental animal model. METHODOLOGY: A mini-screw was inserted into the inferior dental nerve canal of rats to arrest the blood supply, which resulted in a reduced oxygen level in the dental pulps of molar teeth used for the experimental group. The decrease in blood supply was evaluated by injected India ink in transparent specimens. The hypoxia marker hypoxyprobe-1 was investigated by immunohistochemical staining. The mRNA expressions of ATP-binding cassette transporter (ABC) G2 (ABCG2) which is a marker for the capacity to excrete metabolites and for stem-like cells as well as dentine sialophosphoprotein (DSPP) and osteocalcin (OCN) which are markers for mineralization were evaluated by RT-PCR. Protein was evaluated by immunohistochemical staining using ABCG2, dentine sialoprotein (DSP) and OCN. RESULTS: The evaluation of India ink indicated a decreased blood supply in the transparent specimens, and hypoxyprobe-1 immunohistochemical staining showed positive expression. ABCG2, DSPP and OCN mRNA expressions increased at 7 and 14 days. Immunohistochemically, ABCG2, DSP and OCN-positive cells were localized in the odontoblastic layer. CONCLUSIONS: Hypoxic conditions promoted mineralization and differentiation of dental pulp cells of the odontoblastic layer.

Perfusion index derived from a pulse oximeter can predict the incidence of hypotension during spinal anaesthesia for Caesarean delivery.

BACKGROUND: Hypotension during spinal anaesthesia for Caesarean delivery is a result of decreased vascular resistance due to sympathetic blockade and decreased cardiac output due to blood pooling in blocked areas of the body. Change in baseline peripheral vascular tone due to pregnancy may affect the degree of such hypotension. The perfusion index (PI) derived from a pulse oximeter has been used for assessing peripheral perfusion dynamics due to changes in peripheral vascular tone. The aim of this study was to examine whether baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery. METHODS: Parturients undergoing elective Caesarean delivery under spinal anaesthesia with hyperbaric bupivacaine 10 mg and fentanyl 20 µg were enrolled in this prospective study. The correlation between baseline PI and the degree of hypotension during spinal anaesthesia and also the predictability of spinal anaesthesia-induced hypotension during Caesarean delivery by PI were investigated. RESULTS: Baseline PI correlated with the degree of decreases in systolic and mean arterial pressure (r=0.664, P<0.0001 and r=0.491, P=0.0029, respectively). The cut-off PI value of 3.5 identified parturients at risk for spinal anaesthesia-induced hypotension with a sensitivity of 81% and a specificity of 86% (P<0.001). The change of PI in parturients with baseline PI ≤ 3.5 was not significant during the observational period, while PI in parturients with baseline PI>3.5 demonstrated marked decreases after spinal injection. CONCLUSIONS: We demonstrated that higher baseline PI was associated with profound hypotension and that baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery.

Tenascin-C promotes differentiation of rat dental pulp cells in vitro.

AIM: To investigate the effects of tenascin-C (TN-C) on cultured rat dental pulp cells in relation to the expression of Notch signalling. METHODOLOGY: Subcultured dental pulp cells derived from rat incisors were seeded both in wells and on plastic coverslips coated with various concentrations of recombinant human TN-C. Expression of bone-related mRNA was then analysed by RT-PCR and observed by immunohistochemical staining. Encoding of Notch1 and Notch2 (markers of initial differentiation of odontoblast-like cells), alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN) (markers of mineralization) was investigated. Non-TN-C-coated wells were used as controls. Primary antibodies to Notch1, ALP and OCN were used for immunofluorescence staining, and ALP activity was evaluated. Data were compared using Student's t-test. RESULTS: Cell proliferation rate in the experimental groups was significantly higher (P < 0.05) than that in the control group at 72 h. Expression of Notch1, Notch2, ALP, OPN and OCN mRNAs was significantly higher (P < 0.05) in the experimental group than that in the control group. Strongly positive staining for Notch1, ALP and OCN was observed in the experimental group. ALP activity was significantly higher (P < 0.01) in the experimental group than in the control group at 24 h. CONCLUSION: TN-C promoted differentiation of rat dental pulp cells by the activation of Notch.

Search for the Θ+ pentaquark via the π(-)p→K(-)X reaction at 1.92 GeV/c.

The Θ(+) pentaquark baryon was searched for via the π(-)p→K(-)X reaction with a missing mass resolution of 1.4 MeV/c(2) (FWHM) at the Japan Proton Accelerator Research Complex (J-PARC). π(-) meson beams were incident on the liquid hydrogen target with a beam momentum of 1.92 GeV/c. No peak structure corresponding to the Θ(+) mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2° to 15° in the laboratory frame is obtained to be 0.26 µb/sr in the mass region of 1.51-1.55 GeV/c(2). The upper limit of the Θ(+) decay width is obtained to be 0.72 and 3.1 MeV for J(Θ)(P)=1/2(+) and J(Θ)(P)=1/2(-), respectively, using the effective Lagrangian approach.

Massive macroglossia developing fast and immediately after endotracheal extubation.

We report an unusual case of massive macroglossia that developed very rapidly after neurosurgery in the park bench position with neck flexion. A few minutes after endotracheal extubation, massive macroglossia was noticed with marked protrusion of the tongue from the oral cavity. The patient's hospital stay was prolonged due to difficulty in speaking and eating. Macroglossia is a rare complication; however, it may cause life-threatening airway obstruction. It is important to be prepared for managing post-operative macroglossia and keep in mind that it may develop rapidly, especially after prolonged surgery performed with sustained neck flexion. The patient should be informed of the risk of macroglossia and the associated problems prior to the operation.

Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages.

Interleukin (IL)-12 is a key factor that induces T helper cell type 1-mediated immunity and inflammatory diseases. In some colitis models, such as IL-10 knock-out (KO) mice, IL-12 triggers intestinal inflammation. An abundant amount of IL-12 is produced by intestinal macrophages in response to stimulation by commensal bacteria in IL-10 KO mice. Intact bacteria are more potent inducers of macrophage IL-12 production than cell surface components in this model. This suggested that cell surface receptor signalling and intracellular pathogen recognition mechanisms are important for the induction of IL-12. We addressed the importance of intracellular recognition mechanisms and demonstrated that signal transducers and activator of transcription 1 (STAT1) signalling activated bacterial phagocytosis and was involved in the induction of abnormal IL-12 production. In IL-10 KO mouse bone marrow-derived (BM) macrophages, Escherichia coli stimulation induced increased IL-12p70 production compared to lipopolysaccharide combined with interferon (IFN)-γ treatment. Significant repression of IL-12 production was achieved by inhibition of phagocytosis with cytochalasin D, and inhibition of de novo protein synthesis with cycloheximide. Induction of IFN regulatory factors-1 and -8, downstream molecules of STAT1 and the key transcription factors for IK-12 transcription, following E. coli stimulation, were mediated by phagocytosis. Interestingly, STAT1 was activated after stimulation with E. coli in IL-10 KO BM macrophages, although IFN-γ could not be detected. These data suggest that molecules other than IFN-γ are involved in hyper-production mechanisms of IL-12 induced by E. coli stimulation. In conclusion, enteric bacteria stimulate excessive IL-12p70 production in IL-10 KO BM macrophages via phagocytosis-dependent signalling.

Antibody-like proteins that capture and neutralize SARS-CoV-2.

To combat severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and any unknown emerging pathogens in the future, the development of a rapid and effective method to generate high-affinity antibodies or antibody-like proteins is of critical importance. We here report high-speed in vitro selection of multiple high-affinity antibody-like proteins against various targets including the SARS-CoV-2 spike protein. The sequences of monobodies against the SARS-CoV-2 spike protein were successfully procured within only 4 days. Furthermore, the obtained monobody efficiently captured SARS-CoV-2 particles from the nasal swab samples of patients and exhibited a high neutralizing activity against SARS-CoV-2 infection (half-maximal inhibitory concentration, 0.5 nanomolar). High-speed in vitro selection of antibody-like proteins is a promising method for rapid development of a detection method for, and of a neutralizing protein against, a virus responsible for an ongoing, and possibly a future, pandemic.

Different sensitivity to wortmannin of two vacuolar sorting signals indicates the presence of distinct sorting machineries in tobacco cells.

Vacuolar matrix proteins in plant cells are sorted from the secretory pathway to the vacuoles at the Golgi apparatus. Previously, we reported that the NH2-terminal propeptide (NTPP) of the sporamin precursor and the COOH-terminal propeptide (CTPP) of the barley lectin precursor contain information for vacuolar sorting. To analyze whether these propeptides are interchangeable, we expressed constructs consisting of wild-type or mutated NTPP with the mature part of barley lectin and sporamin with CTPP and mutated NTPP in tobacco BY-2 cells. The vacuolar localization of these constructs indicated that the signals were interchangeable. We next analyzed the effect of wortmannin, a specific inhibitor of mammalian phosphatidylinositol (PI) 3-kinase on vacuolar delivery by NTPP and CTPP in tobacco cells. Pulse-chase analysis indicated that 33 microM wortmannin caused almost complete inhibition of CTPP-mediated transport to the vacuoles, while NTPP-mediated transport displayed almost no sensitivity to wortmannin at this concentration. This indicates that there are at least two different mechanisms for vacuolar sorting in tobacco cells, and the CTPP-mediated pathway is sensitive to wortmannin. We compared the dose dependencies of wortmannin on the inhibition of CTPP-mediated vacuolar delivery of proteins and on the inhibition of the synthesis of phospholipids in tobacco cells. Wortmannin inhibited PI 3- and PI 4-kinase activities and phospholipid synthesis. Missorting caused by wortmannin displays a dose dependency that is similar to the dose dependency for the inhibition of synthesis of PI 4-phosphate and major phospholipids. This is different, however, than the inhibition of synthesis of PI 3-phosphate. Thus, the synthesis of phospholipids could be involved in CTPP-mediated vacuolar transport.

The plant vacuolar sorting receptor AtELP is involved in transport of NH(2)-terminal propeptide-containing vacuolar proteins in Arabidopsis thaliana.

Many soluble plant vacuolar proteins are sorted away from secreted proteins into small vesicles at the trans-Golgi network by transmembrane cargo receptors. Cleavable vacuolar sorting signals include the NH(2)-terminal propeptide (NTPP) present in sweet potato sporamin (Spo) and the COOH-terminal propeptide (CTPP) present in barley lectin (BL). These two proteins have been found to be transported by different mechanisms to the vacuole. We examined the ability of the vacuolar cargo receptor AtELP to interact with the sorting signals of heterologous and endogenous plant vacuolar proteins in mediating vacuolar transport in Arabidopsis thaliana. AtELP extracted from microsomes was found to interact with the NTPPs of barley aleurain and Spo, but not with the CTPPs of BL or tobacco chitinase, in a pH-dependent and sequence-specific manner. In addition, EM studies revealed the colocalization of AtELP with NTPP-Spo at the Golgi apparatus, but not with BL-CTPP in roots of transgenic Arabidopsis plants. Further, we found that AtELP interacts in a similar manner with the NTPP of the endogenous vacuolar protein AtALEU (Arabidopsis thaliana Aleu), a protein highly homologous to barley aleurain. We hypothesize that AtELP functions as a vacuolar sorting receptor involved in the targeting of NTPP-, but not CTPP-containing proteins in Arabidopsis.

Density profile measurement with a heavy ion beam probe in a toroidal plasma of the compact helical system.

A possibility of electron density measurements with heavy ion beam probes (HIBPs) has been demonstrated, along with their capability to measure the potential and magnetic field. A method has been proposed to reconstruct the electron density profile [A. Fujisawa et al., Rev. Sci. Instrum. 74, 3335 (2003)]. In the method, the profile of secondary beam currents is converted into a local density profile by taking into account local brightness and so-called path integral effects which mean the effect of beam attenuation along the beam orbit. Here the article presents the HIBP measurement of the electron density profile after the proposed method was first applied on the real experimental data of compact helical system plasmas. In the real application, the hollow density and the peaked profiles are successfully obtained with sufficiently high temporal resolution (a few ms), in accordance with the electron density profile measured with Thomson scattering for electron cyclotron resonance heating and neutral beam injection plasmas.

Anomalously high geothermal flux near the South Pole.

Melting at the base of the Antarctic Ice Sheet influences ice dynamics and our ability to recover ancient climatic records from deep ice cores. Basal melt rates are affected by geothermal flux, one of the least constrained properties of the Antarctic continent. Estimates of Antarctic geothermal flux are typically regional in nature, derived from geological, magnetic or seismic data, or from sparse point measurements at ice core sites. We analyse ice-penetrating radar data upstream of South Pole revealing a ~100 km long and 50 km wide area where internal ice sheet layers converge with the bed. Ice sheet modelling shows that this englacial layer configuration requires basal melting of up to 6 ± 1 mm a-1 and a geothermal flux of 120 ± 20 mW m-2, more than double the values expected for this cratonic sector of East Antarctica. We suggest high heat producing Precambrian basement rocks and hydrothermal circulation along a major fault system cause this anomaly. We conclude that local geothermal flux anomalies could be more widespread in East Antarctica. Assessing their influence on subglacial hydrology and ice sheet dynamics requires new detailed geophysical observations, especially in candidate areas for deep ice core drilling and at the onset of major ice streams.

A Vacuolar-Type H+-ATPase in a Nonvacuolar Organelle Is Required for the Sorting of Soluble Vacuolar Protein Precursors in Tobacco Cells.

In plant cells, vacuolar matrix proteins are separated from the secretory proteins at the Golgi complex for transport to the vacuoles. To investigate the involvement of vacuolar-type ATPase (V-ATPase) in the vacuolar targeting of soluble proteins, we analyzed the effects of bafilomycin A1 and concanamycin A on the transport of vacuolar protein precursors in tobacco cells. Low concentrations of these inhibitors caused the missorting of several vacuolar protein precursors; sorting was more sensitive to concanamycin A than to bafilomycin A1. Secretion of soluble proteins from tobacco cells was also inhibited by bafilomycin A1 and concanamycin A. We next analyzed the subcellular localization of V-ATPase. V-ATPase was found in a wide variety of endomembrane organelles. Both ATPase activity and ATP-dependent proton-pumping activity in the Golgi-enriched fraction were more sensitive to concanamycin A than to bafilomycin A1, whereas these activities in the tonoplast fraction were almost equally sensitive to both reagents. Our observations indicate that the V-ATPase in the organelle that was recovered in the Golgi-enriched fraction is required for the transport of vacuolar protein precursors and that this V-ATPase is distinguishable from the tonoplast-associated V-ATPase.

Using Photoconvertible and Extractable Fluorescent Proteins to Study Autophagy in Plants.

Several methodologies have been employed to understand the kinetics of induced autophagic degradation in plants, but most of them are not capable of distinguishing the autophagic cargo proteins before and after induction of autophagy in cells. Here, we designed a mass photoconverter that allowed us to simultaneously monitor protein synthesis and degradation in tobacco BY-2 cells using a photoconvertible fluorescence marker protein, Kikume Green Red (KikGR). An example of a new protocol for the analysis of autophagy progression using a fusion protein of cytochrome b5 and KikGR under phosphate starvation is described. The other example described is the analysis of the proliferation of Golgi apparatus in tobacco BY-2 cells using the fusion protein of a prolyl 4-hydroxylase NtP4H1.1 and monomeric KikGR. A detailed protocol on key analysis, as well as tips and notes for experiments using KikGR proteins, are described.

Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line.

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers' size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.

Protein transport within the plant cell endomembrane system: an update.

The secretory pathway plays a central role in plant development and morphogenesis. Storage protein deposition, plant cell division and the expansion of the plasma membrane and extracellular matrix all require the synthesis and trafficking of membranes, proteins and polysaccharides through this network of organelles. Increasing evidence demonstrates that the plant secretory pathway is more complex than previously appreciated and that its formation and maintenance are guided/regulated by many different mechanisms.

[Solid variant of aneurysmal bone cyst; report of a case].

We report a rare case of a solid variant of aneurysmal bone cyst (ABC) of the right 4th rib. A 29-year-old woman was admitted to our hospital for an abnormal shadow on chest X-ray. Chest computed tomography (CT) demonstrated the lesion mass to be located in the area of the right 4th rib. Bone scintigram revealed a hot spot in the right 4th rib. The right 4th rib was resected en bloc with the parietal pleura, and adjacent intercostal muscles via right anterior thoracotomy. Postoperative pathological evaluation was consistent with a solid variant of ABC.