Characteristic endoscopic findings of gastrointestinal malignant lymphomas other than mucosa-associated lymphoid tissue lymphoma.

Background and study aims: The gastrointestinal (GI) tract is the most common site of extra-nodal involvement for non-Hodgkin's lymphoma (NHL). The features of GI NHLs remain unclear. The aim of this study was to clarify endoscopic characteristics of GI NHLs. Patients and methods: We retrospectively analyzed the morphological characteristics of 63 GI malignant lymphomas other than mucosa-associated lymphoid tissue lymphoma. Lesions were diagnosed between 2005 and 2020. Macroscopic findings were classified into five subtypes: superficial (S); protruding without ulcer (P); protruding with ulcer (PU); fungating (F); and multiple nodules (MN). Results: Thirty-one lesions in the stomach were classified as S type in 3 cases (9.6%), P type in 6 (19%), PU type in 13 (42%), and F type in 9 (29%). In the stomach, the ulcerated phenotype was more frequent for diffuse large B-cell lymphoma (DLBCL) (89.5%) than for other histological types (41.7%; P = 0.01). In the intestine, 23 tumors were classified as S type in 4 cases (17%), P type in 1 (4%), PU type in 6 (26%), F type in 1 (4%), and MN in 11 (48%). Eleven of the 14 cases (78.6%) of intestinal follicular lymphoma lesions showed MN type. In the colon, eight tumors were classified as S type in 2 cases (25%), P type in 2 (25%), PU type in 1 (13%), and F type in 3 (38%). Conclusion: We have clarified the endoscopic features of GI NHL using macroscopic classifications. The ulcerated phenotype was the most frequent endoscopic finding for DLBCL.

Direct evidence of electronic ferroelectricity in YbFe2O4 using neutron diffraction and nonlinear spectroscopy.

We report the first observation of room temperature spontaneous electric polarization in an electronic ferroelectric material, a YbFe2O4 single crystal. The observation was based on second harmonic generation (SHG), a nonlinear optical process. Tensor analysis of the SHG signal revealed that this material has a polar charge superstructure with Cm symmetry. This result settles the long-term discussion on the uncertainty about electronic ferroelectric properties, including the charge order structure. We present a complete picture of the polar charge ordering of this material via consistent results from two different characterization methods. The SHG signal shows the same temperature dependence as the superlattice signal observed in neutron diffraction experiments. These results prove ferroelectric coupling to electron ordering in YbFe2O4, which results in electronic ferroelectricity which is enabled by the real space ordering of iron cations with different valences. The existence of electronic ferroelectricity holds promise for future electronics technologies where devices run a thousand times faster than frequency of the present CPU (a few gigahertz) embedded in smartphones, etc.

Gender differences in self-perceived changes among Japanese workers with depression.

BACKGROUND: The number of patients living with depression continues to increase in Japan. The economic effects of depression include loss of productivity due to both absenteeism and presenteeism. Gender differences have been reported in prevalence, onset pathways and subjective symptoms of depression. AIMS: To understand how workers with major depressive disorder (MDD) perceive problems in the workplace and examine gender differences in their self-perceived levels of functioning at work, noticed during the initial stages of depression. METHODS: This is a cross-sectional study of Japanese workers with MDD. Participants' self-perceived changes in the level of functioning at work were surveyed after the diagnosis during the first visit. The relationship between gender and changes in the level of functioning at work as initially perceived by the participants themselves was analysed using the chi-square test, supplemented by a residual analysis. RESULTS: We administered the survey to 147 workers with MDD. In terms of gender differences in initial self-perceived changes in the level of functioning at work, the proportion of men reporting reduced work efficiency was significantly higher than that of women, while the proportion of women reporting deterioration in relationships with colleagues and superiors was significantly higher than that of men. CONCLUSIONS: The findings suggest that greater attention to reduced work efficiency by men and to deterioration in work relationships by women with MDD should be essential components of self-care. Managers need to pay attention to the level of functioning and provide adequate social support for employees.

Efficacy of a new blood pressure monitor (inflationary non-invasive blood pressure, iNIBP™): a randomised controlled study.

The inflationary non-invasive blood pressure monitor (iNIBP™) uses a new measurement method, whereby the cuff is slowly inflated whilst simultaneously sensing oscillations, to determine the diastolic blood pressure first and then the systolic pressure. It may measure blood pressure more quickly than the conventional non-invasive blood pressure monitor. We studied 66 patients undergoing general anaesthesia, comparing the time taken to measure the blood pressure between the two monitors at times when there were marked changes (increases or decreases by 30 mmHg or greater) in the systolic blood pressure. The median (IQR) [range]) time was significantly longer for the non-invasive blood pressure monitor (38.8 (31.5-44.7) [18.0-130.0] s) than for the iNIBP (14.6 (13.7-16.4) [11.5-35.5] s), p = 0.001, 95%CI for difference 22-25 s). We also studied 30 volunteers to evaluate the accuracy of the iNIBP, comparing it with the mercury sphygmomanometer. There was good agreement between the two monitors, with a mean difference of 0 (95% limit of agreement -12 to 11) mmHg for the systolic blood pressure. We also compared the degree of pain during cuff inflation between the automated non-invasive blood pressure and iNIBP monitors. Pain was significantly more for the non-invasive blood pressure monitor (22 of 30 volunteers had less pain with the iNIBP). We have shown that the iNIBP measured the blood pressure quicker than the conventional non-invasive blood pressure monitor and the speed of measurement was not significantly affected by marked changes in the blood pressure.

Rescue of Discarded Grafts for Liver Transplantation by Ex Vivo Subnormothermic and Normothermic Oxygenated Machine Perfusion: First Experience in Spain.

BACKGROUND: Ex vivo machine perfusion (MP) has been reported as a possibly method to rescue discarded organs. The main aim of this study was to report an initial experience in Spain using MP for the rescue of severely marginal discarded liver grafts, and to, secondarily, define markers of viability to test the potential applicability of these devices for the real increase in the organ donor pool. METHODS: The study began in January 2016. Discarded grafts were included in a research protocol that consisted of standard retrieval followed by 10 hours of cold ischemia. Next, either normothermic (NMP) or controlled subnormothermic (subNMP) rewarming was chosen randomly. Continuous measurements of portal-arterial pressure and resistance were screened. Lactate, pH, and bicarbonate were measured every 30 minutes. The perfusion period was 6 hours, after which the graft was discarded and evaluated as potentially usable, but never implanted. Biopsies of the donor and at 2, 4, and 6 hours after ex vivo MP were obtained. RESULTS: A total of 4 grafts were included in the protocol. The first 2 grafts were perfused by NMP and grafts 3 and 4 by subNMP. The second and third grafts showed a clear trend toward optimal recovery and may have been used. Lactate dropped to levels below 2.5 mmol/L with stable arterial and portal pressure and resistance. Clear biliary output started during MP. Biopsies showed an improvement of liver architecture with reduced inflammation at the end of the perfusion. CONCLUSION: This preliminary experience has demonstrated the potential of MP devices for the rescue of severely marginal liver grafts. Lactate and biliary output were useful for viability testing of the grafts. The utility of NMP or subNMP protocols requires further research.

A novel in vivo model for predicting myelotoxicity of chemotherapeutic agents using IL-3/GM-CSF transgenic humanized mice.

Evaluating myelotoxicity is essential for ensuring the safety of novel drugs before they are approved for clinical applications. Although in vivo prediction of the maximum tolerated doses (MTDs) of anticancer drugs is usually performed in rodents, the results are not always applicable to clinical treatment because drugs may have different effects in human and rodent cells. Previously, we generated a human IL-3 and GM-CSF transgenic humanized mouse (hu-IL-3/GM Tg), in which human granulocytes effectively differentiated after hematopoietic stem cell transplantation. In this study, we established a novel in vivo preclinical evaluation model for predicting human myelotoxicity of anticancer drugs using these hu-IL-3/GM Tg mice. The myelotoxicity was investigated by kinetic flow cytometry of human or murine granulocytes and by colony-forming unit granulocyte/macrophage (CFU-GM) assays. In both in vivo and in vitro analyses, topotecan was more myelotoxic to human than murine granulocytes. In contrast, oxaliplatin was more myelotoxic to murine granulocytes. The level of myelotoxicity of paclitaxel treatment was comparable between human and mouse cells. These results demonstrate that our humanized mouse model can simultaneously evaluate myelotoxicity against human and mouse cells in vivo, and provides an effective preclinical tool for predicting appropriate doses of anticancer agents for clinical treatment.

Control of the wetting properties of

To investigate whether it is possible to control the wetting of ^{4}He crystals on a wall in superfluid, the contact angles of ^{4}He crystals were measured on rough and smooth walls at very low temperatures. A rough wall was prepared in a simple manner in which a commercially available coating agent for car mirrors, which makes the glass surface superhydrophobic, was used to coat a glass plate. The contact angles of ^{4}He crystals were increased by approximately 10^{∘} on the rough wall coated with the agent. Therefore, the increase in the repellency of ^{4}He crystals in superfluid was demonstrated to be possible on a very rough surface. The enhancement of the contact angles and a scanning electron microscopy image of the coated surface both suggest that a Cassie-Baxter state of ^{4}He crystals was realized on the surface; the crystals did not have full contact with the wall, but entrapped superfluid was present beneath the crystals in the hollow parts of the rough wall.

Spin-dependent acoustic response in the nonunitary A1 and A2 phases of superfluid 3He under high magnetic fields.

The transverse acoustic impedance of superfluid ^{3}He was measured in the A1 and A2 phases up to 13 T to investigate the surface states in nonunitary superfluids. The temperature dependence of the impedance was much larger in the A1 phase than in the A2 phase. This nonsymmetric behavior indicates that momentum exchange with walls for spin-down surface states is quite different from that for spin-up surface states. The spin-dependent response might be a reflection of an essential feature of the nonunitary states where gap amplitudes depend on spin states. Weak-coupling theories ignore any spin-dependent processes and do not account for the nonsymmetric behavior.

Effect of cricoid pressure on placement of the I-gel™ : a randomised study.

We studied 40 adult patients to see if cricoid pressure affected placement of the I-gel(™). In a randomised crossover design, the i-gel was placed with and without cricoid pressure, and we compared the success rate of adequate ventilation through the i-gel, time to placement and the rate of optimal position of the device between the two circumstances. Cricoid pressure significantly decreased the success rate of adequate ventilation through the i-gel (40 vs 34 patients) (p = 0.041, 95% CI for difference 4-26%), and significantly decreased the rate of the optimal position (39 vs 17 patients) (p < 0.001). The time to achieve adequate ventilation was significantly longer (p < 0.001) with cricoid pressure than without (median difference 8 s; 95% CI for median difference 3-12 s). Cricoid pressure significantly decreases the success rate of ventilation through the i-gel, but the success rate of ventilation through the i-gel is reasonably high.

Porcine circovirus type 2 (PCV2) vaccination reduces PCV2 in a PCV2 and Salmonella enterica serovar Choleraesuis coinfection model.

We previously reported that prior porcine circovirus type 2 (PCV2) infection potentiates the severity of clinical signs, lung lesions, and fecal shedding and tissue dissemination of Salmonella enterica serovar Choleraesuis in infected pigs. Here, we evaluated whether PCV2 vaccination is effective in reducing fecal shedding and tissue dissemination of S. Choleraesuis and improving clinical signs associated with PCV2 and S. Choleraesuis infection in 15 Cesarean-derived, colostrum-deprived pigs randomly assigned to 3 groups (n=5/group). The vaccinated and co-infected (VAC-COINF) group received 2 ml of a commercial PCV2 vaccine at age 3 weeks. The VAC-COINF and co-infected (COINF) groups were inoculated intranasally with PCV2 and S. Choleraesuis at 5 and 7 weeks of age, respectively. The CONTROL group pigs received a similar volume of PBS for sham-vaccination and sham-inoculation. PCV2 vaccination clearly reduced PCV2 DNA load in the serum and postmortem tissue samples and decreased PCV2 antigen levels in tissue samples of the VAC-COINF group. After S. Choleraesuis infection, the incidence of several clinical signs increased in the VAC-COINF group compared to that in the COINF group. The microscopic lung lesions and weight gain, fecal shedding and tissue dissemination of S. Choleraesuis except in the spleen were not significantly different in the VAC-COINF and COINF groups. Thus, PCV2 vaccination reduced PCV2 in the S. Choleraesuis and PCV2 coinfection model and the effects on S. Choleraesuis were minimal.

Serum undercarboxylated osteocalcin level increases with 48 weeks of teriparatide treatment in pre-treated elderly rheumatoid arthritis patients who use anti-resorptive drugs.

AIM: The serum undercarboxylated osteocalcin (ucOC) level, a biochemical bone marker of vitamin K insufficiency, is often affected by anti-osteoporosis drugs. There have been no reports regarding the relationship between ucOC and teriparatide. SUBJECTS AND METHODS: We conducted a prospective observational study of 26 female rheumatoid arthritis (RA) patients. The patients were divided into 3 groups: those who underwent a direct switch from anti-resorptive drugs to teriparatide (12 cases), those who started teriparatide without pre-treatment (5 cases), and the control patients (9 cases). The median age (interquartile range) of the patients in each group was 75 (67-77), 82 (78-84), and 69 (62-80) yr, respectively. All patients, except controls, received 48-week treatments of teriparatide. We analyzed the median 48-week changes from baseline of the serum ucOC levels with the Steel-Dwass method. RESULTS: The median change from baseline in the direct switch group was higher than that in other groups (p<0.05). CONCLUSIONS: The serum ucOC levels increased with treatment of teriparatide in elderly RA patients, especially when the patients received pre-treatment.

Surface Andreev bound states of superfluid 3He and Majorana fermions.

Superfluid (3)He is an intensively investigated and well characterized p-wave superfluid. In the bulk Balian-Werthamer state, which is commonly called the (3)He B phase, the superfluid gap is opened isotropically but near a flat boundary such as a wall of a container it can harbor interesting quasi-particle states inside the gap. These states are called surface Andreev bound states, and have not been experimentally explored in detail. Transverse acoustic impedance measurement has revealed their existence and provided spectroscopic details of the dispersion of the bound states. Recent theoretical arguments claim that the surface Andreev bound states of the superfluid (3)He B phase can be recognized as the edge states of the topological superfluid and be regarded as a Majorana fermion, a fancy particle which has not been confirmed in elementary particle physics. In this review, we present up-to-date knowledge on the surface Andreev bound states of the (3)He B phase revealed by acoustic spectroscopy and the possible realization of a Majorana fermion, along with related studies on this topic.

Strong suppression of the Kosterlitz-Thouless transition in a 4He film under high pressure.

We have found that the surface specularity for 3He quasiparticle scattering is closely related to the superfluidity and the Kosterlitz-Thouless (KT) transition of 4He film adsorbed on the surface. The specularity is determined by measurements of the transverse acoustic impedance of bulk liquid 3He. The unique point of our system is that we can control the correlation among 4He atoms in the film by changing the pressure of the bulk 3He. The observed KT transition temperature is significantly suppressed by increasing the pressure, which suggests a strong correlation effect on KT transition.

Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels.

BACKGROUND: Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported. AIM: We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100). SUBJECTS AND METHODS: Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 ≤3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables. RESULTS: Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p<0.01), and between controls and the ALN group (p<0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p<0.01) and oral glucocorticoid dose (p<0.01), which were independent risk factors of lowering ucOC. CONCLUSIONS: Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients.

Porcine circovirus type 2 potentiates morbidity of Salmonella enterica serovar Choleraesuis in Cesarean-derived, colostrum-deprived pigs.

PROBLEM ADDRESSED: Porcine circovirus type 2 (PCV2) and Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) are two leading causes of economic loss in the swine industry. Although S. Choleraesuis infection occurs concurrently with PCV2-associated disease in many swine herds, the pathogenesis of concurrent infection with PCV2 and S. Choleraesuis remains largely undefined. OBJECTIVE: We investigated the interactions between PCV2 and S. Choleraesuis in 20 Cesarean-derived, colostrum-deprived (CDCD) pigs randomly assigned to 4 groups (n=5 per group). METHODS AND APPROACH: Pigs in the dual-infected and PCV2-infected groups were inoculated intranasally with PCV2 at 5 weeks of age, and pigs in the dual-infected and S. Choleraesuis-infected groups were inoculated intranasally with S. Choleraesuis at 7 weeks of age. Pigs in the control group served as uninfected controls. RESULTS: After S. Choleraesuis inoculation, severe clinical signs, reduction of weight gain, and severe microscopic lung lesions were observed in dual-infected pigs compared to those in other groups. In addition, the pigs in the dual-infected group shed significantly (P=0.002) higher quantities of S. Choleraesuis in feces 12 days after S. Choleraesuis inoculation, and S. Choleraesuis was recovered from more tissues in this group 14 days after S. Choleraesuis inoculation. CONCLUSIONS: These results indicate that prior PCV2 infection potentiates the severity of clinical signs, lung lesions, and fecal shedding and tissue dissemination of S. Choleraesuis in infected pigs. Therefore, dual infection of pigs with PCV2 and S. Choleraesuis may increase clinical effects of salmonellosis in the field.

Increases in discontinuous rib cartilage and fused carpal bone in rat fetuses exposed to the teratogens, busulfan, acetazolamide, vitamin A, and ketoconazole.

Skeletal changes induced by treatment of pregnant rats with four potent teratogens, busulfan, acetazolamide, vitamin A palmitate, and ketoconazole, were evaluated using Alizarin Red S and Alcian Blue double-staining to investigate the relationship between drug-induced skeletal malformations and cartilaginous changes in the fetuses. Pregnant rats (N = 8/group) were treated once or twice between gestation days (GDs) 10 to 13 with busulfan at doses of 3, 10, or 30 mg/kg; acetazolamide at 200, 400, or 800 mg/kg; vitamin A palmitate at 100,000, 300,000, or 1,000,000 IU/kg; or ketoconazole at doses of 10, 30, or 100 mg/kg. Uterine evaluations and fetal external and skeletal examinations were conducted on GD 20. Marked skeletal abnormalities in ribs and hand/forelimb bones such as absent/ short/bent ribs, fused rib cartilage, absent/fused forepaw phalanx, and misshapen carpal bones were induced at the mid- and high-doses of busulfan and acetazolamide and at the high-dose of vitamin A palmitate and ketoconazole. Increased incidences of discontinuous rib cartilage (DRC) and fused carpal bone (FCB) were observed from the low- or mid-dose in the busulfan and acetazolamide groups, and incidences of FCB were increased from the mid-dose in the vitamin A palmitate and ketoconazole groups. Therefore, DRC and FCB were detected at lower doses than those at which ribs and hand/forelimb malformations were observed in the four potent teratogens.

New anomaly in the transverse acoustic impedance of superfluid 3He-B with a wall coated by several layers of 4He.

We measured the transverse acoustic impedance of superfluid 3He-B with a wall coated by several layers of 4He. The coating is known to enhance the specularity in quasiparticle scattering by the wall. We found a new anomaly, a bump and a peak, in the temperature dependence of the transverse acoustic impedance. This agrees with a theoretical calculation using a partially specular wall boundary condition. The new anomaly is shown to arise from a change in the surface density of states by coating and the scattering of thermally occupied surface bound states to other states. The change is towards the density of states of Majorana cone in the specular limit.

A new formulation for orally disintegrating tablets using a suspension spray-coating method.

The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants.

Enhancement of superconducting transition temperature due to the strong antiferromagnetic spin fluctuations in the noncentrosymmetric heavy-fermion superconductor CeIrSi3: A 29Si NMR study under pressure.

We report a (29)Si NMR study on the pressure-induced superconductivity (SC) in an antiferromagnetic (AFM) heavy-fermion compound CeIrSi(3) without inversion symmetry. In the SC state at P = 2.7-2.8 GPa, the temperature (T) dependence of the nuclear-spin lattice relaxation rate 1/T(1) below T(c) exhibits a T(3) behavior without any coherence peak just below T(c), revealing the presence of line nodes in the SC gap. In the normal state, 1/T(1) follows a square root T-like behavior, suggesting that the SC emerges under the non-Fermi-liquid state dominated by AFM spin fluctuations enhanced around a quantum critical point. The reason why the maximum T(c) in CeIrSi(3) is relatively high among the Ce-based heavy-fermion superconductors may be the existence of the strong AFM spin fluctuations. We discuss the comparison with the other Ce-based heavy-fermion superconductors.