Determination of Lycopene Concentration in Fresh Tomatoes by Spectrophotometry: A Collaborative Study.

BACKGROUND: Lycopene has been the object of considerable research attention recently, and the effects of the intake of lycopene, or of tomato products, have been studied in various ways. In Japan, interest in the health-promoting function of food components has increased. OBJECTIVE: Developing a method to determine lycopene contents in tomato that meets the Japanese Agricultural Standard (JAS). METHOD: In the proposed JAS method, the test sample consists of fresh tomatoes; a hexane-acetone mixture is utilized as the extraction solvent. A collaborative study was conducted to evaluate the interlaboratory performance of the method. RESULTS: Ten laboratories participated and analyzed six test materials characterized by a lycopene content between 39 and 170 mg/kg as blind duplicates. After removing statistical outliers, RSDr ranged from 1.2 to 3.0% and RSDR ranged from 2.4 to 4.2%. The HorRat values were calculated and found to be in the 0.26-0.49 range. CONCLUSIONS: The method for determining the lycopene content in tomato was evaluated by means of a collaborative study, and the reproducibility of this method was found to be acceptable. HIGHLIGHTS: Intended for standardization in Japan, a method to determine lycopene content in tomato has been developed and shown to have acceptable precision in a collaborative study.

Over-expression of Caj1, a plasma membrane associated J-domain protein in Saccharomyces cerevisiae, stabilizes amino acid permeases.

Hsp70: J-domain protein (JDP) machines, along with the cellular protein degradation systems play a central role in regulating cellular proteostasis. An equally robust surveillance system operates at the plasma membrane too that affects proper sorting, stability as well as the turnover of membrane proteins. Although plausible, a definitive role of the Hsp70: JDP machine in regulating the stability of plasma membrane proteins is not well understood in Saccharomyces cerevisiae. Here we show that a moderate over-expression of Caj1, one of the thirteen JDPs residing in the nucleo-cytosolic compartment of S. cerevisiae reduced the cold sensitivity of tryptophan auxotrophic yeast cells by stabilizing tryptophan permeases, Tat1 and Tat2 in a J-domain dependent manner. Concomitantly, higher Caj1 levels also caused slow growth and increased plasma membrane damage at elevated temperatures possibly due to the stabilization of thermolabile plasma membrane proteins. Finally, we show that although majorly cytosolic, Caj1 also co-localizes with the membrane dye FM4-64 at the cellular periphery suggesting that Caj1 might interact with the plasma membrane. Based on the results presented in this study, we implicate the Hsp70: Caj1 chaperone machine in regulating the stability or turnover of plasma membrane proteins in budding yeast.

North Atlantic climate far more predictable than models imply.

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change1-3. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain4. This leads to low confidence in regional projections, especially for precipitation, over the coming decades5,6. The chaotic nature of the climate system7-9 may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models10, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.

Utility of synthetic MRI in predicting the Ki-67 status of oestrogen receptor-positive breast cancer: a feasibility study.

AIM: To evaluate the utility of synthetic magnetic resonance imaging (MRI) of the breast in predicting the Ki-67 status in patients with oestrogen receptor (ER)-positive breast cancer. MATERIALS AND METHODS: Forty-nine patients with 50 histopathologically proven breast cancers who underwent additional synthetic MRI were enrolled in the present study. Using synthetic MRI images, T1 and T2 relaxation times and their standard deviations (SD) in the breast lesions before (T1-Pre, T2-Pre, PD-Pre, SD of T1-Pre, SD of T2-Pre, SD of PD-Pre) and after (T1-Gd, T2-Gd, PD-Gd, SD of T1-Gd, SD of T2-Gd, SD of PD-Gd) contrast agent injection were obtained. These quantitative values were compared between the low Ki-67 expression (<14%) lesions (low-proliferation group: n=23) and high Ki-67 expression (≥14%) lesions (high-proliferation group: n=27). RESULTS: The univariate analysis showed that the SD of T1-Gd (p<0.001) and T2-Gd (p=0.042) were significantly higher in the high-proliferation group than in the low-proliferation group. Multivariate analysis further showed that the SD of T1-Gd was a significant and independent predictor of Ki-67 expression, with an area under the receiver operating characteristic (AUROC) curve of 0.885. The sensitivity, specificity, and accuracy of the SD of T1-Gd with an optimal cut-off value of 98.5 were 77.8%, 87%, and 82%, respectively. CONCLUSION: The SD of T1-Gd obtained from synthetic MRI was useful to predict Ki-67 status.

Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Effect of augmented datasets on deep convolutional neural networks applied to chest radiographs.

AIM: To evaluate the effect of augmented training datasets in a deep convolutional neural network (DCNN) used for detecting abnormal chest radiographs. MATERIALS AND METHODS: Chest radiographs were corrected to conform to a DCNN dataset, with 288 abnormal and 447 normal radiographs. The radiographic images were divided into training and validation sets (441, 60%), and a test set (294, 40%). The training and validation sets were augmented to generate a total of 12,789 training and validation images. The augmentation consisted of operations such as rotation, horizontal and vertical flipping, Gaussian blur, and brightness variation, either alone or combined. The DCNN performed binary classification of the images as being abnormal or normal chest radiographs, and accuracy was used as measure to assess the model performance. RESULTS: The accuracy of the DCNN trained with the augmented dataset tended to be higher than that of the DCNN trained with the non-augmented dataset. The augmented datasets combining rotation and horizontal flipping had a high accuracy of 0.91, showing the highest accuracy among the applied augmentation techniques and combinations. CONCLUSION: Augmentation of training datasets can improve the performance of DCNN for radiographic image classification depending on the applied augmentation technique.

Itching in a trichophytin contact dermatitis mouse model and the antipruritic effect of antifungal agents.

BACKGROUND: Tinea is an infectious disease by dermatophytes, of which Trichophyton species accounts for the overwhelming majority of case. Tinea often causes itching with inflammation. In terms of pruritus by fungal infection, however, tinea has not been investigated sufficiently to date. AIM: To evaluate itch caused by Trichophyton infection and the effect of antifungal agents on the infection, by measuring scratch behaviour and profiles of inflammatory cytokines and chemokines. METHODS: We used a previously established mouse model of contact hypersensitivity induced by trichophytin, a crude extract from Trichophyton mentagrophytes. Scratching behaviour was recorded using a counting device that measured an electric current induced in a coil by movement of magnets that had been inserted into the hind paws of each animal. We investigated expression of various genes in lesional skin of mice and in normal human epidermal keratinocytes. We also investigated the antipruritic effects of the corticosteroid dexamethasone (DEX) and three antifungal agents: ketoconazole (KCZ), terbinafine (TBF) and liranaftate (LNF). RESULTS: Biphasic peaks of scratching were observed at 1 h and at 6-7 h during an observation period of 14 h after trichophytin induction. For lesional skin, RNA was extracted 24 h after trichophytin challenge, and increased expression was seen in the genes for interleukin (IL)-17A, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-2 and Dectin-1, whereas there was no obvious change in the genes for IL-31 and prostaglandin (PG)E2. Furthermore, KCZ inhibited histidine decarboxylase (HDC) expression in vitro and in vivo, and inhibited scratching in the very early phase. LNF inhibited expression of thymic stromal lymphopoietin (TSLP) and IL-8 in vitro, and TSLP, TNF-α, IL-1α and MIP2 in vivo, and also scratching in the early phase. TBF did not induce any significant alterations in either gene expression or scratching. DEX suppressed expression of all the chemical mediators except HDC in vitro and in vivo, and inhibited scratching. CONCLUSION: Antifungals can inhibit itching induced by fungal infection through different mechanisms.

A Longer History of Hemodialysis Can Lead to Sarcopenia in Renal Transplantation Patients.

BACKGROUND: Sarcopenia is a condition in which the amount of skeletal muscle decreases. Recent studies have suggested that sarcopenia is a risk factor for the incidence of postoperative complications, longer hospitalization, and a poorer prognosis. In this study, we examined the impact of sarcopenia in association with a history of hemodialysis in renal transplantation patients. METHODS: A total of 157 patients who underwent renal transplantation at Yokohama City University Medical Center (Yokohama, Japan) from 2005 to 2016 were analyzed in this study. We determined the presence of sarcopenia using the psoas muscle index (PMI). The PMI was calculated based on the left psoas muscle area of L3 (mm2) divided by the square of the body height (m2). RESULTS: The mean/median length of time that the patients received hemodialysis was 2059/850 days. The PMI in men was significantly higher than that in women (321.9 ± 10.0 vs 226.6 ± 17.3, P < .001). The group with a longer history of hemodialysis (≥851 days) showed a significantly lower PMI than the short-history group (≤850 days) (355.8 ± 15.1 vs 289.7 ± 11.3, P = .001). The PMI showed a negative correlation according to the dialysis period and a positive correlation according to the sex and triglyceride levels. CONCLUSIONS: A longer history of hemodialysis was shown to be associated with a lower PMI in renal transplantation patients. In addition, the higher PMI group showed higher serum triglyceride levels than the lower PMI group.

Long-term Survival in a Kidney Transplantation Patient With Progressive Multifocal Leukoencephalopathy: A Case Report.

Post-kidney transplantation progressive multifocal leukoencephalopathy (PML) is a rare disease on which there are very few published reports on record. PML is a demyelinating disease caused by a destructive infection of the oligodendrocytes by the JC polyomavirus. No effective therapeutic protocol has been established other than measures to revive the immune function by reducing or discontinuing the administration of immunosuppressive agents. Most cases are progressive and show a poor prognosis. We herein report a case in which renal function has been maintained for 2 years following the onset of PML, which was initially diagnosed 3 years after kidney transplantation.

Diagnostic capability of feature-tracking cardiovascular magnetic resonance to detect infarcted segments: a comparison with tagged magnetic resonance and wall thickening analysis.

AIM: To examine the diagnostic capabilities of feature-tracking cardiovascular magnetic resonance (FT-CMR), tagged cine magnetic resonance (MR), and wall thickening (WT) analyses to detect infarcted segments in patients with established myocardial infarction (MI). MATERIALS AND METHODS: Twenty patients with established MI were selected retrospectively and the peak endocardial circumferential strain (CS) was quantified based on the 16-segment model. According to CMR with late gadolinium enhancement, segments were categorised as transmural MI, subendocardial MI, and no MI. RESULTS: A total of 320 segments (62 transmural MI, 50 subendocardial MI, and 208 no MI) were analysed. Peak endocardial CS was significantly lower for transmural MI compared with subendocardial MI (p<0.05) and no MI (p<0.001). Cut-off values of -11.2% for CS by FTCMR, -10.9% for CS by tagged MR, and 23.8% for %WT, differentiated between infarcted and non-infarcted segments with a sensitivity of 72%, 71%, and 56%; specificity of 71%, 75%, and 67%; accuracy of 72%, 73%, and 63%; positive predictive value of 57%, 60%, and 48%; negative predictive value of 83%, 83%, and 74%; and an area-under-the-curve of 0.77, 0.79, and 0.64, respectively. CONCLUSIONS: FT-CMR was diagnostically superior to %WT, and could differentiate between subendocardial and transmural MI. Unlike tagged MR, FT-CMR did not require the acquisition of additional sequences.

FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.

AIM: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children. METHODS: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined. RESULTS: The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]. CONCLUSIONS: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children.

Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21.

AIMS: The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. METHODS: We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. RESULTS: Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. CONCLUSIONS: The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood.

Effective Treatment With Everolimus for Recurrent Granulomatous Interstitial Nephritis in a Renal Transplant Recipient: A Case Report.

BACKGROUND: Granulomatous interstitial nephritis (GIN) is a rare renal disease, and its etiology remains unknown. We report recurrent GIN in renal allograft successfully treated with everolimus (EVR). CASE REPORT: A 22-year-old man with GIN received a kidney from his mother. On follow-up 8 months later, his serum creatinine level was increased, from 1.3 mg/dL to 1.7 mg/dL, and he had microhematuria and proteinuria. A protocol graft biopsy at 1 year after transplantation showed epithelioid granuloma with multinucleated giant cells. He received steroid pulse therapy for recurrent GIN twice, but he developed allograft dysfunction, hematuria, and proteinuria. EVR was started in combination with maintenance immunosuppressants at 28 months after transplantation. Thereafter, the serum creatinine level decreased, from 2.1 mg/dL to 1.6 mg/dL, and microhematuria and proteinuria were stable despite reduction of steroid dose. CONCLUSIONS: Maintenance immunosuppressive therapy combined with EVR may be effective for the recurrence of idiopathic GIN in renal allograft.

Subcycle Optical Response Caused by a Terahertz Dressed State with Phase-Locked Wave Functions.

The coherent interaction of light with matter imprints the phase information of the light field on the wave function of the photon-dressed electronic state. A driving electric field, together with a stable phase that is associated with the optical probe pulses, enables the role of the dressed state in the optical response to be investigated. We observed optical absorption strengths modulated on a subcycle time scale in a GaAs quantum well in the presence of a multicycle terahertz driving pulse using a near-infrared probe pulse. The measurements were in good agreement with the analytical formula that accounts for the optical susceptibilities caused by the dressed state of the excitons, which indicates that the output probe intensity was coherently reshaped by the excitonic sideband emissions.

Terahertz-induced optical emission of photoexcited undoped GaAs quantum wells.

Intense terahertz (THz) pulse induces photoluminescence (PL) flash from undoped high-quality GaAs/AlGaAs quantum wells under continuous wave laser excitation. The number of excitons increases 10,000-fold from that of the steady state under only laser excitation. The THz electric field dependence and the relaxation dynamics of the PL flash intensity suggest that the strong electric field of the THz pulse ionizes impurity states during the 1 ps period of the THz pulse and release carriers from a giant reservoir containing impurity states in the AlGaAs layers.

Initialized near-term regional climate change prediction.

Climate models are seen by many to be unverifiable. However, near-term climate predictions up to 10 years into the future carried out recently with these models can be rigorously verified against observations. Near-term climate prediction is a new information tool for the climate adaptation and service communities, which often make decisions on near-term time scales, and for which the most basic information is unfortunately very scarce. The Fifth Coupled Model Intercomparison Project set of co-ordinated climate-model experiments includes a set of near-term predictions in which several modelling groups participated and whose forecast quality we illustrate here. We show that climate forecast systems have skill in predicting the Earth's temperature at regional scales over the past 50 years and illustrate the trustworthiness of their predictions. Most of the skill can be attributed to changes in atmospheric composition, but also partly to the initialization of the predictions.

Multi-system progressive angiomatosis in a dog resembling blue rubber bleb nevus syndrome in humans.

A six-year-old, neutered, female golden retriever was presented with generalised, dark purple to black cutaneous nodules and gastrointestinal haemorrhage. Histopathologically, all cutaneous nodules were diagnosed as benign cavernous haemangiomas. Endoscopic analysis revealed similar nodules in the oesophagus, stomach and duodenum. At laparotomy, similar nodules were seen on the visceral peritoneal lining of abdominal organs. Metastatic haemangiosarcoma was ruled out based on histological features and lack of primary tumour in spleen, liver or heart ultrasonographically. Blood loss associated with gastrointestinal haemorrhage was managed with blood transfusion. To the authors' knowledge, this is the first canine case of multi-system progressive angiomatosis resembling blue rubber bleb nevus syndrome in humans.

Quick-scanning x-ray absorption spectroscopy system with a servo-motor-driven channel-cut monochromator with a temporal resolution of 10 ms.

We have developed a quick-scanning x-ray absorption fine structure (QXAFS) system and installed it at the recently constructed synchrotron radiation beamline BL33XU at the SPring-8. Rapid acquisition of high-quality QXAFS data was realized by combining a servo-motor-driven Si channel-cut monochromator with a tapered undulator. Two tandemly aligned monochromators with channel-cut Si(111) and Si(220) crystals covered energy ranges of 4.0-28.2 keV and 6.6-46.0 keV, respectively. The system allows the users to adjust instantly the energy ranges of scans, the starting angles of oscillations, and the frequencies. The channel-cut crystals are cooled with liquid nitrogen to enable them to withstand the high heat load from the undulator radiation. Deformation of the reflecting planes is reduced by clamping each crystal with two cooling blocks. Performance tests at the Cu K-edge demonstrated sufficiently high data quality for x-ray absorption near-edge structure and extended x-ray absorption fine-structure analyses with temporal resolutions of up to 10 and 25 ms, respectively.

CT and MR cholangiography: advantages and pitfalls in perioperative evaluation of biliary tree.

Recent developments in imaging technology have enabled CT and MR cholangiopancreatography (MRCP) to provide minimally invasive alternatives to endoscopic retrograde cholangiopancreatography for the pre- and post-operative assessment of biliary disease. This article describes anatomical variants of the biliary tree with surgical significance, followed by comparison of CT and MR cholangiographies. Drip infusion cholangiography with CT (DIC-CT) enables high-resolution three-dimensional anatomical representation of very small bile ducts (e.g. aberrant branches, the caudate branch and the cystic duct), which are potential causes of surgical complications. The disadvantages of DIC-CT include the possibility of adverse reactions to biliary contrast media and insufficient depiction of bile ducts caused by liver dysfunction or obstructive jaundice. Conventional MRCP is a standard, non-invasive method for evaluating the biliary tree. MRCP provides useful information, especially regarding the extrahepatic bile ducts and dilated intrahepatic bile ducts. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRCP may facilitate the evaluation of biliary structure and excretory function. Understanding the characteristics of each type of cholangiography is important to ensure sufficient perioperative evaluation of the biliary system.