[Development for the Simultaneous Analytical Method of Furan and Alkyl Furans in Processed Foods].

A simultaneous analytical method was developed for the determination of alkyl furans (Furan, 2-methylfuran, 3-methylfuran and 2,5-dimethylfuran) in processed foods by headspace-GC-MS. Single-laboratory validation data of furan, 2-methylfuran, 3-methylfuran and 2,5-dimethylfuran showed good precision and accuracy. The mean recoveries ranged from 92 to 116%, the intermediate precision (RSDi) ranged from 0.9 to 12.9%. The level of LOQ ranged from 0.5 to 1.2 µg/kg (coffee), from 3.5 to 4.1 µg/kg (soy sauce), from 0.4 to 1.3 µg/kg (other foods: clear apple juice, infant formula and baby food), respectively. This method has the sensitivity to detect low levels of furan and alkyl furans contaminated in various foods and is thus applicable to surveillance for risk management in food safety.

Pleural thickening on screening chest X-rays: a single institutional study.

Although pleural thickening is a common finding on routine chest X-rays, its radiological and clinical features remain poorly characterized. Our investigation of 28,727 chest X-rays obtained from annual health examinations confirmed that pleural thickening was the most common abnormal radiological finding. In most cases (92.2%), pleural thickening involved the apex of the lung, particularly on the right side; thus, it was defined as a pulmonary apical cap. Pleural thickening was more common in males than in females and in current smokers or ex-smokers than in never smokers. The prevalence increased with age, ranging from 1.8% in teenagers to 9.8% in adults aged 60 years and older. Moreover, pleural thickening was clearly associated with greater height and lower body weight and body mass index, suggesting that a tall, thin body shape may predispose to pleural thickening. These observations allowed us to speculate about the causative mechanisms of pleural thickening that are attributable to disproportionate perfusion, ventilation, or mechanical forces in the lungs.

Debulking surgery for venous hemangioma arising from the epicardium: report of a case.

BACKGROUND: Cardiac hemangiomas are rare benign vascular tumors that can occur in any cardiac layer: endocardium, myocardium, or epicardium. Histologically, cardiac hemangiomas may be classified as capillary, cavernous, or arteriovenous; venous hemangiomas are extremely rare. CASE PRESENTATION: A 46-year-old man reported experiencing precordial discomfort. Computed tomography revealed a massive tumor adjacent to the right ventricle. The right coronary artery was found to be located at the center of the tumor. Cardiovascular angiography showed that the artery was completely encased by the tumor without any obstruction and that the right ventricular lumen was compressed by the tumor. Surgical debulking of the tumor was performed under cardiopulmonary bypass, and the frozen section led to a diagnosis of benign hemangioma. The tumor was debulked as much as possible until the right coronary artery appeared. For decompression of the heart, the pericardium was left open to the thoracic cavity and unsutured. Histopathologic examination revealed a diagnosis of epicardial venous hemangioma. CONCLUSIONS: Cardiac hemangioma should be included in the differential diagnosis of mediastinal tumor in reference to the location and flow of the coronary artery. Surgical resection, or at least tumor debulking, is required to confirm the diagnosis and prevent further complications and has a favorable clinical outcome.

[Tricuspid Valve Replacement in a Case of an Adult Patient with Corrected Transposition of the Great Arteries；Report of a Case].

The patient was a 69-year-old man with corrected transposition of the great arteries. Chest X-ray abnormality had been pointed out since his childhood. Recently he was admitted with congestive heart failure. Examination revealed severe regurgitation of the tricuspid valve (systemic atrioventricular valve) with mild systemic ventricular dysfunction. After a median sternotomy, the operation was conducted with the surgeon standing on the patient's left side. Tricuspid valve was approached through left superior atriotomy. Tricuspid valve was facing almost dorsal to the patient, and there was a big cleft between anterior and posterior leaflets. Tricuspid valve replacement with a mechanical valve was performed with leaflets preserved. The patients had a favorable postoperative course.

[The characteristics of a comprehensive geriatric assessment in patients with mild cognitive impairment with a cerebral white matter lesion].

AIM: Vascular dementia may be referred to as "treatable dementia" because its development and progress can be inhibited by intervention in the early stage. In particular, cerebral white matter lesions are readily encountered the clinical setting. In this study, we aimed to clarify the phenomenon and symptoms of patients with mild cognitive impairment (MCI) with cerebral white matter lesions prior to the onset of dementia. METHODS: The subjects included 181 cases diagnosed with MCI among 643 consecutive new patients of the Center for Comprehensive Care on Memory Disorder at Kyorin University Hospital from January 1, 2013 to January 31, 2014. Patients with particular diseases were excluded. An interview, physical examination, comprehensive geriatric assessment, brain MRI and SPECT were performed for all subjects. The cerebral white matter lesions were evaluated using the modified Fazekas scale. We defined Grades 0 and 1 as the group without apparent cerebral white matter lesions and Grades 2 and 3 as the group with apparent cerebral white matter lesions. We compared the laboratory findings and outcomes of these two groups. RESULTS: The age of the group with apparent cerebral white matter lesions was significantly higher than the group without apparent cerebral white matter lesions (P<0.05). No significant difference was observed regarding gender, MMSE, or "vegetable" term retrieval. A significant difference was observed in the total score and the subordinate component of the 21-item fall risk index and geriatric depression scale between the groups (P<0.05). Additionally, a significant difference was observed regarding the subordinate component of the instrumental ADL, the Dementia Behavior Disturbance Scale and the Zarit Care Burden Scale between the groups (P<0.05). CONCLUSIONS: Our results suggest that the presence of white matter lesions at the stage of MCI has a significant relationship to care burden due to the deterioration of ADL, risk of falling, and the presence of depression and behavior disorders. We speculate that our results are useful for the explanation of the characteristics of MCI with white matter lesion to the patients and the care givers. Furthermore, these results may lead to improvements in the appropriate approach, intervention and appropriate nursing of such patients.

Speciation and determination of inorganic arsenic in rice using liquid chromatography-inductively coupled plasma/ mass spectrometry: collaborative study.

An analytical method to speciate two inorganic As forms [arsenite, As(lll) and arsenate, As(V)] in indica and japonica types of rice (both husked and polished) and determine the inorganic As concentration as the sum of these two was internationally validated. The method can additionally determine two organic As compounds, monomethylarsonic acid and dimethylarsinic acid, in rice as separate LC peaks. The method is based on LC separation and inductively coupled plasma (ICP)-MS detection. The method was evaluated through the International Union of Pure and Applied Chemistry/lnternational Organization for Standardization/AOAC harmonized protocol. Sixteen laboratories from four countries participated in the study, and 13 laboratories returned valid data. Twenty test portions of 10 blind duplicates of indica and japonica type rice samples (both husked and polished) were used in this study. Repeatability RSD (RSDr) and reproducibility RSD (RSDR) were calculated at five concentrations of total inorganic As between 0.03 and 0.68 mg/kg. The RSDr was in a range of 3.8 to 7.7% and the RSDR was in a range of 10 to 36%. These performance characteristics were found to be sufficient for determination of inorganic As at or higher than 0.03 mg/kg. Applicability of the method was estimated to be in a range of 0.02-2.0 mg/kg.

Development and usefulness of a new questionnaire for assessing geriatric syndrome.

AIM: To assess the validity and reliability of a pre-visit questionnaire newly developed to identify geriatric conditions in older adults in an outpatient clinical setting. METHODS: A new self-administered questionnaire consisting of 17 items was distributed to 277 patients or their caregivers visiting a memory clinic. The questionnaire was designed to address common symptoms associated with an increasing age based on yes/no responses with symptom-oriented questions avoiding the use of 'jargon'. The patients also underwent comprehensive geriatric assessments (CGAs), as well as tests of the Barthel index, Lawton instrumental activities of daily living, mini-mental state examination (MMSE), geriatric depression scale and vitality index to assess construct validity in a factor analysis. The differences in the prevalence of symptoms between the patients and their caregivers were also assessed. RESULTS: The factor analysis detected eight components that included symptoms referring to gait disturbance, numbness, urinary incontinence, insomnia or body weight loss and were significantly correlated with the measurements of the CGA. Cronbach's alpha coefficient for the internal consistency of the questionnaire was 0.729. The caregivers tended to respond to the questionnaire for older patients (81.6±5.5 vs. 76±9.7 years of age for patients with caregivers as responders versus patients as responders respectively, p<0.001) and those with lower MMSE scores (19.4±5.8 vs. 24.8±4.2 points, p<0.001). A higher prevalence of falls and episodes of delusions was observed among the patients with caregivers as responders. CONCLUSIONS: These results demonstrate that the current questionnaire is a valid and reliable instrument for use in clinical practice and that obtaining collateral source information is essential for assessing significant geriatric symptoms. Such information also provides clinicians with a guide to conducting more detailed evaluations of geriatric conditions and aids in the diagnostic process in older patients with multidisciplinary complications.

Prevalence and antimicrobial susceptibility of foodborne bacteria in wild boars (Sus scrofa) and wild deer (Cervus nippon) in Japan.

This study aimed to evaluate the role of wild boars and deer as reservoirs of foodborne bacteria. We investigated the prevalence and antimicrobial susceptibility of Campylobacter spp., Salmonella spp., Shiga toxin-producing Escherichia coli (STEC) O157 and O26, and Listeria monocytogenes isolated from wild boars and deer in Japan, from July through December 2010. Campylobacter spp. and Salmonella spp. were isolated from 43.8% (95% confidence interval [CI]: 35.0-52.6) and 7.4% (95% CI: 2.8-12.1) of rectal content samples of wild boars, respectively, but not from wild deer. The most common Campylobacter species was C. lanienae and C. hyointestinalis. The nine Salmonella serovars isolated were S. enterica subsp. enterica serovar Agona (three isolates), S. Narashino (two), S. Enteritidis (one), S. Havana (one), S. Infantis (one), and S. Thompson (one). Five (16%) and 6 (29%) isolates of C. lanienae and C. hyointestinalis, respectively, were resistant to enrofloxacin. STEC O157 and O26 and L. monocytogenes were isolated from 2.3% (95% CI: 0-5.0), 0.8% (95% CI: 0-2.3), and 6.1% (95% CI: 1.7-10.5) of the rectal content samples of wild deer, respectively, but not from wild boars. This first nationwide survey of the prevalence of foodborne bacteria in wild boars and wild deer in Japan suggests that consumption of meat from these animals is associated with the risk of causing infection with these bacteria in humans. Moreover, these animals are potential vehicles for distribution of antimicrobial-resistant bacteria into their habitat. The prevalence and antimicrobial susceptibility of such foodborne bacteria in these wild animals should be monitored periodically.

Clinical Validation of a Neointima-Inducing Inflow Cannula in a Continuous Flow Left Ventricular Assist Device.

Wedge thrombus formation around the inflow cannula of a continuous left ventricular assist device (LVAD) is a source of systemic thromboemboli. We previously reported the potential advantages of a new inflow cannula wrapped with titanium mesh (GU30) over the standard smooth surface oblique cut cannula (GU10). The objective of the present study was to clinically validate this new cannula. A retrospective cohort analysis of patients with implanted LVAD (EVAHEART) comparing the GU10 to the GU30 was conducted. Clinical outcomes, including survival, the incidence of thromboembolism, and bleeding events, were compared. Gross and histopathological analyses of explanted GU30 cannula were conducted following transplant or patient death. No significant differences in the survival rate, severe emboli, or cerebral bleeding were observed during the LVAD implantation. However, severe emboli occurred earlier after LVAD implantation when using the GU30 cannula compared with the GU10. In cases of long LVAD support, the neointima fully covered the inflow of the GU30 cannulae without wedge thrombus formation. The titanium mesh-wrapped inflow cannulae did not reduce the overall incidence of neurological events significantly. However, the titanium mesh-wrapped inflow cannula induced autologous neointimal growth over the cannula and prevented wedge thrombus formation in late-phase LVAD implantation.

Retinoic acid from retinal pigment epithelium induces T regulatory cells.

Primary cultured retinal pigment epithelial (RPE) cells can convert T cells into T regulatory cells (Tregs) through inhibitory factor(s) including transforming growth factor ß (TGFß) in vitro. Retinoic acid (RA) enhances induction of CD4(+) Tregs in the presence of TGFß. We investigated whether RA produced by RPE cells can promote generation of Tregs. We found that in vitro, RA-treated T cells expressed high levels of Foxp3 in the presence of recombinant TGFß. In GeneChip analysis, cultured RPE cells constitutively expressed RA-associated molecules such as RA-binding proteins, enzymes, and receptors. RPE from normal mice, but not vitamin A-deficient mice, contained significant levels of TGFß. RPE-induced Tregs from vitamin A-deficient mice failed to suppress activation of target T cells. Only a few Foxp3(+) T cells were found in intraocular cells from vitamin A-deficient experimental autoimmune uveitis (EAU) mice, whereas expression was higher in cells from normal EAU mice. RA receptor antagonist-pretreated or RA-binding protein-siRNA-transfected RPE cells failed to convert CD4(+) T cells into Tregs. Our data support the hypothesis that RPE cells produce RA, thereby enabling bystander T cells to be converted into Tregs through TGFß promotion, which can then participate in the establishment of immune tolerance in the eye.

Home systolic blood pressure on the morning of dialysis days has prognostic impact for hypertensive hemodialysis patients.

BACKGROUND: Hypertension is a leading cause of cardiovascular (CV) disease in the general population. Although hypertension is very common in maintenance hemodialysis (HD) patients, adequate blood pressure (BP) values and measurement timing have not been defined. METHODS: A total of 49 hypertensive HD patients were recruited. Average age was 63 ± 11 years, and duration of dialysis therapy was 6.2 ± 4.2 years. Dialysis unit BPs and various types of home BPs were separately measured, and which BPs were the most critical markers in evaluating the effect of hypertension on left ventricular hypertrophy and CV events was investigated. RESULTS: Predialysis systolic BPs were not correlated with any home BPs. Left ventricular mass index (LVMI) had a significant positive correlation with home BPs, especially morning systolic BPs on HD days (P < 0.01) and non-HD days (P < 0.05), on univariate and multivariate analysis. In contrast, predialysis BPs did not correlate with LVMI. During the follow-up period (47 ± 18 months), it was demonstrated that diabetes and home BPs, especially systolic BPs on the morning of HD days, were significant predictors of CV events on multivariate Cox regression analysis. A 10 mmHg increase in BP had a significantly elevated relative risk for CV events. CONCLUSIONS: Home BP, especially systolic BPs in the morning on HD days, can provide pivotal information for management of HD patients.

[Total arch replacement for spontaneous rupture of the thoracic aorta;report of a case].

A 75-year-old man without history of trauma and aortic aneurysm presented with chest discomfort. A computed tomography (CT) revealed massive mediastinal hematoma without intimal flap in the aorta. Under hypothermic circulatory arrest, total arch replacement was performed. A transmural tear was found just distal to the left subclavian artery. Aortic dissection was not found macroscopically. When we encounter massive hematoma in the anterior mediastinum or the left thoracic cavity, spontaneous rupture of the thoracic aorta should be suspected, and emergency operation should be performed via optimal surgical approach.

Food Safety-Internationally Agreed Framework.

Food safety is very important to protect the health of consumers. In this manuscript, internationally agreed concepts and requirements of food safety and risk analysis are beiefly explained along with the topics of symposium.

Development of Indirect Quantitative Methods for 3-MCPD Fatty Acid Esters (3-MCPDEs) and Glycidyl Fatty Acid Esters (GEs) in Thermally Processed Foodstuffs.

For indirect determination of 3-chloro-1,2-propanediol fatty acid esters (3-MCPDEs) and glycidyl fatty acid esters (GEs) in thermally processed foodstuffs distributed in Japan, we modified two published methods, an enzymatic method (later approved as JOCS Standard Method for the Analysis of Fats, Oils, and Related Materials 2.4.14-2016 and Joint JOCS/AOCS Official Method Cd 29d-19) and EFSA method developed by the Joint Research Centre of the European Commission. The performance of these methods was demonstrated to be satisfactory. The partially modified enzymatic method showed mean recoveries of 93.7-98.5% for 3-MCPDEs, 94.4-98.4% for GEs, and HorRat(r) values of 0.06-0.78 in analyses of 6 types of foods including Japanese specific foods (fried rice cracker, fried instant noodle, biscuit, karinto, vegetable tempura, and frozen deep-fried chicken) spiked with 3-MCPD dioleate and glycidyl oleate at 0.02-0.04 mg/kg or 0.2-0.4 mg/kg. The partially modified EFSA method showed mean recoveries of 96.6-99.4% for 3-MCPDEs, 95.7-100.1% for GEs, and HorRat(r) values of 0.14-1.05 in analyses of 5 types of foods (not including karinto) spiked simultaneously with 3-MCPD dioleate and glycidyl oleate at either 0.02-0.04 mg/kg or 0.2-0.4 mg/kg. The results of analyses of 9 samples (fried rice cracker, biscuit, 2 potato crisps, fried potato snack, baked cracker, cracker dough, seafood tempura, and frozen deep-fried chicken) using these 2 methods were comparable. The 95% confidence intervals determined with weighted Deming regression analysis between the results of 3-MCPDEs or GEs in the same samples analyzed by the 2 methods showed: the slope around 1 (3-MCPDEs, 0.982-1.025; GEs, 0.887-1.078); and intercept close to 0 (3-MCPDEs, －0.002-0.003; GEs, －0.011-0.015). These data confirmed that the concentrations of 3-MCPDEs and GEs in food samples determined by 2 independent analytical methods were equivalent.

Neointima-inducing inflow cannula with titanium mesh for left ventricular assist device.

The formation of wedge thrombus is a crucial problem in any left ventricular assist device (LVAD) with a left ventricle apical inflow cannula. We therefore developed a new titanium mesh wrapped inflow cannula expecting to induce autologous neointima to avoid such wedge thrombus formation. We performed animal experiments to evaluate the feasibility of this newly developed inflow cannula with titanium mesh for the induction of autologous neointima. Four calves were implanted with the inflow cannula as well as an EVAHEART centrifugal pump LVAD (Sun Medical Technology Research Corp., Nagano, Japan) for a duration of about 2 months. The titanium mesh was enveloped with neointimal tissue grown from the ventricular endocardium. There was no thrombus formation in any of the blood pumps or around the outside of the inflow cannulas. The histological findings showed that the neointimal tissue consisted of a layer of endothelial cells and fibroblasts. The newly developed inflow cannula using a titanium mesh induces autologous neointima formation, avoiding wedge thrombus formation.

Effective long-term surgical management of congenital coronary artery fistulas.

Congenital coronary artery fistula (CAF) is a rare anomaly involving communication between the coronary artery and any cardiac chamber. We retrospectively studied 23 patients with CAF who were surgically treated at 2 institutes over the past 38 years. All patients had continuous murmur and were diagnosed using echocardiography and cardiac catheterization. Eighteen patients had no other heart anomalies, and 5 had an associated anomaly. Fifteen patients were treated using cardiopulmonary bypass via differential surgical approaches (6 patients, CAF orifice closure through cardiac chamber; 6, coronary arteriotomy for CAF orifice closure; and 3, CAF ligation). Eight patients underwent CAF ligation without cardiopulmonary bypass. CAF originated from the right coronary artery in 11 patients; the left coronary artery in 10, and both arteries in 2. Drainage occurred at the following sites: the right ventricle (10 patients), right atrium (6), left ventricle (4), left atrium (2), and pulmonary artery (1). All surgeries were performed through a median sternotomy. There were no mortalities during or after the hospital stay. Aortic root replacement was performed in 1 patient 30 years after the CAF surgery. Three of the 6 patients who underwent coronary arteriotomy for CAF orifice closure showed coronary artery occlusion at the distal coronary arteriotomy site with long-term collateral formation. Surgical management of CAF was thus effective, resulting in 100% long-term survival and closure rates. Dilated CAF-associated vessels have been normalized for the long term. CAF should be therefore considered even in asymptomatic patients because of the risk of future complications.

Single- and Multiple-Laboratory Validation of LC-MS/MS Method for Simultaneous Determination of Fosetyl-Al and Phosphonic Acid in Cereal Grains and Analysis of Rice, Wheat, and Barley.

BACKGROUND: In Japan, the residue definition for fosetyl-Al is "sum of fosetyl-Al and phosphonic acid expressed as fosetyl-Al" and its current provisional maximum residue limit (MRL) in cereals is under review. OBJECTIVE: For establishment and enforcement of fosetyl-Al MRL in cereals, a new analytical method for fosetyl-Al and phosphonic acid in cereals should be developed and validated. METHOD: The new method involves water extraction, cleanup using tandem cation- and anion-exchange mini columns, and determination by LC-MS/MS. It was validated in a single laboratory and multiple laboratories. Using the method, 41 samples of rice, wheat, and barley were analyzed. RESULTS: In the multiple-laboratory validation: repeatability and reproducibility for three concentrations of fosetyl-Al and phosphonic acid were in ranges of 4.8-20 and 5.9-34%; calculated sum of fosetyl-Al and phosphonic acid, expressed as fosetyl-Al, showed good recoveries; linearity was observed for fosetyl-Al and phosphonic acid in ranges of 0.005-0.4 and 0.025-2.0 mg/kg; and specificity was sufficient. The method was verified for rice matrixes. In 41 samples, phosphonic acid was detected up to 0.2 mg/kg while fosetyl was not. CONCLUSIONS: The method was successfully validated with high precision, accuracy, linearity, and specificity and capable of analyzing fosetyl-Al and phosphonic acid with a practical LOQ of 0.01 and 0.05 mg/kg. The LOQs and concentrations of phosphonic acid in samples indicate that a potential MRL would be 0.5 mg/kg for fosetyl-Al in cereals. HIGHLIGHTS: The validated method was simpler than many methods and did not require derivatization, matrix-matched orisotopically-labeled internal standards.

Human retinal pigment epithelium-induced CD4+CD25+ regulatory T cells suppress activation of intraocular effector T cells.

Murine retinal pigment epithelial (RPE) cells suppress T-cell activation by releasing soluble inhibitory factors and promote the generation of regulatory T cells in vitro. These T cells exposed to RPE supernatants (RPE-induced Treg cells) can suppress the activation of bystander effector T cells via the production of transforming growth factor-beta (TGFbeta). In the present study, we showed that human RPE-induced Treg cells are also able to acquire regulatory function when human RPE cell lines were pretreated with recombinant TGF beta 2. These RPE-induced Treg cells produced TGF beta 1 and IL-10 but not IFN gamma, and they significantly suppressed the activation of target cell lines and intraocular T-cell clones established from patients with active uveitis. Moreover, CD4(+)CD25(+) RPE-induced Treg cells expressed CTLA-4 and Foxp3 molecules, and the CD25(+) Treg cells profoundly suppressed the T-cell activation. Thus, in vitro manipulated Treg cells acquire functions that participate in the establishment of immune tolerance in the eye.

[Effects and safety of infliximab administration in refractory uveoretinitis with Behçet's disease].

PURPOSE: To evaluate the efficacy and safety of infliximab administration in refractory uveoretinitis in Behçet's disease (BD). METHODS: The subjects were 22 consecutive BD patients with refractory uveoretinitis treated with infliximab. Three patients dropped out from the therapy. The other 19 patients received the therapy for 6 months or longer. The efficacy was evaluated by the ocular attacks and best corrected visual acuity at remission in the 19 patients and the safety was evaluated in all 22 patients. RESULTS: The incidence of ocular attacks in the 6 months before and after the infliximab therapy were 3.0+/-2.6 and 0.4+/-1.1, respectively (p<0.0005). Infliximab was very effective in 7 patients where no ocular attacks occurred throughout infliximab therapy, effective in 10 patients where ocular attacks was reduced, and non-effective in 2 patients. The vision was either improved or unchanged in all eyes at the 6th months therapy. Various adverse effects were seen in 14 patients, but non were serious. CONCLUSIONS: Infiximab therapy is effective in managing the refractory uveoretinitis in BD, but elucidation of the safety needs more patients and a longer follow-up period.