Detection of norovirus in food samples collected during suspected food-handler-involved foodborne outbreaks in Tokyo.

Although norovirus (NoV) is the major cause of gastroenteritis, with the largest number of NoV food poisoning cases in Japan, limited information is available regarding NoV detection in food. This study aimed to detect NoV in food samples during the 2015-2016 suspected foodborne outbreaks in Tokyo; 352 food samples from 64 NoV food poisoning outbreaks were collected. Bacterial culturing was performed for sample pretreatment and real-time reverse transcription polymerase chain reaction was conducted for NoV screening. The NoV detection rate was 1·7% (6/352). NoV-positive food samples included leftover boxed lunch, mackerel fillet (foodstuff), aburi salmon slice (partially seared salmon slice), raw tuna as a chirashizushi ingredient, raw amberjack as a sushi topping and ice for drinks. Since fresh fish as sushi toppings or ingredients and ice were consumed without heating, they may present a higher risk of viral infection. NoV-positive food samples were obtained from five outbreaks, wherein food handlers were NoV-positive in four. Each partial VP1 sequence from food samples matched completely with those in NoV-positive individuals and food handlers. Hence, food handlers play a potentially important role in food-based NoV transmission in all five outbreaks; therefore, hygiene education among them is essential to prevent NoV foodborne outbreaks. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: Norovirus (NoV) is a leading cause of foodborne outbreak in Japan. The most frequent route of transmission in NoV foodborne outbreaks is secondary contamination via infected food handlers. However, limited information is available regarding NoV contamination in food samples. This study reports the detection of NoV in food samples to elucidate the source and route of NoV infection leading to outbreaks for 2 years in Tokyo. Our data potentially contribute to education and the development of safe food-handling strategies among food handlers and employees in the food industry through elucidation of risk factors associated with NoV contamination.

Structural phase transition and magnetic-field effect on the modulated structure in GdBaCo2O5+δ (δ < 0.5).

We investigated the crystal structures of an ordered perovskite-type cobaltate, GdBaCo2O(5+δ) (δ < 0.5), at elevated temperatures by transmission electron microscopy. Above the magnetic ordering temperature, we observed a first-order structural phase transition between the low-temperature tetragonal 3a(p) × 3a(p) and high-temperature orthorhombic 1a(p) × 2a(p) superstructure phases (where a(p) is the perovskite-unit cell). Upon the application of a magnetic field, an incommensurate phase emerges around the structural phase-transition temperature, which indicates a magnetic-field-induced structural phase transition via no magnetic ordering in the ordered perovskite-type cobaltate.

Effect of dentist's clinical experience on treatment satisfaction of a complete denture.

The relationship between the prosthodontic experience of dentists and satisfaction of complete denture wearers remains unknown. To investigate whether a prosthodontist's clinical experience affects treatment satisfaction of a complete denture wearer. From April 2004 to July 2006, we conducted a randomised controlled trial at two centres, including 74 edentulous patients; of these, 32 and 30 were randomly allocated to the ED or ID group, respectively. All the patients rated their satisfaction with dentures, including general satisfaction and satisfaction of chewing ability, speaking, cleaning, stability, retention, comfort and aesthetics. These satisfaction ratings were measured by a 100-mm visual analog scale (VAS). Perceived chewing ability to foods, divided into five grades, was measured using a questionnaire. The mastication index (MI) was calculated for each grade. General satisfaction and satisfaction of speaking, stability and retention were significantly higher in the ED than in the ID group (P = 0·049, 0·003, 0·019 and 0·041, respectively). No significant difference existed between the MI of the ED (71·3 ± 18·4) and ID group (64·1 ± 16·53). However, the perceived chewing ability of grade 5 food, whose texture was the hardest among all the grades, was significantly higher in the ED group than in the ID group. Within its limitations, this study showed that a clinician's prosthodontic experience affects a complete denture wearer's satisfaction ratings.

Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants.

Background: Immune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear. Methods: This prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron variant). As the immune indicators, we assessed the serum levels of IFN-I/III, IL-6, CXCL10 and VEGF, using an ELISA at within 5 days after the onset of symptoms, and serum neutralizing responses using a pseudovirus assay. We also assessed SARS-CoV-2 viral load by qPCR using nasal-swab specimens and serum, to assess the association of indicators and viral distribution. Results: The study enrolled 117 patients with COVID-19, of which 28 patients developed hypoxemia. None received vaccine before admission. Serum IFN-I levels (IFN-α and IFN-ß), IL-6, CXCL10, LDH and CRP were significantly higher in patients who developed hypoxemia. A significant association with nasopharyngeal viral load was observed only for IFN-I. The serum levels of IFN-α, IL-6, CXCL10 were significantly associated with the presence of RNAemia. Multivariable analysis showed higher odds ratio of IFN-α, with cut-off value of 107 pg/ml, in regard to hypoxemia (Odds ratio [OR]=17.5; 95% confidence interval [CI], 4.7-85; p<0.001), compared to those of IL-6, >17.9 pg/ml (OR=10.5; 95% CI, 2.9-46; p<0.001). Conclusions: This study demonstrated that serum IFN-α levels in the early phase of SARS-CoV-2 infection strongly predict hypoxemic respiratory failure in a manner different from that of the other indicators including IL-6 or humoral immune response, and instead sensitively reflect innate immune response against SARS-CoV-2 invasion.

Near room-temperature formation of a skyrmion crystal in thin-films of the helimagnet FeGe.

The skyrmion, a vortex-like spin-swirling object, is anticipated to play a vital role in quantum magneto-transport processes such as the quantum Hall and topological Hall effects. The existence of the magnetic skyrmion crystal (SkX) state was recently verified experimentally for MnSi and Fe(0.5)Co(0.5)Si by means of small-angle neutron scattering and Lorentz transmission electron microscopy. However, to enable the application of such a SkX for spintronic function, materials problems such as a low crystallization temperature and low stability of SkX have to be overcome. Here we report the formation of SkX close to room temperature in thin-films of the helimagnet FeGe. In addition to the magnetic twin structure, we found a magnetic chirality inversion of the SkX across lattice twin boundaries. Furthermore, for thin crystal plates with thicknesses much smaller than the SkX lattice constant (as) the two-dimensional SkX is quite stable over a wide range of temperatures and magnetic fields, whereas for quasi-three-dimensional films with thicknesses over as the SkX is relatively unstable and observed only around the helical transition temperature. The room-temperature stable SkX state as promised by this study will pave a new path to designing quantum-effect devices based on the controllable skyrmion dynamics.

Subjective Evaluation of Denture Adhesives: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Sensitivity of planktic foraminiferal test bulk density to ocean acidification.

The anthropogenic CO2 accumulating in the ocean is lowering seawater carbonate ion concentration and may reduce calcification rates of marine calcareous organisms. Several proxies based on test weights of planktic foraminifera have been used to evaluate the impact of ocean acidification on these organisms. Unfortunately, because of the absence of a method to evaluate the bulk density of a test, the impact of seawater carbonate chemistry on test calcification is still not fully understood. In this study, we measured bulk densities of living Globigerina bulloides (planktic foraminifera) tests with an X-ray micro-computed tomography (XMCT) scanner and compared them with ambient seawater characteristics. Results demonstrated that test bulk densities were controlled by ambient seawater carbonate ion concentrations and that changes of test bulk densities were accompanied by changes in micron to submicron scale porosity of internal ultrastructure. These results suggest that alteration of the bulk density of foraminiferal tests due to acidification of ambient seawater can be directly observed by XMCT scanning. A useful metric of calcification intensity would therefore be physical measurements of test densities with XMCT.

Soft-diet feeding decreases dopamine release and impairs aversion learning in Alzheimer model rats.

To examine the effects of soft-diet feeding on the dopaminergic system in a model rat for Alzheimer's disease (AD), we measured dopamine release in the hippocampus using a microdialysis approach and assessed learning ability and memory using step-through passive avoidance tests. Furthermore, we immunohistochemically examined the ventral tegmental area (VTA), which is the origin of hippocampal dopaminergic fibers using tyrosine hydroxylase (TH), a marker enzyme for the dopaminergic nervous system. Feeding a soft diet decreased dopamine release in the hippocampus and impaired learning ability and memory in AD model rats in comparison with rats fed a hard diet; however, TH-immunopositive profiles in the VTA seemed not to be notably different between rats fed a soft diet and those fed a hard diet. These observations suggest that soft-diet feeding enhances the impairment of learning ability and memory through the decline of dopamine release in the hippocampus in AD rats.

Direct observation of the bandwidth-disorder induced variation of charge/orbital ordering structure in RE(0.5)(Ca(1-y)Sr(y))(1.5)MnO(4).

Changes in the charge/orbital ordering (CO/OO) structure with the bandwidth of the e(g) band and quenched disorder were investigated in doped manganites RE(0.5)(Ca(1-y)Sr(y))(1.5)MnO(4)(RE = Pr,Eu) with a single-layer perovskite structure. A systematic study of the modulation structure associated with the CO/OO phase demonstrated that the long-range commensurate structure changes to a short-range incommensurate structure with increasing Sr content through the enhancement of the bandwidth and quenched disorder in these systems. At the same time, the transition temperature of CO/OO (T(CO/OO)) decreases. Changes in structure and T(CO/OO) with different A-site combinations reveal that the CO/OO phase is strongly suppressed by the widening of the e(g) band and the stronger quenched disorder in these layered manganites.

Expression and purification of human angiotensinogen in Chinese hamster ovary cells.

We have produced human angiotensinogen in Chinese hamster ovary (CHO) cells. The expression products were purified to homogeneity by a single column chromatography and its 17 amino-terminal sequences were identical to those of the native protein. We demonstrated the recombinant human angiotensinogen to be a substrate for human renin.

Suppression of stress-induced nNOS expression in the rat hypothalamus by biting.

Nitric oxide (.NO) modulates the activity of the endocrine system in the behavioral response to stress. The purpose of this study was to investigate the effect of restraining the body of an animal on expression of neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) of the hypothalamus, and the inhibitory effect of para-masticatory activity on restraint-induced nNOS expression. We observed an increase in nNOS mRNA expression and nNOS-positive neurons in the rat hypothalamus after 30 or 60 min of restraint. Biting on a wooden stick during bodily restraint decreased nNOS mRNA expression in the hypothalamus. In addition, the number of nNOS-positive neurons was significantly reduced in the PVN of the hypothalamus. These observations clearly suggest a possible anti-stress effect of the masticatory activity of biting, and this mechanism might be unconsciously in operation during exposure to psychological stressors.

Regulation of vascular angiotensin release.

To investigate the regulatory mechanism of the vascular renin-angiotensin system, we perfused isolated rat hind legs with plasma-free buffer and quantified angiotensin peptides in the perfusate. Angiotensin release from hind legs was increased in rats pretreated with losartan (DuP 753) and rats fed a low sodium diet with subsequent furosemide and was decreased in nephrectomized rats and rats given dexamethasone, ethynylestradiol, and triiodothyronine. Using these models, we have attempted to identify which step or component of angiotensin metabolism determines angiotensin release level. Changes caused by these manipulations in plasma renin concentration and basal angiotensin release from hind legs were almost parallel, whereas plasma angiotensinogen concentration and the angiotensin release changed in opposite directions. Infusion of renin in hind legs caused a marked increase in angiotensin release and continued even 1 hour after cessation of renin infusion. Infusion of angiotensinogen did not alter the angiotensin release. Angiotensin clearance and angiotensin I conversion were not affected by either nephrectomy or losartan pretreatment. Aortic renin messenger RNA level was extremely low and not increased by nephrectomy or losartan pretreatment, although kidney renin messenger RNA level was increased by losartan pretreatment. These results provide evidence that plasma renin of kidney origin is the major source of vascular functional renin and plays the determining role in the regulation of vascular angiotensin release. Plasma-derived or locally produced angiotensinogen, locally produced renin, converting enzyme, and angiotensin clearance are not considered to be the primary determinant in the regulation of vascular angiotensin release in these acute and subacute experimental models.

Functional regulation of tactile sense by brain-derived neurotrophic factor in adult rats during acute inflammation.

Nerve growth factor is present in skin in limiting amounts and is known to regulate the plasticity and the sensitivity of nociceptive neurons. Recently, knock-out mouse studies showed that neurotrophin-3 and brain-derived neurotrophic factor are required for the postnatal survival and functional maturation, respectively, of tactile sensory neurons. However, the roles of neurotrophin-3 and brain-derived neurotrophic factor in adult sensory neurons have not been clarified. Here, we report an unexpected and marked acute loss of tactile sense in the rat hind paw after adjuvant-induced inflammation. This loss was shown to be closely correlated with decreases in the expression of brain-derived neurotrophic factor, and to a lesser extent of neurotrophin-3 in the inflamed skin. Administration of brain-derived neurotrophic factor, but not neurotrophin-3, after inflammation accelerated the recovery of tactile sense. These results suggested a role of brain-derived neurotrophic factor in the physiological regulation of tactile sense in adulthood.

Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin.

AIM: To investigate the effect of different proton pump inhibitors, S-mephenytoin 4'-hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori. METHODS: One hundred and eighty-seven H. pylori-infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated. RESULTS: The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) and lansoprazole-amoxicillin-clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention-to-treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin-resistant strains was significantly lower than that for clarithromycin-sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin-sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726). CONCLUSIONS: The success of the 1-week proton pump inhibitor-amoxicillin-clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole-based therapy, and the rabeprazole-based regimen has an advantage especially in extensive metabolizers.

Inhibition of adjuvant-induced inflammatory hyperalgesia in rats by local injection of neurotrophin-3.

The induction of nerve growth factor (NGF) in inflammatory tissue has been shown to be involved in hyperalgesia. In the present study, the role of neurotrophin-3 (NT-3) in the regulation of inflammatory hyperalgesia was analyzed. Inflammatory hyperalgesia was induced by intraplantar injection of complete Freund's adjuvant (CFA) to the rat hind paw. NT-3 levels in the plantar skin were much higher than NGF levels (1.24 and 0.14 ng/g tissue, respectively) before CFA injection, but decreased significantly 6 h to 48 h after the injection while NGF was markedly induced at 6 h but decreased thereafter. When 1 microg of NT-3 was locally injected at 5 h after CFA injection at the time NT-3 levels decreased, hyperalgesia was reversed transiently but specifically. These results suggest an inhibitory role of NT-3 in the regulation of pain sensitivity.

Comparison of 1-week and 2-week triple therapy with omeprazole, amoxicillin, and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial.

This study was a comparison of 1-week and 2-week triple therapies with omeprazole, amoxicillin, and clarithromycin (OAC) in patients with peptic ulcer disease and Helicobacter pylori infection. A total of 147 peptic ulcer patients with H. pylori infection assessed by histology and culture were randomly treated with omeprazole 20mg bid + amoxicillin 1000mg bid + clarithromycin 400mg bid for either 1 week (OAC1w) or 2 weeks (OAC2w). Both groups then received omeprazole 20mg daily for 2 weeks followed by ranitidine 300mg daily for 4 weeks. Eradication of H. pylori was assessed by histology, culture, and the 13C-urea breath test (13C-UBT) at least 6 weeks after cessation of antimicrobial therapy. Intention-to-treat eradication rates were 78.2% (95%CI 69%-87%) with OAC1w and 88.4% (95%CI 81%-96%) with OAC2w. Per-protocol eradication rates were 86.0% (95%CI 78%-94%) with OAC1w, 97.0% (95%CI 93%-100%) with OAC2w. There was no significant difference in the eradication rates between OAC1w and OAC2w. Side effects were mild and self-limiting in both groups. In conclusion, both 1- and 2-week triple therapy with OAC are well tolerated and provide good eradication rates in peptic ulcer patients in Japan. The eradication rate of the 2-week regimen was higher than that of the 1-week regimen, but the difference was not statistically significant. Further studies including long-term economic considerations are required to determine the optimal duration of treatment.

Plasmin and thrombin inhibitors in essentially untreated patients with coronary artery spasm.

We examined activities or levels of plasmin and thrombin inhibitors in essentially untreated patients with angiographically documented coronary artery spasm. The patients received the ergonovine malate provocation test and were classified into two groups: (a) those with significant coronary artery spasm that produced reduction of the internal luminal diameter of 50% or greater with chest pain and change of electrocardiography (n = 18), and (b) those without coronary artery spasm (n = 17). There was no significant differences in alpha 1-antitrypsin and alpha 2-macroglobulin levels, and C1-inactivator activity between the control and patients with coronary artery spasm. On the other hand, the lower antithrombin III and alpha 2-plasmin inhibitor activities were noted in patients with coronary artery spasm than the control. Thrombin/antithrombin III complex and alpha 2-plasmin inhibitor/plasmin complex levels were significantly higher in coronary artery spasm patients. These results suggest that the coagulation and fibrinolytic systems may maintain their equilibrium in untreated patients with coronary artery spasm.

Effect of early fosfomycin treatment on prevention of hemolytic uremic syndrome accompanying Escherichia coli O157:H7 infection.

OBJECTIVE: To clarify the effect of early fosfomycin treatment, an antimicrobial agent in common use in Japan, on children with E. coli O157 with the aim of preventing hemolytic uremic syndrome (HUS). DESIGN: Non-randomized prospective study for development of HUS among inpatients with E. coli O157. SETTING: The hospitals where the 292 inpatients were treated. CASES: A total of 292 inpatients aged six to eleven years with E. coli O157 infection, 36 (12.3%) of whom were HUS cases. RESULTS: Most of the HUS inpatients (91.7%) developed this complication between the sixth and ninth day of illness. We therefore analyzed the effects of antimicrobial therapy, especially that of fosfomycin, on prevention of HUS within the first five days of illness, because fosfomycin was the most frequently used (88.0%). To clarify the effect of fosfomycin alone on prevention of HUS, we carried out an analysis using the data for 130 inpatients who received fosfomycin alone or did not receive any antimicrobial agents, within the first five days of illness. multivariate analysis, controlled for age, gender and presence of fever, showed that all adjusted odds ratios for the development of HUS with the use of fosfomycin within the first three days of illness were less than 1.0, with the use of fosfomycin on the second day of illness achieving statistical significance (adjusted OR, 0.09; 95% CI, 0.01-0.79). Furthermore, inpatients who took fosfomycin within the first two days of illness developed HUS significantly less often than those who did not (adjusted OR, 0.15; 95% CI, 0.03-0.78). On the other hand, fosfomycin therapy on and after the third day of illness was not associated with the prevention of HUS. CONCLUSION: The early use of fosfomycin within the first two days of illness might prevent the development of HUS.

Genetic variation in hypoxia-inducible factor 1alpha and its possible association with high altitude adaptation in Sherpas.

Hypoxic stress at high altitude requires adaptations in several physiological functions to ensure the optimal oxygenation of all cells. Several lines of evidence suggested that high-altitude native populations such as Sherpas have been genetically adapted to their stressful environment. We investigated the genetic variation in the hypoxia-inducible factor (HIF)-1alpha gene in Sherpas as compared with Japanese, native lowlanders, and found a novel dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene. GT15 allele was more frequent in Japanese than in Sherpas with statistical significance, while GT14 allele was significantly more frequent in Sherpas as compared with Japanese. A possible genetic variation in the HIF-1alpha gene might function in adaptation to living at high altitude. Because the activity of HIF-1 is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in intron 13 on the cellular hypoxic responses remains to be elucidated.

Amyotrophic lateral sclerosis with anti-acetylcholine receptor antibody.

We report a case of amyotrophic lateral sclerosis (ALS) with anti-acetylcholine receptor (AChR) antibody in a 73-year-old female patient. She showed the typical course of ALS. She had no clinical findings of myasthenia gravis and had never undergone neurotoxin therapy using snake venom. Anti-AChR antibody was positive with a titer of 0.50 nmol/l on admission. We traced the titers during the progression of ALS; the titer was positive when muscle weakness worsened, and it became negative when the general condition became stable. We suppose that the occurrence of anti-AChR antibody may be partially relevant with abnormalities at the neuromuscular junction during the progression of ALS.