Genetic Comparison of Human Parainfluenza Virus Type 3 Detected in Respiratory Samples from Patients with Encephalopathy and Airway Inflammation in Aichi Prefecture, Japan.

Human parainfluenza virus type 3 (HPIV-3, human respirovirus 3) is the second most frequently detected virus in lower respiratory tract infections in children after human respiratory syncytial virus (HRSV). HPIV-3, similar to related respiratory viruses such as HRSV and influenza virus, may cause encephalopathy; however, the relevance of HPIV-3 as a pathogenic factor in encephalopathy is unknown. We attempted to detect HPIV-1, HPIV-2, HPIV-3, HPIV-4, HRSV, and human metapneumovirus (HMPV) in 136 patients with encephalitis/encephalopathy or suspected encephalitis/encephalopathy during a 6-year period from 2014 to 2019. HPIV-3 was detected in 6 patients, followed by HRSV in 3 patients. The HPIV-3 strains detected were closely related to those detected in a patient with respiratory disease during the same period. Although HPIV-3 is less widely recognized than HRSV as a triggering virus of encephalopathy, our results suggest that HPIV-3 is as important as HRSV. Surveillance of the causative viruses of encephalopathy, including HPIV-3, would help clarify the causes of encephalopathy in Japan, as the cause is currently reported in less than half of cases in Japan.

Fatal acute portal vein thrombosis associated with hepatic cysts in a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) often involves polycystic liver disease (PLD). In severe cases, PLD can develop various complications. However, fatal acute portal vein thrombosis (APVT) associated with PLD has not been reported. A 64-year-old male reported mild consciousness disorder. He had been under maintenance hemodialysis for end-stage renal disease due to ADPKD with PLD. Because of recurring hepatic cyst infections, he had sustained high levels of C-reactive protein. Regarding the mild consciousness disorder, a diagnosis of hepatic encephalopathy was made based on an elevation of serum ammonia without any other abnormal liver function tests. Several days after his admission, hepatobiliary enzymes elevated, and acute liver failure progressed. Enhanced abdominal computed tomography suggested the possibility of complete occlusion of the portal vein by a thrombus. Based on an absence of obvious portosystemic collaterals, a diagnosis of APVT was made. The patient died 19 days after admission. Patients with PLD with repeated cystic infections have been seen to develop liver failure, and APVT formation may be one cause of the rapid progression of fatal liver failure. In conclusion, this is the first paper to report on the involvement of APVT in patients with PLD.

Establishment of measles virus receptor-expressing Vero cells lacking functional poliovirus receptors.

Global efforts are underway to eliminate measles and rubella, and active viral surveillance is the key to achieving this goal. In addition, the World Health Organization announced guidelines for handling materials potentially infectious for poliovirus (PV) to minimize the risk of PV reintroduction and to achieve PV eradication. To support global efforts, we established new PV-non-susceptible cell lines that are useful for the isolation of measles virus (MeV) and rubella virus (RuV) (Vero ΔPVR1/2 hSLAM+). In the cell lines, MeV and RuV replicated efficiently, with no concern regarding PV replication.

The effect of casein hydrolysate intake on cerebral neural regulation during cognitive tasks in the elderly.

Human and animal studies have shown that casein peptide (casein hydrolysate) has positive effects on cognitive function. This double-blind randomized controlled study aimed to investigate whether single ingestion of casein peptide could affect cognitive function (executive function) and cognitive neural activity in healthy older adults. We assigned 47 participants to one of the three dietary supplements as follows: casein peptide (TMP, n = 15), casein (TMC, n = 16), and indigestible dextrin (TMF, n = 16). Dietary supplements were ingested 30 min before starting the experiment; moreover, neural activity while performing the task-switching reaction time (SWT) trial was assessed through functional magnetic resonance imaging (fMRI). Additionally, we used a visual analog scale (VAS) test to assess the pre- and post-test feeling and mood. Regarding the parameters of the SWT trial, there were no significant among-group differences in the reaction time, accuracy rate, and %SwitchCost. Contrastingly, the fMRI experiment revealed among-group differences in the main effects in the medial frontal gyrus, Supplementary motor cortex (SMC), posterior cingulate gyrus (PCg), and amygdala (Amyg). Specifically, there was a significant decrease in the neural activities in the SMC and PCg in the TMP group than in the other two groups. Moreover, there was a significant increase in the neural activity in the Amyg in the TMP group compared with the TMF, but not the TMC, group. Furthermore, the VAS score was significantly higher in the TMP group than in the other two groups. There were no recorded adverse outcomes. Our findings suggested that TMP ingestion by older adults could temporarily suppress complementary neural activity in specific brain regions involved in executive functions, as well as default mode network activity, which could improve cognitive neural activities.

Cryptococcus gattii evades CD11b-mediated fungal recognition by coating itself with capsular polysaccharides.

Cryptococcus gattii is a capsular pathogenic fungus causing life-threatening cryptococcosis. Although the capsular polysaccharides (CPs) of C. gattii are considered as virulence factors, the physiological significance of CP biosynthesis and of CPs themselves is not fully understood, with many conflicting data reported. First, we demonstrated that CAP gene deletant of C. gattii completely lacked capsule layer and its virulence, and that the strain was susceptible to host-related factors including oxidizing, hypoxic, and hypotrophic conditions in vitro. Extracellular CPs recovered from culture supernatant bound specifically to C. gattii acapsular strains, not to other fungi and immune cells, and rendered them the immune escape effects. In fact, dendritic cells (DCs) did not efficiently uptake the CP-treated acapsular strains, which possessed no visible capsule layer, and a decreased amount of phosphorylated proteins and cytokine levels after the stimulation. DCs recognized C. gattii acapuslar cells via an immune receptor CD11b- and Syk-related pathway; however, CD11b did not bind to CP-treated acapsular cells. These results suggested that CPs support immune evasion by coating antigens on C. gattii and blocking the interaction between CD11b and C. gattii cells. Here, we describe the importance of CPs in pathogenicity and immune evasion mechanisms of C. gattii.

Selective Homoepitaxial Growth of ZnO Layers on c(+)-Surface by Solvothermal Reaction in Water-Ethylene Glycol Solvent.

Solvothermal deposition of ZnO layers on the c(±)-surfaces of ZnO single crystal substrates in a water-ethylene glycol solvent was investigated. Homoepitaxial growth of nanoparticulate layers was observed on the c(+)-surface. The manner of nanoparticle deposition on the c(+)-surface was similar to that of spherical particles precipitated in the solution, in that both grew through the oriented attachment of small particles during the early growth stage. The growth of the nanoparticulate film on the c(-)-surface was much slower than that on the c(+)-surface. After aging, the top surface of the film on the c(+)-surface transformed into a layer of pyramid-like particles so that the base of the pyramids was directed toward the surface. In contrast, randomly oriented pyramidal particles covered the c(-)-surface. Ostwald ripening through dissolution-recrystallization transformed the nanoparticles into pyramid-shaped particles in the latter stage when they were in contact with the solution. The faster growth on the c(+)-surface than on the c(-)-surface and the pyramidal shape of the particles with c(+)-basal plane deposited on the c(±)-surfaces after aging confirmed that the growth of the c(+)-plane was promoted, whereas the growth of {101̅0} and c(-)-planes was inhibited in this solution.

A small nuclear acidic protein (MTI-II, Zn2+-binding protein, parathymosin) attenuates TNF-α inhibition of BMP-induced osteogenesis by enhancing accessibility of the Smad4-NF-κB p65 complex to Smad binding element.

Pro-inflammatory cytokines prevent bone regeneration in vivo and activation of nuclear factor-κB (NF-κB) signaling has been proposed to lead to suppression of bone morphogenetic protein (BMP)-induced osteogenesis via direct binding of p65 to Smad4 in vitro. Application of a small nuclear acidic protein (MTI-II) and its delivered peptide, MPAID (MTI-II peptide anti-inflammatory drug) has been described to elicit therapeutic potential via strong anti-inflammatory action following the physical association of MTI-II and MPAID with p65. However, it is unclear whether MTI-II attenuates tumor necrosis factor (TNF)-α inhibition of BMP-induced osteogenesis. Herein, we found that TNF-α-mediated suppression of responses associated with BMP4-induced osteogenesis, including expression of the osteocalcin encoding gene Ocn, Smad binding element (SBE)-dependent luciferase activity, alkaline phosphatase activity, and alizarin red S staining were largely restored by MTI-II and MPAID in MC3T3-E1 cells. Mechanistically, MTI-II and MPAID did not inhibit nuclear translocation of p65 or disassociate Smad4 from p65. Further, results from chromatin immunoprecipitation (ChIP) analyses revealed that Smad4 enrichment in cells over-expressing MTI-II and treated with TNF-α was equivalent to that in cells without TNF-α treatment. Alternatively, Smad4 enrichment was considerably decreased following TNF-α treatment in control cells. Moreover, p65 enrichment in the Id-1 promoter SBE was detected only when cells over-expressing MTI-II were stimulated with TNF-α. Overall, our study concludes that MTI-II restored TNF-α-inhibited suppression of BMP-Smad-induced osteogenic differentiation by enhancing accessibility of the Smad4-p65 complex to the SBE rather than by liberating Smad4 from p65.

Two Cases of Dengue Virus Type 2 (DENV-2) Infection in a Japanese Couple Returning from the Maldives during the 2018 Dengue Outbreak.

Annually, more than 1.2 million travelers from other countries visit the Maldives for sightseeing, business, and honeymoon. In 2018, the largest dengue fever outbreak occurred, affecting more than 3,200 people. During this outbreak, we encountered a newly married Japanese couple returning from the Maldives on their honeymoon in October 2018, both were infected by the dengue virus type 2 during the travel. The number of imported dengue fever cases from the Maldives may increase; hence, physicians should stay up to date on dengue outbreak information worldwide.

Structural and Thermal Properties in Formamidinium and Cs-Mixed Lead Halides.

Formamidinium [FA, HC(NH2)2+] lead iodide and its cation mixture have attracted interest as potentials in applications for efficient solar cells superior to well-known methylammonium lead iodide. We investigated the crystal structure and thermodynamic properties of high-quality single crystals of FA1-xCsxPbI3 for x = 0 and 0.1 through X-ray diffraction and heat capacity measurements. Both α-FA0.9Cs0.1PbI3 as well as α-FAPbI3 crystallize in a cubic Pm3̅m structure with orientationally disordered FA molecules confined in the nondistorted Pb-I framework. In FAPbI3, we observed a second-order transition at 280 K and two first-order transitions at 141.2 and 130.2 K in between ß- and γ-phases instead of the previously known single ß-γ transition. After doping with 10% Cs, the multiple first-order transitions disappeared, leading to phase transitions emerging at 300 and 149 K with second-order character. We moreover observed low-energy localized modes for both compounds, which is presumably tied to anomalous thermal motion, rattling, of the FA molecule.

Severe hypermagnesemia induced by magnesium oxide ingestion: a case series.

Hypermagnesemia is generally considered an exceptional iatrogenic condition usually caused by magnesium-containing cathartics. In particular, this condition often develops when magnesium-containing cathartics are administered to elderly patients with renal insufficiency or bowel movement dysfunction. Although magnesium oxide (MgO) is widely prescribed as a laxative, serum magnesium concentration has not been examined in most cases. In this report, we present the cases of four elderly patients with constipation and symptomatic hypermagnesemia caused by MgO ingestion, one of which had a lethal course. All of the patients were older than 65 years and with renal dysfunction. In addition, they had difficulties in expressing their symptoms because of cerebrovascular events or dementia. These cases suggest that hypermagnesemia caused by magnesium-containing cathartics is more likely to develop than previously recognized and that physicians should be aware that patients with chronic kidney disease and the elderly are at risk of hypermagnesemia on magnesium administration. We recommend serum magnesium monitoring for high-risk patients after initial prescription or dose increase.

Atrial Fibrillation Had Less Impact on the Risk of Ischemic Stroke in Non-anticoagulated Patients Undergoing Hemodialysis: Insight from the RAKUEN study.

Objective The progress of non-anticoagulated patients with atrial fibrillation (AF) undergoing hemodialysis has not been determined. Using data from the RAKUEN (Registry of Atrial fibrillation in chronic Kidney disease Under hEmodialysis from Niigata) study, we examined the clinical characteristics and outcomes among hemodialysis patients with AF who were not receiving a vitamin K antagonist (VKA). Methods and Results Forty-three of 423 patients undergoing hemodialysis (-10%) were prescribed a VKA. The remaining 380 patients (age 64.8±12.8 years, male 70%) were enrolled in the present study. During a mean observation period of 36 months, AF (n=55) was independently associated with all-cause death (hazard ratio, 1.82; 95% confidence interval, 1.12-2.94; p=0.014), but was not associated with ischemic stroke (hazard ratio, 1.91; 95% confidence interval, 0.74-4.92; p=0.177) and major bleeding (hazard ratio, 1.80; 95% confidence interval, 0.80-4.08; p=0.150). The crude incidence rates of all-cause death and ischemic stroke in the AF patients were 15.75 (2.5-fold higher compared to the non-AF patients) and 3.63 (1.7-fold higher compared to the non-AF patients) per 100 person-years, respectively. Conclusion A great impact on death, but not ischemic stroke, was observed in non-anticoagulated hemodialysis patients with AF in comparison to those without AF from the analysis of the RAKUEN study.

Renal histopathological findings of retinal vasculopathy with cerebral leukodystrophy.

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare autosomal dominant systemic microvascular disease. Neurological disorders and visual disturbance are highlighted as manifestations of RVCL; however, there are few reports focused on nephropathy. Herein, we describe detailed renal histopathological findings in a daughter and father with RVCL, proven by TREX1 genetic analysis. A kidney biopsy of the daughter, 35-year-old with asymptomatic proteinuria, revealed unique and various glomerular changes. Atypical double contour (not tram track-like) of the capillary wall was widely found, an apparent characteristic finding. Glomerular findings were varied due to a combination of new and old segmental mesangial proliferative changes, mesangiolysis, and segmental glomerulosclerosis-like lesions; these changes may be related to endothelial cell damage. Collapsed tufts were also found and thought to be the result of ischemia due to arterial changes. Glomerular findings in a kidney biopsy of the father revealed similarity to the daughter's glomerulus at a relatively advanced stage, but the degree of variety in the glomerular findings was much less. Kidney biopsy findings suggesting endothelial cell damage of unknown etiology need to be considered for possible RVCL.

Comparison between pre-exercise casein peptide and intact casein supplementation on glucose tolerance in mice fed a high-fat diet.

We hypothesized that along with exercise, casein peptide supplementation would have a higher impact on improving glucose tolerance than intact casein. Male 6-week-old ICR mice were provided a high-fat diet to induce obesity and glucose intolerance. The mice were randomly divided into 4 treatment groups: control (Con), endurance training (Tr), endurance training with intact casein supplementation (Cas+Tr), and endurance training with casein peptide supplementation (CP+Tr). The mice in each group were orally administrated water, intact casein, or casein peptide (1.0 mg/g body weight, every day), and then subjected to endurance training (15-25 m/min, 60 min, 5 times/week for 4 weeks) on a motor-driven treadmill 30 min after ingestion. Our results revealed that total intra-abdominal fat was significantly lower in CP+Tr than in Con (p < 0.05). Following an oral glucose tolerance test, the blood glucose area under the curve (AUC) was found to be significantly smaller for CP+Tr than for Con (p < 0.05). Moreover, in the soleus muscle, glucose transporter 4 (GLUT4) protein levels were significantly higher in CP+Tr than in Con (p < 0.01). However, intra-abdominal fat, blood glucose AUC, and GLUT4 protein content in the soleus muscle did not alter in Tr and Cas+Tr when compared with Con. These observations suggest that pre-exercise casein peptide supplementation has a higher effect on improving glucose tolerance than intact casein does in mice fed a high-fat diet.

An attenuated Shigella mutant lacking the RNA-binding protein Hfq provides cross-protection against Shigella strains of broad serotype.

Few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. Here, immunization with a mutant of Shigella flexneri 2a protected guinea pigs against subsequent infection by S. dysenteriae type 1 and S. sonnei strains. This deletion mutant lacked the RNA-binding protein Hfq leading to increased expression of the type III secretion system via loss of regulation, resulting in attenuation of cell viability through repression of stress response sigma factors. Such increased antigen production and simultaneous attenuation were expected to elicit protective immunity against Shigella strains of heterologous serotypes. Thus, the vaccine potential of this mutant was tested in two guinea pig models of shigellosis. Animals vaccinated in the left eye showed fewer symptoms upon subsequent challenge via the right eye, and even survived subsequent intestinal challenge. In addition, oral vaccination effectively induced production of immunoglobulins without severe side effects, again protecting all animals against subsequent intestinal challenge with S. dysenteriae type 1 or S. sonnei strains. Antibodies against common virulence proteins and the O-antigen of S. flexneri 2a were detected by immunofluorescence microscopy. Reaction of antibodies with various strains, including enteroinvasive Escherichia coli, suggested that common virulence proteins induced protective immunity against a range of serotypes. Therefore, vaccination is expected to cover not only the most prevalent serotypes of S. sonnei and S. flexneri 2a, but also various Shigella strains, including S. dysenteriae type 1, which produces Shiga toxin.

Thymoma with immunodeficiency/Good syndrome associated with myasthenia gravis.

Good syndrome is a rare condition in which thymoma is associated with hypogammaglobulinemia; it is characterized by repeated respiratory or systemic infections caused by bacteria, viruses, and fungi, as well as with various autoimmune disorders such as pure red cell aplasia. A 65-year-old woman was admitted to our hospital with ptosis and abdominal muscle weakness. Based on the presence of anti-acetylcholine receptor (Ach-R) antibodies, she was diagnosed with myasthenia gravis (MG). At that time, invasive thymoma of Masaoka stage IVa was also detected. Regression of thymoma and clinical remission of MG was achieved by chemotherapy followed by high-dose corticosteroid. However, several months later, the patient started developing repeated bacterial respiratory tract infections, cytomegalovirus infections, and esophageal and systemic candidiasis. Laboratory tests revealed a marked decrease of serum gamma-globulin levels (IgG 586 mg/dl, IgA 32 mg/dl, IgM 29 mg/dl) and severe reduction in the B cells ratio, as well as a decrease in the CD4+CD25+T cell to CD4+CD25-T cell ratio indicative of deregulation of CD4+T cell activation. These results suggested that the patient impaired humoral and cell-mediated immune responses. We continued the treatment with antibiotics and regular immunoglobulin supplementation through intravenous injections. Although autoimmune disorders are often observed in Good syndrome, the association with MG is quite rare. The case report is followed by the review of literature.

Two-year clinical comparison of a flowable-type nano-hybrid composite and a paste-type composite in posterior restoration.

AIM: The purpose of the present study was to compare the clinical efficacy between a flowable-type nano-hybrid composite and a paste-type composite for posterior restoration. METHODS: Of 62 posterior teeth in 33 patients (mean age: 34.1 years), 31 were filled with a paste-type composite (Heliomolar [HM] group), and another 31 with a flowable nano-hybrid composite (MI FIL [MI] group). Clinical efficacy was evaluated at 2 years after the restoration. RESULTS: There were no differences for retention, surface texture deterioration, anatomical form change, deterioration of marginal adaptation, and secondary caries, while a statistical difference was found for marginal discoloration, which was significantly greater in the HM group (P < 0.05). Furthermore, color matching in the MI group was superior to that in the HM group immediately after the restoration throughout the study period. CONCLUSIONS: The present 2-year clinical evaluation of different composites showed that the flowable nano-hybrid composite could be an effective esthetic material for posterior restoration.

Visible tunable lighting system based on polymer composites embedding ZnO and metallic clusters: from colloids to thin films.

The development of phosphor devices free of heavy metal or rare earth elements is an important issue for environmental reasons and energy efficiency. Different mixtures of ZnO nanocrystals with Cs2Mo6I8(OOC2F5)6 cluster compound (CMIF) dispersed into polyvinylpyrrolidone matrix have been prepared by very simple and low cost solution chemistry. The resulting solutions have been used to fabricate highly transparent and luminescent films by dip coating free of heavy metal or rare earth elements. The luminescence properties of solution and dip-coated films were investigated. The luminescence of such a system is strongly dependent on the ratios between ZnO and CMIF amounts, the excitation wavelength and the nature of the system. By varying these two parameters (ratio and wavelength), a large variety of colors, from blue to red as well as white, can be achieved. In addition, differences in the luminescence properties have been observed between solutions and thin films as well as changes of CMIF emission band maximum wavelength. This may suggest some possible interactions between the different luminophore centers, such as energy transfer or ligands exchange on the Mo6 clusters.

First confirmed human case of Diphyllobothrium stemmacephalum infection and molecular verification of the synonymy of Diphyllobothrium yonagoense with D. stemmacephalum (Cestoda: Diphyllobothriidea).

Several tapeworm species in the genus Diphyllobothrium Cobbold, 1858 have uncertain taxonomic positions, leading to taxonomic confusion as well as misdiagnosis of infections. Taxonomic revision based on DNA sequence analysis is considered necessary to resolve the taxonomy of several cases, including that between Diphyllobothrium stemmacephalum, the type species of the genus, and Diphyllobothrium yonagoense. Diphyllobothrium yonagoense was synonymized with D. stemmacephalum based on morphological observations by Andersen (1987), however no molecular studies have been undertaken to verify the validity of this synonymization. In the present study, the first human case confirmed molecularly as D. stemmacephalum infection is reported, and the validity of the synonymization of D. yonagoense with D. stemmacephalum was assessed based on molecular phylogenetics. Diphyllobothrium stemmacephalum and D. yonagoense grouped into the same clades with high bootstrap confidence values for both cox1 and nad3. Genetic distances between the two taxa were very small (0.000-0.012 and 0.000-0.017 for cox1 and nad3, respectively) and were considered to fall within the range of intraspecific variation. Using these molecular analyses, this study verified molecularly that D. yonagoense is a junior synonym of D. stemmacephalum. Further, the closer phylogenetic relationship between D. stemmacephalum and Diplogonoporus species rather than other diphyllobothriids, including Diphyllobothrium nihonkaiense and Diphyllobothrium latum, was corroborated. The genus name for D. nihonkaiense and D. latum is also discussed.

Clinical characteristics of hemodialysis patients with atrial fibrillation: The RAKUEN (Registry of atrial fibrillation in chronic kidney disease under hemodialysis from Niigata) study.

BACKGROUND: Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear. METHODS AND RESULTS: We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups. CONCLUSIONS: In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.