Olfactory dysfunction management following unilateral cranial resection for olfactory neuroblastoma.

BACKGROUND: Despite advances in techniques for olfactory neuroblastoma (ONB), such as unilateral cranial resection, preserving the patient's sense of smell remains a challenge. This study aimed to examine the effectiveness of post-operative olfactory training in patients who underwent unilateral resection of ONB. METHODS: This retrospective cohort study assessed the effect of post-operative olfactory training on olfactory preservation in patients with ONB undergoing unilateral cranial resection. Patients were divided into training intervention (n = 5) and non-intervention (n = 6) groups. Olfactory tests were conducted pre-operatively and at multiple post-operative intervals. RESULTS: Partial olfactory function was preserved in all cases in the training intervention group, whereas only 17% of cases in the non-intervention group maintained partial olfactory function. Significant improvements in olfactory test scores were observed in the training intervention group compared with the non-intervention group. CONCLUSIONS: Our findings suggest that post-operative olfactory training could aid in olfactory preservation for patients with ONB after unilateral cranial resection. However, these results should be interpreted with caution, and further research with larger cohorts and extended follow-up periods is needed to confirm these observations.

Changes in the ear canal microbiota of dogs with otitis externa.

AIMS: Otitis externa (OE), one of the most common ear diseases in dogs, is caused by bacterial pathogens such as Staphylococcus sp. To understand the network of microbial communities in the canine ear canal affected with OE, we performed a cross-sectional study using next-generation sequencing. METHODS AND RESULTS: Ear swab samples were collected from 23 OE-affected and 10 healthy control dogs, and the 16S rRNA gene sequenced using Illumina MiSeq. The otic microbiota in the OE-affected dogs showed significantly decreased alpha diversity compared to controls. The community composition also differed in the affected group, with significantly higher relative abundance of the phylum Firmicutes and the genus Staphylococcus (P = 0·01 and 0·04 respectively). Contrary to our expectations, the severity of the disease did not impact the otic microbiota in OE-affected dogs. CONCLUSIONS: The ear canal microbiota of OE-affected dogs is distinct from that of healthy dogs, irrespective of disease status. SIGNIFICANCE AND IMPACT OF THE STUDY: This study, one of the few detailed analyses of the otic microbiota, can provide practical information for the appropriate treatment of canine OE.

Competition for growth substrates in river water between Escherichia coli and indigenous bacteria illustrated by high-resolution mass spectrometry.

Escherichia coli normally cannot grow in the environment. One environmental stress that prevents E. coli growth may be the competition for growth substrates with co-existing micro-organisms. In this study, the growth substrates of E. coli were screened by high-resolution mass spectrometry and compared with those of indigenous bacteria in river water. In an incubation experiment, E. coli multiplied in sterilized river water, but did not multiply when indigenous micro-organisms were present in the water. By analysing dissolved organic matter in the river water before and after E. coli growth, 35 compounds were identified as putative growth substrates of E. coli. Among them, 33 compounds were also identified as putative growth substrates of indigenous bacteria. These results indicate that E. coli and indigenous bacteria compete for organic substrates in river water, which could suppress the growth of E. coli.

Fetal echocardiographic prediction score for perinatal mortality in tricuspid valve dysplasia and Ebstein's anomaly.

OBJECTIVES: Tricuspid valve dysplasia (TVD) and Ebstein's anomaly (EA) diagnosed by fetal echocardiography vary greatly in terms of clinical severity and prognosis. The Celermajer index and Simpson-Andrews-Sharland (SAS) score have been reported previously for the prediction of prognosis in cases of TVD/EA; however, they do not take into account the hemodynamic impact of left ventricular (LV) function, which has recently been implicated as being important in the pathophysiology of TVD/EA. The aim of this study was to develop a novel scoring system that includes LV function for the prediction of perinatal death in fetuses diagnosed with TVD/EA. METHODS: The clinical records of 36 fetuses diagnosed prenatally with TVD/EA between 2000 and 2015 in our hospital were reviewed. Univariate analysis was used to assess the association between perinatal death (defined as death between 22 weeks' gestation and 4 weeks after delivery) and gestational age at diagnosis, cardiothoracic area ratio (CTAR), degree of pulmonary artery flow, direction of ductal flow, right-to-left ventricular diameter ratio, tricuspid regurgitation (TR) maximum velocity, Celermajer index, SAS score and LV-Tei index. A new prognostic score, the TRIPP score (TRIcuspid malformation Prognosis Prediction score), was developed using the parameters found to be associated significantly with perinatal death. The predictive value of this score was assessed in an additional nine fetuses diagnosed with TVD/EA. RESULTS: Thirty-six fetuses were diagnosed prenatally with TVD/EA, two of which were terminated, one was lost to follow-up and two died before 22 weeks' gestation. Of the 31 included fetuses, 10 (32%) died in the perinatal period. Univariate analysis demonstrated that TR maximum velocity was significantly lower (2.22 ± 0.17 m/s vs 3.26 ± 0.12 m/s; P < 0.001) and SAS score was significantly higher (5.7 ± 0.6 points vs 2.8 ± 0.4 points; P = 0.0014) in cases of perinatal death than in surviving fetuses. The degree of pulmonary artery flow and the direction of ductal flow were also associated significantly with perinatal death (P < 0.01 for both). Notably, LV-Tei index was significantly higher in cases of perinatal death than in surviving fetuses (0.81 ± 0.08 vs 0.50 ± 0.05; P < 0.001). In contrast, there was no significant difference in Celermajer index, CTAR or right-to-left ventricular diameter ratio. Finally, we established a novel combinatorial scoring system, the TRIPP score, including the four significant factors: TR maximum velocity, pulmonary artery flow, direction of ductal flow and LV-Tei index. The TRIPP score was found to predict efficiently perinatal mortality in fetuses with TVD/EA. CONCLUSIONS: Our novel combinatorial score of echocardiographic parameters, the TRIPP score, including LV-Tei index, is easy to measure and provides a good tool for the prediction of perinatal mortality in fetuses diagnosed prenatally with TVD/EA. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study.

The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42-75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1-6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1-98.3%), with a CR rate of 86.5% (95% CI 71.2-95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3-83.3%) and 88.9% (95% CI 73.1-95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.

Epidemiology and genotypic characterisation of dissemination patterns of uropathogenic Escherichia coli in a community.

To characterise the dissemination patterns of uropathogenic Escherichia coli (UPEC) in a community, we conducted a study utilising molecular and fundamental descriptive epidemiology. The subjects, consisted of women having community-acquired acute urinary tract infection (UTI), were enrolled in the study from 2011 to 2012. UPEC isolates were subjected to antibacterial-susceptibility testing, O serogrouping, phylotyping, multilocus-sequence typing with phylogenetic-tree analysis and pulsed-field-gel electrophoresis (PFGE). From the 209 unique positive urinary samples 166 UPEC were isolated, of which 129 were fully susceptible to the tested antibiotics. Of the 53 sequence types (STs), the four most prevalent STs (ST95, ST131, ST73 and ST357) accounted for 60% of all UPEC strains. Antimicrobial resistance was less frequently observed for ST95 and ST73 than for the others. A majority of rare STs and a few common STs constituted the diversity pattern within the population structure, which was composed of the two phylogenetically distinct clades. Eleven genetically closely related groups were determined by PFGE, which accounted for 42 of the 166 UPEC isolates, without overt geo-temporal clustering. Our results indicate that a few major lineages of UPEC, selected by unidentified factors, are disseminated in this community and contribute to a large fraction of acute UTIs.

Equol inhibits growth and spore formation of Clostridioides difficile.

AIMS: Equol is a nonsteroidal oestrogen of the isoflavone class. We investigated the antibacterial ability of equol with respect to the growth rate, toxin production and spore-forming abilities of Clostridioides difficile BI/027/NAP1. METHODS AND RESULTS: Isoflavones, or female hormones, were added to bacterial culture, which was grown at 35°C. The absorbance of the culture was measured at various time points for evaluating the growth inhibition. The toxin levels in the media and morphological changes were also assessed. To evaluate the influence of equol on the sporulation of C. difficile, cells were collected at various time points from the equol-supplemented culture and the number of spores was counted. Our results show that equol inhibits bacterial growth in a concentration-dependent manner. However, it does not inhibit the production of toxin by C. difficile. Other isoflavones and female hormones did not inhibit the C. difficile growth. At the 14th day, approximately 600 spores were present in the control medium and only six were seen in the equol-containing medium. CONCLUSION: Our results suggest that equol may directly inhibit the C. difficile growth in a concentration-dependent manner and spore formation. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the antimicrobial ability of equol.

Medial and lateral laxity in knees with advanced medial osteoarthritis.

OBJECTIVE: An increase in coronal laxity is recognized as a risk factor for progression of knee osteoarthritis (OA). The purpose of this study was to evaluate coronal laxity, which was defined as the angular motion from the neutral, unloaded (baseline) position to the loaded position, in patients with advanced medial knee OA. METHOD: Preoperative coronal laxity was assessed using radiographs in patients with medial knee OA undergoing total knee arthroplasty by applying a force of 150 N with an arthrometer. A consecutive series of 211 knees with OA and 40 normal control knees were examined. A knee with OA was defined as clinically "balanced" when the difference between medial and lateral laxity was 3° or less. Values are expressed as median [25th, 75th percentile]. RESULTS: The laxity was 4° [3, 5] from the baseline on the medial side and 3° [2, 4] on the lateral side. The distribution of medial and lateral laxity indicated that 90% (189/211) of patients fell within 3°. The equivalence test showed that the medial and lateral laxity was similar, with an equivalence margin of 3° (P < 0.001). In the control knees, the laxity was 3° [2, 4] from the baseline on the medial side and 2° [2, 4] on the lateral side. The differences between the knees with advanced OA and the controls were significant (P = 0.005, medial; P = 0.006, lateral). CONCLUSION: This study showed that a clinically balanced knee was maintained even in patients with advanced medial knee OA.

Intermetallic: A Pseudoelement for Catalysis.

A clear correlation between electronic structure and CO2 selectivity for steam reforming of methanol (SRM) was obtained with PdZn, PtZn, NiZn, and PdCd intermetallics on the basis of experiments and calculations. In order to rule out the effects of oxide supports, the intermetallic powders were simply prepared by alloying in an arc furnace followed by crushing in a mortar. PdZn and PdCd exhibit valence electronic densities of states similar to that of Cu and significant chemical shifts (larger than 1 eV) of Pd 3d states with respect to pure Pd, as verified by high-resolution hard X-ray photoelectron spectroscopy (HXPS) measurements and density functional theory (DFT) calculations. Consequently, they show the similar high selectivity of CO2 for the SRM reaction. However, this is not the case for PtZn and NiZn because of the slight differences in their valence electronic structures from that of PdZn. The interval between the Fermi level and the top of the d band is closely related to the selectivity of CO2 for the SRM: the larger the interval is, the higher is the selectivity of CO2. According to DFT calculations for bulk PdZn performed by Chen et al. ( Phys. Rev. B 2003 , 68 , 075417 ), the (111) and (100) surfaces exposing Zn and Pd in an equimolar ratio are more stable than the (001) or (110) surfaces terminated by alternative Zn or Pd layers. First-principles slab calculations for PdZn, PtZn, and NiZn show that bond breaking on the surface leads to a reduction in the d bandwidth but that the d band for stable (111) or (100) surfaces remains essentially unchanged from that of the bulk. It is intriguing that PdZn and PdCd do not contain Cu but show similar valence electronic structure and catalytic selectivity, and hence, a concept is proposed where PdZn and PdCd are regarded as pseudoelements of Cu. The basis of this concept is like electronic structure, like catalysis, which has been demonstrated by experiments and calculations. This is a logical way to enable us to look for new catalysts in which precious metals are partially or completely replaced by base metals. We do not expect that this concept can be applied to all catalytic reactions, but this approach is one of most promising ways to derive a better understanding of the origin of catalytic mechanisms and eventually allow us to design useful catalysts intentionally in the future. This Account reviews the authors' published works on this topic.

Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel.

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.

Pressure-induced stacking disorder in boehmite.

The structure of an aluminum layered hydroxide, boehmite (γ-AlOOH), as a function of pressure was studied by using in situ synchrotron X-ray and neutron diffraction. Peak broadening, which is only found for hkl (h ≠ 0) peaks in the X-ray diffraction patterns, is explained by stacking disorder accompanying a continuously increasing displacement of the AlO6 octahedral layer along the a-axis. This finding could be the first experimental result for pressure-induced stacking disorder driven by continuous layer displacement. The magnitude of the layer displacement was estimated from the X-ray scattering profile calculation based on the stacking disordered structure model. Hydrogen bond geometries of boehmite, obtained by structure refinements of the observed neutron diffraction patterns for the deuterated sample up to 10 GPa, show linearly approaching O-D covalent and DO hydrogen bond distances and they merge below 26 GPa. Pressure-induced stacking disorder makes the electrostatic potential of hydrogen bonds asymmetric, yielding less chance for proton-tunnelling.

Clonal Deletion Established via Invariant NKT Cell Activation and Costimulatory Blockade Requires In Vivo Expansion of Regulatory T Cells.

Recently, the immune-regulating potential of invariant natural killer T (iNKT) cells has attracted considerable attention. We previously reported that a combination treatment with a liposomal ligand for iNKT cells and an anti-CD154 antibody in a sublethally irradiated murine bone marrow transplant (BMT) model resulted in the establishment of mixed hematopoietic chimerism through in vivo expansion of regulatory T cells (Tregs). Herein, we show the lack of alloreactivity of CD8(+) T cells in chimeras and an early expansion of donor-derived dendritic cells (DCs) in the recipient thymi accompanied by a sequential reduction in the donor-reactive Vß-T cell receptor repertoire, suggesting a contribution of clonal deletion in this model. Since thymic expansion of donor DCs and the reduction in the donor-reactive T cell repertoire were precluded with Treg depletion, we presumed that Tregs should preform before the establishment of clonal deletion. In contrast, the mice thymectomized before BMT failed to increase the number of Tregs and to establish CD8(+) T cell tolerance, suggesting the presence of mutual dependence between the thymic donor-DCs and Tregs. These results provide new insights into the regulatory mechanisms that actively promote clonal deletion.

IMP-27, a Unique Metallo-ß-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis.

A novel metallo-ß-lactamase gene, blaIMP-27, was identified in unrelated Proteus mirabilis isolates from two geographically distinct locations in the United States. Both isolates harbor blaIMP-27 as part of the first gene cassette in a class 2 integron. Antimicrobial susceptibility testing indicated susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime was a substrate for IMP-27.

Effect of periodontal surgery on oral health-related quality of life in patients who have completed initial periodontal therapy.

BACKGROUND AND OBJECTIVE: Patient-centered assessments are particularly important in periodontal treatment in which their concerns may differ from the traditional clinical endpoints. However, information is limited regarding the influence of periodontal surgery on patients' quality of life (QoL). The aim of the present study was to investigate the impact of surgical periodontal therapy on the oral health-related QoL of patients who have received initial periodontal therapy. METHODS: A three-center prospective clinical study design was used, with the study participants comprising patients with moderate to severe periodontitis. Following initial periodontal therapy, the participants received either surgical or non-surgical periodontal treatment. The Oral Health-related Quality of Life Model for Dental Hygiene (OHRQL instrument), was used to assess participants' oral health-related QoL at each periodontal assessment interval: baseline (phase I), after initial therapy (phase II) and after surgery or during supportive periodontal therapy (phase III). RESULTS: Seventy-six patients (26 non-surgery, 50 surgery) completed the third phase of OHRQL assessment and were subjected to data analysis. From phase II to III, an improvement was achieved in all clinical parameters (p < 0.05-0.001) in the surgery group, whereas no such improvement was observed in the non-surgery group. In both groups, a significant difference in total OHRQL score was noted between phases I and III (p < 0.001 for surgery and p < 0.05 for non-surgery). The OHRQL domain scores for pain and eating/chewing function showed a significant improvement between these time points. However, no further significant improvement in OHRQL scores was achieved from phase II to III. CONCLUSION: A significant improvement in oral health-related QoL was noted between phases I and III in the surgery and non-surgery groups. Such improvement was less pronounced in the non-surgery vs. the surgery group. From phase II to III, neither surgery nor non-surgical treatment yielded significant improvement in oral health-related QoL.

Helicobacter cinaedi bacteremia in four renal transplant patients: clinical features and an important suggestion regarding the route of infection.

Helicobacter cinaedi can cause bacteremia mainly in immunocompromised patients. We present the clinical characteristics of H. cinaedi bacteremia in 4 renal transplant patients. Interestingly, all cases showed triggers of bacterial translocation: 2 cases developed after colonic perforation caused by diverticulitis, 1 case developed post cholecystectomy, and the remaining patient had chronic diarrhea. Accordingly, bacterial translocation caused by severe gastrointestinal complication could be a cause of H. cinaedi bacteremia.

Dielectric-loaded surface plasmon polariton crossing waveguides using multimode interference.

A low-loss low-crosstalk multimode interference (MMI) crossing design for dielectric-loaded surface plasmon polariton waveguides (DLSPPWs), which are SiO2 stripes on Au films, is demonstrated numerically and experimentally. DLSPPWs are compatible with strong surface plasmon polariton (SPP) field confinement and maintain relatively low propagation losses. Unlike simpler crossings without MMI structures, low insertion loss of 0.65 dB and low crosstalk of -20.27 dB is confirmed numerically at a crossing angle of 10° when using tilted mirror-imaged MMI crossings. Similar insertion losses were also confirmed experimentally. The proposed structure will be beneficial for plasmonic device miniaturization and flexible patterning of optical interconnections.

Universality class of the mott transition.

Pressure dependence of the conductivity and thermoelectric power is measured through the Mott transition in the layer organic conductor EtMe_{3}P[Pd(dmit)_{2}]_{2}. The critical behavior of the thermoelectric effect provides a clear and objective determination of the Mott-Hubbard transition during the isothermal pressure sweep. Above the critical end point, the metal-insulator crossing, determined by the thermoelectric effect minimum value, is not found to coincide with the maximum of the derivative of the conductivity as a function of pressure. We show that the critical exponents of the Mott-Hubbard transition fall within the Ising universality class regardless of the dimensionality of the system.

A novel approach inducing transplant tolerance by activated invariant natural killer T cells with costimulatory blockade.

Invariant natural killer T (iNKT) cells are one of the innate lymphocytes that regulate immunity, although it is still elusive how iNKT cells should be manipulated for transplant tolerance. Here, we describe the potential of a novel approach using a ligand for iNKT cells and suboptimal dosage of antibody for CD40-CD40 ligand (L) blockade as a powerful method for mixed chimerism establishment after allogenic bone marrow transplantation in sublethally irradiated fully allo recipients. Mixed-chimera mice accepted subsequent cardiac allografts in a donor-specific manner. High amounts of type 2 helper T cytokines were detected right after iNKT cell activation, while subsequent interferon-gamma production by NK cells was effectively inhibited by CD40/CD40L blockade. Tolerogenic components, such as CD11c(low) mPDCA1(+) plasmacytoid dendritic cells and activated regulatory T cells (Tregs) expressing CD103, KLRG-1 and PD-1, were subsequently augmented. Those activating Tregs seem to be required for the establishment of chimerism because depletion of the Tregs 1 day before allogenic cell transfer resulted in a chimerism brake. These results collectively suggest that our new protocol makes it possible to induce donor-specific tolerance by enhancement of the innate ability for immune tolerance in place of the conventional immunosuppression.

Activation of invariant natural killer T cells in regional lymph nodes as new antigen-specific immunotherapy via induction of interleukin-21 and interferon-γ.

Invariant natural killer T (iNKT) cells play important immunoregulatory functions in allergen-induced airway hyperresponsiveness and inflammation. To clarify the role of iNKT cells in allergic rhinitis (AR), we generated bone marrow-derived dendritic cells (BMDCs), which were pulsed by ovalbumin (OVA) and α-galactosylceramide (OVA/α-GalCer-BMDCs) and administered into the oral submucosa of OVA-sensitized mice before nasal challenge. Nasal symptoms, level of OVA-specific immunoglobulin (IgE), and T helper type 2 (Th2) cytokine production in cervical lymph nodes (CLNs) were significantly ameliorated in wild-type (WT) mice treated with OVA/α-GalCer-BMDCs, but not in WT mice treated with OVA-BMDCs. These anti-allergic effects were not observed in Jα18(-/-) recipients that lack iNKT cells, even after similar treatment with OVA/α-GalCer-BMDCs in an adoptive transfer study with CD4(+) T cells and B cells from OVA-sensitized WT mice. In WT recipients of OVA/α-GalCer-BMDCs, the number of interleukin (IL)-21-producing iNKT cells increased significantly and the Th1/Th2 balance shifted towards the Th1 dominant state. Treatment with anti-IL-21 and anti-interferon (IFN)-γ antibodies abrogated these anti-allergic effects in mice treated with α-GalCer/OVA-BMDCs. These results suggest that activation of iNKT cells in regional lymph nodes induces anti-allergic effects through production of IL-21 or IFN-γ, and that these effects are enhanced by simultaneous stimulation with antigen. Thus, iNKT cells might be a useful target in development of new treatment strategies for AR.

Hydrodynamic fingering instability induced by a precipitation reaction.

We experimentally demonstrate that a precipitation reaction at the miscible interface between two reactive solutions can trigger a hydrodynamic instability due to the buildup of a locally adverse mobility gradient related to a decrease in permeability. The precipitate results from an A+B→C type of reaction when a solution containing one of the reactants is injected into a solution of the other reactant in a porous medium or a Hele-Shaw cell. Fingerlike precipitation patterns are observed upon displacement, the properties of which depend on whether A displaces B or vice versa. A mathematical modeling of the underlying mobility profile confirms that the instability originates from a local decrease in mobility driven by the localized precipitation. Nonlinear simulations of the related reaction-diffusion-convection model reproduce the properties of the instability observed experimentally. In particular, the simulations suggest that differences in diffusivity between A and B may contribute to the asymmetric characteristics of the fingering precipitation patterns.