Analysis of hypoxia-associated dendritic cells in colitic mice and effects of probiotics on IL-10 production in inflammatory dendritic-cells under hypoxia.

The aim of this study was to analyse hypoxia-associated dendritic cells (DCs) in colitic mice and the effects of probiotics on interleukin (IL)-10 production in inflammatory DCs under hypoxic conditions. Extensive hypoxia was observed in the colonic mucosa of dextran sodium sulphate-induced colitic mice. Flow cytometric analysis demonstrated that hypoxia-inducible factor-1α+ DCs in colonic lamina propria (CLP) lymphocytes and mesenteric lymph nodes (MLN) were more abundant in colitic mice than those in controls. Among three subsets of DCs, i.e. plasmacytoid DCs, conventional DCs (cDCs), and monocyte-derived DCs (mDCs), cDCs and mDCs were more abundant in CLP of colitic mice. Bone marrow-derived Flt-3L-induced DCs (Flt-DCs) but not bone marrow-derived GM-CSF-induced DCs (GM-DCs), incubated with 1% O2 exhibited an inflammatory phenotype, with higher CD86, IL-6, and tumour necrosis factor-α expression, and lower IL-10 levels than those in Flt-DCs incubated with 21% O2. The hypoxia-induced decrease in IL-10 expression in Flt-DCs was restored by Bifidobacterium bifidum JCM 1255T promoted IL-10 expression through the p38 pathway under normoxic conditions. The anti-inflammatory effects of B. bifidum JCM 1255T in Flt-DCs were mediated through different cellular mechanisms under hypoxic and normoxic conditions. B. bifidum JCM 1255T could be used therapeutically for its anti-inflammatory effects.

PRUNE1-related disorder: Expanding the clinical spectrum.

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) (OMIM #617481) is an autosomal recessive disease characterized by progressive microcephaly, plagiocephaly, hypotonia, spastic quadriparesis, global developmental delay, intellectual disability, optic features and abnormal brain magnetic resonance imaging (MRI). NMIHBA was recently reported to be caused by PRUNE1 mutations. Eight mutations have been reported in 13 unrelated families. Here, we report 3 PRUNE1 mutations in 1 Caucasian and 3 Japanese families. One recurrent missense mutation (p.Asp106Asn) was previously reported in Turkish and Italian families, while the other 2 mutations (p.Leu18Serfs*8 and p.Cys180*) are novel. We also show that mutant PRUNE1 mRNA can be subject to nonsense-mediated mRNA decay. The patients presented in this study showed atypical NMIHBA phenotypes with no progressive microcephaly. Furthermore, one Caucasian case had significant macrocephaly; therefore, patients with PRUNE1 mutations can exhibit a broad and heterogeneous spectrum of phenotypes.

Cryptic lineage differentiation among Indo-Pacific bottlenose dolphins (Tursiops aduncus) in the northwest Indian Ocean.

Phylogeography can provide insight into the potential for speciation and identify geographic regions and evolutionary processes associated with species richness and evolutionary endemism. In the marine environment, highly mobile species sometimes show structured patterns of diversity, but the processes isolating populations and promoting differentiation are often unclear. The Delphinidae (oceanic dolphins) are a striking case in point and, in particular, bottlenose dolphins (Tursiops spp.). Understanding the radiation of species in this genus is likely to provide broader inference about the processes that determine patterns of biogeography and speciation, because both fine-scale structure over a range of kilometers and relative panmixia over an oceanic range are known for Tursiops populations. In our study, novel Tursiops spp. sequences from the northwest Indian Ocean (including mitogenomes and two nuDNA loci) are included in a worldwide Tursiops spp. phylogeographic analysis. We discover a new 'aduncus' type lineage in the Arabian Sea (off India, Pakistan and Oman) that diverged from the Australasian lineage ∼261 Ka. Effective management of coastal dolphins in the region will need to consider this new lineage as an evolutionarily significant unit. We propose that the establishment of this lineage could have been in response to climate change during the Pleistocene and show data supporting hypotheses for multiple divergence events, including vicariance across the Indo-Pacific barrier and in the northwest Indian Ocean. These data provide valuable transferable inference on the potential mechanisms for population and species differentiation across this geographic range.

Sensory evaluation and chemical analysis of exhaled and dermally emitted bioeffluents.

Conditions in which exhaled and dermally emitted bioeffluents could be sampled separately or together (whole-body emission) were created. Five lightly dressed males exhaled the air through a mask to another, identical chamber or without a mask to the chamber in which they were sitting; the outdoor air supply rate was the same in both chambers. The carbon dioxide concentration in the chamber with exhaled air was 2000 ppm. Chamber temperatures were 23°C or 28°C, and ozone was present or absent in the supply airflow. When dermally emitted bioeffluents were present, the perceived air quality (PAQ) was less acceptable, and the odor intensity was higher than when only exhaled bioeffluents were present. The presence or absence of exhaled bioeffluents in the unoccupied chamber made no significant difference to sensory assessments. At 28°C and with ozone present, the odor intensity increased and the PAQ was less acceptable in the chambers with whole-body bioeffluents. The concentrations of nonanal, decanal, geranylacetone, and 6-MHO were higher when dermally emitted bioeffluents were present; they increased further when ozone was present. The concentration of squalene then decreased and increased again at 28°C. Dermally emitted bioeffluents seem to play a major role in the sensory nuisance experienced when occupied volumes are inadequately ventilated.

Spatiotemporal treadmill gait measurements using a laser range scanner: feasibility study of the healthy young adults.

OBJECTIVE: Spatio-temporal parameters are typically used for gait analysis. Although these parameters are measured by sophisticated systems such as 3D motion capture system or optoelectronic bars, these systems cannot be deployed easily because of their high costs, large space requirements and elaborate set-up. The purpose of this study is to develope a system for measuring spatiotemporal gait parameters using a laser range scanner during treadmill gait. APPROACH: To calculate accurate spatiotemporal parameters, the differences between the laser range scanner measured values and the reference values obtained from a 3D motion capture system were investigated in thirty subjects. From measurements in time and position at foot contact/off, adjustments to compensate for the differences in time and position were derived. Then, to determine the validity of the proposed system, values from the proposed system and the reference system were compared in four additional subjects. MAIN RESULTS: The results indicate that the data from the laser range scanner demonstrate certain differences in time and position compared with reference values. However, when compensation values were introduced, each spatiotemporal parameter correlated well with the reference values. SIGNIFICANCE: This newer system is smaller, is easier to deploy and requires less training than the 3D motion capture system.

The clinical significance of cysteine dioxygenase type 1 methylation in Barrett esophagus adenocarcinoma.

Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patient's specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.

Spatial and temporal trends of alternative flame retardants and polybrominated diphenyl ethers in ringed seals (Phoca hispida) across the Canadian Arctic.

Concentrations of alternative flame retardants and polybrominated diphenyl ethers (PBDEs) were analyzed in ringed seal (Phoca hispida) blubber collected across the Canadian Arctic during subsistence hunts between 1998 and 2013. More than 80% of sampled animals were females and juvenile males. The highest mean ΣPBDE concentrations (sum of 13 congeners) were found in seals from Nain (Nunatsiavut) as well as Inukjuaq and Arviat (Hudson Bay) and the lowest mean levels were found in seals from Lancaster Sound. BDE-47 and -99 were the predominant PBDE congeners quantified in ringed seals. The most frequently detected non-PBDE flame retardants were polybrominated biphenyl 101 (BB-101, 57% of samples analyzed for this chemical), hexabromocyclododecane (HBCDD; 38%), hexabromobenzene (HBB, 30%), and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTeBB, 23%). The relative trophic position of seals, estimated using stable isotopes, did not vary over time and did not influence flame retardant blubber concentrations. The relative carbon source increased over time at Arviat and Resolute Bay and weak relationships were observed with ΣPBDEs in blubber of seals. ΣPBDEs increased significantly from 1998 to 2008 in ringed seals from East Baffin and subsequently decreased in recent years. PBDE levels at other sites fluctuated slightly over time. HBCDD concentrations increased at several sites over the past decade. The presence of flame retardants in ringed seals suggests their persistence and their continuous inputs in the Canadian Arctic environment. Monitoring and research on the effects of these contaminants in seals are warranted given the importance of this species in Arctic marine food webs and for local communities.

Spectroscopic properties and location of the Ce(3+) energy levels in Y3Al2Ga3O12 and Y3Ga5O12 at ambient and high hydrostatic pressure.

In this study, we present the high pressure spectroscopy of Y3Al2Ga3O12 (YAGG) and Y3Ga5O12 (YGG) ceramics doped with Ce(3+) and Cr(3+). We have found that high hydrostatic pressure recovers the Ce(3+) luminescence in YGG. The pressure-induced shifts of the ground state and the 5d1 excited state of Ce(3+) with respect to the conduction band edge were estimated. Our experimental data allowed us to also obtain the shifts of the conduction and valence band edges, and the ground state and the 5d1 state of Ce(3+) ions have been estimated with respect to the vacuum level. It has been shown that simple equivalence between the external hydrostatic pressure and intrinsic chemical pressure related to different compositions of the isostructural matrices does not exist in garnet lattices.

Characterization of unexpected postural changes during robot-assisted gait training in paraplegic patients.

STUDY DESIGN: This is a retrospective study. OBJECTIVES: The objectives of this study were to categorize unexpected postural changes (UPCs) during gait training in paraplegic patients with wearable gait-assist robots, to reveal the incidence of the UPC and its time-dependent changes during initial gait training period and to investigate neurological level-specific differences. SETTING: This study was conducted in Fujita Health University, Aichi, Japan. METHODS: We investigated five patients (46.2±14.6 years; lesion level: T6:3, T12:2). All patients had previously achieved gait with wearable robot and walker at supervision level. The UPCs were counted for 2 years and classified according to their type. The time-course data were calculated from the incidence of UPCs for 10 days from initial gait training with the walker. The neurological level-specific differences were investigated between T6 and T12 injuries. RESULTS: Eighty-five UPCs were observed and classified into three categories: anterior breakdown, posterior breakdown (PBD) and mal-timing. The average rate over the entire period was 0.96±0.62 (incidents/h/subject). PBD, which was defined as hyperflexion of both hip joints, occurred with the highest frequency (0.64±0.64 incidents/h/subject). During initial gait training, there was a gradual decrease in the occurrence of UPC. For neurological level-specific differences, UPCs were observed more frequently in T6 injuries (1.36±0.35 incidents/h/subject) compared with T12 injuries (0.36±0.31 incidents/h/subject). CONCLUSION: PBDs might be the result of near collisions between the trunk of the user and the walker, which make it difficult for the users to move their trunk over an anterior stance limb. Training that is focused upon well-timed forward movements of the walker might be required to avoid the occurrence of this common UPC.

Optical excitation and external photoluminescence quantum efficiency of Eu³âº in GaN.

We investigate photoluminescence of Eu-related emission in a GaN host consisting of thin layers grown by organometallic vapor-phase epitaxy. By comparing it with a reference sample of Eu-doped Y2O3, we find that the fraction of Eu(3+) ions that can emit light upon optical excitation is of the order of 1%. We also measure the quantum yield of the Eu-related photoluminescence and find this to reach (~10%) and (~3%) under continuous wave and pulsed excitation, respectively.

Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer.

BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

Subinhibitory concentrations of tetracyclines induce lipopolysaccharide shedding by Porphyromonas gingivalis and modulate the host inflammatory response.

BACKGROUND AND OBJECTIVE: Antibiotics at below minimal inhibitory concentrations (MICs) may induce various biological responses in bacteria. In this study, we hypothesized that subinhibitory concentrations (subICs) of tetracycline and doxycycline induce the shedding of lipopolysaccharide (LPS) by Porphyromonas gingivalis and, as a consequence, may contribute to enhancing the host inflammatory response associated with periodontitis. MATERIAL AND METHODS: A polymyxin-based enzyme-linked immunosorbent assay was used to quantify LPS shedding by P. gingivalis grown in the presence of subICs of tetracycline and doxycycline. A macrophage model was used to show that tetracycline- and doxycycline-mediated LPS shedding by P. gingivalis can induce cytokine secretion. The secretion of interleukin (IL)-1ß, IL-8, and tumor necrosis factor-α was quantified by enzyme-linked immunosorbent assay. RESULTS: LPS was shed spontaneously in a time-dependent way by P. gingivalis during growth. LPS shedding was significantly increased by growth in the presence of subICs of tetracycline and doxycycline corresponding to 1/20 of their MICs (0.025 µg/mL for tetracycline and 0.0125 µg/mL for doxycycline). This shedding was not associated with an increased rate of bacterial cell lysis. Stimulating macrophages with a P. gingivalis culture supernatant induced the secretion of IL-1ß, IL-8 and tumor necrosis factor-α when the bacteria were grown in the presence of 1/20 MIC of the antibiotics. CONCLUSION: Our study showed that growing P. gingivalis in the presence of subICs of either tetracycline or doxycycline induces LPS shedding. Shed LPS may in turn increase cytokine secretion in a macrophage model.

Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.

Multicentred surgical site infection surveillance using partitioning analysis.

BACKGROUND: Surgical site infection (SSI) is an ongoing major public health problem throughout the world that increases healthcare costs. Utilizing a methodology that can help clinicians to continuously collect data about SSIs, analyse it and implement the feedback into routine hospital practice has been identified as a top national priority in Japan. AIM: To conduct an intervention study through 'operations research' using partitioning at multiple facilities, and to reduce the incidence and consequences of SSI. METHODS: The Setouchi SSI Surveillance Group, which consists of seven institutes, started SSI surveillance in 2006. Until May of 2008, there were four surveillance periods (A-D). In all, 3089 patients underwent gastrointestinal surgery and were followed up for 30 days after their operations. Twenty-six factors that have been reported to be related to SSI were evaluated for all patients. The top three factors from each surveillance period were determined and then actual practice improvements were planned for each subsequent period. FINDINGS: The total SSI occurrence was 6.9% for period A, 6.3% for period B, 6.4% for period C and 3.9% for period D. Comparing periods A and D, there was a statistical significance in the decrease of SSI occurrence (P = 0.012). CONCLUSION: Using the results and partitioning analysis of active SSI surveillance to contribute to action plans for improving clinical practice was effective in significantly reducing SSIs.

ifn-γ-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury.

Transfer of type-1 helper T-conditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-γ (ifn-γ) knockout mice (ifn-γ(-/-) Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ(-/-) Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10(-/-)) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI.

Quantum Faraday and Kerr rotations in graphene.

Graphene, a monolayer sheet of carbon atoms, exhibits intriguing electronic properties that arise from its massless Dirac dispersion of electrons. A striking example is the half-integer quantum Hall effect, which endorses the presence of Dirac cones or, equivalently, a non-zero (π) Berry's (topological) phase. It is curious how these anomalous features of Dirac electrons would affect optical properties. Here we observe the quantum magneto-optical Faraday and Kerr effects in graphene in the terahertz frequency range. Our results detect the quantum plateaus in the Faraday and Kerr rotations at precisely the quantum Hall steps that hallmark the Dirac electrons, with the rotation angle defined by the fine-structure constant. The robust quantum Hall plateaus in the optical regime, besides being conceptually interesting, may open avenues for new graphene-based optoelectronic applications.

Progress in thermal comfort research over the last twenty years.

Climate change and the urgency of decarbonizing the built environment are driving technological innovation in the way we deliver thermal comfort to occupants. These changes, in turn, seem to be setting the directions for contemporary thermal comfort research. This article presents a literature review of major changes, developments, and trends in the field of thermal comfort research over the last 20 years. One of the main paradigm shift was the fundamental conceptual reorientation that has taken place in thermal comfort thinking over the last 20 years; a shift away from the physically based determinism of Fanger's comfort model toward the mainstream and acceptance of the adaptive comfort model. Another noticeable shift has been from the undesirable toward the desirable qualities of air movement. Additionally, sophisticated models covering the physics and physiology of the human body were developed, driven by the continuous challenge to model thermal comfort at the same anatomical resolution and to combine these localized signals into a coherent, global thermal perception. Finally, the demand for ever increasing building energy efficiency is pushing technological innovation in the way we deliver comfortable indoor environments. These trends, in turn, continue setting the directions for contemporary thermal comfort research for the next decades.

Plasmon transport in graphene investigated by time-resolved electrical measurements.

Plasmons, which are collective charge oscillations, could provide a means of confining electromagnetic field to nanoscale structures. Recently, plasmonics using graphene have attracted interest, particularly because of the tunable plasmon dispersion, which will be useful for tunable frequency in cavity applications. However, the carrier density dependence of the dispersion is weak (proportional to n(1/4)) and it is difficult to tune the frequency over orders of magnitude. Here, by exploiting electronic excitation and detection, we carry out time-resolved measurements of a charge pulse travelling in a plasmon mode in graphene corresponding to the gigahertz range. We demonstrate that the plasmon velocity can be changed over two orders of magnitude by applying a magnetic field B and by screening the plasmon electric field with a gate metal; at high B, edge magnetoplasmons, which are plasmons localized at the sample edge, are formed and their velocity depends on B, n and the gate screening effect.

Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and functional recovery after spinal cord injury.

The role of T lymphocytes in central nervous system (CNS) injuries is controversial, with inconsistent results reported concerning the effects of T-lymphocyte transfer on spinal cord injury (SCI). Here, we demonstrate that a specific T-lymphocyte subset enhances functional recovery after contusion SCI in mice. Intraperitoneal adoptive transfer of type 1 helper T (Th1)-conditioned cells 4 days after SCI promoted recovery of locomotor activity and tactile sensation and concomitantly induced regrowth of corticospinal tract and serotonergic fibers. However, neither type 2 helper T (Th2)- nor IL-17-producing helper T (Th17)-conditioned cells had such effects. Activation of microglia and macrophages were observed in the spinal cords of Th1-transfered mice after SCI. Specifically, M2 subtype of microglia/macrophages was upregulated after Th1 cell transfer. Neutralization of interleukin 10 secreted by Th1-conditioned cells significantly attenuated the beneficial effects by Th1-conditioned lymphocytes after SCI. We also found that Th1-conditioned lymphocytes secreted significantly higher levels of neurotrophic factor, neurotrophin 3 (NT-3), than Th2- or Th17-conditioned cells. Thus, adoptive transfer of pro-inflammatory Th1-conditioned cells has neuroprotective effects after SCI, with prospective implications in immunomodulatory treatment of CNS injury.