Although the oral environment significantly affects the risk of pneumonia, there have been few studies regarding its relation with swallowing. There is no doubt that there is a significant link ...between the oral environment and the development of pneumonia; however, there have been few comparative studies of swallowing using video endoscopy (VE) and video fluorography (VF) as indicators to determine the actual availability of oral intake and the choice of food form. This study was performed to examine whether the oral environment or swallowing function contributes more to the development of pneumonia in the elderly.
The study population consisted of 24 patients (7 men and 17 women; age range: 64-97 years; average age: 86 years) assessed using the Oral Health Assessment Tool (OHAT), VE and VF at Fukuoka Dental College Hospital. The most common disease was pneumonia (17 patients), followed by cerebral infarction (5 patients), pyelonephritis (4 patients), bronchitis (2 patients), Parkinson's disease (2 patients), scleroderma (1 patient), diabetes (1 patient), eosophageal cancer (1 patient) and Parkinson's syndrome> (1 patient). Some patients had multiple diseases. Oral intake was possible in 20 patients (80%), whereas tube feeding and gastric banding were required in 4 patients.
The OHAT score was not correlated with either the VE or VF score. Furthermore, the OHAT score was not significantly different between the multiple- and no/single-pneumonia episode groups. The group with multiple episodes of pneumonia had lower VE and VF scores than those with no or only a single episode of pneumonia.
Oral assessment, VE and VF are necessary to evaluate swallowing in patients with suspected dysphagia. Swallowing function, especially as assessed by VE and VF, is more important than examination of the oral environment for evaluating risk of recurrent aspiration pneumonia in the elderly. In addition, multiple factors contribute to recurrent pneumonia in patients with a good oral environment, including subclinical aspiration, pharyngeal clearance and delayed activation of the gag reflex.
Kulldorff's spatial scan statistic and its software implementation - SaTScan - are widely used for detecting and evaluating geographic clusters. However, two issues make using the method and ...interpreting its results non-trivial: (1) the method lacks cartographic support for understanding the clusters in geographic context and (2) results from the method are sensitive to parameter choices related to cluster scaling (abbreviated as scaling parameters), but the system provides no direct support for making these choices. We employ both established and novel geovisual analytics methods to address these issues and to enhance the interpretation of SaTScan results. We demonstrate our geovisual analytics approach in a case study analysis of cervical cancer mortality in the U.S.
We address the first issue by providing an interactive visual interface to support the interpretation of SaTScan results. Our research to address the second issue prompted a broader discussion about the sensitivity of SaTScan results to parameter choices. Sensitivity has two components: (1) the method can identify clusters that, while being statistically significant, have heterogeneous contents comprised of both high-risk and low-risk locations and (2) the method can identify clusters that are unstable in location and size as the spatial scan scaling parameter is varied. To investigate cluster result stability, we conducted multiple SaTScan runs with systematically selected parameters. The results, when scanning a large spatial dataset (e.g., U.S. data aggregated by county), demonstrate that no single spatial scan scaling value is known to be optimal to identify clusters that exist at different scales; instead, multiple scans that vary the parameters are necessary. We introduce a novel method of measuring and visualizing reliability that facilitates identification of homogeneous clusters that are stable across analysis scales. Finally, we propose a logical approach to proceed through the analysis of SaTScan results.
The geovisual analytics approach described in this manuscript facilitates the interpretation of spatial cluster detection methods by providing cartographic representation of SaTScan results and by providing visualization methods and tools that support selection of SaTScan parameters. Our methods distinguish between heterogeneous and homogeneous clusters and assess the stability of clusters across analytic scales.
We analyzed the cervical cancer mortality data for the United States aggregated by county between 2000 and 2004. We ran SaTScan on the dataset fifty times with different parameter choices. Our geovisual analytics approach couples SaTScan with our visual analytic platform, allowing users to interactively explore and compare SaTScan results produced by different parameter choices. The Standardized Mortality Ratio and reliability scores are visualized for all the counties to identify stable, homogeneous clusters. We evaluated our analysis result by comparing it to that produced by other independent techniques including the Empirical Bayes Smoothing and Kafadar spatial smoother methods. The geovisual analytics approach introduced here is developed and implemented in our Java-based Visual Inquiry Toolkit.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Cancer cells acquire drug resistance through the following stages: nonresistant, pre-resistant, and resistant. Although the molecular mechanism of drug resistance is well investigated, the ...process of drug resistance acquisition remains largely unknown. Here we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells can be subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance.
The heart responds to hemodynamic overload through cardiac hypertrophy and activation of the fetal gene program. However, these changes have not been thoroughly examined in individual cardiomyocytes, ...and the relation between cardiomyocyte size and fetal gene expression remains elusive. We established a method of high-throughput single-molecule RNA imaging analysis of in vivo cardiomyocytes and determined spatial and temporal changes during the development of heart failure.
We applied three novel single-cell analysis methods, namely, single-cell quantitative PCR (sc-qPCR), single-cell RNA sequencing (scRNA-seq), and single-molecule fluorescence in situ hybridization (smFISH). Isolated cardiomyocytes and cross sections from pressure overloaded murine hearts after transverse aortic constriction (TAC) were analyzed at an early hypertrophy stage (2 weeks, TAC2W) and at a late heart failure stage (8 weeks, TAC8W). Expression of myosin heavy chain β (Myh7), a representative fetal gene, was induced in some cardiomyocytes in TAC2W hearts and in more cardiomyocytes in TAC8W hearts. Expression levels of Myh7 varied considerably among cardiomyocytes. Myh7-expressing cardiomyocytes were significantly more abundant in the middle layer, compared with the inner or outer layers of TAC2W hearts, while such spatial differences were not observed in TAC8W hearts. Expression levels of Myh7 were inversely correlated with cardiomyocyte size and expression levels of mitochondria-related genes.
We developed a new image-analysis pipeline to allow automated and unbiased quantification of gene expression at the single-cell level and determined the spatial and temporal regulation of heterogenous Myh7 expression in cardiomyocytes after pressure overload.
•Novel pipeline combines scRNA-seq and smFISH with high-throughput image analysis.•Stress response shown by increased Myh7 expression was spatially heterogeneous.•Mitochondria-related genes inversely correlated with Myh7 in scRNA-seq data.
Decreased cell size in Myh7-positive cells suggests energy metabolism crisis.
We have measured the mechanical strain, θ = d L θ L θ , using strain gauges adhered along the circumferential (θ) direction on the EuBaCuO ring bulk reinforced by an aluminum alloy ring during the ...cooling process from 289 K to 50 K, and during field-cooled magnetization (FCM) at 50 K under magnetic fields from Bapp = 5.3 and 6.3 T. To discuss the mechanical reinforcement effect of the aluminum alloy ring and the magnetic strain during FCM, we have performed numerical simulations using the finite element method for the ring bulk assuming realistic superconducting characteristics. The experimental results of the thermal strain during the cooling process, θ c o o l = d L θ c o o l L θ , from 289 K to 50 K on the bulk surface validated our numerical results, in which the θ c o o l value became smaller at the outer edge, compared to that at the inner edge of the bulk surface. These results strongly suggest an inhomogeneous reinforcement of the bulk due to the difference in the thermal contraction along the height direction between the ring bulk and the outer Al alloy ring with finite height. The experimental results of the time step dependence of the magnetic strain during FCM, θ F C M = d L θ F C M L θ , were reproduced qualitatively by the numerical simulation. The measurement of mechanical strain is effective to clarify the reinforcement effect of the metal ring during cooling and the mechanical stress during FCM.
Background Tramadol, a synthetic opioid analgesic, is metabolized to highly active O-desmethylate (ODT) by cytochrome P450 (CYP) 2D6 and to lowly active N-desmethylate (NDT) by CYP2B6 and CYP3A4. The ...aim of this study was to evaluate the influence of CYP2D6 phenotype on the plasma disposition of tramadol and its metabolic...
Abstract
The SuperKEKB accelerator is a electron-positron collider consisting of the 7 GeV electron ring (high energy ring or HER) and the 4 GeV positron ring (low energy ring or LER). The ...commissioning of the SuperKEKB accelerator is underway, aiming to supply a great number of interaction events of electrons and positrons to the Belle II detector which is used for discovering the new physics beyond the standard model. The important milestone is to obtain integrated luminosity of 15 ab
–1
in the next decade, so that the luminosity should exceed 2 × 10
35
cm
–2
s
–1
in several years. To achieve the goal, both rings have to be filled with high current beam of a few amperes, where the high injection efficiency is vitally important because lifetime is expected to be very short. One of the key components of the injection system is the septum magnet. It has been found that a transverse fringe field near the septum plate has sizable multipole components. A tracking simulation shows such fringe fields generate a vertical non-Gaussian tail, which could cause a beam background as well as a bad injection efficiency. Though quadrupole component in the multipoles could be, in principle, cancelled by adjusting the quadrupole magnets in the upstream of the beam line, it turned out to be difficult in actual operation. Even the quadrupole component was perfectly cancelled, components higher than quadrupole would be still harmful, since it generates a beam halo in the ring after injection, which increases the beam backgrounds to the Belle II detector. This paper describes about improvement of the field quality of the septum magnet.
The genome of influenza virus (viral RNA vRNA) is associated with the nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical viral ribonucleoprotein (vRNP) complexes. The ...NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using a Saccharomyces cerevisiae replicon system and a single-gene deletion library of Saccharomyces cerevisiae (T. Naito, Y. Kiyasu, K. Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata, Proc Natl Acad Sci USA, 104:18235-18240, 2007, https://doi.org/10.1073/pnas.0705856104). In infected Prp18 knockdown (KD) cells, the synthesis of vRNA, cRNA, and viral mRNAs was reduced. Prp18 was found to stimulate in vitro viral RNA synthesis through its interaction with NP. Analyses using in vitro RNA synthesis reactions revealed that Prp18 dissociates newly synthesized RNA from the template after the early elongation step to stimulate the elongation reaction. We found that Prp18 functions as a chaperone for NP to facilitate the formation of NP-RNA complexes. Based on these results, it is suggested that Prp18 accelerates influenza virus RNA synthesis as an NP chaperone for the processive elongation reaction.
Templates for viral RNA synthesis of negative-stranded RNA viruses are not naked RNA but rather RNA encapsidated by viral nucleocapsid proteins forming vRNP complexes. However, viral basic proteins tend to aggregate under physiological ionic strength without chaperones. We identified the pre-mRNA processing factor Prp18 as a stimulatory factor for influenza virus RNA synthesis. We found that one of the targets of Prp18 is NP. Prp18 facilitates the elongation reaction of viral polymerases by preventing the deleterious annealing of newly synthesized RNA to the template. Prp18 functions as a chaperone for NP to stimulate the formation of NP-RNA complexes. Based on these results, we propose that Prp18 may be required to maintain the structural integrity of vRNP for processive template reading.
Fabry disease is an X-linked disease caused by mutations in α-galactosidase A (GLA); these mutations result in the accumulation of its substrates, mainly globotriaosylceramide (Gb3). The accumulation ...of glycosphingolipids induces pathogenic changes in various organs, including the heart, and Fabry cardiomyopathy is the most frequent cause of death in patients with Fabry disease. Existing therapies to treat Fabry disease have limited efficacy, and new approaches to improve the prognosis of patients with Fabry cardiomyopathy are required.
We generated induced pluripotent stem cell (iPSC) lines from a female patient and her son. Each iPSC clone from the female patient showed either deficient or normal GLA activity, which could be used as a Fabry disease model or its isogenic control, respectively. Erosion of the inactivated X chromosome developed heterogeneously among clones, and mono-allelic expression of the GLA gene was maintained for a substantial period in a subset of iPSC clones. Gb3 accumulation was observed in iPSC-derived cardiomyocytes (iPS-CMs) from GLA activity-deficient iPSCs by mass-spectrometry and immunofluorescent staining. The expression of ANP was increased, but the cell surface area was decreased in iPS-CMs from the Fabry model, suggesting that cardiomyopathic change is ongoing at the molecular level in Fabry iPS-CMs. We also established an algorithm for selecting proper Gb3 staining that could be used for high-content analysis-based drug screening.
We generated a Fabry cardiomyopathy model and a drug screening system by using iPS-CMs from a female Fabry patient. Drug screening using our system may help discover new drugs that would improve the prognosis of patients with Fabry cardiomyopathy.
•iPSC lines from a female Fabry patient have either normal/deficient GLA.•Accumulation of Gb3 is observed in GLA-deficient iPS-CMs.•ANP expression is increased even in ventricular-subtype of GLA-deficient iPS-CMs.•High-content screening system for investigation of new Fabry drugs is established.•Algorithm for selecting proper Gb3 staining is a key for accurate evaluation.
We have performed numerical simulations of the electromagnetic hoop stress, σθ, in a REBaCuO disk bulk reinforced by a metal ring during pulsed-field magnetization (PFM) using a solenoid coil, in ...which the superconducting characteristics of the bulk material were assumed to have realistic Jc-B-T ones. The compressive and tensile σθ stresses were applied in the bulk during the ascending and descending stages of PFM, respectively. The time and position dependences of the mechanical stresses were estimated. The possibility of mechanical fracture due to these hoop stresses and the effect of the metal ring reinforcement were discussed.
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