The Significance of Age and Causative Bacterial Morphology in the Choice of an Antimicrobial Agent to Treat Acute Uncomplicated Cystitis

Differentiating patients by age and causative bacterial morphology might aid in making the appropriate choice of antimicrobial agent when treating acute uncomplicated cystitis. In this retrospective analysis, the non-susceptibility rates of the causative bacteria to cefcapene-pivoxil (CFPN-PI) and levofloxacin (LVFX) were determined after dividing patients with acute uncomplicated cystitis by age group (15-54 and 55-74 years old) and by bacterial morphology: gram-positive cocci (GPC) or gram-negative rod (GNR). The overall non-susceptibility rates for CFPN-PI and LVFX were 19.4% and 15.3%, respectively. When the subjects were divided by age, only the non-susceptibility rate for LVFX in the younger group significantly decreased (to 8.7%). When the groups were divided by both age and bacterial morphology, the younger GNR group had non-susceptibility rates of 6.9% to CFPN-PI and 7.8% to LVFX, whereas the younger GPC group showed 10.2% non-susceptibility to LVFX. The older GNR group showed 9.8% non-susceptibility to CFPN-PI, while the older GPC group showed 7.2% non-susceptibility to LVFX. All the non-susceptibility rates were lower than 10.2% in the sub-divided groups. Differentiating patients by age and the morphology of causative bacteria can aid in making the appropriate choice of antimicrobial agent and may improve treatment outcomes in patients with acute uncomplicated cystitis

Effects of Rotation on Standing Accretion Shock Instability in Nonlinear Phase for Core-Collapse Supernovae

We studied the effects of rotation on standing accretion shock instability (SASI) by performing three-dimensional hydrodynamics simulations. Taking into account a realistic equation of state and neutrino heating/cooling, we prepared a spherically symmmetric and steady accretion flow through a standing shock wave onto a proto-neutron star (PNS). When the SASI entered the nonlinear phase, we imposed uniform rotation on the flow advecting from the outer boundary of the iron core, whose specific angular momentum was assumed to agree with recent stellar evolution models. Using spherical harmonics in space and Fourier decompositions in time, we performed mode analysis of the nonspherical deformed shock wave to observe rotational effects on the SASI in the nonlinear phase. We found that rotation imposed on the axisymmetric SASI did not make any spiral modes and hardly affected sloshing modes, except for steady l=2, m=0 modes. In contrast, rotation imposed on the non-axisymmetric flow increased the amplitude of spiral modes so that some spiral flows accreting on the PNS were more clearly formed inside the shock wave than without rotation. The amplitudes of spiral modes increased significantly with rotation in the progressive direction.Comment: 27 pages, 11 figures, Submitted to Ap

The Efficacy of Mirabegron for the Relief of Ureteral Stent-Related Symptoms

To investigate the efficacy of mirabegron for lower urinary tract symptoms in patients with an indwelling ureteral stent after ureterorenoscopic lithotripsy. This was a prospective follow-up study of 76 patients with stent-related symptoms (SRSs). Patients with upper urinary calculi who were pre-stented for > 2 weeks before lithotripsy were examined for the presence of SRSs by tests including the International Prostate Symptom Score (IPSS), OAB Symptom Score (OABSS), and urinary bother and pain measured by a Visual Analogue Scale (VAS) before lithotripsy. Mirabegron (50 mg/day) was prescribed post-lithotripsy for 2 weeks. SRSs were assessed at the time of stent removal. The IPSS scores improved significantly from 16.2 to 14.3 (p<0.001) and the IPSS-QoL scores decreased significantly from 5.0 to 4.6 (p=0.012). The OABSS scores improved significantly from 7.7 to 6.8 (p=0.006), and the urinary urgency scores (OABSS-Q3) decreased significantly from 3.24 to 2.68 (p<0.001). The number of nocturia episodes decreased significantly from 2.5 to 2.2 (p=0.045). Urinary bother and pain assessed by the VAS declined from 4.2 and 3.1 to 3.8 (p=0.15) and 2.5 (p=0.075), respectively. Mirabegron significantly improved SRSs and the number of nocturia episodes due to a ureteral stent

Strict De Novo Methylation of the 35S Enhancer Sequence in Gentian

A novel transgene silencing phenomenon was found in the ornamental plant, gentian (Gentiana triflora × G. scabra), in which the introduced Cauliflower mosaic virus (CaMV) 35S promoter region was strictly methylated, irrespective of the transgene copy number and integrated loci. Transgenic tobacco having the same vector did not show the silencing behavior. Not only unmodified, but also modified 35S promoters containing a 35S enhancer sequence were found to be highly methylated in the single copy transgenic gentian lines. The 35S core promoter (−90)-introduced transgenic lines showed a small degree of methylation, implying that the 35S enhancer sequence was involved in the methylation machinery. The rigorous silencing phenomenon enabled us to analyze methylation in a number of the transgenic lines in parallel, which led to the discovery of a consensus target region for de novo methylation, which comprised an asymmetric cytosine (CpHpH; H is A, C or T) sequence. Consequently, distinct footprints of de novo methylation were detected in each (modified) 35S promoter sequence, and the enhancer region (−148 to −85) was identified as a crucial target for de novo methylation. Electrophoretic mobility shift assay (EMSA) showed that complexes formed in gentian nuclear extract with the −149 to −124 and −107 to −83 region probes were distinct from those of tobacco nuclear extracts, suggesting that the complexes might contribute to de novo methylation. Our results provide insights into the phenomenon of sequence- and species- specific gene silencing in higher plants

Effects of Rotation on Stochasticity of Gravitational Waves in Nonlinear Phase of Core-Collapse Supernovae

By performing three-dimensional (3D) simulations that demonstrate the neutrino-driven core-collapse supernovae aided by the standing accretion shock instability (SASI), we study how the spiral modes of the SASI can have impacts on the properties of the gravitational-wave (GW) emission. To see the effects of rotation in the non-linear postbounce phase, we give a uniform rotation on the flow advecting from the outer boundary of the iron core, whose specific angular momentum is assumed to agree with recent stellar evolution models. We compute fifteen 3D models in which the initial angular momentum as well as the input neutrino luminosities from the protoneutron star are changed in a systematic manner. By performing a ray-tracing analysis, we accurately estimate the GW amplitudes generated by anisotropic neutrino emission. Our results show that the gravitational waveforms from neutrinos in models that include rotation exhibit a common feature otherwise they vary much more stochastically in the absence of rotation. The breaking of the stochasticity stems from the excess of the neutrino emission parallel to the spin axis. This is because the compression of matter is more enhanced in the vicinity of the equatorial plane due to the growth of the spiral SASI modes, leading to the formation of spiral flows circulating around the spin axis with higher temperatures. We point out that a recently proposed future space interferometers like Fabry-Perot type DECIGO would permit detection of these signals for a Galactic supernova.Comment: 13 Figures, ApJ in pres

Stochastic Nature of Gravitational Waves from Supernova Explosions with Standing Accretion Shock Instability

We study properties of gravitational waves based on the three-dimensional simulations, which demonstrate the neutrino-driven explosions aided by the standing accretion shock instability (SASI). Pushed by evidence supporting slow rotation prior to core-collapse, we focus on the asphericities in neutrino emissions and matter motions outside the protoneutron star. By performing a ray-tracing calculation in 3D, we estimate accurately the gravitational waveforms from anisotropic neutrino emissions. In contrast to the previous work assuming axisymmetry, we find that the gravitational waveforms vary much more stochastically because the explosion anisotropies depend sensitively on the growth of the SASI which develops chaotically in all directions. Our results show that the gravitational-wave spectrum has its peak near $\sim 100$ Hz, reflecting the SASI-induced matter overturns of $\sim O(10)$ ms. We point out that the detection of such signals, possibly visible to the LIGO-class detectors for a Galactic supernova, could be an important probe into the long-veiled explosion mechanism.Comment: 4 pages, 3 figures, accepted by ApJ

A new cancer diagnostic system based on a CDK profiling technology

AbstractA series of molecular pathological investigations of the molecules that stimulate the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous accumulation of knowledge of the clinical significance of these molecules for cancer diagnosis. However, the molecules have yet to be applied to clinical cancer diagnosis, as there is no available technology for application of the knowledge in a clinical setting. We hypothesized that the direct measurement of CDK activities and expressions (CDK profiling) might produce clinically relevant values for the diagnosis. This study investigated the clinical relevance of CDK profiling in gastrointestinal carcinoma tissues by using originally developed expression and activity analysis methods. We have established novel methods and an apparatus for analyzing the expression and activities of the CDK molecules in lysate of tumor tissue in a clinical setting, and examined 30 surgically dissected gastrointestinal carcinomas and corresponding normal mucosal specimens. We demonstrate here that remarkably elevated CDK2 activity is evident in more than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately mirrored the differences in proliferation between tumor and normal colonic tissues. Our results suggest that CDK profiling is a potent molecular–clinical approach to complement the conventional pathological diagnosis, and to further assist in the individualized medications

Ray-Tracing Analysis of Anisotropic Neutrino Radiation for Estimating Gravitational Waves in Core-Collapse Supernovae

We propose a ray-tracing method to estimate gravitational waves (GWs) generated by anisotropic neutrino emission in supernova cores. To calculate the gravitational waveforms, we derive analytic formulae in a useful form, which are applicable also for three-dimensional computations. Pushed by evidence of slow rotation prior to core-collapse, we focus on asphericities in neutrino emission and matter motions outside the protoneutron star. Based on the two-dimensional (2D) models, which mimic SASI-aided neutrino heating explosions, we compute the neutrino anisotropies via the ray-tracing method in a post-processing manner and calculate the resulting waveforms. With these computations, it is found that the waveforms exhibit more variety in contrast to the ones previously estimated by the ray-by-ray analysis (e.g., Kotake et al. (2007)). In addition to a positively growing feature, which was predicted to determine the total wave amplitudes predominantly, the waveforms are shown to exhibit large negative growth for some epochs during the growth of SASI. These features are found to stem from the excess of neutrino emission in lateral directions, which can be precisely captured by the ray-tracing calculation. Due to the negative contributions and the neutrino absorptions appropriately taken into account by the ray-tracing method, the wave amplitudes become more than one-order-of magnitude smaller than the previous estimation, thus making their detections very hard for a galactic source.On the other hand, it is pointed out that the GW spectrum from matter motions have its peak near $\sim 100$ Hz, which could be characteristic for the SASI-induced supernova explosions.(abridged)Comment: 30 pages, 17 figures, ApJ in pres

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia

Objectives: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. Methods: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). Results: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. Conclusion: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group