Bladder Pain Syndrome Treated with Triple Therapy with Gabapentin, Amitriptyline, and a Nonsteroidal Anti-Inflammatory Drug

PurposeBladder pain syndrome is a chronic disease that manifests as bladder pain, frequency, nocturia, and urgency. Gabapentin, amitriptyline, and nonsteroidal anti-inflammatory drugs are efficacious treatments for bladder pain syndrome. Here, we assessed the effect of triple therapy with these drugs in women with bladder pain syndrome.MethodsBetween May 2007 and May 2010, we conducted a prospective nonrandomized study on 74 patients with bladder pain syndrome. Of these patients, 38 (11 men and 27 women; mean age, 55.9 years; range, 25 to 77 years; mean follow-up, 12.6 months) were administered the interstitial cystitis (IC) symptom scales (O'Leary-Sant Symptom Index) and visual analog scale (VAS) 1, 3, and 6 months after treatment to assess the efficacy of triple therapy.ResultsThe pretreatment O'Leary-Sant IC symptom score was 11.7, and the post-treatment scores were 4.4, 3.8, and 4.0 at 1, 3, and 6 months, respectively; the pretreatment problem index score was 10.5, and the post-treatment scores were 3.7, 2.7, and 2.9 at 1, 3, and 6 months, respectively. The pretreatment VAS score was 6.7, and the post-treatment scores were 1.8, 1.5, and 1.7 at 1, 3, and 6 months, respectively. The O'Leary-Sant IC symptom index and problem index and VAS scores improved considerably 1 month after treatment (P<0.05). However, the results at 1, 3, and 6 months after treatment were not significantly different (P>0.05).ConclusionsTriple therapy was sufficiently effective in patients with bladder pain syndrome and caused no significant adverse effects. However, large-scale studies should be performed to verify our findings

Isolating the Roper Resonance in Lattice QCD

We present results for the first positive parity excited state of the nucleon, namely, the Roper resonance ($N^{{{1/2}}^{+}}$=1440 MeV) from a variational analysis technique. The analysis is performed for pion masses as low as 224 MeV in quenched QCD with the FLIC fermion action. A wide variety of smeared-smeared correlation functions are used to construct correlation matrices. This is done in order to find a suitable basis of operators for the variational analysis such that eigenstates of the QCD Hamiltonian may be isolated. A lower lying Roper state is observed that approaches the physical Roper state. To the best of our knowledge, the first time this state has been identified at light quark masses using a variational approach.Comment: 7pp, 4 figures; minor typos corrected and one Ref. adde

In vitro methods to ensure absence of residual undifferentiated human induced pluripotent stem cells intermingled in induced nephron progenitor cells

ヒトiPS細胞から作製した腎前駆細胞に未分化な細胞が残存していないことを確認する方法の開発. 京都大学プレスリリース. 2022-11-16.A new sensitive method to detect for minute amounts of contaminating undifferentiated iPS cells. 京都大学プレスリリース. 2022-11-21.Cell therapies using human induced pluripotent stem cell (hiPSC)-derived nephron progenitor cells (NPCs) are expected to ameliorate acute kidney injury (AKI). However, using hiPSC-derived NPCs clinically is a challenge because hiPSCs themselves are tumorigenic. LIN28A, ESRG, CNMD and SFRP2 transcripts have been used as a marker of residual hiPSCs for a variety of cell types undergoing clinical trials. In this study, by reanalyzing public databases, we found a baseline expression of LIN28A, ESRG, CNMD and SFRP2 in hiPSC-derived NPCs and several other cell types, suggesting LIN28A, ESRG, CNMD and SFRP2 are not always reliable markers for iPSC detection. As an alternative, we discovered a lncRNA marker gene, MIR302CHG, among many known and unknown iPSC markers, as highly differentially expressed between hiPSCs and NPCs, by RNA sequencing and quantitative RT-PCR (qRT-PCR) analyses. Using MIR302CHG as an hiPSC marker, we constructed two assay methods, a combination of magnetic bead-based enrichment and qRT-PCR and digital droplet PCR alone, to detect a small number of residual hiPSCs in NPC populations. The use of these in vitro assays could contribute to patient safety in treatments using hiPSC-derived cells

The growth and hydrodynamic collapse of a protoplanet envelope

We have conducted three-dimensional self-gravitating radiation hydrodynamical models of gas accretion onto high mass cores (15-33 Earth masses) over hundreds of orbits. Of these models, one case accretes more than a third of a Jupiter mass of gas, before eventually undergoing a hydrodynamic collapse. This collapse causes the density near the core to increase by more than an order of magnitude, and the outer envelope to evolve into a circumplanetary disc. A small reduction in the mass within the Hill radius (R_H) accompanies this collapse as a shock propagates outwards. This collapse leads to a new hydrostatic equilibrium for the protoplanetary envelope, at which point 97 per cent of the mass contained within the Hill radius is within the inner 0.03 R_H which had previously contained less than 40 per cent. Following this collapse the protoplanet resumes accretion at its prior rate. The net flow of mass towards this dense protoplanet is predominantly from high latitudes, whilst at the outer edge of the circumplanetary disc there is net outflow of gas along the midplane. We also find a turnover of gas deep within the bound envelope that may be caused by the establishment of convection cells.Comment: 16 pages, 16 figures. Accepted for publication in MNRA

Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil

BackgroundMood disorder accounts for 13 % of global disease burden. And while therapeutic agents are available, usually orally administered, most have unwanted side effects, and thus making the inhalation of essential oils (EOs) an attractive alternative therapy. Rosmarinus officinalis EO (ROEO), Mediterranean ROEO reported to improve cognition, mood, and memory, the effect on stress of which has not yet been determined. Here, the anti-stress effect of ROEO on stress was evaluated in vivo and in vitro.MethodsSix-week-old male ICR mice were made to inhale ROEO and subjected to tail suspension test (TST). To determine the neuronal differentiation effect of ROEO in vitro, induction of ROEO-treated PC12 cells differentiation was observed. Intracellular acetylcholine and choline, as well as the Gap43 gene expression levels were also determined.ResultsInhalation of ROEO significantly decreased the immobility time of ICR mice and serum corticosterone level, accompanied by increased brain dopamine level. Determination of the underlying mechanism in vitro revealed a PC12 differentiation-induction effect through the modulation of intracellular acetylcholine, choline, and Gap43 gene expression levels. ROEO activates the stress response system through the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production and secretion. The effect of ROEO may be attributed to its bioactive components, specifically to α-pinene, one of its major compounds that has anxiolytic property.ConclusionsThe results of this study suggest that ROEO inhalation has therapeutic potential against stress-related psychiatric disorders

Dynamical ultrametricity in the critical trap model

We show that the trap model at its critical temperature presents dynamical ultrametricity in the sense of Cugliandolo and Kurchan [CuKu94]. We use the explicit analytic solution of this model to discuss several issues that arise in the context of mean-field glassy dynamics, such as the scaling form of the correlation function, and the finite time (or finite forcing) corrections to ultrametricity, that are found to decay only logarithmically with the associated time scale, as well as the fluctuation dissipation ratio. We also argue that in the multilevel trap model, the short time dynamics is dominated by the level which is at its critical temperature, so that dynamical ultrametricity should hold in the whole glassy temperature range. We revisit some experimental data on spin-glasses in light of these results.Comment: 7 pages, 4 .eps figures. submitted to J. Phys.

Modulation of the neurotransmitter systems through the anti-inflammatory and antidepressant-like effects of squalene from Aurantiochytrium sp.

Although algae have been the focal point of biofuel research, studies on their biological activities have been limited. In recent years, however, the importance of algae as sources of functional ingredients has been recognized due to their health beneficial effects. In this study, we evaluated the antidepressant-like activities of ethanol extract of Aurantiochytrium sp. (EEA) in the forced swimming test (FST)-induced depression in ICR mice. Imipramine, a commercially available tricyclic antidepressant drug, was used as positive control. Animals were administered EEA orally for 14 consecutive days and were subjected to the locomotor activity testing. Additionally, changes in gene expression in mice brain were assessed by real-time PCR and microarray assays to understand the molecular mechanisms underlying the effect of EEA. We found that the immobility time in FST was significantly reduced in the EEA-treated mice compared to that of in the control mice. Microarray and real-time PCR results revealed that EEA treatment induced changes in several genes in mice brain associated with pro-inflammation and dopaminergic, cholinergic, glutamatergic, and serotonergic synapses. It has previously been reported that several cytokines, such as IL-6 and TNF-α, which mediate neuroinflammation, are also responsible for indirectly altering brain neurotransmitter levels in neuropsychiatric disorders. Therefore, the regulation of the expression of pro-inflammatory genes in EEA-administered mice brain is considered to contribute to the enhancement of neurotransmitter systems-related gene expression in our study. Moreover, our in vitro study suggested that squalene, a component produced by Aurantiochytrium, was one of the active substances in EEA. In conclusion, our study provides the first evidence that Aurantiochytrium sp. can reduce neuroinflammation that may contribute to the modulation of the neurotransmitter systems, which could underlie its antistress and antidepressant effects

Global distribution and diversity of ovine-associated Staphylococcus aureus

Staphylococcus aureus is an important pathogen of many species, including sheep, and impacts on both human and animal health, animal welfare, and farm productivity. Here we present the widest global diversity study of ovine-associated S. aureus to date. We analysed 97 S. aureus isolates from sheep and sheep products from the UK, Turkey, France, Norway, Australia, Canada and the USA using multilocus sequence typing (MLST) and spa typing. These were compared with 196 sheep isolates from Europe (n = 153), Africa (n = 28), South America (n = 14) and Australia (n = 1); 172 bovine, 68 caprine and 433 human S. aureus profiles. Overall there were 59 STs and 87 spa types in the 293 ovine isolates; in the 97 new ovine isolates there were 22 STs and 37 spa types, including three novel MLST alleles, four novel STs and eight novel spa types. Three main CCs (CC133, CC522 and CC700) were detected in sheep and these contained 61% of all isolates. Four spa types (t002, t1534, t2678 and t3576) contained 31% of all isolates and were associated with CC5, CC522, CC133 and CC522 respectively. spa types were consistent with MLST CCs, only one spa type (t1403) was present in multiple CCs. The three main ovine CCs have different but overlapping patterns of geographical dissemination that appear to match the location and timing of sheep domestication and selection for meat and wool production. CC133, CC522 and CC700 remained ovine-associated following the inclusion of additional host species. Ovine isolates clustered separately from human and bovine isolates and those from sheep cheeses, but closely with caprine isolates. As with cattle isolates, patterns of clonal diversification of sheep isolates differ from humans, indicative of their relatively recent host-jump

Multifield Dynamics in Higgs-otic Inflation

In Higgs-otic inflation a complex neutral scalar combination of the $h^0$ and $H^0$ MSSM Higgs fields plays the role of inflaton in a chaotic fashion. The potential is protected from large trans-Planckian corrections at large inflaton if the system is embedded in string theory so that the Higgs fields parametrize a D-brane position. The inflaton potential is then given by a DBI+CS D-brane action yielding an approximate linear behaviour at large field. The inflaton scalar potential is a 2-field model with specific non-canonical kinetic terms. Previous computations of the cosmological parameters (i.e. scalar and tensor perturbations) did not take into account the full 2-field character of the model, ignoring in particular the presence of isocurvature perturbations and their coupling to the adiabatic modes. It is well known that for generic 2-field potentials such effects may significantly alter the observational signatures of a given model. We perform a full analysis of adiabatic and isocurvature perturbations in the Higgs-otic 2-field model. We show that the predictivity of the model is increased compared to the adiabatic approximation. Isocurvature perturbations moderately feed back into adiabatic fluctuations. However, the isocurvature component is exponentially damped by the end of inflation. The tensor to scalar ratio varies in a region $r=0.08-0.12$, consistent with combined Planck/BICEP results.Comment: 35 pages, 11 figure

Genesis Mission to Return Solar Wind Samples to Earth

The Genesis spacecraft, launched on 8 August 2001 from Cape Canaveral, Florida, will be the first spacecraft ever to return from interplanetary space. The fifth in NASAs line of low-cost, Discovery-class missions, its goal is to collect samples of solar wind and return them to Earth for detailed isotopic and elemental analysis. The spacecraft is to collect solar wind for over 2 years, while circling the L1 point 1.5 million km Sunward of the Earth, before heading back for a capsule-style re-entry in September 2004. After parachute deployments mid-air helicopter recovery will be used to avoid a hard landing. The mission has been in development over 10 years, and its cost, including development, mission operations, and initial sample analysis, is approximately $209 million