The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (νover ¯_{e}) ...oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) νover ¯_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the measured number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=2.68±0.12(stat)±0.07(syst)×10^{-3} eV^{2}.
Summary
Although different injection locations for retrolaminar and erector spinae plane blocks have been described, the two procedures have a similar anatomical basis. In this cadaveric study we ...compared anatomical spread of dye in the thoracic region following these two procedures. Following randomisation, 10 retrolaminar blocks and 10 erector spinae plane blocks were performed on the left or right sides of 10 unembalmed cadavers. For each block, 20 ml of dye solution was injected at the T5 level. The back regions were dissected and the involvement of the thoracic spinal nerve was also investigated. Twenty blocks were successfully completed. A consistent vertical spread, with deep staining between the posterior surface of the vertebral laminae and the overlaying transversospinalis muscle was observed in all retrolaminar blocks. Moreover, most retrolaminar blocks were predominantly associated with fascial spreading in the intrinsic back muscles. With an erector spinae plane block, dye spread in a more lateral pattern than with retrolaminar block, and fascial spreading in the back muscles was also observed. The number of stained thoracic spinal nerves was greater with erector spinae plane blocks than with retrolaminar blocks; median 2.0 and 3.5, respectively. Regardless of technique, the main route of dye spread was through the superior costotransverse ligament to the ipsilateral paravertebral space. Although erector spinae plane blocks were associated with a slightly larger number of stained thoracic spinal nerves than retrolaminar blocks, both techniques were consistently associated with posterior spread of dye and with limited spread to the paravertebral space.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
The aim of this study is to develop a novel method for the accurate diagnosis of the infection status of viral diseases, which requires discriminated and quantitative detection of different ...anti-virus immunoglubulin subtypes. Considering hepatitis A as a representative model disease, viral antigen nanoparticles (vAgNPs) were designed and synthesized by genetically presenting hepatitis A virus (HAV) antigens on the surface of human heavy chain ferritin (hFTH) nanoparticles to detect anti-HAV antibodies with discriminating immunoglobulin subtypes M and G (IgM and IgG, respectively). The vAgNPs also display multi-copies of hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is vital for the autonomous generation of quantitatively meaningful detection signals. The quantitative level of anti-HAV IgM or IgG in 30 patient sera was successfully analyzed using the vAgNPs of HAV, which was performed through label-free one-step-immunoassay based on the self-enhancement of optical signals from gold nanoparticles clustered on the viral antigen nanoparticles. The diagnostic performance was compared with that of enzyme-linked immunosorbent assay (ELISA), which did not enable accurate quantitative assay due to the poor linearity between the antibody concentration and detection signal. Furthermore, these vAgNP-based immunoassays did not produce any false negative/positive signals, indicating 100% sensitivity and 100% specificity.
Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and ...metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis. We found that the loss of STAT3 in ECs did not affect primary Lewis lung carcinoma (LLC) tumor growth, but it reduced in vivo LLC metastasis in experimental and spontaneous metastasis models. Mechanistically, STAT3 activation upregulated cell adhesion molecule expression, including E-selectin and P-selectin, in murine endothelial MS-1 cells treated with tumor cell-conditioned media in vitro and in pre-metastatic lungs of tumor-bearing mice in vivo. We also found that both E-selectin and P-selectin were, at least in part, responsible for STAT3-induced adhesion and invasion of LLC cells through an EC monolayer. However, tumor cell-conditioned media from B16F10 melanoma cells did not activate STAT3 in MS-1 cells. As a result, EC STAT3 knockout did not affect B16F10 melanoma cell metastasis. In addition, various human cancer cells activated STAT3 in human ECs (HUVECs), resulting in increased cell adhesion molecule expression. Collectively, our findings demonstrate that STAT3 activation in ECs promotes tumor metastasis through the induction of cell adhesion molecules, demonstrating a role for ECs in response to tumor cells during tumor metastasis.
Diabet. Med. 27, 1033–1040 (2010)
Aims This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy.
Methods An open, ...randomized, comparative study was conducted. Subjects with painful symmetric neuropathy in the lower limbs and mean pain‐intensity score ≥ 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36‐item Short Form Health Survey, average pain intensity and sleep disturbance.
Results One hundred and sixty‐three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 ± 1.6; gabapentin 6.3 ± 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A −3.1 ± 2.0; gabapentin −2.7 ± 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores.
Conclusion This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.
Summary
Background
Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late‐onset asthma. Recent studies ...suggest staphylococcal enterotoxin IgE (SE‐IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late‐onset elderly asthma.
Objective
We aimed to examine the associations of SE‐IgE sensitization with late‐onset asthma in the elderly, using a database of elderly asthma cohort study.
Methods
A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE‐IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12‐month follow‐up period.
Results
At baseline, serum SE‐IgE concentrations were significantly higher in patients with asthma than in controls median 0.16 (interquartile range 0.04–0.53) vs. 0.10 (0.01–0.19), P < 0.001. Elderly asthma patients with high SE‐IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE‐IgE levels. In multivariate logistic regression analyses, the associations between serum SE‐IgE concentrations and severe asthma were significant, independently of covariables SE‐IgE‐high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86–30.03, P = 0.005. Multiple correspondence analyses also showed that high serum SE‐IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusions and Clinical Relevance
This is the first report on the significant associations of SE‐IgE sensitization with late‐onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late‐onset eosinophilic asthma in the elderly.
We report a fuel-dependent reactor electron antineutrino (νover ¯_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ...νover ¯_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.
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