How glial cells and cytokines are associated with the progression of delayed neuronal death induced by transient global ischemia is still unclear. To further clarify this point, we studied ...morphological changes in glial cells (microglial cells and astrocytes), and cytokine protein levels, during the progression of neuronal cell loss in CA1 (Cornu Ammonis 1) of the hippocampus after transient global ischemia.
Morphological changes in glial cells were studied immuno-histochemically. Nine cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ and TNF-α) were simultaneously measured by a multiplexed bead-based immunoassay from 6 h to day21 after transient four vessel occlusion (4VO) in rats.
During the process of neuronal loss, we observed four distinct phases: (1) lag phase day0-2 (no NeuN+ cell loss observed), (2) exponential phase day2-7 (NeuN+ cells reduced in number exponentially), (3) deceleration phase day7-14 (reduction rate of NeuN+ cells became low), (4) stationary phase day14 onward (NeuN+ cell loss progressed no longer). In the lag phase, activated glial cells were observed in the entire hippocampus but later were gradually restricted to CA1. Cytokine protein levels in the lag and exponential phases were lower than in the deceleration and stationary phases. IL-1α, IL-1β, IL-4, IL-6 and IFN-γ in 4VO were significantly higher in all four phases than in sham. Compared with sham level, GM-CSF was significantly high in the deceleration phase. TNF-α was significantly high in both the deceleration and stationary phases.
Ischemic stress in 4VO activated glial cells in areas beyond CA1 in the lag phase. Pyramidal neurons were injured in CA1 from the end of the lag phase and then neuronal cells reduced in CA1 in the exponential phase. After neuronal death began, the influence of dead cells on glial cells and cytokine expression gradually became stronger than the influence by ischemic stress. Therefore, from the deceleration phase, changes in glial cells and cytokine production were likely caused by dead cells. Cytokine interaction in the microenvironment may determine the functions of IL-1α, IL-1β, IL-4, IL-6 and IFN-γ in all four phases. The function of GM-CSF and TNF-α in the deceleration phase may be neurotrophic.
In rhyolite lavas, the high porosity bands are often developed. They potentially act as pathways for gas movement to the lava surface. Since explosive activities of lavas are generally considered to ...be controlled by degassing system, understanding the origin and deformation process of the high porosity bands is important to assessing volcanic hazards. The Takanoobane rhyolite lava in the middle of Kyushu Island in SW Japan is effused at 51±5ka. The volume, flow length, and thickness are 0.14km3, >2km, and about 90m, respectively. The central crystalline part of the lava is characterized by the light-colored bands defined by the high porosity zone (HPZ). On the basis of geological and petrographical studies, we revealed that the HPZ was primary formed by ductile–brittle tearing of the lava (known as cavitation). According to the AMS results, the HPZs were subsequently stretched and flattened laterally during the concentric spreading of the lava. This deformation process could stretch the HPZ not only radially but also laterally. This effective stretching developed the HPZ into pervasive thin bands. Since the HPZs act as degassing pathways to the lava surface, the pervasive HPZ bands may play a role in providing volcanic gasses to void spaces created in surface fold hinges of rhyolite lavas. Thus, this degassing system may promote explosive activity of the lava surface.
Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents ...a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.
In the forward end-cap of the Belle II spectrometer, particle identification is provided by a proximity focusing RICH detector with an aerogel radiator (ARICH). The ARICH’s primary function is to ...effectively distinguish between pions and kaons in the momentum range of 0.5GeV/c to about 4GeV/c, as well as to contribute to identification of low-momentum leptons. Since its operation began, Belle II has collected over 420fb−1 of data. Based on this large data sample, studies of several effects that impact the performance of the ARICH detector were carried out. In this paper, we present a comparison of the observed Cherenkov ring image and detector particle identification performance in the measured data and detector simulation. Furthermore, we highlight recent efforts aimed at enhancing the ARICH’s performance by taking into account the effects of particle decay in flight and scattering in materials before the detector, as well as by refining the probability density function used for particle identification likelihood evaluation.
Background
We recently demonstrated in humans that the extent of low-dose aspirin (LDA)-induced gastropathy was directly related to the individual gastric acid secretion level. We also established ...reliable cutoff serum pepsinogen (PG) values to predict gastric acid secretion status. In this study, we investigated the clinical usefulness of measuring the serum pepsinogen values for identifying a high-risk group for gastric mucosal injury among chronic LDA users.
Methods
One hundred long-term LDA users were enrolled in this analysis. Serum from each subject was subjected to determination of
H. pylori
status and measurement of pepsinogen values. According to our recent report, a PG I value ≥ 50 ng/mL was defined as estimated hyperchlorhydria in
H. pylori
-negative subjects, while a PG I/II ≥ 3.3 was defined as estimated hyperchlorhydria in
H. pylori
-positive subjects. The grade of gastric mucosal injury was assessed endoscopically, and multiple logistic regression analyses were used to estimate the risk.
Results
Estimated hyperchlorhydria was a strong independent risk for intensive gastric mucosal injury with an OR (95 % CI): 34.0 (4.5–259) and for gastric ulcer with an OR (95 % CI): 10.2 (1.8–58.3) in
H. pylori
-positive subjects, while it was not a significant risk in
H. pylori
-negative subjects. The association persisted even after excluding those with conventional risks for LDA-gastropathy such as ulcer histories.
Conclusion
Using simple serum measurement of
H. pylori
antibody and pepsinogen concentrations, an extremely high-risk group for LDA-induced gastropathy could be extracted, and these patients should become a therapeutic target for prevention of LDA-induced gastropathy.
To evaluate the effect of long-term maximally intensive statin therapy on indices of coronary atheroma composition in a randomized trial, and how these changes relate to modifications of serum ...lipoproteins and systemic inflammation.
The Study of coronary Atheroma by inTravascular Ultrasound: the effect of Rosuvastatin vs. atorvastatiN (SATURN) employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg daily for 24 months. Seventy-one patients underwent serial assessment of indices of plaque composition by spectral analysis of the radiofrequency IVUS signal. Changes in low-density lipoprotein cholesterol LDL-C; -52 (-72, -33) mg/dL, P < 0.001, C-reactive protein CRP -0.2 (-1, 0.1) mg/L, P = 0.01, and high-density lipoprotein cholesterol HDL-C; +2.8 (-0.3, 7.8) mg/dL, P < 0.001 were associated with regression of percent atheroma volume (PAV: -1.6 ± 3.6%, P < 0.001). A reduction in estimated fibro-fatty tissue volume accompanied atheroma regression (P < 0.001), while dense calcium tissue volume increased (P = 0.002). There were no changes in fibrous or necrotic core tissue volumes. Volumetric changes in necrotic core tissue correlated with on-treatment HDL-C (r = -0.27, P = 0.03) and CRP (r = 0.25, P = 0.03) levels. A per-lesion analysis showed a reduction in the number of pathological intimal thickening lesions (defined by ≥3 consecutive IVUS frames containing PAV of ≥40%, predominantly fibro-fatty plaque, with <10% confluent necrotic core and <10% confluent dense calcium) at follow-up (67 vs. 38, P = 0.001). Fibroatheromas and fibrotic lesions remained static in number.
Changes in indices of atheroma composition accompany regression of coronary atheroma with maximally intensive statin therapy, and associate with anti-inflammatory effects of statins.
NCT000620542.
Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. ...It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 microg ml(-1)) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0-1.4 microg ml(-1); 0 of 26 (0%), 1.5-7.4 microg ml(-1); 9 of 30 (30%) and > or =7.5 microg ml(-1); 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 microg ml(-1) was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level > or =1.5 microg ml(-1) should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.
We present photometric and spectroscopic observations of the Type Icn supernova (SN) 2021ckj. This rare type of SNe is characterized by a rapid evolution and high peak luminosity as well as narrow ...lines of highly ionized carbon at early phases, implying an interaction with hydrogen- and helium-poor circumstellar matter (CSM). SN 2021ckj reached a peak brightness of ∼ − 20 mag in the optical bands, with a rise time and a time above half maximum of ∼4 and ∼10 days, respectively, in the g and cyan bands. These features are reminiscent of those of other Type Icn SNe (SNe 2019hgp, 2021csp, and 2019jc), with the photometric properties of SN 2021ckj being almost identical to those of SN 2021csp. Spectral modeling of SN 2021ckj reveals that its composition is dominated by oxygen, carbon, and iron group elements, and the photospheric velocity at peak is ∼10 000 km s−1. Modeling the spectral time series of SN 2021ckj suggests aspherical SN ejecta. From the light curve (LC) modeling applied to SNe 2021ckj, 2019hgp, and 2021csp, we find that the ejecta and CSM properties of Type Icn SNe are diverse. SNe 2021ckj and 2021csp likely have two ejecta components (an aspherical high-energy component and a spherical standard-energy component) with a roughly spherical CSM, while SN 2019hgp can be explained by a spherical ejecta-CSM interaction alone. The ejecta of SNe 2021ckj and 2021csp have larger energy per ejecta mass than the ejecta of SN 2019hgp. The density distribution of the CSM is similar in these three SNe, and is comparable to those of Type Ibn SNe. This may imply that the mass-loss mechanism is common between Type Icn (and also Type Ibn) SNe. The CSM masses of SN 2021ckj and SN 2021csp are higher than that of SN 2019hgp, although all these values are within those seen in Type Ibn SNe. The early spectrum of SN 2021ckj shows narrow emission lines from C II and C III, without a clear absorption component, in contrast with that observed in SN 2021csp. The similarity of the emission components of these lines implies that the emitting regions of SNe 2021ckj and 2021csp have similar ionization states, and thus suggests that they have similar properties as the ejecta and CSM, which is also inferred from the LC modeling. Taking the difference in the strength of the absorption features into account, this heterogeneity may be attributed to viewing angle effects in otherwise common aspherical ejecta. In particular, in this scenario SN 2021ckj is observed from the polar direction, while SN 2021csp is seen from an off-axis direction. This is also supported by the fact that the late-time spectra of SNe 2021ckj and 2021csp show similar features but with different line velocities.
The impact of baseline coronary plaque burden on the clinical outcome in patients receiving aggressive low-density lipoprotein cholesterol (LDL-C) lowering therapy to levels <70 mg/dL is unknown. We ...assessed the prognostic significance of baseline coronary plaque burden following high-intensity statin therapy.
SATURN used serial intravascular ultrasound (IVUS) to measure coronary atheroma volume in 1039 patients before and after 24 months of treatment with rosuvastatin 40 mg or atorvastatin 80 mg. This post hoc analysis compared the relationship between baseline percent atheroma volume (PAV) and major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) in patients with baseline PAV less than (n = 519) or greater than (n = 520) the median. Patients with a higher baseline PAV had a similar LDL-C compared with those with a lower baseline PAV at baseline (119.0 ± 29 vs. 121.0 ± 27 mg/dL, P = 0.09) and at follow-up (65.3 ± 23 vs. 65.8 ± 22 mg/dL, P = 0.47). In multivariable analysis, each standard deviation increase in baseline PAV was associated with a 28% increase in MACE HR 1.28 (1.05, 1.57), P = 0.01. Those with the highest quartile of baseline PAV (>41.8%) had a 2-year cumulative MACE rate of 12%, which was significantly higher (log-rank P = 0.001) than MACE rates of all lower PAV quartiles (MACE: quartile 3, 2, and 1 were 5.7, 7.9, and 5.1%, respectively). LDL-C levels at baseline HR 0.96 (0.79, 1.18), P = 0.73 and on-treatment HR 1.19 (0.83, 1.73), P = 0.35 were not associated with MACE.
Following 2 years of high-intensity statin therapy, a baseline coronary atheroma volume predicted MACE, despite the achievement of very low on-treatment LDL-C levels.
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