While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of ...single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).
Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾ 24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾ 50% MADRS score reduction) was the primary outcome.
By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01-0.22, p < 0.001 and remission (HR 0.11, 95% CI 0.02-0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks (peak = 3 days-2 weeks; effect size (ES) = 1.08-1.18), QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.
Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.
Background and purpose
Tirofiban administration during mechanical thrombectomy (MT) remains controversial. The aim was to evaluate the safety and efficacy of a low‐dose rescue tirofiban regimen ...during MT for Chinese acute ischaemic stroke (AIS) patients.
Methods
Patients from the ANGEL study, a multicentric, prospective registry study that included AIS patients who underwent MT owing to proximal large‐artery occlusion from June 2015 to December 2017, were collected. The patients were dichotomized into tirofiban and non‐tirofiban groups according to whether rescue tirofiban was performed during MT. Safety outcomes symptomatic intracerebral haemorrhage (sICH), total intracerebral haemorrhage (ICH) and distal embolization and efficacy outcomes (artery recanalization and functional outcomes at 3‐month follow‐up) were compared between groups using logistic regression analysis.
Results
A total of 662 patients were included in this study, and 230 (34.7%) were in the tirofiban group. No significant differences in safety outcomes on sICH, total ICH and distal embolization and efficacy outcomes on artery recanalization and 3‐month functional independence were observed between the tirofiban and non‐tirofiban group in the entire cohort or the anterior circulation stroke or posterior circulation stroke patients (P > 0.05 for all groups). However, low‐dose rescue tirofiban was significantly correlated with 3‐month mortality reduction for posterior circulation stroke patients adjusted hazard ratio 0.35 (0.14–0.92), P = 0.03.
Conclusions
Low‐dose rescue tirofiban during MT was not associated with increased risk of sICH, ICH and distal embolization for AIS patients, and may be correlated with 3‐month mortality reduction for posterior circulation stroke.
In nonruminants, the alternative splicing of peroxisome proliferator-activated receptor γ (PPARG) generates PPARG1 and PPARG2 isoforms. Although transcriptional control differences between isoforms ...have been reported in human adipose tissue, their roles in ruminant mammary cells are not well known. To assess which of these isoforms is more closely associated with the regulation of mammary lipogenic pathways, their tissue distribution was analyzed and the expression of key genes regulating lipogenic gene networks was measured after overexpression of the 2 isoforms in goat mammary epithelial cells (GMEC). The expression of PPARG2 was markedly greater in adipose tissue, whereas PPARG1 is the main isoform in goat mammary tissue (ratio of PPARG1:PPARG2 was close to 37:1). As was reported in previous work, PPARG1 upregulated the transcription regulators SREBF1 and PPARG and the lipogenic genes FASN, ACACA, and SCD. Along with a tendency for greater expression of AGPAT6, DGAT1, and PLIN2, these data suggest that PPARG1 is the isoform controlling lipogenesis in mammary cells. Addition of the PPARG ligand rosiglitazone (ROSI) to GMEC overexpressing both isoforms upregulated the expression of LPL and CD36, which help control uptake of long-chain fatty acids into mammary cells. Other responses to ROSI addition to GMEC overexpressing PPARG1 and PPARG2 included upregulation of AGPAT6, DGAT1, INSIG1, SREBF1, and NR1H3. Although the data suggest that both PPARG1 and PPARG2 could affect mammary lipogenesis via control of gene expression when stimulated (e.g., by ROSI), the fact that PPARG1 is more abundant in mammary tissue and that its overexpression alone upregulated key lipogenic gene networks suggest that it is the more important isoform in goat mammary cells.
•The impact of loading conditions on the frequency components is obtained through the dynamic model.•The amplitudes of different peak frequencies are used as the indicator for loading conditions.•The ...loading conditions are proved to change with ball diameter tolerance and adjacent ball diameter difference.•The uneven loading conditions are monitored and evaluated through the comparison of the frequency components.
Considering the effect of ball diameter difference, the full ceramic ball bearings often run in uneven loading conditions in starved lubrication. The uneven loading condition leads to severe friction and wear, and is not conducive to the maintenance of bearing performance. This paper provides a monitoring method for the uneven loading conditions based on the dynamic model, and the monitoring is realized through model-based calculation, signal acquisition and condition recognition. The number of loaded balls is discussed based on the working conditions, and the contacts between balls and rings at different loading conditions are simulated for the derivation of characteristic frequencies. The vibration signals of the inner ring are analyzed in frequency domain, and the amplitudes of the peak frequencies are used as the indicators. Results show that the vibration intensity and uneven loading conditions are revealed by different amplitude indicators, and the loading condition changes with structural parameters of ball diameter tolerance and adjacent ball diameter differences. The monitoring results fit well with the theoretical prediction, and different uneven loading conditions are compared as well. This method provides foundations for the monitoring of bearing working state, and can help with the maintenance of bearing performance.
Reduction or loss of tumor-suppressor mammalian STE20-like kinase 1 (MST1) in Hippo pathway contributes to the tumorigenesis. However, the mechanism leading to reduction of MST1 in cancers remains ...poorly understood. In this study, we explored the hypothesis that the oncoprotein hepatitis B X-interacting protein (HBXIP) is involved in the reduction of MST1 in breast cancer. Immunohistochemical analysis of tissue microarrays revealed that the expression of HBXIP was negatively associated with that of MST1 in 98 clinical breast tissue samples. Then we found that HBXIP could posttranslationally downregulate MST1 in breast cancer cells. Mechanistically, we identified that MST1 could be acetylated on its lysine 35 residue in the cells. Strikingly, the treatment with trichostatin A, an inhibitor of histone deacetylases (HDACs), markedly increased the levels of MST1 acetylation and protein in the cells. Interestingly, the oncoprotein HBXIP could significantly inhibit acetylation of MST1, resulting in the reduction of MST1 protein. Notably, we revealed that the HDAC6 could reduce the protein levels of MST1 through deacetylation modification of MST1 in the cells. Moreover, our data revealed that HBXIP upregulated HDAC6 at the levels of mRNA and protein by activating transcription factor nuclear factor-κB. Deacetylation of MST1 promoted the interaction of MST1 with HSC70 in the cells, resulting in a lysosome-dependent degradation of MST1 via chaperone-mediated autophagy (CMA). Functionally, the reduction of tumor-suppressor MST1 mediated by HBXIP promoted the growth of breast cancer cells in vitro and in vivo. Thus we conclude that the deacetylation of MST1 mediated by HBXIP-enhanced HDAC6 results in MST1 degradation in a CMA manner in promotion of breast cancer growth. Our finding provides new insights into the mechanism of tumor-suppressor MST1 reduction in breast cancer.
Using a first-principles band-structure method and a special quasirandom structure (SQS) approach, we systematically calculate the band gap bowing parameters and
p
-type doping properties of (Zn, Mg, ...Be)O related random ternary and quaternary alloys. We show that the bowing parameters for ZnBeO and MgBeO alloys are large and dependent on composition. This is due to the size difference and chemical mismatch between Be and Zn(Mg) atoms. We also demonstrate that adding a small amount of Be into MgO reduces the band gap indicating that the bowing parameter is larger than the band-gap difference. We select an ideal N atom with lower
p
atomic energy level as dopant to perform
p
-type doping of ZnBeO and ZnMgBeO alloys. For N doped in ZnBeO alloy, we show that the acceptor transition energies become shallower as the number of the nearest neighbor Be atoms increases. This is thought to be because of the reduction of
p
-
d
repulsion. The N
O
acceptor transition energies are deep in the ZnMgBeO quaternary alloy lattice-matched to GaN substrate due to the lower valence band maximum. These decrease slightly as there are more nearest neighbor Mg atoms surrounding the N dopant. The important natural valence band alignment between ZnO, MgO, BeO, ZnBeO, and ZnMgBeO quaternary alloy is also investigated.
To investigate the performance of combined semi-quantitative analysis on dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and histogram analysis of diffusion-weighted imaging (DWI) ...for distinguishing malignant from benign breast masses.
This study included 178 patients with breast masses (benign:malignant=88:9) who underwent both DCE-MRI and DWI. The semi-quantitative parameters, derived from DCE-MRI, included maximum slope of increase (MSI), signal intensity slope (SIslope), initial percentage of enhancement (Einitial), percentage of peak enhancement (Epeak), early signal enhancement ratio (ESER), and second enhancement percentage (SEP). Histogram parameters derived from apparent diffusion coefficient (ADC) maps included ADCmin, ADCmax, ADCmean, ADC10, ADC25, ADC50, ADC75, ADC90, skewness, and kurtosis. All parameters were compared between malignant and benign groups, and their differences were tested using independent-samples t-test or Mann–Whitney test. Receiver operating characteristic (ROC) curves were used to determine the diagnostic value of each significant parameter.
Among semi-quantitative parameters, SIslope exhibited the best diagnostic performance in predicting malignancy (cut-off value, 0.096; ROC, 0.756; sensitivity, 86.7%; specificity, 61.4%). Among histogram parameters, ADC10 exhibited the best diagnostic performance in predicting malignancy (cut-off value, 1.051; ROC, 0.885; sensitivity, 86.7%; specificity, 84.1%). The optimal diagnostic performance of combined ADC10 and SIslope (area under curve AUC, 0.888; sensitivity, 82.2%; specificity, 95.5%) was significantly better than SIslope alone (p<0.001). Moreover, the combination showed higher AUC (0.888 versus 0.885) than ADC10 alone, but the difference was not statistically significant (p=0.914).
SIslope and ADC10 are significant predictors for breast malignancy. The combination of DCE-MRI and DWI improves differentiating performance.
•SIslope exhibited the optimal diagnostic performance in predicting malignancy in the semi-quantitative analysis of DCE-MRI.•ADC10 exhibited the optimal performance in predicting malignancy in the whole-lesion ADC histogram analysis.•ADC histogram analysis might provide additional diagnostic value in predicting breast malignancy.
ABSTRACT
This paper investigated the effect of surface recrystallization (RX) on the low cycle fatigue (LCF) behaviour of a single crystal (SX) superalloy. LCF tests on both raw and recrystallized ...samples showed that fatigue life was significantly reduced by surface RX. Fractography indicated that fatigue cracks initiated from the casting defects in RX layer and multiple crack initiations were commonly observed. Moreover, RX grains exhibited predominantly transgranular cracking, in contrast to the intergranular fracture reported in literature. The fatigue crack propagation behaviour was discussed in light of fracture mechanics and crack growth life model. The fatigue cycles required to penetrate RX layer were estimated to be about one magnitude lower than that in forming an equivalent crack in SX specimens. It is suggested that the earlier crack initiation and promoted crack propagation in RX layer, as well as the trend of multiple initiations, are responsible for the fatigue degradation by RX.
Phenotypic plasticity, which encompasses the diversification of both irreversible and reversible traits, has long been considered an adaptive response by animals to varying environmental conditions. ...However, the process by which irreversible and reversible traits are coordinated to form an adaptive response to the changing environment has yet to be clarified. Here, we investigated the variation in body size of two urban insect species in the context of habitat fragmentation. These species were the Chinese cricket Gryllus chinensis and the stove grasshopper Diestrammena japonica, which are sympatric in urban housing estates. Results indicated that both species changed in body size in patches of urban environment. However, their body size shifts showed opposite tendencies and were influenced by distinct selective forces: Chinese crickets increased their body size with the patch history and predation risk, whereas stove grasshoppers decreased their body size with the degree of fragmentation of the patches. Territorial and competitive Chinese crickets rarely experience resource scarcity during urban environment fragmentation. Thus, a larger body size was preferred in response to intraspecific competition among Chinese crickets. By contrast, stove grasshoppers are group‐living and scramble for resources as competitors, requiring a large territory to secure adequate food for supporting a group of individuals. Consequently, stove grasshoppers frequently experienced resource scarcity in the patchy habitat, favoring small body size to reduce individual requirements throughout the life cycle. Our findings indicate that the body size shift of sympatric insects may be subjected to distinct selective forces in fragmented habitats, depending primarily on their reversible traits.
Fragmented habitats of the urban insects caused by streets and footpaths.
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