Perioperative use of dexmedetomidine is associated with reduction in postoperative analgesic requirements. This study examined whether dexmedetomidine added to i.v. patient-controlled analgesia (PCA) ...morphine could improve analgesia while reducing opioid-related side-effects.
In this double-blinded, randomized, controlled study, 100 women undergoing abdominal total hysterectomy were allocated to receive either morphine 1 mg ml−1 alone (Group M) or morphine 1 mg ml−1 plus dexmedetomidine 5 μg ml−1 (Group D) for postoperative i.v. PCA, which was programmed to deliver 1 ml per demand with a 5 min lockout interval and no background infusion. Cumulative PCA requirements, pain intensities, cardiovascular and respiratory variables, and PCA-related adverse events were recorded for 24 h after operation.
Compared with Group M, patients in Group D required 29% less morphine during the 0–24 h postoperative period and reported significantly lower pain levels from the second postoperative hour onwards and throughout the study. Whereas levels of sedation were similar between the groups at each observational time point, decreases in heart rate and mean blood pressure from presurgery baseline at 1, 2, and 4 h after operation were significantly greater in Group D (by a range of 5–7 beats min−1 and 10–13%, respectively). The 4–24 h incidence of nausea was significantly lower in Group D (34% vs 56.3%, P<0.05). There was no bradycardia, hypotension, oversedation, or respiratory depression.
The addition of dexmedetomidine to i.v. PCA morphine resulted in superior analgesia, significant morphine sparing, less morphine-induced nausea, and was devoid of additional sedation and untoward haemodynamic changes.
Simultaneous enhancement of out-coupling efficiency, internal quantum efficiency, and color purity in thermally activated delayed fluorescence (TADF) emitters is highly desired for the practical ...application of these materials. We designed and synthesized two isomeric TADF emitters, 2DPyM-mDTC and 3DPyM-pDTC, based on di(pyridinyl)methanone (DPyM) cores as the new electron-accepting units and di(tert-butyl)carbazole (DTC) as the electron-donating units. 3DPyM-pDTC, which is structurally nearly planar with a very small ΔE ST, shows higher color purity, horizontal ratio, and quantum yield than 2DPyM-mDTC, which has a more flexible structure. An electroluminescence device based on 3DPyM-pDTC as the dopant emitter can reach an extremely high external quantum efficiency of 31.9% with a pure blue emission. This work also demonstrates a way to design materials with a high portion of horizontal molecular orientation to realize a highly efficient pure-blue device based on TADF emitters.
Virtual photons can mediate interaction between atoms, resulting in an energy shift known as a collective Lamb shift. Observing the collective Lamb shift is challenging, since it can be obscured by ...radiative decay and direct atom-atom interactions. Here, we place two superconducting qubits in a transmission line terminated by a mirror, which suppresses decay. We measure a collective Lamb shift reaching 0.8% of the qubit transition frequency and twice the transition linewidth. We also show that the qubits can interact via the transmission line even if one of them does not decay into it.
MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular ...carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.
This cutting-edge study delves into regional magmatism in northern Taiwan through advanced 3-D P- and S-wave frequency-dependent attenuation tomography. Positioned at the dynamic convergence boundary ...between the Philippine Sea Plate and the Eurasian Plate, Taiwan experiences moderate earthquakes and intriguing volcanic activity, with a focus on the Tatun volcano group. Employing the Formosa seismic array for high-resolution results, our research identifies high-attenuation anomalies (low Q) beneath the northern Taiwan volcanic zone (NTVZ) and offshore submarine volcanoes, indicative of potential hydrothermal activities and magma reservoirs at varying depths. Additionally, we explore low-attenuation anomalies (high Q) in the forearc region of the Ryukyu subduction zone, suggestive of partial saturation linked to serpentinization processes resulting from seawater infiltration or forearc mantle hydration. These findings shed light on the complex geological features and provide essential insights into the crustal properties of northern Taiwan, contributing to a deeper understanding of its magmatic evolution and tectonic processes.
Summary
Background
Ustekinumab, an interleukin‐12/23 inhibitor, is effective in the treatment of psoriasis. A recent Italian study showed more favourable response to ustekinumab in patients with ...positive human leucocyte antigen (HLA)‐Cw6. Nonetheless, there are differences in genetic susceptibility to psoriasis between races, and no studies have specifically assessed the candidate genetic markers in predicting therapy outcome in Chinese patients with psoriasis treated with ustekinumab.
Objectives
To determine whether HLA gene polymorphisms can predict the response to ustekinumab in Chinese patients with psoriasis.
Methods
Sixty‐six patients with psoriasis treated with ustekinumab were included in the study, and the effectiveness of ustekinumab therapy was evaluated at weeks 0, 16 and 28 by Psoriasis Area and Severity Index (PASI).
Results
More HLA‐Cw6‐positive patients achieved a PASI 75 response at week 4 compared with HLA‐Cw6‐negative patients (38% vs. 9%, P = 0·019). Similarly, at week 16, patients carrying the HLA‐Cw6 allele showed a higher likelihood of achieving PASI 50, 75 and 90 than Cw6‐negative patients, although this was not statistically significant. At week 28, a significantly higher percentage of HLA‐Cw6‐positive patients maintained PASI 90 response compared with Cw6‐negative patients (63% vs. 26%, P = 0·035). Further analysis of other HLA allele polymorphisms did not show significant associations with therapeutic response to ustekinumab.
Conclusions
This pharmacogenetic study provides preliminary data indicating that positive HLA‐Cw6 is associated with a good response to ustekinumab treatment in Chinese patients with psoriasis.
What's already known about this topic?
Biological therapies have revolutionized the treatment of psoriasis. Variability in genes involved in the immunological pathways of biological therapy may account for the different treatment outcomes.
Human leucocyte antigen (HLA)‐Cw6 is the major psoriasis susceptibility gene and has a strong association with clinical psoriasis phenotypes.
Studies investigating potential predictors for response to biologics are limited, particularly in Asian populations.
What does this study add?
Our study showed that HLA‐Cw6‐positive patients have a faster response and maintain a longer treatment response to ustekinumab than HLA‐Cw6‐negative patients.
HLA‐Cw6 can be a pragmatic predictor for the response to ustekinumab not only in white patients but also in Chinese patients with psoriasis.
These results will help dermatologists in guiding therapeutic decisions.
Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection are limited. Studies comparing daptomycin or linezolid in treating VRE bloodstream infection have conflicting ...results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied. We conducted a multicentre prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE bloodstream infection. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model for dose-dependent response estimation. Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; p 0.03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21–0.96; p 0.04). The generalized additive model showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6–9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17–0.79; p 0.01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09–0.74; p 0.01) independently predicted lower mortality compared to lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45–4.37; p 0.57). Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared to higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteraemia.
Mineralized biological tissues offer insight into how nature has evolved these components to optimize multifunctional purposes. These mineral constituents are weak by themselves, but interact with ...the organic matrix to produce materials with unexpected mechanical properties. The hierarchical structure of these materials is at the crux of this enhancement. Microstructural features such as organized, layered organic/inorganic structures and the presence of porous and fibrous elements are common in many biological components. The organic and inorganic portions interact at the molecular and micro-levels synergistically to enhance the mechanical function. In this paper, we report on recent progress on studies of the abalone and Araguaia river clam shells, arthropod exoskeletons, antlers, tusks, teeth and bird beaks.
To investigate whether tobacco smoking increases the risk of tuberculosis (TB) recurrence and identify factors associated with TB recurrence among adults who had successfully completed ...anti-tuberculosis treatment in Taipei, Taiwan.
Recurrence was defined as a new clinical or microbiological diagnosis of TB requiring the start of a new course of treatment in a patient who had satisfactorily completed treatment for a previous TB episode. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) for recurrence.
We followed 5567 adults for recurrence after successful anti-tuberculosis treatment. The mean age was 58.5 years; 62.9% were male. Overall, 84 (1.5%) had a recurrence of TB during follow-up. The incidence of TB recurrence was 4.9 episodes/1000 person-years of follow-up. Cox proportional hazards regression showed that after controlling for other variables, the risk of TB recurrence among subjects who smoked >10 cigarettes a day was double that of never/former smokers. Other independent risk factors significantly associated with TB recurrence were homelessness (aHR 3.75, 95%CI 1.17-12.07), presence of comorbidities (aHR 2.66, 95%CI 1.22-5.79) and a positive acid-fast bacilli smear (aHR 2.27, 95%CI 1.47-3.49).
Smoking >10 cigarettes a day was significantly associated with TB recurrence. To reduce the risk of recurrence, we recommend including effective measures of smoking cessation in TB control programmes, as recommended by the World Health Organization Stop TB Strategy.
Stomatal conductance (gs) affects the fluxes of carbon, energy and water between the vegetated land surface and the atmosphere. We test an implementation of an optimal stomatal conductance model ...within the Community Atmosphere Biosphere Land Exchange (CABLE) land surface model (LSM). In common with many LSMs, CABLE does not differentiate between gs model parameters in relation to plant functional type (PFT), but instead only in relation to photosynthetic pathway. We constrained the key model parameter "g1", which represents plant water use strategy, by PFT, based on a global synthesis of stomatal behaviour. As proof of concept, we also demonstrate that the g1 parameter can be estimated using two long-term average (1960–1990) bioclimatic variables: (i) temperature and (ii) an indirect estimate of annual plant water availability. The new stomatal model, in conjunction with PFT parameterisations, resulted in a large reduction in annual fluxes of transpiration (~ 30% compared to the standard CABLE simulations) across evergreen needleleaf, tundra and C4 grass regions. Differences in other regions of the globe were typically small. Model performance against upscaled data products was not degraded, but did not noticeably reduce existing model–data biases. We identified assumptions relating to the coupling of the vegetation to the atmosphere and the parameterisation of the minimum stomatal conductance as areas requiring further investigation in both CABLE and potentially other LSMs. We conclude that optimisation theory can yield a simple and tractable approach to predicting stomatal conductance in LSMs.
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