CMV infection is a common complication in patients undergoing hematopoietic-cell transplantation. The incidence of CMV infection was 23 percentage points lower with prophylactic letermovir, a ...CMV–terminase complex inhibitor, than with placebo, with only low-level toxic effects.
Summary
Background
Ustekinumab, a fully human monoclonal antibody against interleukin‐12/23, may potentially be effective for severe atopic dermatitis (AD) treatment.
Objectives
To evaluate efficacy ...and safety of ustekinumab 45 mg and 90 mg in patients with severe AD.
Methods
In this randomized, placebo‐controlled, phase II study, Japanese patients (aged 20–65 years) with severe or very severe AD entered a 12‐week double‐blind treatment period during which they received (1 : 1 : 1) ustekinumab 45 mg, 90 mg or placebo subcutaneous injections at weeks 0 and 4, with follow‐up until week 24. The primary efficacy end point was percentage change from baseline in Eczema Area and Severity Index (EASI) score at week 12. Major secondary efficacy end points included the proportion of patients achieving EASI 50, EASI 75, Investigator's Global Assessment score 0–1, change from baseline Atopic Dermatitis Itch Scale and Dermatology Life Quality Index.
Results
A total of 79 patients were randomized ustekinumab 45 mg (n = 24), 90 mg (n = 28), placebo (n = 27). Ustekinumab treatment showed nonsignificant improvement in least square mean change from baseline EASI score at week 12 45 mg: –38·2%, 95% confidence interval (CI) –21·02–19·51; P < 0·94 and 90 mg: –39·8%, 95% CI –21·84–17·14; P < 0·81 vs. placebo (–37·5%). A nonsignificant improvement in major secondary efficacy end points was observed in both ustekinumab groups vs. placebo. The most common treatment‐emergent adverse events were nasopharyngitis and worsened AD (higher in placebo vs. ustekinumab groups).
Conclusions
Ustekinumab 45 mg and 90 mg did not demonstrate meaningful efficacy in Japanese patients with severe AD. The treatment was generally well tolerated.
What's already known about this topic?
There are reports suggesting the involvement of T helper 17 cells in the pathogenesis of atopic dermatitis (AD).
Several case studies have reported therapeutic benefits of ustekinumab in patients with severe AD, while a few studies have failed to show the benefits.
What does this study add?
Ustekinumab 45 mg and 90 mg did not demonstrate meaningful efficacy in Japanese patients with severe AD.
Ustekinumab treatment was generally well tolerated in Japanese patients with severe AD.
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Linked Comment: Samuel and Reynolds. Br J Dermatol 2017; 177:339–341
The conventional yeast (Saccharomyces cerevisiae) is the most studied yeast and has been used in many important industrial productions, especially in bioethanol production from first generation ...feedstock (sugar and starchy biomass). However, for reduced cost and to avoid competition with food, second generation bioethanol, which is produced from lignocellulosic feedstock, is now being investigated. Production of second generation bioethanol involves pre-treatment and hydrolysis of lignocellulosic biomass to sugar monomers containing, amongst others, d-glucose and D-xylose. Intrinsically, S. cerevisiae strains lack the ability to ferment pentose sugars and genetic engineering of S. cerevisiae to inculcate the ability to ferment pentose sugars is ongoing to develop recombinant strains with the required stability and robustness for commercial second generation bioethanol production. Furthermore, pre-treatment of these lignocellulosic wastes leads to the release of inhibitory compounds which adversely affect the growth and fermentation by S. cerevisae. S. cerevisiae also lacks the ability to grow at high temperatures which favour Simultaneous Saccharification and Fermentation of substrates to bioethanol. There is, therefore, a need for robust yeast species which can co-ferment hexose and pentose sugars and can tolerate high temperatures and the inhibitory substances produced during pre-treatment and hydrolysis of lignocellulosic materials. Non-conventional yeast strains are potential solutions to these problems due to their abilities to ferment both hexose and pentose sugars, and tolerate high temperature and stress conditions encountered during ethanol production from lignocellulosic hydrolysate. This review highlights the limitations of the conventional yeast species and the potentials of non-conventional yeast strains in commercialization of second generation bioethanol.
The hormone abscisic acid (ABA) regulates stress responses and developmental processes in plants. Calcium-permeable channels activated by reactive oxygen species (ROS) have been shown recently to ...function in the ABA signaling network in Arabidopsis guard cells. Here, we report that ABA activation of these ${\rm I}_{{\rm Ca}}\ {\rm Ca}^{2+}$ channels requires the presence of NAD(P)H in the cytosol. The protein phosphatase 2C (PP2C) mutant abi1-1 disrupted ABA activation of I Ca channels. Moreover, in abi1-1, ABA did not induce ROS production. Consistent with these findings, in abi1-1, H2 O2 activation of I Ca channels and H2 O2-induced stomatal closing were not disrupted, suggesting that abi1-1 impairs ABA signaling between ABA reception and ROS production. The abi2-1 mutation, which lies in a distinct PP2C gene, also disrupted ABA activation of I Ca. However, in contrast to abi1-1, abi2-1 impaired both H2 O2 activation of I Ca and H2 O2-induced stomatal closing. Furthermore, ABA elicited ROS production in abi2-1. These data suggest a model with the following sequence of events in early ABA signal transduction: ABA, abi1-1, NAD(P)H-dependent ROS production, abi2-1, ${\rm I}_{{\rm Ca}}\ {\rm Ca}^{2+}$ channel activation followed by stomatal closing.
For alloy design of hydrogen permeable membrane, it is important to control pressure–composition–isotherm (PCT curve) in an appropriate manner in order to obtain high hydrogen permeability with ...strong resistance to hydrogen embrittlement. Based on this concept, V-based alloy membranes are designed under some given pressure conditions at a temperature in view of the partial molar enthalpy change, ΔH¯0.2, and entropy change, ΔS¯0.2, of hydrogen for hydrogen dissolution. It is demonstrated that the PCT curve can be controlled very precisely in view of ΔH¯0.2 and ΔS¯0.2. Also, the required membrane area to obtain 300 Nm3 h−1 of hydrogen flow is estimated. It is found that, in view of the membrane area, it is favorable to apply at least 400 kPa of hydrogen pressure at feed side.
•A concept for alloy design of H2 permeable membrane has been applied for V–Fe system.•In this concept, hydriding property must be controlled appropriately.•In view of the thermodynamic parameters, hydriding property can be controlled.•Correlation between membrane area and applicable hydrogen pressure is discussed.•A concept for scale up of the membrane area is obtained.
The hydrogen permeability of Pd–27mol%Ag alloy membrane has been analyzed in view of the new description of hydrogen permeation based on hydrogen chemical potential. The hydrogen flux is consistently ...proportional to the PCT factor, fPCT, which reflects the shape of the corresponding pressure–composition–isotherm (PCT curve), regardless of whether hydrogen solubility is expressed in a format of the Sievert's law or not. From the two points of the PCT factor, fPCT, and DBTC (the ductile-to-brittle transition hydrogen concentration), the concept for alloy design of non-Pd-based alloy membranes is obtained. As an example, V–9mol%Al alloy is designed for applied temperature and pressure condition. For this condition, this alloy membrane possesses excellent hydrogen permeability with strong resistance to hydrogen embrittlement.
•A new description of hydrogen permeation and its application are shown.•The hydrogen flux is proportional to the PCT factor consistently.•The concept for alloy design based on the new description is applied to V–Al system.•Designed alloy exhibits high hydrogen permeability without brittle fracture.•Hydriding property is essential to design the hydrogen permeable alloy membrane.
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