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.
Objectives
Supplementation of high protein oral nutrition shakes supplemented with β-hydroxy-β-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance ...in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons.
Methods
This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity.
Results
Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs −22.9±309.1 mm
2
for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. −0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. −1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m
2
, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (−0.38±1.21 vs. −0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (β=0.71, 95% C.I.0.09–1.33, P=0.026).
Conclusions
The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.
The motivation of this study is stimulated by a lack of knowledge about the difference of airflow characteristics between a novel air distribution method i.e., stratum ventilation (SV) and ...conventional air distribution methods i.e., mixing ventilation (MV) and displacement ventilation (DV). Detailed air velocity and temperature measurements were conducted in the occupied zone of a classroom with dimensions of 8.8 m (L) × 6.1 m (W) × 2.4 m (H). Turbulence intensity and power spectrum of velocity fluctuation were calculated using the measured data. Thermal comfort and cooling efficiency were also compared. The results show that in the occupied zone, the airflow characteristics among MV, DV, and SV are different. The turbulent airflow fluctuation is enhanced in this classroom with multiple thermal manikins due to thermal buoyancy and airflow mixing effect. Thermal comfort evaluations indicate that in comparison with MV and DV, a higher supply air temperature should be adopted for SV to achieve general thermal comfort with low draft risk. Comparison of the mean air temperatures in the occupied zone reveals that SV is of highest cooling efficiency, followed by DV and then MV.
Influences of process conditions on microstructure and dielectric properties of ceramic-polymer composites are systematically studied using CaCu
Ti
O
(CCTO) as filler and P(VDF-TrFE) 55/45 mol.% ...copolymer as the matrix by combining solution-cast and hot-pressing processes. It is found that the dielectric constant of the composites can be significantly enhanced-up to about 10 times - by using proper processing conditions. The dielectric constant of the composites can reach more than 1,000 over a wide temperature range with a low loss (tan δ ~ 10
). It is concluded that besides the dense structure of composites, the uniform distribution of the CCTO particles in the matrix plays a key role on the dielectric enhancement. Due to the influence of the CCTO on the microstructure of the polymer matrix, the composites exhibit a weaker temperature dependence of the dielectric constant than the polymer matrix. Based on the results, it is also found that the loss of the composites at low temperatures, including room temperature, is determined by the real dielectric relaxation processes including the relaxation process induced by the mixing.
Room occupants' comfort and health are affected by the airflow. Nevertheless, they themselves also play an important role in indoor air distribution. This study investigated the interaction between ...the human body and room airflow under stratum ventilation. Simplified thermal manikin was employed to effectively resemble the human body as a flow obstacle and/or free convective heat source. Unheated and heated manikins were designed to fully evaluate the impact of the manikin at various airflow rates. Additionally, subjective human tests were conducted to evaluate thermal comfort for the occupants in two rows. The findings show that the manikin formed a local blockage effect, but the supply airflow could flow over it. With the body heat from the manikin, the air jet penetrated farther compared with that for the unheated manikin. The temperature downstream of the manikin was also higher because of the convective effect. Elevating the supply airflow rate from 7 to 15 air changes per hour varied the downstream airflow pattern dramatically, from an uprising flow induced by body heat to a jet‐dominated flow. Subjective assessments indicated that stratum ventilation provided thermal comfort for the occupants in both rows. Therefore, stratum ventilation could be applied in rooms with occupants in multiple rows.
All-organic nanocomposites using conducting polypyrrole (PPy) nano-clips as fillers and poly(vinylidene fluoride-chlorotrifluoroethylene) (PVDF-CTFE) as the matrix are studied. The nanocomposites ...with a uniform microstructure were fabricated via a combination of a solution casting and a hot pressing process. Due to the uniform microstructure, the composites exhibit a single glass transition process, whose temperature decreases with increasing PPy content. The dielectric properties of the nanocomposites are systemically studied and analyzed over a wide temperature range from −60 °C to 140 °C and a broad frequency range from 100 Hz to 1 MHz. The nanocomposites have a low percolation threshold (∼7.4 wt%) and exhibit a high dielectric constant and a low dielectric loss. For the composites with 7 wt% of PPy at room temperature, the dielectric constant at 1 kHz is 23 times higher than that of the polymer matrix and the dielectric loss over a broad frequency range is less than 0.4 which is lower than the loss reported in other composites with the composition close to the percolation threshold. It is concluded that mixing PPy with P(VDF-CTFE) results in a new relaxation process that dominates the observed dielectric loss at low temperatures including room temperature. It is demonstrated that it is the DC conductivity rather than the dielectric constant that should be used to determine the percolation threshold.
Background
Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed‐type hypersensitivity reactions (DHR) induced by PPI, such as ...Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI‐related DHR, followed up their tolerability to alternative anti‐ulcer agents, and investigated the T‐cell reactivity to PPI in PPI‐related DHR patients.
Methods
We retrospectively analyzed patients with PPI‐related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross‐hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon‐γ to confirm the causalities.
Results
There were 69 cases of PPI‐related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI‐related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross‐hypersensitivity reactions, whereas three patients developed cross‐hypersensitivity reactions to alternative structurally similar PPI. The cross‐reactivity to structurally similar PPI was also observed in LAT assay.
Conclusions
PPIs have the potential to induce life‐threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.
To overcome the low discharging efficiency of ceramic-polymer composites using ferroelectric polymers as matrix and to take the advantage in fabrication offered by the polar polymer, a polar but ...non-ferroelectric polymer – poly(methyl methacrylate) (PMMA) – was selected as the matrix in the development of high performance composites for energy storage. Ba0.5Sr0.5TiO3 (BST) nanoparticles were selected as the filler. Freestanding and flexible BST-PMMA ceramic-polymer nanocomposites with BST content up to 30 vol.% were fabricated in thickness of about 5 μm using spin-coating process and were systemically studied. Due to the strong interaction between the polar groups of PMMA and the hydroxyl groups on the surface of BST nanoparticles, the suspension of BST nanoparticles in PMMA solution exhibits excellent stability and, hence, the nanocomposite films have excellent microstructure uniformity and compatibility between the BST nanoparticles and PMMA matrix. All the BST-PMMA films exhibit excellent frequency (100 Hz to 1 MHz) and temperature (−90 to 100 °C) stabilities in their dielectric properties with a high energy-storage density of more than 11 J/cm3. Most importantly, an ultra-high discharging efficiency of almost 100% is obtained in all the nanocomposites.
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•Non-ferroelectric polar polymer is introduced as matrix for the nanocomposites used as energy-storage dielectrics.•High energy density with ultrahigh discharging efficiency (~100%) are demonstrated by BST-PMMA nanocomposite films.•The BST-PMMA nanocomposite films exhibit excellent temperature and frequency stabilities of dielectric properties.
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