Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with ...concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets.
We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis.
We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP.
We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 × 10−6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP.
The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking.
Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied.
To examine the factors associated with PPP severity.
An ...observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020.
Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).
Among the 203 UK patients (43 men 21%, 160 women 79%; median age at onset, 48 interquartile range (IQR), 38-59 years), the PPPASI was inversely correlated with age of onset (r = -0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men 16%, 134 women 84%; median age at onset, 45 IQR, 34-53.3 years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years IQR, 30.5-52 years) compared with those with a clear to mild PGA score (46.5 years IQR, 35-55 years) (P = .04). In the UK sample, the median PPPASI score was higher in women (9.6 IQR, 3.0-16.2) vs men (4.0 IQR, 1.0-11.7) (P = .01). Likewise, moderate to severe PPP was more prevalent among Northern European women (57 of 134 43%) compared with men (5 of 25 20%) (P = .03). In the UK cohort, the median PPPASI score was increased in current smokers (10.7 IQR, 4.2-17.5) compared with former smokers (7 IQR, 2.0-14.4) and nonsmokers (2.2 IQR, 1-6) (P = .003). Comparable differences were observed in the Northern European data set, as the prevalence of moderate to severe PPP was higher in former and current smokers (51 of 130 39%) compared with nonsmokers (6 of 24 25%) (P = .14).
The findings of this study suggest that PPP severity is associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation intervention might be beneficial.
This open-access edited book is a collection of 17 chapters, synthesized primarily from the lectures delivered by eminent Indian and international experts during a series of capacity-building ...programmes organised in India during 2020 and 2021 under the aegis of 'Indo-German Cooperation on Seed Sector Development', a component of the Bilateral Cooperation between the Governments of India and Germany. Seed Science and Technology, a multi-disciplinary subject, is advancing rapidly keeping pace with the development of improved plant varieties and other climate-resilient technologies. Knowledge of the underlying biological processes and application of appropriate technologies for variety maintenance and seed production; quality assurance, testing and enhancement; processing, packaging and storage etc., are important in a seed programme. Chapters presented in the book is a blend of basic seed biology covering seed development, maturation, dormancy, germination, vigour and invigoration, and seed deterioration; variety maintenance and production of genetically pure seed of open-pollinated and hybrid varieties in a few key field crops and vegetables, and fundamentals of seed processing, packaging and storage; and seed quality assurance systems followed in different countries; testing the essential components of seed quality including seed health, application of molecular technologies for precision in testing, and enhancement of seed quality. It concludes by identifying the key areas of future seed research and technology development. The book covers the fundamentals and recent advances of seed science and technology with the latest research information and an exhaustive and updated list of references on different topics. It is expected to benefit the students as well as the scientists, faculty members and seed sector professionals, working in the public and private seed sectors, certification authorities and seed producing agencies in India, and elsewhere.
Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne ...(n=1,893) with controls (n=5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls. We identify three genome-wide significant associations: 11q13.1 (rs478304, Pcombined=3.23 × 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P(combined) = 4.58 × 10(-9), OR = 1.17) and 1q41 (rs1159268, P(combined) = 4.08 × 10(-8), OR = 1.17). All three loci contain genes linked to the TGFβ cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of OVOL1 and TFGB2 have decreased expression in affected compared with normal skin. Collectively, these data support a key role for dysregulation of TGFβ-mediated signalling in susceptibility to acne.
Soft matter provides diverse opportunities for the development of electrolytes for all solid state lithium batteries. Here we review soft matter solid electrolytes for lithium batteriesthat are ...primarily obtained starting from liquid electrolytic systems. This concept of solid electrolyte synthesis from liquid is significantly different from prevalent approaches. The novelty of our approach is discussed in the light of various fundamental issues and in relation to its application to rechargeable lithium batteries.
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Nanofluids are the suspension of nanoparticles (<100 nm) in conventional heat transfer fluids like water, ethylene glycol, etc. They often show enhanced thermal conductivity as compared to the base ...fluids. In the present work, thermal conductivity enhancement of Cu-Cr dispersed nanofluids is being studied by experiments as well as modeling. The modeling of the nanofluid is based on the mechanism that evenly dispersed nanoparticles within a nanofluid undergo Brownian motion. The heat pickup by the nanoparticles from the heat source during collision was estimated from MD simulation. This has been coupled with stochastic stimulation to estimate thermal conductivity enhancement. In experiments, the Cu-1%Cr and Cu-3%Cr nanoparticles have been synthesized by mechanical alloying. The measured quantity of synthesized nanoparticles has been dispersed in ethylene glycol using programmed ultrasonication. Different surfactants like sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and oleic acid have been used to prepare nanofluids. The effect of particle loading and surfactant concentration on stability of ethylene glycol based nanofluids has been visually studied by TEM and Zeta potential analysis. In the best cases of Cu-Cr dispersed nanofluids was stable for 5 days from the time of synthesis. The thermal conductivity of ethylene glycol based Cu-Cr nanofluid has been measured by transient hot wire method using Flucon LAMBDA equipment.
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