Background/Objectives. Cooccurrence of atopic dermatitis (AD) and psoriasis (PS) is not common. However, both diseases are still of interest because of their comprehensive and diverse mechanisms. ...This study aimed to present the clinical and immunological profiles of patients with concomitant AD and PS and compare them with those of patients with only one of the diseases. Methods. In this observational study, 38 children with concomitant AD and PS with a mean age of 6.5±3.2 yrs were compared with 41 similar patients with AD only (5.3±5.1 yrs) and 28 patients with PS only (6.4±4.3 yrs). All patients underwent dermatological examinations, including determination of SCORAD and PASI scores. TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12, IL-17, IL-18, IL-22, I:-33, and TARC/CCL17 were measured by ELISA according to the manufacturer’s instructions. Results. Patients with concomitant AD and PS were frequently boys and overweight and had skin lesions equally distributed throughout the body. Children with concomitant AD and PS were more likely to report a family history of atopic disease than children with only AD or PS, and those with AD were more likely to report a family history of atopic disease than those with PS. Significant differences were observed in the concentration of IL-17 between patients with AD and PS and those with only AD or PS: 9.1±3.7 pg/ml vs. 4.8±2.9 pg/ml; and 9.1±3.7 pg/ml vs. 5.2±3.9 pg/ml, respectively (PD vs. AD, p=0.01; PD vs. PS, p=0.03). Conclusions. AD and PS can coexist. The role of T helper 17 cells may be more essential than believed.
Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM ...stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.
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•Genome-wide CRISPR-Cas9 screens in patient-derived glioblastoma stem cells•Identification of regulators of stemness governing glioblastoma stem cell growth•Multiple stress response pathways are genetic vulnerabilities in glioblastoma•Identification of modulators of sensitivity to standard of care chemotherapy
MacLeod et al. describe genome-wide CRISPR-Cas9 screens identifying genetic vulnerabilities across a panel of patient-derived glioblastoma stem cell cultures. Regulators of stemness (SOX2, SOX9, DOT1L, and SOCS3) and stress response (ufmylation and ERAD pathways) govern the growth of glioblastoma stem cells. Chemogenomic screens using temozolomide identify modulators of sensitivity to chemotherapy.
This article reports world averages of measurements of
b
-hadron,
c
-hadron, and
τ
-lepton properties obtained by the Heavy Flavor Averaging Group using results available through summer 2016. For the ...averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters,
C
P
violation parameters, parameters of semileptonic decays, and Cabbibo–Kobayashi–Maskawa matrix elements.
Summary
Background
Immunotherapy in elderly patients is controversial, and there is still no evidence supporting this treatment's safety and efficacy in this population. This study was performed to ...evaluate the safety and efficacy of specific sublingual immunotherapy for house dust mite (HDM) allergens in patients over 60 years of age with allergic rhinitis and a confirmed allergy to HDM.
Objective
This study sought to assess nasal symptoms during HDM season, reduce medication use and monitor for adverse reactions during immunotherapy.
Methods
One hundred and eleven 60‐ to 75‐year‐old patients with allergic rhinitis and a confirmed Dermatophagoides pteronyssinus and Dermatophagoides farinae allergy were included in the study. The patients were individually randomized to active or placebo groups using a double‐blind method (NCTO01605760 ClinicalTrials.gov). A total of 51 subjects in the sublingual allergen‐specific immunotherapy (SLIT) group (Staloral 300R, Stallergenes, France) and 57 subjects in the placebo group were monitored for 3 years.
Results
Forty‐seven patients completed 3 years of SLIT, and 48 subjects finished the placebo treatment in the same time period. The total nasal symptom score decreased by 44% in the active group and 6% in the placebo group after 3 years of SLIT. This difference was only significant in the active group (P < 0.05). At the end of therapy, the total medication score of the active group decreased significantly by a maximum of 51% (P < 0.05), whereas the total medication score of the placebo control group showed an insignificant decrease (P = 0.56). There were no systemic adverse reactions during the study.
Conclusions & Clinical Relevance
Sublingual allergen‐specific immunotherapy in elderly patients with a HDM allergy to D. pteronyssinus and D. farinae generated a significant clinical improvement in the active group compared with the placebo group, particularly during the heating season. This therapy was well tolerated.
Background
Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this ...condition, especially regarding its clinical characteristics and impact on quality of life is still lacking.
Objectives
Aim of this pan‐European multicentre cross‐sectional study was to establish the clinical profile of CNPG, including its associated burden.
Methods
Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres' own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co‐morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed.
Results
A total of 509 patients (210 male, median age: 64 years 52; 72) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to severe worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the disease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%).
Conclusions
This multicentre cross‐sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe.
Abstract
Histone deacetylases are important epigenetic regulators that have been reported to play essential roles in cancer stem cell functions and are promising therapeutic targets in many cancers ...including glioblastoma. However, the functionally relevant roles of specific histone deacetylases, in the maintenance of key self-renewal and growth characteristics of brain tumour stem cell (BTSC) sub-populations of glioblastoma, remain to be fully resolved. Here, using pharmacological inhibition and genetic loss and gain of function approaches, we identify HDAC2 as the most relevant histone deacetylase for re-organization of chromatin accessibility resulting in maintenance of BTSC growth and self-renewal properties. Furthermore, its specific interaction with the transforming growth factor-β pathway related proteins, SMAD3 and SKI, is crucial for the maintenance of tumorigenic potential in BTSCs in vitro and in orthotopic xenograft models. Inhibition of HDAC2 activity and disruption of the coordinated mechanisms regulated by the HDAC2-SMAD3-SKI axis are thus promising therapeutic approaches for targeting BTSCs.
Mold allergies are common, mainly target the respiratory tract and present as allergic rhinitis and/or bronchial asthma. Molds include a large group of different allergens that induce all types of ...allergic reactions. Allergen specific immunotherapies (AITs) to molds are common; however, at the present time, they are limited to Alternaria. This review presents not only the benefits but also the problems with such types of AIT based on the literature and our experience.
The forced oscillation technique (FOT) is a useful diagnostic respiratory system for children. However, the final value of the FOT in the diagnosis of bronchoconstriction is still open. The aim of ...the study was to evaluate the sensitivity and specificity of the FOT vs. body plethysmography tests in the measure of bronchoconstriction in asthmatic children.
A total of 102 children aged 2 to 6 years diagnosed with early-onset asthma and 52 healthy controls were included in this prospective, randomized study. All asthmatic patients and healthy controls underwent a basic FOT as one measurement, according to the recommendation of the Resmon Pro FOT. Then, the reversibility test was performed 20 min after the administration of 200 mg salbutamol using the FOT and body plethysmography in all patients.
The mean basic Rrs, Xrs and sRaw in asthmatic patients were, respectively, 11.13 ± 1.28 kPa sL
−1
, −4.6 ± 1.18 kPa sL
−
1 and 1.72 ± 0.58 kPa s. Similar parameters were significantly better in the control group (p < 0.05). A total of 73 (71.6%) asthmatic patients had a positive test using the FOT according to Calogero. In 4 (7.7%) patients in the control group, a positive test was obtained. In body plethysmography, similar results were reached, with a positive test in 76 (74.5%) study patients and 5 (9.6%) control patients.
A bronchial reversibility test with the use of the FOT is useful for the diagnosis of bronchial asthma, especially with the use of an Rrs parameter, such as the body plethysmography test.
A new scheduling problem, the continuous flow flexible job shop (CF-FJS) is proposed. The formulation combines the well-known flexible job shop (FJS) problem and a dedicated continuous material flow ...model (MFM). In the MFM, operations are represented by material flow functions derived by integration of arbitrarily defined speed patterns. Two main concepts of the MFM formalism, i.e. variable speed of processing and continuous material flow, lead to position-dependent processing times and overlapping in operations which extend standard FJS formulation. Properties of the CF-FJS are investigated. A tabu search sched uling algorithm utilising these properties is proposed. Effective neighbourhood functions are defined based on elimination approaches. Two auxiliary procedures: search intensification level switching and fast feasibility detection are added to improve algorithm efficiency. The algorithm is verified using dedicated benchmark instances which comprise non-trivial representations of the CF-FJS specific features, i.e. machine efficiency patterns and minimum inter-operation buffers. The research is motivated by task scheduling in a fastener factory, but the presented results can be useful in many domains, such as production of granular goods, steel details, glass and fluids. The solution can be used in real-world applications. The published results can be helpful in testing new CF-FJS scheduling algorithms.
We study B --> K(*)l+l- decays (l = e, mu) based on a data sample of 657 x 10(6) BB pairs collected with the Belle detector at the KEKB e+e- collider. We report the differential branching fraction, ...isospin asymmetry, K* polarization, and the forward-backward asymmetry (A(FB)) as functions of q2 = M(ll)(2)c2. The fitted A(FB) spectrum exceeds the standard model expectation by 2.7 standard deviations. The measured branching fractions are B(B --> K*l+l-) = (10.7(-1.0)(+1.1) +/- 0.9) x 10(-7) and B(B --> Kl+l-) = (4.8(-0.4)(+0.5) +/- 0.3) x 10(-7), where the first errors are statistical and the second are systematic, with the muon to electron ratios R(K*) = 0.83 +/- 0.17 +/- 0.08 and R(K) = 1.03 +/- 0.19 +/- 0.06.
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