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Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome caused by either TSC1 or TSC2 gene mutations. About 15% of TSC patients remain without genetic diagnosis by conventional analysis despite clinical evidence. It is important to identify somatic mosaics, as therapeutic options are now available in patients with TSC1 or TSC2 mutations. Here, we describe the clinical and genetic characteristics of four male TSC patients with low-level mosaicism. Patients presented at ages between 9 months and 32 years. Clinical manifestations varied considerably and included brain lesions in all four patients, cardiac rhabdomyomas in two young patients, skin involvement in two patients, and retinal hamartomas and renal angiomyolipomas in three patients. One patient presented with epileptic seizures and psychomotor delay. Low levels of mosaicism for TSC1 or TSC2 mutation were found in different tissue samples employing next generation sequencing and multiple ligation-dependent probe amplification. The five disease-associated variants, including one second-hit mutation, include three truncating mutations and one deletion in TSC2, and one truncating mutation in TSC1. Sanger sequencing, allele-specific oligonucleotide PCR (ASO-PCR), and droplet digital PCR were used to confirm and quantify the disclosed mutations. Genetic identification of low-level mosaicism for TSC remains challenging but is important for optimal surveillance and management., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Electrospun silk fibroin nanofibrous scaffolds (ESFNSs) were successfully prepared by electrospinning of various Bombyx mori silk fibroin concentrations (10, 12, and 14% in formic acid). After characterizing the purified silk fibroin, the morphology, porosity, fibers' diameter, and uniformity of the prepared scaffolds were examined in detail. In addition, biological responses such as effects on bone marrow cell viability, cytotoxicity, and cell adhesion were evaluated in vitro. Biocompatibility and bioactivity properties of the ESFNSs were evaluated in vitro and in vivo by cell culturing and subcutaneous implantation in rat models for 7 and 28 days, respectively. According to the obtained results, no beaded fibers were seen in any of the prepared scaffolds, whereas ESFNS-10% provided more uniformity and porosity with nanoscaled fibers (90 ± 0.021 nm). Furthermore, the scaffolds also showed good cell adhesion and spreading (68.7 ± 11.8 and 7.6 ± 3.3 total length and width, respectively) with no detectable effect on cell viability and cytotoxicity. The in vivo biocompatibility evaluation indicated that the scaffolds did not stimulate detectable cellular inflammatory response (lymphocytes) and increased the total cell number (cellularity) in the implantation area. Furthermore, the results suggest the potential use of the prepared ESFNS-10% bone marrow cell constructs in direct implantation for tissue engineering applications., (© 2014 International Union of Biochemistry and Molecular Biology, Inc.)

Aim: This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers., Methods: A randomized crossover study was carried out in three phases (n= 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P ≤ 0.05., Results: The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml(-1) h), (-)-ASOX by 358% (0.14 vs. 0.50 µg ml(-1) h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml(-1) h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml(-1) h)., Conclusions: The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

The phenotypic variance (V(P)) may be divided into the genetic variance (V(G)), the general environmental variance (V(Eg)), and the special environmental variance (V(Es)). The latter is estimated through repeatability calculation (b). This value is considered the upper limit of heritability and represents maximum genetic variance proportion (V(Gm) = V(G) + V(Eg)) in relation to V(P) (b = (V(G) + V(Eg))/V(P)). This process allows an improved determination of biological relationships among groups from estimators maximizing the genetic information of quantitative characters. Two hundred and thirty-seven individuals inhabiting the northern coast of Chile for 4,000 years were taken as a sample. Measurement was made of six metric characters at both sides of the cranium. Special environmental values (es) were obtained by regression. The difference between these values and the phenotypic values (p) consists in the genetic values plus the general environmental values (g + eg). A mean b value of 0.83 indicated that V(Es) represents 17% of V(P). The results showed: 1) high stability of the maximum genetic variance in time and space, 2) high correlation between the biological relationships model, the phenotypic model, and the maximum genetic model, and 3) random distribution of the nongenetic variation, as expected from the quantitative genetics theory. These results support the use of phenotypic data for the interpretation of the evolution history of prehistoric populations., ((c) 2006 Wiley-Liss, Inc)

The present paper studies the evolutionary process operating on prehistoric groups from the Azapa valley and coast (northern Chile). The sample consists of 237 crania from the Archaic Late, Early Intermediate, Middle, Late Intermediate, and Late periods. Six metric variables were used, which were transformed to eliminate the special environmental component and to increase the proportion of genetic variance. Population structure was assessed using a method based on quantitative genetic theory, which predicts a lineal relationship between average within-group phenotypic variance and group distance to the population centroid. Results indicate that 17.5% of the total variance accounts for special environmental variance. An excess in extraregional genetic flow is observed in the population corresponding to the Early Intermediate period in the valley. A reduced differentiation is observed between Archaic and Early Intermediate coastal groups, as well as between the latter and the inhabitants of the valley in the same period. Genetic differences between both areas increased substantially since the Middle period. Evidence indicates that long-range gene flow was lower on the coast than in the valley, the lowest estimated Fst being 0.0199 for the total population (coast and valley), 0.0111 for the coastal population, and 0.0057 for the valley. Results are discussed in terms of regional archeological and ethnohistorical evidence, and a microevolutionary model is presented to account for the biological history of the population., (Copyright 2002 Wiley-Liss, Inc.)