A single nucleotide polymorphism −35 kb T > C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw06

HLA class I molecules play a role both in viral infection control and in autoimmune diseases development. rs9264942T > C polymorphism in HLA-C gene was found to impact on HLA-C surface expression level and to be associated with HIV-1 control. It was found that these HLA alleles which protect against AIDS are associated with autoimmune disease e.g. psoriasis vulgaris (PsV). Whether rs9264942 SNP is associated with PsV was investigated here. rs9264942T > C was genotyped in 292 PsV patients, and 254 controls using TaqMan Genotyping Assay.     

Stan odżywienia dzieci z objawami alergii atopowej

Introduction

Bronchial asthma and atopic dermatitis (AD) are chronic diseases potentially influencing the nutritional status.

Aim

The aim of the study was to assess the nutritional status of children with atopic allergy symptoms including the clinical manifestation, severity and duration of the disease and the treatment.

Material and methods

The study covered 92 children aged 2 to 18 years. Atopic allergy was confirmed by positive skin tests results. The control group consisted of 124 healthy children. For both groups height, weight and thickness of the triceps, subscapular and abdominal skinfolds were performed. Based on this body mass index (BMI), Cole index and total of skinfolds were calculated. Additionally, for patients with asthma and for controls fat mass percent was estimated based on the bioelectrical impedance.

Results

It was found that the nutritional status of children with asthma does not differ from the one observed in healthy peers. Children with atopic dermatitis aged 2 to 8 years presented worse nutritional status than the control group; however, no differences were shown between patients with AD aged 9 to 18 years and healthy children. No influence of disease severity on nutritional status of children with bronchial asthma was observed, but more advanced severity grading of AD had a negative effect on the nutritional status. No association between either disease duration or treatment and nutritional status of children with bronchial asthma was shown. Relation of treatment and nutritional status of children with AD was not observed.

Conclusion

Children with AD need nutritional status monitoring.     

Zapobieganie zakażeniom meningokokowym – jak stosować obecnie dostępne szczepionki

Authors have presented the current recommendations for the prevention of meningococcal infections. The epidemiological situation in Poland has been described and the use of currently available meningococcal vaccines has been discussed. The chemoprophylaxis for close contacts of all people with invasive meningococcal disease has been also presented.     

Are synchronous and metachronous bilateral breast cancers different? An immunohistochemical analysis aimed at intrinsic tumor phenotype

The biology and pathomechanism of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous bilateral breast cancers and metachronous bilateral breast cancers, with special focus on intrinsic tumor phenotype. Methods: Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 metachronous bilateral breast cancers and 61 synchronous bilateral breast cancers. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Cutoff levels are provided in the table. Results: Metachronous bilateral breast cancers tumors had lower estrogen receptor expression (p=0.047) and higher expression of cytokeratin 5/6 (p=0.017) and of vimentin (p=0.008); in multivariate analysis only vimentin retained the significance (p=0.01). Ten (13%) and 11 (26%) of metachronous bilateral breast cancers and synchronous bilateral breast cancers had luminal A phenotype, 39 (50%) and 15 (36%) were luminal B HER2-negative, 13 (17%) and 12 (28%) - luminal B HER2-positive, 3 (4%) and 2 (5%) - HER2-positive (not luminal), and 12 (16%) and 2 (5%) had triple negative phenotype (p=0.07). Conclusion: Metachronous bilateral breast cancers, compared to synchronous bilateral breast cancers, are characterized by more aggressive phenotype, expressed by lower expression of estrogen receptor and stronger expression of cytokeratin 5/6 and vimentin; this does not, however, translate into differences in the distribution of intrinsic tumor phenotypes.     

Statistical Models Supporting the High-Performance Self-Compacting Concrete (HPSCC) Design Process for High Strength

The type of test ingredients used for obtaining self-compacting high-performance concrete (HPSCC) has been carefully selected to be universal. For this purpose, an extensive statistical analysis of the obtained results of the literature research was carried out. Then, universal and adapted to the typical range, highly fit statistical models are presented that can support the HPSCC design process for achieving high strength. For this purpose, a broad plan of statistical research was used, namely multivariate selection of sidereal points, which allowed the use of as many as five variable factors at three levels of variability. The sidereal points were equal to the respective minimum and maximum input values. Additionally, based on the analysis of variance (ANOVA) for factorial systems with the interaction of the obtained test results, the significance of the impact of the tested material factors on the compressive strength of the HPSCC tested was determined.     

Interlaboratory Comparison as a Source of Information for the Product Evaluation Process. Case Study of Ceramic Tiles Adhesives

In this study, the results obtained by 19 laboratories participating in 2 editions of the interlaboratory comparison (ILC) determining 2 properties of ceramic tiles adhesives (CTAs), i.e., initial tensile adhesion strength and tensile adhesion strength after water immersion following EN 12004, were analyzed. The results show that participating laboratories maintain a constant quality of their work. The use of z-score analysis, under ISO 13528, allows for classifying 89.5% to 100% of laboratories as satisfactory, depending on the measurement’s kind and edition. The remaining laboratories are classified as questionable. The investigation of the predominant mode of failure of the CTA’s samples tested in the two editions shows significant differences. From the perspective of laboratories, the goal of the ILC has been achieved. From the standpoint of a manufacturer who evaluates a product’s properties when placing it on the market, the results indicate the necessity of a particular treatment of the product evaluation process because the variability of the obtained results is significant. It increases the possibility of the product failing to meet the assessment criteria verified by the construction market supervision authorities. The manufacturer must consider all possible variations in the risk analysis, including the ILC results, to improve the assessment process of CTAs.     

Synthesis of xanthohumol and xanthohumol-d3 from naringenin

A six-step synthesis of xanthohumol (1a) and its d₃-derivative (1b) from easily accessible naringenin is reported. The prenyl side chain was introduced by Mitsunobu reaction followed by the europium-catalyzed Claisen rearrangement and base-mediated opening of chromanone gave access to an α,β-conjugated ketone system. Compound 1b was used as an internal standard in stable isotope dilution assays of 1a in two Polish beers.

A six-step synthesis of xanthohumol and its d₃-derivative from easily accessible naringenin is reported.

Xanthohumol (1a, Scheme 1A) is a naturally occurring prenylated chalcone produced by lupulin glands in female inflorescences of hop plants.¹ In recent years, 1a has attracted significant attention due to its vast range of biological activities including cancer-preventive, antioxidative, anti-inflammatory, and antiviral.^2–8 Such properties combined with low toxicity to the human body make 1a a prospective therapeutic agent, diet supplement, or ingredient of cosmetics.⁹ Although 1a was isolated from natural sources in 1913,¹⁰ the first synthesis of this compound was reported as late as in 2007.¹¹ Several other syntheses have been reported since then, but only minor improvements have been achieved.^12–14Open in a separate windowScheme 1The background of the study.Bioactive compounds labeled with stable isotopes (deuterium, carbon-13) are widely applied in metabolomic studies for tracking metabolic pathways and as internal standards in stable isotope dilution assays.^15,16 Deuterated compounds are also considered as attractive drug candidates due to the influence of the kinetic isotope effect on pharmacokinetics.^17–19 Although approaches to ¹³C-enriched xanthohumol^20,21 and hydrogen/deuterium exchange in 1a²² were reported, no scalable and cost-effective synthesis of the deuterium-labeled derivative of 1a (i.e.1b) has been disclosed to date.Two main challenges have to be faced in the synthesis of 1a: (i) construction of a pentasubstituted aromatic ring containing a prenyl side chain and (ii) selection of suitable protecting groups for phenols. In the case of (i), phloroglucinol is used as a precursor and an acyl-substituent is introduced by Friedel–Crafts acylation with a subsequent Claisen–Schmidt condensation. The prenyl side-chain is introduced by Mitsunobu alkylation, followed by Claisen rearrangement. In the case of (ii), acid-sensitive alkoxymethyl protecting groups, removable under conditions in which 1a does not cyclize to isoxanthohumol (2a), are used most often (Scheme 1A).In this study, we have developed a synthetic approach for the formation of 1a and its deuterated analog 1b. We envisioned that both 1a and 1b can be directly obtained by the base-promoted chromanone ring-opening of 2a or 2b, which in turn can be obtained from easily accessible naringenin (3) (ca. 1 $/1 g) via two-step prenylation and Williamson etherification of the phenolic OH (Scheme 1B). The use of 3 as the starting material is beneficial as only one prenyl substituent has to be introduced.The synthetic route leading to 1a and 1b is depicted in Scheme 2. Our synthesis commenced from naringenin (3), which was selectively converted to diester 4 (Ac₂O, pyridine). O-Alkylation of 4 under Mitsunobu conditions (3-methyl-2-butene-1-ol, Ph₃P, DIAD), followed by the catalytic Claisen rearrangement of 5 (Eu(fod)₃, 1,2-dichloroethane, 80 °C) afforded prenyl-derivative 6. Notably, performing the latter reaction in 1,2-dichloroethane above its boiling point was superior in comparison to earlier reports.^23–26 Alkylation of 6 (CH₃I, Ag₂O or CD₃I, Ag₂O) afforded 7a/7b in good yields. An alternative approach to 7b involving the alkylation of phenolic OH under Mitsunobu conditions (CD₃OD, Ph₃P, DIAD) required a large excess of reagents and afforded the product in moderate yield. Basic hydrolysis (KOH, MeOH) of esters afforded isoxanthohumols 2a/2b. Although the chromane ring was stable during the hydrolysis, it could be opened under more harsh conditions (DBU, DMF, 70 °C),^27,28 leading to 1a/1b in good yields after a mild acidic workup.Open in a separate windowScheme 2The synthetic route to 1a and 1b.With 1a and 1b in hand, we investigated their MS-fragmentation patterns in electrospray ionization in positive and negative ion modes. The MRM transitions were found by an automatic procedure and they are listed in † for details). In positive ion mode, the most intensive product ions in fragmentation of 1a were ions with m/z values of 178.9, 299.0, 113.0, and 150.9. Corresponding ions with m/z +3 values can be found in the fragmentation of 1b. On the other hand, in the negative ion mode, the same product ions are observed both in the case of 1a and 1b, indicating that the CH₃/CD₃ groups were lost during fragmentations.The MRM transitions of 1a and 1b

IL-17A,IL-17E and IL-17F as Potential Biomarkers for the Intensity of Low-Grade Inflammation and the Risk of Cardiovascular Diseases in Obese People

Low-grade inflammation is a factor that predisposes to many obesity-related comorbidities. The immune mechanisms controlling the inflammatory response related to the secretory activity of adipocytes and its consequences for the organism are still under investigation. Methods: 84 obese adult volunteers (BMI ≥ 30 kg/m²) were tested by BIA. Serum samples were collected to analyze the concentrations of interleukins IL-17A, IL-17E and IL-17F. The subjects completed the original questionnaire, the FFQ-6 food consumption frequency questionnaire and the food diary. Results: The level of IL-17E and IL-17F was positively correlated with the BMI value and the level of IL-17E increased with the content of subcutaneous fat. Its increased blood concentration was also observed in individuals who declared that they were diagnosed with atherosclerosis and/or were taking beta-blockers. Products that were related with a low level of the above-mentioned interleukins were vegetables, groats, eggs, red meat, fast-food and alcohol. The level of these interleukins was positively correlated with the frequent consumption of confectionery and breakfast cereals. Nutrients that decreased the concentrations of IL-17 isoforms were potassium, iron, vitamins B6 and C, and folic acid. Conclusions: Both IL-17E and IL-17F may be closely related to the intensity of low-grade inflammation and be biomarkers of cardiovascular disease risk. Food products or the nutrients they contain may affect the levels of the above-mentioned interleukins as well as IL-17A.     

Basal cell carcinoma—Primary closure of moderate defect of mid forehead

This is a case presentation of successful defect repair after radical surgical excision of a moderately large basal cell carcinoma by a simple procedure taking advantage of a patient's individual face features.