Transformation of the domain pattern in the developmet of Fagus silvatica L. cambium

The domain pattcrn of cambium during the first year of its function in Fagus silvatica L. resemblcs a chcckerboard. The longitudinal line along the lcaftracc, its corrcsponding line on the opposite side of the internode and nodcs comprise the domain borders. Starting from the formation of the first annual ring, this checkerboard paltem bcgins to undergo graduał transformation. A transitional domain pat.tern appears during the first few years; in each internodc, duc to the altcmate disappearancc of Z and S domains, a fragmentary domain of one typc and an expanded domain of the opposite type occur in pairs. After further transformations, a ri:gular pattcm of transverse bands of domains moving along the stem appear on older stems (over ten years-old). Tis pattern \s commonly found in othcr studied species of trees

Association of A/T polymorphism of the CHRM2 gene with bronchodilator response to ipratropium bromide in asthmatic children

Wstęp: Celem niniejszej pracy była analiza asocjacyjna polimorfizmu A/T genu receptora muskarynowego typu 2 (CHRM2) z występowaniem astmy oraz analiza farmakogenetyczna tego polimorfizmu z odpowiedzią rozkurczową na bromek ipratropium - lek antycholinergiczny stosowany w astmie. Materiał i metody: Analizę przeprowadzono w grupie 113 dzieci z astmą oskrzelową oraz w grupie 123 dzieci zdrowych stanowiących grupę kontrolną. Ponadto, w grupie 32 dzieci z astmą przeprowadzono ocenę odpowiedzi rozkurczowej na bromek ipratropium w badaniu spirometrycznym w okresie odstawienia β2-agonisty długodziałającego (salmeterolu). Analizą genetyczną objęto polimorfizm A/T (rs6962027) genu CHRM2. Oznaczanie genotypów wykonano metodą PCR-RFLP. Analizę statystyczną przeprowadzono z wykorzystaniem pakietu Statistica 7.1. Wyniki: W analizie asocjacyjnej nie wykazano związku polimorfizmu A/T genu CHRM2 z występowaniem astmy (p = 0,865 dla genotypów i p = 0,782 dla alleli). W analizie farmakogenetycznej w badanej grupie pacjentów zaobserwowano istotny związek między występowaniem genotypu TT genu CHRM2 a słabą odpowiedzią na lek antycholinergiczny (p = 0,035). Wnioski: Wykazano, że genotyp homozygotyczny TT genu CHRM2 w badanej grupie pacjentów chorujących na astmę był istotnie związany ze słabszą odpowiedzią na bromek ipratropium. Wyniki należy jednak interpretować ostrożnie, zważywszy na małą liczebność analizowanej grupy. Do sformułowania jednoznacznych wniosków istotna będzie weryfikacja uzyskanych wyników przez inne grupy badawcze.Introduction: The aim of this study was to analyze the possible association of A/T polymorphism of the CHRM2 gene with asthma, and pharmacogenetic analysis of the polymorphism with bronchodilator response to ipratropium bromide, an anticholinergic drug used in asthma. Material and methods: Analysis was performed in a group of 113 children diagnosed with bronchial asthma, and in a group of 123 healthy children from a control group. Moreover, in the group of 32 asthmatic children without concurrent treatment with long-acting β2-agonists, bronchodilator response to ipratropium bromide was evaluated by the spirometric lung function test. Genetic analysis was performed for A/T polymorphism (rs6962027) of the CHRM2 gene. Genotyping was done with the PCR-RFLP method. Statistical analysis was performed using Statistica v.7.1 software. Results: No association of A/T polymorphism was found with asthma (p = 0.865 for genotypes and p = 0.782 for alleles). In the pharmacogenetic analysis, it was observed that patients carrying TT genotype of CHRM2 gene polymorphism demonstrated significantly poorer response to anticholinergic drug as compared to the patients with other genotypes for this polymorphism (p = 0.035). Conclusions: We found that TT genotype in the CHRM2 gene was associated with poor bronchodilator response in asthmatic patients. The results should be analyzed carefully considering the small sample size and should be confirmed by other research groups

Granulomatosis with polyangiitis (Wegener's granulomatosis) with hard palate and bronchial perforations treated with rituximab : a case report

We present a case of a 57-year-old woman suffering from granulomatosis with polyangiitis (GPA), who in the seventh months of immunosuppressive treatment (cyclophosphamide) progressed with new pulmonary changes and perforations of the hard palate and bronchi. Rituximab was introduced resulting in B-cell depletion and disappearance of anti-PR3 antibody. Palatal holes have substantially diminished and all bronchial perforations disappeared, covered by fibrous tissue. In the fourth month after rituximab administration, large scarring obstruction of the right main bronchus with upper and middle lobes atelectasis emerged. Because of increasing dyspnoea, stenotic bronchus was re-opened by bronchoscopy. Intervention was complicated by bilateral pneumothorax and later, on the seventh day, by fatal pulmonary bleeding. To our knowledge, this is the first report of GPA refractory to cyclophosphamide complicated by palatal and bronchial perforations

Subphenotypes of nonsteroidal antiinflammatory diseaseexacerbated respiratory disease identified by latent class analysis

Background Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID‐exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro‐inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. Objective We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA). Methods A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High‐performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA. Results Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild‐to‐moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE4/logPGE2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro‐inflammatory LTE4 in ISS and the highest logLTE4/logPGE2 ratio. Class 3 subjects had mild‐to‐moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro‐ (LTE4, PGD2 and 11‐dehydro‐TBX2) was balanced by anti‐inflammatory PGE2. The value of logLTE4/logPGE2 was between values calculated for classes 1 and 3, similarly to disease control and severity. Conclusions LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future

Polymorphisms of two histamine-metabolizing enzymes genes and childhood allergic asthma: a case control study

<p>Abstract</p> <p>Background</p> <p>Histamine-metabolizing enzymes (N-methyltransferase and amiloride binding protein 1) are responsible for histamine degradation, a biogenic amine involved in allergic inflammation. Genetic variants of <it>HNMT </it>and <it>ABP1 </it>genes were found to be associated with altered enzyme activity. We hypothesized that alleles leading to decreased enzyme activity and, therefore, decreased inactivation of histamine may be responsible for altered susceptibility to asthma.</p> <p>Methods</p> <p>The aim of this study was to analyze polymorphisms within the <it>HNMT </it>and <it>ABP1 </it>genes in the group of 149 asthmatic children and in the group of 156 healthy children. The genetic analysis involved four polymorphisms of the <it>HNMT </it>gene: rs2071048 (-1637T/C), rs11569723 (-411C/T), rs1801105 (Thr105Ile = 314C/T) and rs1050891 (1097A/T) and rs1049793 (His645Asp) polymorphism for <it>ABP1 </it>gene. Genotyping was performed with use of PCR-RFLP. Statistical analysis was performed using Statistica software; linkage disequilibrium analysis was done with use of Haploview software.</p> <p>Results</p> <p>We found an association of TT genotype and T allele of Thr105Ile polymorphism of <it>HNMT </it>gene with asthma. For other polymorphisms for <it>HNMT </it>and <it>ABP1 </it>genes, we have not observed relationship with asthma although the statistical power for some SNPs might not have been sufficient to detect an association. In linkage disequilibrium analysis, moderate linkage was found between -1637C/T and -411C/T polymorphisms of <it>HNMT </it>gene. However, no significant differences in haplotype frequencies were found between the group of the patients and the control group.</p> <p>Conclusions</p> <p>Our results indicate modifying influence of histamine N-methyltransferase functional polymorphism on the risk of asthma. The other HNMT polymorphisms and ABP1 functional polymorphism seem unlikely to affect the risk of asthma.</p

Sense of happiness in Polish patients with multiple sclerosis

Introduction. Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. Material and methods. Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. Results. Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25–42) vs. 119.88 (25–49), respectively; p = 0.031] and the subscales (OHQ subscale 1 — 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 — 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (β = 0.40; p &lt; 0.001), positive orientation (β = 0.32; p &lt; 0.001), and primary education (β = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. Conclusions. The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies — the Polish experience

Introduction. The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited.Materials and methods. This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health.Results. There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used.Conclusions and clinical implications. Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs