Acute ischemic stroke in humans is associated with profound alterations in the immune system. Hallmarks of this stroke-induced immunodepression syndrome are: lymphocytopenia, impairment of T helper ...cell and monocyte function. We studied which stroke-specific factors predict these immunologic alterations and subsequent infections.
Leukocyte/lymphocyte subsets were assessed serially by white blood cell count and fluorescence-activated cell sorter analysis in ischemic stroke patients (n=50) at baseline, day 1, and day 4 after stroke onset and compared to an age-matched control group (n=40). Concomitantly, monocytic human leukocyte antigen-DR expression and the in vitro function of blood monocytes measured by the production of tumor necrosis factor-alpha upon stimulation with lipopolysaccharide were assessed. Associations of these immunologic parameters with stroke specific factors (National Institutes of Health Stroke Scale, infarct size) were explored. Multivariable logistic regression analysis was applied to identify early predictors for poststroke respiratory and urinary tract infections.
Infarct volume was the main factor associated with lymphocytopenia on day 1 and day 4 poststroke. Particularly, blood natural killer cell counts were reduced after stroke. Monocyte counts increased after ischemia paralleled by a profound deactivation predominantly after extensive infarcts. Reduced T helper cell counts, monocytic human leukocyte antigen-DR expression, and monocytic in vitro production of tumor necrosis factor-alpha were associated with infections in univariate analyses. However, only stroke volume prevailed as independent early predictor for respiratory infections (OR 1.03; CI 1.01 to 1.04).
Infarct volume determines the extent of lymphocytopenia, monocyte dysfunction, and is a main predictor for subsequent infections.
Cranioectodermal dysplasia (CED) is a rare autosomal recessive disorder primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. CED is a chondrodysplasia, which is part of a ...spectrum of clinically and genetically heterogeneous diseases that result from disruptions in cilia. Pathogenic variants in genes encoding components of the ciliary transport machinery are known to cause CED. Intra‐ and interfamilial clinical variability has been reported in a few CED studies and the findings of this study align with these observations. Here, we report on five CED patients from four Polish families with identical compound heterozygous variants c.1922T>G p.(Leu641Ter) and c.2522A>T; p.(Asp841Val) in WDR35. The frequent occurrence of both identified changes in Polish CED families suggests that these variants may be founder mutations. Clinical evaluation of the CED patients revealed interfamilial clinical variability among the patients. This includes differences in skeletal and ectodermal features as well as variability in development, progression, and severity of renal and liver insufficiency. This is the first report showing significant interfamilial clinical variability in a series of CED patients from unrelated families with identical compound heterozygous variants in WDR35. Our findings strongly indicate that other genetic and non‐genetic factors may modulate the progression and expression of the patients' phenotypes.
Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to ...perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%–90% of cases have dominantly inherited heterozygous pathogenic variants located in the
COL1A1
and
COL1A2
genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in α1 and α2 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the
COL1A1
gene and brought new insights into the clinical severity associated with variants localized in “lethal regions”. Our results contribute to a better understanding of the clinical and genetic aspects of OI.
Autism spectrum disorders (ASDs) encompass a broad group of neurodevelopmental disorders with varied clinical symptoms, all being characterized by deficits in social communication and repetitive ...behavior. Although the etiology of ASD is heterogeneous, with many genes involved, a crucial role is believed to be played by copy number variants (CNVs). The present study examines the role of copy number variation in the development of isolated ASD, or ASD with additional clinical features, among a group of 180 patients ranging in age from two years and four months to 17 years and nine months. Samples were taken and subjected to array-based comparative genomic hybridization (aCGH), the gold standard in detecting gains or losses in the genome, using a 4 × 180 CytoSure Autism Research Array, with a resolution of around 75 kb. The results indicated the presence of nine pathogenic and six likely pathogenic imbalances, and 20 variants of uncertain significance (VUSs) among the group. Relevant variants were more prevalent in patients with ASD and additional clinical features. Twelve of the detected variants, four of which were probably pathogenic, would not have been identified using the routine 8 × 60 k microarray. These results confirm the value of microarrays in ASD diagnostics and highlight the need for dedicated tools.
AbstractIn many cases, structural damping of lightweight structures is quite low. Therefore, additional damping systems have to be applied. These systems are, in most instances, passive ones. ...Concerning lightweight structures, live loads become decisive with respect to the eigenfrequencies of the system affected. Resultant changes in dynamic behavior lead to a loss of the optimal adjustment of the passive systems, which is often followed by disturbing vibrations. This in turn leads directly to an impairment of serviceability. Semiactive damping systems can solve these problems by actively reacting to changes of the system. The following article focusses on the development of a semiactive friction damper using piezoelectric stack actuators in order to reduce the vibrations of a large-scale model of a pedestrian bridge.
Wolf-Hirschhorn syndrome (WHS, MIM 194190) is caused by the loss of the genetic material of the distal segment of chromosome 4p. We present a case of the fetus diagnosed in the second trimester of ...pregnancy by genetic amniocentesis which was prompted by abnormalities detected on ultrasound.
Heterodera schachtii, a plant-parasitic cyst nematode, invades host roots and induces a specific syncytial feeding structure, from which it withdraws all required nutrients, causing severe yield ...losses. The system H. schachtii–Arabidopsis is an excellent research model for investigating plant defence mechanisms. Such responses are suppressed in well-established syncytia, whereas they are induced during early parasitism. However, the mechanisms by which the defence responses are modulated and the role of phytohormones are largely unknown.
The aim of this study was to elucidate the role of hormone-based defence responses at the onset of nematode infection. First, concentrations of main phytohormones were quantified and the expression of several hormone-related genes was analysed using quantitative real-time (qRT)-PCR or GeneChip. Further, the effects of individual hormones were evaluated via nematode attraction and infection assays using plants with altered endogenous hormone concentrations.
Our results suggest a pivotal and positive role for ethylene during nematode attraction, whereas jasmonic acid triggers early defence responses against H. schachtii. Salicylic acid seems to be a negative regulator during later syncytium and female development.
We conclude that nematodes are able to impose specific changes in hormone pools, thus modulating hormone-based defence and signal transduction in strict dependence on their parasitism stage.
ABSTRACT
Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual ...disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause. Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up‐to‐date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well‐defined X‐linked KS type 2, and comment on phenotype–genotype correlations as well as sex‐specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki‐like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients.
Kabuki syndrome is a rare genetic condition that is caused by mutations in the KMT2D gene in approximately 56%–75% of cases and by mutations in KDM6A in 5%–8%. We present a mutation screening of 347 patients with Kabuki syndrome, which identified 208 mutations in KMT2D, as well as twelve novel KDM6A mutations. We discuss the molecular and clinical findings in this large cohort and compare them to the literature with a focus on the rarer X‐linked Kabuki syndrome type 2.
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