Proinflammatory Cytokines (IL-1, -6, -8, -15, -17, -18, -23, TNF-α) Single Nucleotide Polymorphisms in Rheumatoid Arthritis-A Literature Review.

Conducted studies highlight that a mixture of genetic and environmental factors is responsible for rheumatoid arthritis (RA) development. This study aimed to analyze the available literature for the relationship between, on the one hand, single-nucleotide polymorphisms (SNPs) in the proinflammatory cytokines genes interleukin-1 (IL-1), -6, -8, -15, -17, -18, and -23, and tumor necrosis factor-alpha (TNF-α), and on the other hand, RA susceptibility, severity, and patients' response to applied treatment. The PubMed database was searched for sources. Preference was given to articles which were published within the past 20 years. Data indicate that the relationship between selected SNPs in proinflammatory cytokines genes and susceptibility to developing RA is inconclusive, and it depends on the ethnicity of the population. Although the allelic and genotypic frequencies of many SNPs in proinflammatory cytokines genes analyzed did not differ between RA patients and healthy controls, deeper analysis showed that these polymorphisms have a relationship with clinicopathological features of RA. SNPs in proinflammatory cytokines genes also "modify patients' response" to applied treatment. Further studies, on larger cohorts of subjects and in different populations, should be conducted to elucidate the role of SNPs in IL-1, -6, -8, -15, -17, -18, and -23, and TNF-α genes in RA patients.

The preliminary study suggests an association between NF-ĸB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients.

The significant role of increased activation of 20S proteasomes in the development of abdominal aortic aneurysms has been well-established in a mouse model. The available literature lacks similar studies concerning brain aneurysms. The aim of the study was to verify the hypothesis that patients with unruptured intracranial aneurysms (UIA) have increased 20S proteasome ChT-L activity compared to the control group of individuals without vascular lesions in the brain. In the next step, the relationship between the activity of 20S proteasomes ChT-L and precursor proteins from the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family, namely NF-κB1 (p105), NF-κB2 (p100), NF-κB p65, and the inflammatory chemokine MCP-1, was examined. Patients with UIA had significantly higher 20S ChT-L proteasome activity compared to the control group. Patients with multiple aneurysms had significantly higher 20S proteasome ChT-L activity compared to those with single aneurysms. In patients with UIA, the activity of the 20S proteasome ChT-L negatively correlated with the concentration of NF-κB1 (p105) and NF-κB p65 precursor proteins and positively correlated with the concentration of the cerebrospinal fluid chemokine MCP-1. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-κB pathway.

Sources of patients' knowledge about cardiovascular disease prevention in Poland - a pilot study.

Introduction: Education about coronary artery disease (CAD) is the basis of the prevention programs to limit the impact of CAD on patients' health. Aim: To identify patterns characterizing several groups of patients that might help to create targeted and more efficient education projects. Material and methods: Data were collected using a self-designed questionnaire assessing sociodemographic and clinical profile, sources of knowledge, and expectations about education on heart diseases. It was conducted among patients at the cardiology department and at the patients' congress. Data were collected between July 2016 and October 2018 at the cardiology department and 5-7 December 2018 during a patients' congress. Results: Of 486 respondents 74% were male, and the median age was 68 years (interquartile range (IQR): 62-73). History of CAD was reported by 68% of patients. Cardiologists were reported as a source of knowledge more often by men than women. Patients with higher education were more likely to use books and internet sources, but they relied less on education provided by cardiologists. Conclusions: Regardless of the sociodemographic or clinical factors, appointments with health care professionals were indicated as the most preferable form of education, and physicians were perceived as the most reliable and trusted source of knowledge.

Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients.

The NBN (NBS1) gene belongs to a group of double-strand break repair genes. Mutations in any of these genes cause genome instability syndromes and contribute to carcinogenesis. NBN gene mutations cause increased tumor risk in Nijmegen breakage syndrome (NBS) homozygotes as well as in NBN heterozygotes. NBS patients develop different types of malignancies; among solid tumors, medulloblastoma (MB), an embryonal tumor of the cerebellum, has been reported most frequently. The majority of medulloblastomas occur sporadically, some of them manifest within familial cancer syndromes. Several signaling pathways are known to be engaged in hereditary and sporadic MB. The aim of our study was to identify mutations in selected exons of the NBN gene and to determine the frequency of the most common NBN gene mutations in pediatric patients with different types of medulloblastoma. We screened a total of 104 patients with MB and identified 7 heterozygous carriers (6.7%) of two different germ-line mutations of NBN gene; all of them had classic MB. Our results indicate that heterozygous carriers of the germ-line NBN gene mutations (c.511A>G and c.657_661del5) may exhibit increased susceptibility to developing MB. The risk of medulloblastoma is estimated to be 3.0 (for c.511A>G) and 4.86 (for c.657_661del5) times higher than in the general Polish population (p<0.05). These results suggest that heterozygous NBN germ-line mutations may contribute to the etiology of medulloblastoma.

The frequency of NBN molecular variants in pediatric astrocytic tumors.

Gliomas, particularly those of astrocytic origin, are the most frequent primary central nervous system tumors that develop in children. The majority of them are benign and slow growing, with relatively good prognosis. Several genomic and gene alterations are known to be involved in astrocytoma development, but the precise mechanisms remain poorly understood. The NBN gene, which participates in DNA double-strand break repair and maintenance of genome stability, has been postulated to be a susceptibility factor for a number of cancers. Here we report the results of NBN gene analyses performed in 127 children with various astrocytic tumors. PCR-SSCP analysis followed by DNA sequencing was used for molecular variant screening. Three carriers (2.37%) of different germline mutations on one NBN allele were found. The common Slavic deletion c.657_661del5 (p.K219fsX19) was detected in a patient with pilocytic astrocytoma; a known mutation, c.643C>T (p.R215W), and a new substitution, c.565C>G (p.Q189E), were identified in two patients with primary glioblastoma. The risk of developing astrocytic malignancies is estimated to be 1.33 times higher for c.657_661del5 and 3.2 times higher for c.643C>T than in the general Polish population (P > 0.05). Because of the low frequency of the mutations identified in the studied group, we were unable to determine the exact role of NBN in the development of astrocytoma in children. The presence of two potentially pathogenic NBN molecular variants among 16 glioblastoma cases (12.5%) could be a remarkable finding in our study. We thus cannot exclude a possible role of NBN in the tumorigenesis of a certain type of astrocytic tumors.

Low serum IgA and increased expression of CD23 on B lymphocytes in peripheral blood in children with regressive autism aged 3-6 years old.

INTRODUCTION: Immune system dysfunction is considered to be one of many medical disorders found in children with autism. The primary objective of the study was to assess if blood tests reflecting humoral immunity (IgA, IgG, IgM, IgE) are useful in identifying children with regressive autism. The secondary objective was to evaluate a part of the cellular arm of immunity (CD4/CD25 Tregs, CD4/CD23 cells) in those children. MATERIAL AND METHODS: Using a clinical case-control design, the systemic levels of immunoglobulins and lymphocyte subpopulations analysed by flow cytometry were compared in children aged 3-6 years old with a new diagnosis of regressive autism (n = 24; mean age: 4.25 ±1.70 years; male 23/24) and in sex- and age-matched healthy children (n = 24; aged 4.25 ±2.20 years; male 23/24). RESULTS: The humoral immunity profile, described by three binary variables, IgA < 0.97 g/l, IgE > 36 IU/ml, and IgG > 6.3 g/l, with a sensitivity of 79% and a specificity of 83% (p < 0.0001), was able to identify children with autism. The highest risk of autism diagnosis was associated with IgA < 0.97g/l (OR - 23.0; p < 0.001). A higher number of CD19/CD23 was found in children diagnosed with autism than in the control group (36.82 ±6.72% vs. 18.20 ±3.95%; p < 0.02). No correlation between the number of CD23-positive cells and serum IgE levels was observed. CONCLUSIONS: A subtle shift of serum immunoglobulins consisting of low-normal IgA and B cell activation expressed by an increase of CD23-positive cells may characterize children with regressive autism aged 3-6 years old.

[Central venous catheters in children with cancer. Risk of complications. One centre experience]. / Centralne dostepy dozylne u dzieci z choroba nowotworowa. Ryzyko powiklan. Doswiadczenia jednego osrodka.

OBJECTIVE: To describe the incidence and type of central venous catheters (CVC) complications in children treated for solid tumours. MATERIAL AND METHODS: Between 1997-2005, 500 paediatric patients were treated for cancer. The CVC complications were analyzed according to the CVC type, blood product transfusion (BT) and parenteral nutrition (TPN). Chi-square test was used for statistics. RESULTS: For 566 surgically inserted CVCs: 147 (25.8%) were ports, 413 (73,6%) tunnelled catheters: Broviacs--227 (39.9%), Groshongs--186 (32.7%) and other--6 (1%). total number of CVC days was 288 944, (median: 422, range: 2-2583). 297 complications (rate of 1.02/1000 CVC days) were observed: 81 catheter infections (0.28), 77 mechanical complications (0.266), 59 no aspiration events (0.204), 52 thrombotic occlusions (0.179) and 28 tunnel infections (0.096). At the end of the study period 121 (28%) CVCs were prematurely removed due to: infection (52), mechanical cause (49), thrombotic occlusion (14), no aspiration (6). Mechanical complications in catheters comparing to ports were more frequent (p= 0.007). There were more infections in Broviacs than Groshongs catheters (p=0.022) and in children receiving BT and TPN (p=0.046 and 0.003). CONCLUSIONS: CVC's related complications were relatively rare. Most common were infections and concerned catheters and these complications were most frequent in patients receiving BP and TPN. Risk of mechanical complications was higher in catheters than ports.