Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile

Objectives

To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies.

Material and methods

The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays.

Results

The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (–0.87 ±0.85), SOC PSMM (–0.47 ±0.97), PAL (–1.88 ±3.58), and BLC (–0.31 ±1.90). GNT scores under –0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than –0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = –0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = –0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = –0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = –0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = –0.43). The level of anti-Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87).

Conclusions

CANTAB reveals a decrease in selected cognitive functions in patients with SLE. ACL IgG and anti-dsDNA antibodies indicated SLE patients prone to develop a decrease in cognitive functions.     

In Vitro Activity of the Novel Antimicrobial Peptide Dendrimer G3KL against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

The in vitro activity of the novel antimicrobial peptide dendrimer G3KL was evaluated against 32 Acinetobacter baumannii (including 10 OXA-23, 7 OXA-24, and 11 OXA-58 carbapenemase producers) and 35 Pseudomonas aeruginosa (including 18 VIM and 3 IMP carbapenemase producers) strains and compared to the activities of standard antibiotics. Overall, both species collections showed MIC_50/90 values of 8/8 μg/ml and minimum bactericidal concentrations at which 50% or 90% of strains tested are killed (MBC_50/90) of 8/8 μg/ml. G3KL is a promising molecule with antibacterial activity against multidrug-resistant and extensively drug-resistant A. baumannii and P. aeruginosa isolates.     

IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.     

Cysteine desulfurase Nfs1 and Pim1 protease control levels of Isu, the Fe-S cluster biogenesis scaffold

Fe-S clusters are critical prosthetic groups for proteins involved in various critical biological processes. Before being transferred to recipient apo-proteins, Fe-S clusters are assembled on the highly conserved scaffold protein Isu, the abundance of which is regulated posttranslationally on disruption of the cluster biogenesis system. Here we report that Isu is degraded by the Lon-type AAA+ ATPase protease of the mitochondrial matrix, Pim1. Nfs1, the cysteine desulfurase responsible for providing sulfur for cluster formation, is required for the increased Isu stability occurring after disruption of cluster formation on or transfer from Isu. Physical interaction between the Isu and Nfs1 proteins, not the enzymatic activity of Nfs1, is the important factor in increased stability. Analysis of several conditions revealed that high Isu levels can be advantageous or disadvantageous, depending on the physiological condition. During the stationary phase, elevated Isu levels were advantageous, resulting in prolonged chronological lifespan. On the other hand, under iron-limiting conditions, high Isu levels were deleterious. Compared with cells expressing normal levels of Isu, such cells grew poorly and exhibited reduced activity of the heme-containing enzyme ferric reductase. Our results suggest that modulation of the degradation of Isu by the Pim1 protease is a regulatory mechanism serving to rapidly help balance the cell's need for critical iron-requiring processes under changing environmental conditions.     

Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis

Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features.     

New European initiatives in colorectal cancer screening: Budapest Declaration. Official appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.     

Experience with intraoperative high frequency Doppler sonography in neurosurgical practice

Abstract

The method of blood flow velocity (BFV) evaluation by intraoperative application of the high frequency Doppler is presented. The device is used to estimate BFV changes in small caliber arteries by direct placement of the probe upon the examined vessel. BFVexaminations were performed on the site during aneurysm operations, during transsphenoidal approaches to identify the intracavernous portion of leA embedded in the tumor mass and in patients after encephalodurosynangiosis evaluated on the outpatient basis. Technical characteristics of the flowmeter used are described and examples of the BFV pictures in cerebral arteries are presented. The device allows a precise BFVevaluation in the selected vessel and detection of changes in BFV patterns particularly useful during aneurysms surgery. This method of identifying cerebral vessels may become applicable in other types of neurosurgical operations. [Neural Res 1998; 20: 655–657]