Rebiopszia és ismételt gefitinibkezeléssel elért remisszió tüdőrákban

The authors present a case of a 81-year-old non-smoker woman who was diagnosed with extended, bilateral bronchial adenocarcinoma in 2008. Two years later the tumor showed marked progression. EGFR sensitizing mutation (exon 19 deletion) was detected and gefitinib treatment was started in March 2010. After 12 months of spectacular and complete remission and 8 months of slow progression docetaxel therapy was applied and yielded partial remission. When progression redeveloped rebiopsy was performed and revealed EGFR exon 19 deletion again. Gefitinib retreatment was introduced in February 2013 and resulted in partial remission with excellent clinical status. In March, 2014 the patient is still on gefitinib treatment without any signs or symptoms of lung cancer but with very slow radiological progression. The authors overview the most important theoretical and practical questions regarding rebiopsy and retreatment in lung cancer with EGFR-TKI therapy

Reading Disability and Quality of Life Based on Both Self- and Parent-Reports: Importance of Gender Differences

Purpose: The aim of this study is to investigate self- and parent-rated quality of life (QoL) in children with a reading disability (RD) and the impact of comorbid psychopathology, with special focus on age and gender differences. Methods: Using the Dyslexia Differential Diagnosis Maastricht-Hungarian standard test, 127 children (aged < 18) were included in the RD group and 81 in the control group. To measure comorbid psychopathology, the Strengths and Difficulties Questionnaire (SDQ) was administered. To evaluate the children’s QoL self- and parent-rated versions of the Measure of Quality of Life for Children and Adolescents (ILK) were used. Group differences in QoL and psychopathology were assessed using Mann-Whitney U tests. Moderated mediational models were tested in which comorbid psychopathology mediated the relationship between group membership and self- and parent-rated QoL, which was dependent on gender. Child’s age and parents’ level of education were included as covariates. Results: The RD group showed lower QoL than the controls in several domains, according to the parent-report, while no differences between the two groups were found, according to self-report. In boys, results revealed conditional and indirect effects of group membership on self- and parent-rated QoL through comorbid psychopathology (-.046, BCa 95%CI: -.135 −.043 and .064, BCa 95%CI: .024−.111, respectively) as well as a conditional direct effect of group membership on parent-reported (-.098, BCa 95%CI: .012−.184), but not self-rated, QoL. No relationship was found for girls. Conclusions: This study highlights the importance of measuring QoL and comorbid psychopathology in children with RDs from more sources and accounting for gender and age differences

Long-Term Effects of Multimodal Treatment on Psychopathology and Health-Related Quality of Life of Children With Attention Deficit Hyperactivity Disorder

Aim: The current study aimed to examine the association between long-term (36 months) multimodal (pharmacological and psychological) treatment and psychopathology and health-related quality of life (HRQoL) in children with attention deficit/hyperactivity disorder (ADHD) from the perspectives of both the children and parents.Methods: The sample consisted of 23 children with ADHD (21 boys, 2 girls, mean age = 13.46 years, SD = 2.36) and 23 healthy control children (11 boys, 12 girls, mean age = 12.49 years, SD = 1.75). The Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) was applied to measure psychopathology and both parent and self-rated versions of the Inventory for the Measure of the Quality of Life in Children and Adolescents were used to assess HRQoL at baseline and at the 36-month follow-up visit. The ADHD group took part in multimodal (medical and behavioral) therapy. The healthy control group did not get any intervention.Results: At the baseline, the ADHD group was characterized with higher scores in nine MINI Kid scales and showed lower HRQoL than the control group according to both children and their parents. At the 36-month follow-up visit six scale scores (ADHD, social phobia, oppositional defiance and conduct disorder, major depressive episode, dysthymic disorder) showed statistically significant decreases in the ADHD group, while these scores were constant in the control group. Parent-rated HRQoL was significantly lower in the clinical group at baseline than at the end of the study, but there were no significant changes in the control group. Self-reported changes in HRQoL matched parent-reported changes.Interpretation: Multimodal therapy is associated with decreased psychopathology and improved HRQoL over the long term

Critical point analysis and biocide treatment in a microbiologically contaminated water purification system of a power plant

Many industries use ultrapure water (UPW) for their operation. In spite of purification efforts, microbial contaminations are the major cause of manufacturing problems in these systems. In our experiments, the water purification system of a power plant was investigated: the microbiologically critical points of the ultrapure water purification system were located by checking the number and diversity of bacteria to determine the optimum operational unit for chemical intervention: the most contaminated site was the mixed-bed ion-exchange resin containing unit. Biocides were tested against bacteria previously isolated from the same system; effect of biocides was checked also in laboratory model systems, and based on the results, a biocide treatment was carried out in the mixed-bed ion-exchange resin columns of the working power plant. Kathon WT was the most effective from the studied chemicals, being effective already in low concentration against most studied microorganisms. In case of the handling of the mixed-bed ion-exchange resin, 8-h treatment with 25ppm biocide concentration was effective. Following the treatment, the quality of the produced UPW met the standards (specific electric conductivity was<1.0x10(-3)mu Scm(-1) at 25 degrees C) and water production capacity increased; moreover, the run-down time of the mixed-bed ion-exchange resin significantly grew

Multiple Benefits of Plasmid-Mediated Quinolone Resistance Determinants in Klebsiella pneumoniae ST11 High-Risk Clone and Recently Emerging ST307 Clone

International high-risk clones of Klebsiella pneumoniae are among the most common nosocomial pathogens. Increased diversity of plasmid-encoded antimicrobial resistance genes facilitates spread of these clones causing significant therapeutic difficulties. The purpose of our study was to investigate fluoroquinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing strains, including four K. pneumoniae and a single K. oxytoca, isolated from blood cultures in Hungary. Whole-genome sequencing and molecular typing including multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed in selected strains. Gene expression of plasmid-mediated quinolone resistance determinants (PMQR) was investigated by quantitative-PCR. MLST revealed that three K. pneumoniae strains belonged to ST11 and one to ST307 whereas K. oxytoca belonged to ST52. The isolates harbored different β-lactamase genes, however, all K. pneumoniae uniformly carried blaCTX-M-15. The K. pneumoniae isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored qnrB4, the ST307 strain harbored qnrB1 and all K. pneumoniae harbored oqxAB efflux pump. Levofloxacin and moxifloxacin MIC values of K. pneumoniae ST11 and ST307 clones correlated with qnr and oqxAB expression levels. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of qnr genes in parallel with chromosomal mutations indicate an additional protective role of Qnr proteins that can support dissemination of high-risk clones. During development of high-level fluoroquinolone resistance, high-risk clones retain fitness thus, enabling them for dissemination in hospital environment. Based on our knowledge this is the first report of ST307 clone in Hungary, that is emerging as a potential high-risk clone worldwide. High-level fluoroquinolone resistance in parallel with upregulated PMQR gene expression are linked to high-risk K. pneumoniae clones

Reorganizing the familyParvoviridae : a revised taxonomy independent of the canonical approach based on host association

Parvoviridae, a diverse family of small single-stranded DNA viruses was established in 1975. It was divided into two subfamilies,ParvovirinaeandDensovirinae, in 1993 to accommodate parvoviruses that infect vertebrate and invertebrate animals, respectively. This relatively straightforward segregation, using host association as the prime criterion for subfamily-level classification, has recently been challenged by the discovery of divergent, vertebrate-infecting parvoviruses, dubbed "chapparvoviruses", which have proven to be more closely related to viruses in certainDensovirinaegenera than to members of theParvovirinae. Viruses belonging to these genera, namelyBrevi-,Hepan- andPenstyldensovirus, are responsible for the unmatched heterogeneity of the subfamilyDensovirinaewhen compared to theParvovirinaein matters of genome organization, protein sequence homology, and phylogeny. Another genus ofDensovirinae,Ambidensovirus, has challenged traditional parvovirus classification, as it includes all newly discovered densoviruses with an ambisense genome organization, which introduces genus-level paraphyly. Lastly, current taxon definition and virus inclusion criteria have significantly limited the classification of certain long-discovered parvoviruses and impedes the classification of some potential family members discovered using high-throughput sequencing methods. Here, we present a new and updated system for parvovirus classification, which includes the introduction of a third subfamily,Hamaparvovirinae, resolves the paraphyly within genusAmbidensovirus, and introduces new genera and species into the subfamilyParvovirinae. These proposals were accepted by the ICTV in 2020 March.Peer reviewe

Massive Withdrawal Symptoms and Affective Vulnerability Are Associated with Variants of the CHRNA4 Gene in a Subgroup of Smokers

Peer reviewe

Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution

Small cell lung cancer (SCLC) has recently been subcategorized into neuroendocrine (NE)-high and NE-low subtypes showing 'immune desert' and 'immune oasis' phenotypes, respectively. Here, we aimed to characterize the tumor microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes. Immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded TMAs with antibodies against CD45, CD3, CD8, MHCII, TIM3, immune checkpoint poliovirus receptor (PVR), and indoleamine 2,3-dioxygenase (IDO). The stroma was significantly more infiltrated by immune cells both in primary tumors and in LN metastases compared to tumor nests. Immune cell (CD45+ cell) density was significantly higher in tumor nests (P = 0.019), with increased CD8+ effector T-cell infiltration (P = 0.003) in NE-low vs NE-high tumors. The expression of IDO was confirmed on stromal and endothelial cells and was positively correlated with higher immune cell density both in primary tumors and in LN metastases, regardless of the NE pattern. Expression of IDO and PVR in tumor nests was significantly higher in NE-low primary tumors (vs NE-high, P < 0.05). We also found significantly higher MHC II expression by malignant cells in NE-low (vs NE-high, P = 0.004) tumors. TIM3 expression was significantly increased in NE-low (vs NE-high, P < 0.05) tumors and in LN metastases (vs primary tumors, P < 0.05). To our knowledge, this is the first human study that demonstrates in situ that NE-low SCLCs are associated with increased immune cell infiltration compared to NE-high tumors. PVR, IDO, MHCII, and TIM3 are emerging checkpoints in SCLC, with increased expression in the NE-low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies