Эпидемиологическая характеристика парвовирусной В19 инфекции у детей с гематологическими заболеваниями

ДЕТИ, СЛУЖБЫ ОХРАНЫ ЗДОРОВЬЯКРОВИ БОЛЕЗНИПАРВОВИРУСНЫЕ ИНФЕКЦИИЭПИДЕМИОЛОГИ

Center for Fishery and Applied Hydrobiology “Little Danube”, Experimental School Estate “Radmilovac”: Synergy of Research, Economy and Society

In every society, initiators and promoters of the development are individuals, teams or institutions with a vision, good ideas, seriousness, but above enthusiasm to work hard. They trace the road and drive activities related to research and/or economy. In the Serbian aquaculture sector such institutions is the Faculty of Agriculture and its Center for Fishery and Applied Hydrobiology (CEFAH) (or the “Little Danube”), which operates within the Experimental school estate “Radmilovac”. The Center started to be established in 2007. Unlike other similar Centers built by state resources intended for research and scientific work, the “Little Danube” was created much more as a result of enthusiasm of a group of researchers and their readiness to cooperate with national and international institutions, but also by enthusiasm of individuals ready to financially or materially help some of the Center’s programs. The Center’s activities are directed towards improving and developing the research and economy in aquaculture. Today the Center in “Radmilovac” and its laboratories located in the building of the Faculty of Agriculture represent an education and research polygon for aquaculture development. The education part is aimed at all levels: from pre-school and elementary school level by educational visits to the “Little Danube”, where they get to know different fish species and other aquatic organisms, their culture, fishing, fishing tools; to PhD level students and researchers that increase their knowledge and skills in the Center. CEFAH is a scientific polygon: in its aquaria, tanks, RAS systems, as well as in a number of earthen ponds a range of various experiments in different areas of aquaculture are carried out and knowledge is transferred directly in aquaculture economy. The development of Serbian aquaculture is directly affected by the connection of the Center with the economy through realization of biotechnology projects, fish selective breeding programs, and experiments

Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory

The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling

Microarray-Based Maps of Copy-Number Variant Regions in European and Sub-Saharan Populations

The genetic basis of phenotypic variation can be partially explained by the presence of copy-number variations (CNVs). Currently available methods for CNV assessment include high-density single-nucleotide polymorphism (SNP) microarrays that have become an indispensable tool in genome-wide association studies (GWAS). However, insufficient concordance rates between different CNV assessment methods call for cautious interpretation of results from CNV-based genetic association studies. Here we provide a cross-population, microarray-based map of copy-number variant regions (CNVRs) to enable reliable interpretation of CNV association findings. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to scan the genomes of 1167 individuals from two ethnically distinct populations (Europe, N = 717; Rwanda, N = 450). Three different CNV-finding algorithms were tested and compared for sensitivity, specificity, and feasibility. Two algorithms were subsequently used to construct CNVR maps, which were also validated by processing subsamples with additional microarray platforms (Illumina 1M-Duo BeadChip, Nimblegen 385K aCGH array) and by comparing our data with publicly available information. Both algorithms detected a total of 42669 CNVs, 74% of which clustered in 385 CNVRs of a cross-population map. These CNVRs overlap with 862 annotated genes and account for approximately 3.3% of the haploid human genome

Genetic drivers of kidney defects in the digeorge syndrome

BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P = 4.5×1014). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-Altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver

Preschool hyperactivity specifically elevates long-term mental health risks more strongly in males than females: a prospective longitudinal study through to young adulthood

Evidence of continuities between preschool hyperactivity and adult mental health problems highlight the potential value of targeting early identification and intervention strategies. However, specific risk factors are currently unclear. This large-scale prospective longitudinal study aimed to identify which hyperactive preschoolers are at greatest long-term risk of poor mental health. One hundred and seventy children (89 females) rated as hyperactive by their parents and 88 non-hyperactive controls (48 females) were identified from a community sample of 4,215 3 year-olds. Baseline data relating to behavioral/emotional problems and background characteristics were collected. Follow-up mental health and functional impairment outcomes were collected between 14 and 25 years of age. At age 3 years, males and females in the hyperactive group had similarly raised levels of hyperactivity and other behavior problems. In adolescence/young adulthood, these individuals showed elevated symptoms of ADHD, conduct disorder, mood disorder, anxiety and autism, as well as functional impairment. Preschool hyperactivity was strongly predictive of poor adolescent/adult outcomes for males across domains with effects being specifically driven by hyperactivity. For females, the effects of preschool hyperactivity were smaller and dropped to non-significant levels when other preschool problems were taken into account. Environmental risk factors also differed between the sexes, although these may also have been mediated by genetic risk. In conclusion, these results demonstrate marked sex differences in preschool predictors of later adolescent/adult mental health problems. Future research should include a measure of preschool inattention as well hyperactivity. The findings highlight the potential value of tailored approaches to early identification strategies

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Dental fear and anxiety in older children: an association with parental dental anxiety and effective pain coping strategies

Anka Coric,1 Adriana Banozic,2 Miro Klaric,3 Katarina Vukojevic,4 Livia Puljak5 1School of Medicine, University of Mostar, Health Center Mostar, Mostar, Bosnia and Herzegovina; 2Laboratory for Pain Research, University of Split School of Medicine, Split, Croatia; 3Department of Psychiatry, School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina; 4Department of Anatomy, University of Split School of Medicine, Split, Croatia; 5Laboratory for Pain Research, University of Split School of Medicine, Split, Croatia Abstract: An association between dental fear and anxiety (DFA) has been confirmed for children younger than 8 years, but this association in older children is less clear. The aim of this study was to fill this knowledge gap by studying DFA in older children and their parents with validated measures. This cross-sectional study, conducted at Community Health Centre Mostar, Bosnia and Herzegovina, included 114 children and their parents. DFA, coping, and sociodemographic variables were studied using Corah Dental Anxiety Questionnaire (CDAS), Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS), Dental Cope Questionnaire, and sociodemographic questionnaire. Maternal CDAS scores had significant positive correlation with child DFA measured with CFSS-DS (r=0.35, P<0.001) and CDAS (r=0.32, P<0.001). Fathers' CDAS scores were not associated with child CFSS-DS, but showed a moderate correlation with child CDAS (r=0.19, P<0.05). There were no significant differences in children's fear and anxiety based on age, sex, or socioeconomic variables. Children used internal coping strategies most frequently and external coping strategies were rated by the children as the most effective. We did not find differences in number and type of effective coping strategies in children with high DFA compared with children with low DFA. In conclusion, there is evidence of the coexistence of dental fear in parents and older children. These findings may help to devise interventions that will prevent or alleviate children's DFA. Keywords: fear of dental pain, pain behavior, coping skills, adaptive behavior, school children, parent