•This is the first Croatian national study describing the molecular epidemiology of rotavirus strains.•The prevalence of the world’s ‘common’ G/P combinations was 88.8% overall.•A high prevalence of ...human–human reassortants (7.7%) was also detected.•The appearance of the G6 type was reported for the first time in Croatia.•There is a need for continuous surveillance of circulating rotavirus strains.
Rotavirus is the major cause of severe diarrhea in young children worldwide. In countries like Croatia, where rotavirus vaccine has not been introduced in the national immunization program, prospective surveillance is necessary to establish the diversity of rotavirus strains. The aim of this study was to describe the prevalence and geographical distribution of rotavirus strains in Croatia and to detect the possible emergence of novel strains.
The study was conducted among children ≤5 years of age with acute gastroenteritis at three hospitals located in different geographical regions of Croatia, during the years 2012 to 2014. Rotavirus was detected in stools using an immunochromatographic assay and then sent for further molecular analysis.
Genotyping of 822 rotaviruses showed that the predominant circulating strain was G1P8 (61.9%), followed by G2P4 (19.5%), G1P4 (3.9%), and G3P8 (2.9%). A high prevalence of reassortants among common human rotavirus genotypes was detected (7.7%). Possible zoonotic reassortants were found, including G8 and G6 strains. The latter is described for the first time in Croatia.
This study represents pre-vaccination data that are important for decisions regarding immunization strategies in Croatia. The high prevalence of ‘common’ rotavirus strains circulating in Croatia may advocate for rotavirus vaccine introduction, but further surveillance is necessary to monitor the possible emergence of novel genotypes.
We present a rare case of a neonate with PHACES syndrome (posterior fossa malformations, large facial hemangiomas, cerebral arterial anomalies, cardiovascular anomalies, eye anomalies and sternal ...clefting or supraumbilical raphe) and diffuse hemangiomatosis of the ileum, presenting with multiple intestinal perforations and peritonitis. The infant was successfully treated with propranolol and methylprednisolone as well as octreotide, tranexamic acid, and supportive therapy for massive intestinal bleeding.
Classic galactosemia is an autosomal recessive disorder of galactose metabolism caused by severely decreased activity of galactose-1-phosphate uridylyltransferase (GALT) due to pathogenic mutations ...in the GALT gene. To date more than 330 mutations have been described, with p.Q188R and p.K285N being the most common in Caucasian populations. Although acute manifestations can be fully avoided by a galactose-restricted diet, chronic complications, such as neurological ones, cannot be prevented in a significant number of patients despite compliance with the dietary treatment.
A cohort of 16 galactosemic Croatian patients, including one pair of siblings, was studied. Molecular characterization was performed by direct sequence analysis of the GALT gene.
Sixteen patients were analyzed and only four different mutations were detected. As expected, p.Q188R and p.K285N were common, accounting for 40% and 37% of unrelated alleles, respectively. The third mutation accounting for 20% of mutant alleles was p.R123X causing a premature stop codon, is thus considered to be severe, which is in accordance with the phenotype presented by the homozygous patient described here. The fourth mutation p.E271D was found in a single allele. More than half of our patients manifested some chronic neurological complications.
This is the first report on mutational and phenotypic spectra of classic galactosemia in Croatia that expands the knowledge on the mutational map of the GALT gene across Europe and reveals the genetic homogeneity of the Croatian population.
Involvement of development-related gene polymorphisms in multifactorial/polygenic etiology of stillborn/neonatal deaths due to malformations has been insufficiently tested. Since these genes showed ...evolutional stability and their mutations are very rare, we can assume that their polymorphic variants may be a risk factor associated with the occurrence of developmental disorders of unknown etiology or can enhance the phenotypic variability of known genetic disorders.
To determine the association of 3 polymorphisms involved in the regulation of the early embryonic development of different organs, we conducted an association study of their relation to the particular malformation. We selected 140 samples of archived paraffin tissue samples from deceased patients in which fetal/neonatal autopsy examination had shown congenital abnormalities as the most likely cause of death. The polymorphisms of OSR1 rs12329305, rs9936833 near FOXF1, and HOXA1 rs10951154 were genotyped using the TaqMan allelic discrimination assay.
After Bonferroni correction for multiple testing, significant allelic association with stillborn/neonatal deaths was observed for rs12329305 (p=7×10-4). In addition, association analysis for the same polymorphism was shown in the subgroup with isolated anomalies (1.25×10^-5), particularly in the subgroup of cases with kidney and heart anomalies (p=4.18×10^-5, p=5.12×10^-8, respectively).
The findings of the present study showed, for the first time, the role of the OSR1 rs12329305 polymorphism in the development of congenital malformations in cases of stillborn/neonatal death, particularly in those with congenital kidney and heart developmental defects.
Nephrotic syndrome (NS) is pathological condition characterized by heavy proteinuria. Our study investigates hypothesis that change in cell proliferation of proximal tubules influences primary cilia ...structure and function and promotes cystogenesis in congenital nephrotic syndrome of the Finnish type (CNF) and focal segmental glomerulosclerosis (FSGS).
CNF kidneys were analyzed genetically. Proliferation (Ki-67), apoptosis (caspase-3), and primary cilia (α-tubulin) length and structure were analyzed immunohistochemically and ultrastructurally in healthy, CNF and FSGS kidneys. Cyst diameters were measured and correlated with proliferation index.
Proximal tubules cells of healthy kidneys did not proliferate. In nephrotic kidneys, tubules with apparently normal diameter covered by cuboidal/columnar epithelium (PTNC) contained 81.54% of proliferating cells in CNF and 36.18% in FSGS, while cysts covered with columnar epithelium (CC) contained 37.52% of proliferating cells in CNF and 45.23% in FSGS. The largest cysts, covered with squamous epithelium (CS) had 11.54% of proliferating cells in CNF and 13.76% in FSGS. Increase in cysts diameter correlated with changes in proliferation index, tubular cells shape, primary cilia formation and appearance of apoptotic cells.
We present a novel histopathological data on the structure and possible changes in function of tubular cell in NS kidneys during cystogenesis. We suggest existence of common principles of cystogenesis in CNF and FSGS kidneys, including serious disturbances of tubular cells proliferation and apoptosis, and faulty primary cilia signaling leading to deterioration of proteinuria in NS kidneys.
Atherosclerosis is a pathological condition that begins in early childhood, but clinically the disease manifests in older age. The aim of work was to determine frequency of atherosclerosis risk ...factors in healthy school children. Cross-sectional study included 214 children in mean age 10,99+/-2,52 years, within range 7 to 15 years. Patients body mass index, blood pressure, lipid status, dietary habits, physical activity and sedentary habits have been evaluated. Cardiovascular risk factors are significantly present in children (P<0,05) i.e. one cardiovascular risk factor is present in 47/214 (21,96%) children, two risk factors had 25/214 (11,68%) children, while 17/214 (7,94%) children had three or more cardiovascular risk factors. Obesity was present in 20/214 (9,34%) children, while overweight was present in 23/214 (10,74%) children. Hypertension was present in 10/214 (4,67%) children, and it was significantly present (p<0,05) in obese and overweight children. Total cholesterol was increased in 17/214 (7,94%) children, LDL-cholesterol was increased in 11/214 (5,14%) corrected, increased triglycerides had 4/214 (1,86%) children, while decreased HDL-cholesterol was found in (3/214, 1,40%) children. Unhealthy dietary habits were present in 45/214 (21,02%) children, 42/214 (19,62%) children is physically inactive, while sedentary habits were shown in 39/214 (18,22%) children. Research shows that a large number within study group has one or more cardiovascular risk factors that can lead to premature atherosclerosis. Using massive screening of cardiovascular risk factors, along with adequate physical activity, healthy dietary habits, reduced sedentary habits, doctors and teacher's education, parents and children can reduce premature clinical sequels in atherosclerotic process.
To test the association of NOS3 gene with hypoxic-ischemic encephalopathy (HIE).
The study included 110 unrelated term or preterm born children (69 boys and 41 girls) with HIE and 128 term and ...preterm born children (60 boys and 68 girls) without any neurological problems after the second year of life. Children with perinatal HIE fulfilled the diagnostic criteria for perinatal asphyxia. All children were admitted to the Clinical Hospital Split between 1992 and 2008. We analyzed 6 tagging single nucleotide polymorphisms (SNP) within NOS3 gene (rs3918186, rs3918188, rs1800783, rs1808593, rs3918227, rs1799983), in addition to previously confirmed NOS3-associated SNP rs1800779. Genotyping was conducted using real-time polymerase chain reaction (PCR). Association analyses were performed according to allelic and genotypic distribution.
Allelic test did not show any SNP association with HIE. SNP rs1808593 showed genotype association (P=0.008) and rs1800783-rs1800779 TG haplotype showed an association with HIE (P<0.001). The study had 80% statistical power to detect (α=0.05) an effect with odds ratio (OR)=2.07 for rs3918186, OR=1.69 for rs3918188, OR=1.70 for rs1800783, OR=1.80 for rs1808593, OR=2.10 for rs3918227, OR=1.68 for rs1800779, and OR=1.76 for rs1799983, assuming an additive model.
Despite the limited number of HIE patients, we observed genotypic and haplotype associations of NOS3 polymorphisms with HIE.
Our study aimed to assess differences in the susceptibility to severe acute illness in children with and without chronic health conditions treated in a pediatric intensive care unit (PICU).
Data on ...age, gender, need for ventilator support, length of stay, as well as other parameters for the Paediatric Index of Mortality (PIM2) score were collected. Data were analyzed and compared across three patient groups: those with a neurodevelopmental disability, those with a chronic condition other than a neurodevelopmental disability, and those with no chronic condition. Reasons for admission of patients were classified according to the Australia and New Zealand Paediatric Intensive Care Registry (ANZPIC Registry) diagnostic codes. In the multidisciplinary, seven-bed, level I PICU of the Split University Hospital, the admission data were collected prospectively for 591 consecutively admitted patients aged<or=18 years.
Patients with a neurodevelopmental disability had a significantly higher rate of respiratory-related admissions compared to patients with other chronic health conditions and those with no chronic condition (chi2=33.72, P<0.001). There was a significant difference in the age at admission (f=6.04, P=0.003), median length of stay (f=7.94, P<0.001), need for ventilation during the first hour of admission (chi2=14.74, P<0.001) and PICU mortality (chi2=9.91, P=0.007) of patients with neurodevelopmental disabilities, compared to the other two groups of patients.
Children with neurodevelopmental disabilities are more susceptible to acute illness compared to children with other chronic health conditions and those with no chronic condition.
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