Association analysis of serotonin 2A receptor gene T102c polymorphism and schizophrenia.

The serotonin neurotransmitter has been associated with the pathogenesis of mood disorders and schizophrenia. Serotonin receptors genes may therefore be candidate genes for the study of the genetics of these disorders. In this study, patients with schizophrenia (n=235) and controls (n=344) were analysed to determine the correlation between the 5HT(2A) receptor gene T102C polymorphism and schizophrenia. No association was found between the studied polymorphism and schizophrenia (p=0.854 for alleles and p=0.945 for genotypes). Results were also not significant when analysed by gender (for male p=0.861-allele frequency and p=0.467-genotype frequency, for female p=0.857-allele frequency and p=0.833-genotype frequency). Subgroups with regard to schizophrenia subtypes, age of onset and clinical course of schizophrenia were analysed with negative results.     

BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland

Sixty high-risk breast and/or ovarian cancer families from North-Eastern Poland were screened for germline mutations in BRCA1 (MIM# 113705) and BRCA2 (MIM# 600185), using a combination of protein truncation test, denaturing high-performance liquid chromatography and direct sequencing. Sixteen (27%) of the families were found to carry nine different BRCA mutations, including 14 families with BRCA1 mutation and two families with BRCA2 mutation. The results suggest the presence of two strong BRCA1 founder mutations in the Polish population - 5382insC (6 families) and 300T>G (Cys61Gly; 3 families). The remaining seven mutations were found in single families and included three previously reported BRCA1 mutations (185delAG, 2682C>T [Gln855Ter] and 3819del5), a novel BRCA1 mutation (IVS14+1G>A), as well as two BRCA2 mutations (4088delA and 7985G>A [Trp2586Ter]) not previously observed in Polish families. We confirm the strong influence of two Central-Eastern European BRCA1 founder mutations in familial breast and/or ovarian cancer in Poland. We also conclude that the Polish population has a more dispersed BRCA mutation spectrum than had been earlier thought. This warrants further careful BRCA mutation screening in order to optimise genetic counselling and disease prevention in affected families.     

Unaffected patients with a homozygous absence of the SMN1 gene

In this report, we present three families in which we identified asymptomatic carriers of a homozygous absence of the SMN1 gene. In the first family, the bialleleic deletion was found in three of four siblings: two affected brothers (SMA type 3a and 3b) and a 25-years-old asymptomatic sister. All of them have four SMN2 copies. In the second family, four of six siblings are affected (three suffer from SMA2 and one from SMA3a), each with three SMN2 copies. The clinically asymptomatic 47-year-old father has the biallelic deletion and four SMN2 copies. In the third family, the biallelic SMN1 absence was found in a girl affected with SMA1 and in her healthy 53-years-old father who had five SMN2 copies. Our findings as well as those of other authors show that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one.     

Regional distribution of antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 in men and women in Ontario,Canada

This study estimated the regional and age- and gender-specific seroprevalences of herpes simplex virus type 1 (HSV-1) and HSV-2 in Ontario, Canada. Stored serum specimens from subjects aged 15 to 44 years, including men (n = 979), women not under prenatal care (n = 638), and women under prenatal care (n = 701) submitted for routine viral serology were randomly selected according to regional population size from public health laboratories. HSV-1 and HSV-2 testing was done with the MRL enzyme immunoassay (EIA) (Focus Technologies), and HSV-2 was also tested by the Gull/Meridian EIA. Specimens discordant for HSV-2 antibodies between the two EIAs were resolved by a recombinant immunoblot assay (Focus Technologies). The overall age- and gender-standardized seroprevalences of HSV-1 and HSV-2 were 51.1% (95% confidence interval [CI], 50.1 to 52.1) and 9.1% (95% CI, 8.6 to 9.7), respectively. The seroprevalence of HSV-1 antibodies increased from 26.9 to 54.7% in men between 15 to 16 and 40 to 44 years of age, from 32.0 to 88.7% in women not under prenatal care, and from 55.2 to 69.2% in women under prenatal care. The seroprevalence of HSV-2 increased from 3.8 to 21.3% in men between 15 to 16 and 40 to 44 years of age, from 0 to 18.9% in women not under prenatal care, and from 3.4 to 23.1% in women under prenatal care. HSV-2 results were discordant for 3.3% (76 of 2,318) of specimens. Both types of HSV antibodies appeared to be acquired earlier among women under prenatal care than among men and women not under prenatal care. Antibodies were more prevalent among people in northern Ontario (72.9% of subjects [range, 68.4 to 77.4%] for HSV-1 and 13.7% of subjects [95% CI, 10.2 to 17.2%] for HSV-2) than elsewhere.     

Air particulate matter SRM 1648a primes macrophages to hyperinflammatory response after LPS stimulation

Objective

Exposure to air particulate matter (PM) is associated with chronic inflammatory and autoimmune diseases. Macrophages are responsible for the regulation of chronic inflammation. However, whether PM affects macrophage polarization remains unclear. The aim of this study was to evaluate whether nontoxic concentrations of urban PM are able to prime macrophages to altered inflammatory response upon LPS challenge.

Methods

We used two forms of the urban particulate matter SRM 1648a, intact PM and PM deprived of organic compounds (PM?C). Peritoneal murine macrophages were exposed to different concentrations of PM for 24 h and then challenged with LPS. Production of inflammatory mediators by macrophages was measured to test immunostimulatory/priming capacity of PM.

Results

Particulate matter used at non-cytotoxic concentrations induced a dose-dependent production of proinflammatory cytokines (TNF-α, IL-6, IL-12p40). By contrast, PM?C were not able to stimulate macrophages. However, macrophages primed with both forms of PM show proinflammatory response upon LPS challenge.

Conclusions

Our data indicate that exposure of macrophages to low concentrations of PM may prime the cells to hyperinflammatory response upon contact with LPS. Further studies are necessary to explain whether the exposure of patients suffering from chronic inflammatory diseases to particulate matter is responsible for the exacerbation of clinical symptoms during bacterial infections.

     

Obstetric consequences of uncontrolled gestational diabetes--a case study

This paper presents a case of a pregnant woman who was admitted to the obstetrics and gynecology department because of a new onset of uncontrolled diabetes in 27 weeks gestation. The maternal and fetal diabetic complications suggested a chronic character of the disease which must have been undiagnosed before pregnancy. Many of the co-existing infections caused a life-threatening ketoacidosis. Fortunately with the adequate treatment it was possible to ensure appropriate birth weight of the newborn baby despite the ultrasound markers for LGA (Large For Gestational Age) observed during pregnancy. Intensive insulin therapy was obligatorily continued by the mother after the delivery.     

A European network for virtual microscopy—design,implementation and evaluation of performance

Web-based virtual microscopy has enabled new applications within pathology. Here, we introduce and evaluate a network of academic servers, designed to maximize image accessibility to users from all regions of Europe. Whole-slide imaging was utilized to digitize the entire slide set (n = 154) for the slide seminars of the 21st European Congress of Pathology. The virtual slides were mirrored to five academic servers across Europe using a novel propagation method. Functionality was implemented that automatically selects the fastest server connection in order to optimize the slide-viewing speed (). Results show that during 6 months of monitoring the uptime of the network was 100%. The average viewing speed with the network was 3.1 Mbit/s, as compared to 1.9 Mbit/s using single servers. A good viewing speed (>2Mbit/s) was observed in 32 of 37 countries (86%), compared to 25 of 37 (68%) using single servers. Our study shows that implementing a virtual microscopy network spanning a large geographical area is technically feasible. By utilizing existing academic networks and cost-minimizing image compression, it is also economically feasible. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Discussions and decisions of the 2012–2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group,January 2012–June 2013

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.     

Severe bronchopulmonary dysplasia – incidence and predictive factors in a prospective,multicenter study in very preterm infants with respiratory distress syndrome

Background: Severe bronchopulmonary dysplasia (BPD) remains a major complication of prematurity and can have significant impact on long-term pulmonary sequelae and adverse neurodevelopmental outcomes.

Objective: To assess the incidence and evaluate the predictive factors for severe BPD in very preterm infants with respiratory distress syndrome.

Methods: Of the 846 premature infants born at ≤32-week gestation who developed respiratory distress syndrome (RDS), 707 infants with known oxygen dependency at 36 weeks gestational age were included in the analysis of BPD incidence. With univariate and multiple logistic regression models we evaluated the risk factors for the development of severe BPD and calculated odds ratios (ORs).

Results: The overall incidence of BPD was 45.2%. Severe BPD accounted for 6%, with morbidity pertaining mainly to infants <29-week gestation (incidence 10%). The risk factors for severe BPD included male gender (OR 3.02 95%CI 1.30–7.46), intubation in the delivery room (OR 2.57, 95%CI 1.00–7.18), and invasive ventilation >7 days (OR 7.05, 95%CI 2.63–22.4). The protective factors were early continuous positive airway pressure (CPAP) in the univariate analysis and receiving surfactant <15?min after birth in the multivariate model.

Conclusions: Mechanical ventilation >7 days is the most prevalent risk factor for severe BPD. CPAP initiated in the delivery room and early surfactant are key preventive measures.