Case-control study of congenital malformations

To determine potentially teratogenic influencies in Belgrade, a group of 113 mothers who gave birth to severely malformed infants and a control group of 195 mothers with normal infants were interviewed using a structured questionnaire.Statistically significant differences between the two groups were found in the mother's family history of congenital malformations (P < 0.05) and the mother's diseases during the pregnancy (P < 0.01). Infections in the first trimester were particularly more prevalent in case mothers (OR = 7.70; P < 0.01). Mothers did not differ significantly according to exposure to organic solvents, supportive therapy during the pregnancy, use of oral contraceptives, or other personal habits.Corresponding author.     

Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.     

Human health risk assessment of lead,cadmium, and mercury co-exposure from agricultural soils in the Tuzla Canton (Bosnia and Herzegovina)

The aim of this study was to assess the risk of human exposure to lead (Pb), cadmium (Cd), and mercury (Hg) through agricultural soil by considering both uncertainty and variability in key exposure parameters. For this reason we collected soil samples from 29 locations in the Tuzla Canton (Bosnia and Herzegovina) and measured their metal levels with inductively coupled plasma atomic emission or absorption spectrometry (ICP-AES and ICP-AAS, respectively). The levels of Pb ranged from 13.33 to 1692.33 mg/kg, of Cd from 0.05 to 3.67 mg/kg, and of Hg from 0.02 to 2.73 mg/kg. To estimate cancer and non-cancer risks we used deterministic and semi-probabilistic methods. Lead was found to involve higher health risk than the other two heavy metals. Its hazard index (HI) decreased between population groups (children>women>men) and exposure routes (ingestion>skin contact>inhalation). Our Monte Carlo simulations indicated that Pb HIs for both adult populations had a 0.6 % probability to exceed the threshold value of 1, while in children this probability was 14.2 %. Cd and Hg showed no probability to exceed the threshold in any scenario. Our simulation results raise concern about possible adverse health effects of heavy metals from soil, especially in children. It is very important to continue monitoring environmental pollution and assess human health risk, not only with respect to soil, but also with other important environmental compartments, such as air and water.KEY WORDS: cancer risk, deterministic methodology, heavy metals, Monte Carlo simulations, non-cancer risk, probabilistic methodology     

Characterisation of Bacteriophage vB_SmaM_Ps15 Infective to Stenotrophomonas maltophilia Clinical Ocular Isolates

Recent acknowledgment that multidrug resistant Stenotrophomonas maltophilia strains can cause severe infections has led to increasing global interest in addressing its pathogenicity. While being primarily associated with hospital-acquired respiratory tract infections, this bacterial species is also relevant to ophthalmology, particularly to contact lens-related diseases. In the current study, the capacity of Stenotrophomonas phage vB_SmaM_Ps15 to infect ocular S. maltophilia strains was investigated to explore its future potential as a phage therapeutic. The phage proved to be lytic to a range of clinical isolates collected in Australia from eye swabs, contact lenses and contact lens cases that had previously shown to be resistant to several antibiotics and multipurpose contact lenses disinfectant solutions. Morphological analysis by transmission electron microscopy placed the phage into the Myoviridae family. Its genome size was 161,350 bp with a G + C content of 54.2%, containing 276 putative protein-encoding genes and 24 tRNAs. A detailed comparative genomic analysis positioned vB_SmaM_Ps15 as a new species of the Menderavirus genus, which currently contains six very similar globally distributed members. It was confirmed as a virulent phage, free of known lysogenic and pathogenicity determinants, which supports its potential use for the treatment of S. maltophilia eye infections.     

Ecto-F_1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ...