Factor V Leiden Is Associated with Higher Risk of Deep Venous Thrombosis of Large Blood Vessels

Aim: To determine the prevalence of factor V Leiden mutation in patients with different presentation of venous thromboembolic disease and healthy individuals in the Republic of Macedonia. Methods: The retrospective study involved 190 patients with venous thromboembolic disease and 200 healthy individuals, who were screened for the presence of factor V Leiden mutation with a polymerase chain reaction-restriction fragment length polymorphism method. The prevalence of factor V Leiden was analyzed according to the localization of thrombosis, presence of risk factors, and family history of thrombosis. The odds of deep venous thrombosis were calculated with respect to the presence of factor V Leiden mutation. Results: The prevalence of factor V Leiden mutation among patients with venous thromboembolic disease was 21.1%, compared with 5.5% in the healthy individuals. Factor V Leiden positive patients had the first episode of deep venous thrombosis at a younger age, and the prevalence of the mutation was the highest among patients with a positive family history of thrombosis (33.9%, P=0.003) and in patients with deep venous thrombosis affecting a large blood vessel (37.7%, P=0.001). The prevalence of factor V Leiden mutation was lower in patients with calf deep venous thrombosis and primary thromboembolism (13.3% and 13.1%, respectively; P>0.05). The odds ratio for iliofemoral or femoral deep venous thrombosis in factor V Leiden carriers was 10.4 (95% confidence interval, 4.7-23.1). Conclusion: The prevalence of factor V Leiden mutation was high in both patients with venous thromboembolic disease and healthy individuals in Republic of Macedonia. Factor V Leiden carriers have the highest odds of developing deep venous thrombosis affecting a large venous blood vessel

Factor V Leiden Is Associated with Higher Risk of Deep Venous Thrombosis of Large Blood Vessels

Aim: To determine the prevalence of factor V Leiden mutation in patients with different presentation of venous thromboembolic disease and healthy individuals in the Republic of Macedonia. Methods: The retrospective study involved 190 patients with venous thromboembolic disease and 200 healthy individuals, who were screened for the presence of factor V Leiden mutation with a polymerase chain reaction-restriction fragment length polymorphism method. The prevalence of factor V Leiden was analyzed according to the localization of thrombosis, presence of risk factors, and family history of thrombosis. The odds of deep venous thrombosis were calculated with respect to the presence of factor V Leiden mutation. Results: The prevalence of factor V Leiden mutation among patients with venous thromboembolic disease was 21.1%, compared with 5.5% in the healthy individuals. Factor V Leiden positive patients had the first episode of deep venous thrombosis at a younger age, and the prevalence of the mutation was the highest among patients with a positive family history of thrombosis (33.9%, P=0.003) and in patients with deep venous thrombosis affecting a large blood vessel (37.7%, P=0.001). The prevalence of factor V Leiden mutation was lower in patients with calf deep venous thrombosis and primary thromboembolism (13.3% and 13.1%, respectively; P>0.05). The odds ratio for iliofemoral or femoral deep venous thrombosis in factor V Leiden carriers was 10.4 (95% confidence interval, 4.7-23.1). Conclusion: The prevalence of factor V Leiden mutation was high in both patients with venous thromboembolic disease and healthy individuals in Republic of Macedonia. Factor V Leiden carriers have the highest odds of developing deep venous thrombosis affecting a large venous blood vessel

Genomic test ends a long diagnostic odyssey in a patient with resistance to thyroid hormones

Background: Resistance to thyroid hormones is a very rare condition, which is often misdiagnosed and mistreated. The cases where there is a concomitant autoimmune thyroid disorder are ultra-rare and particularly challenging to treat. Diagnostic and research-based genomic testing can sometimes identify pathogenic variants unrelated to the primary reason for testing (incidental findings)

Association of Methylenetetrahydrofolate Reductase (MTHFR-677 and MTHFR-1298) Genetic Polymorphisms with Occlusive Artery Disease and Deep Venous Thrombosis in Macedonians

Cilj Ispitati moguću povezanost genetičkog polimorfizma metilen-tetrahidrofolatne reduktaze (MTHFR-677, MTHFR-1298) s okluzivnom arterijskom bolešću i dubokom venskom trombozom u Makedonaca. Postupci Radili smo s 83 zdrave osobe, 76 bolesnika s okluzivnom arterijskom bolešću i 67 bolesnika s dubokom venskom trombozom. Od njih su prikupljeni su uzorci krvi i iz leukocita je izolirana DNA. Mutacije gena za MTHFR identificirane su testom CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Beč, Austrija), a za analizu je uporabljen sustav za genetičku analizu PyPop. Potom su izračunani Pearsonove P vrijednosti, grubi omjer izgleda (odds ratio, OR) i Waldovi 95% intervali pouzdanosti (confidence intervals, CI). Rezultati Frekvencija alela C lokusa za MTHFR-677 bila je 0,575 u bolesnika s dubokom venskom trombozom, 0,612 u onih a okluzivnom arterijskom bolešću i 0,645 u zdravih osoba. Frekvencija alela T lokusa za MTHFR-677 bila je niža u zdravih osoba (0,355) nego u bolesnika s okluzivnom arterijskom bolešću (0,388) i dubokom venskom trombozom (0,425). Frekvencija alela A u lokusu MTHFR-1298 bila je 0,729 u zdravih osoba, 0,770 u bolesnika s okluzivnom arterijskom bolešću i 0,746 u bolesnika s dubokom venskom trombozom. Frekvencija alela C lokusa za MTHFR-1298 bila je 0,271 u zdravih osoba, 0,230 u bolesnika s okluzivnom arterijskom bolešću i 0,425 u bolesnika s dubokom venskom trombozom. Nije opažena povezanost polimorfizma MTHFR-677 i MTHFR-1289 s okluzivnom arterijskom bolešću ili dubokom venskom trombozom, nego se samo pokazao protektivni učinak diplotipa MTHFR/CA:CC za okluzivnu arterijsku bolest. Zaključak Osim protektivnoga učinka diplotipa MTHFR/CA:CC za okluzivnu arterijsku bolest, nismo našli značajnu povezanost polimorfizma lokusa MTHFR-677 i MTHFR-1289 s okluzivnom arterijskom bolešću i dubokom venskom trombozom.Aim To analyze the association of methylenetetrahydrofolate reductase polymorphisms (MTHFR-677 and MTHFR-1298) with occlusive artery disease and deep venous thrombosis in Macedonians. Methods We examined 83 healthy respondents, 76 patients with occlusive artery disease, and 67 patients with deep venous thrombosis. Blood samples were collected and DNA was isolated from peripheral blood leukocytes. Identification of MTHFR mutations was done with CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Vienna, Austria) and the population genetics analysis package, PyPop, was used for the analysis. Pearson P values, crude odds ratio, and Wald’s 95% confidence intervals were calculated. Results The frequency of C alleles of MTHFR-677 was 0.575 in patients with deep venous thrombosis, 0.612 in patients with occlusive artery disease, and 0.645 in healthy participants. The frequency of T allele of MTHFR-677 was lower in healthy participants (0.355) than in patients with occlusive artery disease (0.388) and deep venous thrombosis (0.425). The frequency of A allele for MTHFR-1298 was 0.729 in healthy participants, 0.770 in patients with occlusive artery disease, and 0.746 in patients with deep venous thrombosis. The frequency of C allele of MTHFR-1298 was 0.271 in healthy participants, 0.230 in patients with occlusive artery disease, and 0.425 in patients with deep venous thrombosis. No association of MTHFR-677 and MTHFR- 1289 polymorphisms with occlusive artery disease and deep venous thrombosis was found, except for the protective effect of MTHFR/CA: CC diplotype for occlusive artery disease. Conclusion We could not confirm a significant association of MTHFR- 677 and MTHFR-1289 polymorphisms with occlusive artery disease or deep venous thrombosis in Macedonians, except for the protective effect of MTHFR/CA:CC diplotype against occlusive artery disease

Classifying aerosol type using in situ surface spectral aerosol optical properties

Knowledge of aerosol size and composition is important for determining radiative forcing effects of aerosols, identifying aerosol sources and improving aerosol satellite retrieval algorithms. The ability to extrapolate aerosol size and composition, or type, from intensive aerosol optical properties can help expand the current knowledge of spatiotemporal variability in aerosol type globally, particularly where chemical composition measurements do not exist concurrently with optical property measurements. This study uses medians of the scattering Ångström exponent (SAE), absorption Ångström exponent (AAE) and single scattering albedo (SSA) from 24 stations within the NOAA/ESRL Federated Aerosol Monitoring Network to infer aerosol type using previously published aerosol classification schemes. Three methods are implemented to obtain a best estimate of dominant aerosol type at each station using aerosol optical properties. The first method plots station medians into an AAE vs. SAE plot space, so that a unique combination of intensive properties corresponds with an aerosol type. The second typing method expands on the first by introducing a multivariate cluster analysis, which aims to group stations with similar optical characteristics and thus similar dominant aerosol type. The third and final classification method pairs 3-day backward air mass trajectories with median aerosol optical properties to explore the relationship between trajectory origin (proxy for likely aerosol type) and aerosol intensive parameters, while allowing for multiple dominant aerosol types at each station. The three aerosol classification methods have some common, and thus robust, results. In general, estimating dominant aerosol type using optical properties is best suited for site locations with a stable and homogenous aerosol population, particularly continental polluted (carbonaceous aerosol), marine polluted (carbonaceous aerosol mixed with sea salt) and continental dust/biomass sites (dust and carbonaceous aerosol); however, current classification schemes perform poorly when predicting dominant aerosol type at remote marine and Arctic sites and at stations with more complex locations and topography where variable aerosol populations are not well represented by median optical properties. Although the aerosol classification methods presented here provide new ways to reduce ambiguity in typing schemes, there is more work needed to find aerosol typing methods that are useful for a larger range of geographic locations and aerosol populations

Seasonality of the particle number concentration and size distribution : a global analysis retrieved from the network of Global Atmosphere Watch (GAW) near-surface observatories

Aerosol particles are a complex component of the atmospheric system which influence climate directly by interacting with solar radiation, and indirectly by contributing to cloud formation. The variety of their sources, as well as the multiple transformations they may undergo during their transport (including wet and dry deposition), result in significant spatial and temporal variability of their properties. Documenting this variability is essential to provide a proper representation of aerosols and cloud condensation nuclei (CCN) in climate models. Using measurements conducted in 2016 or 2017 at 62 ground-based stations around the world, this study provides the most up-to-date picture of the spatial distribution of particle number concentration (N-tot) and number size distribution (PNSD, from 39 sites). A sensitivity study was first performed to assess the impact of data availability on N-tot's annual and seasonal statistics, as well as on the analysis of its diel cycle. Thresholds of 50% and 60% were set at the seasonal and annual scale, respectively, for the study of the corresponding statistics, and a slightly higher coverage (75 %) was required to document the diel cycle. Although some observations are common to a majority of sites, the variety of environments characterizing these stations made it possible to highlight contrasting findings, which, among other factors, seem to be significantly related to the level of anthropogenic influence. The concentrations measured at polar sites are the lowest (similar to 10(2) cm(-3)) and show a clear seasonality, which is also visible in the shape of the PNSD, while diel cycles are in general less evident, due notably to the absence of a regular day-night cycle in some seasons. In contrast, the concentrations characteristic of urban environments are the highest (similar to 10(3)-10(4) cm(-3)) and do not show pronounced seasonal variations, whereas diel cycles tend to be very regular over the year at these stations. The remaining sites, including mountain and non-urban continental and coastal stations, do not exhibit as obvious common behaviour as polar and urban sites and display, on average, intermediate N-tot (similar to 10(2)-10(3) cm(-3)). Particle concentrations measured at mountain sites, however, are generally lower compared to nearby lowland sites, and tend to exhibit somewhat more pronounced seasonal variations as a likely result of the strong impact of the atmospheric boundary layer (ABL) influence in connection with the topography of the sites. ABL dynamics also likely contribute to the diel cycle of N-tot observed at these stations. Based on available PNSD measurements, CCN-sized particles (considered here as either >50 nm or >100 nm) can represent from a few percent to almost all of N-tot, corresponding to seasonal medians on the order of similar to 10 to 1000 cm(-3), with seasonal patterns and a hierarchy of the site types broadly similar to those observed for N-tot. Overall, this work illustrates the importance of in situ measurements, in particular for the study of aerosol physical properties, and thus strongly supports the development of a broad global network of near surface observatories to increase and homogenize the spatial coverage of the measurements, and guarantee as well data availability and quality. The results of this study also provide a valuable, freely available and easy to use support for model comparison and validation, with the ultimate goal of contributing to improvement of the representation of aerosol-cloud interactions in models, and, therefore, of the evaluation of the impact of aerosol particles on climate.Peer reviewe

GLUT-1 DEFICIENCY: FROM PATHOPHYSILOGY AND GENETICS TO ABROAD CLINICAL SPECTRUM

The classical GLUT-1 deficiency syndrome (GLUT-1 DS, De Vivo disease) was described over 2 decades ago as a metabolic encephalopathy characterized by developmental delay, secondary microcephaly paroxysmal neurological symptoms (epilepsy) and movement disorders. The biochemical parameters of this disease, used in diagnosis, are low levels of glucose in the cerebrospinal fluid, normal level of glucose in the blood and consequent low ratio of cerebrospinal fluid vs. blood glucose levels (<40-45%). So far, more than 200 cases of the classical GLUT-1 DS have been described in the literature. Genetic research demonstrated that this disease is caused by mutations in SLC2A1 gene coding for GLUT-1, a transporter of glucose across the blood brain barrier. Over the last few years the clinical spectrum of GLUT-1 deficiencywas expanded to include other rare diseases such as paroxysmal exertional dyskinesia and early-onset absence epilepsy, but also some more common diseases such as idiopathic generalised epilepsy (1-2%). GLUT-1 deficiency is an important pathophysiological basis of these diseases as early diagnosis (aided by DNA mutation testing) and treatment (ketogenic diet) could lead to improved disease outcomes

Noise Dispersion Modelling in Small Urban Areas with CUSTIC 3.2 Software

Noise pollution is genuine threat to human health and the quality of life and presents one of serious factors that local agencies and state authorities have to consider in development planning. Noise dispersion modeling can be helpful in the planning and decision making processes for reducing the noise pollution. Noise dispersion models are used to assess and monitor the influence of the noise effects and for land-use planning as one of the method of effective and economic noise control. In this paper Noise dispersion model has been developed using the possibilities of low costs CUSTIC 3.2, Noise Pollution Modelling Software, produced by the Spanish company Canarina, and according to noise level measurements in the central part of Stip, in Eastern Macedonia that is typical, and thus representative, of most smaller urban areas in this region