Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors

Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage

Mice lacking endoglin in macrophages show an impaired immune response

24 p.-9 fig.-1 tab. Ojeda Fernández, Luisa et al.Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-OslerWeber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Engfl/flLysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Engfl/flLysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients.This work was funded by: Ministerio de Economía y Competitividad of Spain (SAF2011-23475 to LMB; SAF2013-43421-R and SAF2010- 19222 to CB.Peer reviewe

Investigating the purpose of an online discussion group for health professionals: a case example from forensic occupational therapy

Background: Thousands of health-related online discussion groups are active world-wide however, very little is known about the purpose and usefulness of such groups. In 2003 an online discussion group called ‘forensic occupational therapy' was established in the United Kingdom. This group was examined to gain an understanding of the purpose and use of online discussion groups for health professionals who may be practically and geographically isolated from others in similar areas of practice. Methods: Following a case study design, descriptive characteristics on members' locations and number of posts were collected from the forensic occupational therapy online discussion group. Eight years of posts (2003-2011) were examined using a theoretical thematic analysis process to identify and describe the purposes for which members were using the group. Results: Members from 20 countries contributed to the discussion group; the vast majority of posts being from members in the United Kingdom. Activity within the group was consistently high for the first five years however, activity within the group declined in the final three years. Six purposes for which members use the online discussion group were identified: seeking and giving advice, networking, requesting and sharing material resources, service development, defining the role of occupational therapists, and student learning. Conclusions: Findings suggest that health professionals in specialized and often isolated areas of practice are keen to connect with colleagues and learn from each other's experiences. The main purposes for which the online discussion group was used could be summarized as communication, information sharing and networking; though activity within the group declined significantly during the last three years of the data collection period. This raises questions about the sustainability of online discussion groups within the rapidly developing social media environment

Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation

Ovarian clear cell carcinoma (OCCC) accounts for a small but significant proportion of all ovarian cancers and is a distinct clinical and pathological entity. It tends to be associated with poorer response rates to chemotherapy and with a worse prognosis. Little is known about possible underlying genetic changes. DNA extracted from paraffin-embedded samples of 18 pure OCCC cases was analysed for genetic imbalances using comparative genomic hybridisation (CGH). All of the 18 cases showed genomic alterations. The mean number of alterations detected by CGH was 6 (range 1–15) indicating a moderate level of genetic instability. Chromosome deletions were more common than amplifications. The most prominent change involved chromosome 9 deletions in 10 cases (55%). This correlates with changes seen in other epithelial ovarian cancers. This deletion was confirmed using microsatellite markers to assess loss of heterozygosity (LOH) at four separate loci on chromosome 9. The most distinct region of loss detected was around the IFNA marker at 9p21 with 41% (11 out of 27cases) LOH. Other frequent deletions involved 1p (five out of 18; 28%); 11q (four out of 18; 22%) and 16 (five out of 18; 28%). Amplification was most common at chromosome 3 (six out of 18; 33%); 13q (four out of 18; 22%) and 15 (three out of 18; 17%). No high-level amplifications were identified. These features may serve as useful prognostic indicators in the management of OCCC

Association of metabolic syndrome and its components with arterial stiffness in Caucasian subjects of the MARK study: a cross-sectional trial

BACKGROUND: The cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) can reflect both central and peripheral arterial stiffness. Metabolic syndrome (MetS) and its components may increase arterial stiffness and the risk of cardiovascular diseases. However, the correlation of MetS and its components with arterial stiffness is still not clear. The primary aim of this study is thus the relationship using baPWV and CAVI in Caucasian adults with intermediate cardiovascular risk. The secondary aim is to analyze sex differences. METHODS: This study analyzed 2351 subjects aged 35–74 years (mean, 61.4 ± 7.7 years) comprising 61.7 % males and enrolled in the improving interMediAte Risk management (MARK) study. CAVI was measured using a VaSera VS-1500 (®) device, and baPWV was calculated using a validated equation. MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. RESULTS: MetS was found in 51.9 % of the subjects. All MetS components except reduced HDL-cholesterol (p = 0.578) were associated with CAVI. High density lipoprotein cholesterol (p = 0.075) and waist circumference (p = 0.315) were associated with baPWV. The different MetS components that assess dyslipidemia using the stiffness measures show different associations according to patient sex. The high blood pressure component had a greater odds ratio (OR) for both baPWV ≥ 17.5 m/sec (OR = 6.90, 95 % CI 3.52–13.519) and CAVI ≥ 9 (OR = 2.20, 95 % CI 1.63–1.90). CONCLUSIONS: MetS and all its components (except HDL-cholesterol with baPWV and CAVI and WC with baPWV) were associated with baPWV and CAVI. However, there were sex differences in the association of MetS and its components with baPWV and CAVI. Data from this study suggest a greater association of CAVI and baPWV values with MetS components in males than in females and indicate greater arterial stiffness in the event of simultaneously elevated blood pressure, fasting plasma glucose, and waist circumference. Trial Registration Clinical Trials.gov Identifier: https://clinicaltrials.gov/ct2/show/ NCT01428934. Registered 2 September 2011. Last updated September 8, 2016 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-016-0465-7) contains supplementary material, which is available to authorized users

Air pollution by allergenic spores of the genus Alternaria in the air of central and eastern Europe

Spores of the genus Alternaria belong to one of the most prevailing constituents of the air in all regions of the world. They form infectious inoculum of numerous plant species as well as severe inhaled allergies. The aim of this study was to compare the biological pollution with Alternaria spores of the air of 12 cities located in central and eastern Europe. The experiment was done in 2010 and it covered the territory of Latvia (LV), Lithuania (LT), Poland (PL) and Ukraine (UA). The spores were counted using an identical method and standard equipment (7-day Lanzoni volumetric sampler) followed by extensive statistical calculations. The timing of the day of maximum concentration changed mainly along the N-S direction and had a positive correlation with latitude. The most important factor determining the increase in Alternaria spore concentration was the temperature, whereas other weather parameters were not related or of low significance. Regardless of geographical location, the first phase of the season (0–0.9 % of Alternaria spores in the air) was the longest (up to 60 days) and the last (97.5 to 99 %) was the shortest (22 days or less). The means of daily concentrations of Alternaria spores ranged from 11 spores m(−3) in Klaipeda (LT, Baltic Sea coast) to 187 in Poznan (west PL, agricultural plain). The threshold value of 80 spores m(−3) that triggers the first allergy symptoms was exceeded in 8 to 86 days (Vinnitsa, UA, temperate continental, forest-steppes region). There were considerable differences between the highest number of spores per cubic metre of air, varying from 139 in the north (Klaipeda, LT) to 2,295 in central west (Poznan, PL). The biological pollution by Alternaria spores in several places of central and eastern Europe was high; the number of days exceeding the threshold value of 300 spores m(−3) connected with serious health problems of atopic people ranged from 0 to 1 on the north (LV, LT) to 29 in central west (Poznan, PL)