No interaction between alcohol consumption and HDL-related genes on HDL cholesterol levels.

OBJECTIVE: To assess the relationships and possible interactions between polymorphisms related to HDL levels and alcohol consumption. METHODS: Cross-sectional population-based study including 2863 women and 2546 men aged 35-75 years (CoLaus study). Alcohol intake was assessed by the reported alcohol consumption of the last 7 days. Nineteen candidate genes known to influence HDL levels were studied. RESULTS: Alcohol consumption increased HDL cholesterol levels in both genders. After multivariate adjustment for gender, age, body mass index, smoking, hypolipidaemic drug treatment, physical activity and alcohol consumption, APOA5, CETP, LIPC and LPL gene polymorphisms were significantly (10(-5) threshold) related with HDL cholesterol levels, while no genexalcohol intake interaction was found for all SNPs studied. ABCA1 polymorphisms were related to HDL cholesterol levels on bivariate analysis but the relationship was no longer significant after multivariate analysis. CONCLUSION: Our data confirm the association of alcohol consumption and of APOA5, CETP, LIPC and LPL gene polymorphisms with HDL cholesterol levels. Conversely, no genexalcohol consumption interactions were found, suggesting that the effect of alcohol consumption on HDL cholesterol levels is not mediated via a modulation of HDL related genes.

High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate.

Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid - BEH - Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48h at room temperature and at +4°C (<6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections.

Computer-assisted placement technique in hip resurfacing arthroplasty: improvement in accuracy?

Freehand positioning of the femoral drill guide is difficult during hip resurfacing and the surgeon is often unsure of the implant position achieved peroperatively. The purpose of this study was to find out whether, by using a navigation system, acetabular and femoral component positioning could be made easier and more precise. Eighteen patients operated on by the same surgeon were matched by sex, age, BMI, diagnosis and ASA score (nine patients with computer assistance, nine with the regular ancillary). Pre-operative planning was done on standard AP and axial radiographs with CT scan views for the computer-assisted operations. The final position of implants was evaluated by the same radiographs for all patients. The follow-up was at least 1 year. No difference between both groups in terms of femoral component position was observed (p > 0.05). There was also no difference in femoral notching. A trend for a better cup position was observed for the navigated hips, especially for cup anteversion. There was no additional operating time for the navigated hips. Hip navigation for resurfacing surgery may allow improved visualisation and hip implant positioning, but its advantage probably will be more obvious with mini-incisions than with regular incision surgery.

Development of Ascaris lumbricoides eggs from females eliminated after chemotherapy in man

The development of Ascaris lumbricoides eggs obtained from females eliminated after treatment of infected individuals with a single oral dose of the antihelminthic drugs thiabendazole (50 mg/kg - 33 patients) or levamisole (250 mg - independent of body weigth - 20 patients) was studied. Every female eliminated up to 72 h after treatment were dissected, the uterus isolated and sectioned into small fragments. The eggs were transferred to plastics tubes and incubated at 28 degrees centigrades in 0.1 N H2 SO4 for 100 days. Every 20 days, starting from the 20 th up to the 100 th day, the extent of egg embryonation ratio was determined. The culture of A. lumbricoides eggs obtained from females from patients treated with thiabendazole did not contain embryonated eggs until the final period of observation. In contrast, the eggs obtained from females eliminated by patients treated with levamisole (control) presented an embryonation rate of 0.0 - 98.0% in the same period.

Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed.

Sistema de monitorització Open Source: projecte d'empresa per Computer Technology Catalunya

L’objectiu del projecte consisteix en l’estudi, simulació i implantació d’un conjunt d’aplicacions que permeten tenir un control sobre possibles problemes que puguin succeir a la nostra xarxa. Aquest projecte és la solució als problemes de detecció d’errors en el funcionament de les infraestructures de networking de les que disposen els nostres clients.

Protein interaction data curation: the International Molecular Exchange (IMEx) consortium.

The International Molecular Exchange (IMEx) consortium is an international collaboration between major public interaction data providers to share literature-curation efforts and make a nonredundant set of protein interactions available in a single search interface on a common website (http://www.imexconsortium.org/). Common curation rules have been developed, and a central registry is used to manage the selection of articles to enter into the dataset. We discuss the advantages of such a service to the user, our quality-control measures and our data-distribution practices.

Mutagenesis and modelling of the alpha(1b)-adrenergic receptor highlight the role of the helix 3/helix 6 interface in receptor activation.

Computer simulations on a new model of the alpha1b-adrenergic receptor based on the crystal structure of rhodopsin have been combined with experimental mutagenesis to investigate the role of residues in the cytosolic half of helix 6 in receptor activation. Our results support the hypothesis that a salt bridge between the highly conserved arginine (R143(3.50)) of the E/DRY motif of helix 3 and a conserved glutamate (E289(6.30)) on helix 6 constrains the alpha1b-AR in the inactive state. In fact, mutations of E289(6.30) that weakened the R143(3.50)-E289(6.30) interaction constitutively activated the receptor. The functional effect of mutating other amino acids on helix 6 (F286(6.27), A292(6.33), L296(6.37), V299(6.40,) V300(6.41), and F303(6.44)) correlates with the extent of their interaction with helix 3 and in particular with R143(3.50) of the E/DRY sequence.

Estudi d'interfícies multitàctils i multiusuàri

Actualment, les interfícies multitàctils estan guanyant popularitat, tant entre els usuaris com entre els desenvolupadors i fabricants. En aquest projecte s'estudien les interfícies multitàctils basades en visió per computador: el seu funcionament, la seva construcció i la implementació del software que permet la interacció amb més d'un dit simultàniament. En la memòria es presenta aquest estudi, com s'ha construït una taula i els resultats que s'han obtingut amb ella.

Early mother-child interaction and later quality of attachment in infants with an orofacial cleft compared to infants without cleft.

Objective : The main objective of this study was to assess mother-child patterns of interaction in relation to later quality of attachment in a group of children with an orofacial cleft compared with children without cleft. Design : Families were contacted when the child was 2 months old for a direct assessment of mother-child interaction and then at 12 months for a direct assessment of the child's attachment. Data concerning socioeconomical information and posttraumatic stress symptoms in mothers were collected at the first appointment. Participants : Forty families of children with a cleft and 45 families of children without cleft were included in the study. Families were recruited at birth in the University Hospital of Lausanne. Results : Results showed that children with a cleft were more difficult and less cooperative during interaction at 2 months of age with their mother compared with children without a cleft. No significant differences were found in mothers or in dyadic interactive styles. Concerning the child's attachment at 12 months old, no differences were found in attachment security. However, secure children with a cleft were significantly more avoidant with their mother during the reunion episodes than secure children without cleft. Conclusion : Despite the facial disfigurement and the stress engendered by treatment during the first months of the infant's life, children with cleft and their mothers are doing as well as families without cleft with regard to the mothers' mental health, mother-child relationships, and later quality of attachment. A potential contribution for this absence of difference may be the pluridisciplinary support that families of children with cleft benefit from in Lausanne.