Dual stimuli-responsive coating designed through layer-by-layer assembly of PAA-b-PNIPAM block copolymers for the control of protein adsorption.

In this paper, we describe the successful construction, characteristics and interaction with proteins of stimuli-responsive thin nanostructured films prepared by layer-by-layer (LbL) sequential assembly of PNIPAM-containing polyelectrolytes and PAH. PAA-b-PNIPAM block copolymers were synthesized in order to benefit from (i) the ionizable properties of PAA, to be involved in the LbL assembly, and (ii) the sensitivity of PNIPAM to temperature stimulus. The impact of parameters related to the structure and size of the macromolecules (their molecular weight and the relative degree of polymerization of PAA and PNIPAM), and the interaction with proteins under physico-chemical stimuli, such as pH and temperature, are carefully investigated. The incorporation of PAA-b-PNIPAM into multilayered films is shown to be successful whatever the block copolymer used, resulting in slightly thicker films than the corresponding (PAA/PAH)n film. Importantly, the protein adsorption studies demonstrate that it is possible to alter the adsorption behavior of proteins on (PAA-b-PNIPAM/PAH)n surfaces by varying the temperature and/or the pH of the medium, which seems to be intimately related to two key factors: (i) the ability of PNIPAM units to undergo conformational changes and (ii) the structural changes of the film made of weak polyelectrolytes. The simplicity of construction of these PNIPAM block copolymer-based LbL coatings on a large range of substrates, combined with their highly tunable features, make them ideal candidates to be employed for various biomedical applications requiring the control of protein adsorption.

HPV vaccination among French girls and women aged 14-23 years and the relationship with their mothers' uptake of Pap smear screening: a study in general practice.

INTRODUCTION: HPV vaccination is recommended in France for girls aged 14 and for those aged 15-23 before sexual debut or who have become sexually active within the previous year. The first aim was to describe vaccination practice among 14-23-year-old girls visiting a general practitioner. A second objective was to investigate factors associated with starting vaccination among girls aged 14-18, in particular the regular practice of Pap-smear screening (PSS) by their mothers. METHODS: A cross-sectional study was conducted from June to August 2009. A total of 87 general practitioners from the large Rhône-Alpes region contributed data on 502 girls/women who came for consultation. RESULTS: 231 (46.0%) of these girls/women had begun the process of HPV vaccination (68.2%, 56.9% and 18.7% of the 14-16, 17-20 and 21-23-year-olds respectively) of whom 139 (60.2%) had received all three doses. 92 girls/women (39.8%) had received only one or two doses at the time of study. However, in 71 (77.2%) cases, the gap between the last dose received and the time of study was within the between-dose interval recommended in the vaccination schedule. GPs reported that 16 (11.5%) had mentioned side effects following injections. Having a mother who practised regular PSS (Odds Ratio 6.2 [1.5-25.8]), having never lived with a partner (4.6 [1.6-13.5]) and vaccination against hepatitis B (3.2 [1.6-6.1]) were found to be independently correlated with the initiation of HPV vaccination among girls/women aged 14-18 years. CONCLUSION: Two years after the start of the programme, only half of girls/women aged 14-23 years had begun the process of HPV vaccination. HPV vaccination status was correlated with PSS in the mother, family status and hepatitis B vaccination. Such information may help to better target girls who are less likely to be vaccinated.

Factors associated with Pap smear screening among French women visiting a general practitioner in the Rhône-Alpes region.

BACKGROUND: To help prevent cervical cancer, three yearly opportunistic Pap smear screening is recommended in France for women aged 25-65 years. Pap smear screening coverage varies with age and socioeconomic level. The aim of this cross-sectional study was to identify factors associated with a low uptake of Pap smear screening among women with no limited access to healthcare. METHODS: We analyzed data from women aged 25-65 living in the Rhône-Alpes region who completed a self-administered questionnaire given to them by general practitioners between June and August 2008. The questionnaire covered knowledge about cervical cancer and its prevention as well as the women's history of Pap smear screening and other health-related behaviors. The relationship between low uptake of Pap smear screening--defined as not having had the test within the past 3 years--and a range of possible contributing factors was investigated using logistic regression. RESULTS: Of 1186 women with an intact uterus who completed the questionnaire, 89.1% said they had had a Pap smear within the past 3 years. On multivariate analysis, the 10.9% who had not were significantly more likely to live alone (1.76 [1.13-2.74]), to have no children (2.17 [1.31-3.62]), to have never used contraception (5.35 [2.98-9.62]), to have less knowledge about Pap smear screening (3.40 [1.55-7.49]), and to be unvaccinated against hepatitis B (0.55 [0.35-0.87]). CONCLUSION: Despite high overall compliance with Pap smear screening recommendations among women who consulted general practitioners, several factors were significantly associated with a low uptake of the service. Considering these factors may help to refine messages aimed at cervical cancer prevention.

[Description of patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit and identification of severity risk factors]. / Description des cas confirmés de grippe A(H1N1)pdm09 admis en réanimation et identification des facteurs de gravité

OBJECTIVE: The authors had for objective to describe patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit (ICU) in a university hospital and to identify risk factors correlated with the severity of the disease. DESIGN: A prospective study was conducted in an university hospital during the A(H1N1)pdm09 influenza pandemic. Severe laboratory confirmed cases (admitted to an ICU) were described and compared with non-severe confirmed cases (not admitted to an ICU). RESULTS: Sixty-nine patients were included; 36 (52%) were 15 to 44 years of age. Sixteen (23%) cases were defined as severe, ten of these (63%) concerned patients 45 to 64 years of age. The independent factors associated with severity were: a history of heart disease, obesity, and tobacco abuse. CONCLUSIONS: This work reinforces the need to identify and protect groups at risk of severe outcomes.

[Anticoagulant clinics are they effective in France? Performance evaluation of six anticoagulant clinics concerning the management of vitamin K antagonists]. / Les cliniques d'anticoagulants sont-elles efficaces en France ? Évaluation des performances de six cliniques dans la gestion des traitements par antivitamines K.

PURPOSE: Recent data show that the quality of anticoagulation evaluated in patients receiving vitamin K antagonists (VKA) is not optimal in France. The aim of this retrospective study was to estimate the performances of six French anticoagulant clinics that manage VKA treatments over a 3-year period, from 2009 to 2011. METHODS: All clinics used the same rule based software. We determined the time spent in the therapeutic range (TTR), a surrogate end-point of quality of treatment with VKA. RESULTS: The overall duration of follow-up was 2755 patient-years concerning 2385 patients. The time spent in the therapeutic range 2 to 3 assigned for 89% of the patients, was 73%. On the other hand the time spent in the therapeutic range for the other two INR ranges (2.5-3.5 and 3-4.5) concerning 11% of patients with prosthetic heart valve was lower (63.7% and 68.8% respectively) with an imbalance in favour of the time below the range. In this study, warfarin (Coumadine(®)) and fluindione (Previscan(®)) allowed an equivalent quality of anticoagulation. The 1728 patients of age ranged from 60 to 100 years spent more time in TTR than the 651 younger patients. The percentage of time spent with an INR greater than 5 was extremely reduced which is a guarantee of safety. CONCLUSION: These results prove that anticoagulant clinics in France have the same good performances as their counterparts abroad. It can be assumed that a high TTR contributes to a low incidence of both bleedings and thrombosis.

[Gynaecologists' attitudes and practices towards HPV vaccination: a quantitative-qualitative study in Rhône-Alpes]. / Perception et pratique de la vaccination HPV par les gynécologues : une étude quantitative et qualitative en Rhône-Alpes.

OBJECTIVES: Acceptance of the human papilloma virus (HPV) vaccine by targeted population will mainly depend on its acceptability among gynaecologists. We examined the perceptions, attitudes and practices of gynaecologists in relation to HPV vaccination 1 year after licensing. POPULATION AND METHODS: From November 2007 to April 2008, a cross-sectional survey was carried among a representative 10% sample of gynaecologists in the French Rhône-Alpes region. Both quantitative (self-administered questionnaire) and qualitative (interview) approaches were used. RESULTS: Among the 52 respondents, 90.4% of gynaecologists reported a favourable opinion about HPV vaccination, 5.8% were uncertain and 1.9% was opposed (one did not answer). The main justification for a favourable opinion related to the public health effects of the HPV vaccination (cited by 31.9% of those favouring vaccination). The main justification for an uncertain or opposed opinion was the too recent introduction of the vaccine (cited by 100%). During the month preceding the survey, 40.4% had provided HPV vaccination, mainly in 15-23 years old girls (38.5%). The major difficulties in providing HPV vaccination were questions asked by patients (cited by 44.2% of the respondents) and the targeted age of 14 years (13.5%). A total of 87.5% of respondents reported to have discussed with 14-year-old vaccinated girls of Pap-smear and 12.5% of STI prevention. CONCLUSION: One year after HPV vaccine licensing, gynaecologists of Rhône-Alpes region had a favourable opinion about it, despite some difficulties. Little information about STI prevention to vaccinated girls was reported opposite to information about Pap-smear.

Human papillomavirus (HPV) vaccination: perception and practice among French general practitioners in the year since licensing.

Acceptance of the Human Papillomavirus (HPV) vaccine by targeted populations will depend to a large extent on its acceptability among physicians. We examined the perceptions, attitudes and practices of general practitioners (GPs) in relation to HPV vaccination. From November 2007 to April 2008, a cross-sectional survey was carried out among a representative 5% sample of GPs in the large Rhône-Alpes region of France. Both quantitative (self-administered questionnaire) and qualitative (interview) approaches were used. During the month preceding the survey, 75.6% of the 279 GPs who responded had given at least one HPV vaccination and 47.6% had given a vaccination at the routine target age of 14 years. Overall, 80.8% of GPs reported a favourable opinion about HPV vaccination, 17.4% were uncertain and 1.8% were opposed. The main justification for a favourable opinion related to the public health benefits of the HPV vaccination (cited by 60% of those favouring vaccination). The main justification for an "opposed or uncertain" opinion was the too recent introduction of the vaccine (cited by 43.4%). The major difficulties in providing HPV vaccination were patients' concerns about potential side effects (cited by 37% of the respondents) and the target age of 14 years (28.9%). Interviews suggested that the concern about age may relate to the need, as perceived by GPs, to discuss sexually transmitted infections with adolescent patients. A favourable opinion about HPV vaccination was associated with seeing more female patients per week, younger age, and GPs' intention to recommend hepatitis B vaccination. This representative survey of GPs in a major region of France finds a favourable opinion about the HPV vaccine and widespread use of it, despite some concerns that the recent introduction of the vaccine means that we do not yet fully understand the potential for side effects and about the recommended target age of recipients.

Functionalization of magnetic nanowires by charged biopolymers.

We report on a facile method for the preparation of biocompatible and bioactive magnetic nanowires. The method consists of the direct deposition of polysaccharides by layer-by-layer (LbL) assembly onto a brush of metallic nanowires obtained by electrodeposition of the metal within the nanopores of an alumina template supported on a silicon wafer. Carboxymethylpullulan (CMP) and chitosan (CHI) multilayers were grown on brushes of Ni nanowires; subsequent grafting of an enzyme was performed by conjugating free amine side groups of chitosan with carboxylic groups of the enzyme. The nanowires are finally released by a gentle ultrasonic treatment. Transmission electron microscopy, electron energy-dispersive loss spectroscopy, and x-ray photoelectron spectroscopy indicate the formation of an homogeneous coating onto the nickel nanowires when one, two, or three CMP/CHI bilayers are deposited. This easy and efficient route to the biochemical functionalization of magnetic nanowires could find widespread use for the preparation of a broad range of nanowires with tailored surface properties.

[Evaluation of management of infarction in the Franche Comté province by the use of the Franche Comté Cardiology Registry, May 2005-May 2006]. / L'évaluation des pratiques professionnelles pour la prise en charge des infarctus en Franche-Comté. Expérience d'une évaluation à l'échelle régionale par l'utilisation des données du registre franc-comtois de cardiologie, mai 2005-mai 2006.

RATIONALE: The management of acute infarction often necessitates a network of organisation between different centres, thus making it the object of an evaluation of professional practices (EPP). We report the experience in the Franche Comté province of an EPP at a regional level in the management of infarction. METHODS: All of the patients admitted to 10 of the 11 centres in the region were included in a prospective survey. Quality indicators for acute and chronic care were defined, as well as scores, on the basis of use of treatments specified in guidelines. RESULTS: Between May 2005 and May 2006, 1,170 patients were admitted. The patients' risk levels and quality scores were calculated. The rate of use of the quality indicators was higher in our survey than that observed in all of the published studies, except for the use of betablockers. The quality of care could therefore be considered as highly satisfactory. Comparison between the centres revealed some differences. Even after adjustment for the risk score on admission, the quality score for acute care was related to mortality at 1 month. CONCLUSIONS: An EPP is possible for the management of infarction, on a regional scale such as in the province of Franche Comté. The acute quality score turned out to be an independent factor for mortality. The indicators showed that the quality of care was highly satisfactory, even though more progress could be made in the prescription of betablockers.

Lipase immobilization into porous chitoxan beads: activities in aqueous and organic media and lipase localization.

Lipases were noncovalently immobilized in Chitoxan, a polyionic hydrogel obtained by complexation between chitosan and xanthan. The properties of free and immobilized lipases have been compared. In the aqueous medium, the activity was twice as high for immobilized lipases as for free lipases. Immobilized lipases in chitoxan were able to hydrolyze triacylglycerols in three distinct organic solvent media. At the microstructural level, lipases were not distributed uniformly in the chitoxan beads. Higher concentrations of lipase were found in the outer membrane-like layer of the beads, as compared with lower concentrations in the inner part of the beads.

A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.

A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

Lack of agreement between left ventricular volumes and ejection fraction determined by two-dimensional echocardiography and contrast cineangiography in postinfarction patients.

OBJECTIVE: To assess the agreement between left ventricular (LV) volumes and ejection fraction (EF) determined by two-dimensional echocardiography (2-D echo) and by cineangiography in postinfarction patients. DESIGN: LV end-diastolic and end-systolic volumes indexed (EDVI and ESVI) to body surface area as well as EF were determined by both methods in all patients. SETTING: Multicenter trial conducted in five university hospitals. PATIENTS: 63 patients, 61 male, two female, mean age 55.5 +/- 10.4 years, suffering from a recent myocardial infarction. Eighty-one pairs of measurements were available. METHODS: The results of biplane 2-D echo measures, using apical four-chamber (4C) and two-chamber (2C) views were compared to those of a 30 degrees right anterior oblique cineangiography projection, using either the apical method of discs or the area-length 2-D echo method. Moreover, eyeball EF was estimated at 2-D echo and cineangiography, and was compared to the conventional methods. The agreement between results was assessed by the Bland and Altman method. RESULTS: The agreement between 2-D echo and cineangiography results was poor. Mean differences (MD) were -21.8 (EDVI, ml/m(2)), -9.5 (ESVI, ml/m(2)), and -0.9 (EF, %), respectively for 2-D echo method of discs versus cineangiography, and -23.2, -9.3, and -5.7 for area-length 2-D echo versus cineangiography. For EF (%), MD was -3.6 for eyeball cineangiography versus cineangiography, -1.3 for eyeball 2-D echo versus method of discs, and +0.30 for eyeball 2-D echo versus area-length 2-D echo, respectively. Two-dimensional echo is likely to underestimate LV volumes compared to cineangiography, especially for largest volumes. Even for EF, discrepancies are large, with a lack of agreement of 21%-25% between conventional methods, but agreement is better between eyeball EF and usual methods. CONCLUSIONS: Even with modern echocardiographic devices, agreement between 2-D echo and cineangiography-derived LV volumes and EF remains moderate, and both methods must not be considered interchangeable in clinical practice.

An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

Planimetry of aortic valve area using multiplane transoesophageal echocardiography is not a reliable method for assessing severity of aortic stenosis.

OBJECTIVE: To assess the reliability of aortic valve area planimetry by multiplane transoesophageal echocardiography (TOE) in aortic stenosis. DESIGN: Study of the diagnostic value of aortic valve area planimetry using multiplane TOE, compared with catheterisation and the continuity equation, both being considered as criterion standards. SETTING: University hospital. PATIENTS: 49 consecutive patients (29 male, 20 female, aged 44 to 82 years, average 66.6 (SD 8.5)), referred for haemodynamic evaluation of an aortic stenosis, were enrolled in a prospective study. From this sample, 37 patients were eligible for the final analysis. METHODS: Transthoracic and multiplane transoesophageal echocardiograms were performed within 24 hours before catheterisation. At transthoracic echo, aortic valve area was calculated by the continuity equation. At TOE, the image of the aortic valve opening was obtained with a 30-65 degrees rotation of the transducer. Numerical dynamic images were stored on optical discs for off-line analysis and were reviewed by two blinded observers. Catheterisation was performed in all cases and aortic valve area was calculated by the Gorlin formula. RESULTS: Feasibility of the method was 92% (48/52). The agreement between aortic valve area measured at TOE (mean 0.88 (SD 0.35) cm2) and at catheterisation (0.79 (0.24) cm2) was very poor. The same discrepancies were found between TOE and the continuity equation (0.72 (0.26) cm2). TOE planimetry overestimated aortic valve area determined by the two other methods. Predictive positive and negative values of planimetry to detect aortic valve area < 0.75 cm2 were 62% (10/16) and 43% (9/21) respectively. CONCLUSIONS: Planimetry of aortic valve area by TOE is difficult and less accurate than the continuity equation for assessing the severity of aortic stenosis.

[Lithium poisoning]. / Intoxication au lithium.

A case of therapeutic overdosage in a 58-year-old woman is reported. Lithium plasma level was 3.7 mmol.l. All clinical and biological disturbances regressed in 3 days after controlled rehydration only. Aetiology, clinical picture, biological characteristics and treatment according to the severity of the lithium poisoning are discussed.

1,1-Bisphosphonate squalene synthase inhibitors: interplay between the isoprenoid subunit and the diphosphate surrogate.

Inhibitors of squalene synthase have the potential to be superior cholesterol-lowering agents. We previously disclosed that lipophilic 1,1-bisphosphonates I are potent squalene synthase inhibitors and orally active cholesterol-lowering agents in animal models (Ciosek, C. P., Jr.; et al. J. Biol. Chem. 1993, 268, 24832-24837). In this paper, we describe modifications to the bisphosphonate moiety, in an attempt to reduce the number of acidic functions contained in these inhibitors. Replacing one of the acidic groups with a methyl (II, R2 = CH3) results in potent inhibitors when paired with a close mimic of the naturally occurring farnesyl moiety (R1 = farnesylethyl) but not when paired with the shorter isoprene surrogates (R1 = geranylethyl or 4-biphenylpropyl). In contrast, all three corresponding bisphosphonates I are potent squalene synthase inhibitors. Inhibitory potency is recovered with the shorter isoprene surrogates when R2 is CH2OH or CH2OCH3. It is proposed that these R2 groups serve as hydrogen bond acceptors with the active site of the enzyme. The properties of these compounds as cholesterol biosynthesis inhibitors in rats are described, and synthetic routes to these and related compounds are detailed.