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This data paper contains information about the in vivo model for peritoneal implants used in the paper "Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells" (De Vlieghere et al., 2015) [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included.

Breastfeeding induces a different metabolic and endocrine response than feeding conventional infant formula, and it has also been associated with slower weight gain and reduced disease risk in later life. The underlying programming mechanisms remain to be explored. Breastfeeding has been reported to induce lower levels of insulin, insulin-like growth factor-1 and some amino acids (AAs) than formula feeding. In the Childhood Obesity Project (CHOP), infants fed a conventional protein-rich formula had a higher BMI at 2 and 6 years than those fed a protein-reduced formula. At 6 months, higher protein intakes induced increased plasma concentrations of branched-chain AAs (BCAAs) and their oxidation products, short-chain acylcarnitines. With increasing BCAA levels, these short-chain acylcarnitines increased proportionally only until a break point was reached, after which BCAAs seemed to escape their degradation. The resulting marked elevation in BCAA levels with high-protein (HP) intakes appears to contribute to increased insulin levels and to affect β-oxidation of fatty acids. The ratios of long-chain acylcarnitines to free carnitine decreased in infants who received a HP formula, which indicates a reduced initiation of β-oxidation. We conclude that HP intakes inducing high BCAA plasma levels may inhibit fat oxidation and thereby enhance body fat deposition and adiposity., (© 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Background: Nutrition in childhood has an influence on the cardiovascular function later on in life. European Childhood Obesity Project is a multicenter, randomized clinical intervention trial examining the effect of early protein intake on later health outcomes, particularly adiposity and related disorders. The aim of the study was to examine the effect of nutritional intervention--different protein intake in infancy on carotid intima-media thickness (cIMT) at 5 years. The association of cardiovascular risk factors with cIMT was also assessed., Methods: Healthy term formula-fed infants in five European countries were enrolled either to the higher (HP) or to the lower (LP) protein group. Observational group consisted of breastfed infants. Plasma insulin, glucose, lipid profile, IGF-1, apolipoprotein A1 and B were measured as well as anthropometric parameters of parents and a child, blood pressure and physical activity., Results: No difference in cIMT between HP and LP group was observed. Insulin, HOMA-IR index and total IGF-1 were positively associated with cIMT but after adjustment for confounders only an inverse association between ApoA1 and positive between ApoB/ApoA1 and cIMT were significant., Conclusion: High versus low protein intake in infancy does not influence cIMT at 5 years. cIMT in healthy children at 5 years is associated with their apolipoprotein profile., (© 2015 S. Karger AG, Basel.)

Context: The protective effect of breast-feeding against later obesity may be explained by the lower protein content compared with formula milk. However, the metabolic mechanisms remain unknown., Objective: We studied the metabolic response to a higher or lower protein supply in infancy., Design and Setting: The Childhood Obesity Project study is a double-blind, randomized, multicenter intervention trial. Infants were randomized to receive a higher (HP) or lower protein (LP) content infant formula or were breast-fed., Patients and Interventions: Plasma samples of 691 infants who received formula milk with different protein content (HP, 2.05 g per 100 mL; LP, 1.25 g per 100 mL) or were breast-fed were collected., Main Outcome Measures: Changes in plasma amino acid and acylcarnitine concentrations of 6-month-old infants according to different dietary protein supply were determined by liquid chromatography coupled to tandem mass spectrometry., Results: Twenty-nine metabolites differed significantly between the formula groups. Branched-chain amino acids (BCAAs) were the most discriminant metabolites. Their degradation products, the short-chain acylcarnitines C3, C4, and C5, were also significantly elevated in the HP group. A breakpoint analysis confirmed that with increasing BCAAs, the ratio between acylcarnitines and BCAAs decreases. Long-chain acylcarnitines were decreased in HP infants., Conclusions: BCAAs seem to play a pivotal role in the effect of a high-protein diet on β-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high-protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the β-oxidation, thus leading to high early weight gain and body fat deposition.

Objective(s): Assess the efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of postpartum haemorrhage., Study Design: Systematic review with meta-analysis., Material and Methods: Systematic review of the literature with the aim of identifying prospective, randomised, controlled trials that assessed the effect of tranexamic acid on peripartum blood loss and transfusion requirement in three clinical contexts: (i) prevention of post-partum haemorrhage in case of elective caesarean section, (ii) prevention of post-partum haemorrhage in case of vaginal delivery, (iii) treatment of post-partum haemorrhage., Results: Prophylactic administration of tranexamic acid reduced blood loss (mean difference for intraoperative blood loss: -177.9mL, IC 95%: -189.51 to -166.35, total blood loss: -183.94, IC 95%: -198.29 to -169.60), and the incidence of severe post-partum haemorrhage (OR: 0.49, IC 95%: 0.33 to 0.74). None of the published trials assessed the effect of tranexamic acid on blood products administration or transfusion requirement. Only one study assessed and reported the efficacy of tranexamic acid when administered as a treatment for postpartum haemorrhage. A significant reduction in blood loss was reported within 30 minutes after randomisation (P=0.03) and confirmed after 6 hours (median: 170mL (58-323) vs 221mL (110-543), P=0.04). None of the included studies adequately studied the incidence of side effects after tranexamic acid administration., Conclusion: Although tranexamic acid administration seemed to significantly reduce blood loss and the incidence of severe post-partum haemorrhage, further prospective trials are needed to confirm the efficacy and safety of tranexamic administration in the treatment of postpartum haemorrhage. Those studies should assess the pharmacokinetic profile and the safety of this drug in pregnant women., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Falls in geriatry are associated with important morbidity, mortality and high healthcare costs. Because of the large number of variables related to the risk of falling, determining patients at risk is a difficult challenge. The aim of this work was to validate a tool to detect patients with high risk of fall using only bibliographic knowledge. Thirty articles corresponding to 160 studies were used to modelize fall risk. A retrospective case-control cohort including 288 patients (88 ± 7 years) and a prospective cohort including 106 patients (89 ± 6 years) from two geriatric hospitals were used to validate the performances of our model. We identified 26 variables associated with an increased risk of fall. These variables were split into illnesses, medications, and environment. The combination of the three associated scores gives a global fall score. The sensitivity and the specificity were 31.4, 81.6, 38.5, and 90 %, respectively, for the retrospective and the prospective cohort. The performances of the model are similar to results observed with already existing prediction tools using model adjustment to data from numerous cohort studies. This work demonstrates that knowledge from the literature can be synthesized with Bayesian networks.

Objectives: Studies have emphasized the importance of normal fibrinogen concentrations in surgical patients. The primary hypothesis of this study was that fibrinogen levels significantly decrease in on-pump coronary artery bypass graft (CABG) surgery versus off-pump coronary artery bypass graft (OPCAB) surgery. The second objective was to show that ROTEM (TEM International, GmbH, Munich, Germany) rapidly detects these abnormalities compared with standard tests., Design: A prospective, nonrandomized study., Setting: A university hospital., Participants: Forty-two and 62 patients in the CABG and OPCAB groups, respectively, undergoing first-time bypass surgery were included., Interventions: CABG versus OPCAB surgery., Measurements and Main Results: Routine coagulation tests and ROTEM values were measured before anesthesia (T0), after the first dose of heparin (T1), after protamine (T2), upon intensive care unit arrival (T3), and 4 hours postoperatively (T4). The outcome measures were followed until 4 hours postoperatively. Fibrinogen concentrations were significantly lower in the CABG versus the OPCAB group at T2 (170 ± 44 v 243 ± 73 mg/dL, p < 0.001) and T3 (179 ± 42 v 232 ± 68 mg/dL, p < 0.001). This was confirmed by significantly lower FIBTEM maximal clot firmness values at T2 (9 ± 4 v 14 ± 5 mm, p < 0.001) and T3 (9 ± 4 v 13 ± 6 mm, p < 0.001). In the CABG group, patients received significantly more transfusions of all blood products except fresh frozen plasma., Conclusions: Fibrinogen concentration significantly decreases after cardiopulmonary bypass. ROTEM helps in its fast detection., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This is a case report, for the first time in the literature, of a third trimester pregnant woman with acute abdominal pain for which the diagnosis of varicose veins rupture was achieved by MRI., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Cell adhesion controls various embryonic morphogenetic processes, including the development of the enteric nervous system (ENS). Ablation of β1-integrin (β1-/-) expression in enteric neural crest cells (ENCC) in mice leads to major alterations in the ENS structure caused by reduced migration and increased aggregation properties of ENCC during gut colonization, which gives rise to a Hirschsprung's disease-like phenotype. In the present study, we examined the role of N-cadherin in ENS development and the interplay with β1 integrins during this process. The Ht-PA-Cre mouse model was used to target gene disruption of N-cadherin and β1 integrin in migratory NCC and to produce single- and double-conditional mutants for these two types of adhesion receptors. Double mutation of N-cadherin and β1 integrin led to embryonic lethality with severe defects in ENS development. N-cadherin-null (Ncad-/-) ENCC exhibited a delayed colonization in the developing gut at E12.5, although this was to a lesser extent than in β1-/- mutants. This delay of Ncad-/- ENCC migration was recovered at later stages of development. The double Ncad-/-; β1-/- mutant ENCC failed to colonize the distal part of the gut and there was more severe aganglionosis in the proximal hindgut than in the single mutants for N-cadherin or β1-integrin. This was due to an altered speed of locomotion and directionality in the gut wall. The abnormal aggregation defect of ENCC and the disorganized ganglia network in the β1-/- mutant was not observed in the double mutant. This indicates that N-cadherin enhances the effect of the β1-integrin mutation and demonstrates cooperation between these two adhesion receptors during ENS ontogenesis. In conclusion, our data reveal that N-cadherin is not essential for ENS development but it does modulate the modes of ENCC migration and acts in concert with β1-integrin to control the proper development of the ENS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Benzodiazepines are widely used in the elderly, but may induce potentially severe iatrogenic events like falls. The analysis of their use is difficult because of the numerous molecules and dosages available. The aim of the present study is to build a tool to monitor their consumption and to evaluate the relation between this consumption and patient's falls reported in three geriatric institutions., Methods: Conversion coefficients found in the literature allowed the expression of benzodiazepine action with a unique comparator: diazepam. Benzodiazepine consumption observed during 20 consecutive months was collected and weighted by hospital activity. A correlation between benzodiazepine consumption and the number of falls reported during the same period was researched., Results: Benzodiazepine consumption expressed in milligrams of diazepam-equivalent per hospitalization day is significantly linked to the number of falls expressed during the same period (R=0.63; p<0.01). However, no statistical bound was found between monthly falls variations and monthly benzodiazepine consumption variations. These results corroborate others published studies: benzodiazepine consumptions are statistically linked to falls, but the reduction of this consumption is of poor predictive value, maybe because of the multifactorial nature of falls., Discussion and Conclusion: The expression of benzodiazepine consumption in diazepam-equivalent enables one to estimate the general exposition of patients and to compare the use of each molecule. The statistical link between this indicator and a major iatrogenic event like falls makes it a tool worth interest for both clinicians and pharmacists., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

During embryonic development and wound healing, the mechanical signals transmitted from cells to their neighbors induce tissue rearrangement and directional movements. It has been observed that forces exerted between cells in a developing tissue under stress are not always monotonically varying, but they can be pulsatile. Here we investigate the response of model tissues to controlled external stresses. Spherical cellular aggregates are subjected to one-dimensional stretching forces using micropipette aspiration. At large enough pressures, the aggregate flows smoothly inside the pipette. However, in a narrow range of moderate aspiration pressures, the aggregate responds by pulsed contractions or "shivering." We explain the emergence of this shivering behavior by means of a simple analytical model where the uniaxially stretched cells are represented by a string of Kelvin-Voigt elements. Beyond a deformation threshold, cells contract and pull on neighboring cells after a time delay for cell response. Such an active behavior has previously been found to cause tissue pulsation during dorsal closure of Drosophila embryo.

Background: Previous studies have reported postpartum depression to be associated with both positive and negative effects on early infant growth. This study examined the hypothesis that maternal postnatal depression may be a risk factor for later child growth faltering or overweight., Methods: A total of 929 women and their children participating in a European multicenter study were included at a median age of 14 days. Mothers completed the Edinburgh postnatal depression scale (EPDS) at 2, 3 and 6 months after delivery. EPDS scores of 13 and above at any time were defined as maternal depression. Weight, length, triceps and subscapular skinfold thicknesses were measured, and body mass index (BMI) were calculated when the children were two years old and converted to standard deviation scores based on the WHO Multicentre Growth Reference Study (MGRS)., Results: Z-scores for weight-for-length at inclusion of infants of mothers with high EPDS scores (-0.55, SD 0.74) were lower than of those with normal scores (-0.36, SD 0.74; p = 0.013). BMI at age 24 months did not differ in the high (16.3 kg/m2, SD 1.3) and in the normal EPDS groups (16.2 kg/m2, SD 1.3; p = 0.48). All other anthropometric indices also did not differ between groups, with no change by multivariate adjustment., Conclusions: We conclude that a high maternal postnatal depression score does not have any major effects on offspring growth in high income countries.

Background: The purpose of this paper is to evaluate costs associated with the online intervention trial, Making Effective Nutritional Choices for Cancer Prevention (MENU), and to connect the findings to the study outcomes., Methods: Using prospective data collected during the MENU development and implementation phases, we estimated overall costs per person, incremental costs for the three arms of the MENU intervention, and incremental costs per change in fruit and vegetable (F&V) consumption across the studied population. The MENU study was conducted in five HMO sites of the Cancer Research Network. The number of eligible study participants who were enrolled in the study was 2,540. Recruited participants were randomized into (1) an untailored website program, (2) tailored website program, or (3) tailored web program plus personalized counseling (HOBI) via email. The primary measures for these analyses include the total intervention costs, average cost per participant, and the average cost per mean change in daily intake of F&V, stratified by study arm., Results: The mean change in F&V consumption was greater in both the tailored arm and statistically higher in the HOBI arm relative to the untailored arm. The untailored arm achieved +2.34 servings increase vs. the tailored website arm (+2.68) and the HOBI arm (+2.80) servings increase. Total intervention costs for MENU participants who completed the 12-month follow-up assessment, by study arm, were estimated to be $197,197 or $110 respectively. This translates to $69 per participant in the untailored web site intervention, $81 per participant in the tailored website intervention, and $184 per participant in the HOBI intervention and a cost per average change in F&V consumption to be $35, $27 and $61 respectively., Conclusions: Providing personalized "tailored" messages and additional personalized support via email generated an additional $12-$115 per participant, over the untailored web program. Incremental increases in F&V consumption associated with the email support arm were associated with considerable increases in intervention costs, suggesting that the most cost effective arm of the MENU study by servings gained was the tailored website.

Aim: To study if infant crying is associated with maternal postnatal depression., Methods: Data from 1015 mothers and their children participating in a prospective European multicentre study were analysed. Infantile colic and prolonged crying were defined as excessive crying as reported by the mothers 2 and 6 months after delivery, and at the same time the mothers completed the Edinburgh Postnatal Depression Scale (EPDS)., Results: In cross-sectional analyses, infant crying was associated with high EPDS scores both 2 (OR: 4.4; 95% CI: 2.4-8.2) and 6 months postpartum (OR: 10.8; 95% CI: 4.3-26.9). More than one-third of the others of infants with prolonged crying had high EPDS scores 6 months postpartum. Longitudinal analyses showed that mothers of infants with colic had increased odds of having high EPDS scores 6 months after delivery even if crying had resolved (OR: 3.7; 95% CI: 1.4-10.1)., Conclusion: Both infantile colic and prolonged crying were associated with high maternal depression scores. Most noteworthy, infantile colic at 2 months of age was associated with high maternal depression scores 4 months later.

Background: Web-based programs for health promotion, disease prevention, and disease management often experience high rates of attrition. There are 3 questions which are particularly relevant to this issue. First, does engagement with program content predict long-term outcomes? Second, which users are most likely to drop out or disengage from the program? Third, do particular intervention strategies enhance engagement?, Objective: To determine: (1) whether engagement (defined by the number of Web sections opened) in a Web-based smoking cessation intervention predicts 6-month abstinence, (2) whether particular sociodemographic and psychographic groups are more likely to have lower engagement, and (3) whether particular components of a Web-based smoking cessation program influence engagement., Methods: A randomized trial of 1866 smokers was used to examine the efficacy of 5 different treatment components of a Web-based smoking cessation intervention. The components were: high- versus low-personalized message source, high- versus low-tailored outcome expectation, efficacy expectation, and success story messages. Moreover, the timing of exposure to these sections was manipulated, with participants randomized to either a single unified Web program with all sections available at once, or sequential exposure to each section over a 5-week period of time. Participants from 2 large health plans enrolled to receive the online behavioral smoking cessation program and a free course of nicotine replacement therapy (patch). The program included: an introduction section, a section focusing on outcome expectations, 2 sections focusing on efficacy expectations, and a section with a narrative success story (5 sections altogether, each with multiple screens). Most of the analyses were conducted with a stratification of the 2 exposure types. Measures included: sociodemographic and psychosocial characteristics, Web sections opened, perceived message relevance, and smoking cessation 6-months following quit date., Results: The total number of Web sections opened was related to subsequent smoking cessation. Participants who were younger, were male, or had less formal education were more likely to disengage from the Web-based cessation program, particularly when the program sections were delivered sequentially over time. More personalized source and high-depth tailored self-efficacy components were related to a greater number of Web sections opened. A path analysis model suggested that the impact of high-depth message tailoring on engagement in the sequentially delivered Web program was mediated by perceived message relevance., Conclusions: Results of this study suggest that one of the mechanisms underlying the impact of Web-based smoking cessation interventions is engagement with the program. The source of the message, the degree of message tailoring, and the timing of exposure appear to influence Web-based program engagement.

Gayet-Wernicke syndrome is a rare neurological pathology due to a deficit in vitamin B1. It occurs in alcoholics but several reports have been published of cases in a context of intractable vomiting. The frequency is probably under-estimated because there have been many cases described at autopsy. The diagnosis is clinical with the triad (found in 60% of cases) of mental confusion, oculomotor disorders and ataxia. MRI can confirm the diagnosis by hyper signal images most frequently in a peri-acqueductal location, the thalamus and mamillary bodies. We report 3 observations of Gayet-Wernicke encephalopathy discovered in a context of hyperemesis gravidarum. These 3 cases, which occurred within the past two years in the West of France, give us the opportunity to assess 3 different outcomes for this pathology. In a second section we review the main publications in the literature. Hyperemesis gravidarum is a frequent pathology and can be the cause of serious neurological complications. Early vitamin supplementation should be instituted in case of severe vomiting in order to ensure the pregnancy can continue together with the mother's well-being.

The concept "inborn error of metabolism" (IEM) arose from the observations of Sir A. Garrod at the beginning of the XXth century. The exponential development, during the last decades, of our knowledge in cellular biology and molecular genetics, and the availability of increasingly more precise diagnostic tools, allow the identification of a still growing number of inborn errors of metabolism. Their physiopathology is better understood. Treatments have considerably improved: more specific diets, new medical treatments, enzyme replacement therapy, organ transplantation, hepatocyte or stem cell transplantation... New techniques are under development, including various strategies of gene therapy. Improved therapeutic efficacy combined with earlier diagnosis have dramatically changed the prognosis of many disorders. As a consequence, new challenging questions have to be answered. Today, patients with an IEM, because of the extreme complexity of their management, need to be looked after by a multidisciplinary team of physicians (pediatricians and internists), dieticians, social workers, psychologists... It is essential, in this complex and rapidly expanding field, that experiences should be shared at national and international level, in order to provide the most adequate care for patients.

Objective: To report two cases of coasting during receipt of GnRH antagonists., Design: Case report., Setting: University hospital., Patient(s): One 27-year-old and one 28-year-old woman, both with risk factors for the ovarian hyperstimulation syndrome (OHSS)., Intervention(s): Two IVF treatments during which hMG treatment was stopped until E2 decreased to a safer level during receipt of GnRH antagonist., Main Outcome Measure(s): Development of OHSS and pregnancy., Result(s): Embryos were transferred in both women. Neither woman developed OHSS and one ongoing pregnancy was obtained., Conclusion(s): Coasting is feasible when a GnRH antagonist is used during IVF. Further studies are needed to evaluate its preventive role in OHSS.

Shoulder dislocation is a frequent pathology with a high level of recurrences especially in young patients. One week immobilization in a Dessault dressing is sufficient if it is followed by free mobilization avoiding external rotation and abduction. A 6 weeks rehabilitation program seems to prevent recurrences.

A reliable and rapid speciation method for the simultaneous determination of butyl- and phenyltin species in sediment samples has been developed. Two extraction procedures are compared: methanolic hydrochloric acid (at four different concentrations) and ethanoic acid leaching. Derivatization is carried out by the one-step ethylation/extraction procedure using the sodium tetraethylborate reagent directly in aqueous phase in the presence of an isooctane layer. Analysis is performed by capillary gas chromatography hyphenated to flame photometric detection (GC-FPD). Detection limits range from 0.5 to 1.5 ng(Sn) g(-1)(dry weight). Analysis of environmental samples and certified reference materials demonstrate the accuracy of the analytical method.

Mass treatment of onchocerciasis has changed radically in the last 20 years. With implementation of the Onchocerciasis Control Programme (OCP), use of insecticides to control vector larvae has been effective but has not been extended to all infected areas due to the cost. The consequences of this problem have been lessened thanks to ivermectin, an effective drug that can be administered in a single yearly dose. Although ivermectin does not appear to induce major side-effects, surveillance is necessary after administration in polyparasitized subjects living in zones where loaiasis is present and in hypermicrofilaremic subjects. To assist in the fight against onchocerciasis, ivermectin is distributed free of charge through the Mectizan Foundation by Merck Laboratories. Inexpensive community distribution programs with active participation of the populations at risk have demonstrated their usefulness. The results of mass treatment through the Mectizan Foundation have been excellent. Non-governmental organizations and in particular the Organization for the Prevention of Blindness (OPB) have become increasingly involved in the fight against onchocerciasis. The campaign conducted by the OPB in Mali, Senegal and Guinea illustrate this involvement. The role of non-governmental organizations expanded greatly with the implementation of the APOC programme supported by the World Bank.

The sat4 streptothricin resistance gene from Campylobacter coli BE/G4 was cloned into pUC18, and its nucleotide sequence was determined. Streptothricin acetyltransferase activity was detected in Escherichia coli cells containing recombinant plasmid pAT132 which carries the sat4 gene as an insert. The deduced amino acid sequence displayed 21-27% amino acid identity with streptothricin acetyltransferases from E. coli and streptothricin producers Streptomyces lavendulae and Streptomyces noursei. The sat4 gene was detected by hybridization in clinical and environmental isolates of Campylobacter spp.

Objectives: To determine whether beta carotene is therapeutically equivalent to retinyl palmitate in the formulation currently recommended by the World Health Organisation., Design: Randomised blind equivalence trial., Setting: Rural area in Senegal., Subjects: Children aged 2-15 years suffering from vitamin A deficiency as defined by abnormal results on eye cytology were randomly allocated treatment with retinyl palmitate (n = 256) and beta carotene (n = 254)., Main Outcome Measure: Reversion to normal results on eye cytology as defined by the reappearance of goblet cells and normalisation of the epithelial cells., Results: Seven weeks after the supplement was given the percentages were 51.2% (124/242) children taking retinyl palmitate and 50.0% (123/246) of those taking beta carotene, who had reverted to normal eye cytology, a difference of 1.2% (95% confidence interval 6.2% to 8.6%) [corrected]. According to an equivalence testing procedure, the two treatments were statistically equivalent; the null hypothesis of non-equivalence was rejected (one tailed p value = 0.03)., Conclusions: beta Carotene supplementation seems to be a promising candidate for the alleviation of vitamin A deficiency. It could be given either as high dose capsule or through increased dietary intake. The challenge now is to improve dietary intake of vitamin A in programmes that are effective and sustainable at the community level.

Excision and integration of Tn1545 occur by reciprocal site-specific recombination between 6 (or 7) bp variable sequences present in the recombining attachment (att) sites and designated overlap regions. We devised an assay for Tn1545 transposition in which derivatives containing the cis-acting transposition sequences (attTn 1545) integrate into a target replicon when complemented in trans by the transposon-encoded integrase Int-Tn. This assay was used to determine the characteristics of the DNA sequence that influence target site selection. Characterization of several integration sites indicated that a 20 bp segment, designated attB, contains the sequences required for target activity. It also appeared that (i) the target activity depends upon the extent of homology between the 7bp segments flanking the overlap regions in attB and attTn 1545, and (ii) the degree of homology between the two recombining overlap regions does not affect the level of target activity and has no influence on integration orientation.

The historical background to angioscopy shows that the principal successes recorded by its use result from the miniaturization of fibroscopes and the progress in video imaging. The first tentative use of angioscopy was by surgeons during operations carried out at about 1970, that of percutaneous angioscopy dating from 1984. The material used for diagnostic (fibroscope, cinecamera, video system, flushing pump) and interventional (fibroscope, clamps, Dormia cage, endoprostheses ... ) angioscopy is such that the basic equipment requires an outlay of about 150 to 200,000 francs. Percutaneous angioscopy implies the insertion of a catheter allowing flushing of the arterial lumen by means of a pressurized perfusion pump which, when reversed, is transformed into an aspirating pump for removal of the clot and/or atheromatous debris. The procedure is simple and does not expose to more complications than conventional arteriography.

Since 1987, routine angioscopic examination has been performed in 191 patients undergoing angioplasty, with interventions (196) after a 2 year surveillance period (55). Angioscopy allowed follow up "de visu" of the performance of angioplasty, details of its mechanism to be precise and under dilatation to be carried out. For femoral artery occlusions it allowed treatment "à la carte": conventional dilatation of vegetating atheroma, specific treatment of established thrombi (5) and abstention from therapy of atheroma covered by endothelium (3). It also enabled fresh thrombi complicating a stenosis or at the origin of a thrombus to be detected. The extraction technique employed (15) is described. It facilitated catheterization by directing the probe, enabled avoidance of bypassing of stenosis and flaps and of dissection or false introduction into collaterals (10). Directed biopsy could be carried out in inflammatory arteritis (7). Vegetating atheromatous lesions could be opened and extracted, facilitating subsequent dilatation and allowing an approach to removal of iliac artery obstructions without major risks of complications (13). Finally, after an ineffective dilatation or the presence of a dissection, it assisted making the decision to introduce a stent (9), the tolerance and outcome of these stents are described. Or the 196 patients considered suitable for angioplasty, our therapeutic conduct was modified by angioscopy in 58 cases (29%). Not simply a new diagnostic tool, it plays a role in interventional vascular techniques.

Efficacy of percutaneous treatments of arterial affections requires the correct choice of indications, necessitating precise knowledge of elementary arterial lesions. Arterial endoscopy appears to be more specific than angiography for this use, since it allows direct vision in vivo of the lesion, a histopathologic approach compared with the non univocal images produced by angiography (for example, an arterial obstruction can result from varied causes). Different accidents to the endothelial surface can be observed: golden yellow atheromatous elevations on a straw yellow background, intimal flaps, mobile intra-luminal vegetations. Established atheromatous stenosis are smooth and regular, or on the contrary ulcerated and edged with irregular flaps capable of provoking an eccentric residual lumen. The vegetating atheromatous lesions may project into the lumen, often as calcified and thus pearly white scales adhering to the wall, or as larger occlusive lesions. When capable of being isolated, a thrombus often completes the stenosis: its recognition is therefore fundamental since its removal exposes the subjacent lesions to be treated. The fresh clot is coral shaped, bright red and mobile in the blood flow. Established clots are compact and greenish brown. At an advanced stage of atheroma the surface of the occluding clot is covered with a regular straw yellow endothelium. In the presence of a dissecting vessel the fibroscope may be introduced into the false channel, no longer showing typical endothelium but a coagulated mass interspersed with fibrous bands. Prosthetic stenosis result from either intimal hyperplasia or a suturing fault with plication.

Administration of large oral doses of retinyl palmitate has become the most widely practised vitamin A deficiency prevention strategy in developing countries. We conducted a follow-up study among 220 Senegalese children aged 2-7 years suffering from moderate undernutrition to determine the efficacy of vitamin A treatment on their vitamin A status assessed by biochemical and cytological (impression cytology with transfer) methods. The first examination (T = 0 m[onth]) was carried out during April 1989, before the mango (Mangifera indica L,) harvest. The second examination (T = 2 m) was carried out 2 months after vitamin A treatment during June 1989 when ripe mangoes become widely available. Conjunctival cells of the eyes of the children with or without ocular inflammation were responsive to vitamin A administration (P < 0.01). There was a significant increase (P < 0.001) in mean serum retinol and beta-carotene levels between T = 0 m and T = 2 m. Mean serum retinol-binding protein (RBP) and transthyretin (TTR) levels did not differ significantly (P > 0.05) at T = 0 m and T = 2 m. Despite the intake of vitamin A, 54% of the children who had abnormal cytology at T = 0 m remained abnormal at T = 2 m. This was due to inadequate levels of TTR and RBP, presumably due to the cereal diet eaten by the Senegalese population. children with abnormal eye cytology had lower serum retinol levels than those with normal eyes at T = 0 m, and beta-carotene values did not correlate with eye cytological abnormalities at T = 0 m. Children with normal cytology had higher serum retinol and also beta-carotene levels than those with abnormal cytology after massive oral doses of vitamin A and consumption of mangoes at T = 2 m. Retinyl palmitate may, therefore, only lead to partial cytological improvement due to a lack of retinol-carrier proteins but dietary beta-carotene may also be involved.

The increasing importance of vitamin A deficiency in even its mild subclinical form underlines the need for a mass screening test. Clinical, biochemical and cytological methods of assessing vitamin A deficiency in a public health setting have been described and widely used. The cytological method shows promise because it enables early detection of vitamin A deficiency. However interpretation is problematic since histopathological changes are gradual with the progressive disappearance of goblet cells and appearance of enlarged epithelial cells. The reliability and validity of the impression cytology with transfer (ICT) test were assessed in order to produce a meaningful standard for this cytological method. The ICT test was performed in Senegal on 1451 children, in the course of two surveys conducted in 1989 and 1990 in rural areas. Reliability, estimated by Cohen's kappa test for evaluating intra-reader variability, and sensitivity were highest for the abnormal-normal classification (kappa = 0.91; 95% confidence interval (CI): 0.89-0.93; and sensitivity = 74%; 95% CI 66-82%). The ICT method is a cheap, noninvasive and easy test to perform in the field. This method is also reproducible and fairly sensitive according to the abnormal-normal classification. As illustrated by our proposed 50% cutoff of abnormal cytology calculated in relation to 5% of serum retinol values below 0.35 mumol/L criterion, ICT only requires a small sample for the assessment of the overall health of a community in contrast to xerophthalmia and blood vitamin A deficiency tests.

The genetic basis of tetracycline resistance was studied in 25 clinical isolates of Listeria monocytogenes. Resistance to tetracycline was associated with resistance to minocycline and due to the presence of the tet(M) gene in 24 strains. Association of tet(M) with int-Tn, the gene encoding the protein required for the movements of Tn1545-like conjugative transposons, was found in all strains. Cotransfer of tet(M) and int-Tn among L. monocytogenes cells and from L. monocytogenes to Enterococcus faecalis was detected in 7 of the 12 strains studied at frequencies similar to those obtained with the prototype element Tn1545. tet(L), the second most prevalent tetracycline resistance gene in enterococci and streptococci, was detected in the remaining strain, where it was borne by a 5-kb plasmid. These observations indicate that two types of movable genetic elements, transposons and plasmids, in enterococci and streptococci are responsible for emergence of drug resistance in L. monocytogenes.

In a countrywide survey, we assessed the prevalence of vitamin A deficiency by clinical examination and impression cytology with transfer method (ICT) in a randomized sample of 2445 subjects representative of the population of the Republic of Djibouti. A plasma retinol determination was made on a part of this sample. Results lead to believe that serious vitamin A deficiency may periodically occur in Republic of Djibouti when nutritional conditions become poor. Meanwhile a large number of children, mostly in the rural area, have a marginal vitamin A status and are exposed to a high level of risk.

The changes in the vitamin A and nutritional status of children from a rural area in Senegal were determined by the same team during two cross-sectional surveys distant from exactly one year. At baseline (T = 0 year) 1,259 children were chosen at random. One year later (T = 1 year), 1,008 children were re-examined. Vitamin A and nutritional status were assessed by clinical and cytological methods, and by anthropometrical indicators for the 1,008 participants, respectively. No signs of xerophthalmia were recorded at T = 0 and T = 1 year. The proportions of children deficient in vitamin A as defined by abnormal cytology and suffering from stunting were similar at these two measuring points. Even though these percentages remained similar at T = 0 and T = 1 year, there existed little movement between the abnormal and normal eye cytology group and the stunted and non-stunted group. Since vitamin A is required for normal growth, we calculated the mean linear gain in height according to the eye cytological changes assessed between the two examinations. We found that mean linear growth increments were higher in the groups of children who remained abnormal or reverted to abnormal cytology than in those who remained normal or reverted to normal cytology.

The increasing concern about vitamin A deficiency in even its mild subclinical form has created the need for a mass screening test. Various clinical, biochemical and cytological methods for assessing the vitamin A status have been widely used but all are unsatisfactory for technical, ethical or public health reasons. The two prevalence criteria defined by the World Health Organization (WHO) for a vitamin A deficiency problem of public health significance are xerophthalmia and serum retinol concentrations. Recently we proposed a prevalence criterion for impression cytology with transfer (ICT) at the level of 50% of ICT results being abnormal. We conducted a cross-sectional survey of the prevalence of vitamin A deficiency and also undernutrition during the dry season in a random sample of 1,259 children (n = 442 for the 2-6 years and n = 817 for the 7-14 years) from a rural area in Senegal. Prevalence was 0 times and 4.2 times the WHO criteria for xerophthalmia and deficient serum retinol levels, respectively in preschool children. Abnormal ICT results were more frequent in preschool than in school children (53.4% versus 21.0%). There was an association between abnormal ICT results and stunting. Vitamin A deficiency was a public health problem in preschool children as assessed by the biochemical criterion (20.9% of serum retinol values under 0.35 mumol/l) or the cytological cut-off (53.4% of abnormal ICT results) but was also found in school children (21.0% of abnormal ICT results).

We have constructed and used an integrative vector, pAT112, that takes advantage of the transposition properties (integration and excision) of transposon Tn1545. This 4.9-kb plasmid is composed of: (i) the replication origin of pACYC184; (ii) the attachment site (att) of Tn1545; (iii) erythromycin-and kanamycin-resistance-encoding genes for selection in Gram- and Gram+ bacteria; and (iv) the transfer origin of IncP plasmid RK2, which allows mobilization of the vector from Escherichia coli to various Gram+ recipients. Integration of pAT112 requires the presence of the transposon-encoded integrase, Int-Tn, in the new host. This vector retains the insertion specificity of the parental element Tn1545 and utilises it to carry out insertional mutagenesis, as evaluated in Enterococcus faecalis. Since pAT112 contains the pACYC184 replicon and lacks most of the restriction sites that are commonly used for molecular cloning, a gene from a Gram+ bacterium disrupted with this vector can be recovered in E. coli by cleavage of genomic DNA, intramolecular ligation and transformation. Regeneration of the gene, by excision of pAT112, can be obtained in an E. coli strain expressing the excisionase and integrase of Tn1545. The functionality of this system was illustrated by characterization of an IS30-like structure in the chromosome of En. faecalis. Derivatives pAT113 and pAT114 contain ten unique cloning sites that allow screening of recombinants having DNA inserts by alpha-complementation in E. coli carrying the delta M15 deletion of lacZ alpha. These vectors are useful to clone and introduce foreign genes into the genomes of Gram+ bacteria.

The distributions of tet(M) and conjugative transposons related to Tn1545 were studied by hybridization in 47 clinical isolates of Streptococcus pneumoniae resistant to tetracycline. Resistance to tetracycline was always associated with resistance to minocycline and was due to the presence of the tet(M) gene. Association of tet(M) with int-Tn, the gene encoding the protein required for the movements of Tn1545-like transposons, was found in all but one strain of S. pneumoniae. In contrast, int-Tn was detected in only 2 of 37 strains of Staphylococcus spp. harboring tet(M).

The mobilizable shuttle cloning vectors, pAT18 and pAT19, are composed of: (i) the replication origins of pUC and of the broad-host-range enterococcal plasmid pAM beta 1; (ii) an erythromycin-resistance-encoding gene expressed in Gram- and Gram+ bacteria; (iii) the transfer origin of the IncP plasmid RK2; and (iv) the multiple cloning site and the lacZ alpha reporter gene of pUC18 (pAT18) and pUC19 (pAT19). These 6.6-kb plasmids contain ten unique cloning sites that allow screening of derivatives containing DNA inserts by alpha-complementation in Escherichia coli carrying the lacZ delta M15 deletion, and can be efficiently mobilized by self-transferable IncP plasmids co-resident in the E. coli donors. Plasmids pAT18, pAT19 and recombinant derivatives have been successfully transferred by conjugation from E. coli to Bacillus subtilis, Bacillus thuringiensis, Listeria monocytogenes, Enterococcus faecalis, Lactococcus lactis, and Staphylococcus aureus at frequencies ranging from 10(-6) to 10(-9). The presence of a restriction system in the recipient dramatically affects (by three orders of magnitude) the efficiency of conjugal transfer of these vectors from E. coli to Gram+ bacteria.

The evaluation of the prevalence of ophthalmological diseases and vitamin A deficiency in Senegalese preschool-aged children enabled us to confirm the method of impression cytology with transfer (ICT) and to assess the impact of ophthalmological diseases on the cytological appearance of conjunctival cells. A simplification of the ICT method consisted of transferring cells present on a strip of paper to a glass slide by finger pressure. Harris-Schorr staining of the sample papers confirmed the results obtained by the transfer. Inflammatory trachoma influenced the results of the test. This simple method will prove very helpful for detection of vitamin A deficiency in children in underdeveloped areas.

Two hundred and six Senegalese preschool children included in an epidemiological study were selected by their results from impression cytology with transfer (ICT) for assessment of their nutritional state by means of biological variables and for assessment of the diagnostic values of the ICT. A problem of protein-calorie malnutrition existed (transthyretin and retinol-binding protein concentrations were low) associated with vitamin A deficiency (retinol concentrations were low). The sensitivity and specificity of the ICT defined with respect to retinol (threshold fixed at 0.35 mumol/L) varied with the classification criteria of ICT and seemed to be fairly insensitive but specific.

The purpose of our study was to determine the prevalence of protein-calorie malnutrition (PCM), ocular diseases, and vitamin A deficiency in preschool children selected at random in a rural zone of the groundnut belt of Senegal. The prevalence of PCM was 37.1% (95% CI 33.8-40.2%) according to the Waterlow classification, with a majority of stunting, and prevalence of hypovitaminosis A was estimated to be 11.4% (95% CI 9.3-13.5%) by using impression cytology. Furthermore, 19.4% (95% CI 15.8-22.0%) of the children might be defined at risk of deficiency. The prevalence of Bitot's spots was equal to 0.2% (95% CI 0.03-0.9%). A problem of PCM associated with a health-endangering vitamin A deficiency existed.

Aminoglycoside-resistant strains of Staphylococcus and Enterococcus, approximately 500 of each, were screened by dot blot hybridization for the presence of genes encoding aminoglycoside-modifying enzymes. The MICs of various aminoglycosides for the strains were determined, and the enzyme contents of the cells were inferred from the resistance phenotypes. The agreements (in percent) of the hybridization results with the deduced enzyme contents for Staphylococcus and Enterococcus species were, respectively, 80 and 87.6 for ANT(6) (aminoglycoside nucleotidyltransferase), 99.8 and 100 for both APH(3') (aminoglycoside phosphotransferase) and APH(2")-AAC(6') (aminoglycoside acetyltransferase), and 100 and 100 for ANT(4'). The weak correlation obtained with the probe for ANT(6) was due to the fact that gram-positive cocci can also be streptomycin resistant by synthesis of APH(3") or ANT(3")(9) and by ribosomal mutation. The remaining probes appeared to be specific: they hybridized with all the resistant clinical isolates but not with the susceptible strains. These results indicate that, except for streptomycin, nucleic acid hybridization is a valid approach for the detection and characterization of aminoglycoside resistance in gram-positive cocci.

Excision of Tn1545 and related conjugative transposons of Gram-positive bacteria occurs by reciprocal site-specific recombination between non-homologous regions of the transposon-target junctions. Excisive recombination requires two transposon-encoded proteins designated Xis-Tn and Int-Tn. We have shown that, following excision, Tn1545 is a circular structure with ends separated by either of the two hexanucleotides that were present at the transposon-target junctions. Using a trans-complementation assay, we have demonstrated that Int-Tn is able to catalyse in vivo integration of a circular intermediate of Tn1545 defective for integration and excision. comparison of integration sites suggests that limited sequence homology at the vicinity of the recombining sites is required for integration of the element. These data support the hypothesis that the integration/excision systems of conjugative transposons from Gram-positive cocci and of lambdoid phages from Gram-negative bacilli have evolved from a common ancestor.

Enterococcus faecium BM4102 was resistant to macrolide-lincosamide-streptogramin B-type (MLS) antibiotics; tetracycline-minocycline; and high levels of kanamycin, neomycin, tobramycin, and dibekacin but not gentamicin. This aminoglycoside resistance phenotype is new in enterococci. The genes conferring resistance to aminoglycosides and MLS antibiotics in this strain were carried on a plasmid, pIP810, that was self-transferable to to other Enterococcus strains. Resistance to tobramycin and structurally related aminoglycosides, kanamycin, neomycin, and dibekacin, was due to synthesis of a 4',4"-aminoglycoside nucleotidyltransferase. Homology was detected by hybridization between pIP810 DNA and a probe specific for a gene encoding an enzyme with identical site specificity in staphylococci. The bacteriostatic activity of amikacin apparently was not affected by the presence of the enzyme, although it was modified in vitro. However, the bactericidal activity of amikacin and the synergism of this aminoglycoside with penicillin were abolished.