Modifications neurocomportementales secondaires à la sclérose en plaques [Neurobehavioral changes occurring during multiple sclerosis]

Behavioral changes occurring in patients affected by multiple sclerosis (MSI are often neglected by physicians but are actually part of the clinical spectrum of the disease. In addition, they are known to be responsible for a decline in the quality of life of MS patients. Recently, there has been a growing interest to investigate changes in the emotional experience of MS patients and their decision making, showing that the ability to take advantageous decisions was altered in MS. This paper reviews existing data on this topic.

An easy and safe procedure for temporal artery biopsy.

BACKGROUND: Temporal arteritis is a very serious form of vasculitis. Early treatment is essential to avoid blindness. Surgical biopsy of the temporal artery is the gold standard for the diagnosis, but facial nerve injuries may occur. OBJECTIVE: To describe a simple and safe procedure for temporal artery biopsy. METHODS: Case report. RESULTS: A 62-year-old-woman with presumed temporal arteritis was referred. Precise localization of temporal arteries and its branches was obtained with color duplex ultrasonography. Arterial wall thickening (halo sign) was observed in the affected arterial segments. A frontal branch was precisely localized and infiltrated with 1% lidocaine. About 1 cm was removed for histopathologic examination. Thirty minutes was required to perform this outpatient procedure. The diagnosis of temporal arteritis was confirmed, and the patient was rapidly and successfully treated with prednisone. CONCLUSIONS: Color duplex ultrasonography allows precise localization of temporal arteries and its branches. This echocardiography-guided surgical procedure is easy and safe. Most dermatologic surgeons can perform it.

Transapical aortic valve implantation without angiography: proof of concept.

Background: Cardiac computed tomographic scans, coronary angiograms, and aortographies are routinely performed in transcatheter heart valve therapies. Consequently, all patients are exposed to multiple contrast injections with a following risk of nephrotoxicity and postoperative renal failure. The transapical aortic valve implantation without angiography can prevent contrast-related complications. Methods: Between November 2008 and November 2009, 30 consecutive high-risk patients (16 female, 53.3%) underwent transapical aortic valve implantation without angiography. The landmarks identification, the stent-valve positioning, and the postoperative control were routinely performed under transesophageal echocardiogram and fluoroscopic visualization without contrast injections. Results: Mean age was 80.1 +/- 8.7 years. Mean valve gradient, aortic orifice area, and ejection fraction were 60.3 +/- 20.9 mm Hg, 0.7 +/- 0.16 cm(2), and 0.526 +/- 0.128, respectively. Risk factors were pulmonary hypertension (60%), peripheral vascular disease (70%), chronic pulmonary disease (50%), previous cardiac surgery (13.3%), and chronic renal insufficiency (40%) (mean blood creatinine and urea levels: 96.8 +/- 54 mu g/dL and 8.45 +/- 5.15 mmol/L). Average European System for Cardiac Operative Risk Evaluation was 32.2 +/- 13.3%. Valve deployment in the ideal landing zone was 96.7% successful and valve embolization occurred once. Thirty-day mortality was 10% (3 patients). Causes of death were the following: intraoperative ventricular rupture (conversion to sternotomy), right ventricular failure, and bilateral pneumonia. Stroke occurred in one patient at postoperative day 9. Renal failure (postoperative mean blood creatinine and urea levels: 91.1 +/- 66.8 mu g/dL and 7.27 +/- 3.45 mmol/L), myocardial infarction, and atrioventricular block were not detected. Conclusions: Transapical aortic valve implantation without angiography requires a short learning curve and can be performed routinely by experienced teams. Our report confirms that this procedure is feasible and safe, and provides good results with low incidence of postoperative renal disorders. (Ann Thorac Surg 2010; 89: 1925-33) (C) 2010 by The Society of Thoracic Surgeons

Origin and outcome of multiple pregnancies in Bern, Switzerland, 1995-2006 and the current proposal of the Swiss parliament to revise the Swiss law of reproductive medicine: Switzerland quo vadis?

INTRODUCTION: Infertility treatments are a major source of the increase in multiple pregnancies (MPs). AIMS: The aims of the present study were (1.) to investigate the origin and maternal/neonatal outcomes of MP and (2.) to review the different measures that can be adopted to reduce these serious complications. METHODS: The study included all women with multiple births between 1 January 1995 and 31 December 2006 at the University Hospital of Bern, Switzerland. The outcomes associated with the various origins of MP (natural conception, ovarian stimulation [OS] ‒ in-vitro fertilisation [IVF-ICSI]) were analysed using a multinomial logistic regression model. An analysis of the Swiss law on reproductive medicine and its current proposed revision, as well as a literature review using Pubmed, was carried out. RESULTS: A total of 592 MP were registered, 91% (n = 537) resulted in live births. There was significantly more neonatal/maternal morbidity in MP after OS compared with natural conception and even with the IVF-ICSI group. With a policy of elective single embryo transfer (eSET), twin rates after IVF-ICSI can be reduced to <5% and triplets to <1%. CONCLUSIONS: After OS, more triplets are found and the outcome of MP is worse. MP is known to be associated with morbidity, mortality, and economic and social risks. To counteract these complications (1.) better training for physicians performing OS should be encouraged and (2.) the Swiss law on reproductive medicine needs to be changed, with the introduction of eSET policies. This would lead to a dramatic decrease in neonatal and maternal morbidity/mortality as well as significant cost reductions for the Swiss healthcare system.

A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL

Background: Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA) and total number of piglets born (TNB) in a three generation Iberian by Meishan F2 intercross. Results: The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P < 0.001) and SSC17 (P < 0.01) with effects on both traits. This relative paucity of significant results contrasted very strongly with the wide array of highly significant epistatic QTL that emerged in the bi-dimensional genome-wide scan analysis. As much as 18 epistatic QTL were found for NBA (four at P < 0.01 and five at P < 0.05) and TNB (three at P < 0.01 and six at P < 0.05), respectively. These epistatic QTL were distributed in multiple genomic regions, which covered 13 of the 18 pig autosomes, and they had small individual effects that ranged between 3 to 4% of the phenotypic variance. Different patterns of interactions (a × a, a × d, d × a and d × d) were found amongst the epistatic QTL pairs identified in the current work.Conclusions: The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17), dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.

Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events

Genomic plasticity of human chromosome 8p23.1 region is highly influenced by two groups of complex segmental duplications (SDs), termed REPD and REPP, that mediate different kinds of rearrangements. Part of the difficulty to explain the wide range of phenotypes associated with 8p23.1 rearrangements is that REPP and REPD are not yet well characterized, probably due to their polymorphic status. Here, we describe a novel primate-specific gene family, named FAM90A (family with sequence similarity 90), found within these SDs. According to the current human reference sequence assembly, the FAM90A family includes 24 members along 8p23.1 region plus a single member on chromosome 12p13.31, showing copy number variation (CNV) between individuals. These genes can be classified into subfamilies I and II, which differ in their upstream and 5′-untranslated region sequences, but both share the same open reading frame and are ubiquitously expressed. Sequence analysis and comparative fluorescence in situ hybridization studies showed that FAM90A subfamily II suffered a big expansion in the hominoid lineage, whereas subfamily I members were likely generated sometime around the divergence of orangutan and African great apes by a fusion process. In addition, the analysis of the Ka/Ks ratios provides evidence of functional constraint of some FAM90A genes in all species. The characterization of the FAM90A gene family contributes to a better understanding of the structural polymorphism of the human 8p23.1 region and constitutes a good example of how SDs, CNVs and rearrangements within themselves can promote the formation of new gene sequences with potential functional consequences.

Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy.

Anti-angiogenic therapies are currently in cancer clinical trials, but to date there are no established tests for evaluating the angiogenic status of a patient. We measured 11 circulating angiogenesis-associated molecules in cancer patients before and after local treatment. The purpose of our study was to screen for possible relationships among the different molecules and between individual molecules and tumor burden. We measured VEGF-A, PlGF, SCF, MMP-9, EDB+ -fibronectin, sVEGFR-2, sVEGFR-1, salphaVbeta3, sTie-2, IL-8 and CRP in the blood of 22 healthy volunteers, 17 early breast, 17 early colorectal, and 8 advanced sarcoma/melanoma cancer patients. Breast cancer patients had elevated levels of VEGF-A and sTie-2, colorectal cancer patients of VEGF-A, MMP-9, sTie-2, IL-8 and CRP, and melanoma/sarcoma patients of sVEGFR-1. salphaVbeta3 was decreased in colorectal cancer patients. A correlation between VEGF-A and MMP-9 was found. After tumor removal, MMP-9 and salphaVbeta3 significantly decreased in breast and CRP in colorectal cancer, whereas sVEGFR-1 increased in colorectal cancer patients. In sarcoma/melanoma patients treated regionally with TNF and chemotherapy we observed a rise in VEGF-A, SCF, VEGFR-2, MMP-9, Tie-2 and CRP, a correlation between CRP and IL-8, and a decreased in sVEGFR-1 levels. In conclusion, among all factors measured, only VEGF-A and MMP-9 consistently correlated to each other, elevated CRP levels were associated with tumor burden, whereas sVEGF-R1 increased after tumor removal in colorectal cancer. Treatment with chemotherapy and TNF induced changes consistent with an angiogenic switch. These results warrant a prospective study to compare the effect of surgical tumor removal vs. chemotherapy on some of these markers and to evaluate their prognostic/predictive value.

Multiple non-collinear TF-map alignments of promoter regions

Background: The analysis of the promoter sequence of genes with similar expression patterns isa basic tool to annotate common regulatory elements. Multiple sequence alignments are on thebasis of most comparative approaches. The characterization of regulatory regions from coexpressedgenes at the sequence level, however, does not yield satisfactory results in manyoccasions as promoter regions of genes sharing similar expression programs often do not shownucleotide sequence conservation.Results: In a recent approach to circumvent this limitation, we proposed to align the maps ofpredicted transcription factors (referred as TF-maps) instead of the nucleotide sequence of tworelated promoters, taking into account the label of the corresponding factor and the position in theprimary sequence. We have now extended the basic algorithm to permit multiple promotercomparisons using the progressive alignment paradigm. In addition, non-collinear conservationblocks might now be identified in the resulting alignments. We have optimized the parameters ofthe algorithm in a small, but well-characterized collection of human-mouse-chicken-zebrafishorthologous gene promoters.Conclusion: Results in this dataset indicate that TF-map alignments are able to detect high-levelregulatory conservation at the promoter and the 3'UTR gene regions, which cannot be detectedby the typical sequence alignments. Three particular examples are introduced here to illustrate thepower of the multiple TF-map alignments to characterize conserved regulatory elements inabsence of sequence similarity. We consider this kind of approach can be extremely useful in thefuture to annotate potential transcription factor binding sites on sets of co-regulated genes fromhigh-throughput expression experiments.

Complete Maxillo-Mandibular Syngnathia in a Newborn with Multiple Congenital Malformations.

Syngnathia is an extremely rare condition involving congenital fusion of the maxilla with the mandible. Clinical presentations vary from simple mucosal bands (synechiae) to complete bony fusion (synostosis). Most cases are unilateral incomplete fusions. We report the case of a severely growth-retarded newborn infant with complete synostosis of the mandible with the maxilla and the zygoma associated with cleft palate, choanal atresia, deafness, delayed cerebral white matter development, and genital and limb malformations. Extensive genetic analysis did not reveal any mutations. This association of multiple congenital malformations may represent an entity distinct from previously described syndromes associated with syngnathia.

δ 15N measurement of organic and inorganic substances by EA-IRMS: a speciation-dependent procedure

Little attention has been paid so far to the influence of the chemical nature of the substance when measuring δ 15N by elemental analysis (EA)-isotope ratio mass spectrometry (IRMS). Although the bulk nitrogen isotope analysis of organic material is not to be questioned, literature from different disciplines using IRMS provides hints that the quantitative conversion of nitrate into nitrogen presents difficulties. We observed abnormal series of δ 15N values of laboratory standards and nitrates. These unexpected results were shown to be related to the tailing of the nitrogen peak of nitrate-containing compounds. A series of experiments were set up to investigate the cause of this phenomenon, using ammonium nitrate (NH4NO3) and potassium nitrate (KNO3) samples, two organic laboratory standards as well as the international secondary reference materials IAEA-N1, IAEA-N2-two ammonium sulphates [(NH4)2SO4]-and IAEA-NO-3, a potassium nitrate. In experiment 1, we used graphite and vanadium pentoxide (V2O5) as additives to observe if they could enhance the decomposition (combustion) of nitrates. In experiment 2, we tested another elemental analyser configuration including an additional section of reduced copper in order to see whether or not the tailing could originate from an incomplete reduction process. Finally, we modified several parameters of the method and observed their influence on the peak shape, δ 15N value and nitrogen content in weight percent of nitrogen of the target substances. We found the best results using mere thermal decomposition in helium, under exclusion of any oxygen. We show that the analytical procedure used for organic samples should not be used for nitrates because of their different chemical nature. We present the best performance given one set of sample introduction parameters for the analysis of nitrates, as well as for the ammonium sulphate IAEA-N1 and IAEA-N2 reference materials. We discuss these results considering the thermochemistry of the substances and the analytical technique itself. The results emphasise the difference in chemical nature of inorganic and organic samples, which necessarily involves distinct thermochemistry when analysed by EA-IRMS. Therefore, they should not be processed using the same analytical procedure. This clearly impacts on the way international secondary reference materials should be used for the calibration of organic laboratory standards.

Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces.

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm(-2)) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

In vitro effect of malachite green on Candida albicans involves multiple pathways and transcriptional regulators UPC2 and STP2.

In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC(50)], 100 ng ml(-1)) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis.

Parallel Research, Multiple Intellectual Property Right Protection Instruments, and the Correlation among R&D Projects, September 2005

The choice of a research path in attacking scientific and technological problems is a significant component of firms’ R&D strategy. One of the findings of the patent races literature is that, in a competitive market setting, firms’ noncooperative choices of research projects display an excessive degree of correlation, as compared to the socially optimal level. The paper revisits this question in a context in which firms have access to trade secrets, in addition to patents, to assert intellectual property rights (IPR) over their discoveries. We find that the availability of multiple IPR protection instruments can move the paths chosen by firms engaged in an R&D race toward the social optimum.

Microbial contamination of procedure gloves after opening the container and during exposure in the environment

The objective of this study was to quantify the colony forming units (cfu) on latex procedure gloves in the beginning, middle, and end of the containers in real (professional) and controlled (researcher) gloving situations; evaluate the microbial load of the gloves, considering the time of exposure in the environment. This comparative prospective study was conducted at an intensive care unit of a teaching hospital. The microbiological data was collected from the gloves using digital-pressure. Microbiological evaluations were performed on 186 pairs of gloves: 93 in the control group and 93 in real gloving situations. In the control group, the average cfu was 4.7 against 6.2 in the real gloving situation. Hence, no statistically significant difference was found (p=.601). In addition, the cfu values of gloves in the beginning, middle and end of the containers also did not show any significant differences (p>.05). The most common strain was Staphylococcus spp. The time of exposure in the environment did not increase the cfu value of the latex gloves.

Education as a mirror of Spanish society: challenges and policies towards multiple diversity

The ways in which the dominant cultural majority frames the educationalsystem determine perceptions of its own identity and understandings ofthe ‘other.’ In this article I take a political approach, by examining themanagement of cultural diversity within Spanish education policies, treating“education as the mirror of society”. This article analyzes Spanish challengesand policies approaches towards the management of immigrationrelated diversity in education. The main finding is that there is not one approach,but several, due to both the decentralized character of the educationsystem and the multiplicity of diversity that is at stake (i.e. language,religion, culture etc.)