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What Is Known and Objective: The dofetilide label recommends using actual body weight (ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients., Methods: This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome., Results and Discussion: Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15)., What Is New and Conclusion: Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients., (© 2015 John Wiley & Sons Ltd.)

Objective: Trends indicate that clinical psychologists' theoretical orientations have changed over the last decades in North America, but research on this topic in Canada is scarce. We analyzed the orientation of psychologists over the last 20 years in the province of Quebec, where 46% of Canadian psychologists are located., Method: Data were collected annually through the board registration form of Quebec psychologists' professional order from 1993 to 2013. Univariate statistical analyses were realized on aggregated data., Results: In 20 years, the proportion of clinicians choosing cognitive-behavioral therapy (CBT) as their main orientation grew from 18.4% to 38%, while preference for other orientations slightly declined. Existential-humanistic and psychodynamic-psychoanalytic approaches remained the primary orientation for around 21.7% and 21.5%, respectively. In 2013 (N = 8608), when taking into account 2 choices of theoretical orientation, 55.8% of clinicians chose CBT, 34.3% existential-humanistic orientation, 27.9% psychodynamic-analytic theories, and 21.8% systemic-interactional orientation., Conclusions: Findings underline trends in Quebec clinical practice characterized by an increase in the number of psychologists identifying cognitive-behavioral approach as their primary self-reported theoretical orientation., (© 2015 Wiley Periodicals, Inc.)

Ebola virus disease (EVD) went in the space of a few months from being a forgotten tropical disease to a global "health emergency". The scope of this Ebola virus epidemic (Zaire strain), which has broken out in West Africa, its spread and the high number of deaths reported among frontline health workers are unprecedented. This article describes how a specialist hospital deals with imported cases of EVD., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

In intensive farmland habitats, pollination of wild flowers and crops may be threatened by the widespread decline of pollinators. The honey bee decline, in particular, appears to result from the combination of multiple stresses, including diseases, pathogens, and pesticides. The reduction of semi-natural habitats is also suspected to entail floral resource scarcity for bees. Yet, the seasonal dynamics and composition of the honey bee diet remains poorly documented to date. In this study, we studied the seasonal contribution of mass-flowering crops (rapeseed and sunflower) vs. other floral resources, as well as the influence of nutritional quality and landscape composition on pollen diet composition over five consecutive years. From April to October, the mass of pollen and nectar collected by honey bees followed a bimodal seasonal trend, marked by a two-month period of low food supply between the two oilseed crop mass-flowerings (ending in May for rapeseed and July for sunflower). Bees collected nectar mainly from crops while pollen came from a wide diversity of herbaceous and woody plant species in semi-natural habitats or from weeds in crops. Weed species constituted the bulk of the honey bee diet between the mass flowering crop periods (up to 40%) and are therefore suspected to play a critical role at this time period. The pollen diet composition was related to the nutritional value of the collected pollen and by the local landscape composition. Our study highlights (1) a food supply depletion period of both pollen and nectar resources during late spring, contemporaneously with the demographic peak of honey bee populations, (2) a high botanical richness of pollen diet, mostly proceeding from trees and weeds, and (3) a pollen diet composition influenced by the local landscape composition. Our results therefore support the Agri-Environmental Schemes intended to promote honey bees and beekeeping sustainability through the enhancement of flower availability in agricultural landscapes.

Invertebrate and vertebrate development relies on complex processes that require many coordinated cell functions including cell adhesion, migration, proliferation and polarization. These processes depend on tissues and are spatio-temporally regulated by specific interactions between cells and between cells and the extracellular matrices. The dystroglycan, a transmembrane receptor that binds multiple extracellular matrix proteins, is expressed from oogenesis to organogenesis. There are increasing data suggesting that the axis, consisting of extracellular component-dystroglycan-cytoplasmic proteins, controls both the adhesion of cells to matrices as well as the transduction of signals coming from or directed to matrices. In this article, we review current advances leading to consider that the dystroglycan is a key protein nestled in an adhesome involved in mechanisms of cell adhesion during embryonic development., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The NLR is a prognostic factor for outcome and survival in cardiology, oncology and digestive surgery. NLR has not yet been studied in HF., Methods: Retrospective analysis of a prospective cohort of 247 consecutive patients, older than 65 years, operated for HF. Mortality at 12 months was registered, as the perioperative NLR values., Results: After hip surgery in the 247 patients (women 71%, median age 85 years, range: 66-102), the mortality was 27.2% [95%confidence interval (CI): 21.4-33.0] at 12 months. Univariate analysis detected four risk factors for mortality: age (Hazard Ratio (HR)--by 10 year-increments: 2.08 [95%CI: 1.37-3.17], P<0.001), male gender (HR: 1.92 [95%CI: 1.17-3.14], P=0.009, MCM (≥3) (HR: 1.71 [95%CI: 1.006-2.92], P=0.047 and NLR>5 at day 5 (HR: 1.8 [95%CI: 1.11-2.94], P=0.002). In multivariate analysis, two factors remained significantly associated with mortality: age (HR: 2.28 [95%CI: 1.49-3.47], P<0.001) and male gender (HR: 2.26 [95%CI: 1.38-3.72], P=0.001). Two independent risk factors of postoperative cardiovascular complications were identified: NLR>5 at day 5 (Odds Ratio (OR): 3.34 [95%CI: 2.33-4.80], P=0.001) and MCM (OR: 3.04 [95%CI: 2.16-4.29], P=0.006). A higher risk of infection was independently associated with a NLR>5 at day 5 (OR: 2.12 [95%CI: 1.44-3.11], P=0.02)., Conclusions: The NLR at fifth postoperative day is a risk factor of postoperative mortality and cardiovascular complications., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Current orthodontic treatments must answer an increasing demand for faster yet as efficient treatments, especially in adult patients. These past years, the amelioration of orthodontic, anesthetic and orthognathic surgery techniques have allowed considerable improvement of orthodontico-surgical treatments and of adult orthodontic treatments. Alveolar corticotomy (an example of such techniques) accelerates orthodontic tooth movements by local modifications of bone metabolism, inducing a transient osteopenia. This osteopenia allows greater tooth movements than conventional techniques. Whereas there is a growing understanding of the underlying biological mechanisms of alveolar corticotomies, there is little data regarding the osteogenic potential of such technique. In the present article, we review the literature pertaining to alveolar corticotomies and their underlying biological mechanisms and present a clinical case underlining the osteogenic potential of the technique., (© EDP Sciences, SFODF, 2015.)

During the H1N1 pandemic, governments tailored their communications plans in order to influence risk perception and promote public compliance with the public health plan measures. Considering the volume and the content of calls to flu information centres as indicators of the public risk perception, this mixed method study compares the relation between public communications, risk perception and immunization behaviour in Quebec and France. Results suggest that advocating for clear information and coordination between health authorities and the media promotes adherence to preventive behaviour. However, over-exaggerating the risks and minimizing the population's agency may undermine health authority credibility., (© The Author(s) 2013.)

Introduction: Early integrated palliative care is recommended in patients with incurable disease. Despite their development, hospital-based palliative care teams (PCT) are introduced late in the course of standard oncology care. The objective of this study is to describe the activity of an academic hospital-based PCT, using a standard format, which integrates indicators of early introduction and quality of end of life care, thus allowing a systematic analysis of its practice., Methods: The annual activity of the PCT is described from 2007 to 2012. Data are collected for each patient prospectively by the team: reasons for referral and activities of PCT, performance status and chemotherapy at the time of first referral, visit to emergency and admission to ICU., Results: The number of patients referred to the PCT increased from 337 patients in 2007 to 539 in 2012, among whom 90% were cancer patients, 84% at metastatic stage. Relief of symptoms was the most frequent reason for referral. In 2012, 280 (64%) patients were receiving chemotherapy and 41% had a PS≤2 at the time of first referral. Half patients died each year (270 in 2012); 17% of these received chemotherapy in their last 14 days of life, 3% visited emergency room twice and 13% were admitted in ICU, once during their last month of life, 48% died in hospice or at home., Conclusion: The use of a standard format to describe the activity of hospital-based PCTs, the timing of their introduction and the quality of care is feasible. The generalization of this format for monitoring to assess the curative medicine interface/palliative could be a lever for improving the integration of palliative care., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Theory of Mind refers to the ability to infer other’s mental states, their beliefs, intentions, or knowledge. To date, only two studies have reported the presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the present study,we evaluated 20 MCI patients and compared them with 25 healthy control participants using two Theory of Mind tasks. The first task was a false belief paradigm as frequently used in the literature, and the second one was a referential communication task,assessing Theory of Mind in a real situation of interaction and which had never been used before in this population. The results showed that MCI patients presented difficulties inferring another person’s beliefs about reality and attributing knowledge to them in a situation of real-life interaction. Two different patterns of Theory of Mind emerged among the patients. In comparison with the control group, some MCI patients demonstrated impairment only in the interaction task and presented isolated episodicmemory impairment, while others were impaired in both Theory of Mind tasks and presented cognitive impairment impacting both episodic memory and executive functioning. Theory of Mind is thus altered in the very early stages of cognitive impairment even in real social interaction, which could impact precociously relationships in daily life.

Dystroglycan (Dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. The function of Dg was examined in Xenopus laevis embryos by knockdown of Dg and overexpression and replacement of the endogenous Dg with a mutated form of the protein. This analysis revealed that Dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuoles. Using mutations in the cytoplasmic domain, we identified two sites that are involved in cell polarization and are required for mediolateral cell intercalation, and a site that is required for vacuolation. Furthermore, using a proteomic analysis, the cytoskeletal non-muscle myosin IIA has been identified for the first time as a molecular link between the Dg-cytoplasmic domain and cortical actin. The data allowed us to identify the adhesome laminin-Dg-myosin IIA as being required to maintain the cortical actin cytoskeleton network during vacuolation, which is crucial to maintain the shape of notochordal cells., (© 2014. Published by The Company of Biologists Ltd.)

This cross-sectional study conducted in prisons in the city of Salvador, Bahia, Brazil, investigated the association between the presence of psychiatric disorders in 462 prisoners and the types of crimes committed by them. Psychiatric diagnosis was obtained by means of the Brazilian Portuguese version of the Mini-International Neuropsychiatric Interview. A statistically significant association was found between some psychiatric disorders and specific groups of crime: lifelong substance addiction with sex crimes and homicide; antisocial personality disorder with robbery and with kidnapping and extortion; borderline personality disorder with sex crimes; and lifelong alcohol addiction with fraud and conspiracy and with armed robbery and murder. It was concluded that the mental disorders considered more severe (psychosis and bipolar disorder) were not associated with violent crimes, suggesting that the severity of the psychotic disorder may be the factor that has caused psychosis to be associated with violent crimes in previous studies., (© 2014 American Academy of Forensic Sciences.)

In a recent article, Achim et al. (2013) discussed the different sources of information that contribute to mentalizing judgments in current theory-of-mind (ToM) tasks. The authors rightly emphasized the dynamic aspect of real-life social interaction, suggesting that taking account of the ongoing changes occurring during social interaction would make ToM tasks more ecological. They proposed a framework (i.e., the Eight Sources of Information Framework) that specifies the 8 sources of information we get from the environment and/or from our memories to attribute mental states to others. Nevertheless, we believe that a central aspect of ToM is missing in this framework: the engagement (or not) of the participant in the social interaction during ToM assessment. Indeed, this framework fails to consider how the participant who takes part in the ToM task manages this information, depending on the fact that he or she is involved in the interaction or not and how the information concerning the agent may impact the participant attribution of mental states. We reviewed several arguments and results from the ToM literature suggesting that merely observing a social interaction is not equivalent to participating in an interaction in terms of cognitive processes involved in the attribution of mental states to others., ((c) 2013 APA, all rights reserved.)

Theory of mind (TOM) refers to the ability to infer one's own and other's mental states. Growing evidence highlighted the presence of impairment on the most complex TOM tasks in Alzheimer disease (AD). However, how TOM deficit is related to other cognitive dysfunctions and more specifically to episodic memory impairment - the prominent feature of this disease - is still under debate. Recent neuroanatomical findings have shown that remembering past events and inferring others' states of mind share the same cerebral network suggesting the two abilities share a common process .This paper proposes to review emergent evidence of TOM impairment in AD patients and to discuss the evidence of a relationship between TOM and episodic memory. We will discuss about AD patients' deficit in TOM being possibly related to their difficulties in recollecting memories of past social interactions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study analyses the roles of collective self-esteem and religiosity in the relationship between discrimination and psychological distress among a sample of 432 recent immigrants from Haiti and Arab countries living in Montreal, Quebec. Collective self-esteem (CSE), religiosity, discriminatory experiences, and psychological symptoms of depression and anxiety were assessed. Regression analyses revealed direct negative effects of discrimination, CSE, and religiosity on psychological distress for the entire sample. CSE, however, also appeared to moderate the effects of discrimination on psychological distress. Participants with higher CSE reported lower levels of anxiety and depression as a result of discrimination compared to those who expressed lower CSE levels. The results suggest that the relationship between CSE, discrimination, and psychological distress must be reexamined in light of recent sociopolitical changes and the upsurge in ethnic and religious tensions following the war on terror.

Adherent-invasive Escherichia coli (AIEC) have previously been shown to induce gut inflammation in patients with Crohn's disease (CD). We developed a set of mannosides to prevent AIEC attachment to the gut by blocking the FimH bacterial adhesin. The crystal structure of the FimH lectin domain in complex with a lead thiazolylaminomannoside highlighted the preferential position for pharmacomodulations. A small library of analogues showing nanomolar affinity for FimH was then developed. Notably, AIEC attachment to intestinal cells was efficiently prevented by the most active compound and at around 10000-fold and 100-fold lower concentrations than mannose and the potent FimH inhibitor heptylmannoside, respectively. An ex vivo assay performed on the colonic tissue of a transgenic mouse model of CD confirmed this antiadhesive potential. Given the key role of AIEC in the chronic intestinal inflammation of CD patients, these results suggest a potential antiadhesive treatment with the FimH inhibitors developed.

Throughout the process of being treated for mood and anxiety disorders, people dream of the "normal life" that awaits them. However, post-therapy, the distinctiveness of clinical normality (i.e., reduced symptomatology) and social normativity become more apparent. In this article we suggest that for people who have long felt socially excluded because of their psychiatric symptoms, being "normally shy" or "normally awkward" is not enough. Instead they aspire to an ideal life. This confusion between means and ends, between a nonsymptomatic self, a normative self, and an ideal self, leads these individuals to long-term self-doubt and confusion about how to reach their elusive goals. Yet, their never-ending pursuit of normative ideals applies to "normal" and "abnormal" people alike. An analysis of narratives of exclusion allows us to reflect the life-long search for social inclusion via a normal life.

Dystroglycan (Dg) is a transmembrane protein involved both in the assembly and maintenance of basement membrane structures essential for tissue morphogenesis, and the transmission of signals across the plasma membrane. We used a morpholino knockdown approach to investigate the function of Dg during Xenopus laevis skin morphogenesis. The loss of Dg disrupts epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin, and organization of fibronectin in the extracellular matrix (ECM). Depletion of Dg also affects cell-cell adhesion, as shown by the reduction of E-cadherin expression at the intercellular contacts, without affecting the distribution of β(1) integrins. This was associated with a decrease of cell proliferation, a disruption of multiciliated-cell intercalation, and the down-regulation of the transcription factor P63, a marker of differentiated epidermis. In addition, we demonstrated that inhibition or activation of the Notch pathway prevents and promotes transcription of X-dg. Our study showed for the first time in vivo that Dg, in addition to organizing laminin in the ECM, also acts as a key signaling component in the Notch pathway.

Objectives: We compared the evolution of perception of discrimination from 1998 to 2007 among recent Arab (Muslim and non-Muslim) and Haitian immigrants to Montreal; we also studied the association between perception of discrimination and psychological distress in 1998 and 2007., Methods: We conducted this cross-sectional comparative research with 2 samples: one recruited in 1998 (n = 784) and the other in 2007 (n = 432). The samples were randomly extracted from the registry of the Ministry of Immigration and Cultural Communities of Quebec. Psychological distress was measured with the Hopkins Symptom Checklist-25., Results: The perception of discrimination increased from 1998 to 2007 among the Arab Muslim, Arab non-Muslim, and Haitian groups. Muslim Arabs experienced a significant increase in psychological distress associated with discrimination from 1998 to 2007., Conclusions: These results confirm an increase in perception of discrimination and psychological distress among Arab Muslim recent immigrant communities after September 11, 2001, and highlight the importance this context may have for other immigrant groups.

Surface properties of nanoparticles to be used for radioimmunotherapy need to be optimized to allow antibody conjugation while ensuring biocompatibility. We aimed to investigate cell adhesion and proliferation onto different coatings to be used for nanoparticles. C, CH(x) or SiO(x) coatings deposited onto glass coverslips by magnetron deposition as well as nitrogen functionalized materials synthetized using different reactive sputtering conditions and PPAA (plasma polymerized allylamine) coating, were compared. Amine functionalization did increase hydrophilicity in all the materials tested. Biocompatibility was assessed by measuring cell viability, morphology, attachment, spreading, and pro-inflammatory cytokine secretion. The results show that C and CN(x) were the most biocompatible substrates while SiO(x) and SiO(x)N(y) were the most toxic materials. PPAA coatings displayed unexpectedly an intermediate biocompatibility. A correlation could be observed between wettability and cell proliferation except for C coated surface, indicating that more complex processes than hydrophilicity alone are taking place that affect cell functions.

A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.

Caribbean and Filipino immigrant families in Canada have much in common: the women have often immigrated as domestic workers, first-generation children may be separated from their parents for long periods, and they must deal with negative stereotypes of their ethnic group. This transcultural study looks at the associations between family relations and adolescents' perceptions of both their own group and the host society, and analyzes how these affect their mental health. The results suggest that family cohesion plays a key role in shaping adolescents' perceptions of racism in the host country and in promoting a positive appraisal of their own community, thus highlighting the need for a systemic understanding of family and intergroup relations.

This brief report illustrates how the migration context can affect specific item validity of mental health measures. The SCL-25 was administered to 432 recently settled immigrants (220 Haitian and 212 Arabs). We performed descriptive analyses, as well as Infit and Outfit statistics analyses using WINSTEPS Rasch Measurement Software based on Item Response Theory. The participants' comments about the item You feel everything requires a lot of effort in the SCL-25 were also qualitatively analyzed. Results revealed that the item You feel everything requires a lot of effort is an outlier and does not adjust in an expected and valid fashion with its cluster items, as it is over-endorsed by Haitian and Arab healthy participants. Our study thus shows that, in transcultural mental health research, the cultural and migratory contexts may interact and significantly influence the meaning of some symptom items and consequently, the validity of symptom scales.

Dystroglycan (Dg) is a cell adhesion receptor for laminin that has been reported to play a role in skeletal muscle cell stability, cytoskeletal organization, cell polarity, and signaling. Here we show that Dg is expressed at both the notochord/somite and the intersomitic boundaries, where laminin and fibronectin are accumulated during somitogenesis. Inhibition of Dg function with morpholino antisense oligonucleotides or a dominant negative mutant results in the normal segmentation of the presomitic mesoderm but affects the number, the size, and the integrity of somites. Depletion of Dg disrupts proliferation and alignment of myoblasts without affecting XMyoD and XMRF4 expression. It also leads to defects in laminin deposition at the intersomitic junctions, whereas expression of integrin beta1 subunits and fibronectin assembly occur normally. Our results show that Dg is critical for both proliferation and elongation of somitic cells and that the Dg-cytoplasmic domain is required for the laminin assembly at the intersomitic boundaries. Developmental Dynamics 238:1332-1345, 2009. (c) 2008 Wiley-Liss, Inc.

This article describes a collaborative mental health care project for youths, implemented in Montreal in a multiethnic setting. The authors examine the adjustments needed in the shared-care model to address the complexity of cultural and cooperation issues raised in the provision of services to a multiethnic population. A preliminary qualitative evaluation of the project shows how first-line workers face many uncertainties, stemming from both the institutional context and the multicultural reality of the population served. Results from this study advance the hypothesis that although uncertainties may generate discomfort and confusion, they may also open a space for innovation and acceptance of otherness.

Experimental studies indicate that carbon nanotubes (CNTs) have the potential to induce adverse pulmonary effects, including alveolitis, fibrosis, and genotoxicity in epithelial cells. Here, we explored the physicochemical determinants of these toxic responses with progressively and selectively modified CNTs: ground multiwall CNTs modified by heating at 600 degrees C (loss of oxygenated carbon functionalities and reduction of oxidized metals) or at 2400 degrees C (annealing of structural defects and elimination of metals) and by grinding the material that had been heated at 2400 degrees C before (introduction of structural defects in a metal-deprived framework). The CNTs were administered intratracheally (2 mg/rat) to Wistar rats to evaluate the short-term response (3 days) in bronchoalveolar lavage fluid (LDH, proteins, cellular infiltration, IL-1beta, and TNF-alpha). The long-term (60 days) lung response was assessed biochemically by measuring the lung hydroxyproline content and histologically. In vitro experiments were also performed on rat lung epithelial cells to assess the genotoxic potential of the modified CNTs with the cytokinesis block micronucleus assay. The results show that the acute pulmonary toxicity and the genotoxicity of CNT were reduced upon heating but restored upon grinding, indicating that the intrinsic toxicity of CNT is mainly mediated by the presence of defective sites in their carbon framework.

Dystroglycan (Dg) is a laminin receptor that is expressed at the interface between the basement membrane and the cell membrane. Dg has been reported to play a role in skeletal muscle cell stability, morphogenesis of neuroepithelial tissues, and in regulating cytoskeletal organization, cell polarization, and cell signalling. In this study, we have focused our analysis on the expression of Dg-mRNA and protein at different developmental stages in the pronephros of Xenopus laevis. In order to study its role, we performed loss-of-function experiments mediated by Dg antisense morpholinos and dominant negative mutant. We show that Dg expression is first detectable when epithelialization begins in the pronephric anlage and persists later during tubulogenesis. Loss-of-function experiments induced a disorganization of the basement membrane, a drastic reduction of pronephric tubules and duct that can lead to a renal agenesis. A diminished proliferation of pronephric cell progenitors was also observed in Dg depleted embryos. Together, these data indicate that Dg plays a key role for laminin-1 assembly and pronephric cell anchoring to the basement membrane during early development of the pronephros. They also indicate that Dg may induce a signal transduction pathway controlling cell proliferation needed for the formation of tubules and their growth.

Purpose: To develop a reliable and feasible isokinetic fatigue protocol for the knee flexors and extensors in individuals with cerebral palsy (CP) who are ambulatory., Methods: Twelve subjects with CP, 10 to 23 years old, participated in the study. The protocol consisted of repeated maximum voluntary concentric knee flexion and extensions at 60 degrees /sec for a minimum of 35 repetitions. Fatigue Index (FI) and slope of the linear regression were computed. Reliability tests conducted a week later with five of the 12 subjects. Intraclass correlation coefficients were calculated for test-retest reliability., Results: All subjects completed 35 repetitions, with only half reaching a 50% decline. All fatigue parameters were reliable for both knee flexors and extensors (slope: 0.94 and 0.97; slope/peak torque: 0.83 and 0.99; FI: 0.73 and 0.86, respectively)., Conclusions: This isokinetic fatigue protocol is reliable and feasible for children and young adults with mild to moderate CP.

A small library of simple 1,4-disubstituted 1,2,3-triazoles was prepared using a known one-pot procedure starting from organic halides and terminal alkynes. The compounds were then tested for their antibacterial activity against normal and resistant species of Staphylococcus aureus.

The synthesis based on palladium catalytic coupling of 38 new-arylated benzo[b]thiophenes or thiophenes is described in a few steps. We also report the direct arylation of the position 3 of the benzo[b]thiophenic structure, a 'one pot' 2,5-heterodiarylation of thiophenes as well as the synthesis of precursors of amino-acids with a 2-arylated benzo[b]thiophene core. These compounds were evaluated on bacteria strains: most of them did not exhibit any antibiotic activity but were found to selectively inhibit the NorA multidrug transporter of Staphylococcus aureus. As such, they restored the activity of the NorA substrates ciprofloxacin against a resistant S. aureus strain in which this efflux pump is over-expressed.

Extracts from various organs of 25 plants of Brazilian traditional medicine were assayed with respect to their anti-bacterial activities against Escherichia coli, a susceptible strain of Staphylococcus aureus and two resistant strains of Staphylococcus aureus harbouring the efflux pumps NorA and MsrA. Amongst the 49 extracts studied, 14 presented anti-bacterial activity against Staphylococcus aureus, including the ethanolic extracts from the rhizome of Jatropha elliptica, from the stem barks of Schinus terebinthifolius and Erythrina mulungu, from the stems and leaves of Caesalpinia pyramidalis and Serjania lethalis, and from the stem bark and leaves of Lafoensia pacari. The classes of compounds present in the active extracts were determined as a preliminary step towards their bioactivity-guided separation. No extracts were active against Escherichia coli.

The purpose of this study was to compare long-term outcomes of multi-level surgery with and without rectus femoris transfer (RFT) in a group of children with cerebral palsy. Forty-one subjects with a diagnosis of cerebral palsy were divided into a RFT group (28 subjects with 50 sides) and non-RFT group (13 subjects with 22 sides). The study protocol included pre-operative gait analysis, multi-level orthopedic surgical intervention, one year post-operative gait analysis, and three year or greater post-operative gait analysis. All participants received inpatient physical therapy for 2-12 weeks either following surgery or following a period of immobilization, depending on surgical procedures performed. Results showed improved peak knee flexion during swing phase (PKFS) for the RFT group one year after surgery. The deviation from normal in PKFS in the RFT group improved, on average, from seven to five degrees. The deviation from normal in PKFS in the non-RFT group increased approximately four degrees in the same period of time. The knee flexion swing range (KFSR) of the RFT group increased dramatically by 11 degrees after surgery, where no significant KFSR changes observed in the non-RFT group. Those parameters maintained relatively stable from one to three years post surgery for both groups. These observations support our hypothesis that improvements after RFT surgery persist over time, counteracting the negative effects of growth and time.

Carbon nanotubes focus the attention of many scientists because of their huge potential of industrial applications, but there is a paucity of information on the toxicological properties of this material. The aim of this experimental study was to characterize the biological reactivity of purified multi-wall carbon nanotubes in the rat lung and in vitro. Multi-wall carbon nanotubes (CNT) or ground CNT were administered intratracheally (0.5, 2 or 5 mg) to Sprague-Dawley rats and we estimated lung persistence, inflammation and fibrosis biochemically and histologically. CNT and ground CNT were still present in the lung after 60 days (80% and 40% of the lowest dose) and both induced inflammatory and fibrotic reactions. At 2 months, pulmonary lesions induced by CNT were characterized by the formation of collagen-rich granulomas protruding in the bronchial lumen, in association with alveolitis in the surrounding tissues. These lesions were caused by the accumulation of large CNT agglomerates in the airways. Ground CNT were better dispersed in the lung parenchyma and also induced inflammatory and fibrotic responses. Both CNT and ground CNT stimulated the production of TNF-alpha in the lung of treated animals. In vitro, ground CNT induced the overproduction of TNF-alpha by macrophages. These results suggest that carbon nanotubes are potentially toxic to humans and that strict industrial hygiene measures should to be taken to limit exposure during their manipulation.

Proteins often stabilize food emulsions and are also able to promote or delay lipid oxidation in complex systems. The purpose of this work was to investigate the relationship between metal ion availability and oxidative stability of oil-in-water emulsions stabilized by bovine serum albumin (BSA) or sodium caseinate (NaCas). Emulsions with similar and stable droplet size distributions were prepared with stripped sunflower oil (30 vol %) and protein solutions (20 g L(-)(1); pH = 6.5). In the absence of the water-soluble metal chelator EDTA, oxygen uptake, conjugated dienes, and volatile compounds developed faster in NaCas-stabilized emulsions than in those prepared with BSA. This effect is attributed to the chelating properties of NaCas and to electrostatic interactions that attract some metal ions at the interface where they could initiate lipid oxidation. When EDTA (100 muM) was present, oxidation was delayed to a greater extent in emulsions made with NaCas than in BSA stabilized emulsions. These conditions probably enabled NaCas to exert free-radical-scavenging activity.

Introduction: A study on the relationship between the ANDEM--Agence Nationale pour le Développement de l'Evaluation Médicale (French agency for the development of health technology assessment) and the learned societies showed that a definition of the role of these organisations and criteria to define learned societies were lacking. We conducted a survey among the learned societies in the field of medicine so as to elaborate a definition., Methods: We used the files of the learned societies of the Anaes--Agence Nationale d'Accréditation et d'Evaluation en Santé (French Agency for accreditation and evaluation in health) in 1998, which included 225 organisations. We sent a letter together with a single-page questionnaire and copies of the 2 publications on the relationship between the ANDEM and the learned societies. To analyse the suggestions for a definition, having read the replies, a segmentation of the population, the means and modalities of action and the aims and fields of action were used. A proposal for a definition was discussed during 2002/2003 with the board of the Fédération des Spécialités Médicales (FSM) (Federation of medical specialties) regrouping 33 medical and 12 surgical societies. Three meetings between a representative of the Anaes and the board of the FSM resulted in the proposition of so-called "validation" criteria for learned societies. A search on the French Internet listing such societies was made using a research motor (March 20, 2004)., Results: Out of the 225 organisations contacted, 129 (57%) replied. Among the latter, 115 considered themselves as a learned society and 14 did not. Among the 115 organisations defining themselves as a learned society, 97 proposed a definition, 16 made use of the definitions proposed in the questionnaire and 81 proposed their own definition. The analysis identified 6 important elements (reporting, knowledge, education, research, diffusion, promotion). The data analysed permitted the elaboration of a definition based on the proposals of the learned societies: "An organised group, within the framework of a given discipline, the members' aim of which is to report on their work, to improve knowledge on their discipline, to ensure education and research, to diffuse information on their work and research and to support and promote their discipline". Thirty-two of the 45 societies of the FSM accepted the 11 validation criteria proposed, some of which were commented on. Only one society abstained and 12 did not reply. No French Internet web site listing the learned societies specified a definition of criteria for inclusion in the lists., Discussion: A definition of the learned societies and validation criteria, obtained through the participation of the principle actors, could serve as a basis for the recognition and identification of such societies.

Dystroglycan is a cell surface receptor involved in the pathogenesis of muscular dystrophy, and plays a critical role in the assembly and homeostasis of basement membranes. Since data about the amphibian homologue are limited, we have cloned the full-length dystroglycan cDNAs from the frog Xenopus laevis. Using in situ hybridization, we show that mRNA expression is dynamic, particularly in the notochord at the end of gastrulation and during neurulation, suggesting that the protein might play unexplored roles in the specification and/or formation of this tissue. Subsequently, the transcripts are detected in the otic vesicle, the developing brain, and in mesenchymal cells of the visceral arches, as well as in pharyngeal endoderm, the pronephros, pronephric ducts, proctodaeum and the somites.

Driving the equilibrium between selenides and osmium(VIII) reagents with selenoxides and osmium(VI) by a subsequent reaction (rearrangement of allyl selenoxides to allyl alcohols or addition of osmium(VIII) species on C=C double bonds) to one side, allows the transformation of methyl geranyl selenides to linalool and of methyl citronellyl selenoxide to 6,7-dihydroxy citronellyl selenide.

To identify gene products important for gastrulation in the amphibian Pleurodeles waltl, a screen for regional differences in new protein expression at the early gastrula stage was performed. A 45 kDa protein whose synthesis was specific for progenitor endodermal cells was identified. Microsequencing and cDNA cloning showed that P45 is highly homologous to rat NUDC, a protein suggested to play a role in nuclear migration. Although PNUDC can be detected in all regions of the embryo, its de novo synthesis is tightly regulated spatially and temporally throughout oogenesis and embryonic development. New PNUDC synthesis in the progenitor endodermal cells depends on induction by the mesodermal cells in the gastrula. During development, PNUDC is localized in the egg cortical cytoplasm, at the cleavage furrow during the first embryonic division, around the nuclei and cortical regions of bottle cells in the gastrula, and at the basal region of polarized tissues in the developing embryo. These results show for the first time the expression and compartmentalization of PNUDC at distinct stages during amphibian development.

The DNA gyrases from Mycobacterium avium, Mycobacterium smegmatis and Mycobacterium fortuitum bv. peregrinum, which are species naturally resistant, moderately susceptible and susceptible to fluoroquinolones, respectively, were purified by affinity chromatography on novobiocin-Sepharose columns. The DNA gyrase inhibiting activities (IC50 values) of classical quinolones and fluoroquinolones were determined from the purified enzymes and were compared to the corresponding antibacterial activities (MICs). Regarding M. fortuitum bv. peregrinum, which is nearly as susceptible as Escherichia coli, the corresponding MIC and IC50 values of quinolones were significantly lower than those found for M. avium and M. smegmatis (e.g. for ofloxacin, MICs of 0.25 versus 32 and 1 microg ml(-1), and IC50 values of 1 versus 8 and 6 microg ml(-1), respectively). Such a result could be related to the presence of Ser-83 in the quinolone-resistance-determining region of the gyrase A subunit of M. fortuitum bv. peregrinum, as found in wild-type E. coli, instead of Ala-83 in M. avium and M. smegmatis, as found in fluoroquinolone-resistant E. coli mutants. The IC50 values of quinolones against the M. avium and M. smegmatis DNA gyrases were similar, while the corresponding MICs were 32-fold higher for M. avium when compared to M. smegmatis, suggesting that an additional mechanism, such as a low cell wall permeability or a drug efflux, could contribute to the low antibacterial potency of quinolones against M. avium.

In spite of much work on DNA gyrase and quinolones for many years, our knowledge of the molecular basis of quinolone-gyrase action is still incomplete. We designed a photoaffinity labeling reagent for the quinolone target, and synthesized a norfloxacin analogue with an azide function which, under UV irradiation, becomes covalently linked to its target. For that, a large amount of purified gyrase was needed. Both subunits were purified using exclusion and affinity chromatography. A plasmid was used that allowed the overproduction of GyrA as a fusion-protein with six histidine residues at its carboxy-terminal domain. GyrA-(His)6 was purified after chromatography on a nickel-containing column, and native GyrB after chromatography on immobilized novobiocin. Reconstituted DNA gyrase (A2B2) had supercoiling activity. Photoaffinity labeling showed covalent binding of the 3H-photoaffinity analogue of norfloxacin to the gyrase-DNA complex, and mainly to the GyrA. The specific binding site remains to be explored.

The contribution of autoantibodies, HLA markers and age to long-term estimates of risk of type 1 diabetes were examined after a median of 11 years (range 7.5-14) during the follow-up in a cohort of 234 siblings (aged 2-29 years) of French children with recent-onset type 1 diabetes, of whom 12 (5.1%) developed diabetes. We evaluated islet cell antibodies (ICA) by indirect immunofluorescence and autoantibodies to insulin (IAA), to the 65 kDa isoform of glutamic acid decarboxylase (GADA) and to the IA-2 protein (IA-2A) by radioligand assay in sequential serum samples. Among the 234 siblings of type 1 diabetic patients screened, 27 were positive for at least one antibody, 11 of whom progressed to develop type 1 diabetes during the follow-up (sensitivity, 92%, predictive value, 41%). Among the four antibodies tested individually, ICA had the highest sensitivity (83%) but a poor predictive value (59%) and IA-2A the highest predictive value (70%). IAA and GADA both exhibited poor sensitivity and predictive value. Combinations of antibodies achieved better predictive values than antibodies tested individually. Satisfactory predictive values were obtained for the combination of GADA with IA-2A (83%), for any combination of at least two antibodies other than ICA (70%) and for the combination of ICA with at least one other antibody (69%). The risk estimates were highest in the presence of three or four antibodies, whether comprising ICA or not, but with a concomitant loss of sensitivity. For most antibody combinations, cumulative risks showed progression from approximately 50% after 5 years to 100% after 13 years. HLA-DR3/4 was significantly more frequent in siblings developing type 1 diabetes than in non-diabetic siblings (9/12 vs. 39/217, relative risk (RR)=14, P

Using immunocytochemical methods, we analyzed the localization of the HSP70 protein constitutively expressed during embryogenesis in the amphibian Pleurodeles waltl. Our results provide evidence for nuclear transfer of the protein during gastrulation, and particularly for predominant nuclear labeling in gastrula internalized cells. Using two inhibitors of DNA replication -hydroxyurea (HUA) and aphidicolin- or/and an inhibitor of transcription -actinomycin D- applied to embryos, we demonstrated that nuclear transfer of HSP70 is related to the transcriptional activity of the cells during the early S phase of the cell cycle.

Pleurodeles exhibits a ZZ/ZW system of GSD (genotype sex determination). However, the Z and W sex chromosomes appear to be morphologically identical. A short RNA sequence is described that was specifically bound to lampbrush loops in the differential segment of the sexual bivalent IV. The distribution of these labeled loops in experimentally produced ZZ and WW females enabled us to demonstrate that such labeled loops were perfectly correlated with the W chromosome. Therefore, this RNA sequence constitutes an excellent marker for the W differential segment. Furthermore, analysis of the labeled loops under various experimental conditions suggested that their labeling is caused by specific interactions between this RNA sequence and lampbrush loop-associated proteins (RNA/protein interactions). North-western assays revealed that nuclear polypeptide(s) of 65 kDa could be responsible for such binding.

The optimal conditions capable of inducing an increase in HSP70 neosynthesis during development of the urodele amphibian Pleurodeles waltl were determined in this study. These conditions depend on temperature, heat shock duration and recovery duration. In oocytes, a heat shock response was repeatedly obtained at 37 degrees C for 15 min followed by 1 h recovery. These results provided evidence for heat shock response at every stage considered. An increase in HSP70 synthesis was noted throughout oogenesis, but it did not lead to an increase in the amount of soluble HSP70, except for stage VI oocytes. Such results suggest that from stage II to stage IV oocytes, an equilibrium occurs between the HSP70 used and the HSP70 neosynthesized. In contrast, in stage VI oocytes, heat shock led to overproduction of HSP70. During early development, the heat shock response was repeatedly obtained only from the gastrula stage with a 37 degrees C shock and a 15 min duration of treatment. Surprisingly, during cleavage stage, the soluble HSP70 total amount increased after heat shock at a time when no HSP70 neosynthesis occurred.