Aziz Chaouch

Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis

ABSTRACT Animal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles of Staphylococcus aureus surface adhesins and platelet aggregation in the infection process. In humans, however, S. aureus IE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions of S. aureus virulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 106 CFU of Lactococcus lactis pIL253 or a recombinant L. lactis strain expressing an individual S. aureus surface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred on L. lactis (ClfA strain) (52%; P = 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%; P < 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1β and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation of S. aureus IE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE.

Correlations Between Motor and Intellectual Functions in Normally Developing Children Between 7 and 18 Years

The relationship between motor and intellectual functions was examined in 252 healthy children from 7 to 18 years using the Zurich Neuromotor Assessment and standardized intelligence tests. The magnitude of Spearman correlations between neuromotor and intellectual scores was generally weak (r = 0.15–0.37). The strongest correlations were found between performance in the pegboard task and visuomotor intelligence (r = 0.35) and between contralateral associated movements and intelligence in boys (r = 0.37). We conclude that specific connections between motor and intellectual functions may exist. However, because the magnitude of correlations is generally weak, we suggest that motor and intellectual domains in healthy children are largely independent.

Neuromotor development in children. Part 3: motor performance in 3‐ to 5‐year‐olds

Aim  The aim of this cross‐sectional study was to provide normative data (ordinal scores and timed performances) for gross and fine motor tasks in typically developing children between 3 and 5 years of age using the Zurich Neuromotor Assessment (ZNA).

Prophylaxis of Experimental Endocarditis with Antiplatelet and Antithrombin Agents: a Role for Long-term Prevention of Infective Endocarditis in Humans?

BACKGROUND Infective endocarditis (IE) mostly occurs after spontaneous low-grade bacteremia. Thus, IE cannot be prevented by circumstantial antibiotic prophylaxis. Platelet activation following bacterial-fibrinogen interaction or thrombin-mediated fibrinogen-fibrin polymerization is a critical step in vegetation formation. We tested the efficacy of antiplatelet and antithrombin to prevent experimental IE. METHODS A rat model of experimental IE following prolonged low-grade bacteremia mimicking smoldering bacteremia in humans was used. Prophylaxis with antiplatelets (aspirin, ticlopidine [alone or in combination], eptifibatide, or abciximab) or anticoagulants (antithrombin dabigatran etexilate or anti-vitamin K acenocoumarol) was started 2 days before inoculation with Streptococcus gordonii or Staphylococcus aureus. Valve infection was assessed 24 hours later. RESULTS Aspirin plus ticlopidine, as well as abciximab, protected 45%-88% of animals against S. gordonii and S. aureus IE (P < .05). Dabigatran etexilate protected 75% of rats against IE due to S. aureus (P < .005) but failed to protect against S. gordonii (<30% protection). Acenocoumarol was ineffective. CONCLUSIONS Antiplatelet and direct antithrombin agents may be useful in the prophylaxis of IE in humans. In particular, the potential dual benefit of dabigatran etexilate might be reconsidered for patients with prosthetic valves, who require life-long anticoagulation and in whom S. aureus IE is associated with high mortality.

Infant motor milestones: poor predictive value for outcome of healthy children

The acquisition of motor skills is among the most remarkable achievements in the first years of life. Motor milestones such as the emergence of sitting without support or the first independent steps provide a framework for developmental monitoring of children in health supervision visits because these milestones belong to the most salient and best demarcated markers of developmental processes that parents and healthcare professionals can observe. In clinical practice, general paediatricians, child neurologists and developmental paediatricians are often asked to predict future outcomes on the basis of early developmental milestones. While there is some evidence from the study of preterms or children who have experienced early brain injury that a delay in motor development is a predictor of subsequent motor and cognitive problems [see e.g. (1)], the association between infant motor milestones and later developmental outcome in normal healthy children without risks is less clear. Several papers have been recently published assessing this relationship in large-scale birth cohorts [e.g. 1946 National Survey of Health and Development in the United Kingdom (2) or Northern Finland 1966 Birth Cohort (3,4)]. Although these studies described an association between early motor milestones and later developmental outcome, the magnitude of the reported effects was generally small and the findings were questioned by others (5). In fact, infant milestone information in these studies was acquired either at age 12 months (before all children were able to walk independently) or at 24 months (past the time most children learned to sit without support or made their first steps), and later cognitive functions were not measured with existing standards (5). In our longitudinal study of normally developing children, milestones were recorded at a time point contemporaneous with the emergence of motor milestones and later outcomes were repeatedly assessed up to 18 years using standardized intelligence and neuromotor tests. Our cohort consisted of 222 healthy, term-born individuals [119 boys, 103 girls, median gestational age 40 weeks, MAD (median absolute deviation) 1.2 weeks, range 37– 44 weeks; median birth weight 3.26 kg, MAD 0.4 kg, range 2.37–4.57 kg] of the Zurich Generational Study [community sample of children born between 1978 and 1993 (6)]. Participants did not have mental retardation [full-scale intelligence quotient (IQ) < 70] or a motor disorder that required therapeutic interventions (physiotherapy, occupational therapy, etc.). The mean socioeconomic status (SES) according to Largo et al. (7) was 8 (range 3–12). Informed consent was obtained at birth from the parents. The institutional review board of the Canton Zurich confirmed that the study was performed according to the Declaration of Helsinki and conformed to legal and ethical norms. All children were followed with comprehensive neurodevelopmental assessments from birth to age 18 years by experienced developmental paediatricians (visits at the centre at ages 1, 3, 6, 9, 12, 18 and 24 months, and then in yearly intervals). Depending on the outcome variable considered, between 79% and 85% of children with a milestone record participated in the endpoint visit at age 18 years, and these children were representative of those included at baseline (i.e. same age distribution for milestones). Parents were asked to record the date when their child achieved motor milestones. At each visit, the

Similarities and dissimilarities between the movement ABC-2 and the Zurich neuromotor assessment in children with suspected developmental coordination disorder.

An established tool for the assessment of motor performance in children with developmental coordination disorder (DCD) is the Movement-ABC-2 (M-ABC-2). The Zurich Neuromotor Assessment (ZNA) is also widely used for the evaluation of childrens motor performance, but has not been compared with the M-ABC-2. Fifty-one children (39 males) between 5 and 7 years of age with suspected DCD were assessed using the M-ABC-2 and the ZNA. Rank correlations between scores of different test components were calculated. The structure of the tests was explored using canonical-correlation analysis. The correlation between total scores of the two motor tests was reasonable (0.66; p<0.001). However, ZNA scores were generally lower than those of M-ABC-2, due to poor performance in the fine motor adaptive component and increased contralateral associated movements (CAM). The canonical-correlation analysis revealed that ZNA measures components like pure motor skills and CAM that are not represented in the M-ABC-2. Furthermore, there was also no equivalent for the aiming and catching items of the M-ABC-2 in ZNA. The two tests measure different motor characteristics in children with suspected DCD and, thus, can be used complementary for the diagnosis of the disorder.

Stability of cognitive performance in children with mild intellectual disability

Longitudinal studies that have examined cognitive performance in children with intellectual disability more than twice over the course of their development are scarce. We assessed population and individual stability of cognitive performance in a clinical sample of children with borderline to mild non‐syndromic intellectual disability.

Comparison between the Movement ABC-2 and the Zurich Neuromotor Assessment in Preschool Children.

An established test instrument for the assessment of motor performance in children between 3 and 16 years is the Movement Assessment Battery for Children – Second Edition (M-ABC-2). The Zurich Neuromotor Assessment (ZNA) is also widely used for the evaluation of children’s motor performance but has not been compared with the M-ABC-2 for children below five years for the purpose of convergent validity. Forty-seven children (26 boys, 21 girls) between three and five years of age were assessed using the M-ABC-2 and the ZNA3-5. Rank correlations between scores of different test components were calculated. Only low-to-moderate correlations were observed when separate components of these tests were compared (.31 to .68, p < .05), especially when involving the associated movements from the ZNA3-5 (−.05 to −.13, p > .05). However, the correlation between summary scores of the two tests was .77 (p < .001), and it increased to .84 when associated movements were excluded, which was comparable in magnitude to the test–retest reliability of the M-ABC-2, supporting convergent validity between the two tests. Although the ZNA3-5 and M-ABC-2 measure different aspects of motor behavior, the two instruments may thus measure essentially the same construct.

Impact of age, sex, socioeconomic status, and physical activity on associated movements and motor speed in preschool children

ABSTRACT Introduction: Young children generally show contralateral associated movements (CAMs) when they are making an effort to perform a unimanual task. CAM and motor speed are two relevant aspects of motor proficiency in young children. These CAMs decrease over age, while motor speed increases. As both CAM and motor speed are associated with age, we were interested in whether these two parameters are also linked with each other. Method: In this study, three manual dexterity tasks with the dominant and nondominant hands (pegboard, repetitive hand, and repetitive finger tasks) were used to investigate the effect of covariates (age, sex, socioeconomic status, total physical activity) on both motor speed and CAMs in preschool children. Results: There was a significant age effect for both motor speed and CAMs in all tasks when the dominant hand was used. When the nondominant hand was used, the decrease in the intensity of CAMs over age was not consistently significant. The influence of physical activity and socioeconomic status on motor proficiency was small. Furthermore, the correlation between motor speed and CAMs, although significant, was low. Conclusions: Motor speed improved with age over three fine motor tasks in preschool children. Decrease in CAMs was observed but it was not always significant when the nondominant hand was working. Motor speed and CAMs were only weakly associated. We conclude that the excitatory pathways responsible for motor speed and inhibitory pathways responsible for reducing CAMs occupy two different domains in the brain and therefore mostly behave independently of each other.

Neuromotor development in children. Part 4: new norms from 3 to 18 years

The aim of this cross‐sectional study was to provide normative data for motor proficiency (motor performance and contralateral associated movements [CAMs]) in typically developing children between 3 years and 18 years of age using an updated version of the Zurich Neuromotor Assessment (ZNA‐2).