Primary ectocervical epithelial cells display lower permissivity to Chlamydia trachomatis than HeLa cells and a globally higher pro-inflammatory profile.

The tumoral origin and extensive passaging of HeLa cells, a most commonly used cervical epithelial cell line, raise concerns on their suitability to study the cell responses to infection. The present study was designed to isolate primary epithelial cells from human ectocervix explants and characterize their susceptibility to C. trachomatis infection. We achieved a high purity of isolation, assessed by the expression of E-cadherin and cytokeratin 14. The infectious progeny in these primary epithelial cells was lower than in HeLa cells. We showed that the difference in culture medium, and the addition of serum in HeLa cultures, accounted for a large part of these differences. However, all things considered the primary ectocervical epithelial cells remained less permissive than HeLa cells to C. trachomatis serovar L2 or D development. Finally, the basal level of transcription of genes coding for pro-inflammatory cytokines was globally higher in primary epithelial cells than in HeLa cells. Transcription of several pro-inflammatory genes was further induced by infection with C. trachomatis serovar L2 or serovar D. In conclusion, primary epithelial cells have a strong capacity to mount an inflammatory response to Chlamydia infection. Our simplified purification protocol from human explants should facilitate future studies to understand the contribution of this response to limiting the spread of the pathogen to the upper female genital tract.

Action verbs drive motor activity in adolescents but not in children.

In adults, grip force has reliably been used to investigate motor simulation evoked by linguistic action, suggesting that motor phenomena are linked to semantic action. The parietal and frontal lobes and their connexions are essential neural structures for pragmatic aspects of hand semantic action. In this perspective, the aim of the study was to determine the extent to which two groups of children and adolescents, classically characterized by degree of axonal myelination in fronto-parietal circuits, monitored the occurrence of nouns and manual action verbs presented auditorily while holding a grip force sensor. Differential effects of grip force were seen only in the adolescents when monitoring action verbs. Interestingly, weaker effects of grip force were modulated by noun targets only in the younger children, revealing that the ability to profit from a full semantic representation of verbs is not clearly established in the younger children. Grip force modulation was observed as early as 300 ms post target onset and peaked at the 500-750 ms window of observation for both groups. These group differences are in line with the motor simulation difficulties seen in younger children. The results may also indicate that degree of grip force in response to specific linguistic categories parallels the maturation of the parietal-frontal circuits, including the anterior intra-parietal area which plays a determining role in semantic aspects of hand action.

Hand Switching Costs are not Uniform Across Response Components.

We investigated the extent to which a complex finger sequence impacts on hand switching costs in a sequential action. Response component latencies (premotor, motor, and movement) were compared in no-switch (same finger performed the action of pressing and reaching) and switch conditions (pressing with one finger and completing the reaching action with the homologous finger from the other hand). Results showed that the switch condition presented longer latency for premotor and movement components. For the motor component, however, switch condition was faster. This expands the previous literature investigating switching costs using simple finger movements in more complex tasks. A mechanical explanation of the interplay between response subcomponents is provided to explain the inversion of response pattern for the motor component.

A key for perinatal depression early diagnosis: The body dissatisfaction.

OBJECTIVE: To test if the evaluation of body dissatisfaction by images could be an interesting tool to detect perinatal depression early in pregnancy, questioning patients about their body image instead of their depressive symptoms. METHODS: A sample of 457 women was recruited in a longitudinal study. Three evaluations were performed at the 4th and 8th months of pregnancy and during post-partum. During these evaluations, sociodemographic data were collected and psychiatric scales were completed, including Edinburgh Postnatal Depression Scale (EPDS), Eating Disorder Examination-Questionnaire (EDE-Q), Pictorial Body Image Scale (PBIS) and Body Shape Questionnaire (BSQ). RESULTS: 33% of the women who were unsatisfied with their body image suffered from perinatal depression vs. 11.3% of the women who were not (p < 0.0001). The risk of perinatal depression was 4 times higher in women dissatisfied with their body image (p < 0.001) if unintended pregnancy and age are taken into account and is 3 times significantly higher in women with higher levels of eating disorders symptoms (p < 0.001) if unintended pregnancy and age are taken into account. Our sample was a privileged population, as often in the literature. CONCLUSION: The administration of a simple scale (PBIS) during an early visit during pregnancy allows detecting perinatal depression. This should prevent the stigmatization of women during pregnancy and reduce the risk of not diagnosing depression during pregnancy and post-partum.

Diagnostic accuracy of fetal rhesus D genotyping using cell-free fetal DNA during the first trimester of pregnancy.

BACKGROUND: Rhesus D genotyping with cell-free fetal DNA currently is used throughout the world. Although this technique has spread rapidly, its optimal use is still a matter of debate. This screening test has been introduced mainly for the treatment of RhD-negative pregnant women during the third trimester of pregnancy, thereby avoiding systematic anti-D prophylaxis, yet such a strategy has proved cost-ineffective. Publications reporting on fetal RHD genotyping with cell-free DNA in maternal plasma, specifically during the first trimester of pregnancy, are scarce in the scientific literature. OBJECTIVE: This study sought to assess the performance of noninvasive fetal Rhesus D genotyping in the first trimester of pregnancy with a single-exon real-time polymerase chain reaction assay. STUDY DESIGN: This was a retrospective observational multicenter study. Cell-free fetal DNA was extracted from maternal blood of both nonimmunized and immunized women at 10-14 weeks of gestation. RHD sequence was determined by quantitative polymerase chain reaction, with amplification of exon 10. Results were compared with RhD phenotype data that were obtained by cord blood sampling of neonates. RESULTS: In total, 416 serum samples from RhD-negative pregnant women were collected during the first trimester of pregnancy. The test's overall sensitivity and specificity were 100% (95% confidence interval, 96.9-100.0) and 95.2% (95% confidence interval, 90.5-97.6), respectively. The negative and positive predictive values were 99.8% (95% confidence interval, 94.9-100.0) and 97.1% (95% confidence interval, 94.2-98.6), respectively. Fetal RHD status was inconclusive in 9 cases (2.2%). CONCLUSION: Noninvasive fetal RHD determination by single-exon quantitative polymerase chain reaction during the first trimester of pregnancy exhibits high accuracy.

Interference effects between memory systems in the acquisition of a skill.

There is now converging evidence that the declarative memory system (hippocampus dependent) contributes to sequential motor learning in concert with the procedural memory system (striatum dependent). Because of the competition for shared neuronal resources, introducing a declarative memory task can impair learning of a new motor sequence and interference may occur during the procedural consolidation process. Here, we investigated the extent to which interference effects between memory systems are seen at the retrieval phase of skill learning. Healthy participants were assigned to a control (n = 15) or a declarative condition (n = 15) and trained on a sequence of finger movements (FOS task). Both groups showed similar improvement at the end of the practice session on the first day. Twenty-four hours later, controls were tested solely on the FOS task, while subjects in the declarative condition first engaged in a visuospatial task. Additional offline gains in performance were observed only in the control condition. The introduction of a visuospatial memory task just before retrieval of the motor skill was sufficient to eliminate these gains. This suggests that interference between procedural and declarative memory systems may also occur during subsequent motor recall. It is proposed that the interference effects are linked, in part, to the spatial nature of the motor and declarative tasks, which specifically depends upon hippocampal involvement.

Interference effects between manual and oral motor skills.

Consolidation of a motor skill is characterized by spontaneous improvement in performance between practice sessions. These offline gains can be eliminated if another skill is introduced soon afterward-a phenomenon called retroactive interference. Interference effects have been found in studies using two similar tasks involving the same motor effectors in a manual mode. The present study aimed to determine the extent to which differences in motor production mode modulate interference in skill learning. Healthy participants were assigned to one of three conditions and trained on a finger opposition sequence (FOS) learning task. All subjects were tested 24 h later on the original FOS learning task. Control subjects who were not exposed to a secondary learning task exhibited the expected offline gains after 24 h. Subjects who immediately learned a secondary task after the FOS training, either in the same manual mode (French Sign Language) or in an oral mode (CVC syllables), did not show any offline gains. Interestingly, the amount of interference was equivalent in the manual and oral learning conditions. The results reveal that interference effects in motor skill learning can occur when different effectors are involved in the primary and secondary tasks. The sequence processing abilities of the basal ganglia appear to play a major role in these interference effects.

Long-term cognitive effects of glucocorticoid excess in Cushing's syndrome.

CONTEXT AND OBJECTIVE: We previously found that patients with Cushing's syndrome (CS) scored lower than controls in several domains of cognitive function and that correction of hypercortisolism is not necessarily correlated with short-term improvement in intellectual performance. Here, we examined the long-term outcome in patients treated for CS by assessing the extent to which the detrimental effects of glucocorticoid (GC) excess on cognition can be reversed three years after corrective surgery. DESIGN: A battery of neuropsychological tests, including tests of attention, visuospatial processing, learning and memory, and executive functioning were administered pre-treatment and 12, 24 and 36 months post-treatment. PATIENTS AND CONTROL SUBJECTS: We included 18 patients with endogenous CS recruited before surgical treatment and 18 controls matched for age, sex and education. RESULTS: CS patients performed worse than controls on tests of attention, executive functioning and nonverbal aspects of memory. Moreover, at 36 months following eucortisolism, executive function performance and, to a lesser extent, attention tasks showed limited change compared to pre-treatment testing. CONCLUSION: Chronic hypercortisolism is accompanied by a deleterious impact on aspects of cognitive function. This negative effect on attention, executive performance and nonverbal memory seen in patients with CS suggests a differential effect of excess GCs upon different brain areas and networks. This influence persists years after the return to normal cortisol secretion levels.

Polarimetric imaging of uterine cervix: a case study.

We present a preliminary investigation of macroscopic polarimetric imaging of uterine cervix. Orthogonal state contrast (OSC) images of healthy and anomalous cervices have been taken in vivo at 550 nm. Four ex vivo cervix samples have been studied in full Muller polarimetry, at 550 nm and 700 nm, and characterized in detail by standard pathology. One sample was totally healthy, another one carried CIN lesions at very early stage (CIN1) in its visible exocervical region, while for the other two samples more advanced (CIN3) lesions were present, together with visible glandular epithelium (ectropion). Significant birefringence has been observed in the healthy regions of all six samples, both in vivo and ex vivo. Standard treatments of the Mueller images of the ex vivo samples allowed to quantify both retardation and depolarization. Retardation reached 60° in healthy regions, and disappeared in the anomalous regions of the other three ex vivo samples. The depolarization power was largest in healthy regions, and lower in CINs and ectropion. Possible origins of the observed effects are briefly discussed.

Influence of risperidone on balance control in young healthy individuals.

RATIONALE: It has previously been shown that impairment of postural stability is a side effect of typical antipsychotic drugs, which are largely administered to control psychosis and behavioral symptoms in elderly patients. Surprisingly, no study has yet addressed this problem with second-generation antipsychotics. OBJECTIVE: The objective of this study was to determine the extent to which risperidone at low doses altered balance control in healthy participants. METHODS: Twelve healthy young adults received, following a randomized double-blind crossover design, a single oral dose of placebo, 1 and 3 mg of risperidone on separate days at least 14 days apart. Evaluation of extrapyramidal symptoms using the Extrapyramidal Symptom Rating Scale-abbreviated scoring form (ESRS-A) and measures of postural sway using a force platform were assessed over 9 h following drug ingestion. RESULTS: There is a significant increase in the postural stability item of the ESRS-A parkinsonism subscale at 3 and 6 h following 3 mg of risperidone only when compared to placebo. With regard to balance control, body sway measures were increased at 1 mg of risperidone but more pronounced at 3 mg. The peak effects were observed at 3 h after administration of the drug and had not completely returned to baseline after 9 h. CONCLUSIONS: Risperidone administered at low doses did not elicit clinically detectable EPS but had significant effects on balance control. A dose-response effect on impairment of balance was observed that followed the expected time course of the drug pharmacokinetics. These results are likely to apply to older or demented individuals who have pre-existing balance control deficit.

Working memory for braille is shaped by experience.

Tactile working memory was found to be more developed in completely blind (congenital and acquired) than in semi-sighted subjects, indicating that experience plays a crucial role in shaping working memory. A model of working memory, adapted from the classical model proposed by Baddeley and Hitch1 and Baddeley2 is presented where the connection strengths of a highly cross-modal network are altered through experience.

The nature of working memory for Braille.

Blind individuals have been shown on multiple occasions to compensate for their loss of sight by developing exceptional abilities in their remaining senses. While most research has been focused on perceptual abilities per se in the auditory and tactile modalities, recent work has also investigated higher-order processes involving memory and language functions. Here we examined tactile working memory for Braille in two groups of visually challenged individuals (completely blind subjects, CBS; blind with residual vision, BRV). In a first experimental procedure both groups were given a Braille tactile memory span task with and without articulatory suppression, while the BRV and a sighted group performed a visual version of the task. It was shown that the Braille tactile working memory (BrWM) of CBS individuals under articulatory suppression is as efficient as that of sighted individuals' visual working memory in the same condition. Moreover, the results suggest that BrWM may be more robust in the CBS than in the BRV subjects, thus pointing to the potential role of visual experience in shaping tactile working memory. A second experiment designed to assess the nature (spatial vs. verbal) of this working memory was then carried out with two new CBS and BRV groups having to perform the Braille task concurrently with a mental arithmetic task or a mental displacement of blocks task. We show that the disruption of memory was greatest when concurrently carrying out the mental displacement of blocks, indicating that the Braille tactile subsystem of working memory is likely spatial in nature in CBS. The results also point to the multimodal nature of working memory and show how experience can shape the development of its subcomponents.

Discovering structure in auditory input: evidence from Williams syndrome.

We examined auditory perception in Williams syndrome by investigating strategies used in organizing sound patterns into coherent units. In Experiment 1, we investigated the streaming of sound sequences into perceptual units, on the basis of pitch cues, in a group of children and adults with Williams syndrome compared to typical controls. We showed that individuals with Williams syndrome were sensitive to the same pitch cues as typical children and adults when streaming these patterns. In Experiment 2, we evaluated differences in reliance on pitch and contour cues in unfamiliar melody perception in a group of adults with Williams syndrome relative to typical control children and adults. Unlike controls who demonstrated greater proficiency when contour cues were available, adults with Williams syndrome showed no such advantage.

Grip force is part of the semantic representation of manual action verbs.

Motor actions and action verbs activate similar cortical brain regions. A functional interference can be taken as evidence that there is a parallel treatment of these two types of information and would argue for the biological grounding of language in action. A novel approach examining the relationship between language and grip force is presented. With eyes closed and arm extended, subjects listened to words relating (verbs) or not relating (nouns) to a manual action while holding a cylinder with an integrated force sensor. There was a change in grip force when subjects heard verbs that related to manual action. Grip force increased from about 100 ms following the verb presentation, peaked at 380 ms and fell abruptly after 400 ms, signalling a possible inhibition of the motor simulation evoked by these words. These observations reveal the intimate relationship that exists between language and grasp and show that it is possible to elucidate online new aspects of sensorimotor interaction.

Emotion and object processing in Parkinson's disease.

The neuropsychological literature on the processing of emotions in Parkinson's disease (PD) reveals conflicting evidence about the role of the basal ganglia in the recognition of facial emotions. Hence, the present study had two objectives. One was to determine the extent to which the visual processing of emotions and objects differs in PD. The other was to assess the impact of cognitive load on the processing of these types of information. Thirty-one patients with idiopathic PD (IPD) under dopamine replacement therapy (DRT) were compared to 30 control subjects on emotion and object recognition tasks. Recognition of objects was more accurate and faster than recognition of facial expressions of emotion, for both groups of subjects. In a second experiment using an N-back procedure with the same stimuli-a more demanding task with a higher cognitive load-patients with IPD were as accurate as control subjects in detecting the correct sequential presentation of stimuli, but were much slower in their decision responses. This indicates that IPD patients under DRT are not impaired in encoding emotion or object information, but that they have difficulty with the processing demands of the N-back task. Thus, patients with IPD appear to be more sensitive to cognitive load than to type of information, whether facial emotions or objects. In this perspective, one must consider that a deafferented dopaminergic system has problems processing more complex information before one can posit the existence of deficits affecting a specific type of information.

Affect in Parkinson's disease: validation of the two-factor approach.

Depression in Idiopathic Parkinson's disease (IPD) is frequent, difficult to recognize, under managed and has a profound impact on quality of life. Current categorization of diagnosis in psychiatry poorly applies to the protean manifestations of mood disorders presented by parkinsonian patients. In this study we have chosen to dissect the state of depressive mood as assessed with the Beck Depression Inventory (BDI) at different points in time of pharmacological interventions using a dimensional approach. The 21 items of the BDI were classified in two new categories or factors: hyperkinetic and hypokinetic. The hyperkinetic factor included all items related to unbalanced intrusions of negative feelings and ideas, as well as to behavioral hyperactivity. The hypokinetic factor included all items related to loss of drive for appetitive behaviors and loss of mental and physical energy. The objectives were to (1) compare different pharmacological treatments on the two-factor approach in PD depression, (2) determine the influence of levodopa therapy on the two-factor approach, and (3) explore the two-factor approach in placebo conditions. Three sets of analyses using the hypo/hyperkinetic dichotomy favour a neurobiological dissociation of these factors in response to pharmacological intervention: symptoms of the hyperkinetic factor are responsive to serotonergic drugs while those of the hypokinetic one are not and may even show deterioration under SSRIs. In contrast, the hypokinetic factor is responsive to dopaminergic drugs and may show deterioration under serotonergic drugs. Furthermore, the two factors seem to transiently dissociate on placebo intervention aiming at correcting either mood or motor status. The dimensional approach to depression symptomatology may thus be of heuristic value in probing aminergic modulation of mood in IPD and establishing new correlations between affective and motor symptoms.

Long-term skill proceduralization in schizophrenia.

Previous studies had revealed no specific effect under haloperidol (typical) and risperidone (atypical) neuroleptic (NLP) treatments for schizophrenia (SZ) on a variety of neurocognitive functions relying on the dopaminergic meso-cortico-limbic system (Rémillard et al., 2005, 2008). Considering the different affinities of D2 dopamine receptors for typical and atypical NLPs, these drugs may differentially affect the functions of the striatum, a determinant brain structure involved in procedural learning. The influence of risperidone (2-6 mg) and haloperidol (2-40 mg) on a nonmotor procedural task involving semantically related pairs of words with inverted letters was investigated in this double-blind study. The performance of 26 patients with SZ, randomly assigned to risperidone or haloperidol, was compared to that of 18 healthy controls at baseline, 3, 6, and 12 months. Results revealed that all patients with SZ exhibited slower reading speed of the word pairs than healthy controls at all assessment periods. In addition, procedural learning - characterized as a significant decrease in the time taken to read aloud the target word pairs - was more impaired in the haloperidol- than in the risperidone-treated group at all assessment periods. Healthy controls showed steady improvement in reading speed over the 12 months of the study, in contrast to SZ patients, who reached a plateau in their capacity to improve mirror-reading skill over time. However, all SZ participants in the study showed near normal learning profiles from exposure to semantic associations embedded in the procedural memory task, providing evidence for the preservation of associative connections in the semantic network of these patients. The observed impairment in procedural learning in SZ may thus reflect, at least in part, the influence of neuroleptic medication on striatal functions.

Compulsive habits in restless legs syndrome patients under dopaminergic treatment.

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8 months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52+/-0.59 mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences.