Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis.

Cancer cells are exposed to major compressive and shearing forces during invasion and metastasis, leading to extensive plasma membrane damage. To survive this mechanical stress, they need to repair membrane injury efficiently. Targeting the membrane repair machinery is thus potentially a new way to prevent invasion and metastasis. We show here that annexin-A2 (ANXA2) is required for membrane repair in invasive breast and pancreatic cancer cells. Mechanistically, we show by fluorescence and electron microscopy that cells fail to reseal shear-stress damaged membrane when ANXA2 is silenced or the protein is inhibited with neutralizing antibody. Silencing of ANXA2 has no effect on proliferation in vitro, and may even accelerate migration in wound healing assays, but reduces tumor cell dissemination in both mice and zebrafish. We expect that inhibiting membrane repair will be particularly effective in aggressive, poor prognosis tumors because they rely on the membrane repair machinery to survive membrane damage during tumor invasion and metastasis. This could be achieved either with anti-ANXA2 antibodies, which have been shown to inhibit metastasis of breast and pancreatic cancer cells, or with small molecule drugs.

Muscle-only versus chimeric musculocutaneous gastrocnemius pedicled flap in complex orthoplastic reconstructions of the knee region: A retrospective study.

BACKGROUND: The knee region represents a challenging area of soft tissue reconstruction. Specifically, in the context of total knee arthroplasty (TKA) or following high-energy trauma with fractures and hardware fixation, soft tissue defects can expose critical structures such as joint, bone or tendon, besides the implant/plates themselves, with dramatic consequences in terms of postoperative infection and hardware contamination. METHODS: A retrospective study was conducted on a prospectively maintained database from January 2016 to February 2021. Inclusion criteria involved all patients who underwent an implant-associated infection of the knee and upper third of the leg coupled with a soft tissue reconstruction (STR) using the traditional gastrocnemius muscle (GM) pedicled flap or the chimeric GM-MSAP (medial sural artery perforator) flap. RESULTS: Thirty-eight patients were included (group A, GM flap, 22 patients; group B, chimeric GM-MSAP flap, 16 patients). No statistically significant differences were detected in terms of age, comorbidities, defect size, follow-up, and flap complications. A statistically significant difference was seen among the groups in terms of successful flap re-raise (required because of a persistent infection of the implant or in a two-stage procedure setting, including the use of a cemented spacer) in favour of the GM-MSAP group. CONCLUSION: The chimeric GM-MSAP, being safer to reraise if required, can be a significantly more powerful tool in those cases in which a two-stage procedure is planned or when there is a high probability for secondary intervention need, reducing the need to convert to either free flap coverage or amputation.

Comparative study on the relations between backfat thickness in late-pregnant gilts, mammary development and piglet growth.

The potential relation between body condition of gilts in late-pregnancy and litter BW gain as well as mammary development was studied using 2 sets of data. Gilts either from a commercial herd (Part 1, n = 182) or from a series of trials looking at mammary development (Part 2, n = 172) were separated in 3 groups according to backfat thickness (BF) on d 110 of gestation. Group categorization was similar for Parts 1 and 2 of the study and was: low (LOW), 13.6 ± 1.6 mm (mean ± SD); medium (MED), 17.6 ± 1.0 mm (mean ± SD); and high BF (HIGH), 21.8 ± 1.8 mm (mean ± SD) for Part 1, and LOW, 14.2 ± 1.3 mm (mean ± SD); MED, 18.1 ± 1.0 mm (mean ± SD), and HIGH 23.4 ± 2.6 mm (mean ± SD) for Part 2. The effects of BF group on piglet BW gain (Part 1) or on various mammary gland characteristics (Part 2) were determined using ANOVA. Litters from HIGH sows tended to have a greater lactation BW gain than those from LOW sows (P < 0.10). Sows with HIGH BF had more mammary parenchymal tissue and more total protein and total DNA than MED and LOW sows (P < 0.05), which led to greater total protein and total DNA contents (P < 0.05). There were strong positive correlations (P < 0.0001) between parenchymal weight and total protein, total DNA, and total RNA. Results suggest that it is beneficial for primiparous sows to have greater BF (i.e., 20 to 26 mm) at the end of gestation to achieve optimal mammary development and greater litter BW gain in the subsequent lactation.

Discrimination between biological motion with and without social intention: a pilot study using visual scanning in healthy adults.

Human beings have a detailed understanding of others' action and body language allowing them to adapt their behaviour for effective social interaction. A proper selection of human motion deserving a social intention over the many human motion surrounding them may be executed by overt visual-spatial attention. The aim of this study was to characterize eye movements in 32 healthy adults while exploring Social and Non-social human biological motion using an eye tracking method according to two paradigms. The "preferential looking paradigm" revealed that the first fixation is more often on the Non-social Motion than Social Motion but the first fixations duration are longer on Social Motion. Moreover, with the same paradigm, subjects spent a greater looking time percentage on Social Motion than Non-social Motion, no matter whether discrimination between categories was asked for or not. In the "blocks paradigm" the looking time percentage varied by the body parts (chests, pelvis and legs) and its distribution was different between categories. Eye movements revealed a spontaneous, fast and durable bias of overt visual-spatial attention favouring the perception of Social Motion and a different visual scanpath for Social compared to Non-social human biological motion. These findings constitute a basis for the investigation of a 'social intention' bias in perception of human biological motion.

Nutritional status of long-term patients in the acute care setting.

The nutritional status of 926 patients (51.4% female) at an acute tertiary private hospital with a length of stay ≥14 days was assessed using Subjective Global Assessment. The prevalence of malnutrition was 42.5% (37.2% length of stay of 14-27 days, 51.6% ≥28 days). From logistic regression analysis, length of stay and age were independent predictors of malnutrition. It is important that the nutritional status of longer stay patients is monitored and appropriate nutrition support is commenced.

Functional morphological imaging of autism spectrum disorders: current position and theories proposed.

Autism is a pervasive disorder of childhood development. Polymorphous clinical profiles combining various degrees of communication and social interaction with restricted and stereotyped behaviour are grouped under the heading of 'autism spectrum disorders' (ASD). Many teams are trying to pick out the underlying cerebral abnormalities in order to understand the neuronal networks involved in relationships with others. Here we review the morphological, spectroscopic and functional abnormalities in the amygdala-hippocampal circuit, the caudate nuclei, the cerebellum, and the frontotemporal regions, which have been described in subjects with ASD. White matter abnormalities have also been described in diffusion tensor imaging, leading to suspected damage to the subjacent neural networks, such as mirror neurones or the social brain.

Nutritional status of patients who have fallen in an acute care setting.

BACKGROUND: Falls may result in injury, loss of independence and higher healthcare costs. The aim of this study was to examine the nutritional status of patients who had fallen in an acute care setting. METHODS: Forty-nine patients who had experienced a fall while admitted at an Australian private hospital participated in the study (age: 71.2 (SD 14.1) years; 21 male: 28 female). Nutritional status was assessed using subjective global assessment. Protein and energy intake was determined by dietary history and analysed using Australian computerised food composition data. RESULTS: According to subjective global assessment, 27 patients were well nourished and 22 malnourished (21 moderately, one severely malnourished). Well nourished fallers had significantly higher BMI (mean difference 3.7 kg/m(2), CI: 1.2-6.2), dietary protein (mean difference 19.8 g, CI: 2.0-37.5) and energy intake (mean difference 1751 kJ, CI: 332-3170) compared to malnourished fallers. There was no difference in severity of falls based on nutritional status, weight or BMI. CONCLUSIONS: There was a high prevalence of malnutrition and poor intake in this sample of patients who had fallen in hospital. Nutrition assessment and intervention for patients who have fallen in the acute care setting should be considered.

Visual perception in children: human, animal and virtual movement activates different cortical areas.

This study was designed to relate visual perception of motion (HUMAN, ANIMAL and VIRTUAL) to cortical activity (qEEG parameters). Thirty-four healthy right-handed children (29 months-94 months, mean age 5 years) viewed a video film showing a still image (a lake) and animated images with human, animal and virtual movement. EEGs were recorded while the children watched the video film. The power values of each frequency band theta 1: 3.5-5.5 Hz, theta 2: 5.5-7.5 Hz, alpha 1: 7.5-10.5 Hz, alpha 2: 10.5-13 Hz, beta 1: 13-18 Hz, beta 2: 18-25 Hz and beta 3: 25-35 Hz were analyzed in a four-way repeated-measures ANOVA (age x hemisphere x electrode x type of activation). Three main results were obtained: (1) younger children (< 5 years) showed higher power spectral values than older children; (2) there was specificity for real human movement in the left hemisphere; and (3) activations in the left- and right-hemispheres were different according to the movement visualized. These results indicate that in healthy children, human, animal and virtual movement activates different cortical areas.

Regulation of cognitive activity and early communication development in young autistic, mentally retarded, and young normal children.

Based on the Piagetian framework, this study examined regulation of cognitive activity and developmental communication profiles and their interrelationship in groups of autistic, mentally retarded, and normal children of comparable overall, verbal, and oculo-manual developmental ages (from 6 to 24 months). Regulation of activity was assessed with both an object permanence test and an original behavior grid, and development of communication skills with the Guidetti-Tourrette scales (French adaptation of the Seibert-Hogan scales). The results showed evidence of certain types of dysregulation of cognitive activity and a general delay in communication ability in autistic children compared to the other two groups. Moreover, although the intensity of some of these disorders decreased in relation to the developmental levels of social interaction and joint attention in normal children, they were related to both high and low levels of development of social interaction only in autistic children. These findings raise the hypothesis of a relationship between a disorder of disengaging from an activity and developmental levels of social interaction noted at two transitory periods of early development (12 and 24 months) only in children with autism. Developmental and neuropsychological interpretations of this particular pattern are proposed.

Plasma fatty acid levels in autistic children.

Phospholipid fatty acids are major structural components of neuronal cell membranes, which modulate membrane fluidity and hence function. Evidence from clinical and biochemical sources have indicated changes in the metabolism of fatty acids in several psychiatric disorders. We examined the phospholipid fatty acids in the plasma of a population of autistic subjects compared to mentally retarded controls. Our results showed a marked reduction in the levels of 22: 6n-3 (23%) in the autistic subjects, resulting in significantly lower levels of total (n-3) polyunsaturated fatty acids (PUFA) (20%), without significant reduction in the (n-6) PUFA series, and consequently a significant increase in the (n-6)/(n-3) ratio (25%). These variations are discussed in terms of potential differences in PUFA dietary intake, metabolism, or incorporation into cellular membranes between the two groups of subjects. These results open up interesting perspectives for the investigation of new biological indices in autism. Moreover, this might have new therapeutic implications in terms of child nutrition.

Electroencephalographic activity during perception of motion in childhood.

The purpose of the present study was to relate observations of biological motion to cortical activity by evaluation of the association of quantified electroencephalogram (qEEG) parameters with a video film projection. Thirty right-handed healthy children (2-8-year-olds) viewed a video film showing still shots and moving shots with human movement or object movement. The EEG was recorded while children watched the video movie and was then subjected to spectral analysis; the spectral powers for theta, alpha and beta bands were matched with corresponding sequences of video film. The power values of each frequency band were analysed in a four-way repeated-measures ANOVA (Age x Hemisphere x Electrode x Sequence). Three main results were obtained: (i) younger children (2-4-year-olds) had higher power spectral values than older children (5-8-year-olds); (ii) greater EEG desynchronization of the left hemisphere was observed; (iii) observation of biological movement was related to a significant decrease in theta 1 and theta 2 power values of EEG in fronto-temporal and central regions of the left hemisphere compared with visual perception of still shots or nonhuman movement. These results indicated some support for the theory that the sensori-motor cortex and Broca's area are activated during visual observation of human motion.

Association study of the NF1 gene and autistic disorder.

Neurofibromatosis type 1 (NF1) is increased about 150-fold in autistic patients. The aim of this study was to test for an association between the NF1 locus and autistic disorder. The allele distributions of three markers of the NF1 gene were studied in 85 autistic patients and 90 controls. No differences in allele distributions were observed. However, we found a new allele (allele 5) of the GXAlu marker in four autistic patients. Allele 5 was absent in a larger control population (213 individuals). The patients with allele 5 had a more severe clinical picture, mainly in the fields of motility and tonus. Our preliminary results suggest that the NF1 region is not a major susceptibility locus for autism. However, the GXAlu marker of the NF1 gene appears as a possible candidate for a susceptibility locus in a small subgroup of severely affected autistic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:729-732, 1999.

Observation and execution of movement: similarities demonstrated by quantified electroencephalography.

Quantified electroencephalography (qEEG) was used to compare cerebral electrical variations while human subjects (10 males and 10 females) were observing and executing finger movements and while they were resting. Video recording enabled elimination of subjects performing involuntary movements. EEGs were recorded from 14 sites in seven frequency bands: theta 1, theta 2, alpha 1, alpha, beta 1, beta 2 and beta 3. Analyses were performed on logarithmically transformed absolute spectral power values. Both observation and execution of finger movements involved a decrease in spectral power compared with resting. This decrease was significant only for the alpha 1 frequency band (7.5-10.5 Hz) and it involved nine of the 14 electrode locations (F7, F8, F4, T6, T5, C3, C4, P3 and P4). This indicates that the motor cortex and the frontal cortex are specifically activated by both observation and execution of finger movements. These results provide evidence that observation and execution of movement share the same cortical network.

Immunoreactivity of sera to a peptide derived from the serotonin 5-HT1A receptor in a group of children with developmental disorders: possible role in non-autistic epilepsy.

The presence of autoantibodies against the serotoninergic 5-HT1A receptor has been reported in serum from an autistic child using radioligand binding studies. It is now well established that, in cardiovascular diseases with an autoimmune component, patients present in their sera autoantibodies directed against the second extracellular loop of some G-protein coupled membrane receptors. We thus investigated by an enzyme-immunoassay method the presence of anti-5-HT1A receptor antibodies in sera of children with developmental disorders using synthetic peptides corresponding to the first and the second extracellular loops of this receptor. The population of children with developmental disorders was divided in autistic children with or without EEG abnormalities, and in non-autistic children with or without EEG abnormalities. We found that 6 out of 10 sera of non-autistic children with an abnormal EEG recognized the second extracellular loop of the 5-HT1A receptor. This is significantly higher than the other groups of children with developmental disorders or a healthy control group. These observations support the existence of an autoimmune component in epilepsy.

[Latent imitation of human movements presented on a videoscopic screen, disclosed by electroencephalographic mapping in the spectator]. / Imitation latente de mouvements humains présentés sur écran vidéoscopique, mise en évidence par cartographie électro-encéphalographique chez le spectateur.

Trend to imitate human movement is studied here by EEG mapping. The effects of three kinds of situations are compared: a movement on a TV screen is presented to the subject; a movement is realized by the experimenter in front of the subject; the subject is asked to perform a movement. These three situations elicited important modifications in alpha 1 rhythms over the centroparietal area of the scalp. These results are discussed according to neurophysiological and neuropsychological data, including the possible role of frontal lobe in imitation. Preliminary experiments in psychopathology concern imitation disturbances in autistic children.

Sry and the testis: molecular pathways of organogenesis.

The gene Sry acts as a switch, initiating pathways leading to the differentiation of a testis rather than an ovary from the indifferent gonad (genital ridge) in mammals. The early events following Sry expression include rapid changes in the topographical organization of cells in the XY gonad. Sry must therefore initiate signaling pathways that direct male-specific patterns of proliferation, migration, cell-cell organization, and vascularization. We have identified an increase in male-specific proliferation by 12.0 days post coitum, while proliferation in the female gonad declines. We have also observed male-specific cell migration from the mesonephros into the gonad in a composite organ culture system in which gonads from wild-type mice (CD1) and mesonephroi from a transgenic strain expressing beta-galactosidase in all its cells (ROSA26) were grafted together in vitro at the indifferent stage of gonadogenesis. Migration depends on an active signal that requires the presence of a Y chromosome in the gonadal portion of the graft. The signals that trigger migration operate over considerable distances, suggesting either a long-range diffusible factor or the involvement of a rapid and efficient relay mechanism. Identification of the somatic cells contributed from the mesonephros with cell-specific markers indicated that some of the migrating cells were endothelial, revealing differences in processes of vascularization between male and female gonads. A second distinct population of migrating cells lay in close apposition to endothelial cells, and a third population occupied positions circumscribing areas of condensing Sertoli cells.

[Further clinical evaluations elicited by functional biological investigations in childhood autism]. / Evaluations cliniques complémentaires suscitées par des explorations biologiques fonctionnelles dans l'autisme de l'enfant.

As childhood autism is usually considered as a developmental disorder, complete assessment of each patient requires non only clinical examination but various biological investigations: EEG and evoked potentials recordings, biochemical dosages and sometimes, cerebral blood flow measures, molecular biologic explorations.... These investigations help to understand neurophysiological dysfunctionings which underly different autistic syndromes. It therefore seems necessary to develop quantified clinical tools which could allow closer matching between clinical evaluations and biological numerical data. These complementary evaluations must be both simple and quick to perform in medical practice, as they are added to an already heavy clinical examination. The main tools used in our bioclinical Department are described here. For each child, psychiatric, pediatric and neurological examination was performed. Different scales were progressively elaborated and validated to complete and precise behavioral parameters. Attention and perception were evaluated by a Behavior Summarized Evaluation (BSE) scale, association and imitation by appropriate scales, language by the Pre-Verbal Behavior Summarized Evaluation (PV-BSE) scale, early symptoms by the Infant Behavior Summarized Evaluation (t-BSE) scale. The main neurophysiological dysfunctionings were grouped in a Behavioral Functional Inventory (BFI). Clinical genetic data were scored in a summarized assessment carrying both on the antecedents and on the somatic abnormalities. The completed clinical data were gathered in a Quantified Multidimensional Assessment (QMA), with four axes: socialization, communication, cognition and neurological observation. These clinical evaluations provide behavioral details that can be integrated into a bioclinical database and give an objective approach to the heterogeneity of autism. They invite both clinicians and biologists to deepen the description of individual profiles which allow better understanding of physiopathological mechanisms in autistic children.

Perception of motion and qEEG activity in human adults.

This study was designed to relate visual perception of motion to cortical activity, by evaluation of the association of quantified electroencephalogram (qEEG) parameters with a video film projection. The EEG was recorded from 14 sites according to the International 10-20 system and a common average reference was used. Forty right-handed volunteers (mean age = 24 years) were examined. The video film consisted of 20 s sequences showing still shots and moving shots with human movements or object movements. The EEG was then subjected to spectral analysis; the spectral powers for the theta, alpha and beta bands were calculated for 14 s epochs and compared with sequences of the video film. All analyses were based on logarithmically transformed absolute spectral power values. The power values of each frequency band were analysed in a 3-way repeated measure ANOVA (Hemisphere x Electrode x Sequence). The results were represented by EEG cartography. Significant decreases in the alpha 1, beta 1 and beta 2 power values of EEG in centro-parietal regions of both hemispheres were shown during perception of human motion sequences. This suggests participation of the sensorimotor cortex during visual observation of human motion.

Male-specific cell migration into the developing gonad.

BACKGROUND: The gene Sry acts as a developmental switch, initiating a pathway of gene activity that leads to the differentiation of testis rather than ovary from the indifferent gonad (genital ridge) in mammalian embryos. The early events following Sry expression include rapid changes in the topographical organization of cells in the XY gonad. To investigate the contribution of mesonephric cells to this process, gonads from wild-type mice (CD1), and mesonephroi from a transgenic strain ubiquitously expressing beta-galactosidase (ROSA26), were grafted together in vitro. After culture, organs were fixed and stained for beta-galactosidase activity to identify cells contributed from the mesonephros to the male or female gonad. RESULTS: Migration of mesonephric cells occurred into XY but not XX gonads from 11.5-16.5 days post coitum (dpc). Somatic cells contributed from the mesonephros were distinguished by their histological location and by available cell-specific markers. Some of the migrating cells were endothelial; a second population occupied positions circumscribing areas of condensing Sertoli cells; and a third population lay in close apposition to endothelial cells. CONCLUSIONS: OFFgration from the mesonephros to the gonad is male specific at this stage of development and depends on an active signal that requires the presence of a Y chromosome in the gonad. The signals that trigger migration operate over considerable distances and behave as chemoattractants. We suggest that migration of cells into the bipotential gonad may have a critical role in initiating the divergence of development towards the testis pathway.

Serotonin and autism: biochemical and molecular biology features.

Whole blood and urinary levels of serotonin (5-hydroxytryptamine; 5-HT) and the derivative urinary 5-hydroxyindoleacetic acid (5-HIAA) were measured in normal and autistic subjects. An association was tested between autism and a marker coding for the 5-HT2A serotonergic receptor gene. Significant group (high urinary 5-HT and low whole blood 5-HT in autism) and age effects (urinary 5-HT decrease with age) were found. Moreover, whole blood 5-HT levels were correlated with clinical state. No differences in allele and genotype frequencies for the 5-HT2A receptor marker were found in this autistic population compared with age-matched healthy students.