Microstates and power envelope hidden Markov modeling probe bursting brain activity at different timescales.

State modeling of whole-brain electroencephalography (EEG) or magnetoencephalography (MEG) allows to investigate transient, recurring neurodynamical events. Two widely-used techniques are the microstate analysis of EEG signals and hidden Markov modeling (HMM) of MEG power envelopes. Both reportedly lead to similar state lifetimes on the 100 ms timescale, suggesting a common neural basis. To investigate whether microstates and power envelope HMM states describe the same neural dynamics, we used simultaneous MEG/EEG recordings at rest and compared the spatial signature and temporal activation dynamics of microstates and power envelope HMM states obtained separately from EEG and MEG. Results showed that microstates and power envelope HMM states differ both spatially and temporally. Microstates reflect sharp events of neural synchronization, whereas power envelope HMM states disclose network-level activity with 100-200 ms lifetimes. Further, MEG microstates do not correspond to the canonical EEG microstates but are better interpreted as split HMM states. On the other hand, both MEG and EEG HMM states involve the (de)activation of similar functional networks. Microstate analysis and power envelope HMM thus appear sensitive to neural events occurring over different spatial and temporal scales. As such, they represent complementary approaches to explore the fast, sub-second scale bursting electrophysiological dynamics in spontaneous human brain activity.

Cannabinoid receptor type 2 is upregulated in synovium following joint injury and mediates anti-inflammatory effects in synovial fibroblasts and macrophages.

OBJECTIVE: Joint injury-induced perturbations to the endocannabinoid system (ECS), a regulator of both inflammation and nociception, remain largely uncharacterized. We employed a mouse model of ACL rupture to assess alterations to nociception, inflammation, and the ECS while using in vitro models to determine whether CB2 agonism can mitigate inflammatory signaling in macrophages and fibroblast-like synoviocytes (FLS). DESIGN: Mice underwent noninvasive ACL rupture (ACLR) via tibial compression-based loading. Nociception was measured longitudinally using mechanical allodynia and knee hyperalgesia testing. Synovitis was assessed using histological scoring and histomorphometry. Gene and protein markers of inflammation were characterized in whole joints and synovium. Immunohistochemistry assessed injury-induced alterations to CB1+, CB2+, and F4/80+ cells in synovium. To assess whether CB2 agonism can inhibit pro-inflammatory macrophage polarization, murine bone marrow-derived macrophages (mBMDM) were stimulated with IL-1ß or conditioned medium from IL-1ß-treated FLS and treated with vehicle (DMSO), the CB2 agonist HU308, or cannabidiol (CBD). Macrophage polarization was assessed as the ratio of M1-associated (IL1b, MMP1b, and IL6) to M2-associated (IL10, IL4, and CD206) gene expression. Human FLS (hFLS) isolated from synovial tissue of OA patients were treated with vehicle (DMSO) or HU308 following TNF-α or IL-1ß stimulation to assess inhibition of catabolic/inflammatory gene expression. RESULTS: ACLR induces synovitis, progressively-worsening PTOA severity, and an immediate and sustained increase in both mechanical allodynia and knee hyperalgesia, which persist beyond the resolution of molecular inflammation. Enrichment of CB2, but not CB1, was observed in ACLR synovium at 3d, 14d, and 28d, and CB2 was found to be associated with F4/80 (+) cells, which are increased in number in ACLR synovium at all time points. The CB2 agonist HU308 strongly inhibited mBMDM M1-type polarization following stimulation with either IL-1ß or conditioned medium from IL-1ß-treated mFLS, which was characterized by reductions in Il1b, Mmp1b, and Il6 and increases in Cd206 gene expression. Cannabidiol similarly inhibited IL-1ß-induced mBMDM M1 polarization via a reduction in Il1b and an increase in Cd206 and Il4 gene expression. Lastly, in OA hFLS, HU308 treatment inhibited IL-1ß-induced CCL2, MMP1, MMP3, and IL6 expression and further inhibited TNF-α-induced CCL2, MMP1, and GMCSF expression, demonstrating human OA-relevant anti-inflammatory effects by targeting CB2. CONCLUSIONS: Joint injury perturbs the intra-articular ECS, characterized by an increase in synovial F4/80(+) cells, which express CB2, but not CB1. Targeting CB2 in murine macrophages and human FLS induced potent anti-inflammatory and anti-catabolic effects, which indicates that the CB2 receptor plays a key role in regulating inflammatory signaling in the two primary effector cells in the synovium. The intraarticular ECS is therefore a potential therapeutic target for blocking pathological inflammation in future disease-modifying PTOA treatments.

Comparing MEG and high-density EEG for intrinsic functional connectivity mapping.

Magnetoencephalography (MEG) has been used in conjunction with resting-state functional connectivity (rsFC) based on band-limited power envelope correlation to study the intrinsic human brain network organization into resting-state networks (RSNs). However, the limited availability of current MEG systems hampers the clinical applications of electrophysiological rsFC. Here, we directly compared well-known RSNs as well as the whole-brain rsFC connectome together with its state dynamics, obtained from simultaneously-recorded MEG and high-density scalp electroencephalography (EEG) resting-state data. We also examined the impact of head model precision on EEG rsFC estimation, by comparing results obtained with boundary and finite element head models. Results showed that most RSN topographies obtained with MEG and EEG are similar, except for the fronto-parietal network. At the connectome level, sensitivity was lower to frontal rsFC and higher to parieto-occipital rsFC with MEG compared to EEG. This was mostly due to inhomogeneity of MEG sensor locations relative to the scalp and significant MEG-EEG differences disappeared when taking relative MEG-EEG sensor locations into account. The default-mode network was the only RSN requiring advanced head modeling in EEG, in which gray and white matter are distinguished. Importantly, comparison of rsFC state dynamics evidenced a poor correspondence between MEG and scalp EEG, suggesting sensitivity to different components of transient neural functional integration. This study therefore shows that the investigation of static rsFC based on the human brain connectome can be performed with scalp EEG in a similar way than with MEG, opening the avenue to widespread clinical applications of rsFC analyses.

Neuromagnetic Cerebellar Activity Entrains to the Kinematics of Executed Finger Movements.

This magnetoencephalography (MEG) study aims at characterizing the coupling between cerebellar activity and the kinematics of repetitive self-paced finger movements. Neuromagnetic signals were recorded in 11 right-handed healthy adults while they performed repetitive flexion-extensions of right-hand fingers at three different movement rates: slow (~ 1 Hz), medium (~ 2 Hz), and fast (~ 3 Hz). Right index finger acceleration was monitored with an accelerometer. Coherence analysis was used to index the coupling between right index finger acceleration and neuromagnetic signals. Dynamic imaging of coherent sources was used to locate coherent sources. Coupling directionality between primary sensorimotor (SM1), cerebellar, and accelerometer signals was assessed with renormalized partial directed coherence. Permutation-based statistics coupled with maximum statistic over the entire brain volume or restricted to the cerebellum were used. At all movement rates, maximum coherence peaked at SM1 cortex contralateral to finger movements at movement frequency (F0) and its first harmonic (F1). Significant (statistics restricted to the cerebellum) coherence consistently peaked at the right posterior lobe of the cerebellum at F0 with no influence of movement rate. Coupling between Acc and cerebellar signals was significantly stronger in the afferent than in the efferent direction with no effective contribution of cortico-cerebellar or cerebello-cortical pathways. This study demonstrates the existence of significant coupling between finger movement kinematics and neuromagnetic activity at the posterior cerebellar lobe ipsilateral to finger movement at F0. This coupling is mainly driven by spinocerebellar, presumably proprioceptive, afferences.

Neural Basis of Early Somatosensory Change Detection: A Magnetoencephalography Study.

The mismatch negativity (MMN) reflects the early detection of changes in sensory stimuli at the cortical level. The mechanisms underlying its genesis remain debated. This magnetoencephalography study investigates the spatio-temporal dynamics and the neural mechanisms of the magnetic somatosensory MMN. Somatosensory evoked magnetic fields elicited by tactile stimulation of the right fingertip (Single), tactile stimulation of the right middle phalanx and fingertip (Double) or omissions (Omitted) of tactile stimuli were studied in different paradigms: in oddballs where Double/Omitted followed a sequence of four Single, in sequences of two stimuli where Double occurred after one Single, and in random presentation of Double only. The predictability of Double occurrence in oddballs was also manipulated. Cortical sources of evoked responses were identified using equivalent current dipole modeling. Evoked responses elicited by Double were significantly different from those elicited by Single at the contralateral secondary somatosensory (cSII) cortex. Double elicited higher cSII cortex responses than Single when preceded by a sequence of four Single, compared to when they were preceded by one Single. Double elicited higher cSII cortex response when presented alone compared to when Double were preceded by one or a sequence of Single. Omitted elicited similar cSII cortex response than Single. Double in oddballs led to higher cSII cortex responses when less predictable. These data suggest that early tactile change detection involves mainly cSII cortex. The predictive coding framework probably accounts for the SII cortex response features observed in the different tactile paradigms.

Movement Kinematics Dynamically Modulates the Rolandic ~ 20-Hz Rhythm During Goal-Directed Executed and Observed Hand Actions.

This study investigates whether movement kinematics modulates similarly the rolandic α and ß rhythm amplitude during executed and observed goal-directed hand movements. It also assesses if this modulation relates to the corticokinematic coherence (CKC), which is the coupling observed between cortical activity and movement kinematics during such motor actions. Magnetoencephalography (MEG) signals were recorded from 11 right-handed healthy subjects while they performed or observed an actor performing the same repetitive hand pinching action. Subjects' and actor's forefinger movements were monitored with an accelerometer. Coherence was computed between acceleration signals and the amplitude of α (8-12 Hz) or ß (15-25 Hz) oscillations. The coherence was also evaluated between source-projected MEG signals and their ß amplitude. Coherence was mainly observed between acceleration and the amplitude of ß oscillations at movement frequency within bilateral primary sensorimotor (SM1) cortex with no difference between executed and observed movements. Cross-correlation between the amplitude of ß oscillations at the SM1 cortex and movement acceleration was maximal when acceleration was delayed by ~ 100 ms, both during movement execution and observation. Coherence between source-projected MEG signals and their ß amplitude during movement observation and execution was not significantly different from that during rest. This study shows that observing others' actions engages in the viewer's brain similar dynamic modulations of SM1 cortex ß rhythm as during action execution. Results support the view that different neural mechanisms might account for this modulation and CKC. These two kinematic-related phenomena might help humans to understand how observed motor actions are actually performed.

[Positron emission tomography : from classical indications to new and future applications]. / La tomographie par émission de positons : des indications classiques aux applications récentes et futures.

First clinical indications of positron emission tomography (PET) were in the fields of neurology and cardiology, but oncology is the domain in which PET got its recognition as an essential diagnostic tool. Its fast diffusion as an imaging method for diagnosis and follow-up of cancer has been facilitated by the existence of a single tracer for all kinds of oncological PET explorations. Nowadays, this tracer, fluorodeoxyglucose (FDG), is so largely distributed that non oncological PET indications have emerged. For instance, PET with FDG has totally supplanted gallium-67 for the evaluation of inflammatory conditions. Another non oncological domain in which PET with FDG has kept an important clinical role is neurology. The strong local relationship between neuronal activity and cerebral glucose uptake confers to PET with FDG a primordial role in neurological conditions in which structural changes are insufficient to establish a firm diagnosis. This is the case for focal epilepsy that remains an undisputed indication of PET with FDG, and for neurodegenerative disorders, in particular those that lead to dementia for which tracers detecting amyloid and tau depositions are now available. New tracers have enlarged PET indications in oncology, in particular for cancers that are not well evaluated with FDG. Since the early clinical PET introduction, patients with brain tumours are benefiting from PET exploration with amino-acid tracers, in particular for therapeutic tumour targeting. The recent development of tracers for neuroendocrine and prostatic cancers has opened a new field of applications for PET, linked to innovative radiotherapeutic approaches.

La tomographie par émission de positons (TEP) a connu ses premières indications dans le domaine des affections neurologiques et cardiaques, mais c'est en oncologie que cette méthode va s'implanter comme un outil diagnostique essentiel. Sa diffusion rapide en imagerie oncologique a été facilitée par le fait qu'un unique traceur permet de pratiquer la très grande majorité des explorations. Ce traceur, le fluoro-désoxyglucose (FDG), est aujourd'hui distribué de façon très large de sorte que les indications non oncologiques de la TEP se sont également développées. La TEP au FDG a ainsi totalement supplanté la scintigraphie au citrate de gallium-67 pour l'évaluation des affections inflammatoires. La neurologie est restée un autre champ d'application non oncologique de la TEP au FDG. La relation qui lie l'activité neuronale locale à la consommation de glucose confère à la TEP au FDG un rôle déterminant pour l'évaluation de maladies du cerveau dans lesquelles les modifications structurelles sont insuffisantes pour établir un diagnostic. C'est le cas de l'épilepsie focale et des maladies neurodégénératives, principalement les démences pour lesquelles de nouveaux traceurs ciblant les dépôts amyloïdes ou de protéines tau, sont apparus. S'agissant de nouveaux traceurs, notons que certains ont étendu l'usage de la TEP à des cancers mal évalués par le FDG. Les cancers cérébraux bénéficient depuis longtemps de l'utilisation en TEP d'acides aminés marqués, en particulier pour le ciblage thérapeutique des tumeurs. L'apparition de traceurs des cancers neuroendocrines et prostatiques a ouvert un nouveau champ d'indications de la TEP, en lien avec de nouvelles approches radiothérapeutiques.

Is there an association between dietary intake and academic achievement: a systematic review.

BACKGROUND: The majority of literature examining the effect of dietary behaviour on academic achievement has focused on breakfast consumption only. Here, we aim to systematically review the literature investigating the broader effects of dietary intake and behaviours on school-aged children's academic achievement. METHODS: A search was undertaken across seven databases using keywords. For studies to be included, they needed to be conducted in: school-aged children (5-18 years); assess and report: (i) a measure of academic performance; (ii) a measure of dietary intake/behaviour; and (iii) the association between dietary intake/behaviours and academic performance. Forty studies were included in the review. RESULTS: The majority of studies were cross-sectional in design (n = 33) and studied children aged >10 years, with very few reports in younger age groups. More than 30 different dietary assessment tools were used, with only 40% of those using a validated/standardised assessment method. Half the studies collected outcomes of academic achievement objectively from a recognised educational authority, whereas 10 studies used self-reported measures. The dietary outcomes most commonly reported to have positive associations with academic achievement were: breakfast consumption (n = 12) and global diet quality/meal patterns (n = 7), whereas negative associations reported with junk/fast food (n = 9). CONCLUSIONS: This review highlights that moderate associations exist for dietary intakes characterised by regular breakfast consumption, lower intakes of energy-dense, nutrient-poor foods and overall diet quality with respect to outcomes of academic achievement. Future studies should consider the use of validated dietary assessment methods and standardised reporting of academic achievement.

Annexin A2, autoimmunity, anxiety and depression.

OBJECTIVES: Antiphospholipid syndrome (APS) is associated with neurological manifestations and one of the novel autoantigens associated with this disease is Annexin A2 (ANXA2). In this work we have examined the effect of high levels of autoantibodies to ANXA2 on the brain in a mouse model. METHODS: Recombinant ANXA2 emulsified in adjuvant was used to immunize mice while mice immunized with adjuvant only served as controls. At peak antibody levels the animal underwent behavioral and cognitive tests and their brains were examined for ANXA2 immunoglobulin G (IgG) and expression of ANXA2 and the closely linked protein p11. RESULTS: Very high levels of anti-ANXA2 antibodies (Abs) were associated with reduced anxiety in the open field 13.14% ± 0.89% of the time in the center compared to 8.64% ± 0.91% observed in the control mice (p < 0.001 by t-test). A forced swim test found significantly less depression manifested by immobility in the ANXA2 group. The changes in behavior were accompanied by a significant reduction in serum corticosteroid levels of ANXA2 group compared to controls. Moreover, higher levels of total IgG and p11 expression were found in ANXA2 group brains. Lower levels of circulating anti-ANXA2 Abs were not associated with behavioral changes. CONCLUSIONS: We have established an animal model with high levels of anti-ANXA2 Abs which induced IgG accumulation in the brain and specific anxiolytic and anti-depressive effects. This model promises to further our understanding of autoimmune disease such as APS and to provide better understanding of the role of the ANXA2-p11 complex in the brain.

Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing.

OBJECTIVES: Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma. METHODS AND RESULTS: To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3(+) lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively. CONCLUSIONS: These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma.

Outcomes of pregnancies with more than one positive prenatal screening result in the first or second trimester.

OBJECTIVE: To describe adverse outcomes and fetal abnormalities in women with a positive prenatal screening result for more than one disorder. STUDY DESIGN: Study participants were drawn from a population of 452 901 women pregnant with singletons entering the California Prenatal Screening Program in their first-trimester. Risk assessment was provided for trisomy 21 and trisomy 18 in the first-trimester and trisomy 21, trisomy 18, neural tube defects, and Smith-Lemli-Opitz syndrome in the second-trimester. Inclusion in this study required positive screening for more than one of the screened conditions and a completed outcome of pregnancy survey. RESULTS: A total of 874 women met our study inclusion criteria. Over 25% of these pregnancies had a fetus with a chromosomal abnormality. Of the euploid pregnancies, 6.9% had a fetus with a major birth defect. Of the pregnancies with a fetus with neither a chromosomal abnormality nor a major birth defect, 9.3% ended in fetal demise. Overall, more than 50% of women with multiple positive screening results had either a fetus with a birth defect or a poor pregnancy outcome. CONCLUSION: Although it is rare to screen positive for more than one condition, such results indicate a very high risk for chromosomal abnormality, fetal demise, or structural abnormality.

CVRmap-a complete cerebrovascular reactivity mapping post-processing BIDS toolbox.

Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards.

Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts.

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.

Sustained induction of neuronal addition to the adult rat neostriatum by AAV4-delivered noggin and BDNF.

Intraventricular ependymal infection by adenoviruses expressing brain-derived neurotrophic factor (BDNF) and noggin is sufficient to induce the heterotopic recruitment of new medium spiny neurons to the adult neostriatum, from endogenous subependymal neural progenitor cells. This approach was found to slow disease progression and extend survival in an R6/2 mouse model of Huntington's disease (HD). However, the practical therapeutic value of this strategy is limited by the transient expression and immunogenicity of adenoviral vectors. In addition, it has been unclear whether sustained overexpression of BDNF and noggin would yield similarly sustained neuronal production and striatal recruitment, or whether progenitor depletion or tachyphylaxis might supervene to limit the therapeutic potential of this approach. To address these issues, we used adeno-associated virus serotype 4 (AAV4), an ependymotrophic vector that is neither immunogenic nor neurotoxic, to achieve sustained BDNF and noggin expression. Using AAV4, we found that BDNF and noggin achieved levels sufficient to initiate and maintain, for at least 4 months, ongoing neuronal addition to the neostriatum and olfactory bulb. Over this period, we noted no diminution of treatment-associated neuronal recruitment from resident progenitors. AAV4:BDNF and noggin-induced neuronal addition may thus provide a means to provide longlasting and persistent striatal neuronal replacement in conditions of striatal neuronal loss, such as HD.

Sleep in children and adolescents with Angelman syndrome: association with parent sleep and stress.

BACKGROUND: Sleep concerns are common in children with Angelman syndrome, with 20-80% of individuals having a decreased sleep need and/or abnormal sleep-wake cycles. The impact of these sleep behaviours on parental sleep and stress is not known. METHOD: Through the use of standardised questionnaires, wrist actigraphy and polysomnography, we defined the sleep behaviours of 15 children/adolescents with Angelman syndrome and the association of the child/adolescents sleep behaviours on parental sleep behaviours and parental stress. RESULTS: Both children/adolescents and their parents exhibited over 1 h of wake time after sleep onset and fragmented sleep. Prolonged sleep latency in the child was associated with parent insomnia and daytime sleepiness. Additionally, variability in child total sleep time was associated with parental stress. CONCLUSIONS: Poor sleep in children/adolescents with Angelman syndrome was associated with poor parental sleep and higher parental stress. Further work is warranted to identify the underlying causes of the poor sleep, and to relate these findings to daytime functioning, behaviour and the family unit.

[Positron emission tomography in inflammatory disorders]. / La tomographie par emission de positons dans les affections inflammatoires.

Value of positron emission tomography (PET) applied to the metabolic evaluation of inflammatory disorders is increasingly recognized. PET with fluorodeoxyglucose (FDG) has now taken the place occupied by citrate of Gallium-67 in this domain, in which it has several advantages compared to other diagnostic imaging methods such as scintigraphy with labelled leucocytes. Visualization of inflammatory lesions does not just rely on the presence of immune cells. Uptake of the tracer actually requires the activation of these immune cells, an important point to consider to adequately interpreting PET imaging in this context. For systemic inflammatory disorders, FDG-PET has the advantage to provide whole body evaluation. This advantage, combined to the fact that the tracer used reveals infectious, non-infectious inflammatory diseases on one hand, and malignant diseases on the other hand, is crucial for the etiologic diagnosis of fever of unknown origin. Various chronic infectious diseases that are frequent clinical challenges are better diagnosed with the use of PET, particularly when this imaging method is combined with X-ray computed tomography (CT). Such infectious diseases are osteomyelitis, infection of orthopaedic and vascular prostheses, and infectious diseases with systemic distribution such as tuberculosis. For what concerns noninfectious inflammatory diseases, FDG-PET has proved particularly helpful for the diagnosis and management of large vessels arteritis and inflammatory bowel disease.

Effect of primary human endometrial stromal cells on epithelial cell receptivity and protein expression is dependent on menstrual cycle stage.

BACKGROUND: Successful implantation requires a receptive endometrium. We hypothesized that effects of endometrial stromal cells (ESC) on epithelial cell receptivity and trophoblast-endometrium interaction are menstrual cycle dependent. METHODS: An endometrial in vitro 3D co-culture model of primary human ESC with the endometrial epithelial cell line (RL95-2) was constructed. Co-cultures were prepared using primary ESC from biopsies taken before the window of implantation (ESCbw) and during the window of implantation (ESCw), on cycle days 10-17 and 19-23, respectively. RL95-2 served as a constant parameter upon which the influence of ESC from different phases of the cycle was investigated. proMMP-2 (MMP, matrix metalloproteinase) and proMMP-9 secretion was tested in response to progesterone. Progesterone receptor B (PR-B) and plexin B1 protein expression and mRNA levels were investigated using immunofluorescence and RT-PCR, respectively. RESULTS: Progesterone increased proMMP-2 secretion in primary ESCbw (P = 0.0046) but decreased proMMP-2 and proMMP-9 secretion in ESCw (P < 0.0005). In the presence of ESCbw, JAR spheroid attachment rate to overlying RL95-2 cells was decreased (P < 0.0001), whereas in the presence of ESCw, attachment rate was unchanged. Progesterone treatment restored epithelial cell receptivity in co-culture with ESCbw (P = 0.00004). A correlation between spheroid attachment rate and plexin B1 mRNA level was observed (P = 0.01). PR-B protein and mRNA level were influenced by the interplay between RL95-2 and stromal cells. CONCLUSION: The effects of human primary ESC on epithelial cell receptivity and trophoblast-endometrium interaction depended upon whether the ESC were taken before or during the window of implantation.

Environmental influences on activity patterns in altered states of consciousness.

BACKGROUND AND PURPOSE: To evaluate in disorders of consciousness (DOC) circadian variations in motor patterns and their possible synchronization with physiologically regulated light variations and/or a social environmental factor, i.e. presence and actions of other persons. METHODS: Actimetric and ambient light levels recordings were obtained during 4-9 days in two patients with traumatic brain injury (TB1 and TB2) in a minimally conscious state (MCS), one MCS (AI1) and one comatose (AI2) anoxic-ischaemic patients. Environmental changes were automatically recorded using a video system. RESULTS: Minute light variations correlated with motor activity in all patients. However, motor activity was significantly higher during day than nighttime and correlated with social environmental changes, in patients TB1 and TB2 only. CONCLUSIONS: Night-day circadian variations in motor activity patterns and influence of social stimulations were observed in traumatic MCS patients only. Nonetheless, rapid light variations may temporarily promote increased arousal, and consequently motor activity, in all DOCs.

In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus.

Neurogenesis persists in the adult mammalian hippocampus. To identify and isolate neuronal progenitor cells of the adult human hippocampus, we transfected ventricular zone-free dissociates of surgically-excised dentate gyrus with DNA encoding humanized green fluorescent protein (hGFP), placed under the control of either the nestin enhancer (E/nestin) or the Talpha1 tubulin promoter (P/Talpha1), two regulatory regions that direct transcription in neural progenitor cells. The resultant P/Talpha1:hGFP+ and E/nestin:enhanced (E)GFP+ cells expressed betaIII-tubulin or microtubule-associated protein-2; many incorporated bromodeoxyuridine, indicating their genesis in vitro. Using fluorescence-activated cell sorting, the E/nestin:EGFP+ and P/Talpha1:hGFP+ cells were isolated to near purity, and matured antigenically and physiologically as neurons. Thus, the adult human hippocampus contains mitotically competent neuronal progenitors that can be selectively extracted. The isolation of these cells may provide a cellular substrate for re-populating the damaged or degenerated adult hippocampus.

Determining the amount, timing and causes of mortality among infants with Down syndrome.

OBJECTIVE: To examine the amount, timing and causes/correlates of infant mortality among newborns with Down syndrome. METHODS: Using the Tennessee Department of Health Birth, Hospital Discharge and Death records, infants were identified who were born with Down syndrome from 1990 to 2006. Those who died during the first year were separated into three groups (first day death, neonatal mortality, post-neonatal mortality) and data from the Birth and Death records were used to compare the three death groups and the survival group on correlates of mortality. RESULTS: Of 1305 infants born in Tennessee with Down syndrome from 1990 to 2006, 97 died within the first year, for a mortality rate of 74 per 1000. Most Down syndrome infant deaths occurred during the post-neonatal period (56%), although many occurred during the first day (27%). Newborns who died during the first day had significantly lower birthweight, 5-min Apgar scores and gestational lengths, whereas those who died in the post-neonatal period had significantly more heart-related causes of death (all Ps < 0.001). No associations were found in this sample between increased infant mortality and maternal age, education, race, marital status or familial urban residence. CONCLUSIONS: Infants with Down syndrome experience high rates of mortality occurring at three distinct times during the first year. These groupings are tied to specific, different causes of death.