Multicenter evaluation of electrical stimulation systems for walking.

OBJECTIVE: To test the long-term benefits of several noninvasive systems for functional electrical stimulation (FES) during walking. DESIGN: Forty subjects (average years since injury, 5.4) were studied in four centers for an average time of 1 year. Gait parameters were tested for all subjects with and without FES. Thus, subjects served as their own controls, since the specific effect of using FES could be separated from improvements resulting from other factors (e.g., training). SETTING: Subjects used the devices in the community, but were tested in a university or hospital setting. PATIENTS: Subjects with spinal cord injury (n = 31) were compared to subjects with cerebral damage (n = 9). MAIN OUTCOME MEASURES: Gait parameters (speed, cycle time, stride length). Acceptance was studied by means of a questionnaire. RESULTS: Some initial improvement in walking speed (average increase of >20%) occurred, and continuing gains were seen (average total improvement, 45%). The largest relative gains were seen in the slowest walkers (speeds of <0.3 m/sec). Acceptance of the FES systems was good and improved systems have been developed using feedback from the subjects. CONCLUSIONS: Based on the improvements in speed and the acceptance of these FES systems, a greatly increased role for FES in treating gait disorders is suggested.     

From the Cover: A functional analysis reveals extremely low redundancy in global mangrove invertebrate fauna

Deforestation results in habitat fragmentation, decreasing diversity, and functional degradation. For mangroves, no data are available on the impact of deforestation on the diversity and functionality of the specialized invertebrate fauna, critical for their functioning. We compiled a global dataset of mangrove invertebrate fauna comprising 364 species from 16 locations, classified into 64 functional entities (FEs). For each location, we calculated taxonomic distinctness (Δ+), functional richness (FRi), functional redundancy (FRe), and functional vulnerability (FVu) to assess functional integrity. Δ+ and FRi were significantly related to air temperature but not to geomorphic characteristics, mirroring the global biodiversity anomaly of mangrove trees. Neither of those two indices was linked to forest area, but both sharply decreased in human-impacted mangroves. About 60% of the locations showed an average FRe < 2, indicating that most of the FEs comprised one species only. Notable exceptions were the Eastern Indian Ocean and west Pacific Ocean locations, but also in this region, 57% of the FEs had no redundancy, placing mangroves among the most vulnerable ecosystems on the planet. Our study shows that despite low redundancy, even small mangrove patches host truly multifunctional faunal assemblages, ultimately underpinning their services. However, our analyses also suggest that even a modest local loss of invertebrate diversity could have significant negative consequences for many mangroves and cascading effects for adjacent ecosystems. This pattern of faunal-mediated ecosystem functionality is crucial for assessing the vulnerability of mangrove forests to anthropogenic impact and provides an approach to planning their effective conservation and restoration.

Mangrove forests, once dominant intertidal ecosystems in the tropics (1), are disappearing at devastating rates worldwide (2, 3). Estimates of their loss are often uncertain due to the nature of available datasets (4) and the imprecision in determining mangrove area (5), but the current consensus on mangrove loss in the last quarter century ranges between 35 to 86% in the worst affected countries (2). Although recent estimates show a decrease in mangrove deforestation (6), global destruction is still happening, putting mangrove ecosystem functionality and, ultimately, provisioning of ecosystem services at risk (7). As recently reassessed (8), mangroves are unrivaled carbon sinks (9) and often contribute significant carbon and nitrogen to offshore habitats (10). They also act as nurseries for species from connected ecosystems (11) and protect tropical coasts from erosion (12) as well as extreme events (13).As theoretical and empirical studies have shown (14, 15), species extinctions in natural ecosystems often lead to loss in functional diversity, reflected by a decrease in the number of functional traits (16). Models predict that species-poor systems have low functional redundancy and are more likely to experience functional loss with species extinction (14, 17). In comparison with many tropical terrestrial forests, mangroves are characterized by low tree species diversity (1). The continued reduction of mangrove area and cover, coupled with simplistic restoration efforts often establishing monocultures (18), is expected to result in a sharp decrease in mangrove tree biodiversity at a global scale (2). A relationship between such decline in tree diversity and the loss of mangrove ecosystem functionality has been assumed rather than demonstrated (19), as this relationship has proven difficult to measure. Significant positive correlations, however, have been demonstrated between the species richness of mangrove trees, the associated macrofauna, and potential influence on aboveground primary productivity (20). The nexus between biodiversity and ecosystem functionality of species-poor systems is yet to be clarified, but a recent study of scavenging (measured by rate of fish carcasses consumed by scavengers) in Australian mangrove-fringed estuaries has highlighted the vulnerability of such systems to species loss (21).While reliable datasets are available on global mangrove tree diversity (1, 5), no such information exists for the species composition, functional diversity, and functional redundancy of the associated fauna. The harsh environmental conditions characteristic of mangrove forests (i.e., wide daily or seasonal variability in salinity and pH, hypo-, or even anoxia of the soil) and the small number of foundation plant species compared to terrestrial forests (2) suggest a lower niche availability among mangrove resident macrofauna (22).Mangrove ecosystems support unique faunal assemblages (22, 23), including a diverse array of sessile and mobile invertebrates, particularly crustaceans and mollusks (24, 25). Brachyuran crab assemblages are highly diverse in Indo-West Pacific (IWP) mangroves (25, 26) and are known to play a major role in ecosystem functioning (8, 20, 23). Their bioturbation activity has a significant engineering effect on the sediment through constant irrigation and oxygenation (27, 28). These crabs can also play a critical role in shaping tree dominance (29), influencing carbon cycling (30, 31), and structuring the sediment microbiome (32). The diversity of mangrove-associated gastropods also peaks in the IWP region but shows a bimodal distribution, with modes in the eastern Pacific coast of Central and South America and in Southeast Asia (33). Both gastropods and bivalves are known to be important bioengineers and bio-irrigators, playing a major role in shaping the biochemical properties of mangrove sediment and water (23).Despite growing evidence that the functions of mangrove forests are strongly dependent on viable and diverse invertebrate assemblages (20, 23), only few studies at local scales have focused on the diversity and taxonomic structure of such assemblages. The functional richness and redundancy of the latter, critical to the ecosystems’ capacity for essential services, are unknown, as are their functional vulnerability. The functional diversity of a community with species distributed in a multidimensional functional space within a given ecosystem can be quantified through indices such as functional richness [FRi—the volume of multidimensional space occupied by all species in a community within functional space (34, 35)] and functional redundancy [FRe—how redundant species and functional groups are at a given location (36)], which are increasingly used for assessing ecosystem functioning. Recently, these measures, used in parallel with functional vulnerability [FVu—the potential decrease of functional diversity as a consequence of species loss (36)], have also proven to be useful tools for assessing impacts of disturbances on ecosystems (37, 38) and for forecasting possible responses to anthropogenic perturbations (16).In this study, we assessed the vulnerability of global mangrove ecosystems to the loss of functions mediated by macrobenthic species by computing taxonomic distinctness Δ+ (39), FRi, FRe, and FVu indices based on crustacean and mollusk assemblages recorded from 16 different mangrove forests across the world. We assigned functional traits to the 209 crustacean and 155 mollusk species in our database according to their respective 1) feeding habits, 2) behavioral traits potentially affecting ecosystem characteristics, and 3) microhabitats. By using functional traits as proxies for functions, this approach allowed us to establish global patterns of macrobenthic taxonomic richness and ecosystem functionality in mangroves and to assess the vulnerability of the mangrove fauna as well as resilience of ecosystem functions mediated by them to current and future anthropogenic threats.     

Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons

It is well known that Rett Syndrome, a severe postnatal childhood neurological disorder, is mostly caused by mutations in the MECP2 gene. However, how deficiencies in MeCP2 contribute to the neurological dysfunction of Rett Syndrome is not clear. We aimed to resolve the role of MeCP2 epigenetic regulation in postnatal brain development in an Mecp2-deficient mouse model. We found that, while Mecp2 was not critical for the production of immature neurons in the dentate gyrus (DG) of the hippocampus, the newly generated neurons exhibited pronounced deficits in neuronal maturation, including delayed transition into a more mature stage, altered expression of presynaptic proteins and reduced dendritic spine density. Furthermore, analysis of gene expression profiles of isolated DG granule neurons revealed abnormal expression levels of a number of genes previously shown to be important for synaptogenesis. Our studies suggest that MeCP2 plays a central role in neuronal maturation, which might be mediated through epigenetic control of expression pathways that are instrumental in both dendritic development and synaptogenesis.     

Molecular layer perforant path-associated cells contribute to feed-forward inhibition in the adult dentate gyrus

New neurons, which have been implicated in pattern separation, are continually generated in the dentate gyrus in the adult hippocampus. Using a genetically modified rabies virus, we demonstrated that molecular layer perforant pathway (MOPP) cells innervated newborn granule neurons in adult mouse brain. Stimulating the perforant pathway resulted in the activation of MOPP cells before the activation of dentate granule neurons. Moreover, activation of MOPP cells by focal uncaging of glutamate induced strong inhibition of granule cells. Together, these results indicate that MOPP cells located in the molecular layer of the dentate gyrus contribute to feed-forward inhibition of granule cells via perforant pathway activation.     

Stimulation-produced spinal inhibition from the midbrain in the rat is mediated by an excitatory amino acid neurotransmitter in the medial medulla

It has been previously established that a bulbar relay plays an important role in descending inhibition of spinal dorsal horn nociceptive neurons and nociceptive reflexes produced by stimulation in the midbrain periaqueductal gray (PAG). In the present study, selected receptor antagonists were microinjected into the medial medullary nucleus raphe magnus (NRM) to determine whether descending inhibition of the tail flick (TF) reflex in the rat produced by focal electrical stimulation in the midbrain PAG was mediated by serotonin, opioid, or glutamate receptors on bulbospinal neurons in the NRM. It was determined in initial experiments that the serotonin receptor antagonist methysergide, the opioid receptor antagonist naloxone, the local anesthetic lidocaine, and the glutamate receptor antagonists gamma-D-glutamylglycine (DGG) and DL-2-amino-5-phosphonovalerate (APV) microinjected into the medulla all significantly increased the threshold of focal electrical stimulation in the medulla required to inhibit the TF reflex. The antinociceptive efficacy of agonists at opioid, serotonin, and glutamate receptors was also tested in other experiments. The microinjection of morphine (2.5-10 micrograms) into the NRM increased significantly TF latencies in a dose-dependent manner in rats in the awake or lightly anesthetized state; morphine was more potent in awake rats. Inhibition of the TF reflex produced by the microinjection of morphine was reversed by a subsequent microinjection of naloxone into the same site in the medulla. The microinjection of serotonin (5 and 10 micrograms), however, did not affect the latency of the TF reflex in either awake or lightly anesthetized rats. Glutamate (100 microM, 0.5 microliter) microinjected into the rostral ventral medulla produced an inhibition of the TF reflex of short duration that could be blocked or attenuated significantly by the glutamate receptor antagonists DGG or APV microinjected into the same site. In subsequent experiments, a nonspecific functional block was introduced adjacent to the NRM bilaterally in the medullary reticular formations (MRFs) by the microinjection of the local anesthetic lidocaine; receptor antagonists were then microinjected into the NRM and their effect on the threshold of focal electrical stimulation in the PAG to inhibit the TF reflex determined. No increase was seen in stimulation thresholds in the PAG following the microinjection of either methysergide or naloxone into the NRM. Following the microinjection of lidocaine, DGG or APV into the NRM, the stimulation threshold in the PAG for inhibition of the TF reflex was increased significantly.(ABSTRACT TRUNCATED AT 400 WORDS)     

The Role of Fetal,Infant, and Childhood Nutrition in the Timing of Sexual Maturation

Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to central neurotransmitters, hormones, and environmental factors leading to hypothalamic-pituitary-gonadal axis maturation. The connection between hormones and nutrition during critical periods of growth, like fetal life or infancy, is fundamental for metabolic adaptation response and pubertal development control and prediction. Since birth weight is an important indicator of growth estimation during fetal life, restricted prenatal growth, such as intrauterine growth restriction (IUGR) and small for gestational age (SGA), may impact endocrine system, affecting pubertal development. Successively, lactation along with early life optimal nutrition during infancy and childhood may be important in order to set up timing of sexual maturation and provide successful reproduction at a later time. Sexual maturation and healthy growth are also influenced by nutrition requirements and diet composition. Early nutritional surveillance and monitoring of pubertal development is recommended in all children, particularly in those at risk, such as the ones born SGA and/or IUGR, as well as in the case of sudden weight gain during infancy. Adequate macro and micronutrient intake is essential for healthy growth and sexual maturity.     

Use of fibrin glue (Tissucol) for mesh fixation in laparoscopic transabdominal hernia repair

The aim of this study was to demonstrate the efficacy and safety and report the results of prosthesis fixation by means of fibrin glue during laparoscopic treatment of inguinal and femoral hernias. From September 2001 to December 2004 we employed fibrin glue (Tissucol, Baxter, Maurepas) as a means of fixation during a transabdominal preperitoneal procedure in 230 patients (225 M, 5 F) with an average age of 45 years (range: 20-75) presenting a total of 320 hernias: 140/230 (60.8%) were monolateral and 90 (39.2%) bilateral; 267/320 hernias (83.6%) were primary and 53 (16.4%) recurrent. We had no perioperative complications. After an average follow-up of 26 months (range: 1-40) the only postoperative complications we encountered were 6 seromas (1.8%) and 1 trocar-site haematoma (0.3%). None of the patients developed scrotal haematomas. None of the patients complained of immediate or subsequent paraesthesia or cruralgia. No recurrences have occurred to date. The mean operative time was 30 minutes for monolateral hernias (range: 15-45) and about 50 minutes for bilateral hernias (range: 30-75). This was true of both primary and recurrent hernias. Patients are usually discharged on day 1 postoperatively. In the absence of pain, working activities are resumed after 5 days and sports can be practiced after 10 days. In our experience, fibrin glue (Tissucol) is the best way of fixing the mesh during a transabdominal preperitoneal procedure. It is better than mechanical devices because, though guaranteeing prosthetic stability, it is completely non-traumatic and presents none of the problems of metal clips.