Cellular Bases of Barbiturate and Phenytoin Anticonvulsant Drug Action

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65509/1/j.1528-1157.1982.tb06093.x.pd

Development Trends of White Matter Connectivity in the First Years of Life

The human brain is organized into a collection of interacting networks with specialized functions to support various cognitive functions. Recent research has reached a consensus that the brain manifests small-world topology, which implicates both global and local efficiency at minimal wiring costs, and also modular organization, which indicates functional segregation and specialization. However, the important questions of how and when the small-world topology and modular organization come into existence remain largely unanswered. Taking a graph theoretic approach, we attempt to shed light on this matter by an in vivo study, using diffusion tensor imaging based fiber tractography, on 39 healthy pediatric subjects with longitudinal data collected at average ages of 2 weeks, 1 year, and 2 years. Our results indicate that the small-world architecture exists at birth with efficiency that increases in later stages of development. In addition, we found that the networks are broad scale in nature, signifying the existence of pivotal connection hubs and resilience of the brain network to random and targeted attacks. We also observed, with development, that the brain network seems to evolve progressively from a local, predominantly proximity based, connectivity pattern to a more distributed, predominantly functional based, connectivity pattern. These observations suggest that the brain in the early years of life has relatively efficient systems that may solve similar information processing problems, but in divergent ways

A steep decline of malaria morbidity and mortality trends in Eritrea between 2000 and 2004: the effect of combination of control methods

BACKGROUND: Malaria is a huge public health problem in Africa that is responsible for more than one million deaths annually. In line with the Roll Back Malaria initiative and the Abuja Declaration, Eritrea and other African countries have intensified their fight against malaria. This study examines the impact of Eritrea's Roll Back Malaria Programme: 2000–2004 and the effects and possible interactions between the public health interventions in use. METHODS: This study employed cross-sectional survey to collect data from households, community and health facilities on coverage and usage of Insecticide-Treated Nets (ITNs), Indoor Residual Spraying (IRS), larvicidal activities and malaria case management. Comparative data was obtained from a similar survey carried out in 2001. Data from the Health Management Information System (HMIS) and reports of the annual assessments by the National Malaria Control Programme was used to assess impact. Time series model (ARIMA) was used to assess association. RESULTS: In the period 2000–2004, approximately 874,000 ITNs were distributed and 13,109 health workers and community health agents were trained on malaria case management. In 2004, approximately 81% households owned at least one net, of which 73% were ITNs and 58.6% of children 0–5 years slept under a net. The proportion of malaria cases managed by community health agents rose from 50% in 1999 to 78% in 2004. IRS coverage increased with the combined amount of DDT and Malathion used rising from 6,444 kg, in 2000 to 43,491 kg, in 2004, increasing the population protected from 117,017 to 259,420. Drug resistance necessitated regimen change to chloroquine plus sulfadoxine-pyrimethamine. During the period, there was a steep decline in malaria morbidity and case fatality by 84% and 40% respectively. Malaria morbidity was strongly correlated to the numbers of ITNs distributed (β = -0.125, p < 0.005) and the amount (kg) of DDT and Malathion used for IRS (β = -2.352, p < 0.05). The correlation between malaria case fatality and ITNs, IRS, population protected and annual rainfall was not statistically significant. CONCLUSION: Eritrea has within 5 years attained key Roll Back Malaria targets. ITNs and IRS contributed most to reducing malaria morbidity

Quantal Glutamate Release Is Essential for Reliable Neuronal Encodings in Cerebral Networks

Background: The neurons and synapses work coordinately to program the brain codes of controlling cognition and behaviors. Spike patterns at the presynaptic neurons regulate synaptic transmission. The quantitative regulations of synapse dynamics in spike encoding at the postsynaptic neurons remain unclear. Methodology/Principal Findings: With dual whole-cell recordings at synapse-paired cells in mouse cortical slices, we have investigated the regulation of synapse dynamics to neuronal spike encoding at cerebral circuits assembled by pyramidal neurons and GABAergic ones. Our studies at unitary synapses show that postsynaptic responses are constant over time, such as glutamate receptor-channel currents at GABAergic neurons and glutamate transport currents at astrocytes, indicating quantal glutamate release. In terms of its physiological impact, our results demonstrate that the signals integrated from quantal glutamatergic synapses drive spike encoding at GABAergic neurons reliably, which in turn precisely set spike encoding at pyramidal neurons through feedback inhibition. Conclusion/Significance: Our studies provide the evidences for the quantal glutamate release to drive the spike encodings precisely in cortical circuits, which may be essential for programming the reliable codes in the brain to manage wellorganize

Sex-specific effects of the local social environment on juvenile post-fledging dispersal in great tits

An individual’s decision to disperse from the natal habitat can affect its future fitness prospects. Especially in species with sex-biased dispersal, we expect the cost–benefit balance for dispersal to vary according to the social environment (e.g., local sex ratio and density). However, little is known about the social factors affecting dispersal decisions and about the temporal and spatial patterns of the dispersal process. In our study, we investigated experimentally the effects of the social environment on post-fledging dispersal of juvenile great tits by simultaneously manipulating the density and sex ratio of fledglings within forest plots. We expected young females in the post-fledging period mainly to compete for resources related to food and, as they are subordinate to males, we predicted higher female dispersal from male-biased plots. Juvenile males compete for vacant territories already in late summer and autumn; thus, we predicted increased male dispersal from high density and male-biased plots. We found that juvenile females had a higher probability to leave male-biased plots and had dispersed further from male-biased plots in the later post-fledging phase when juvenile males start to become territorial and more aggressive. Juvenile males were least likely to leave male-biased plots and had smallest dispersal distances from female-biased plots early after fledging. The results suggest that the social environment differentially affected the costs and benefits of philopatry for male and female juveniles. The local sex ratio of individuals is thus an important social trait to be considered for understanding sex-specific dispersal processes

Motor activity improves temporal expectancy

Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1) pointing with a whole-body movement, (2) pointing only with the arm, (3) imagining pointing with a whole-body movement, (4) simply watching the stimulus presentation, (5) pointing with a whole-body movement in response to a target that appeared at irregular intervals (6) reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments

Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex

In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC

What should an ideal spinal injury classification system consist of? A methodological review and conceptual proposal for future classifications

Since Böhler published the first categorization of spinal injuries based on plain radiographic examinations in 1929, numerous classifications have been proposed. Despite all these efforts, however, only a few have been tested for reliability and validity. This methodological, conceptual review summarizes that a spinal injury classification system should be clinically relevant, reliable and accurate. The clinical relevance of a classification is directly related to its content validity. The ideal content of a spinal injury classification should only include injury characteristics of the vertebral column, is primarily based on the increasingly routinely performed CT imaging, and is clearly distinctive from severity scales and treatment algorithms. Clearly defined observation and conversion criteria are crucial determinants of classification systems’ reliability and accuracy. Ideally, two principle spinal injury characteristics should be easy to discern on diagnostic images: the specific location and morphology of the injured spinal structure. Given the current evidence and diagnostic imaging technology, descriptions of the mechanisms of injury and ligamentous injury should not be included in a spinal injury classification. The presence of concomitant neurologic deficits can be integrated in a spinal injury severity scale, which in turn can be considered in a spinal injury treatment algorithm. Ideally, a validation pathway of a spinal injury classification system should be completed prior to its clinical and scientific implementation. This review provides a methodological concept which might be considered prior to the synthesis of new or modified spinal injury classifications

Vaccination with a non-human random sequence amyloid oligomer mimic results in improved cognitive function and reduced plaque deposition and micro hemorrhage in Tg2576 mice

BACKGROUND: It is well established that vaccination of humans and transgenic animals against fibrillar Aβ prevents amyloid accumulation in plaques and preserves cognitive function in transgenic mouse models. However, autoimmune side effects have halted the development of vaccines based on full length human Aβ. Further development of an effective vaccine depends on overcoming these side effects while maintaining an effective immune response. RESULTS: We have previously reported that the immune response to amyloid oligomers is largely directed against generic epitopes that are common to amyloid oligomers of many different proteins and independent of a specific amino acid sequence. Here we have examined whether we can exploit this generic immune response to develop a vaccine that targets amyloid oligomers using a non-human random sequence amyloid oligomer. In order to study the effect of vaccination against generic oligomer epitopes, a random sequence oligomer (3A) was selected as it forms oligomers that react with the oligomer specific A11 antibody. Oligomer mimics from 3A peptide, Aβ, islet amyloid polypeptide (IAPP), and Aβ fibrils were used to vaccinate Tg2576 mice, which develop a progressive accumulation of plaques and cognitive impairment. Vaccination with the 3A random sequence antigen was just as effective as vaccination with the other antigens in improving cognitive function and reducing total plaque load (Aβ burden) in the Tg2576 mouse brains, but was associated with a much lower incidence of micro hemorrhage than Aβ antigens. CONCLUSION: These results shows that the amyloid Aβ sequence is not necessary to produce a protective immune response that specifically targets generic amyloid oligomers. Using a non-human, random sequence antigen may facilitate the development of a vaccine that avoids autoimmune side effects