A balance and proprioception intervention programme to enhance combat performance in military personnel.

BACKGROUND: Optimal functioning of the lower extremities under repeated movements on unstable surfaces is essential for military effectiveness. Intervention training to promote proprioceptive ability should be considered in order to limit the risk for musculoskeletal injuries. The aim of this study was to assess the effect of a proprioceptive intervention programme on static and dynamic postural balance among Israel Defense Forces combat soldiers. METHODS: Twenty-seven male soldiers, aged 18-20 years, from a physical fitness instructor's course, were randomly divided into two groups matched by age and army unit. The intervention group (INT) underwent 4 weeks of proprioceptive exercises for 10 min daily; the control group underwent 4 weeks of upper body stretching exercises for 10 min daily. All participants were tested pre and postintervention for both static and dynamic postural balance. RESULTS: Significant interaction (condition*pre-post-test*group) was found for static postural balance, indicating that for the INT group, in condition 3 (on an unstable surface-BOSU), the post-test result was significantly better compared with the pretest result (p<0.05). Following intervention, the INT group showed significant correlations between static postural stability in condition 2 (eyes closed) and the dynamic postural stability (length of time walked on the beam following fatigue) (r ranged from 0.647 to 0.822; p<0.05). CONCLUSIONS: The proprioceptive intervention programme for combat soldiers improved static postural balance on unstable surfaces, and improved the correlation between static postural balance in the eyes closed condition and dynamic postural balance following fatigue. Further longitudinal studies are needed to verify the relationship between proprioception programmes, additional weight bearing and the reduction of subsequent injuries in combat soldiers.

The relationship between back handspring step out performance and take-off technique in female gymnasts.

Although the back handspring step out (BHS) is a foundational skill in balance beam routines, it can be performed using different take-off techniques. Back injuries are highly prevalent in the BHS due to the combination of high spine extension and joint loading. However, it is unclear which technique minimises injury risk or leads to better BHS performance. The purpose of the study was to identify techniques used for the BHS take-off and analyse the resulting BHS performance. Gymnasts were found to use either: Simultaneous Flexion-trunk and knees flex at the same time; Sequential Flexion-trunk reaches its maximum flexion followed by knee flexion; or Double-Bounce-knees and trunk both flex and then the knees extend and flex again. To assess performance, point deductions were calculated, and dynamic balance, ground reaction forces (GRFs) and relevant joint angles were analysed. The techniques had no differences in point deductions or dynamic balance, but there were differences in GRFs, spine extension and knee flexion. The Sequential Flexion technique had the lowest spine extension, which potentially reduces back injuries and the lowest knee flexion, which is a BHS requirement. These results support the use of Sequential Flexion technique when performing the BHS.

Spreading Depolarizations Contribute to the Acute Behavior Deficits Associated With a Mild Traumatic Brain Injury in Mice.

Concussions or mild traumatic brain injuries (mTBIs) are often described and diagnosed by the acute signs and symptoms of neurological dysfunction including weakness, dizziness, disorientation, headaches, and altered mental state. The cellular and physiological mechanisms of neurological dysfunction and acute symptoms are unclear. Spreading depolarizations (SDs) occur after severe TBIs and have recently been identified in closed-skull mouse models of mTBIs. SDs are massive waves of complete depolarization that result in suppression of cortical activity for multiple minutes. Despite the clear disruption of brain physiology after SDs, the role of SDs in the acute neurological dysfunction and acute behavioral deficits following mTBIs remains unclear. We used a closed-skull mouse model of mTBI and a series of behavioral tasks collectively scored as the neurological severity score (NSS) to assess acute behavior. Our results indicate that mTBIs are associated with significant behavioral deficits in the open field and NSS tasks relative to sham-condition animals. The behavioral deficits associated with the mTBI recovered within 3 h. We show here that the presence of mTBI-induced bilateral SDs were significantly associated with the acute behavioral deficits. To identify the role of SDs in the acute behavioral deficits, we used exogenous potassium and optogenetic approaches to induce SDs in the absence of the mTBI. Bilateral SDs alone were associated with similar behavioral deficits in the open field and NSS tasks. Collectively, these studies demonstrate that bilateral SDs are linked to the acute behavioral deficits associated with mTBIs.

Positron emission tomography neuroimaging of [18F]fluorodeoxyglucose uptake and related behavior in the Pink1-/- rat model of Parkinson disease.

Introduction: Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The Pink1-/- rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in Pink1-/- and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior. Methods: Pink1-/- (n = 12) and WT (n = 14) rats were imaged by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified a priori for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam. Results: Relative glucose metabolism was significantly different in Pink1-/- rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, Pink1-/- rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra. Conclusion: FDG PET reveals abnormalities in relative regional brain glucose metabolism in Pink1-/- rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the Pink1-/- PD model.

Gymnastic skills on a balance beam with simulated height.

Virtual reality (VR) is a valuable tool for simulating dangerous situations and training under these conditions with a reduced possibility of injury. This could be beneficial within different sports scenarios. In gymnastics, the height of the balance beam can be dangerous and frightening, especially for beginners. Here, a simulated height can reduce the participant's risk of injury and facilitate entry to balance beam gymnastics. However, the investigation of sports performance in a virtual environment is rare. Therefore, the current study aims to compare beginners' performance in balance beam tasks between the real world (RW) and VR. 34 sports students executed gymnastic balancing forward, backward and the extension of one leg to the front, the side and the back on a regular balance beam in the RW and on a balance beam with simulated height in VR (using a head-mounted display). We analyzed beginners' performance in both conditions (RW and VR) regarding different criteria for each balance beam task. Statistical analyses show significant differences in performance with better results in RW (p < .05). Especially the body tension and the upper body posture were superior in RW. One explanation can be the more difficult regulation of the balance in VR. For the tasks where the motion took part in a fixed position on the beam, the further performance aspects were similar for RW and VR. When the participants moved along the beam, further performance aspects, like the leg extension, were better in RW. In total, the participants executed the VR balance beam tasks with decreased danger of injury due to the simulated height of the balance beam, but their performance was slightly limited. We conclude that for the first contact with the height of a balance beam, VR is a suitable tool to reduce the danger of injury occurring from falling off the beam and facilitate entry to balance beam gymnastics.

Cerebellar granule cell signaling is indispensable for normal motor performance.

Within the cerebellar cortex, mossy fibers (MFs) excite granule cells (GCs) that excite Purkinje cells (PCs), which provide outputs to the deep cerebellar nuclei (DCNs). It is well established that PC disruption produces motor deficits such as ataxia. This could arise from either decreases in ongoing PC-DCN inhibition, increases in the variability of PC firing, or disruption of the flow of MF-evoked signals. Remarkably, it is not known whether GCs are essential for normal motor function. Here we address this issue by selectively eliminating calcium channels that mediate transmission (CaV2.1, CaV2.2, and CaV2.3) in a combinatorial manner. We observe profound motor deficits but only when all CaV2 channels are eliminated. In these mice, the baseline rate and variability of PC firing are unaltered, and locomotion-dependent increases in PC firing are eliminated. We conclude that GCs are indispensable for normal motor performance and that disruption of MF-induced signals impairs motor performance.

Faster ≠ Smarter: Children with Higher Levels of Ability Take Longer to Give Incorrect Answers, Especially When the Task Matches Their Ability.

The stereotype that children who are more able solve tasks quicker than their less capable peers exists both in and outside education. The F > C phenomenon and the distance-difficulty hypothesis offer alternative explanations of the time needed to complete a task; the former by the response correctness and the latter by the relative difference between the difficulty of the task and the ability of the examinee. To test these alternative explanations, we extracted IRT-based ability estimates and task difficulties from a sample of 514 children, 53% girls, M(age) = 10.3 years; who answered 29 Piagetian balance beam tasks. We used the answer correctness and task difficulty as predictors in multilevel regression models when controlling for children's ability levels. Our results challenge the 'faster equals smarter' stereotype. We show that ability levels predict the time needed to solve a task when the task is solved incorrectly, though only with moderately and highly difficult items. Moreover, children with higher ability levels take longer to answer items incorrectly, and tasks equal to children's ability levels take more time than very easy or difficult tasks. We conclude that the relationship between ability, task difficulty, and answer correctness is complex, and warn education professionals against basing their professional judgment on students' quickness.

Intermittent Visual Occlusions Increase Balance Training Effectiveness.

Improving dynamic balance can prevent falls in humans with neurological and mechanical deficits. Dynamic balance requires the neural integration of multisensory information to constantly assess the state of body mechanics. Prior research found that intermittent visual rotations improved balance training during walking on a narrow beam, but limitations from the immersive virtual reality headset hindered balance training effectiveness overall. We theorized that intermittent visual occlusions with electrically controlled liquid crystal glasses would overcome the previous limitations of the immersive virtual reality headset and provide a means to enhance dynamic balance training efficacy. Forty healthy young individuals walked on a treadmill-mounted balance beam for 30 min (20 subjects with intermittent visual occlusions and 20 subjects with unperturbed vision). Balance performance, in number of step-offs of the beam, improved by 78% for the visual occlusions group on the same day of the training, a near fourfold improvement compared to the 21% improvement for the unperturbed vision group (t(38) = -5.2, p < 0.001). The difference between groups was also apparent 2 weeks later testing for retention (60% improvement for the visual occlusions group, 5% for the unperturbed vision group; t(38) = -4.2, p < 0.001). Intermittent visual occlusions are likely a simple method for enhancing balance training in dynamic motor tasks.

Repression of long non-coding RNA MEG3 restores nerve growth and alleviates neurological impairment after cerebral ischemia-reperfusion injury in a rat model.

OBJECTIVE: This study was performed to investigate effect of long non-coding RNA (lncRNA) MEG3 on nerve growth and neurological impairment in a rat model after cerebral ischemia-reperfusion injury (IRI) through the Wnt/ß-catenin signaling pathway. METHODS: Rat models of middle cerebral artery occlusion (MCAO) were established to stimulate an environment of cerebral IRI. The modeled rats were subjected to negative control (NC), MEG3, si-MEG3, classical Wnt pathway inhibitor DKK1 or classical Wnt pathway activator LiCl to validate the effect of MEG3 on neurological impairment and nerve growth. Neurological deficit scoring, fault-foot test and balance beam test were performed to assess neurological impairment. TTC staining, dry-wet weight method and Evan's blue (EB) staining were employed to determine infarct area, water content of brain tissues and blood-brain barrier (BBB) permeability, respectively. Neuronal apoptosis and necrosis were observed by TUNEL staining and Fluoro-Jade C staining. ELISA was adopted to identify levels of nerve growth factors to identify neurogenesis conditions, including brain derived neurotrophic factor (BDNF), nerve growth factor (NGF) and basic fibroblast growth factor (bFGF). Nissl staining was used to detect the survival of neurons in brain tissues of rats. Western blot analysis was used to detect the expression of key proteins in Wnt/ß-catenin signaling pathway in brain tissues. RESULTS: High expression of MEG3 was identified in rat models of MACAO, the brain tissues of which manifested obvious neurological impairment, increased infarct area, water content, BBB permeability, accelerated neuronal apoptosis and necrosis, increased surviving neurons, upregulated expression of key proteins in Wnt/ß-catenin signaling pathway and elevated levels of BDNF, NGF and bFGF. With the treatment of si-MEG3, the MEG3 expression was reduced; whereby, modeled rats showed ameliorated neurological impairment, reduced infarct area, water content, BBB permeability, neuronal apoptosis and necrosis and significantly enhanced neurogenesis. The treatment of MEG3 exhibited an opposite trend. After treatment with DKK1, the effect of si-MEG3 was reversed. After treatment with LiCl, the effect of MEG3 was reversed. CONCLUSION: Based on the findings of this study, down-regulation of lncRNA MEG3 expression enhanced nerve growth and alleviated neurological impairment of rats after cerebral IRI through the activation of the Wnt/ß-catenin signaling pathway.

Manganese contamination affects the motor performance of wild northern quolls (Dasyurus hallucatus).

Neuromotor deficits are an important sign of manganese (Mn) toxicity in humans and laboratory animals. However, the impacts of Mn exposure on the motor function of wild animals remains largely unknown. Here, we assessed the impact of chronic exposure to Mn from active mining operations on Groote Eylandt, Australia on the motor function of the semi-arboreal northern quoll (Dasyurus hallucatus), an endangered species. The three motor tests conducted-maximum sprint speed on a straight run, manoeuvrability around a corner, and motor control on a balance beam-showed that elevated Mn body burden did not diminish performance of these traits. However, quolls with higher Mn body burden approached a corner at a significantly narrower range of speeds, due to a significantly lower maximum approach speed. Slower speeds approaching a turn may reduce success at catching prey and avoiding predators. Given that maximum sprint speed on a straight run was not affected by Mn body burden, but maximum speed entering a corner was, slower speeds approaching a turn may reflect compensation for otherwise impaired performance in the turn.

Task difficulty has no effect on haptic anchoring during tandem walking in young and older adults.

This study assessed the contribution of the "anchor system's" haptic information to balance control during walking at two levels of difficulty. Seventeen young adults and seventeen older adults performed 20 randomized trials of tandem walking in a straight line, on level ground and on a slightly-raised balance beam, both with and without the use of the anchors. The anchor consists of two flexible cables, whose ends participants hold in each hand, to which weights (125 g) are attached at the opposing ends, and which rest on the ground. As the participants walk, they pull on the cables, dragging the anchors. Spatiotemporal gait variables (step speed and single- and double-support duration) were processed using retro-reflective markers on anatomical sites. An accelerometer positioned in the cervical region registered trunk acceleration. Walking on the balance beam increased single- and double-support duration and reduced step speed in older adults, which suggests that this condition was more difficult than walking on the level ground. The anchors reduced trunk acceleration in the frontal plane, but the level of difficulty of the walking task showed no effect. Thus, varying the difficulty of the task had no influence on the way in which participants used the anchor system while tandem walking. The older adults exhibited more difficulty in walking on the balance beam as compared to the younger adults; however, the effect of the anchor system was similar in both groups.

Mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the substantia nigra of mice with MPTP-induced Parkinson's disease.

We examined whether exposure to mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the substantia nigra of a neurotoxic animal model with Parkinson's disease. Mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride and probenecid twice a week were divided into two groups: mice with mild hyperbaric oxygen and those without. The mice with mild hyperbaric oxygen were exposed to 1317hPa with 45% oxygen for 3h, three times a week. The decrease in dopaminergic neurons of mice with Parkinson's disease was inhibited by 11 weeks of exposure to mild hyperbaric oxygen. We conclude that exposure to mild hyperbaric oxygen is effective in preventing the progression of Parkinson's disease.

Gradual Cerebral Hypoperfusion Impairs Fear Conditioning and Object Recognition Learning and Memory in Mice: Potential Roles of Neurodegeneration and Cholinergic Dysfunction.

In the present study, male C57BL/6J mice were subjected to gradual cerebral hypoperfusion by implanting an ameroid constrictor (AC) on the left common carotid artery (CCA) and a stenosis on the right CCA. In the sham group, all surgical procedures were kept the same except no AC was implanted and stenosis was not performed. One month following the surgical procedures, fear conditioning and object recognition tests were conducted to evaluate learning and memory functions and motor functions were assessed using a balance beam test. At the experimental endpoint, mice were perfused and brains were collected for immunostaining and histology. Learning and memory as well as motor functions were significantly impaired in the hypoperfusion group. The immunoreactivity to choline acetyltransferase was decreased in dorsal striatum and basal forebrain of the hypoperfusion group indicating that cholinergic tone in these brain regions was compromised. In addition, an increased number of Fluoro-Jade positive neurons was also found in cerebral cortex, dorsal striatum and hippocampus indicating neurodegeneration in these brain regions. Based on this pattern of data, we argued that this mouse model would be a useful tool to investigate the therapeutic interventions for the treatment of vascular dementia. Additionally, this model could be employed to exploit the effect of microvascular occlusions on cognitive impairment in the absence and presence of Alzheimer's disease pathology.

WHOLE BODY VIBRATION IMPROVES ATTENTION AND MOTOR PERFORMANCE IN MICE DEPENDING ON THE DURATION OF THE WHOLE-BODY VIBRATION SESSION.

BACKGROUND: Whole body vibration (WBV) is a form of physical stimulation via mechanical vibrations transmitted to a subject. It is assumed that WBV induces sensory stimulation in cortical brain regions through the activation of skin and muscle receptors responding to the vibration. The effects of WBV on muscle strength are well described. However, little is known about the impact of WBV on the brain. Recently, it was shown in humans that WBV improves attention in an acute WBV protocol. Preclinical research is needed to unravel the underlying brain mechanism. As a first step, we examined whether chronic WBV improves attention in mice. MATERIAL AND METHODS: A custom made vibrating platform for mice with low intensity vibrations was used. Male CD1 mice (3 months of age) received five weeks WBV (30 Hz; 1.9 G), five days a week with sessions of five (n=12) or 30 (n=10) minutes. Control mice (pseudo-WBV; n=12 and 10 for the five and 30 minute sessions, respectively) were treated in a similar way, but did not receive the actual vibration. Object recognition tasks were used as an attention test (novel and spatial object recognition - the primary outcome measure). A Balance beam was used for motor performance, serving as a secondary outcome measure. RESULTS: WBV sessions of five (but not WBV sessions of 30 minutes) improved balance beam performance (mice gained 28% in time needed to cross the beam) and novel object recognition (mice paid significantly more attention to the novel object) as compared to pseudo WBV, but no change was found for spatial object performance (mice did not notice the relocation). Although 30 minutes WBV sessions were not beneficial, it did not impair either attention or motor performance. CONCLUSION: These results show that brief sessions of WBV improve, next to motor performance, attention for object recognition, but not spatial cues of the objects. The selective improvement of attention in mice opens the avenue to unravel the underlying brain mechanisms.

Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences.

Two tests often used in aging research, the elevated path test and the Morris water maze test, were examined for their application to the study of brain aging in a large sample of C57BL/6JNia mice. Specifically, these studies assessed: (1) sensitivity to age and the degree of interrelatedness among different behavioral measures derived from these tests, (2) the effect of age on variation in the measurements, and (3) the reliability of individual differences in performance on the tests. Both tests detected age-related deficits in group performance that occurred independently of each other. However, analysis of data obtained on the Morris water maze test revealed three relatively independent components of cognitive performance. Performance in initial acquisition of spatial learning in the Morris maze was not highly correlated with performance during reversal learning (when mice were required to learn a new spatial location), whereas performance in both of those phases was independent of spatial performance assessed during a single probe trial administered at the end of acquisition training. Moreover, impaired performance during initial acquisition could be detected at an earlier age than impairments in reversal learning. There were modest but significant age-related increases in the variance of both elevated path test scores and in several measures of learning in the Morris maze test. Analysis of test scores of mice across repeated testing sessions confirmed reliability of the measurements obtained for cognitive and psychomotor function. Power calculations confirmed that there are sufficiently large age-related differences in elevated path test performance, relative to within age variability, to render this test useful for studies into the ability of an intervention to prevent or reverse age-related deficits in psychomotor performance. Power calculations indicated a need for larger sample sizes for detection of intervention effects on cognitive components of the Morris water maze test, at least when implemented at the ages tested in this study. Variability among old mice in both tests, including each of the various independent measures in the Morris maze, may be useful for elucidating the biological bases of different aspects of dysfunctional brain aging.

Behavior Test Relevant to α2/α3Na(+)/K(+)-ATPase Gene Modified Mouse Models.

The behavioral phenotypes of mice are the result of a complex interplay between overall health, sensory abilities, learning and memory, motor function as well as developmental milestones, feeding, sexual, parental, and social behaviors. This chapter lists a selected number of key behavioral tests, specifically designed to assay fundamental behavioral features such as memory, activity, and motor skills in mice models.

Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits.

The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS-/- mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS-/- mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS-/- mice and their wild type controls received alcohol (0.0, 2.2, or 4.4mg/g) daily over postnatal days 4-9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS-/- and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS-/- mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS-/- mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS-/- mice, but not in wild type. Thus, homozygous mutation of the nNOS gene increases vulnerability to alcohol-induced cerebellar dysfunction and neuronal loss. nNOS is the first gene identified whose mutation worsens alcohol-induced cerebellar behavioral deficits.

Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats.

Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT) involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of 'learned non-use' and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model) group, a CIMT + model (CIMT) group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinson׳s disease.

Deferoxamine (DFO) has shown therapeutic promise for the treatment of Parkinson׳s disease (PD) as it has reduced both behavioral and biochemical deficits when injected into the brain of rodent models of PD. Intranasally administered DFO targets the brain directly but non-invasively and has been effective in animal models of stroke and Alzheimer׳s disease. In this study we sought to determine whether intranasal (IN) DFO could be neuroprotective for PD in a rat model. PD was induced with a unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, while sham surgery rats received saline injections. Rats were pre-treated three times with either IN DFO or saline (starting 4 days before 6-OHDA), and post-treated twice/wk for one month before behavioral tests. In the apomorphine-induced rotational test, IN DFO significantly decreased the number of contralateral turns after injection of apomorphine HCl (p<0.05). Also, IN DFO significantly decreased limb asymmetry in the rearing tube as measured with contralateral limb touches (p<0.05). The IN DFO treatment yielded a trend towards decreased contralateral foot-slips on the tapered balance beam, though the difference was not significant. Finally, IN DFO-treated rats had increased preservation of tyrosine hydroxylase immunoreactive neurons in the substantia nigra (p<0.05). These results confirm that DFO is beneficial in a 6-OHDA model and demonstrate improvement in motor deficits and dopaminergic neuronal survival with non-invasive intranasal delivery, making this an attractive potential treatment for PD.

The balance beam metaphor: a perspective on clinical diagnosis.

Understanding the impact of clinical findings in discriminating between possible causes of a patient's presentation is essential in clinical judgment. A balance beam is a natural physical analogue that can accurately represent the combination of several pieces of evidence with varying ability to discriminate between disease hypotheses. Calculation of Bayes' theorem using log(posterior odds) as a function of log(prior odds) and the logarithms of the evidence's likelihood ratios maps onto the physical forces affecting objects placed on a balance beam. We describe the rules governing the functioning of tokens representing clinical findings in the comparison of 2 competing diseases. The likelihood ratios corresponding to positive (LR+) or negative (LR-) observations for each symptom determine the lateral position at which the symptom's token is placed on the beam, using a weight if the finding is present and a helium balloon if it is absent. We discuss how a balance beam could represent concepts of dynamic specificity (due to changes in competitor diseases' probabilities) and dynamic sensitivity (due to class-conditional independence). Utility-based thresholds for acting on a diagnosis could be represented by moving the balance beam's fulcrum. It is suggested that a balance beam can be a useful aid for students learning clinical diagnosis, allowing them to build on existing intuitive understanding to develop an appreciation of how evidence combines to influence degree of belief. The balance beam could also facilitate exploration of the potential impact of available questions or investigations.