Glycaemic control for painful diabetic peripheral neuropathy is more than fasting plasma glucose and glycated haemoglobin.

BACKGROUND: The relationship between postprandial hyperglycaemia and diabetic peripheral neuropathy (DPN), whether painful or painless, has yet to be determined. Thus, the aim of this study was to investigate the relationship in patients with type 2 diabetes (T2D). METHODS: This cross-sectional study was conducted in adults with T2D between January and October 2013. Blood samples were collected after overnight fasting every 3 months prior to enrolment. For this study, increased postprandial glycaemic exposure was defined as high glycated haemoglobin (HbA1c) and near-normal mean fasting plasma glucose (FPG) levels. Both painless and painful DPN were evaluated using two validated tools, the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire. RESULTS: This study included 1040 participants with mean FPG levels<140mg/dL, 535 of which were<126mg/dL. Of these patients, 200/1040 (19.2%) and 105/535 (19.6%) had DPN. Multivariate analysis demonstrated that higher HbA1c levels (≥7%) did not increase risk of painless DPN, but did significantly increase risk of painful DPN in T2D patients with FPG<140mg/dL and<126mg/dL, with corresponding odds ratios of 2.49 and 3.77 (95% confidence intervals: 1.09-5.71 and 1.20-11.79), respectively, after adjusting for demographic factors, diabetes-related variables and comorbidities. CONCLUSION: This study is the first to reveal that increased postprandial glycaemic exposure, as assessed by high HbA1c and near-normal FPG levels, is associated with an increased risk of painful DPN in adults with T2D.

Microstructure, physical properties, and bone regeneration effect of the nano-sized ß-tricalcium phosphate granules.

The nano-sized ß-tricalcium phosphate granules for the practical application of bone graft substitutes could be prepared from the wet chemically precipitated ß-TCP powders by the liquid-solid mixture route and by controlling the pH of mixture solution to 7.5 within a shorter processing time. The phase purity of prepared ß-TCP granules was higher above 99% and their particle sizes ranged from 200 to 650 nm. Also, their average compressive strength was higher at 2.22 MPa. It is considered that the phase purity, particle refinement, and mechanical compressive strength of ß-TCP granules could be significantly improved through the ß-TCP powders synthesized through the liquid-solid mixture precipitation at pH of 7.5. Meanwhile both the porosity and the specific surface area positively associated with the osteoconductivity for bone regeneration were higher at 75% and 2.50 m(2)/g respectively due to the nano-sized particles of porous ß-TCP granules. Furthermore, the histological analysis in beagle mandibular defect showed that ß-TCP granules demonstrated remarkable bone regeneration effect compared with that of the non-treatment group, indicating the increased new formation of bone (except for callus) (48.42 ± 6.57%) and rapid resorption (69.49 ± 2.40%) without toxicologically significant changes at 12 weeks after implantation.

Dynamic stability and compensatory stepping responses during anterior gait-slip perturbations in people with chronic hemiparetic stroke.

To examine the control of dynamic stability and characteristics of the compensatory stepping responses to an unexpected anterior gait slip induced under the non-involved limb in people with hemi-paretic stroke (PwHS) and to examine any resulting adaptive changes in these on the second slip due to experience from prior slip exposure. Ten PwHS experienced overground slip (S1) during walking on the laboratory walkway after 5-8 regular walking (RW) trials followed by a second consecutive slip trial (S2). The slip outcome (backward loss of balance, BLOB and no loss of balance, NLOB) and COM state (i.e. its COM position and velocity) stability were examined between the RW and S1 and S1 and S2 at touchdown (TD) of non-involved limb and at liftoff (LO) of the contralateral limb. At TD there was no difference in stability between RW and S1, however at LO, subjects demonstrated a lower stability on S1 than RW resulting in a 100% backward loss of balance (BLOB) with compensatory stepping response (recovery step, RS, 4/10 or aborted step, AS, 6/10). On S2, although there was no change in stability at TD, there was a significant improvement in stability at LO with a 40% decrease in BLOB. There was also a change in step strategy with a decrease in AS response (60% to 35%, p<0.05) which was replaced by an increase in the ability to step (increased compensatory step length, p<0.05) either via a recovery step or a walkover step. PwHS have the ability to reactively control COM state stability to decrease fall-risk upon a novel slip; prior exposure to a slip did not significantly alter feedforward control but improved the ability to use such feedback control for improved slip outcomes.

Adaptation and generalization to opposing perturbations in walking.

Little is known on how the CNS would select its movement options when a person faces a novel or recurring perturbation of two opposing types (slip or trip) while walking. The purposes of this study were (1) to determine whether young adults' adaptation to repeated slips would interfere with their recovery from a novel trip, and (2) to investigate the generalized strategies after they were exposed to a mixed training with both types of perturbation. Thirty-two young adults were assigned to either the training group, which first underwent repeated-slip training before encountering a novel, unannounced trip while walking, or to the control group, which only experienced the same novel, unannounced trip. The former group would then experience a mix of repeated trips and slips. The results indicated that prior adaptation to slips had only limited interference during the initial phase of trip recovery. In fact, the prior repeated-slip exposure had primed their reaction, which mitigated any error resulting from early interference. As a result, they did not have to take a longer compensatory step for trip recovery than did the controls. After the mixed training, subjects were able to converge effectively the motion state of their center of mass (in its position and velocity space) to a stable and generalized "middle ground" steady-state. Such movement strategies not only further strengthened their robust reactive control of stability, but also reduced the CNS' overall reliance on accurate context prediction and on feedback correction of perturbation-induced movement error.

Age, co-morbidity and poor mobility: no evidence of predicting in-patient death and acute hospital length of stay in the oldest old.

BACKGROUND: The oldest old (aged over 90 years) are the fastest growing section of the UK population. Limited data exist regarding the effect of age, location, co-morbidity and physical performance status on outcome of acute illness in this age group. METHODS: We performed a prospective study in people aged ≥ 90 years using hospital audit data in three hospitals in England and Scotland. We examined the characteristics of those admitted over three consecutive calendar months and calculated risk ratios of death and prolonged length of acute hospital stay (>7 days). RESULTS: A total of 419 patients were included in this study (68% female, median age 93 years). There were similarities in presentation and diagnoses, but patients in Scotland (n = 164) were more likely to be admitted from sheltered housing or nursing homes than those in England (n = 255). Patients in England were significantly less likely to be able to mobilize < 10 m (41 vs. 34%, P < 0.001) but had lower prevalence of hypertension (40 vs. 55%, P = 0.02), ischaemic heart disease (30% vs. 45%, P = 0.02) and fewer prescribed medications (median 2 vs. 3, P < 0.001). Mortality was similar for the England and Scotland centres (P = 0.98). Previously recognized risk factors for death following hospital admission and length of stay e.g. older age, higher number of co-morbidities and poor mobility were not predictive in this study. CONCLUSION: The 'oldest old' should not be considered as a homogenous group and findings from single-centre studies involving this age group may not be generalizable. We found no conclusive evidence that patient-related factors predict outcome in this age group in acute medical admission settings.

Generalization of motor adaptation to repeated-slip perturbation across tasks.

Similar adaptations improve both proactive and reactive control of center-of-mass (COM) stability and limb support against gravity during different daily tasks (e.g., sit-to-stand and walking) as a consequence of perturbation training for resisting falls. Yet it is unclear whether--or to what extent--such similarities actually promote inter-task generalization. The purpose of this study was therefore to determine whether young adults could indeed transfer their adaptive control, acquired from sit-to-stand-slip, to improve their likelihood of a recovery from an unannounced novel slip in walking. Subjects underwent either repeated slips during sit-to-stand before experiencing an unannounced, novel slip during walking (training group, n=20), or they received no prior training before the same gait-slip (control group, n=23). The subjects demonstrated training-induced generalization of their improved proactive control of stability in post-training (unperturbed) gait pattern that was more stable against backward balance loss than was that of their own pre-training pattern as well the gait pattern of the subjects in the control group. Upon the unannounced novel gait-slip, the training group showed significantly lower incidence of both falls and balance loss than that shown by the control, resulting from the improvements in the reactive control of limb support and slip velocity, which directly influenced the control of their COM stability. Such transfer could occur when the subjects' central nervous system recalibrates the non-task-specific, generalized representation of stability limits during the initial training to guide both their feed-forward adjustments and their feedback responses. The findings of the inter-task generalization suggests that behavioral changes induced via the perturbation training paradigm have the potential to prevent falls across the spectrum of cyclic and non-cyclic activities.

Independent influence of gait speed and step length on stability and fall risk.

With aging, individuals' gaits become slower and their steps shorter; both are thought to improve stability against balance threats. Recent studies have shown that shorter step lengths, which bring the center of mass (COM) closer to the leading foot, improve stability against slip-related falls. However, a slower gait, hence lower COM velocity, does the opposite. Due to the inherent coupling of step length and speed in spontaneous gait, the extent to which the benefit of shorter steps can offset the slower speed is unknown. The purpose of this study was to investigate, through decoupling, the independent effects of gait speed and step length on gait stability and the likelihood of slip-induced falls. Fifty-seven young adults walked at one of three target gait patterns, two of equal speed and two of equal step length; at a later trial, they encountered an unannounced slip. The results supported our hypotheses that faster gait as well as shorter steps each ameliorates fall risk when a slip is encountered. This appeared to be attributable to the maintenance of stability from slip initiation to liftoff of the recovery foot during the slip. Successful decoupling of gait speed from step length reveals for the first time that, although slow gait in itself leads to instability and falls (a one-standard-deviation decrease in gait speed increases the odds of fall by 4-fold), this effect is offset by the related decrease in step length (the same one-standard-deviation decrease in step length lowers fall risk by 6 times).

Control of center of mass motion state through cuing and decoupling of spontaneous gait parameters in level walking.

Can the center of mass (COM) motion state, i.e., its position and velocity relative to the base of support (BOS), which dictate gait stability, be predictably controlled by the global gait parameters of step length and gait speed, or by extension, cadence? The precise relationships among step length and gait speed, and the COM motion state are unknown, partially due to the interdependence between step length and gait speed and the difficulty in independent control of both parameters during spontaneous level walking. The purposes of this study were to utilize simultaneous audio-visual cuing to independently manipulate step length and gait speed, and to determine the extent to which the COM position and velocity can be subsequently controlled. Fifty-six young adults were trained at one of the three gait patterns in which both the step length and gait speed were targeted simultaneously. The results showed that the cuing could successfully "decouple" gait speed from step length. Although this approach did yield reliable control of the COM velocity through manipulation of gait speed (R(2)=0.97), the manipulation of step length yielded less precise control of COM position (R(2)=0.60). This latter control appears to require manipulation of an additional degree-of-freedom at the local segment level, such that the inclusion of trunk inclination with step length improved the prediction of COM position (R(2)=0.80).

Generalization of gait adaptation for fall prevention: from moveable platform to slippery floor.

A person's ability to transfer the acquired improvements in the control of center of mass (COM) state stability to slips induced in everyday conditions can have profound theoretical and practical implications for fall prevention. This study investigated the extent to which such generalization could take place. A training group (n=8) initially experienced 24 right-side slips in blocked-and-random order (from the 1st unannounced, novel slip, S-1 to the last, S-24) resulting from release of a low-friction moveable platform in walking. They then experienced a single unannounced slip while walking on an oil-lubricated vinyl floor surface (V-T). A control group (n=8) received only one unannounced slip on the same slippery floor (V-C). Results demonstrated that the incidence of balance loss and fall on V-T was comparable to that on S-24. In both trials, fall and balance-loss incidence was significantly reduced in comparison with that on S-1 or on V-C, resulting from significant improvements in the COM state stability. The observed generalization indicates that the control of COM stability can be optimally acquired to accommodate alterations in environmental constraints, and it may be broadly coded and easily modifiable within the CNS. Because of such mechanisms, it is possible that the locomotor-balance skills acquired with the aid of low-friction moveable platforms can translate into resisting falls encountered in daily living.

Immediate and latent interlimb transfer of gait stability adaptation following repeated exposure to slips.

The authors trained 21 participants by using blocked-and-mixed exposure to right-side slips and then caused them to slip unexpectedly on the untrained left side. Authors retested participants with a right slip and a left slip at 1 week, 2 weeks, 1 month, and 4 months. The authors found that preslip stability on the first untrained left slip improved and was significantly greater than that on the first right slip, which probably contributed to the reduction in incidence of falls from approximately 30% to approximately 10%. Postslip stability and base of support (BOS) slip velocity were similar to those on the first right slip and much lower than those on the last right slip. Increases in pre- and postslip stabilities and BOS slip velocity during the left slip led to reductions in backward balance loss (BLOB) from approximately 95% on initial left slip to approximately 60% and to approximately 25% on the 1st and 3rd retest sessions, respectively. In contrast, BLOB remained at a constant approximately 40% level on the right slip of the same retest sessions. The results indicate a partial immediate transfer and a possible latent transfer.

Can observational training substitute motor training in preventing backward balance loss after an unexpected slip during walking?

A person's awareness of potential slippery walking conditions induces a cautious gait pattern. The purposes of this study were to determine whether neuromechanical changes associated with such cognitive conditioning are sufficient to alter the outcome of a slip and whether the effects of such conditioning are comparable to those of motor training. Prior to their own first slip exposure, 18 young subjects watched videos and slides demonstrating where and how the slip would occur and how people adapted to repeated-slip exposure (observe). The outcomes of the first slip exposure experienced by another 16 subjects who did not receive any such information were used as controls (naïve). The latter subjects subsequently experienced an additional 23 slips and thus served in a dual-role as the motor training group (motor). Gait stability as measured against backward loss of balance (BLOB) was obtained for pre- and postslip instances. A protective step landing posterior to the slipping-limb identified each BLOB outcome. The observe group had a greater postslip stability and lower slip displacement and velocity than the naïve group. However, such effects were insufficient to prevent balance loss (100% BLOB). The motor group showed significantly better performance on the last training slip (0% BLOB) than did the observe group. The results indicated that updating the cognitive centers of the CNS with awareness and perceptual knowledge through observational training can yield tangible benefits. Nonetheless observation could not replace the task-specific motor training that adaptively updated the internal representations of stability limits for prevention of BLOB.

Retention of adaptive control over varying intervals: prevention of slip- induced backward balance loss during gait.

Stability improvements made in a single acquisition session with merely five slips in walking are sufficient to prevent backward balance loss (BLOB) at the end of session, but not after 12 mo. The purpose of this study was to determine whether the effect of an enhanced single acquisition session would be retainable if tested sooner, at intervals of < or =4 mo. Twenty-four young subjects were exposed to blocks of slip, nonslip, and both types of trials during walking at their preferred speed in the acquisition session. In each of the four follow-up sessions around 1 wk, 2 wk, 1 mo, and 4 mo later, these same subjects experienced only a single slip after eight to 13 unperturbed walking trials in an otherwise identical setup. Gait stability was obtained as the shortest distance between the measured center of mass (COM) state (position and velocity) and the mathematically predicted threshold for BLOB at pre- and postslip, corresponding to the instants of touchdown of the slipping limb and liftoff of the contralateral limb, respectively. During the acquisition session, pre- and postslip stability improved significantly, resulting in a reduction of BLOB from 100% in the first slip (S1) to 0% in the last slip (S24), with improvements converging to a steady state, that enabled all of the subjects to avoid BLOB, regardless of whether a slip occurred. During retest sessions, subjects' preslip stability was not different from that in S24, but was greater than that in S1. Their postslip stability was also greater than that in S1 but less than that in S24, resulting in BLOB at a 40% level. No difference was found in any of these aspects between each follow-up session. These adaptive changes were associated with a range of individual differences, varying from no detectable deterioration in all aspects (n = 8) to a consistent BLOB in all follow-ups (n = 3). Our findings demonstrated the extent of plasticity of the CNS, characterized by rapid acquisition of a stable COM state under unpredictable slip conditions and retention of such improvements for months, resulting in a reduced occurrence of unintended backward falling.

Adaptive control of gait stability in reducing slip-related backward loss of balance.

The properties of adaptation within the locomotor and balance control systems directed towards improving one's recovery strategy for fall prevention are not well understood. The purpose of this study was to examine adaptive control of gait stability to repeated slip exposure leading to a reduction in backward loss of balance (and hence in protective stepping). Fourteen young subjects experienced a block of slips during walking. Pre- and post-slip onset stability for all slip trials was obtained as the shortest distance at touchdown (slipping limb) and lift-off (contralateral limb), respectively, between the measured center of mass (COM) state, that is, position and velocity relative to base of support (BOS) and the mathematically predicted threshold for backward loss of balance. An improvement in pre- and post-slip onset stability correlated with a decrease in the incidence of balance loss from 100% (first slip) to 0% (fifth slip). While improvements in pre-slip stability were affected by a proactive anterior shift in COM position, the significantly greater post-slip onset improvements resulted from reductions in BOS perturbation intensity. Such reactive changes in BOS perturbation intensity resulted from a reduction in the demand on post-slip onset braking impulse, which was nonetheless influenced by the proactive adjustments in posture and gait pattern (e.g., the COM position, step length, flat foot landing and increased knee flexion) prior to slip onset. These findings were indicative of the maturing process of the adaptive control. This was characterized by a shift from a reliance on feedback control for postural correction to being influenced by feedforward control, which improved pre-slip stability and altered perturbation intensity, leading to skateover or walkover (>0.05 m or <0.05 m displacement, respectively) adaptive strategies. Finally, the stability at contralateral limb lift-off was highly predictive of balance loss occurrence and its subsequent rapid reduction, supporting the notion of the internal representations of stability limits that could be modified and updated, as a key component in the adaptive control.

Isolated oculomotor nerve palsy from minor head trauma.

Isolated third cranial nerve palsies in head trauma patients can be the result of direct or indirect damage to the oculomotor nerve. They are usually associated with severe head trauma. We reported a case of isolated oculomotor nerve palsy associated with minor head injury. No initial loss of consciousness was recalled. Computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) of the brain were normal. Previous reports in the literature were reviewed and the possible mechanism of injury was discussed. Head injuries are commonly seen in sports settings. Our case illustrated that even minor head trauma can cause isolated oculomotor nerve palsy in the absence of abnormal brain imaging findings.

Long-term retention of gait stability improvements.

Evidence of long-term modification of behavior-in particular, gait alterations in response to repeated exposure to slips-within the locomotor-balance control system is limited. The purpose of this study was to examine whether improvements in fall-resisting behavior as reflected by improvements in gait stability could be retained on a long-term basis. Eight healthy young subjects were exposed to a block of repeated slip trials during a single acquisition session consisting of five repeated slip exposures; the same subjects were then re-tested using the same protocol at a minimum of 12 mo later. Pre- and postslip gait stability for all slip trials was measured at touchdown (slipping limb) and liftoff (contralateral limb) based on the center of mass state (i.e., its instantaneous position and velocity) relative to the base of support (BOS) and the predicted thresholds for backward loss of balance. In the acquisition session, subjects were able to increase pre- and postslip stability, which significantly correlated with a decrease in the incidence of balance loss from 100% (1st slip) to 0% (5th slip). All subjects exhibited a similar balance loss on the first slip of the follow-up session. Nonetheless, subjects were able to retain the acquired preslip stability with feedforward control on the first slip but not the postslip stability related to the reactive response. Also, the subjects demonstrated a faster re-acquisition, with only one balance loss on the second slip of the follow-up session, as compared with seven balance losses on the acquisition session. Such rapid improvements were achieved by the significantly greater increase in post- compared with preslip stability; this increase was for the most part, a consequence of reductions in slip intensity (i.e., the peak BOS velocity). We concluded that a single acquisition session could only produce limited long-term retainable effects within the locomotor-balance control system. It appeared, however, that the CNS was still primed to more rapidly update its internal representation of gait stability during re-acquisition.

Influence of gait speed on stability: recovery from anterior slips and compensatory stepping.

Falls precipitated by slipping are a major health concern, with the majority of all slip-related falls occurring during gait. Recent evidence shows that a faster and/or more anteriorly positioned center of mass (COM) is more stable against backward balance loss, and that compensatory stepping is the key to recovering stability upon balance loss. The purposes of this paper were to determine whether walking speed affected gait stability for backward balance loss at slip onset and touchdown of compensatory stepping, and whether compensatory stepping response resembled the regular gait pattern. Forty-seven young subjects were slipped unexpectedly either at a self-selected fast, natural or slow speed. Speed-related differences in stability at slip onset and touchdown of the subsequent compensatory step were analyzed using the COM position-velocity state. The results indicate that gait speed highly correlated with stability against backward balance loss at slip onset. The low COM velocity of the slow group was not sufficiently compensated for by a more anteriorly positioned COM associated with a shorter step length at slip onset. At touchdown of the compensatory step, the speed-related differences in stability diminished, due to the continued advantage of anterior COM positioning from a short compensatory step retained by the slow group, coupled with an increase in COM velocity. Compensatory step length and relative COM position altered as a function of gait speed, indicating the motor program for gait regulation may play a role in modulating the compensatory step.

Role of feedforward control of movement stability in reducing slip-related balance loss and falls among older adults.

Human upright posture is inherently unstable. To counter the mechanical effect of a large-scale perturbation such as a slip, the CNS can make adaptive adjustments in advance to improve the stability of the body center-of-mass (COM) state (i.e., its velocity and position). Such feedforward control relies on an accurate internal representation of stability limits, which must be a function of anatomical, physiological, and environmental constraints and thus should be computationally deducible based on physical laws of motion. We combined an empirical approach with mathematical modeling to verify the hypothesis that an adaptive improvement in feedforward control of COM stability correlated with a subsequent reduction in balance loss. Forty-one older adults experienced a slip during a sit-to-stand task in a block of slip trials, followed by a block of nonslip trials and a re-slip trial. Their feedforward control of COM stability was quantified as the shortest distance between its state measured at seat-off (slip onset) and the mathematically predicted feasible stability region boundary. With adaptation to repeated slips, older adults were able to exponentially reduce their incidence of falls and backward balance loss, attributable significantly to their improvement in feedforward control of stability. With exposure to slip and nonslip conditions, subjects began to select "optimal" movements that improved stability under both conditions, reducing the reliance on prior knowledge of forthcoming perturbations. These results can be fully accounted for when we assume that an internal representation of the COM stability limits guides the adaptive improvements in the feedforward control of stability.

Preparation and evaluation of an imidazole-coated capillary column for the electrophoretic separation of aromatic acids.

An imidazole-coated capillary column for electrophoresis has been prepared by means of organosilanization. With mesityl oxide as neutral marker, the results indicated that the electroosmotic flow of the bonded phase displays a dramatic difference in pH dependence in comparison with that of the bare fused-silica column. The presence of positive charges on the coating surface and the anionic exchange property, due to the cationic property of the imidazole group at pH values below 6, allows the separation of geometric isomers that are very similar in ionic mobility. Separation parameters including buffer composition and concentration, pH, applied voltage, and the influence of other additives were investigated. By using acetate buffer (100 mM, pH 5.2) and an applied voltage of -15 kV with UV detection at 212 nm, the separation of 11 aromatic acids including mono-, di-, tri- and tetra-carboxylic acids could be achieved in less than 14 min. The average plate number was 3 x 10(5)/m. With acetate buffer (25 mM, pH 5.5) and an applied voltage of -25 kV, the addition of silver nitrate or beta-cyclodextrin significantly improved the resolution of some more highly charged carboxylic acids.

Relative stability improves with experience in a dynamic standing task.

This study tested the hypothesis that subjects improve their relative stability as they learn a dynamic pulling task. Healthy adult subjects practiced making brief horizontal pulls (<300 ms) on a handle to a range of target forces ranging from 20 to 80% of their estimated maximum for 5 days. They were instructed to always keep their feet flat and begin and end their motion in an upright posture. In order to do this, subjects had to develop the appropriate body momentum prior to the pull and then recover their balance following the pull. We analyzed relative stability during balance recovery, using two measures: spatial safety margin (minimum distance of the center of pressure, COP, to the edges of the feet) and temporal safety margin (minimum extrapolated time for the COP to reach the edges of the feet). We hypothesized that: (1) spatial and temporal safety margins would be uncorrelated; (2) safety-margin means would increase with practice; and (3) safety-margin standard deviations would decrease with practice. Two experiments were conducted: one where subjects practiced three force targets and positioned their initial COP in a small window, and one where subjects practiced two force targets with no initial COP constraint. Results showed that spatial and temporal safety margins were correlated but shared less than 6% variance, indicating that they reflected different aspects of control. Safety-margin averages increased with practice and standard deviations decreased with practice, indicating that the stability of balance control in the execution of this task became more robust. We suggest that the nervous system could use safety margins in both feedback and feedforward control of balance.