Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated?

The IkappaB kinases (IKKs) IKK-alpha and IKK-beta, and the IKK-related kinases TBK1 and IKK-epsilon, have essential roles in innate immunity through signal-induced activation of NF-kappaB, IRF3 and IRF7, respectively. Although the signaling events within these pathways have been extensively studied, the mechanisms of IKK and IKK-related complex assembly and activation remain poorly defined. Recent data provide insight into the requirement for scaffold proteins in complex assembly; NF-kappaB essential modulator coordinates some IKK complexes, whereas TANK, NF-kappaB-activating kinase-associated protein 1 (NAP1) or similar to NAP1 TBK1 adaptor (SINTBAD) assemble TBK1 and IKK-epsilon complexes. The different scaffold proteins undergo similar post-translational modifications, including phosphorylation and non-degradative polyubiquitylation. Moreover, increasing evidence indicates that distinct scaffold proteins assemble IKK, and potentially TBK1 and IKK-epsilon subcomplexes, in a stimulus-specific manner, which might be a mechanism to achieve specificity.     

How do load carriage and walking speed influence trunk coordination and stride parameters?

To determine the effects of load carriage and walking speed on stride parameters and the coordination of trunk movements, 12 subjects walked on a treadmill at a range of walking speeds (0.6-1.6 m s(-1)) with and without a backpack containing 40% of their body mass. It was hypothesized that compared to unloaded walking, load carriage decreases transverse pelvic and thoracic rotation, the mean relative phase between pelvic and thoracic rotations, and increases hip excursion. In addition, it was hypothesized that these changes would coincide with a decreased stride length and increased stride frequency. The findings supported the hypotheses. Dimensionless analyses indicated that there was a significantly larger contribution of hip excursion and smaller contribution of transverse plane pelvic rotation to increases in stride length during load carriage. In addition, there was a significant effect of load carriage on the amplitudes of transverse pelvic and thoracic rotation and the relative phase of pelvic and thoracic rotation. It was concluded that the shorter stride length and higher stride frequency observed when carrying a backpack is the result of decreased pelvic rotation. During unloaded walking, increases in pelvic rotation contribute to increases in stride length with increasing walking speed. The decreased pelvic rotation during load carriage requires an increased hip excursion to compensate. However, the increase in hip excursion is insufficient to fully compensate for the observed decrease in pelvis rotation, requiring an increase in stride frequency during load carriage to maintain a constant walking speed.     

Movement behavior of high-heeled walking: how does the nervous system control the ankle joint during an unstable walking condition?

The human locomotor system is flexible and enables humans to move without falling even under less than optimal conditions. Walking with high-heeled shoes constitutes an unstable condition and here we ask how the nervous system controls the ankle joint in this situation? We investigated the movement behavior of high-heeled and barefooted walking in eleven female subjects. The movement variability was quantified by calculation of approximate entropy (ApEn) in the ankle joint angle and the standard deviation (SD) of the stride time intervals. Electromyography (EMG) of the soleus (SO) and tibialis anterior (TA) muscles and the soleus Hoffmann (H-) reflex were measured at 4.0 km/h on a motor driven treadmill to reveal the underlying motor strategies in each walking condition. The ApEn of the ankle joint angle was significantly higher (p<0.01) during high-heeled (0.38±0.08) than during barefooted walking (0.28±0.07). During high-heeled walking, coactivation between the SO and TA muscles increased towards heel strike and the H-reflex was significantly increased in terminal swing by 40% (p<0.01). These observations show that high-heeled walking is characterized by a more complex and less predictable pattern than barefooted walking. Increased coactivation about the ankle joint together with increased excitability of the SO H-reflex in terminal swing phase indicates that the motor strategy was changed during high-heeled walking. Although, the participants were young, healthy and accustomed to high-heeled walking the results demonstrate that that walking on high-heels needs to be controlled differently from barefooted walking. We suggest that the higher variability reflects an adjusted neural strategy of the nervous system to control the ankle joint during high-heeled walking.     

Influence of normative data’s walking speed on the computation of conventional gait indices

The pathology’s impact on gait pattern may be overestimated by conventional gait indices (Gillette Gait Index – GGI, Gait Deviation Index – GDI, Gait Profile Score – GPS), since impairments’ consequences on kinematics may be amplified by a change in walking speed. The objectives of this study were to evaluate the influence of walking speed on the computation of gait indices and to propose a corrective method to cancel the effects of walking speed. Spatiotemporal parameters and kinematics of fifty-four asymptomatic participants (30 M/24 W, 37.9 ± 13.7 years, 72.8 ± 13.3 kg, 1.74 ± 0.10 m) were collected at four speed conditions (C₁:[0,0.4] m s⁻¹, C₂:[0.4,0.8] m s⁻¹, C₃:[0.8,1.2] m s⁻¹, C₄:spontaneous). Four values of each index were computed for each trial using successively the four conditions as normative data repository. Mean values over all participants were statistically compared (paired t-tests, 95% confidence level). Indices values computed with normative at equivalent walking speed were not statistically different from reference values. Meanwhile, deviations appeared when the walking speed discrepancy between conditions and normative increased. These drifts related to walking speed mismatch have been quantified and fitting functions proposed. A correction was applied to indices. GGI was efficiently adjusted while GDI and GPS remain different from their reference values for C₁ and C₂. Gait indices must be interpreted cautiously in function of the normative data repository’s walking speed used for computation. Furthermore, a coupled use of conventional and corrected gait indices could lead to a better comprehension of the contribution of impairments and walking speed on gait deviations and overall gait quality.     

Hospital Expenditure at the End-of-Life: What Are the Impacts of Health Status and Health Risks?

Background

It is important for health policy and expenditure projections to understand the relationship between age, death and expenditure on health care (HC). Research has shown that older age groups incur lower hospital costs than previously anticipated and that remaining time to death (TTD) was a much stronger indicator for expenditure than age. How health behaviour or risk factors impact on HC utilisation and costs at the end of life is relatively unknown. Smoking and Body Mass Index (BMI) have featured most prominently and mixed findings exist as to the exact nature of this association.

Methods

This paper considers the relationship between TTD, age and expenditure for inpatient care in the last 12 quarters of life; and introduces measures of health status and risks. A longitudinal dataset covering 35 years is utilised, including baseline survey data linked to hospital and death records. The effect of age, TTD and health indicators on expenditure for inpatient care is estimated using a two-part model.

Results

As individuals approach death costs increase. This effect is highly significant (p<0.01) from the last until the 8th quarter before death and influenced by age. Statistically significant effects on costs were found for: smoking status, systolic blood pressure and lung function (FEV1). On average, smokers incurred lower quarterly costs in their last 12 quarters of life than non-smokers (~7%). Participants’ BMI at baseline did show a negative association with probability of HC utilisation however this effect disappeared when costs were estimated.

Conclusions

Health risk measures obtained at baseline provide a good indication of individuals’ probability of needing medical attention later in life and incurring costs, despite the small size of the effect. Utilising a linked dataset, where such measures are available can add substantially to our ability to explain the relationship between TTD and costs.     

Are T cells at the origin of B cell lymphomas?

Lymphoma pathogenesis is at least in some cases related to transformed B cells (BCs) arising from germinal centre reactions (GCRs). In this article possible deregulations of GCRs are investigated using in silico simulations. It is found that the final differentiation of BCs as regulated by helper T cells (TCs) is the best candidate mechanism for such a deregulation. This shifts the paradigm of BC lymphoma pathogenesis from BC transformations to an emphasized role of TC-BC interactions.     

Are Lay People Good at Recognising the Symptoms of Schizophrenia?

Aim

The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seek-help for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis.

Method

Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment.

Results

Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help.

Conclusion

There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis.     

Assessment of intersegmental coordination of rats during walking at different speeds – Application of continuous relative phase

The present study investigated the feasibility and reliability of continuous relative phase (CRP) and deviation phase (DP) to assess intersegmental hind limb coordination pattern and coordination variability in rats during walking. Twenty-six adult rats walked at 8 m/min, 12 m/min and 16 m/min while two-dimensional kinematics were recorded. Segment angles and segment angular velocities of the paw, shank and thigh on the left hind-limb were extracted from 15 strides and CRP was calculated for the paw-shank and shank-thigh coupling. The effect of walking speed on the time point average curve of the CRP (ACRP) and DP and on the mean ACRP and mean DP was established by statistical parametric mapping (SPM) and a one-way ANOVA for repeated measures. Absolute and relative reliability were assessed by measurement error and intra-class correlation coefficient. The SPM analysis revealed time dependent differences in the effect of speed. Thus, the CRP of the paw-shank coupling decreased with increasing speed during most of the gait cycle while the CRP of the shank-thigh coupling was decreased during the swing phase. The session-to-session reliability was fair to good for the coordination measure and poor for the variability measure.     

The tree of life and the rock of ages: Are we getting better at estimating phylogeny?

In a recent paper,(1) palaeontologist Mike Benton claimed that our ability to reconstruct accurately the tree of Life may not have improved significantly over the last 100 years. This implies that the cladistic and molecular revolutions may have promulgated as much bad "black box" science as rigorous investigation. Benton's assessment was based on the extent to which cladograms (typically constructed with reference only to distributions of character states) convey the same narrative as the geochronological ages of fossil taxa (an independent data set). Fossil record quality varies greatly between major clades, and the palaeontological dating "yardstick" may be more appropriate for some groups than others.     

Proprioception, gait kinematics, and rate of loading during walking: are they related?

The cyclic nature of walking can lead to repetitive stress and associated complications due to the rate of loading (ROL) experienced by the body at the initial contact of the foot with the ground. An individual's gait kinematics at initial contact has been suggested to give rise to the ROL, and a repetitive, high ROL may lead to several disorders, including osteoarthritis. Additionally, proprioception, the feedback signaling of limb position and movement, may play a role in how the foot strikes the ground and thus, the ROL. Our goal was to explore the relationship between proprioception, gait kinematics and ROL. Thirty-eight women were recruited for gait analysis, and the gait characteristics 50 ms prior to and at initial contact were examined. Two proprioception tests, joint angle reproduction and threshold to detect passive motion were used to examine the subject's proprioceptive acuity. Our results indicate that individuals with a larger knee angle (i.e., greater extension) 50 ms prior to initial contact (IC) experience a higher ROL during gait and have poorer proprioceptive scores. However, it remains unclear whether poor proprioception causes a high ROL or if a high ROL damages the mechanoreceptors involved in proprioception, but the apparent relationship is significant and warrants further investigation.     

Development and validation of a new method to measure walking speed in free-living environments using the actibelt® platform

Walking speed is a fundamental indicator for human well-being. In a clinical setting, walking speed is typically measured by means of walking tests using different protocols. However, walking speed obtained in this way is unlikely to be representative of the conditions in a free-living environment. Recently, mobile accelerometry has opened up the possibility to extract walking speed from long-time observations in free-living individuals, but the validity of these measurements needs to be determined. In this investigation, we have developed algorithms for walking speed prediction based on 3D accelerometry data (actibelt?) and created a framework using a standardized data set with gold standard annotations to facilitate the validation and comparison of these algorithms. For this purpose 17 healthy subjects operated a newly developed mobile gold standard while walking/running on an indoor track. Subsequently, the validity of 12 candidate algorithms for walking speed prediction ranging from well-known simple approaches like combining step length with frequency to more sophisticated algorithms such as linear and non-linear models was assessed using statistical measures. As a result, a novel algorithm employing support vector regression was found to perform best with a concordance correlation coefficient of 0.93 (95%CI 0.92-0.94) and a coverage probability CP1 of 0.46 (95%CI 0.12-0.70) for a deviation of 0.1 m/s (CP2 0.78, CP3 0.94) when compared to the mobile gold standard while walking indoors. A smaller outdoor experiment confirmed those results with even better coverage probability. We conclude that walking speed thus obtained has the potential to help establish walking speed in free-living environments as a patient-oriented outcome measure.     

Are the Tastes of Polycose and Monosodium Glutamate Unique?

To study whether Polycose and monosodium L-glutamate (L-MSG)have unique tastes differing from the traditional four basictastes, chemosensory profiles were established for Polycose,L-MSG and a group of related compounds (sucrose, maltose, monosodiumD-glutamate (D-MSG), sodium chloride, calcium chloride). Flavourswere assessed using whole-mouth tests in human subjects withnose open or clamped to reduce olfactory input. Polycose (amixture of glucose-based oligosaccharides) had a flavor consistingof an olfactory component and a maltose-like taste. L-MSG andD-MSG profiles differed from each other, and from NaCl and CaCl₂.L-MSG had a lower threshold and a higher frequency of ‘other’tastes than the D form. The data do not support a ‘polysaccharide’taste, but suggest a chiral receptor site for ‘umami’taste. Chem. Senses 21: 341–347, 1996.