3D propagation of the shock-induced vibrations through the whole lower-limb during running.

Shock-induced vibrations to the feet have been related to the feel of comfort, the biomechanical control of performance, and the risk of fatigue or injury. Up to recently, the complexity of measuring the human biodynamic response to vibration exposure implied to focus most of the research on the axial acceleration at the tibia. Using wireless three-dimensional accelerometers, this paper investigates the propagation of shock-induced vibrations through the whole lower-limb during running in the temporal and the spectral domains. Results indicated that the vibrations were not consistent across the lower-limb, showing various spatial and spectral distributions of energy. The amount of energy was not constantly decreasing from the distal to the proximal extremity of the runner's lower-limb, especially regarding the lateral epicondyle of the femur. Vibrations in the transversal plane of the segments were substantial compared to the longitudinal axis regarding the distal extremity of the tibia, and the lateral epicondyle of the femur. Further, the spectral content was wider at the distal than at the proximal end of the lower-limb. Finally, to get a thorough understanding of the risks incurred by the runners, the need to account for shock-induced vibrations up to 50 Hz has been stressed when investigating three-dimensional vibrations. The overall study raises attention on the substantial importance of the transverse components of the acceleration, and their potential relation to shear fatigue and injury during running.

Mitochondrial complex I defect resulting from exercise-induced lower limb ischemia in patients with peripheral arterial disease.

This study aims to compare the structural and mitochondrial alterations between muscle segments affected by exercise-induced ischemia and segments of the same muscle without ischemia, in the same subject. In a prospective analysis, 34 patients presenting either peripheral arterial disease or chronic coronary syndrome without any evidence of peripheral arterial disease were eligible for inclusion based on findings indicating a need for either a femoro-popliteal bypass or a saphenous harvesting for coronary bypass. Before surgery, we assessed the level of exercise-induced ischemia in proximal and distal sections of the thigh by the measurement of transcutaneous oxygen pressure during an exercise treadmill test. Distal and proximal biopsies of the sartorius muscle were procured during vascular surgical procedures to assess mitochondrial function and morphometric parameters of the sartorius myofibers. Comparisons were made between the distal and proximal biopsies, with respect to these parameters. Thirteen of the study patients that initially presented with peripheral arterial disease had evidence of an isolated distal thigh exercise-induced ischemia, associated with a 35% decrease in the mitochondrial complex I enzymatic activity in the distal muscle biopsy. This defect was also associated with a decreased expression of the manganese superoxide dismutase enzyme and with alterations of the shapes of the myofibers. No functional or structural alterations were observed in the patients with coronary syndrome. We validated a specific model ischemia in peripheral arterial disease characterized by muscular alterations. This "Distal-Proximal-Sartorius Model" would be promising to explore the physiopathological consequences specific to chronic ischemia. NEW & NOTEWORTHY We compared proximal versus distal biopsies of the sartorius muscle in patients with superficial femoral artery stenosis or occlusion and proof of, distal only, regional blood flow impairment with exercise oximetry. We identified a decrease in the mitochondrial complex I enzymatic activity and antioxidant system impairment at the distal level only. We validate a model to explore the physiopathological consequences of chronic muscle ischemia.

Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration.

In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. 14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of YWHAH, the gene encoding the 14-3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non-synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness. In vitro, variants of YWHAH induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that YWHAH variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells.

AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages.

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation.

[The pro-social nature of blood donation]. / Nature pro sociale du don de sang.

"L'établissement français du sang" faces chronic shortages of blood to meet the growing needs of the health system. This article aims at clarifying the pro social nature of blood donation. An analysis of the literature allows us to characterize the act as being altruist. The prospective of this focus is to test the labeling paradigm, which is to return to the experiment that makes a preparatory behaviour, information enabling someone to perceive themselves as generous versus stingy or helpful versus not helpful. Being true to nature as reasons and motivations that conduct to the act of giving blood, seems to be essential for fundamental and experimental approach.

Phenotypic spectrum of MFN2 mutations in the Spanish population.

INTRODUCTION: The most common form of axonal Charcot-Marie-Tooth (CMT) disease is type 2A, caused by mutations in the mitochondrial GTPase mitofusin 2 (MFN2). OBJECTIVE: The objective of our study is to establish the incidence of MFN2 mutations in a cohort of Spanish patients with axonal CMT neuropathy. MATERIAL AND METHODS: Eighty-five families with suspected axonal CMT were studied. All MFN2 exons were studied through direct sequencing. A bioenergetics study in fibroblasts was conducted using a skin biopsy taken from a patient with an Arg468His mutation. RESULTS: Twenty-four patients from 14 different families were identified with nine different MFN2 mutations (Arg94Trp, Arg94Gln, Ile203Met, Asn252Lys, Gln276His, Gly296Arg, Met376Val, Arg364Gln and Arg468His). All mutations were found in the heterozygous state and four of these mutations had not been described previously. MFN2 mutations were responsible for CMT2 in 16% +/- 7% of the families studied and in 30.8 +/- 14.2% (12/39) of families with known dominant inheritance. The bioenergetic studies in fibroblasts show typical results of MFN2 patients with a mitochondrial coupling defect (ATP/O) and an increase of the respiration rate linked to complex II. CONCLUSION: It is concluded that mutations in MFN2 are the most frequent cause of CMT2 in this region. The Arg468His mutation was the most prevalent (6/14 families), and our study confirms that it is pathological, presenting as a neuropathy in a mild to moderate degree. This study also demonstrates the value of MFN2 studies in cases of congenital axonal neuropathy, especially in cases of dominant inheritance, severe clinical symptoms or additional symptoms such as optic atrophy.

[A meta-analysis of job burnout using the MBI scale]. / Une méta-analyse de la mesure du burnout à l'aide de l'instrument MBI.

BACKGROUND AND AIM: The aim of this study was to investigate the theoretical dimensionality of burnout measurement (MBI). The objective of the study was to check the working hypothesis according to which the subscales of the Maslach Burnout Inventory (MBI) such as "emotional exhaustion" and "cynicism" (depersonalization) were not correlated with that of "personal achievement" (professional efficacy). To do so, we performed a meta-analysis [Maslach and Jackson, The Maslach Burnout Inventory, 1981, 1986]. METHODS: The sample included 12,112 participants (sample size range from 100-3312 participants; estimated mean=448.59; standard deviation=648.51). Doctheses, Francis, Interscience, Kluweronline, Medline, PsycInfo, and ScienceDirect were searched to identify papers. Exploring references identified 83 publications (1998-2001). Two keywords were used: "Maslach Burnout Inventory" and "organizational stress". The criteria for this meta-analysis included: using the MBI "human services survey (HSS)" for professional care givers, "educators' survey (ES)" for professional educators, "general survey (GS)" for other workers). RESULTS: About 58% of the population concerned professional caregivers, 13% professional educators, 11% social workers, and 18% correctional officers and other workers. In this meta-analysis, effect sizes should be reported with the number of studies and confidence intervals to test the consistency and reliability of the mean estimated (effect size). In this case, each correlation can be corrected. The meta-analysis can therefore be conducted on this corrected correlation. The aim will be to control any artefact and sampling error. Meta-analysis showed that the value of the corrected correlation is not always negative in the case of a relation between the dimension of "emotional exhaustion" and "personal achievement" (professional efficacy). In the case of the dimension "emotional exhaustion" and "cynicism" (depersonalization), we observed that the value of the corrected correlation studies and confidence intervals showed that this dimension was always correlated positively in the studies included. For the relationship between the value of corrected correlation studies and confidence intervals of the dimension of "cynicism" (depersonalization) and "personal achievement" (professional efficacy), the studies included showed that they were always correlated negatively. These results confirm the hypothesis studied. CONCLUSION: The study revealed two points: (1) the homogeneity of the studies included concerning the fact that assessment of emotional exhaustion and cynicism (depersonalization) are always correlated positively; (2) the heterogeneity of the studies included concerning the fact that personal achievement is correlated with the other subscales of burnout (MBI). This study confirms the hypothesis.

Tactile precision in right-handed archery experts with visual disabilities: a pseudoneglect effect?

Space perception was investigated in two groups of participants with severe visual deficiencies performing a tactile bisection task: the participants in the first group (Archers) regularly practised a high-precision sport, whereas those in the second group (Non-Archers) had never practised this activity. Experiments were carried out to determine whether practising this sport might affect the pseudoneglect (resulting in a deviation to the left of the perceived midpoint with respect to the actual physical midpoint) occurring in sighted persons (Bowers & Heilman, 1980) as well as in completely blind children (Sampaio, Gouarir, & Mvondo Mvondo, 1995). No particular deviation was observed in the group of Non-Archers, whereas pseudoneglect was present in the Archers' group. A significant hand effect (left/right), and a significant effect of starting point of tactile exploration were observed across groups. This confirms the existence of a relationship between hemisphere-hands and hemisphere-hemispace mechanisms. The results obtained here show that practising archery affects pseudoneglect.

Sensori-motor adaptation to knee osteoarthritis during stepping-down before and after total knee replacement.

BACKGROUND: Stepping-down is preceded by a shift of the center of mass towards the supporting side and forward. The ability to control both balance and lower limb movement was investigated in knee osteoarthritis patients before and after surgery. It was hypothesized that pain rather than knee joint mobility affects the coordination between balance and movement control. METHODS: The experiment was performed with 25 adult individuals. Eleven were osteoarthritic patients with damage restricted to one lower limb (8 right leg and 3 left leg). Subjects were recruited within two weeks before total knee replacement by the same orthopedic surgeon using the same prosthesis and technics of surgery. Osteoarthritic patients were tested before total knee replacement (pre-surgery session) and then, 9 of the 11 patients were tested one year after the surgery when re-educative training was completed (post-surgery session). 14 adult individuals (men: n = 7 and women: n = 7) were tested as the control group. RESULTS: The way in which the center of mass shift forward and toward the supporting side is initiated (timing and amplitude) did not vary within patients before and after surgery. In addition knee joint range of motion of the leading leg remained close to normal before and after surgery. However, the relative timing between both postural and movement phases was modified for the osteoarthritis supporting leg (unusual strategy for stepping-down) before surgery. The "coordinated" control of balance and movement turned to be a "sequential" mode of control; once the body weight transfer has been completed, the movement onset is triggered. This strategy could be aimed at shortening the duration-time supporting on the painful limb. However no such compensatory response was observed. CONCLUSION: The change in the strategy used when supporting on the arthritis and painful limb could result from the action of nociceptors that lead to increased proprioceptor thresholds, thus gating the proprioceptive inputs that may be the critical afferents in controlling the timing of the coordination between balance and movement initiation control.

Ca2+-activated myosin-ATPases, creatine and adenylate kinases regulate mitochondrial function according to myofibre type in rabbit.

Mitochondrial respiration rates and their regulation by ADP, AMP and creatine, were studied at different free Ca(2+) concentrations (0.1 versus 0.4 microm) on permeabilized fibre bundles of rabbit skeletal muscles differing in their myosin heavy chain profiles. Four fibre bundle types were obtained: pure types I and IIx, and mixed types IIax (approximately 50% IIa and 50% IIx fibres) and IIb+ (60% IIb fibres, plus IIx and IIa). At rest, pure type I fibres displayed a much higher apparent K(m) for ADP (212 microm) than IIx fibres (8 microm). Within the IIax and IIb+ mixed fibre bundle types, two K(ADP)(m) values were observed (70 microm and 5 microm). Comparison between pure IIx and mixed types indicates that the intermediate K(m) of 70 microm most probably corresponds to the mitochondrial affinity for ADP in IIa fibres, the lowest K(m) for ADP (5 microm) corresponding to IIx and IIb types. Activation of mitochondrial creatine and adenylate kinase reactions stimulated mitochondrial respiration only in type I and IIax fibre bundles, indicating an efficient coupling between both kinases and ADP rephosphorylation in type I and, likely, IIa fibres, since no effect was observed in pure IIx fibres. Following Ca(2+)-induced activation of myosin-ATPase, an increase in mitochondrial sensitivity to ADP of 45% and 250% was observed in type IIax and I bundles, respectively, an effect mostly prevented by addition of vanadate, an inhibitor of myosin-ATPase. Ca(2+)-induced activation of myosin-ATPase also prevented the stimulation of respiration rates by creatine and AMP in I and IIax bundles. In addition to differential regulation of mitochondrial respiration and energy transfer systems at rest in I and IIa versus IIx and IIb muscle fibres, our results indicate a regulation of phosphotransfer systems by Ca(2+) via the stimulation of myosin-ATPases in type I and IIa fibres of rabbit muscles.

Control of skeletal muscle mitochondria respiration by adenine nucleotides: differential effect of ADP and ATP according to muscle contractile type in pigs.

Skeletal muscle exhibits considerable variation in mitochondrial content among fiber types, but it is less clear whether mitochondria from different fiber types also present specific functional and regulatory properties. The present experiment was undertaken on ten 170-day-old pigs to compare functional properties and control of respiration by adenine nucleotides in mitochondria isolated from predominantly slow-twitch (Rhomboideus (RM)) and fast-twitch (Longissimus (LM)) muscles. Mitochondrial ATP synthesis, respiratory control ratio (RCR) and ADP-stimulated respiration with either complex I or II substrates were significantly higher (25-30%, P<0.05) in RM than in LM mitochondria, whereas no difference was observed for basal respiration. Based on mitochondrial enzyme activities (cytochrome c oxidase [COX], F0F1-ATPase, mitochondrial creatine kinase [mi-CK]), the higher ADP-stimulated respiration rate of RM mitochondria appeared mainly related to a higher maximal oxidative capacity, without any difference in the maximal phosphorylation potential. Mitochondrial K(m) for ADP was similar in RM (4.4+/-0.9 microM) and LM (5.9+/-1.2 microM) muscles (P>0.05) but the inhibitory effect of ATP was more marked in LM (P<0.01). These findings demonstrate that the regulation of mitochondrial respiration by ATP differs according to muscle contractile type and that absolute muscle oxidative capacity not only relies on mitochondrial density but also on mitochondrial functioning per se.

Anticipatory balance control is affected by loadless training experiences.

The main purpose of this study was to identify whether a lot of sports training had any effect on the balance control associated with a leg movement. The nature of the training experience was also an important concern and we chose subject who had undergone specific training experience in absence of equilibrium constraints. To this end a comparison between control (untrained) subjects, triathletes and swimmers was designed to establish whether a general training in sports (triathletes) or a specific loadless training (swimmers), leads to differences in the balance control. A leg movement is preceded by a shift of the center of mass (CM) towards the supporting side to maintain equilibrium and forward to create the condition for progression. To provide an acceleration of the CM sideward and forward, an initial displacement of the center of pressure (CP) towards the moving limb and in posterior direction was performed. Interestingly, the lateral pressure onto the ground was greater increased in swimmers in both leg raising and obstacle avoidance tasks compared to the control group and/or triathletes whereas the backward CP shift in all group was the same. The initial control of the CM shift is very different in swimmers compared to triathletes and controls. The increased lateral pressure onto the ground in swimmers may be a result of a prolonged training in water. This suggests that prolonged training in the absence of equilibrium constraints has more of an effect on balance control than a prolonged general training. In addition, the lack of differences in the backward CP shift suggests that M/L and A/P controls support two functional goals: equilibrium maintenance and movement initiation.

Is perception of upper body orientation based on the inertia tensor? Normogravity versus microgravity conditions.

During lateral leg raising, a synergistic inclination of the supporting leg and trunk in the opposite direction to the leg movement is performed in order to preserve equilibrium. As first hypothesized by Pagano and Turvey (J Exp Psychol Hum Percept Perform, 1995, 21:1070-1087), the perception of limb orientation could be based on the orientation of the limb's inertia tensor. The purpose of this study was thus to explore whether the final upper body orientation (trunk inclination relative to vertical) depends on changes in the trunk inertia tensor. We imposed a loading condition, with total mass of 4 kg added to the subject's trunk in either a symmetrical or asymmetrical configuration. This changed the orientation of the trunk inertia tensor while keeping the total trunk mass constant. In order to separate any effects of the inertia tensor from the effects of gravitational torque, the experiment was carried out in normo- and microgravity. The results indicated that in normogravity the same final upper body orientation was maintained irrespective of the loading condition. In microgravity, regardless of loading conditions the same (but different from the normogravity) orientation of the upper body was achieved through different joint organizations: two joints (the hip and ankle joints of the supporting leg) in the asymmetrical loading condition, and one (hip) in the symmetrical loading condition. In order to determine whether the different orientations of the inertia tensor were perceived during the movement, the interjoint coordination was quantified by performing a principal components analysis (PCA) on the supporting and moving hips and on the supporting ankle joints. It was expected that different loading conditions would modify the principal component of the PCA. In normogravity, asymmetrical loading decreased the coupling between joints, while in microgravity a strong coupling was preserved whatever the loading condition. It was concluded that the trunk inertia tensor did not play a role during the lateral leg raising task because in spite of the absence of gravitational torque the final upper body orientation and the interjoint coupling were not influenced.

Effect of a perfume on prosocial behavior of pedestrians.

Several studies have shown that perfumes encourage prosocial behavior of people from whom help is requested in the street. Implicit requests for help were studied. On a pedestrian walk, a woman confederate, with or without a heavy perfume, walked by the subject while dropping a packet of paper handkerchiefs or a glove apparently without noticing. Results show that the confederate was warned more often when wearing a perfume.