Intentional on-line adaptation of stride length in human walking

The intentional control of stride length is a fundamental basis for the adaptation of the stride to environmental constraints (obstacle avoidance, for example). Controlling the propulsive forces during the stance and/or controlling the pendular movement of the oscillating leg constitute the two potential and non-exclusive mechanisms underlying intentional stride length modulation. The present experiment was conducted in order to determine if these two mechanisms contribute to voluntary length modulation and, if so, how they cooperate according to whether the subject has to lengthen or shorten a stride and how these mechanisms are implemented at the neuromuscular level. Subjects had to produce a temporarily modulated stride of the same length, but originating from two different initial steady-states: one from shorter stride length and one from longer stride length. We found that the shortening was essentially realized by a swing-duration decrease (an increased activity in the hip extensor--biceps femoris--during the swing of the ipsilaterally shortened stride stopped the pendular leg movement earlier). The lengthening was realized by two mechanisms: (1) an increase in the propulsive forces (via an increased activity of the ankle extensor muscles--soleus--and the hip extensors--biceps femoris--from the stance of the ipsilaterally modulated stride, which was prolonged during the following stance of the contralateral leg), and (2) an increase in swing duration on the ipsilateral leg (an increased activity in hip and ankle flexors--rectus femoris and tibialis anterior--maintained the ipsilateral leg in flexion during the lengthened swing so that the foot landed later). In this experiment, the subjects were faced with a spatial constraint of the same magnitude in the direction of stride lengthening and stride shortening. However, under these conditions, subjects used a different balance between swing control (that directly modifies the foot trajectory without affecting the trajectory of the head-arm-trunk system) and/or the control of propulsive forces (that indirectly influences foot trajectory by modifying the trajectory of the head-arm-trunk system). In the first case, this concerns a voluntary control of gesture produced by the legs and usually implicated in the locomotor pointing; in the second case, this concerns a voluntary control of propulsive forces.     

Methicillin-resistant Staphylococcus aureus in pig farming

We conducted a study among a group of 26 regional pig farmers to determine the methicillin-resistant Staphylococcus aureus prevalence rate and found it was >760 times greater than the rate of patients admitted to Dutch hospitals. While spa-type t108 is apparently a more widespread clone among pig farmers and their environment, we did find other spa-types.     

Protection against experimental visceral leishmaniasis infection in dogs immunized with purified excreted secreted antigens of Leishmania infantum promastigotes

The capacity of naturally excreted secreted antigens easily purified from culture supernatant of Leishmania infantum promastigotes (LiESAp), successfully cultivated in completely defined medium called CDM/LP [Lemesre JL. Methods for the culture in vitro of different stages of tissue parasites. International publication WO 94/26899, 1994; Merlen T, Sereno D, Brajon N, Rostand F, Lemesre JL. Leishmania spp: completely defined medium without serum and macromolecules (CDM/LP) for the continuous in vitro cultivation of infective promastigote forms. Am J Trop Med Hyg 1999;60(1):41-50] to protect dogs against experimental L. infantum infections is described. Eighteen healthy Beagle dogs were allocated into four groups that received at a 3-week interval either two subcutaneous injections of 50 microg (group 2, n = 3), 100 microg (group3, n = 6) and 200 microg (group 4, n = 3) LiESAp in formulation with muramyl dipeptide (MDP) or similar injections of placebo (group 1, n = 6). Dogs were intravenously infected with 10(8) metacyclic L. infantum promastigotes. Promastigotes of the MHOM/MA/67/ITMAP-263 and MHOM/FR/78/LEM75 strains were, respectively, administered 2 months (at day 84, homologous challenge 1) and 8 months post-immunization (at day 273, heterologous challenge 2). The data indicated that vaccine candidate confers total protection (100%) against challenges 1 and 2 in dogs from groups 3 and 4 and intermediate protection (66.7%) against challenge 1 in dogs from group 2 as determined by parasite detection in bone marrow aspirates during 14 months post-challenge follow-up. All placebo dogs of group 1 were found infected and failed to respond to LiESAp in cell-mediated assays before and after both challenges. Increased levels of total anti-leishmanial antibodies were exclusively detected in infected dogs from group 1. Vaccine-induced protection correlates with an early establishment of a long lasting predominantly Th1-type cellular immune response specifically directed against LiESAp before and after experimental infections, as demonstrated by: (i) anti-LiESAp IgG2 reactivity, and (ii) LiESAp-specific lymphocyte proliferation assays and enhanced NO-mediated anti-leishmanial activity of canine monocyte-derived macrophages (CM-DM) in response to higher IFNgamma production by T-cells, when L. infantum-infected CM-DM were co-cultured with autologous lymphocytes. Overall, our results support the view that a LiESAp vaccine might be useful in a promising vaccination approach against natural L. infantum infection.     

Familial influences on basal salivary cortisol in an adult population

To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30 min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.     

Surgical management of endometriosis

The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain is a source of ongoing controversy. Complete resolution of endometriosis is not yet possible and current therapy has three main objectives: (1) to reduce pain; (2) to increase the possibility of pregnancy; and (3) to delay recurrence for as long as possible. It is possible that a consensus will never be reached on the optimal treatment of minimal and mild endometriosis. In case of moderate and severe endometriosis-associated infertility, the combined approach (operative laparoscopy with a gonadotropin-releasing hormone (GnRH) agonist) should be considered as 'first-line' treatment. The mean pregnancy rate of 50% reported in the literature following surgery provides scientific proof that operative treatment should first be undertaken to give our patients the best chance of conceiving naturally. In case of rectovaginal adenomyotic nodules, surgery must be considered as first-line therapy, medical therapy being relatively in-efficacious.     

Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results

OBJECT: Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation. METHODS: Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation. The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (+/- standard deviation) clinical and functional BFMDRS scores had improved by 79 +/- 19% and 65 +/- 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95). CONCLUSIONS: Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.     

Interactions between cognitive and sensorimotor functions in the motor cortex: evidence from the preparatory motor sets anticipating a perturbation

The many signs of cognitive processes in the activation pattern of the primary motor cortex or in corticospinal (CS) excitability gave rise to the idea that the motor cortex is a crucial node in the processing of cognitive information related to sensorimotor functions. Moreover, it became clear that the preparatory motor sets offer a privileged window to investigate the interaction between cognitive and sensorimotor function in the motor cortex. In the present review, we examine how the study of the preparatory motor sets anticipating a mechanical movement perturbation contributes to enlightening this question. Following the initial observation made by Hammond that some components of the stretch reflex can be modulated by a prior intention either to resist or to relax in response to a subsequent perturbation, first evidence of the phenomenon was obtained in behaving monkeys. Moreover, this study related this peripheral fact to the observed anticipatory activity of motor cortex neurons after a prior instruction telling the animal how to respond to the subsequent perturbation, which triggered the instructed movement. Indeed, this anticipatory activity was found to be different according to the instruction. In the 1980s, this work inspired a lot of studies in human beings that brought support to the idea of a cognitive tuning of the long latency stretch response (LLSR). Specifically, the MI component of the response was shown to be modulated by a prior intent to resist versus to let go when faced with the perturbation. Recently, new approaches have been developed to obtain evidence of a cognitive tuning of CS excitability, thanks to transcranial magnetic stimulation (TMS). TMS has been used both as a reliable tool for quantifying the CS excitability via the motor evoked potentials (MEPs), and to centrally perturb the organization of movement. Such central perturbations offer the unique opportunity to activate the descending motor tracts while shunting, for a short time period, the ascending tracts assisting the movement. Thus, CS excitability was measured before the movement was perturbed. These studies demonstrated the readiness of the CS tract to be involved in anticipatory compensatory responses to central movement perturbations induced by TMS in relation to the subject's cognitive attitudes. The question of the cerebral regions upstream of the motor cortex that could be responsible for this modulation in CS excitability remains largely open.     

Cognitive tuning of corticospinal excitability during human gait: adaptation to the phase

The aim of this study was to investigate how the cognitive tuning of corticospinal (CS) excitability adapts to the type of evoked-movement (Flexion vs. Extension) during human gait. Transcranial magnetic stimulation (TMS) was used both as a central perturbation evoking a movement and as a tool for quantifying the CS excitability of the muscles under study (RF/BF). In the first condition (Dst), the TMS occurred at mid-stance, inducing hip extension, whereas in the second condition (Dsw), the TMS occurred at the beginning of the swing phase, inducing hip flexion. In both conditions, the subjects were asked to cognitively prepare to either not intervene (NINT) or to compensate (COMP) for the evoked-movements. The results showed that, regardless of the type of evoked-movement, preparing to compensate resulted in a selective increase in the CS excitability to those muscles that would be involved in counteracting the possible central perturbation, i.e. the hip extensor muscle (BF) to compensate for an evoked flexion during the swing phase or the hip flexor muscle (RF) to compensate for an evoked extension during the stance phase. This latter result offers the first evidence of a modulation in CS excitability to the proximal muscles during the stance phase. In conclusion, the cognitive tuning of CS excitability was found to adapt to the gait phases. Moreover, the same selective preparation strategy was observed whether the central perturbation occurred during the stance or the swing phase of the step cycle.     

Growth hormone stimulates the selective trafficking of thymic CD4+CD8- emigrants to peripheral lymphoid organs

Growth hormone (GH) has been shown to stimulate T cell development. However, its mechanisms of action on the peripheral T cell pool remain unknown. To address this question, intrathymic injection of GH in combination with fluorescein isothiocyanate (FITC) was used to assess the effects of GH on T cell trafficking from the thymus to the periphery. GH promoted a significant increase in the percentage and differential distribution of thymic CD4+CD8-FITC+ cells in secondary lymphoid organs. A significantly higher percentage of CD4+CD8-FITC+ cells was observed in the lymph nodes, while a relative decrease of these cells was found in the spleen. Moreover, we verified that GH treatment resulted in increased numbers of CD62L+CD4+CD8-FITC+ T cells in the lymph nodes, while the same treatment resulted in a decline in the percentage of VLA-6+CD4+CD8-FITC+ T cells in the spleen. Together, these findings suggest that GH is a potent immunoregulatory molecule which selectively stimulates the preferential homing of CD4+CD8- thymic emigrants to the subcutaneous lymph nodes possibly via the differential expression of CD62L and VLA-6.