Relationship of aerobic fitness and motor skills with memory and attention in preschoolers (Ballabeina): a cross-sectional and longitudinal study.

BACKGROUND: The debate about a possible relationship between aerobic fitness and motor skills with cognitive development in children has recently re-emerged, because of the decrease in children's aerobic fitness and the concomitant pressure of schools to enhance cognitive performance. As the literature in young children is scarce, we examined the cross-sectional and longitudinal relationship of aerobic fitness and motor skills with spatial working memory and attention in preschool children. METHODS: Data from 245 ethnically diverse preschool children (mean age: 5.2 (0.6) years, girls: 49.4%) analyzed at baseline and 9 months later. Assessments included aerobic fitness (20 m shuttle run) and motor skills with agility (obstacle course) and dynamic balance (balance beam). Cognitive parameters included spatial working memory (IDS) and attention (KHV-VK). All analyses were adjusted for age, sex, BMI, migration status, parental education, native language and linguistic region. Longitudinal analyses were additionally adjusted for the respective baseline value. RESULTS: In the cross-sectional analysis, aerobic fitness was associated with better attention (r=0.16, p=0.03). A shorter time in the agility test was independently associated with a better performance both in working memory (r=-0.17, p=0.01) and in attention (r=-0.20, p=0.01). In the longitudinal analyses, baseline aerobic fitness was independently related to improvements in attention (r=0.16, p=0.03), while baseline dynamic balance was associated with improvements in working memory (r=0.15, p=0.04). CONCLUSIONS: In young children, higher baseline aerobic fitness and motor skills were related to a better spatial working memory and/or attention at baseline, and to some extent also to their future improvements over the following 9 months. TRIAL REGISTRATION: clinicaltrials.gov NCT00674544.

Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100 209-2M peptide.

Patients with stage I-III melanoma were vaccinated with the modified HLA-A2-binding gp100(209-2M)-peptide after complete surgical resection of their primary lesion and sentinel node biopsy. Cytoplasmic interferon-gamma production by freshly thawed peripheral blood mononuclear cells (direct ex vivo analysis) or by peripheral blood mononuclear cells subjected to 1 cycle of in vitro sensitization with peptide, interleukin-2, and interleukin-15 was measured following restimulation with the modified and native gp100 peptides, and also A2gp100 melanoma cell lines. Peptide-reactive and tumor-reactive T cells were detected in 79% and 66% of selected patients, respectively. Patients could be classified into 3 groups according to their vaccine-elicited T-cell responses. One group of patients responded only to the modified peptide used for immunization, whereas another group of patients reacted to both the modified and native gp100 peptides, but not to naturally processed gp100 antigen on melanoma cells. In the third group of patients, circulating CD8 T cells recognized A2gp100 melanoma cell lines and also both the modified and native peptides. T cells with a low functional avidity, which were capable of lysing tumor cells only if tumor cells were first pulsed by the exogenous administration of native gp100(209-217) peptide were identified in most patients. These results indicate that vaccination with a modified gp100 peptide induced a heterogeneous group of gp100-specific T cells with a spectrum of functional avidities; however, high avidity, tumor-reactive T cells were detected in the majority of patients.

Vedolizumab as induction and maintenance therapy for Crohn's disease.

BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.).

Ultraviolet induction of antifungal activity in plants.

Ultraviolet-C irradiation as a method to induce the production of plant compounds with antifungal properties was investigated in the leaves of 18 plant species. A susceptibility assay to determine the antifungal susceptibility of filamentous fungi was developed based on an agar dilution series in microtiter plates. UV irradiation strongly induced antifungal properties in five species against a clinical Fusarium solani strain that was responsible for an onychomycosis case that was resistant to classic pharmacological treatment. The antifungal properties of three additional plant species were either unaffected or reduced by UV-C irradiation. This study demonstrates that UV-C irradiation is an effective means of modulating the antifungal activity of very diverse plants from a screening perspective.

FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases.

FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division septum. FtsK(50C) also promotes a complete Xer recombination reaction between dif sites by switching the state of activity of the XerCD recombinases so that XerD makes the first pair of strand exchanges to form Holliday junctions that are then resolved by XerC. The reaction between directly repeated dif sites in circular DNA leads to the formation of uncatenated circles and is equivalent to the formation of chromosome monomers from dimers.

Electro-cortical correlates of motor inhibition : a comparison between selective and non-selective stop tasks

In this study, we compared a selective stop task (transition from a bimanual in-phase to a unimanual index fingers' tapping), with a non-selective stop task (stopping a bimanual in-phase tapping at all), and with a switching task (transition from in-phase to anti-phase bimanual tapping). The aim was twofold: 1) to identify the electro-cortical correlates of selective and non-selective inhibition processes and 2) to investigate which type of inhibition - selective or not - is required when switching between two bimanual motor patterns. The results revealed that all tasks led to enhanced activation (alpha power) of the left sensorimotor and posterior regions which seems to reflect an overall effort to stop the preferred bimanual in-phase tendency. Each task implied specific functional connectivity reorganizations (beta coherence) between cerebral motor areas, probably reflecting engagement in a new unimanual or bimanual movement.

Pilot study of induction chemotherapy followed by concomitant chemotherapy and IMRT or tomotherapy for nasopharyngeal carcinoma

Objective: Standard treatment of locally advanced (stages III and IV A-B) nasopharyngeal carcinoma (NPC) consists in chemoradiotherapy with 5-y survival rates of around 60%. However, acute toxicity prevents the administration of adequate adjuvant chemotherapy in nearly half of the patients. This situation has led to the hypothesis that induction chemotherapy followed by chemoradiotherapy may be a superior approach. Many ongoing studies are testing the role of induction chemotherapy in this setting. Newer radiotherapy techniques are becoming available (intensity modulated radiotherapy [IMRT] and tomotherapy). They can achieve a higher degree of accuracy in conforming the radiation to the planned target volume while sparing normal tissue resulting in less acute and long-term toxicity. Methods: We report here our local experience of 11 consecutive locally advanced NPC patients treated between June 2004 and October 2007. Median age was 46 years (range, 17-65). All but one were male patients. Initial stage was stage III in 5, and stage IVA-B in 6 patients. Treatment consisted of 3 cycles of induction TCF (Docetaxel 75 mg/m2- Cisplatin 75 mg/m2- 5-fluorouracil 750 mg/m2/d 5 days) chemotherapy followed by concomitant chemoradiotherapy with 3 cycles of cisplatin (100 mg/m2), or carboplatin (AUC 5) in case of renal impairment. Radiotherapy was delivered by either IMRT or tomotherapy. Macroscopic disease (tumor + involved lymph nodes) was treated with 70 Gy, 2 Gy/fraction (IMRT), or 69.6 Gy, 1.12 Gy/fraction (simultaneus integrated boost [SIB] technique). Elective nodal irradiation of 46-54 Gy lymph was performed in all patients, whereas elective irradiation of the entire nasopharynx (60 Gy) half of patients. Results: All but one tumor were EBV positive. Induction chemotherapy was done as planned for 8 patients (73%). Two patients had only 2 cycles, 1 patient had only1 cycle of TCF, and the other without docetaxel. Concomitant chemotherapy was given as planned in 7 patients (64%). Four patients had only 2 cycles. Radiotherapy could be delivered as planned in all patients. Eight weeks post treatment all patients proved to have a CR (CR or uCR). After a median follow-up of 11 months (range, 6-38 months) only one patient has relapsed. Details on acute and 1 year toxicities will be presented. Conclusion: Treatment of locally advancedNPC with induction and concomitant chemotherapy is feasible and well tolerated. The use of IMRT or tomotherapy technique seems to ameliorate the therapeutic index particularly in regard with xerostomia. All our patients presented a complete response. For the assessment of survival and long-term toxicity, a longer follow-up period is needed.

Induction of calmodulin kinase IV by the thyroid hormone during the development of rat brain.

This communication reports the specific induction of calmodulin kinase IV by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) in a time- and concentration-dependent manner at a very early stage of brain differentiation using a fetal rat telencephalon primary cell culture system, which can grow and differentiate under chemically defined conditions. The induction of the enzyme that can be observed both on the mRNA and on the protein level is T3-specific, i.e. it cannot be induced by retinoic acid or reverse T3, and can be inhibited on both the transcriptional and the translational level by adding to the culture medium actinomycin D or cycloheximide, respectively. The earliest detection of calmodulin kinase IV in the fetal brain tissue of the rat is at days E16/E17, both on the mRNA as well as on the protein level. This is the first report in which a second messenger-dependent kinase involved in the control of cell regulatory processes is itself controlled by a primary messenger, the thyroid hormone.

Direct electrical stimulation using a battery-operated device for induction and modulation of colonic contractions in pigs.

Direct electrical stimulation of the colon offers a promising approach for the induction of propulsive colonic contractions by using an implantable device. The objective of this study was to assess the feasibility to induce colonic contractions using a commercially available battery-operated stimulator (maximum pulse width of 1 ms and maximum amplitude of 10 V). Three pairs of pacing electrodes were inserted into the cecal seromuscular layer of anesthetized pigs. During a first set of in vivo experiments conducted on six animals, a pacing protocol leading to cecum contractions was determined: stimulation bursts with 1 ms pulse width, 10 V amplitude (7-15 mA), 120 Hz frequency, and 30-s burst duration, repeated every 2-5 min. In a second testing phase, an evaluation of the pacing protocol was performed in four animals (120 stimulation bursts in total). By using the battery-operated stimulator, contractions of the cecum and movement of contents could be induced in 92% of all stimulations. A cecal shortening of about 30% and an average intraluminal pressure increase of 10.0 +/- 6.0 mmHg were observed.

Recombinant human insulin-like growth factor I (rhIGF-I) for the treatment of amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Recombinant human insulin-like growth factor I (rhIGF-I) is a possible disease modifying therapy for amyotrophic lateral sclerosis (ALS, which is also known as motor neuron disease (MND)). OBJECTIVES: To examine the efficacy of rhIGF-I in affecting disease progression, impact on measures of functional health status, prolonging survival and delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival in ALS. Occurrence of adverse events was also reviewed. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (21 November 2011), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to November 2011) and EMBASE (January 1980 to November 2011) and sought information from the authors of randomised clinical trials and manufacturers of rhIGF-I. SELECTION CRITERIA: We considered all randomised controlled clinical trials involving rhIGF-I treatment of adults with definite or probable ALS according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months of treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: Each author independently graded the risk of bias in the included studies. The lead author extracted data and the other authors checked them. We generated some missing data by making ruler measurements of data in published graphs. We collected data about adverse events from the included trials. MAIN RESULTS: We identified three randomised controlled trials (RCTs) of rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European trial (183 participants) the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a North American trial (266 participants), the MD after nine months was -6.00 (95% CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. There was an increased risk of injection site reactions with rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial (330 participants) used a novel primary end point involving manual muscle strength testing. No differences were demonstrated between the treated and placebo groups in this study. All three trials were at high risk of bias. AUTHORS' CONCLUSIONS: Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias.

Monitoring of vaccine-specific gamma interferon induction in genital mucosa of mice by real-time reverse transcription-PCR.

Monitoring of T-cell responses in genital mucosa has remained a major challenge because of the absence of lymphoid aggregates and the low abundance of T cells. Here we have adapted to genital tissue a sensitive real-time reverse transcription-PCR (TaqMan) method to measure induction of gamma interferon (IFN-gamma) mRNA transcription after 3 h of antigen-specific activation of CD8 T cells. For this purpose, we vaccinated C57BL/6 mice subcutaneously with human papillomavirus type 16 L1 virus-like particles and monitored the induction of CD8 T cells specific to the L1(165-173) H-2D(b)-restricted epitope. Comparison of the responses induced in peripheral blood mononuclear cells and lymph nodes (LN) by L1-specific IFN-gamma enzyme-linked immunospot assay and TaqMan determination of the relative increase in L1-specific IFN-gamma mRNA induction normalized to the content of CD8b mRNA showed a significant correlation, despite the difference in the readouts. Most of the cervicovaginal tissues could be analyzed by the TaqMan method if normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA was used and a significant L1-specific IFN-gamma induction was found in one-third of the immunized mice. This local response did not correlate with the immune responses measured in the periphery, with the exception of the sacral LN, an LN draining the genital mucosa, where a significant correlation was found. Our data show that the TaqMan method is sensitive enough to detect antigen-specific CD8 T-cell responses in the genital mucosa of individual mice, and this may contribute to elaborate effective vaccines against genital pathogens.

Maintien des capacités des myopathes ou l'art de prescrire l'exercice physique [How to maintain the motor capacities in neuromuscular disorders or the art to prescribe physical exercises].

Optimum management of non-acquired neuromuscular disorders requires a multidisciplinary approach in order to prevent secondary complications related to the progression of the disease and to maintain the patient's independency in daily activities. For treatments, the physiotherapists and occupational therapists must have precise and measurable goals to quantify muscle strength and functions in conjunction with a specialist in neurorehabilitation. Examples of simple motor scores or scales are given in order to transmit precise information to the GP and the multidisciplinary team, and type of orthosis and physiotherapy programmes are given as pieces of advice to assume the follow-up of patients.

Diethyldithiocarbamic acid inhibits the octadecanoid signaling pathway for the wound induction of proteinase-inhibitors in tomato leaves

The induction of proteinase inhibitor I synthesis in tomato (Lycopersicon esculentum) leaves in response to wounding is strongly inhibited by diethyldithiocarbamic acid (DIECA). DIECA also inhibits the induction of inhibitor I synthesis by the 18-amino acid polypeptide systemin, polygalacturonic acid (PCA), and linolenic acid, but not by jasmonic acid, suggesting that DIECA interferes with the octadecanoid signaling pathway. DIECA only weakly inhibited tomato lipoxygenase activity, indicating that DIECA action occurred at a step after the conversion of linolenic acid to 13(S)-hydroperoxylinolenic acid (HPOTrE). DIECA was shown to efficiently reduce HPOTrE to 13-hydroxylinolenic acid (HOTrE), which is not a signaling intermediate. Therefore, in vivo, DIECA is likely inhibiting the signaling pathway by shunting HPOTrE to HOTrE, thereby severely reducing the precursor pool leading to cyclization and eventual synthesis of jasmonic acid. Phenidone, an inhibitor of lipoxygenase, inhibited proteinase inhibitor I accumulation in response to wounding, further supporting a role for its substrate, linolenic acid, and its product, HPOTrE, as components of the signal-transduction pathway that induces proteinase inhibitor synthesis in response to wounding, systemin, and PCA.