Ion-Induced Dipole Interactions and Fragmentation Times: Cα-Cß Chromophore Bond Dissociation Channel.

The fragmentation times corresponding to the loss of the chromophore (Cα-Cß bond dissociation channel) after photoexcitation at 263 nm have been investigated for several small peptides containing tryptophan or tyrosine. For tryptophan-containing peptides, the aromatic chromophore is lost as an ionic fragment (m/z 130), and the fragmentation time increases with the mass of the neutral fragment. In contrast, for tyrosine-containing peptides the aromatic chromophore is always lost as a neutral fragment (mass = 107 amu) and the fragmentation time is found to be fast (<20 ns). These different behaviors are explained by the role of the postfragmentation interaction in the complex formed after the Cα-Cß bond cleavage.

UV Photofragmentation Dynamics of Protonated Cystine: Disulfide Bond Rupture.

Disulfide bonds (S-S) play a central role in stabilizing the native structure of proteins against denaturation. Experimentally, identification of these linkages in peptide and protein structure characterization remains challenging. UV photodissociation (UVPD) can be a valuable tool in identifying disulfide linkages. Here, the S-S bond acts as a UV chromophore and absorption of one UV photon corresponds to a σ-σ* transition. We have investigated the photodissociation dynamics of protonated cystine, which is a dimer of two cysteines linked by a disulfide bridge, at 263 nm (4.7 eV) using a multicoincidence technique in which fragments coming from the same fragmentation event are detected. Two types of bond cleavages are observed corresponding to the disulfide (S-S) and adjacent C-S bond ruptures. We show that the S-S cleavage leads to three different fragment ions via three different fragmentation mechanisms. The UVPD results are compared to collision-induced dissociation (CID) and electron-induced dissociation (EID) studies.

Photofragmentation at 263 nm of small peptides containing tyrosine: the role of the charge transfer on CO.

The photofragmentation pathways at 263 nm of several small peptides containing tyrosine as the UV chromophore have been characterized using a multi-coincidence technique. A detailed study of the fragmentation dynamics of protonated Glycine-Tyrosine (GYH(+)), Tyrosine-Glycine (YGH(+)), Glycine-Tyrosine-Glycine (GYGH(+)), Alanine-Tyrosine (AYH(+)) and Tyrosine-Alanine (YAH(+)) is presented in this paper. Fragmentations occurring or initiated in an excited state are distinguished from those occurring after internal conversion to the ground electronic state by their rapid fragmentation times and binary nature. For the studied systems, it is shown that fragmentations occurring after internal conversion to the ground state are the dominant processes compared to fragmentations occurring in the excited state. The low abundances associated with the observed UV photospecific channels, i.e. Cα-Cß bond breakage in YGH(+) and YAH(+) and direct z-type bond breakage in GYGH(+), respectively, can be rationalized upon consideration of charge transfer states accessible after absorption of one UV photon. Indeed, excited state calculations performed at the RI-CC2 level of theory indicate that charge transfer on the active CO group is a prerequisite for photospecific bond ruptures. The fragmentation mechanisms and the localization of the charge on the side chain after fragmentation are discussed in terms of ionization energies of the fragments.

Photofragmentation in selected tautomers of protonated adenine.

The photofragmentation by UV excitation of selectively prepared 1(+) and 3(+) tautomers of protonated adenine is studied after excitation at a 266 and 263 nm wavelengths with two different experimental set-ups located in Seoul and Orsay. While the production of 1(+) tautomers with an electrospray ion source is now well accepted, calculations were used to ascribe the preparation of 3(+) tautomers from cold adenine dimers. The fragmentation patterns are rather similar for both tautomers, suggesting similar mechanisms as a statistical fragmentation in the ground electronic state after internal conversion.

Exploring theory of mind after severe traumatic brain injury.

Previous studies have reported a dissociation between social behavioral impairments after severe traumatic brain injury (TBI) and relatively preserved performances in traditional tasks that investigate cognitive abilities. Theory of mind (ToM) refers to the ability to make inferences about other's mental states and use them to understand and predict others' behavior. We tested a group of 15 patients with severe TBI and 15 matched controls on a series of four verbal and non-verbal ToM tasks: the faux pas test, the first-order and second-order false belief task, the character intention task and the Reading the Mind in the Eyes Test. Participants with severe TBI were also compared to controls on non-ToM inference tasks of indirect speech act from the Montreal Evaluation of Communication (M.E.C.) Protocol and empathy (Davis Interpersonal Reactivity Index - I.R.I.) and tests for executive functions. Subjects with TBI performed worse than control subjects on all ToM tasks, except the first-order false belief task. The findings converge with previous evidence for ToM deficit in TBI and dissociation between ToM and executive functions. We show that ToM deficit is probably distinct from other aspects of social cognition like empathy and pragmatic communication skills.

Maximal and sustained isokinetic lower-limb muscle strength in hospitalized older people.

Maximal strength decreases with aging whereas sustained strength is less affected. Strength decline may be worsened by hospitalization. The aim of this study was to estimate the maximal and sustained isokinetic muscle strength of lower limbs in hospitalized elderly subjects. We evaluated 43 hospitalized elderly subjects (86 +/- 5 years), 28 elderly community-dwelling control subjects (75.4 +/- 6.2 years), and 25 young subjects (28.2 +/- 3.7 years). Among hospitalized subjects, 30 underwent isokinetic evaluation at clinical stability (T0) and again 1 month later (T1). Maximal peak torque (MPT) of the plantarflexors was measured at 30 degrees and 60 degrees /s, and knee flexors and extensors at 90 degrees /s. Evolution of the MPT and the endurance coefficient (EC) on 20 repetitions of plantarflexion at 60 degrees /s were calculated. MPT of plantarflexors and knee flexors and extensors had improved at T1 compared with T0, in hospitalized subjects. MPT evolution and EC values during the sustained strength test revealed no decrease in strength over time in hospitalized subjects at T0 and at T1 compared with community-dwelling control subjects and young subjects. In hospitalized subjects, the absence of an initial phase of fast decrease in muscle strength, which is observed in young subjects during the sustained strength test, could explain this result. It could be related to the modifications of muscle-fiber composition described in elderly subjects and enhanced by hospitalization.

Defective reproduction of passive meaningless gestures in right brain damage: a perceptual disorder of one's own body knowledge?

Right Hemisphere Damaged Patients (RHDP) with left hemiparesis are known to experience motor programming difficulties and to have poorer functional outcome when compared with Left Hemisphere Damaged Patients (LHDP). The role played by body-related cognitive disorders remains unclear. In this study we investigate whether reproduction of passive meaningless gestures may contribute to a further development of this question. Ten RHDP with neglect, 10 RHDP without neglect, 10 LHDP, and 10 controls were given a battery of tasks requiring reproduction of passive meaningless gestures. The gestures were passively applied by the examiner on either the ipsilesional or the contralesional upper limb of the subject who was asked to reproduce them with his ipsilesional- non-paretic -limb. LHDP performed virtually as well as controls when the influence of deafferentation was controlled. The performance of RHDP with and without neglect did not differ from each other but both groups were significantly impaired when compared with either controls or LHDP, whether the gestures were applied on the contralesional or ipsilesional limb. RHDP performed defectively whether they had closed or open eyes, which tends to indicate a perceptual multimodal integration disorder rather than a modality-related sensory disorder. The left hemisphere is generally considered dominant for deliberate motor control of both sides of the body, not only for symbolic gestures but also for (visual) imitation of meaningless gestures. The results of this study raise the question of why reproduction of meaningless gestures is more impaired for LHDP than RHDP when stimulus presentation is visual and vice versa when stimulation is passively applied upon the subject's body. One reason may be that in visual imitation, the model is given by another person's body, whereas passive gestures, directly applied upon one's body, place demands on perceptual analysis of one's own body experience. These results might give evidence for a disorder of bilateral, perceptual, multimodal integration of knowledge about one's own body in RHDP.

Functional MRI follow-up study of language processes in healthy subjects and during recovery in a case of aphasia.

BACKGROUND AND PURPOSE: The goal of this study was to develop a functional MRI (fMRI) paradigm robust and reproducible enough in healthy subjects to be adapted for a follow-up study aiming at evaluating the anatomical substratum of recovery in poststroke aphasia. METHODS: Ten right-handed subjects were studied longitudinally using fMRI (7 of them being scanned twice) and compared with a patient with conduction aphasia during the first year of stroke recovery. RESULTS: Controls exhibited reproducible activation patterns between subjects and between sessions during language tasks. In contrast, the patient exhibited dynamic changes in brain activation pattern, particularly in the phonological task, during the 2 fMRI sessions. At 1 month after stroke, language homotopic right areas were recruited, whereas large perilesional left involvement occurred later (12 months). CONCLUSIONS: We first demonstrate intersubject robustness and intrasubject reproducibility of our paradigm in 10 healthy subjects and thus its validity in a patient follow-up study over a stroke recovery time course. Indeed, results suggest a spatiotemporal poststroke brain reorganization involving both hemispheres during the recovery course, with an early implication of a new contralateral functional neural network and a later implication of an ipsilateral one.

Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study.

PURPOSE: Chemical defunctionalization of C-fiber bladder afferents with intravesical vanilloids such as capsaicin (CAP) or resiniferatoxin (RTX) improves detrusor hyperreflexia in humans and animals. The little existing data comparing the efficacy and tolerance of these 2 vanilloid agents seem to favor RTX in 10% alcohol over CAP, which is usually diluted in 30% alcohol. We compared the efficacy and tolerability of the 2 vanilloid agonists in what to our knowledge is the first randomized, controlled study comparing nonalcohol CAP vs RTX in 10% alcohol in neurogenic patients with detrusor hyperreflexia. MATERIALS AND METHODS: This single center, randomized, double-blind, parallel groups study included 39 spinal cord injured adults with detrusor hyperreflexia. On day 0 patients were randomized to receive 1, 100 ml intravesical instillation of 100 nMol/l RTX diluted in 10% ethanol or 1 mmol/l CAP diluted in glucidic solvent. Efficacy (voiding chart and cystomanometry) and tolerability were evaluated during a 3-month followup. RESULTS: On day 30 clinical and urodynamical improvement was found in 78% and 83% of patients with CAP vs 80% and 60% with RTX, respectively, without a significant difference between the 2 treated groups. The benefit remained in two-thirds of the 2 groups on day 90. There were no significant differences in regard to the incidence, nature or duration of side effects in CAP vs RTX treated patients. CONCLUSIONS: Our results strongly argue for the importance of accounting for the role of vanilloid solute when interpreting the efficacy and tolerance of vesical vanilloid instillation in detrusor hyperreflexia cases. They suggest that a glucidic solute is a valuable solvent for vanilloid instillation.

[Autonomic hyperreflexia induced by sacral root stimulation is detected by spectral analysis of the EEG]. / L'hyperréflexie autonome induite par la stimulation des racines sacrées est détectée par l'analyse spectrale de l'ECG.

PURPOSE: To compare spectral analysis of the electrocardiogram (ECG) with mean arterial pressure (MAP) and heart rate (HR) monitoring in the detection of autonomic hyperreflexia (AHR) induced by sacral root stimulation. METHODS: Ten spinal cord injured patients scheduled for implantation of a sacral root stimulator for bladder retention were included. Under target controlled anesthesia with propofol 4 micro g*mL(-1) and remifentanil 4 ng*mL(-1), the patients were placed in the knee chest position. The sacral roots were exposed by laminectomy (L2-S1) and their function assessed by electrostimulation under urodynamic and cardiovascular monitoring. Online power spectrum densities were calculated from the ECG R-R interval by the MemCalc(TM) software using the maximum entropy method. Low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) spectra were associated with sympathetic and parasympathetic activities respectively. The most extreme value of each variable was noted before and during each stimulation. A difference ( triangle up ) of more than 10% signified AHR. The comparison ( triangle up LF vs triangle up MAP and triangle up HF vs triangle up HR) was done by a concordance test with a kappa coefficient (k): -1 = total discordance to 1 = total concordance. RESULTS: AHR was detected in six patients as an increase in LF and MAP (n = 4); an increase in LF, HF, MAP with a decrease in HR (n = 2). The detection delay was 5.3 +/- 1 sec (LF, HF) and 10.4 +/- 1.2 sec (MAP and HR). Concordance was 85% (LF vs MAP: k = 0.7) and 90% (HF vs HR: k = 0.8). CONCLUSION: AHR induced by sacral root stimulation is detected by spectral analysis of the ECG earlier than MAP and HR. Other studies are needed to confirm these results.

Botulinum a toxin and detrusor sphincter dyssynergia: a double-blind lidocaine-controlled study in 13 patients with spinal cord disease.

OBJECTIVE: To compare the efficacy and tolerance of botulinum A toxin (BTx) versus lidocaine (L), applied in the external urethral sphincter with a single transperineal injection in order to treat detrusor sphincter dyssynergia (DSD) in spinal cord injured patients. METHODS: Thirteen patients (1F, 12 M) suffering from chronic urinary retention due to DSD were randomised to receive one transperineal injection of 100 IU BTx Botox degrees in 4 ml of 9% saline (botulinum group, (BG)) or 4 ml of 0.5% L (lidocaine group, (LG)). The main criteria of efficacy was post-voiding residual urine volume (PRUV), assessed three times daily on day one (D1), D7 and D30 after each injection. Other criteria were micturition diary, satisfaction score (SS), maximal urethral pressure (MUP), maximum detrusor pressure (DP) and type of DSD, recorded on D0 and D30. RESULTS: In the BG, there was a significant decrease in PRUV (D7: -141.4 ml (p<0.03); D30: -159.4 ml (p<0.01)), in MUP (D30: -32 cm H(2)O, p<0.04) whereas no significant improvement was shown in the LG. SS was higher in BG than LG (p<0.02). DSD improved in BG whereas it remained unchanged in LG. All LG patients also received one injection of BTx on D30. They still presented improvement in PRUV and MUP 1 month later (D30'). Tolerance appeared satisfactory in both groups. CONCLUSIONS: The preliminary results of this initial randomised double-blind study clearly demonstrated the superiority of BTx compared to L in improving clinical symptoms and urethral hypertonia associated with DSD in spinal cord injured patients.