The timing of prehensile movements in subjects with cerebral palsy

In this study, a paradigm is presented for the assessment of manual dexterity in subjects With cerebral palsy (CP) that divides the prehensile action into a 'time-to-contact' phase and a 'time-in-contact' phase. Two experiments were performed that determined the effect of object weight on the timing of both phases for the impaired hand and non-impaired hand of subjects with spastic hemiparesis ( N = 14). In the first experiment, subjects had to reach for and lift a tube at their own preferred speed. The results showed that the prehensile deficit of the impaired limb is to a large degree manifested by a longer time spent in contact with the object before it was lifted. The time-in-contact phase was decreased after repeated lifts, suggesting that subjects with CP can control and modify force output in advance based on weight information from preceding lifts. In the second experiment speed of movement execution was stressed to examine whether the observed timing pattern of the first experiment is characteristic of prehensile movements of the paretic arm or represents a movement strategy adapted to the disorder. The results of the second experiment showed that subjects could comply with the instruction by reducing the absolute duration of both phases of the prehensile movement. Furthermore, the anticipation effects were eliminated to a large degree. In both experiments the time-in-contact phase was longer for the impaired limb. These results indicate a pathological constant in the time-in-contact phase for the impaired limb. This assumption is discussed in relation to the application of grip and lift forces during this phase. It is concluded that the paradigm is well suited for use in a practical setting as a simple and broad clinical test to assess the prehensile decrements of subjects with CP.     

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography

Background

In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity.

Task-evoked reconfiguration of the fronto-parietal network is associated with cognitive performance in brain tumor patients

Brain Imaging and Behavior - In healthy participants, the strength of task-evoked network reconfigurations is associated with cognitive performance across several cognitive domains. It is, however,...     

Effects of the GABAB receptor-positive modulators CGP7930 and rac-BHFF in baclofen- and γ-hydroxybutyrate-discriminating pigeons

Serotonin (5-hydroxytryptamine; 5-HT) is involved in heart valve tissue fibrosis, pulmonary arterial fibrosis, and pulmonary hypertension. We aimed at characterizing the antiserotonergic properties of the ergot alkaloid derivative terguride [1,1-diethyl-3-(6-methyl-8α-ergolinyl)urea] by using functional receptor assays and valvular interstitial cell culture. Terguride showed no vasoconstrictor effect in porcine coronary arteries (5-HT(2A) receptor bioassay) and no relaxant effect in porcine pulmonary arteries (5-HT(2B) receptor bioassay). Terguride behaved as a potent antagonist at 5-HT(2A) receptors (noncompetitive antagonist parameter pD'? 9.43) and 5-HT(2B) receptors (apparent pA? 8.87). Metabolites of terguride (N″-monodeethylterguride and 6-norterguride) lacked agonism at both sites. N″-monodeethylterguride and 6-norterguride were surmountable antagonists at 5-HT(2A) receptors (pA? 7.82 and 7.85, respectively) and 5-HT(2B) receptors (pA? 7.30 and 7.11, respectively). Kinetic studies on the effects of terguride in pulmonary arteries showed that the rate to reach drug-receptor equilibrium for terguride was fast. Washout experiments showed that terguride easily disappeared from the receptor biophase. Pretreatment with terguride inhibited 5-HT-induced amplification of ADP-stimulated human platelet aggregation (IC?? 16 nM). In porcine valvular interstitial cells, 5-HT-induced activation of extracellular signal-regulated kinase (ERK) 1/2, an initiator of cellular proliferation and activity, was blocked by terguride as shown by Western blotting. In these cells, the stimulatory effect of 5-HT on [3H]proline incorporation (index of extracellular matrix collagen) was blocked by terguride. Because of the inhibition of both 5-HT(2A) and 5-HT(2B) receptors, platelet aggregation, and cellular proliferation and activity (ERK1/2 phosphorylation and collagen production) terguride may have therapeutic potential in the treatment of fibrotic disorders.     

Glutamine synthetase is essential in early mouse embryogenesis.

Glutamine synthetase (GS) is expressed in a tissue-specific and developmentally controlled manner, and functions to remove ammonia or glutamate. Furthermore, it is the only enzyme that can synthesize glutamine de novo. Since congenital deficiency of GS has not been reported, we investigated its role in early development. Because GS is expressed in embryonic stem (ES) cells, we generated a null mutant by replacing one GS allele in-frame with a beta-galactosidase-neomycine fusion gene. GS(+/LacZ) mice have no phenotype, but GS(LacZ/LacZ) mice die at ED3.5, demonstrating GS is essential in early embryogenesis. Although cells from ED2.5 GS(LacZ/LacZ) embryos and GS(GFP/LacZ) ES cells survive in vitro in glutamine-containing medium, these GS-deficient cells show a reduced fitness in chimera analysis and fail to survive in tetraploid-complementation assays. The survival of heavily (>90%) chimeric mice up to at least ED16.5 indicates that GS deficiency does not entail cell-autonomous effects and that, after implantation, GS activity is not essential until at least the fetal period. We hypothesize that GS-deficient embryos die when they move from the uterine tube to the harsher uterine environment, where the embryo has to catabolize amino acids to generate energy and, hence, has to detoxify ammonia, which requires GS activity.     

Assessment of Antibody Response Elicited by a 7-valent Pneumococcal Conjugate Vaccine in Pediatric Human Immunodeficiency Virus Infection

We investigated antibody responses against pneumococci of serotypes 6B, 14, and 23F in 56 children and adolescents with perinatal human immunodeficiency virus (HIV) infection who were vaccinated with 7-valent pneumococcal conjugate vaccine. Overall immune responses differed greatly between serotypes. Correlation coefficients between immunoglobulin G (IgG) measured by enzyme-linked immunosorbent assay (ELISA) and functional antibodies measured by a flow cytometry opsonophagocytosis assay (OPA) varied with serotype and time points studied. After 3 months of administering a second PCV7 dose we got the highest correlation (with significant r values of 0.754, 0.414, and 0.593 for serotypes 6B, 14, and 23F, respectively) but no significant increase in IgG concentration and OPA titers compared to the first dose. We defined a responder to a serotype included in the vaccine with two criteria: frequency of at least twofold OPA and ELISA increases for each serotype and frequency of conversion from negative to positive OPA levels. Responders varied from 43.9% to 46.3%, 28.5% to 50.0%, and 38.0% to 50.0% for serotypes 6B, 14, and 23F, respectively, depending on the response criterion. The present research highlights the importance of demonstrating vaccine immunogenicity with suitable immunological endpoints in immunocompromised patients and also the need to define how much antibody is required for protection from different serotypes, since immunogenicity differed significantly between serotypes.     

Cognitive vs. affective listening modes and judgments of music - An ERP study

The neural correlates of processing deviations from Western music rules are relatively well known. Less is known of the neural dynamics of top-down listening modes and affective liking judgments in relation with judgments of tonal correctness. In this study, subjects determined if tonal chord sequences sounded correct or incorrect, or if they liked them or not, while their electroencephalogram (EEG) was measured. The last chord of the sequences could be congruous with the previous context, ambiguous (unusual but still enjoyable) or harmonically inappropriate. The cognitive vs. affective listening modes were differentiated in the event-related potential (ERP) responses already before the ending chord, indicating different preparation for the judgment tasks. Furthermore, three neural events tagged the decision process preceding the behavioral responses. First, an early negativity, peaking at about 280 ms, was elicited by chord incorrectness and by disliking judgments only over the right hemisphere. Second, at about 500 ms from the end of the sequence a positive brain response was elicited by the negative answers of both tasks. Third, at about 1200 ms, a late positive potential (LPP) was elicited by the liking judgment task whereas a large negative brain response was elicited by the correctness judgment task, indexing that only at that late latency preceding the button press subjects decided how to judge the cadences. This is the first study to reveal the dissociation between neural processes occurring during affective vs. cognitive listening modes and judgments of music.     

In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(ε-caprolactone)

The aim of this study was to evaluate the in vivo biodegradation and biocompatibility of three-dimensional (3D) scaffolds based on a hydroxyl-functionalized polyester (poly(hydroxymethylglycolide-co-ε-caprolactone), PHMGCL), which has enhanced hydrophilicity, increased degradation rate, and improved cell-material interactions as compared to its counterpart poly(ε-caprolactone), PCL. In this study, 3D scaffolds based on this polymer (PHMGCL, HMG:CL 8:92) were prepared by means of fiber deposition (melt-plotting). The biodegradation and tissue biocompatibility of PHMGCL and PCL scaffolds after subcutaneous implantation in Balb/c mice were investigated. At 4 and 12 weeks post implantation, the scaffolds were retrieved and evaluated for extent of degradation by measuring the residual weight of the scaffolds, thermal properties (DSC), and morphology (SEM) whereas the polymer was analyzed for both its composition ((1)H NMR) and molecular weight (GPC). The scaffolds with infiltrated tissues were harvested, fixed, stained and histologically analyzed. The in vitro enzymatic degradation of these scaffolds was also investigated in lipase solutions. It was shown that PHMGCL 3D-scaffolds lost more than 60% of their weight within 3 months of implantation while PCL scaffolds showed no weight loss in this time frame. The molecular weight (M(w)) of PHMGCL decreased from 46.9 kDa before implantation to 23.2 kDa after 3 months of implantation, while the molecular weight of PCL was unchanged in this period. (1)H NMR analysis showed that the degradation of PHMGCL was characterized by a loss of HMG units. In vitro enzymatic degradation showed that PHMGCL scaffolds were degraded within 50 h, while the degradation time for PCL scaffolds of similar structure was 72 h. A normal foreign body response to both scaffold types characterized by the presence of macrophages, lymphocytes, and fibrosis was observed with a more rapid onset in PHMGCL scaffolds. The extent of tissue-scaffold interactions as well as vascularization was shown to be higher for PHMGCL scaffolds compared to PCL ones. Therefore, the fast degradable PHMGCL which showed good biocompatibility is a promising biomaterial for tissue engineering applications.