Distinct Contributions of Dorsal and Ventral Streams to Imitation of Tool-Use and Communicative Gestures.

Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively.

Componential Network for the Recognition of Tool-Associated Actions: Evidence from Voxel-based Lesion-Symptom Mapping in Acute Stroke Patients.

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively.

Predictors and signatures of recovery from neglect in acute stroke.

OBJECTIVE: Spatial neglect can either spontaneously resolve or persist after stroke; the latter is associated with a poorer outcome. We aimed to investigate the neural correlates and predictors of favorable versus poor recovery from neglect in acute stroke. METHODS: In addition to neuropsychological testing, we explored task-related functional magnetic resonance imaging activation and functional connectivity in 34 patients with neglect and/or extinction. Patients were examined at 2 to 3 days (acute phase I) and 8 to 10 days (acute phase II), and some of them at 4 to 6 months (chronic phase) poststroke. RESULTS: Course of recovery was predicted by the strength of functional connectivity between the right parietal and left prefrontal and parietal regions, as early as acute phase I. During acute phase II, favorable recovery from neglect was associated with increased activation in the left prefrontal and right parietal regions, an effect not observed at any time point in patients with poor acute recovery. The extent of neglect amelioration correlated with activation gain in the right attention centers; stronger activation of their left functional homologues correlated with better spatial processing in the neglected hemispace during both of the acute examination phases. INTERPRETATION: System excitability and early recruitment of contralesional functional homologues represented specific features of favorable recovery in acute stroke. In severe strokes leading to neglect, contralesional functional homologues support recovery by modulating the preserved ipsilesional network, and initial functional connectivity between them might predict recovery course and help to identify patients with potentially poor recovery requiring more intensive early rehabilitation.

Visual neglect after left-hemispheric lesions: a voxel-based lesion-symptom mapping study in 121 acute stroke patients.

Visual neglect after left-hemispheric lesion is thought to be less frequent, less severe, and shorter lived than visuospatial attention deficits resulting from right-hemispheric lesions. However, reports exist opposing this assumption, and it is unclear how these findings fit into the current theories of visuospatial processing. Furthermore, only little is known about the exact structure-function relationship between visuospatial attention deficits and left-hemispheric stroke. We investigated neglect in 121 patients with acute left-hemispheric ischemic stroke by following clinical development from within the first 24 h of stroke onset until hospital discharge. Visuospatial attention deficits occurred in 17.4 % (n = 21). Voxel-based lesion-symptom mapping associated visual neglect to the right with lesion in the left superior and middle temporal gyrus, temporal pole, frontal operculum, and insula. Neglect severity, captured by the Center of Cancellation Score of the Bells test, was associated with lesion in the left anterior temporal lobe and the left frontal operculum. The left-hemispheric lesion pattern of neglect thus involves areas of the ventral attention system and partly mirrors the critical regions of the right hemisphere known to be associated with neglect. Based on our prospective analysis on a large cohort of patients with left-hemispheric stroke, this study shows that in a remarkable number of patients, the left hemisphere essentially contributes to an intact representation of space and clarifies the impact of the distinct left-hemispheric structures involved in visuospatial processing.

Brain activity underlying tool-related and imitative skills after major left hemisphere stroke.

Apraxia is a debilitating cognitive motor disorder that frequently occurs after left hemisphere stroke and affects tool-associated and imitative skills. However, the severity of the apraxic deficits varies even across patients with similar lesions. This variability raises the question whether regions outside the left hemisphere network typically associated with cognitive motor tasks in healthy subjects are of additional functional relevance. To investigate this hypothesis, we explored regions where functional magnetic resonance imaging activity is associated with better cognitive motor performance in patients with left hemisphere ischaemic stroke. Thirty-six patients with chronic (>6 months) large left hemisphere infarcts (age ± standard deviation, 60 ± 12 years, 29 male) and 29 control subjects (age ± standard deviation, 72 ± 7, 15 male) were first assessed behaviourally outside the scanner with tests for actual tool use, pantomime and imitation of tool-use gestures, as well as for meaningless gesture imitation. Second, functional magnetic resonance imaging activity was registered during the passive observation of videos showing tool-associated actions. Voxel-wise linear regression analyses were used to identify areas where behavioural performance was correlated with functional magnetic resonance imaging activity. Furthermore, lesions were delineated on the magnetic resonance imaging scans for voxel-based lesion-symptom mapping. The analyses revealed two sets of regions where functional magnetic resonance imaging activity was associated with better performance in the clinical tasks. First, activity in left hemisphere areas thought to mediate cognitive motor functions in healthy individuals (i.e. activity within the putative 'healthy' network) was correlated with better scores. Within this network, tool-associated tasks were mainly related to activity in supramarginal gyrus and ventral premotor cortex, while meaningless gesture imitation depended more on the anterior intraparietal sulcus and superior parietal lobule. Second, repeating the regression analyses with total left hemisphere lesion volume as additional covariate demonstrated that tool-related skills were further supported by right premotor, right inferior frontal and left anterior temporal areas, while meaningless gesture imitation was also driven by the left dorso-lateral prefrontal cortex. In summary, tool-related and imitative skills in left hemisphere stroke patients depend on the activation of spared left hemisphere regions that support these abilities in healthy individuals. In addition, cognitive motor functions rely on the activation of ipsi- and contralesional areas that are situated outside this 'healthy' network. This activity may explain why some patients perform surprisingly well despite large left brain lesions, while others are severely impaired.

Differential Roles of Ventral and Dorsal Streams for Conceptual and Production-Related Components of Tool Use in Acute Stroke Patients.

Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel-based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams.

Autoclaving time-related reduction in amino acid digestibility of poultry meal in broiler chickens and growing pigs.

Poultry meal, a rendered byproduct of poultry slaughter, is a valuable protein source in swine and poultry diets because of its highly digestible protein content and balanced amino acid (AA) profile. Rendering of poultry meal may reduce its AA digestibility because of heat damage to the byproduct. The effect of heat damage on AA digestibility of poultry meal may be different between broiler chickens and growing pigs. For this reason, the objective of this study was to determine the effect of autoclaving time on standardized ileal digestibility (SID) of AA in poultry meal fed to broiler chickens and growing pigs. Poultry meal from the same batch was autoclaved at 134 °C for 0, 30, 60, 90, 120, 150, or 180 min to produce seven heat-treated samples. Eight experimental diets were formulated. Poultry meal served as the sole source of nitrogen in seven diets that each contained one of the heat-treated byproducts and a nitrogen-free diet was formulated to assess basal ileal endogenous losses of AA. In experiment 1, 656 male broiler chickens (initial body weight = 719 ±â€…97 g) at day 18 post hatching were assigned to the eight diets in a randomized complete block design with body weight as a blocking factor. On day 23, birds were euthanized by CO2 asphyxiation and dissected for the collection of ileal digesta. In experiment 2, 16 barrows (initial body weight = 23.3 ±â€…0.7 kg) were surgically fitted with T-cannulas at the distal ileum and allotted to a duplicate 8 × 4 incomplete Latin square design with the eight diets and four periods. Each experimental period consisted of 5-day adaptation and 2-day ileal digesta collection periods. Data for experiments 1 and 2 were pooled and analyzed as a 2 × 7 factorial treatment arrangement with the effects of species (i.e., pigs and broiler chickens) and autoclaving time (i.e., 0 to 180 min) as the two factors. Increasing autoclaving time decreased SID of nitrogen and all AA in both species, but the decrease in SID values except for leucine was greater (interaction, P < 0.05) or tended to be greater in pigs compared with broiler chickens. Given the species differences in AA utilization response to the severity of heat damage, target species should be considered when using SID of AA values of poultry meal in diet formulation.

Poultry meal, a rendered byproduct of poultry slaughter, is a valuable protein source in swine and poultry diets. Rendering is required during the processing of poultry meal to inactivate potential harmful bacteria and to reduce moisture content in the raw byproduct. However, rendering can induce heat damage to poultry meal, which may reduce amino acid (AA) digestibility. To mimic heat damage to poultry meal, the byproduct was autoclaved at 134 °C for 0, 30, 60, 90, 120, 150, or 180 min in the current study. These seven heat-treated poultry meal samples were then fed to broiler chickens and growing pigs. AA digestibility in poultry meal decreased with increasing autoclaving time, but the decrease in digestibility of most AAs by autoclaving was larger in growing pigs compared with broiler chickens.

Rapid narrow band elution for on-line SPE using a novel solvent plug injection technique.

Determination of trace constituents in biological and environmental samples usually requires a pre-concentration step. While solid-phase extraction (SPE) has been widely used, it is slow, labor intensive and adversely affected by analytical errors from handling. On-line SPE eliminates some of the flaws but often suffers from solvent compatibility problems with the subsequent chromatography separation. In this study, we are presenting a technical solution for overcoming some of these compatibility issues, by utilizing a fully automated, focused SPE sample transfer technique utilizing narrow-band solvent plugs, for seamless hyphenation with high-performance liquid chromatography (HPLC) or flow injection mass spectrometry (MS). A wide range of pharmaceutical compounds was studied in different sample matrices. Short plugs of high elution strength solvent were generated by means of an electrically actuated sample loop and enrichment and transfer steps monitored using on-line SPE-MS. The impact of the solvent plugs on chromatographic separation was studied using hyphenated SPE-LC-MS. By carefully examining elution profiles of solvent plugs of different compositions, optimum conditions for quantitative elution within well-defined volumes were found for all substances. In addition, the highly focused elution bands resulted in excellent retention time and peak area reproducibilities when injected on-line onto HPLC columns. Finally, to demonstrate proof-of-principle, the fully integrated on-line SPE-LC-MS system was applied to the analysis of spiked urine and river water samples.

Does residency training improve cognitive competence in obstetric and gynaecologic surgery?

OBJECTIVE: To develop an operative knowledge assessment tool to evaluate the cognitive competence of trainees in obstetric and gynaecologic surgery and to determine the rate of change in competence during a five-year residency program. METHODS: Twenty-eight participants in five training groups (PGY-1 to PGY-5) in McGill University's residency program in obstetrics and gynaecology underwent an evaluation based on surgical cognitive competence (SCC) assessment tools developed for three different obstetric and gynaecologic operations: open total abdominal hysterectomy (TAH), Caesarean section, and laparoscopic bilateral tubal sterilization (BTL). The tools were developed as checklists listing every step in each operation based on techniques described in current surgical texts. Using analysis of variance and linear regressions, statistical significance was established for procedure-specific scores and overall SCC scores. In addition, the rate of change of cognitive competence throughout the training years was calculated. Finally, using a t test, the overall SCC score was compared to a "critical steps score". RESULTS: Critical steps scores and overall SCC scores increased with training experience at an average yearly rate of 13.36% (P < 0.001). Procedure-specific scores increased yearly, by 15.73% for TAH (P < 0.001), 8.06% for Caesarean section (P < 0.001), and 16.31% for BTL (P < 0.001). The difference between overall scores and critical steps scores was not statistically significant for the study cohort (P = 0.94). CONCLUSION: Surgical cognitive competence among obstetrics and gynaecology residents can be reliably assessed with our evaluation tool, and it increases proportionally with residency education, reaching maximum scores during the final year of training. This type of information may be helpful in ascertaining how long a residency program should be.

Influence of Conditioning and Expansion Characteristics on the Apparent Metabolizable Energy and Standardized Ileal Amino Acid Digestibility of Full-Fat Soybeans for Broilers.

This study investigated the influence of short-term and long-term conditioning and expansion on the nitrogen-corrected apparent metabolizable energy (AMEn) and standardized ileal digestibility (SID) of amino acids (AA) in full-fat soybeans (FFSB) for broilers. A batch of raw soybeans was used to manufacture 10 FFSB products (T0 to T9) by applying various combinations of conditioning and expansion. The AMEn and SID AA of FFSB were determined by difference and direct methods, respectively. All heat treatments increased (p < 0.001) the AMEn compared to raw FFSB. The sample subjected to long-term conditioning at 100 °C for 6 min and expansion at 18 kWh/t (T5) supported 3.88 MJ/kg higher AMEn than the raw FFSB. Raw FFSB had the poorest (p < 0.05) AA digestibility. Among the heat-treated samples, the highest (p < 0.05) SID AA was recorded for T5. The results demonstrated that the long-term conditioning of FFSB at 100 °C for 6 min prior to expansion with 18 kWh/t specific energy input enhanced metabolizable energy and SID AA. Further increases in conditioning time from 6 to 9 min or expansion of specific energy input from 18 to 28 kWh/t did not yield additional benefits to energy utilization and AA digestibility of FFSB.

Autoclaving time-related reduction in metabolizable energy of poultry meal is greater in growing pigs compared with broiler chickens.

The objective of this study was to determine the energy utilization responses of growing pigs and broiler chickens to poultry meal that was autoclaved at 134 °C for 0 to 180 min. Poultry meal from the same batch was autoclaved at 134 °C for 7 autoclaving times of 0, 30, 60, 90, 120, 150, or 180 min to generate 7 samples. Eight experimental diets consisting of a basal diet based on corn and soybean meal, and seven test diets in which 15% of energy-contributing ingredients in the basal diet were replaced with each of the seven poultry meal samples were used. In experiment 1, there were 64 barrows (initial body weight = 19.4 ± 1.0 kg) allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Each pig received an experimental diet during 5 d of adaptation followed by 5 d of quantitative total, but separate, collection of urine and feces. In experiment 2, a total of 512 male broiler chickens at day 17 post-hatching (initial body weight = 660 ± 80 g) in 8 replicate cages were allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Excreta were collected from days 20 to 22 post-hatching, and birds were euthanized by CO2 asphyxiation for ileal digesta collection. Data from experiments 1 and 2 were pooled together for statistical analysis as a 2 × 7 factorial treatment arrangement with the effect of species (pigs or broiler chickens) and autoclaving time of poultry meal (7 autoclaving times between 0 and 180 min). An interaction between species and their linear effect of autoclaving time was observed (P < 0.05) in metabolizable energy (ME) of poultry meal. Specifically, linear decrease in ME values in poultry meal with increasing autoclaving time was greater (P < 0.05) in growing pigs (4,792 to 3,897 kcal/kg dry matter) compared with broiler chickens (3,591 to 3,306 kcal/kg dry matter). The ME value of unautoclaved poultry meal was greater (P < 0.01) for pigs than broiler chickens at 4,792 vs. 3,591 kcal/kg dry matter. Although decrease in ME values with autoclaving time of poultry meal was greater in growing pigs than in broiler chickens, the ME in autoclaved poultry meal fed to pigs was greater than ME in non-autoclaved poultry meal fed to broiler chickens. Furthermore, the ratio of cysteine to crude protein concentration is a potential indicator for estimating the ratio of ME to gross energy in poultry meal for growing pigs (r2 = 0.81) and broiler chickens (r2 = 0.84).

Poultry meal is a rendered product that consists of clean flesh and skin-derived from the parts of whole carcasses of slaughtered poultry. Because poultry meal has a highly digestible protein concentration and optimal amino acid profile, it is widely used in swine and poultry diets. During the rendering process, poultry meal is heated, which may affect energy utilization. In the current study, poultry meal was autoclaved at 134 °C for 0, 30, 60, 90, 120, 150, or 180 min to mimic heating of poultry meal. These seven poultry meal samples were fed to growing pigs and broiler chickens. Reduction in energy utilization with autoclaving time of poultry meal was greater in growing pigs compared with broiler chickens. However, despite a larger decrease in energy utilization in poultry meal by autoclaving in growing pigs, metabolizable energy values were still greater in growing pigs compared with broiler chickens.

Application of Apparent Metabolizable Energy versus Nitrogen-Corrected Apparent Metabolizable Energy in Poultry Feed Formulations: A Continuing Conundrum.

In the present investigation, N retention, AME, and AMEn data from six energy evaluation assays, involving four protein sources (soybean meal, full-fat soybean, rapeseed meal and maize distiller's dried grains with solubles [DDGS]), are reported. The correction for zero N retention, reduced the AME value of soybean meal samples from different origins from 9.9 to 17.8% with increasing N retention. The magnitude of AME penalization in full-fat soybean samples, imposed by zero N correction, increased from 1.90 to 9.64% with increasing N retention. The Δ AME (AME minus AMEn) in rapeseed meal samples increased from 0.70 to 1.09 MJ/kg as N-retention increased. In maize DDGS samples, the correction for zero N retention increased the magnitude of AME penalization from 5.44 to 8.21% with increasing N retention. For all protein sources, positive correlations (p < 0.001; r = 0.831 to 0.991) were observed between the N retention and Δ AME. The present data confirms that correcting AME values to zero N retention for modern broilers penalizes the energy value of protein sources and is of higher magnitude for ingredients with higher protein quality. Feed formulation based on uncorrected AME values could benefit least cost broiler feed formulations and merits further investigation.

Anatomical correlates of recovery in apraxia: A longitudinal lesion-mapping study in stroke patients.

OBJECTIVE: This study investigates the clinical course of recovery of apraxia after left-hemisphere stroke and the underlying neuroanatomical correlates for persisting or recovering deficits in relation to the major processing streams in the network for motor cognition. METHODS: 90 patients were examined during the acute (4.74 ± 2.73 days) and chronic (14.3 ± 15.39 months) stage after left-hemisphere stroke for deficits in meaningless imitation, as well as production and conceptual errors in tool use pantomime. Lesion correlates for persisting or recovering deficits were analyzed with an extension of the non-parametric Brunner-Munzel rank-order test for multi-factorial designs (two-way repeated-measures ANOVA) using acute images. RESULTS: Meaningless imitation and tool use production deficits persisted into the chronic stage. Conceptual errors in tool use pantomime showed an almost complete recovery. Imitation errors persisted after occipitotemporal and superior temporal lesions in the dorso-dorsal stream. Chronic pantomime production errors were related to the supramarginal gyrus, the key structure of the ventro-dorsal stream. More anterior lesions in the ventro-dorsal stream (ventral premotor cortex) were additionally associated with poor recovery of production errors in pantomime. Conceptual errors in pantomime after temporal and supramarginal gyrus lesions persisted into the chronic stage. However, they resolved completely when related to angular gyrus or insular lesions. CONCLUSION: The diverging courses of recovery in different apraxia tasks can be related to different mechanisms. Critical lesions to key structures of the network or entrance areas of the processing streams lead to persisting deficits in the corresponding tasks. Contrary, lesions located outside the core network but inducing a temporary network dysfunction allow good recovery e.g., of conceptual errors in pantomime. The identification of lesion correlates for different long-term recovery patterns in apraxia might also allow early clinical prediction of the course of recovery.

Interaction between cognitive reserve and age moderates effect of lesion load on stroke outcome.

The concepts of brain reserve and cognitive reserve were recently suggested as valuable predictors of stroke outcome. To test this hypothesis, we used age, years of education and lesion size as clinically feasible coarse proxies of brain reserve, cognitive reserve, and the extent of stroke pathology correspondingly. Linear and logistic regression models were used to predict cognitive outcome (Montreal Cognitive Assessment) and stroke-induced impairment and disability (NIH Stroke Scale; modified Rankin Score) in a sample of 104 chronic stroke patients carefully controlled for potential confounds. Results revealed 46% of explained variance for cognitive outcome (p < 0.001) and yielded a significant three-way interaction: Larger lesions did not lead to cognitive impairment in younger patients with higher education, but did so in younger patients with lower education. Conversely, even small lesions led to poor cognitive outcome in older patients with lower education, but didn't in older patients with higher education. We observed comparable three-way interactions for clinical scores of stroke-induced impairment and disability both in the acute and chronic stroke phase. In line with the hypothesis, years of education conjointly with age moderated effects of lesion on stroke outcome. This non-additive effect of cognitive reserve suggests its post-stroke protective impact on stroke outcome.

CE-ESI-MS/MS as a rapid screening tool for the comparison of protein-ligand interactions.

In drug development, the combinatorial synthesis of drug libraries is common use, therefore efficient tools for the characterization of drug candidates and the extent of interaction between a drug and its target protein is a central question of analytical interest. While biological activity is tested today by enzyme assays, MS techniques attract more and more attention as an alternative for a rapid comparison of drug-target interactions. CE enables the separation of proteins and drug-enzyme complexes preserving their physiological activity in aqueous media. By hyphenating CE with ESI-MS/MS, the binding strength of enzyme inhibitors can be deduced from MS/MS experiments, which selectively release the inhibitor from the drug-target complex after CID. In this study, alpha-chymotrypsin (CT), a serine protease, was chosen as a model compound. Chymostatin is a naturally occurring peptide aldehyde binding to CT through a hemiacetal bond and electrostatic interaction. First, a CE separation was developed, which allows the analysis of alpha-CT and a chymotrypsin-chymostatin complex under MS-compatible conditions. The use of neutral-coated CE capillaries was mandatory to reduce analyte-wall interactions. ESI-quadrupole ion trap-MS was worked out to demonstrate the selective drug release after CID. Fragmentation of the drug-enzyme complex was monitored in dependence from the excitation energy in the ion trap, leading to the V(50) voltage that enables 50% complex fragmentation as a reference value for chymotrypsin-chymostatin complex. A stable CE-ESI-MS/MS setup was established, which preserves the drug-enzyme complexes during ionization-desolvation processes. With this optimized setup, different CT inhibitors could be investigated and compared.

Effects of titanium contamination caused by iron-free high-performance liquid chromatography systems on peak shape and retention of drugs with chelating properties.

Iron-free HPLC systems, better known as biocompatible systems, are generally regarded to be chemically more inert compared to conventional HPLC systems. In this work, we studied the chromatographic behavior of some classes of compounds of pharmaceutical interest, analyzed with iron-free systems. Issues typically associated with metal contamination, i.e. strong peak tailing, were observed when using an amide polar-embedded column. Effects of the contamination were visible when anhydrous methanol-acetonitrile was used, indicating that this solvent, albeit generally considered safe for conventional HPLC systems, induce corrosion of iron-free systems. The confirmation of titanium as main acting contaminant came from systematically studying the contribution of each wetted component of the HPLC system on peak shape of affected molecules. Quantification of titanium by ICP-MS analysis of effluents provided further evidence on the source of contamination. A mechanistic description of the complex interaction between titanium ions, organic molecules, and column stationary phase is proposed. In the perspective of developing methods that are fully portable between stainless steel and titanium systems, recommendations are given in terms of potentially sensitive molecules, suitable mobile phase conditions, and type of column to be used.

The correlation between apraxia and neglect in the right hemisphere: A voxel-based lesion-symptom mapping study in 138 acute stroke patients.

Apraxia is frequently described after left hemisphere stroke and results from lesions to a complex network for motor cognition with dorso-dorsal, ventro-dorsal and ventral processing streams. Apraxia also occurs after right hemisphere stroke, but lesion correlates and underlying mechanisms remain to be elucidated. To clarify the role of the right hemisphere in apraxic deficits and the influence of neglect, we prospectively examined apraxia (imitation of meaningless postures and pantomime of tool use) and neglect in 138 acute right hemisphere stroke patients with first-ever ischemic stroke in the middle cerebral artery territory and identified corresponding lesion correlates using voxel-based lesion-symptom mapping. Imitation of meaningless postures was impaired as frequently as after left hemisphere stroke (38.4%) and was significantly associated with neglect. Imitation of meaningless postures was related to temporal (middle temporal gyrus, temporoparietal junction, superior temporal gyrus and sulcus), parietal (angular gyrus, parieto-occpitpial sulcus), secondary sensorimotor cortex and (peri-)insular lesions. Presence of neglect dichotomized the results: a lesion correlate for isolated imitation without neglect was found in the right parieto-occipital cortex, while imitation deficits, when co-occurring with neglect, were related to lateral occipito-temporal, superior temporal sulcus and (peri-)insular lesions. Pantomime of tool use deficits, typical for apraxia after left hemisphere lesions, were found in only 5 cases (3.6%) and only in the context of neglect, and were associated with occipital lobe, ventral and anterior temporal lobe, and inferior frontal (areas 45/47) lesions. The syndrome of apraxia after right hemisphere stroke differs from apraxia after left hemisphere stroke. Imitation deficits are found in both hemispheres after dorso-dorsal stream lesions. Neglect also leads to and explains deficits in imitation and pantomime in patients with right ventral stream lesions. Therefore, in right hemisphere lesions, apraxia can either be explained as impaired visuomotor transformation or as a result of visuospatial deficits.

Excessive heating of 00-rapeseed meal reduces not only amino acid digestibility but also metabolizable energy when fed to growing pigs.

Two experiments were conducted to test the hypothesis that both the degree of heating and the time that heat is applied will affect the concentration of DE and ME, and the apparent ileal digestibility (AID) and the standardized ileal digestibility (SID) of amino acids (AA) in 00-rapeseed meal (00-RSM) fed to growing pigs. The nine treatments were prepared using a conventional 00-RSM that was either not autoclaved or autoclaved at 110 °C for 15 or 30 min or at 150 °C for 3, 6, 9, 12, 15, or 18 min. In experiment 1, 20 growing barrows with an average initial BW of 21.2 ± 1.2 kg were randomly allotted to the 10 diets in a replicated 10 × 4 Youden square with 10 diets and four periods in each square. A corn-based basal diet and nine diets containing corn and each source of 00-RSM were formulated. Urine and fecal samples were collected for 5 d after 7 d of adaptation. In experiment 2, nine diets contained one of the nine sources of 00-RSM as the sole source of AA, and an N-free diet that was used to measure basal endogenous losses of AA and CP was formulated. Twenty growing barrows with an initial BW of 69.8 ± 5.7 kg had a T-cannula installed in the distal ileum and were allotted to a 10 × 7 Youden square design with 10 diets and 7 periods. Ileal digesta were collected on days 6 and 7 of each 7-d period. Results from the experiments indicated that there were no effects of autoclaving at 110 °C on DE and ME or on AID and SID of AA in 00-RSM, but DE and ME, and AID and SID of AA were less (P < 0.01) if 00-RSM was autoclaved at 150 °C compared with 110 °C. At 150 °C, there were decreases (quadratic, P < 0.05) in DE and ME, and in AID and SID of AA as heating time increased. In conclusion, autoclaving at 110 °C did not affect ME or SID of AA in 00-RSM, but autoclaving at 150 °C had negative effects on ME and SID of AA and the negative effects increased as heating time increased.

Dissociation of visual extinction and neglect in the left hemisphere.

Visual neglect and extinction are two distinct visuospatial attention deficits that frequently occur after right hemisphere cerebral stroke. However, their different lesion profiles remain a matter of debate. In the left hemisphere, a domain-general dual-loop model with distinct computational abilities onto which several cognitive functions may project, has been proposed: a dorsal stream for sensori-motor mapping in time and space and a ventral stream for comprehension and representation of concepts. We wondered whether such a distinction may apply to visual extinction and neglect in left hemisphere lesions. Of 165 prospectively studied patients with acute left hemispheric ischemic stroke with a single lesion on MRI, 122 had no visuospatial attention deficit, 10 had extinction, 31 neglect and 2 had both, visual extinction and neglect. Voxel-based-lesion-symptom mapping (VLSM, FDR<.05) showed a clear anatomical dissociation. Extinction occurred after damage to the parietal cortex (anterior bank of the intraparietal sulcus, inferior parietal lobe, and supramarginal gyrus), while visual neglect occurred after damage mainly to the temporal lobe (superior and middle temporal lobe, anterior temporal pole), inferior ventral premotor cortex, frontal operculum, angular gyrus, and insula. Direct comparison of both conditions linked extinction to intraparietal sulcus and supramarginal gyrus (FDR<.05). Thus, in the left hemisphere extinction seems to be related to dorsal stream lesions, whereas neglect maps more on the ventral stream. These data cannot be generalized to the right hemisphere. However, a domain-general point-of-view may stimulate discussion on visuospatial attention processing also in the right hemisphere.

Dissociation among preserved resistance to proactive interference and impaired behavioral inhibition in a patient with bilateral lesions in the inferior frontal gyrus: A single-case study.

Inhibition is not a unitary construct, as different inhibition-related functions have been disentangled. The present single-case study compares performance of a patient with bilateral lesions in the inferior frontal gyrus (IFG) and anterior insula to healthy age-matched controls in different inhibition-related tasks. Particular focus was on the resolution of proactive interference that is supposed to rely on bilateral IFG and anterior insula. Two working memory tasks previously proven sensitive to deficits in proactive interference (recent-probes, n-back) and two tasks measuring behavioral inhibition (verb generation task, Stroop task) were administered. Against expectations, the patient did not show any deficits in measures of proactive interference. However, compared to controls, she demonstrated considerably reduced performance in both measures of behavioral inhibition, thus resulting in a classical dissociation between proactive interference and behavioral inhibition. Although performance improved during the chronic phase post stroke, the overall pattern of a classical dissociation between proactive interference and behavioral inhibition remained stable across time. Taken together, the present data support the role of the IFG in inhibition-related functions, but a direct relationship between lesions in the IFG and difficulties in resolution of proactive interference could not be corroborated.