Muscle metabolites: functional MR spectroscopy during exercise imposed by tetanic electrical nerve stimulation

Permission from the ethics committee and informed consent were obtained. The purpose of this study was to prospectively evaluate a method developed for the noninvasive assessment of muscle metabolites during exercise. Hydrogen 1 magnetic resonance (MR) spectroscopy peaks were measured during tetanic isometric muscle contraction imposed by supramaximal repetitive nerve stimulation. The kinetics of creatine-phosphocreatine and acetylcarnitine signal changes (P < .001) could be assessed continuously before, during, and after exercise. The control peak (trimethylammonium compounds), which served as an internal reference, did not change. This technique-that is, functional MR spectroscopy-opens the possibility for noninvasive diagnostic muscle metabolite testing in a clinical setting.

Ex vivo assessment of chemotherapy-induced apoptosis and associated molecular changes in patient tumor samples

BACKGROUND: There are inherent conceptual problems in investigating the pharmacodynamics of cancer drugs in vivo. One of the few possible approaches is serial biopsies in patients. However, this type of research is severely limited by methodological and ethical constraints. MATERIALS AND METHODS: A modified 3-dimensional tissue culture technique was used to culture human tumor samples, which had been collected during routine cancer operations. Twenty tumor samples of patients with non-small cell lung cancer (NSCLC) were cultured ex vivo for 120 h and treated with mitomycin C, taxotere and cisplatin. The cytotoxic activity of the anticancer agents was quantified by assessing the metabolic activity of treated tumor cultures and various assays of apoptosis and gene expression were performed. RESULTS: The proliferative activity of the tissue was maintained in culture as assessed by Ki-67 staining. Mitomycin C, cisplatin and taxotere reduced the metabolic activity of the tumor tissue cultures by 51%, 29% and 20%, respectively, at 120 h. The decrease in metabolic activity corresponded to the induction of apoptosis as demonstrated by the typical morphological changes, such as chromatin condensation and nuclear fragmentation. In addition, activated caspase-3 could be verified in apoptotic cells by immunohistochemistry. To verify functional aspects of apoptosis, the induction of chemotherapy-induced cell death was inhibited with the caspase inhibitor z-VAD.fmk. RNA was extracted from the tissue cultures after 120 h of ex vivo drug treatment and was of sufficient quality to allow quantitative PCR. CONCLUSION: The 3-dimensional ex vivo culture technique is a useful method to assess the molecular effects of pharmacological interventions in human cancer samples in vitro. This culture technique could become an important tool for drug development and for the prediction of in vivo drug efficacy.

Benefits of cardiac surgery in octogenarians--a postoperative quality of life assessment

OBJECTIVE: Assessment of postoperative quality of life in patients over 80 years after cardiac surgery including coronary artery bypass grafting (CABG), aortic valve replacement (AVR) and combined procedures. METHODS: Quality of life of n=136 patients over 80 years at operation (82.3+/-2.1 years), undergoing isolated CABG in 61 patients (45%), isolated AVR in 34 patients (25%) and a combination of CABG and AVR in 41 patients (30%) between January 1999 and December 2003 was reviewed. Preoperatively 66.2% presented in NYHA-class III/IV or CCS-class III/IV. Mean ejection fraction (EF) was 59.5%+/-14.0 (range 25-90%). Quality of life assessment was performed via a Seattle Angina Questionnaire. Follow-up was 100% complete for a total of 890 days (69-1853 days). RESULTS: Five-year survival was 70% for the CABG group, 75% for the AVR group and 65% for the CABG/AVR group. Quality of life was remarkable in all of the three groups after surgery. Overall 97 patients (81%) were not or little disabled in their daily activity. One hundred and twelve patients (93%) were free or considerably less symptomatic. Seventy-eight patients or 65% reported to be very satisfied with their current quality of life and 112 patients (93%) felt very reassured to have continuous full access to medical treatment despite of their advanced age. CONCLUSIONS: A remarkable quality of life and important improvement in the functional status after cardiac surgery in patients over 80 paired with a satisfactory medium-term survival justify early intervention for heart disease in this age group. Therefore, referral practice for patients over 80 years for heart surgery should be handled liberally.

Quantitative assessment of oral orbicular muscle deformation after cleft lip reconstruction: an ultrasound elastography study

Reconstruction of a cleft lip leads inevitably to scar tissue formation. Scar tissue within the restored oral orbicular muscle might be assessed by quantification of the local contractility of this muscle. Furthermore, information about the contraction capability of the oral orbicular muscle is crucial for planning the revision surgery of an individual patient. We used ultrasound elastography to determine the local deformation (strain) of the upper lip and to differentiate contracting muscle from passive scar tissue. Raw ultrasound data (radio-frequency format; rf-) were acquired, while the lips were brought from normal state into a pout condition and back in normal state, in three patients and three normal individuals. During this movement, the oral orbicular muscle contracts and, consequently, thickens in contrast to scar tissue that will not contract, or even expand. An iterative coarse-to-fine strain estimation method was used to calculate the local tissue strain. Analysis of the raw ultrasound data allows estimation of tissue strain with a high precision. The minimum strain that can be assessed reproducibly is 0.1%. In normal individuals, strain of the orbicular oral muscle was in the order of 20%. Also, a uniform strain distribution in the oral orbicular muscle was found. However, in patients deviating values were found in the region of the reconstruction and the muscle tissue surrounding that. In two patients with a successful reconstruction, strain was reduced by 6% in the reconstructed region with respect to the normal parts of the muscle (from 22% to 16% and from 25% to 19%). In a patient with severe aesthetical and functional disability, strain decreased from 30% in the normal region to 5% in the reconstructed region. With ultrasound elastography, the strain of the oral orbicular muscle can be quantified. In healthy subjects, the strain profiles and maximum strain values in all parts of the muscle were similar. The maximum strain of the muscle during pout was 20% +/- 1%. In surgically repaired cleft lips, decreased deformation was observed.

Structural characterization and reliable biomechanical assessment of integrative cartilage repair

Structural and functional characterization of integrative cartilage repair in controlled model systems can play a key role in the development of innovative strategies to improve the long-term outcome of many cartilage repair procedures. In this work, we first developed a method to reproducibly generate geometrically defined disk/ring cartilage composites and to remove outgrown fibrous layers which can encapsulate cartilaginous tissues during culture. We then used the model system to test the hypothesis that such fibrous layers lead to an overestimation of biomechanical parameters of integration at the disk/ring interface. Transmission electron microscopy images of the composites after 6 weeks of culture indicated that collagen fibrils in the fibrous tissue layer were well integrated into the collagen network of the cartilage disk and ring, whereas molecular bridging between opposing disk/ring cartilage surfaces was less pronounced and restricted to regions with narrow interfacial regions (< 2 microm). Stress-strain profiles generated from mechanical push-out tests for composites with the layers removed displayed a single and distinct peak, whereas profiles for composites with the layers left intact consisted of multiple superimposed peaks. As compared to composites with removed layers, composites with intact layers had significantly higher adhesive strengths (161+/-9 vs. 71+/-11 kPa) and adhesion energies (15.0+/-0.7 vs. 2.7+/-0.4 mJ/mm2). By combining structural and functional analyses, we demonstrated that the outgrowing tissue formed during in vitro culture of cartilaginous specimens should be eliminated in order to reliably quantify biomechanical parameters related to integrative cartilage repair.

Histological assessment of testicular residues in lambs and calves after Burdizzo castration

To assess the reliability of the Burdizzo procedure for castrating calves and lambs, testicular tissue from 63 bull calves (15 intact and 48 castrated) and 69 male lambs (35 intact and 34 castrated) was collected at slaughter and assessed histologically. The bull calves were castrated at either one, four to five or 12 to 16 weeks of age and the lambs at either one or 10 weeks. There was clear evidence of spermatogenesis in testicular tissue from all the intact animals. In the samples from the calves that had been castrated at 12 to 16 weeks functional testicular tissue was completely lacking. However, there was evidence of spermatogenesis and steroidogenesis in the calves that had been castrated at one week or four to five weeks, respectively. Failure to achieve complete involution of the testicular parenchyma was observed in the majority of lambs, irrespective of the age at which they had been castrated.

Relationships between structural and functional measures of nutritional status in a normally nourished population

Both anthropometric and functional measurements have been used in nutritional assessment and monitoring. Hand dynamometry is a predictor of surgical outcome and peak expiratory flow rate has been used as an index of respiratory muscle function. This study aims to measure in normal subjects the relationship between anthropometric measurements, voluntary muscle strength by hand grip dynamometry and respiratory muscle function by peak expiratory flow rate.

More severe functional impairment in dementia with Lewy bodies than Alzheimer disease is related to extrapyramidal motor dysfunction.

OBJECTIVE The objective of this study was to compare functional impairments in dementia with Lewy bodies (DLB) and Alzheimer disease (AD) and their relationship with motor and neuropsychiatric symptoms. METHODS The authors conducted a cross-sectional study of 84 patients with DLB or AD in a secondary care setting. Patients were diagnosed according to published criteria for DLB and AD. The Bristol Activities of Daily Living Scale (BADLS) was used to assess functional impairments. Participants were also assessed using the Unified Parkinson's Disease Rating Scale (motor section), the Neuropsychiatric Inventory, and the Mini-Mental Status Examination. RESULTS Patients with DLB were more functionally impaired and had more motor and neuropsychiatric difficulties than patients with AD with similar cognitive scores. In both AD and DLB, there were correlations between total BADLS scores and motor and neuropsychiatric deficits. There was more impairment in the mobility and self-care components of the BADLS in DLB than in AD, and in DLB, these were highly correlated with UPDRS score. In AD, orientation and instrumental BADLS components were most affected. CONCLUSION The nature of functional disability differs between AD and DLB with additional impairments in mobility and self-care in DLB being mainly attributable to extrapyramidal motor symptoms. Consideration of these is important in assessment and management. Activities of daily living scales for use in this population should attribute the extent to which functional disabilities are related to cognitive, psychiatric, or motor dysfunction.

Functional hoarseness in children: short-term play therapy with family dynamic counseling as therapy of choice

Children with nonorganic voice disorders (NVDs) are treated mainly using direct voice therapy techniques such as the accent method or glottal attack changes and indirect methods such as vocal hygiene and voice education. However, both approaches tackle only the symptoms and not etiological factors in the family dynamics and therefore often enjoy little success. The aim of the "Bernese Brief Dynamic Intervention" (BBDI) for children with NVD was to extend the effectiveness of pediatric voice therapies with a psychosomatic concept combining short-term play therapy with the child and family dynamic counseling of the parents. This study compares the therapeutic changes in three groups where different procedures were used, before intervention and 1 year afterward: counseling of parents (one to two consultations; n = 24), Brief Dynamic Intervention on the lines of the BBDI (three to five play therapy sessions with the child plus two to four sessions with the parents; n = 20), and traditional voice therapy (n = 22). A Voice Questionnaire for Parents developed by us with 59 questions to be answered on a four-point Likert scale was used to measure the change. According to the parents' assessment, a significant improvement in voice quality was achieved in all three methods. Counseling of parents (A) appears to have led parents to give their child more latitude, for example, they stopped nagging the child or demanding that he/she should behave strictly by the rules. After BBDI (B), the mothers were more responsive to their children's wishes and the children were more relaxed and their speech became livelier. At home, they called out to them less often at a distance, which probably improved parent-child dialog. Traditional voice therapy (C) seems to have had a positive effect on the children's social competence. BBDI seems to have the deepest, widest, and therefore probably the most enduring therapeutic effect on children with NVD.

Functional Multiparametric Magnetic Resonance Imaging of the Kidneys Using Blood Oxygen Level-Dependent and Diffusion-Weighted Sequences: a Reliable Tool for Monitoring Acute Upper Urinary Tract Obstruction.

PURPOSE Little data is available on noninvasive MRI-based assessment of renal function during upper urinary tract (UUT) obstruction. In this study, we determined whether functional multiparametric kidney MRI is able to monitor treatment response in acute unilateral UUT obstruction. MATERIAL AND METHODS Between 01/2008 and 01/2010, 18 patients with acute unilateral UUT obstruction due to calculi were prospectively enrolled to undergo kidney MRI with conventional, blood oxygen level-dependent (BOLD) and diffusion-weighted (DW) sequences on emergency admission and after release of obstruction. Functional imaging parameters of the obstructed and contralateral unobstructed kidneys derived from BOLD (apparent spin relaxation rate [R2*]) and DW (total apparent diffusion coefficient [ADCT], pure diffusion coefficient [ADCD] and perfusion fraction [FP]) sequences were assessed during acute UUT obstruction and after its release. RESULTS During acute obstruction, R2* and FP values were lower in the cortex (p=0.020 and p=0.031, respectively) and medulla (p=0.012 and p=0.190, respectively) of the obstructed compared to the contralateral unobstructed kidneys. After release of obstruction, R2* and FP values increased both in the cortex (p=0.016 and p=0.004, respectively) and medulla (p=0.071 and p=0.044, respectively) of the formerly obstructed kidneys to values similar to those found in the contralateral kidneys. ADCT and ADCD values did not significantly differ between obstructed and contralateral unobstructed kidneys during or after obstruction. CONCLUSIONS In our patients with acute unilateral UUT obstruction due to calculi, functional kidney MRI using BOLD and DW sequences allowed for the monitoring of pathophysiologic changes of obstructed kidneys during obstruction and after its release.

A novel comparative research platform designed to determine the functional significance of tree species diversity in European forests

One of the current advances in functional biodiversity research is the move away from short-lived test systems towards the exploration of diversity-ecosystem functioning relationships in structurally more complex ecosystems. In forests, assumptions about the functional significance of tree species diversity have only recently produced a new generation of research on ecosystem processes and services. Novel experimental designs have now replaced traditional forestry trials, but these comparatively young experimental plots suffer from specific difficulties that are mainly related to the tree size and longevity. Tree species diversity experiments therefore need to be complemented with comparative observational studies in existing forests. Here we present the design and implementation of a new network of forest plots along tree species diversity gradients in six major European forest types: the FunDivEUROPE Exploratory Platform. Based on a review of the deficiencies of existing observational approaches and of unresolved research questions and hypotheses, we discuss the fundamental criteria that shaped the design of our platform. Key features include the extent of the species diversity gradient with mixtures up to five species, strict avoidance of a dilution gradient, special attention to community evenness and minimal covariation with other environmental factors. The new European research platform permits the most comprehensive assessment of tree species diversity effects on forest ecosystem functioning to date since it offers a common set of research plots to groups of researchers from very different disciplines and uses the same methodological approach in contrasting forest types along an extensive environmental gradient. (C) 2013 Elsevier GmbH. All rights reserved.

Short-term functional outcome and premorbid adjustment in clinical high-risk patients. Results of the EPOS project

PURPOSE In patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment. METHODS In all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed. RESULTS During the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model. CONCLUSION A great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.

Assessment of Skill and Portability in Regional Marine Biogeochemical Models: Role of Multiple Planktonic Groups

Application of biogeochemical models to the study of marine ecosystems is pervasive, yet objective quantification of these models' performance is rare. Here, 12 lower trophic level models of varying complexity are objectively assessed in two distinct regions (equatorial Pacific and Arabian Sea). Each model was run within an identical one-dimensional physical framework. A consistent variational adjoint implementation assimilating chlorophyll-a, nitrate, export, and primary productivity was applied and the same metrics were used to assess model skill. Experiments were performed in which data were assimilated from each site individually and from both sites simultaneously. A cross-validation experiment was also conducted whereby data were assimilated from one site and the resulting optimal parameters were used to generate a simulation for the second site. When a single pelagic regime is considered, the simplest models fit the data as well as those with multiple phytoplankton functional groups. However, those with multiple phytoplankton functional groups produced lower misfits when the models are required to simulate both regimes using identical parameter values. The cross-validation experiments revealed that as long as only a few key biogeochemical parameters were optimized, the models with greater phytoplankton complexity were generally more portable. Furthermore, models with multiple zooplankton compartments did not necessarily outperform models with single zooplankton compartments, even when zooplankton biomass data are assimilated. Finally, even when different models produced similar least squares model-data misfits, they often did so via very different element flow pathways, highlighting the need for more comprehensive data sets that uniquely constrain these pathways.

Cardiopulmonary performance testing using a robotics-assisted tilt table: Feasibility assessment in able-bodied subjects

BACKGROUND: Robotics-assisted tilt table technology was introduced for early rehabilitation of neurological patients. It provides cyclical stepping movement and physiological loading of the legs. The aim of the present study was to assess the feasibility of this type of device for peak cardiopulmonary performance testing using able-bodied subjects. METHODS: A robotics-assisted tilt table was augmented with force sensors in the thigh cuffs and a work rate estimation algorithm. A custom visual feedback system was employed to guide the subjects' work rate and to provide real time feedback of actual work rate. Feasibility assessment focused on: (i) implementation (technical feasibility), and (ii) responsiveness (was there a measurable, high-level cardiopulmonary reaction?). For responsiveness testing, each subject carried out an incremental exercise test to the limit of functional capacity with a work rate increment of 5 W/min in female subjects and 8 W/min in males. RESULTS: 11 able-bodied subjects were included (9 male, 2 female; age 29.6 ± 7.1 years: mean ± SD). Resting oxygen uptake (O_{2}) was 4.6 ± 0.7 mL/min/kg and O_{2}peak was 32.4 ± 5.1 mL/min/kg; this mean O_{2}peak was 81.1% of the predicted peak value for cycle ergometry. Peak heart rate (HRpeak) was 177.5 ± 9.7 beats/min; all subjects reached at least 85% of their predicted HRpeak value. Respiratory exchange ratio (RER) at O_{2}peak was 1.02 ± 0.07. Peak work rate) was 61.3 ± 15.1 W. All subjects reported a Borg CR10 value for exertion and leg fatigue of 7 or more. CONCLUSIONS: The robotics-assisted tilt table is deemed feasible for peak cardiopulmonary performance testing: the approach was found to be technically implementable and substantial cardiopulmonary responses were observed. Further testing in neurologically-impaired subjects is warranted.

Objective assessment of patient compliance with removable orthodontic appliances: a cross-sectional cohort study.

OBJECTIVE To assess objectively patient compliance with removable orthodontic appliances and the effect of possible influential factors. MATERIALS AND METHODS Wearing times of 45 White patients were recorded with the aid of the TheraMon microsensor. Patient compliance was assessed relative to wear prescription and other parameters, such as age and sex. RESULTS There was high individual variation in most measured variables and in all groups/subgroups. During a median observation period of 186 days (range, 55-318 days) the actual wear time was 9.0 h/d (range, 0.0-16.0 h/d) and did not differ between distinct prescriptions (P = .49). Eight patients wore their appliances less than 2 h/d, and six of them did not wear their appliances at all. Overall, the median wear per day relative to prescription was 62.5% (range, 0.0-89.3%) for the 14 h/d and 112.5% (range, 0.0-200.0%) for the 8 h/d prescription wear (P = .01) groups. There was a strong negative correlation of age (median: 12.5 years) with the daily percentage of actual wear time per day relative to wear prescription (14 h/d prescription: n = 21, rho = -0.61, P = .00; 8 h/d prescription: n = 24, rho = -0.73, P = .00), while sex did not exert a significant influence on compliance (P = .58). CONCLUSIONS Despite the fact that patients and parents were informed about wear time recording, compliance was insufficient with regard to functional treatment (14 h/d prescription), while it was sufficient for retention purposes (8 h/d prescription). Objective measures are necessary to assess compliance with removable orthodontic appliances since patient compliance is a highly variable issue.