Separation of small metabolites and lipids in spectra from biopsies by diffusion-weighted HR-MAS NMR: a feasibility study.

High Resolution Magic Angle Spinning (HR-MAS) NMR allows metabolic characterization of biopsies. HR-MAS spectra from tissues of most organs show strong lipid contributions that are overlapping metabolite regions, which hamper metabolite estimation. Metabolite quantification and analysis would benefit from a separation of lipids and small metabolites. Generally, a relaxation filter is used to reduce lipid contributions. However, the strong relaxation filter required to eliminate most of the lipids also reduces the signals for small metabolites. The aim of our study was therefore to investigate different diffusion editing techniques in order to employ diffusion differences for separating lipid and small metabolite contributions in the spectra from different organs for unbiased metabonomic analysis. Thus, 1D and 2D diffusion measurements were performed, and pure lipid spectra that were obtained at strong diffusion weighting (DW) were subtracted from those obtained at low DW, which include both small metabolites and lipids. This subtraction yielded almost lipid free small metabolite spectra from muscle tissue. Further improved separation was obtained by combining a 1D diffusion sequence with a T2-filter, with the subtraction method eliminating residual lipids from the spectra. Similar results obtained for biopsies of different organs suggest that this method is applicable in various tissue types. The elimination of lipids from HR-MAS spectra and the resulting less biased assessment of small metabolites have potential to remove ambiguities in the interpretation of metabonomic results. This is demonstrated in a reproducibility study on biopsies from human muscle

Upregulation of Interleukin 8 by Oxygen-deprived Cells in Glioblastoma Suggests a Role in Leukocyte Activation, Chemotaxis, and Angiogenesis

Leukocyte infiltration and necrosis are two biological phenomena associated with the development of neovascularization during the malignant progression of human astrocytoma. Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8–binding receptors in astrocytoma. IL-8 expression is first observed in low grade astrocytoma in perivascular tumor areas expressing inflammatory cytokines. In glioblastoma, it further localizes to oxygen-deprived cells surrounding necrosis. Hypoxic/anoxic insults on glioblastoma cells in vitro using anaerobic chamber systems or within spheroids developing central necrosis induced an increase in IL-8 messenger RNA (mRNA) and protein expression. mRNA for IL-8–binding chemokine receptors CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC) were found in all astrocytoma grades by reverse transcription/PCR analysis. In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes. These results support a model where IL-8 expression is initiated early in astrocytoma development through induction by inflammatory stimuli and later in tumor progression increases due to reduced microenvironmental oxygen pressure. Augmented IL-8 would directly and/or indirectly promote angiogenesis by binding to DARC and by inducing leukocyte infiltration and activation by binding to CXCR1 and CXCR2

A Boosting Approach to P300 Detection with Application to Brain-Computer Interfaces

Gradient boosting is a machine learning method, that builds one strong classifier from many weak classifiers. In this work, an algorithm based on gradient boosting is presented, that detects event-related potentials in single electroencephalogram (EEG) trials. The algorithm is used to detect the P300 in the human EEG and to build a brain-computer interface (BCI), specifically a spelling device. Important features of the method described here are its high classification accuracy and its conceptual simplicity. The algorithm was tested with datasets recorded in our lab and one benchmark dataset from the BCI Competition 2003. The number of correctly inferred symbols with the P300 speller paradigm varied between 90% and 100%. In particular, all of the inferred symbols were correct for the BCI competition dataset

Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells.

Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo

Self-reported health needs and use of primary health care services by adolescents enrolled in post-mandatory schools or vocational training programmes in Switzerland.

BACKGROUND: The second Swiss Multicenter Adolescent Survey on Health (SMASH02) was conducted among a representative sample (n = 7428) of students and apprentices aged 16 to 20 from the three language areas of Switzerland during the year 2002. This paper reports on health needs expressed by adolescents and their use of health care services over the 12 months preceding the survey. METHODS: Nineteen cantons representing 80% of the resident population agreed to participate. A complex iterative random cluster sample of 600 classes was drawn with classes as primary sampling unit. The participation rate was 97.7% for the classes and 99.8% for the youths in attendance. The self-administered questionnaire included 565 items. The median rate of item non-response was 1.8%. Ethical and legal requirements applying to surveys of adolescent populations were respected. RESULTS: Overall more than 90% of adolescents felt in good to excellent health. Suffering often or very often from different physical complaints or pain was also reported such as headache (boys: 15.9%, girls: 37.4%), stomach-ache (boys: 9.7%, girls: 30.0%), joint pain (boys: 24.7%, girls: 29.5%) or back pain (boys: 24.3%, girls: 34.7%). Many adolescents reported a need for help on psychosocial and lifestyle issues, such as stress (boys: 28.5%, girls: 47.7%) or depression (boys: 18.9%, girls: 34.4%). Although about 75% of adolescents reported having consulted a general practitioner and about one-third having seen another specialist, reported reasons for visits do not correspond to the expressed needs. Less than 10% of adolescents had visited a psychiatrist, a family planning centre or a social worker. CONCLUSIONS: The reported rates of health services utilisation by adolescents does not match the substantial reported needs for help in various areas. This may indicate that the corresponding problems are not adequately detected and/or addressed by professionals from the health and social sectors

Technology-assisted stroke rehabilitation in Mexico: a pilot randomized trial comparing traditional therapy to circuit training in a Robot/technology-assisted therapy gym

Background Stroke rehabilitation in low- and middle-income countries, such as Mexico, is often hampered by lack of clinical resources and funding. To provide a cost-effective solution for comprehensive post-stroke rehabilitation that can alleviate the need for one-on-one physical or occupational therapy, in lower and upper extremities, we proposed and implemented a technology-assisted rehabilitation gymnasium in Chihuahua, Mexico. The Gymnasium for Robotic Rehabilitation (Robot Gym) consisted of low- and high-tech systems for upper and lower limb rehabilitation. Our hypothesis is that the Robot Gym can provide a cost- and labor-efficient alternative for post-stroke rehabilitation, while being more or as effective as traditional physical and occupational therapy approaches. Methods A typical group of stroke patients was randomly allocated to an intervention (n = 10) or a control group (n = 10). The intervention group received rehabilitation using the devices in the Robot Gym, whereas the control group (n = 10) received time-matched standard care. All of the study subjects were subjected to 24 two-hour therapy sessions over a period of 6 to 8 weeks. Several clinical assessments tests for upper and lower extremities were used to evaluate motor function pre- and post-intervention. A cost analysis was done to compare the cost effectiveness for both therapies. Results No significant differences were observed when comparing the results of the pre-intervention Mini-mental, Brunnstrom Test, and Geriatric Depression Scale Test, showing that both groups were functionally similar prior to the intervention. Although, both training groups were functionally equivalent, they had a significant age difference. The results of all of the upper extremity tests showed an improvement in function in both groups with no statistically significant differences between the groups. The Fugl-Meyer and the 10 Meters Walk lower extremity tests showed greater improvement in the intervention group compared to the control group. On the Time Up and Go Test, no statistically significant differences were observed pre- and post-intervention when comparing the control and the intervention groups. For the 6 Minute Walk Test, both groups presented a statistically significant difference pre- and post-intervention, showing progress in their performance. The robot gym therapy was more cost-effective than the traditional one-to-one therapy used during this study in that it enabled therapist to train up to 1.5 to 6 times more patients for the approximately same cost in the long term. Conclusions The results of this study showed that the patients that received therapy using the Robot Gym had enhanced functionality in the upper extremity tests similar to patients in the control group. In the lower extremity tests, the intervention patients showed more improvement than those subjected to traditional therapy. These results support that the Robot Gym can be as effective as traditional therapy for stroke patients, presenting a more cost- and labor-efficient option for countries with scarce clinical resources and funding. Trial registration ISRCTN98578807

Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma

The expression and function in growth and apoptosis of the renin-angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT(2) and/or AT(1) mRNAs and proteins determined by RT-PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1-14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy