AEROBIC AND ANAEROBIC METABOLISM DURING LOCOMOTION WITH TWO DIFFERENT WHEELCHAIR TYPES

Wheelchair design is extremely important in order to improve efficiency of locomotion and reduce physical stress in subjects whose muscular and cardiopulmonary fitness are impaired. Purpose of this study was to evaluate the effect of different wheelchair design on the aerobic and anaerobic metabolism during locomotion at different speeds in paraplegic subjects. The experiments were carried out on a group of 5 male paraplegic subjects (25 ±3 years; body weight 65±7kg) during locomotion on a roller ergometer (Sopur, Ergotronic mod.) at 3-4 different speeds from 2 to 9 km/h. At each speed oxygen consumption and heart rate were determined after at least 6 min of exercise. Lactic acid (LA) venous blood concentration was evaluated before and at the 5th min of recovery and lactate production was calculated. The oxygen equivalent of LA was assumed to be 3.15ml O2 per kg body weight for an increase of blood LA of 1 mmol/L. For each subject the test was repeated using two different types of daily use active wheelchairs: type A., foldable, 13.95kg; type B, demountable, 13.35kg. The main difference in size was in the horizontal location of the wheel axle, in seat height and in handrim diameter. Results indicate that: a) oxygen consumption increased linearly with speed being 2050±350ml/min and 1780±270ml/min at 9km/h for wheelchair type A and B, respectively; b)lactic acid concentrations were significantly higher, at a given speed, while using wheelchair type A than B (at 9km/h; 7.4±1.5 mmol/l and 6.0±1.6 mmol/l, respectively),c) the total energy required , aerobic and anaerobic, increased linearly with speed and was 15-20% higher with wheelchair type A than B at all speeds; d) the energy cost of locomotion at a given speed was in the 15-25% range higher for wheelchair A than B; e) at corresponding oxygen uptake, heart rate and pulmonary ventilation were not different with the two wheelchair types. The main results of this study concern the large difference existing in the energy cost of locomotion and in the lactate production in the same subject when two different wheelchairs, even if apparently similar are used. In particular the much higher lactate production suggests that wheelchair design affects the limb and trunk movements in such a way that the metabolism of some muscle group requires a greater participation of anaerobic mechanism of energy supply, this leading to early onset of muscular fatigue. Further studies, in particular the combined biomechanical analysis of user and wheelchair during locomotion are required to increase the optimum fitting of wheelchair –user interface

Matrigel plug assay: evaluation of the angiogenic response by reverse transcription-quantitative PCR

The subcutaneous Matrigel plug assay in mice is a method of choice for the in vivo evaluation of pro- and anti-angiogenic molecules. However, quantification of the angiogenic response in the plug remains a problematic task. Here we report a simple, rapid, unbiased and reverse transcription-quantitative PCR (RT-qPCR) method to investigate the angiogenic process occurring in the Matrigel plug in response to fibroblast growth factor-2 (FGF2). To this purpose, a fixed amount of human cells were added to harvested plugs at the end of the in vivo experimentation as an external cell tracer. Then, mRNA levels of the panendothelial cell markers murine CD31 and vascular endothelial-cadherin were measured by species-specific RT-qPCR analysis of the total RNA and data were normalized for human GAPDH or b-actin mRNA levels. RTqPCR was used also to measure the levels of expression in the plug of various angiogenesis/inflammation-related genes. The procedure allows the simultaneous, quantitative evaluation of the newly-formed endothelium and of nonendothelial/ inflammatory components of the cellular infiltrate in the Matrigel implant, as well as the expression of genes involved in the modulation of the angiogenesis process. Also, the method consents the quantitative assessment of the effect of local or systemic administration of anti-angiogenic compounds on the neovascular response triggered by FGF

A variational approach to strongly damped wave equations

We discuss a Hilbert space method that allows to prove analytical well-posedness of a class of linear strongly damped wave equations. The main technical tool is a perturbation lemma for sesquilinear forms, which seems to be new. In most common linear cases we can furthermore apply a recent result due to Crouzeix--Haase, thus extending several known results and obtaining optimal analyticity angle.Comment: This is an extended version of an article appeared in \emph{Functional Analysis and Evolution Equations -- The G\"unter Lumer Volume}, edited by H. Amann et al., Birkh\"auser, Basel, 2008. In the latest submission to arXiv only some typos have been fixe

Antiangiogenic activity of semisynthetic biotechnological heparins: low-molecular-weight-sulfated Escherichia coli K5 polysaccharide derivatives as fibroblast growth factor antagonists.

OBJECTIVE: Low-molecular-weight heparin (LMWH) exerts antitumor activity in clinical trials. The K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor. Chemical and enzymatic modifications of K5 polysaccharide lead to the production of biotechnological heparin-like compounds. We investigated the fibroblast growth factor-2 (FGF2) antagonist and antiangiogenic activity of a series of LMW N,O-sulfated K5 derivatives. METHODS AND RESULTS: Surface plasmon resonance analysis showed that LMW-K5 derivatives bind FGF2, thus inhibiting its interaction with heparin immobilized to a BIAcore sensor chip. Interaction of FGF2 with tyrosine-kinase receptors (FGFRs), heparan sulfate proteoglycans (HSPGs), and alpha(v)beta3 integrin is required for biological response in endothelial cells. Similar to LMWH, LMW-K5 derivatives abrogate the formation of HSPG/FGF2/FGFR ternary complexes by preventing FGF2-mediated attachment of FGFR1-overexpressing cells to HSPG-bearing cells and inhibit FGF2-mediated endothelial cell proliferation. However, LMW-K5 derivatives, but not LMWH, also inhibit FGF2/alpha(v)beta3 integrin interaction and consequent FGF2-mediated endothelial cell sprouting in vitro and angiogenesis in vivo in the chick embryo chorioallantoic membrane. CONCLUSIONS: LMW N,O-sulfated K5 derivatives affect both HSPG/FGF2/FGFR and FGF2/alpha(v)beta3 interactions and are endowed with FGF2 antagonist and antiangiogenic activity. These compounds may provide the basis for the design of novel LMW heparin-like angiostatic compounds

The thymidine phosphorylase inhibitor 5′-O-tritylinosine (KIN59) is an antiangiogenic multitarget fibroblast growth factor-2 antagonist

5′-O-Tritylinosine (KIN59) is an allosteric inhibitor of the angiogenic enzyme thymidine phosphorylase. Previous observations showed the capacity of KIN59 to abrogate thymidine phosphorylase-induced as well as developmental angiogenesis in the chicken chorioallantoic membrane (CAM) assay. Here, we show that KIN59 also inhibits the angiogenic response triggered by fibroblast growth factor-2 (FGF2) but not by VEGF in the CAM assay. Immunohistochemical and reverse transcriptase PCR analyses revealed that the expression of laminin, the major proteoglycan of the basement membrane of blood vessels, is downregulated by KIN59 administration in control as well as in thymidine phosphorylase- or FGF2-treated CAMs, but not in CAMs treated with VEGF. Also, KIN59 abrogated FGF2-induced endothelial cell proliferation, FGF receptor activation, and Akt signaling in vitro with no effect on VEGF-stimulated biologic responses. Accordingly, KIN59 inhibited the binding of FGF2 to FGF receptor-1 (FGFR1), thus preventing the formation of productive heparan sulphate proteoglycan/FGF2/FGFR1 ternary complexes, without affecting heparin interaction. In keeping with these observations, systemic administration of KIN59 inhibited the growth and neovascularization of subcutaneous tumors induced by FGF2-transformed endothelial cells injected in immunodeficient nude mice. Taken together, the data indicate that the thymidine phosphorylase inhibitor KIN59 is endowed with a significant FGF2 antagonist activity, thus representing a promising lead compound for the design of multi-targeted antiangiogenic cancer drugs. ©2012 AACR.Peer Reviewe

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life

Dynamic response and impact energy loss in controlled rocking members

Unbonded posttensioning anchors a rocking structural member to its foundation and produces its controlled rocking response when the member undergoes seismic action. Unlike rocking of free‐standing bodies, little attention has been given to the dynamic behavior of these controlled rocking members. This paper utilizes experiments of concrete structural members with unbonded posttensioning, varying member geometries, and levels of initial posttensioning force to (a) characterize the associated impact energy loss and (b) improve modeling of controlled rocking motions. Experimental results show that impact energy loss in controlled rocking members can be captured accurately using the coefficient of restitution (r) approach of the modified simple rocking model (MSRM). Based on the MSRM, a controlled rocking model (CRM) is developed that additionally accounts for the variations in contact length at the member‐to‐foundation (rocking) interface. The CRM reproduces the experimental responses of controlled rocking members with good accuracy and is used to investigate controlled rocking motions under horizontal base excitations

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Abstract: Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (N ROP = 79, N ROD = 30, N CHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (N ROP = 61, N ROD = 100, N CHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. Clinical trial registry name: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042