Conditioned climbing fiber responses in cerebellar cortex and nuclei.

The eyeblink conditioning paradigm captures an elementary form of associative learning in a neural circuitry that is understood to an extraordinary degree. Cerebellar cortical Purkinje cell simple spike suppression is widely regarded as the main process underlying conditioned responses (CRs), leading to disinhibition of neurons in the cerebellar nuclei that innervate eyelid muscles downstream. However, recent work highlights the addition of a conditioned Purkinje cell complex spike response, which at the level of the interposed nucleus seems to translate to a transient spike suppression that can be followed by a rapid spike facilitation. Here, we review the characteristics of these responses at the cerebellar cortical and nuclear level, and discuss possible origins and functions.

SU-E-T-580: Does Arc Therapy Have the Potential to Improve Radiation Treatment of Hodgkin's Lymphoma Patients?

PURPOSE: To evaluate whether arc therapy (helical Tomotherapy and volumetric arc therapy; VMAT) is superior to step and shoot IMRT regarding sparing of lungs while maintaining adequate planning target volume (PTV) coverage in Hodgkin's lymphoma patients . METHODS: Radiation treatment plans for eleven Hodgkin's lymphoma patients were created employing the following techniques: coplanar and noncoplanar Step & Shoot IMRT, VMAT and Tomotherapy, i.e., for every patient 4 different treatment plans were created. The IMRT and VMAT planning was performed with Pinnacle software (v. 8 and 9, Philips) suitable for delivery with an Elekta linear accelerator, Tomotherapy plans were calculated with Tomotherapy planning software (v. 3.4). Four patients received a single prescription dose of 30 or 36 Gy, and 7 patients received a simultaneous integrated boost (30 Gy/36 Gy). Treatment plans were optimized such that the normal tissue constraints for the lung [volume receiving more than 20 Gy (V20) is less than 30% and mean lung dose (MLD) is less than 14 Gy] were met, even if PTV coverage (V95%=99%) had to be sacrificed. RESULTS: All 4 techniques delivered clinically acceptable treatment plans. Tomotherapy achieved the highest dose homogeneity in the PTV and highest dose coverage of the boost volume (on average 98% versus 96% for the other 3 techniques). Since lung sparing was the first planning objective, all techniques scored equally well for V20 en MLD. CONCLUSIONS: The strength of arc therapy lies in the large number of beamlets entering the patient from a high number of angles. For Hodgkin's lymphoma patients this does not automatically translate into a superior treatment due to the high weight on the lung objectives limiting the number of beamlets allowed to pass through the lung. This means that for Hodgkin's lymphoma arc therapy has no added value for sparing of the lungs.

Nematode species at risk--a metric to assess pollution in soft sediments of freshwaters.

Soft sediments are often highly polluted as many of the toxic chemicals introduced into surface waters bind to settling particles. The resulting accumulation of pollutants in the sediments poses a risk for benthic communities. However, pollution induced changes in benthic communities have been difficult to determine when using macro-invertebrates as bioindicators, as these organisms are often absent in soft sediment. The present study therefore examined the ability of meiofaunal organisms, specifically, nematodes, to assess the ecological status of soft sediments. Over a 9-year period, nematode communities present in sediments collected from large rivers and lake Constance in Germany were studied. These sediments showed a large range of physico-chemical properties and anthropogenic contamination. After the degree of metal and organic contamination was translated into ecotoxicologically more relevant toxic units (TUs), multivariate methods were used to classify nematode taxa in species at risk (NemaSPEAR) or not at risk (NemaSPE(not)AR). This approach clearly distinguished the influence of sediment texture from that of the toxic potential of the samples and thus allowed classification of the nematode species according to their sensitivity to or tolerance of toxic stress. Two indices, expressing the proportion of species at risk within a sample (NemaSPEAR[%](metal), NemaSPEAR[%](organic)), were calculated from independent data sets obtained in field and experimental studies and showed good correlations with the toxic potential (field data) or chemical concentrations (microcosm data). NemaSPEAR[%] indices for metal and organic pollution were therefore judged to be suitable for assessing the impact of chemical contamination of freshwater soft sediments.

[Botulinum toxin in the treatment of adult spasticity. An interdisciplinary German 10-point consensus 2010]. / Botulinum-Neurotoxin in der Behandlung der Spastizität im Erwachsenenalter. Ein interdisziplinärer deutscher 10-Punkte-Konsensus 2010.

Spasticity is one of the major causes of functional impairment in adults with lesions of the central nervous system. For instance, approximately 30% of post-stroke patients suffer from different degrees of spasticity with possible consecutive impairments. Numerous studies or meta-analyses showed that local injections of botulinum toxin in spastic muscles lead to dose-dependent reduction in muscle tone and improvement of passive movements (e. g. facilitated care), especially following repeated injections.However, country-specific regulations and patient-remote administration in German health care often do not allow adequate provision of this therapy. Thus, the present consensus statement based on the EBM analyses of the published international literature tries to highlight recent advances and the standard in the field of local spasticity treatment, aiming to facilitate communication between the decision makers and German reimbursement institutions in health care. Prior to initiation of BoNT-A injections, patient-oriented goals should be identified in a multiprofessional context to assure realistic goals for this specific treatment and patient expectations. In Germany for the treatment of focal spasticity following stroke three products have been approved: Botox® (Pharm Allergan, Ettlingen), Dysport® (Ipsen Pharma, Ettlingen) and Xeomin® (Merz Pharma, Frankfurt/Main). For all preparations safety has been repeatedly shown. Functional improvements have also been illustrated for selected patients concerning hand/arm function and gait. The dose per muscle and the selection of muscles to be injected have to be individualized according to the patient's symptoms and should be accompanied by modern neurorehabilitative therapies such as redression or repetitive activation of the injected and antagonistic muscles.

Leukocyte removal efficiency of cell-washed and unwashed whole blood: an in vitro study.

Leukocyte filtration of the cardiopulmonary bypass (CPB) perfusate after cardiac surgery has evolved as an important technique to prevent effector functions mediated by activated leukocytes. However, little is known about the filtration efficiency. Therefore, an in vitro study was conducted to define the leukocyte removal rate of a transfusion leukocyte-depletion filter, using cell-washed and unwashed whole porcine blood. In addition, the influence of different cell-washing protocols on the elimination rate of blood cells (leukocytes and platelets) was investigated. Fresh, diluted, pooled, heparinized, porcine blood was processed using either a high-flow (HF, n = 5) or quality-wash (QW, n = 5) protocol on a continuous auto-transfusion system, or was left unprocessed (control n=5). Thereafter, all samples were filtered using a transfusion leukocyte-depletion filter. Blood samples for measurement of hematocrit, white blood cell count, including leukocyte differentiation and platelet count, were taken before and after filtration. To compare the experimental groups, the removal rate was presented as the fraction of leukocytes or platelets removed per plasma volume. Cell washing significantly altered the fraction of leukocytes removed per plasma volume when compared to unprocessed blood (2.07 and 2.36 in the HF and QW groups, respectively, versus 1.34 in the control group, p = 0.008 for both). No statistically significant difference in leukocyte removal rate was observed between the different cell-washing protocols. The leukocyte differential count showed that, during all experiments, the neutrophils were removed most efficiently (99.7%). Overall, significantly more platelets were depleted after cell washing compared to the control group (1.47 and 1.60 in the HF and QW groups, respectively, versus 1.12 in the control group, p =0.008 and 0.032, respectively). Furthermore, the amount of blood that could be filtered using a single pass technique did not significantly differ between the experimental groups. However, a larger variation in the total amount of filtered blood was observed in the unprocessed group (570+/-398 mL) compared to the cell-washed groups (360+/-42 and 430+/-97 mL in the HF and QW groups, respectively). In conclusion, blood processing with an auto-transfusion system significantly enhances the leukocyte and platelet removal efficiency of the transfusion leukocyte-depletion filter that was studied. In particular, neutrophils were efficiently removed.