Cholinergic modulation of dopamine overflow in the rat neostriatum: A fast cyclic voltammetric study in vitro

Stimulus-evoked dopamine overflow in rat neostriatal slices was determined using fast cyclic voltammetry. The dopamine efflux induced by intrastriatal stimulation increased with stimulus intensity and was found to be enhanced by more than 100% upon application of the dopamine uptake inhibitor nomifensine. The acetylcholine esterase inhibitor eserine concentration-dependently and reversibly depressed stimulus-induced dopamine overflow. This effect was mediated by both, muscarinic and nicotinic cholinergic receptors: the action of eserine was mimicked by cholinergic agonists (muscarine and nicotine) and the effects of these agonists were blocked by muscarinic and nicotinic antagonists (atropine and dihydro-β-erythroidine). These experiments suggest that endogenous acetylcholine exerts an inhibitory control on stimulus-evoked (i.e. phasic) dopamine overflow in vitro by affecting striatal dopaminergic nerve terminals

High functional diversity is related to high nitrogen availability in a deciduous forest - evidence from a functional trait approach

The current study tested the assumption that floristic and functional diversity patterns are negatively related to soil nitrogen content. We analyzed 20 plots with soil N-contents ranging from 0.63% to 1.06% in a deciduous forest near Munich (Germany). To describe species adaptation strategies to different nitrogen availabilities, we used a plant functional type (PFT) approach. Each identified PFT represents one realized adaptation strategy to the current environment. These were correlated, next to plant species richness and evenness, to soil nitrogen contents. We found that N-efficient species were typical for low soil nitrogen contents, while N-requiring species occur at high N-contents. In contrast to our initial hypotheses, floristic and functional diversity measures (number of PFTs) were positively related to nitrogen content in the soil. Every functional group has its own adaptation to the prevailing environmental conditions; in consequence, these functional groups can co-exist but do not out-compete one another. The increased number of functional groups at high N-contents leads to increased species richness. Hence, for explaining diversity patterns we need to consider species groups representing different adaptations to the current environmental conditions. Such co-existing ecological strategies may even overcome the importance of competition in their effect on biodiversity

Incidence of graft-versus-host-disease in Germany:evidence from health care claims data

Objective Graft-versus-host disease (GvHD) can occur as an immunological response after an allogeneic hematopoietic cell transplantation (allo-HCT). Due to the rarity of the disease, German epidemiological data are scarce. Moreover, not all cases of GvHD are properly documented in daily practice. Against this background, this study aims at providing new estimates on the incidence of GvHD in Germany. Methods Based on a large German claims database, a retrospective longitudinal analysis was conducted over a 6-year period. Patients were selected that received allo-HCT between 2014 and 2015. Follow up period was 3 years. To adjust the incidence for undocumented cases, steroid prescriptions after an allo-HCT was used as an approximation. Based on both documented and undocumented GvHD patients, incidence rates were calculated for the population of the German statutory health insurance (SHI). Results Among 4,395,540 eligible database enrollees 3,737,317 were continuously insured. Among them we identified 297 patients who received an allo-HCT between 2014 and 2015. Depending on the extrapolation method, this corresponds to a yearly incidence of 2415-2840 for the SHI population. Of the 297 patients, 134 (i.e., 45.1%) developed a documented GvHD within three years after the transplantation which translates into a yearly incidence of 1125-1300 GvHD patients. Based on the medication regimens, we identified 83 additional patients with an suspected GvHD without a documented diagnosis. Extrapolated to the German SHI population, our estimates suggest that the annual incidence of GvHD, including undocumented cases, could be as high as 1822-2105, which is higher than previously reported. Conclusion More patients may be affected by GvHD in Germany than reported. Appropriate adjustments need to be made when utilizing administrative data.</p

Incidence of graft-versus-host-disease in Germany:evidence from health care claims data

Objective Graft-versus-host disease (GvHD) can occur as an immunological response after an allogeneic hematopoietic cell transplantation (allo-HCT). Due to the rarity of the disease, German epidemiological data are scarce. Moreover, not all cases of GvHD are properly documented in daily practice. Against this background, this study aims at providing new estimates on the incidence of GvHD in Germany. Methods Based on a large German claims database, a retrospective longitudinal analysis was conducted over a 6-year period. Patients were selected that received allo-HCT between 2014 and 2015. Follow up period was 3 years. To adjust the incidence for undocumented cases, steroid prescriptions after an allo-HCT was used as an approximation. Based on both documented and undocumented GvHD patients, incidence rates were calculated for the population of the German statutory health insurance (SHI). Results Among 4,395,540 eligible database enrollees 3,737,317 were continuously insured. Among them we identified 297 patients who received an allo-HCT between 2014 and 2015. Depending on the extrapolation method, this corresponds to a yearly incidence of 2415-2840 for the SHI population. Of the 297 patients, 134 (i.e., 45.1%) developed a documented GvHD within three years after the transplantation which translates into a yearly incidence of 1125-1300 GvHD patients. Based on the medication regimens, we identified 83 additional patients with an suspected GvHD without a documented diagnosis. Extrapolated to the German SHI population, our estimates suggest that the annual incidence of GvHD, including undocumented cases, could be as high as 1822-2105, which is higher than previously reported. Conclusion More patients may be affected by GvHD in Germany than reported. Appropriate adjustments need to be made when utilizing administrative data.</p

Deep Brain Stimulation in KMT2B-Related Dystonia: Case Report and Review of the Literature With Special Emphasis on Dysarthria and Speech

Objective: KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. With increasing age, children frequently show prominent laryngeal or facial dystonia manifesting in dysarthria. Bilateral deep brain stimulation of the globus pallidus internus (GPi-DBS) is reported to be an efficient therapeutic option. Especially improvement of dystonia and regaining of independent mobility is commonly described, but detailed information about the impact of GPi-DBS on dysarthria and speech is scarce. Methods: We report the 16-months outcome after bilateral GPi-DBS in an 8-year-old child with KMT2B-related dystonia caused by a de-novo c.3043C>T (p.Arg1015*) non-sense variant with special emphasis on dysarthria and speech. We compare the outcome of our patient with 59 patients identified through a PubMed literature search. Results: A remarkable improvement of voice, articulation, respiration and prosodic characteristics was seen 16 months after GPi-DBS. The patients' speech intelligibility improved. His speech became much more comprehensible not only for his parents, but also for others. Furthermore, his vocabulary and the possibility to express his feelings and wants expanded considerably. Conclusion: A positive outcome of GPi-DBS on speech and dysarthria is rarely described in the literature. This might be due to disease progression, non-effectiveness of DBS or due to inadvertent spreading of the electrical current to the corticobulbar tract causing stimulation induced dysarthria. This highlights the importance of optimal lead placement, the possibility of horizontal steering of the electrical field by applying directional stimulation with segmented leads as well as the use of the lowest possible effective stimulation intensity

Low impact of climate change on subalpine grasslands in the Swiss Northern Alps?

While phenological shifts and migration of isolated species under climate change have already been observed on alpine summits, very few studies have focused on community composition changes in subalpine grasslands. Here we use permanent plots monitored since 1954 and precisely located phytosociological censuses from 1970 to study compositional changes of subalpine grasslands in two distinct regions of the Swiss Northern Alps. In both areas, warming trends during the monitoring period were associated with changes in land management (abandonment of goat and sheep pasturing or grazing replaced by mowing). Old and recent inventories were compared with correspondence analyses (CA). Ecological indicator values, community-affinities and biological traits of the species were used to infer the factors responsible for triggering the observed changes. In both regions, subalpine grasslands were stable with smaller changes than have previously been observed in alpine environments. Only a few species appeared or disappeared and changes were generally limited to increasing or decreasing frequency and cover of certain taxa. At one site, grazing abandonment favoured fallow species. Some of these species were located at their upper altitudinal distribution limits and may have spread because of rising temperatures. In both areas, declining species were predominantly alpine and low growing species; their decline was probably due to increased competition (e.g., shade) with more vigorous subalpine taxa no longer limited by grazing. We conclude that vegetation communities can respond rapidly to warming as long as colonisation is facilitated by available space or structural change. In the subalpine grasslands studied, changes were mainly driven by land management. These communities have a dense vegetation cover and newly arriving herbaceous species preferring warmer conditions may take some time to establish themselves. However, climate disturbances, such as exceptional drought, may accelerate community changes by opening gaps for new species

ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow temporal biodiversity change to be assessed at the community scale, reaching back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century

Neurologic phenotypes associated with COL4A1/2 mutations

Objective: To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype–phenotype correlation. Methods: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. Results: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype–phenotype correlation did not emerge. Conclusion: COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall

Directional turnover towards larger-ranged plants over time and across habitats

Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

BACKGROUND: Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. / METHODS: We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). / RESULTS: The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. / CONCLUSIONS: In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.