The effect of non-specific LTD on pattern recognition in cerebellar Purkinje cells

© 2010 Safaryan et al; licensee BioMed Central Ltd.Poster presented at CNS 2010Peer reviewe

The Role of Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Primary Staging of Newly Diagnosed Prostate Cancer: A Systematic Review of the Literature

Context Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial. Objective To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging). Evidence acquisition We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Evidence synthesis A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging. Conclusions A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT. Patient summary We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases

Midlatitude shelf seas in the Cenomanian-Turonian greenhouse world: Temperature evolution and North Atlantic circulation

An 8 million year record of subtropical and midlatitude shelf-sea temperatures, derived from oxygen isotopes of well-preserved brachiopods from a variety of European sections, demonstrates a long-term Cenomanian temperature rise (16–20°C, midlatitudes) that reached its maximum early in the late Turonian (23°C, midlatitudes). Superimposed on the long-term trend, shelf-sea temperatures vary at shorter timescales in relation to global carbon cycle perturbations. In the mid-Cenomanian and the late Turonian, two minor shelf-sea cooling events (2–3°C) coincide with carbon cycle perturbations and times of high-amplitude sea level falls. Although this evidence supports the hypothesis of potential glacioeustatic effects on Cretaceous sea level, the occurrence of minimum shelf-sea temperatures within transgressive beds argues for regional changes in shelf-sea circulation as the most plausible mechanism. The major carbon cycle event in the latest Cenomanian (oceanic anoxic event 2) is accompanied by a substantial increase in shelf-sea temperatures (4–5°C) that occurred ∼150 kyr after the commencement of the δ13C excursion and is related to the spread of oceanic conditions in western European shelf-sea basins. Our oxygen isotope record and published δ18O data of pristinely preserved foraminifera allow the consideration of North Atlantic surface water properties in the Cenomanian along a transect from the tropics to the midlatitudes. On the basis of fossil-derived δ18O, estimated δw ranges, and modeled salinities, temperature-salinity-density ranges were estimated for tropical, subtropical, and midlatitude surface waters. Accordingly, the Cenomanian temperate shelf-seas waters have potentially the highest surface water density and could have contributed to North Atlantic intermediate to deep waters in the preopening stage of the equatorial Atlantic gateway

Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

Copyright: © 2015 Sudhakar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNeurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.Peer reviewedFinal Published versio

Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe

<p>Abstract</p> <p>Background</p> <p>The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto^®, Bayer AnimalHealth, Investigational Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP)).</p> <p>Methods</p> <p>232 (IVP) and 81 (CP) cats and 271(IVP) and 129 (CP) dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups.</p> <p>Results</p> <p>Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period.</p> <p>Conclusions</p> <p>The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in cats and dogs under field conditions. Therefore, it can be used as sustainable long-term preventative, covering the whole flea and tick season.</p

Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells

Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than −70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum

Duration of Purkinje cell complex spikes increases with their firing frequency

Climbing fiber (CF) triggered complex spikes (CS) are massive depolarization bursts in the cerebellar Purkinje cell (PC), showing several high frequency spikelet components (\ub1600 Hz). Since its early observations, the CS is known to vary in shape. In this study we describe CS waveforms, extracellularly recorded in awake primates (Macaca mulatta) performing saccades. Every PC analyzed showed a range of CS shapes with profoundly different duration and number of spikelets. The initial part of the CS was rather constant but the later part differed greatly, with a pronounced jitter of the last spikelets causing a large variation in total CS duration. Waveforms did not effect the following pause duration in the simple spike (SS) train, nor were SS firing rates predictive of the waveform shapes or vice versa. The waveforms did not differ between experimental conditions nor was there a preferred sequential order of CS shapes throughout the recordings. Instead, part of their variability, the timing jitter of the CS\u2019s last spikelets, strongly correlated with interval length to the preceding CS: shorter CS intervals resulted in later appearance of the last spikelets in the CS burst, and vice versa. A similar phenomenon was observed in rat PCs recorded in vitro upon repeated extracellular stimulation of CFs at different frequencies in slice experiments. All together these results strongly suggest that the variability in the timing of the last spikelet is due to CS frequency dependent changes in PC excitability

First case of Anaplasma platys infection in a dog from Croatia

<p>Abstract</p> <p>Background</p> <p>It is known that <it>Anaplasma (A.) platys</it>, the causative agent of infectious canine cyclic thrombocytopenia, is endemic in countries of the Mediterranean basin. However, few reports are available from the Balkans. This case report describes a dog, which was imported from Croatia to Germany in May 2010. One month later the dog was presented to a local veterinarian in Germany due to intermittent/recurrent diarrhoea. Diagnostic tests were performed to identify infections caused by <it>Anaplasma </it>spp., <it>Ehrlichia </it>spp., <it>Hepatozoon canis, Babesia </it>spp., <it>Leishmania </it>spp., <it>Borrelia burgdorferi </it>and/or <it>Dirofilaria immitis</it>.</p> <p>Findings</p> <p>Haematological examination of a blood smear revealed basophilic inclusions in thrombocytes, which were confirmed as <it>A. platys </it>with a species-specific real-time PCR. Additionally, an infection with <it>Babesia (B.) vogeli </it>was also detected (PCR and serology). No specific antibodies against <it>Anaplasma </it>antigen were detectable. Although the dog showed no specific clinical signs, thrombocytopenia, anaemia and elevated C-reactive protein (CRP) were observed. Sequencing of a 1,348-bp partial ribosomal RNA gene revealed highest homology to <it>A. platys </it>sequences from Thailand, Japan and France.</p> <p>Conclusions</p> <p><it>A. platys </it>was detected for first time in a dog imported from Croatia. As the dog was also co-infected by <it>B. vogeli</it>, unique serological and haematological findings were recorded. Thrombocytopenia, anaemia and elevated values of C-reactive protein were the laboratory test abnormalities observed in this case. <it>A. platys </it>infections should be considered in dogs coming from Croatia and adjacent regions.</p

Tracking the Feeding Patterns of Tsetse Flies (Glossina Genus) by Analysis of Bloodmeals Using Mitochondrial Cytochromes Genes

Tsetse flies are notoriously difficult to observe in nature, particularly when populations densities are low. It is therefore difficult to observe them on their hosts in nature; hence their vertebrate species can very often only be determined indirectly by analysis of their gut contents. This knowledge is a critical component of the information on which control tactics can be developed. The objective of this study was to determine the sources of tsetse bloodmeals, hence investigate their feeding preferences. We used mitochondrial cytochrome c oxidase 1 (COI) and cytochrome b (cytb) gene sequences for identification of tsetse fly blood meals, in order to provide a foundation for rational decisions to guide control of trypanosomiasis, and their vectors. Glossina swynnertoni were sampled from Serengeti (Tanzania) and G. pallidipes from Kenya (Nguruman and Busia), and Uganda. Sequences were used to query public databases, and the percentage identities obtained used to identify hosts. An initial assay showed that the feeds were from single sources. Hosts identified from blood fed flies collected in Serengeti ecosystem, included buffaloes (25/40), giraffes (8/40), warthogs (3/40), elephants (3/40) and one spotted hyena. In Nguruman, where G. pallidipes flies were analyzed, the feeds were from elephants (6/13) and warthogs (5/13), while buffaloes and baboons accounted for one bloodmeal each. Only cattle blood was detected in flies caught in Busia and Uganda. Out of four flies tested in Mbita Point, Suba District in western Kenya, one had fed on cattle, the other three on the Nile monitor lizard. These results demonstrate that cattle will form an integral part of a control strategy for trypanosomiasis in Busia and Uganda, while different approaches are required for Serengeti and Nguruman ecosystems, where wildlife abound and are the major component of the tsetse fly food source