Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels

Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signals that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signals involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of release from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes

Dental treatment and risk of variant CJD - a case control study

Abstract Objective: Knowledge of risk factors for variant CJD (vCJD) remains limited, but transmission of prion proteins via re-useable medical devices, including dental instruments, or enhanced susceptibility following trauma to the oral cavity is a concern. This study aimed to identify whether previous dental treatment is a risk factor for development of vCJD. Design: Case control study Methods: Risk factor questionnaires completed by interview with relatives of 130 vCJD patients and with relatives of 66 community and 53 hospital controls were examined by a dental surgeon. Responses regarding dental treatments were analysed. Results: We did not find a statistically significant excess of risk of vCJD associated with dental treatments with the exception of extractions in an unmatched analysis of vCJD cases with community controls (p=0.02). However, this result may be explained by multiple testing. Conclusions: This is the first published study to date to examine potential links between vCJD and dental treatment. There was no convincing evidence found of an increased risk of variant CJD associated with reported dental treatment. However, the power of the study is restricted by the number of vCJD cases to date and does not preclude the possibility that some cases have resulted from secondary transmission via dental procedures. Due to the limitations of the data available, more detailed analyses of dental records are required to fully exclude the possibility of transmission via dental treatment

Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life

Objectives: Data quantifying outcomes of recurrent Clostridium difficile infection (rCDI) are lacking. We sought to determine the UK hospital resource use and health-related quality of life (HrQoL) associated with rCDI hospitalisations. Patients and methods: A non-interventional study in 6 UK acute hospitals collected retrospective clinical and resource use data from medical records of 64 adults hospitalised for rCDI and 64 matched inpatient controls with a first episode only (f)CDI. Patients were observed from the index event (date rCDI/fCDI confirmed) for 28-days (or death, if sooner); UK-specific reference costs were applied. HrQoL was assessed prospectively in a separate cohort of 30 patients hospitalised with CDI, who completed the EQ-5D-3L questionnaire during their illness. Results: The median total management cost (post-index) was £7,539 and £6,294 for rCDI and fCDI, respectively (cost difference, p=0.075); median length of stay (LOS) was 21 days and 15.5 days, respectively (p=0.269). The median cost difference between matched rCDI and fCDI cases was £689 (IQR=£-1,873-£3,954). Subgroup analysis demonstrated the highest median costs (£8,542/patient) in severe rCDI cases. CDI management costs were driven primarily by hospital LOS, which accounted for >85% of costs in both groups. Mean EQ-5D index values were 46% lower in CDI patients compared with UK population values (0.42 and 0.78, respectively); EQ-VAS scores were 38% lower (47.82 and 77.3, respectively). Conclusions: CDI has considerable impact on patients and healthcare resources. This multicentre study provides a contemporaneous estimate of the real-world UK costs associated with rCDI management, which are substantial and comparable to fCDI costs

Acute fat igue in chronic fat igue syndrome pat ients

ABSTRACT Background. Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding

Vector Positronium States in QED3

The homogeneous Bethe-Salpeter equation is solved in the quenched ladder approximation for the vector positronium states of 4-component quantum electrodynamics in 2 space and 1 time dimensions. Fermion propagator input is from a Rainbow approximation Dyson-Schwinger solution, with a broad range of fermion masses considered. This work is an extension of earlier work on the scalar spectrum of the same model. The non-relativistic limit is also considered via the large fermion mass limit. Classification of states via their transformation properties under discrete parity transformations allows analogies to be drawn with the meson spectrum of QCD.Comment: 24 pages, 2 encapsulated postscript figure

Acute fatigue in chronic fatigue syndrome

BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding. METHODS: Sixty-seven patients who fulfilled the criteria for CFS proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was assessed by comparing performance at the start and end of a lengthy test session and by examining changes over the course of individual tasks. RESULTS: CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session. CONCLUSIONS: The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease

Predictions for the 4 GeV TJNAF inclusive electron scattering experiment and for FSI effects in EMC ratios

We express nuclear structure functions $F_i^A$ as generalized convolutions of the structure function of a nucleon and of a nucleus, composed of point-nucleons. In computations of the latter we include Final State Interactions and results for $F_2^A$ are compared with a few directly measured data on C and Fe. The above $F_i^A$ are primarily used for predictions of the TJNAF 89-008 inclusive scattering experiment of 4 GeV electrons on various targets. Those cover a broad angular, and correspondingly wide $x,Q^2$ range, where the nucleon-inelastic part dominates large sections of the covered kinematics. The same model has been applied to the study of hitherto neglected Final State Interaction effects in the nuclear component in EMC ratios in the region $0.85\lesssim x\lesssim 0.25$.Comment: 12 page

Description of inclusive scattering of 4.045 GeV electrons from D

We exploit a relationship between the Structure Functions of nucleons, the physical deuteron and of a deuteron, composed of point-nucleons to compute angular distributions of inclusive cross sections of 4.05 GeV electrons. We report general agreement with data and interpret the remaining discrepancies. We discuss the potential of the data for information on neutron structure functions $F_k^n(x,Q^2)$ and the static form factor $G_M^n(Q^2)$.Comment: 9 pages,1 Fig., PS fil

Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity

Prior to a joint meeting of the Neurodiab Association and International Symposium on Diabetic Neuropathy held in Toronto, Ontario, Canada, 13‐18 October 2009, Solomon Tesfaye, Sheffield, UK, convened a panel of neuromuscular experts to provide an update on polyneuropathies associated with diabetes (Toronto Consensus Panels on DPNs, 2009). Herein, we provide definitions of typical and atypical diabetic polyneuropathies (DPNs), diagnostic criteria, and approaches to diagnose sensorimotor polyneuropathy as well as to estimate severity. Diabetic sensorimotor polyneuropathy (DSPN), or typical DPN, usually develops on long‐standing hyperglycaemia, consequent metabolic derangements and microvessel alterations. It is frequently associated with microvessel retinal and kidney disease—but other causes must be excluded. By contrast, atypical DPNs are intercurrent painful and autonomic small‐fibre polyneuropathies. Recognizing that there is a need to detect and estimate severity of DSPN validly and reproducibly, we define subclinical DSPN using nerve conduction criteria and define possible, probable, and confirmed clinical levels of DSPN. For conduct of epidemiologic surveys and randomized controlled trials, it is necessary to pre‐specify which attributes of nerve conduction are to be used, the criterion for diagnosis, reference values, correction for applicable variables, and the specific criterion for DSPN. Herein, we provide the performance characteristics of several criteria for the diagnosis of sensorimotor polyneuropathy in healthy subject‐ and diabetic subject cohorts. Also outlined here are staged and continuous approaches to estimate severity of DSPN. Copyright © 2011 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87100/1/1226_ftp.pd