Pathfinder cells provide a novel therapeutic intervention for acute kidney injury

Pathfinder cells (PCs) are a novel class of adult-derived cells that facilitate functional repair of host tissue. We used rat PCs to demonstrate that they enable the functional mitigation of ischemia reperfusion (I/R) injury in a mouse model of renal damage. Female C57BL/6 mice were subjected to 30 min of renal ischemia and treated with intravenous (i.v.) injection of saline (control) or male rat pancreas-derived PCs in blinded experimentation. Kidney function was assessed 14 days after treatment by measuring serum creatinine (SC) levels. Kidney tissue was assessed by immunohistochemistry (IHC) for markers of cellular damage, proliferation, and senescence (TUNEL, Ki67, p16ink4a, p21). Fluorescence in situ hybridization (FISH) was performed to determine the presence of any rat (i.e., pathfinder) cells in the mouse tissue. PC-treated animals demonstrated superior renal function at day 14 post-I/R, in comparison to saline-treated controls, as measured by SC levels (0.13 mg/dL vs. 0.23 mg/dL, p<0.001). PC-treated kidney tissue expressed significantly lower levels of p16ink4a in comparison to the control group (p=0.009). FISH analysis demonstrated that the overwhelming majority of repaired kidney tissue was mouse in origin. Rat PCs were only detected at a frequency of 0.02%. These data confirm that PCs have the ability to mitigate functional damage to kidney tissue following I/R injury. Kidneys of PC-treated animals showed evidence of improved function and reduced expression of damage markers. The PCs appear to act in a paracrine fashion, stimulating the host tissue to recover functionally, rather than by differentiating into renal cells. This study demonstrates that pancreatic-derived PCs from the adult rat can enable functional repair of renal damage in mice. It validates the use of PCs to regenerate damaged tissues and also offers a novel therapeutic intervention for repair of solid organ damage in situ

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

A Minimal Model of Signaling Network Elucidates Cell-to-Cell Stochastic Variability in Apoptosis

Signaling networks are designed to sense an environmental stimulus and adapt to it. We propose and study a minimal model of signaling network that can sense and respond to external stimuli of varying strength in an adaptive manner. The structure of this minimal network is derived based on some simple assumptions on its differential response to external stimuli. We employ stochastic differential equations and probability distributions obtained from stochastic simulations to characterize differential signaling response in our minimal network model. We show that the proposed minimal signaling network displays two distinct types of response as the strength of the stimulus is decreased. The signaling network has a deterministic part that undergoes rapid activation by a strong stimulus in which case cell-to-cell fluctuations can be ignored. As the strength of the stimulus decreases, the stochastic part of the network begins dominating the signaling response where slow activation is observed with characteristic large cell-to-cell stochastic variability. Interestingly, this proposed stochastic signaling network can capture some of the essential signaling behaviors of a complex apoptotic cell death signaling network that has been studied through experiments and large-scale computer simulations. Thus we claim that the proposed signaling network is an appropriate minimal model of apoptosis signaling. Elucidating the fundamental design principles of complex cellular signaling pathways such as apoptosis signaling remains a challenging task. We demonstrate how our proposed minimal model can help elucidate the effect of a specific apoptotic inhibitor Bcl-2 on apoptotic signaling in a cell-type independent manner. We also discuss the implications of our study in elucidating the adaptive strategy of cell death signaling pathways.Comment: 9 pages, 6 figure

Exciton Condensation and Perfect Coulomb Drag

Coulomb drag is a process whereby the repulsive interactions between electrons in spatially separated conductors enable a current flowing in one of the conductors to induce a voltage drop in the other. If the second conductor is part of a closed circuit, a net current will flow in that circuit. The drag current is typically much smaller than the drive current owing to the heavy screening of the Coulomb interaction. There are, however, rare situations in which strong electronic correlations exist between the two conductors. For example, bilayer two-dimensional electron systems can support an exciton condensate consisting of electrons in one layer tightly bound to holes in the other. One thus expects "perfect" drag; a transport current of electrons driven through one layer is accompanied by an equal one of holes in the other. (The electrical currents are therefore opposite in sign.) Here we demonstrate just this effect, taking care to ensure that the electron-hole pairs dominate the transport and that tunneling of charge between the layers is negligible.Comment: 12 pages, 4 figure

A multi-metric approach to investigate the effects of weather conditions on the demographic of a terrestrial mammal, the European badger (Meles meles)

Models capturing the full effects of weather conditions on animal populations are scarce. Here we decompose yearly temperature and rainfall into mean trends, yearly amplitude of change and residual variation, using daily records. We establish from multi-model inference procedures, based on 1125 life histories (from 1987 to 2008), that European badger (Meles meles) annual mortality and recruitment rates respond to changes in mean trends and to variability in proximate weather components. Variation in mean rainfall was by far the most influential predictor in our analysis. Juvenile survival and recruitment rates were highest at intermediate levels of mean rainfall, whereas low adult survival rates were associated with only the driest, and not the wettest, years. Both juvenile and adult survival rates also exhibited a range of tolerance for residual standard deviation around daily predicted temperature values, beyond which survival rates declined. Life-history parameters, annual routines and adaptive behavioural responses, which define the badgers’ climatic niche, thus appear to be predicated upon a bounded range of climatic conditions, which support optimal survival and recruitment dynamics. That variability in weather conditions is influential, in combination with mean climatic trends, on the vital rates of a generalist, wide ranging and K-selected medium-sized carnivore, has major implications for evolutionary ecology and conservation

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Fellowship training:a qualitative study of scope and purpose across one department of medicine

BACKGROUND: Fellowship training follows certification in a primary specialty or subspecialty and focusses on distinct and advanced clinical and/or academic skills. This phase of medical education is growing in prevalence, but has been an "invisible phase of postgraduate training" lacking standards for education and accreditation, as well as funding. We aimed to explore fellowship programs and examine the reasons to host and participate in fellowship training, seeking to inform the future development of fellowship education. METHODS: During the 2013-14 academic year, we conducted interviews and focus groups to examine the current status of fellowship training from the perspectives of division heads, fellowship directors and current fellows at the Department of Medicine, University of Ottawa, Canada. Descriptive statistics were used to depict the prevailing status of fellowship training. A process of data reduction, data analysis and conclusions/verifications was performed to analyse the quantitative data. RESULTS: We interviewed 16 division heads (94%), 15 fellowship directors (63%) and 8 fellows (21%). We identified three distinct types of fellowships. Individualized fellowships focus on the career goals of the trainee and/or the recruitment goals of the division. Clinical fellowships focus on the attainment of clinical expertise over and above the competencies of residency. Research fellowships focus on research productivity. Participants identified a variety of reasons to offer fellowships: improve academic productivity; improve clinical productivity; share/develop enhanced clinical expertise; recruit future faculty members/attain an academic position; enhance the reputation of the division/department/trainee; and enhance the scholarly environment. CONCLUSIONS: Fellowships serve a variety of purposes which benefit both individual trainees as well as the academic enterprise. Fellowships can be categorized within a distinct taxonomy: individualized; clinical; and research. Each type of fellowship may serve a variety of purposes, and each may need distinct support and resources. Further research is needed to catalogue the operational requirements for hosting and undertaking fellowship training, and establish recommendations for educational and administrative policy and processes in this new phase of postgraduate education

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Surface modification of starch based biomaterials by oxygen plasma or UV-irradiation

Radiation is widely used in biomaterials science for surface modification and sterilization. Herein, we describe the use of plasma and UV-irradiation to improve the biocompatibility of different starch-based blends in terms of cell adhesion and proliferation. Physical and chemical changes, introduced by the used methods, were evaluated by complementary techniques for surface analysis such as scanning electron microscopy, atomic force microscopy, contact angle analysis and X-ray photoelectron spectroscopy. The effect of the changed surface properties on the adhesion of osteoblast-like cells was studied by a direct contact assay. Generally, both treatments resulted in higher number of cells adhered to the modified surfaces. The importance of the improved biocompatibility resulting from the irradiation methods is further supported by the knowledge that both UV and plasma treatments can be used as cost-effective methods for sterilization of biomedical materials and devices.I. P. thanks the FCT for providing her a postdoctoral scholarship (SFRH/BPD/8491/2002). This work was partially supported by FCT, through funds from the POCTI and/or FEDER programs, The European Union funded STREP Project HIPPOCRATES (NNM-3-CT-2003-505758) and the European NoE EXPERTISSUES (NMP3-CT-2004-500283)

Telephone follow-up of patients after radical prostatectomy : a systematic review

Objective: to assess and summarize the best scientific evidence from randomized controlled clinical trials about telephone follow-up of patients after radical prostatectomy, based on information about how the phone calls are made and the clinical and psychological effects for the individuals who received this intervention. Method: the search was undertaken in the electronic databases Medline, Web of Science, Embase, Cinahl, Lilacs and Cochrane. Among the 368 references found, five were selected. Results: two studies tested interventions focused on psychological support and three tested interventions focused on the physical effects of treatment. The psychoeducative intervention to manage the uncertainty about the disease and the treatment revealed statistically significant evidences and reduced the level of uncertainty and anguish it causes. Conclusion: the beneficial effects of telephone follow-up could be determined, as a useful tool for the monitoring of post-prostatectomy patients.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)