Patient experiences of nurse-led telephone follow-up after treatment for colorectal cancer.

Purpose Colorectal cancer is the third most prevalent cancer worldwide, although mortality rates across most of Europe have decreased in recent years. Historically, patients are asked to return to hospital outpatient clinics following treatment to monitor for disease progression. However, new approaches are being called for that focus on meeting the information and support needs of patients. Telephone follow-up (TFU) by specialist nurses is an alternative approach; this study aimed to explore patient views of TFU. Methods Qualitative interviews were conducted with 26 colorectal cancer patients who had received TFU. One interview was also conducted with the specialist nurse who had used a structured intervention to provide TFU. Data were analysed using content analysis. Results All patients found TFU to be a positive experience and all stated a preference for continuing with TFU. Three main themes emerged from the patient interviews; 1) accessible and convenient care, 2) personalised care, and 3) relationship with the specialist nurse. The themes from the specialist nurse interview were 1) knowing the patient, 2) the benefits of TFU and 3) the challenges of TFU. Conclusions TFU was well received by patients; it was perceived as highly convenient and had distinct advantages over hospital follow-up. Continuity of care was an important factor in building a trusting relationship between patient and nurse. Training in the use of the intervention is recommended and it may be useful for specialist nurses to initially meet eligible patients face to face to establish rapport before implementing TFU

Flicker-assisted localization microscopy reveals altered mitochondrial architecture in hypertension

Mitochondrial morphology is central to normal physiology and disease development. However, in many live cells and tissues, complex mitochondrial structures exist and morphology has been difficult to quantify. We have measured the shape of electrically-discrete mitochondria, imaging them individually to restore detail hidden in clusters and demarcate functional boundaries. Stochastic “flickers” of mitochondrial membrane potential were visualized with a rapidly-partitioning fluorophore and the pixel-by-pixel covariance of spatio-temporal fluorescence changes analyzed. This Flicker-assisted Localization Microscopy (FaLM) requires only an epifluorescence microscope and sensitive camera. In vascular myocytes, the apparent variation in mitochondrial size was partly explained by densely-packed small mitochondria. In normotensive animals, mitochondria were small spheres or rods. In hypertension, mitochondria were larger, occupied more of the cell volume and were more densely clustered. FaLM provides a convenient tool for increased discrimination of mitochondrial architecture and has revealed mitochondrial alterations that may contribute to hypertension

Chapter 9 Mitochondria Structure and Position in the Local Control of Calcium Signals in Smooth Muscle Cells

Features of Ca2+ signals including the amplitude, duration, frequency and location are encoded by various physiological stimuli. These features of the signals are decoded by cells to selectively activate smooth muscle functions that include contraction and proliferation [1–3]. Central, therefore, to an appreciation of how smooth muscle is controlled is an understanding of the regulation of Ca2+

Multi-omics studies demonstrate Toxoplasma gondii-induced metabolic reprogramming of murine dendritic cells

Toxoplasma gondii is capable of actively invading almost any mammalian cell type including phagocytes. Early events in phagocytic cells such as dendritic cells are not only key to establishing parasite infection, but conversely play a pivotal role in initiating host immunity. It is now recognized that in addition to changes in canonical immune markers and mediators, alteration in metabolism occurs upon activation of phagocytic cells. These metabolic changes are important for supporting the developing immune response, but can affect the availability of nutrients for intracellular pathogens including T. gondii. However, the interaction of T. gondii with these cells and particularly how infection changes their metabolism has not been extensively investigated. Herein, we use a multi-omics approach comprising transcriptomics and metabolomics validated with functional assays to better understand early events in these cells following infection. Analysis of the transcriptome of T. gondii infected bone marrow derived dendritic cells (BMDCs) revealed significant alterations in transcripts associated with cellular metabolism, activation of T cells, inflammation mediated chemokine and cytokine signaling pathways. Multivariant analysis of metabolomic data sets acquired through non-targeted liquid chromatography mass spectroscopy (LCMS) identified metabolites associated with glycolysis, the TCA cycle, oxidative phosphorylation and arginine metabolism as major discriminants between control uninfected and T. gondii infected cells. Consistent with these observations, glucose uptake and lactate dehydrogenase activity were upregulated in T. gondii infected BMDC cultures compared with control BMDCs. Conversely, BMDC mitochondrial membrane potential was reduced in T. gondii-infected cells relative to mitochondria of control BMDCs. These changes to energy metabolism, similar to what has been described following LPS stimulation of BMDCs and macrophages are often termed the Warburg effect. This metabolic reprogramming of cells has been suggested to be an important adaption that provides energy and precursors to facilitate phagocytosis, antigen processing and cytokine production. Other changes to BMDC metabolism are evident following T. gondii infection and include upregulation of arginine degradation concomitant with increased arginase-1 activity and ornithine and proline production. As T. gondii is an arginine auxotroph the resultant reduced cellular arginine levels are likely to curtail parasite multiplication. These results highlight the complex interplay of BMDCs and parasite metabolism within the developing immune response and the consequences for adaptive immunity and pathogen clearance

Implementing performance improvement in New Zealand emergency departments: the six hour time target policy national research project protocol

<p>Abstract</p> <p>Background</p> <p>In May 2009, the New Zealand government announced a new policy aimed at improving the quality of Emergency Department care and whole hospital performance. Governments have increasingly looked to time targets as a mechanism for improving hospital performance and from a whole system perspective, using the Emergency Department waiting time as a performance measure has the potential to see improvements in the wider health system. However, the imposition of targets may have significant adverse consequences. There is little empirical work examining how the performance of the wider hospital system is affected by such a target. This project aims to answer the following questions: How has the introduction of the target affected broader hospital performance over time, and what accounts for these changes? Which initiatives and strategies have been successful in moving hospitals towards the target without compromising the quality of other care processes and patient outcomes? Is there a difference in outcomes between different ethnic and age groups? Which initiatives and strategies have the greatest potential to be transferred across organisational contexts?</p> <p>Methods/design</p> <p>The study design is mixed methods; combining qualitative research into the behaviour and practices of specific case study hospitals with quantitative data on clinical outcomes and process measures of performance over the period 2006-2012. All research activity is guided by a Kaupapa Māori Research methodological approach. A dynamic systems model of acute patient flows was created to frame the study. Consequences of the target (positive and negative) will be explored by integrating analyses and insights gained from the quantitative and qualitative streams of the study.</p> <p>Discussion</p> <p>At the time of submission of this protocol, the project has been underway for 12 months. This time was necessary to finalise both the case study sites and the secondary outcomes through key stakeholder consultation. We believe that this is an appropriate juncture to publish the protocol, now that the sites and final outcomes to be measured have been determined.</p

Mitochondria structure and position in the local control of calcium signals in smooth muscle cells

In smooth muscle mitochondria are major regulators of contractility, proliferation and growth through the organelles' control of cytoplasmic Ca2+ concentrations. Mitochondria regulate cytoplasmic Ca2+ over concentrations of the ion that range from 200nM – 50 µM. An acknowledged feature of the organelle’s ability to control Ca2+ over the higher Ca2+ concentrations (>10 µM) is the position and structure of the organelles at sites near ion channels. However, the precise relationship between Ca2+ signalling and mitochondria is preliminary in large part because the structure and position of the organelles is not well understood. We recently developed methods to determine the structure and position of each mitochondrion and the entire organelle complement in live, fully-differentiated cells smooth muscle cells. In fully differentiated smooth muscle, mitochondria are distributed through the cytoplasm mainly as spherical or short rod shaped structures (mean length 0.9 µm). Mitochondrial Ca2+ uptake regulates Ca2+ release from IP3R clusters. However, the organelles do not appear to regulate the gating of voltage-dependent Ca2+ channels on the plasma membrane. Nonetheless the position of mitochondria correlates with an increased magnitude of voltage-dependent Ca2+ entry. Voltage-dependent Ca2+ channel expression or distribution, or both, may be regulated by mitochondria

Limited mitochondrial permeabilisation causes DNA-damage and genomic instability in the absence of cell death

During apoptosis, the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases. Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell, leading to rapid caspase activation and apoptosis. Using a new imaging approach, we demonstrate that MOMP is not an all-or-nothing event. Rather, we find that a minority of mitochondria can undergo MOMP in a stress-regulated manner, a phenomenon we term "minority MOMP." Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death. Instead, this caspase activity leads to DNA damage that, in turn, promotes genomic instability, cellular transformation, and tumorigenesis. Our data demonstrate that, in contrast to its well-established tumor suppressor function, apoptosis also has oncogenic potential that is regulated by the extent of MOMP. These findings have important implications for oncogenesis following either physiological or therapeutic engagement of apoptosis

Elevations of intracellular calcium reflect normal voltage-dependent behavior, and not constitutive activity, of voltage-dependent calcium channels in gastrointestinal and vascular smooth muscle

In smooth muscle, the gating of dihydropyridine-sensitive Ca2+ channels may either be stochastic and voltage dependent or coordinated among channels and constitutively active. Each form of gating has been proposed to be largely responsible for Ca2+ influx and determining the bulk average cytoplasmic Ca2+ concentration. Here, the contribution of voltage-dependent and constitutively active channel behavior to Ca2+ signaling has been studied in voltage-clamped single vascular and gastrointestinal smooth muscle cells using wide-field epifluorescence with near simultaneous total internal reflection fluorescence microscopy. Depolarization (−70 to +10 mV) activated a dihydropyridine-sensitive voltage-dependent Ca2+ current (ICa) and evoked a rise in [Ca2+] in each of the subplasma membrane space and bulk cytoplasm. In various regions of the bulk cytoplasm the [Ca2+] increase ([Ca2+]c) was approximately uniform, whereas that of the subplasma membrane space ([Ca2+]PM) had a wide range of amplitudes and time courses. The variations that occurred in the subplasma membrane space presumably reflected an uneven distribution of active Ca2+ channels (clusters) across the sarcolemma, and their activation appeared consistent with normal voltage-dependent behavior. Indeed, in the present study, dihydropyridine-sensitive Ca2+ channels were not normally constitutively active. The repetitive localized [Ca2+]PM rises (“persistent Ca2+ sparklets”) that characterize constitutively active channels were observed rarely (2 of 306 cells). Neither did dihydropyridine-sensitive constitutively active Ca2+ channels regulate the bulk average [Ca2+]c. A dihydropyridine blocker of Ca2+ channels, nimodipine, which blocked ICa and accompanying [Ca2+]c rise, reduced neither the resting bulk average [Ca2+]c (at −70 mV) nor the rise in [Ca2+]c, which accompanied an increased electrochemical driving force on the ion by hyperpolarization (−130 mV). Activation of protein kinase C with indolactam-V did not induce constitutive channel activity. Thus, although voltage-dependent Ca2+ channels appear clustered in certain regions of the plasma membrane, constitutive activity is unlikely to play a major role in [Ca2+]c regulation. The stochastic, voltage-dependent activity of the channel provides the major mechanism to generate rises in [Ca2+]