Story in health and social care

This paper offers a brief consideration of how narrative, in the form of people‟s own stories, potentially figures in health and social care provision as part of the impulse towards patient-centred care. The rise of the epistemological legitimacy of patients‟ stories is sketched here. The paper draws upon relevant literature and original writing to consider the ways in which stories can mislead as well as illuminate the process of making individual treatment care plans

The Extinction of Dengue through Natural Vulnerability of Its Vectors

Dengue transmission has not always been confined to tropical areas. In some cases, this has been due to a reduced geographic range of the mosquitoes that are able to carry dengue viruses. In Australia, Aedes aegypti mosquitoes once occurred throughout temperate, drier parts of the country but are now restricted to the wet tropics. We used a computer modelling approach to determine whether these mosquitoes could inhabit their former range. This was done by simulating dengue mosquito populations in virtual environments that experienced 10 years of actual daily weather conditions (1998–2007) obtained for 13 locations inside and outside the current tropical range. We discovered that in areas outside the Australian wet tropics, Ae. aegypti often becomes extinct, particularly when conditions are too cool for year-round egg-laying activity, and/or too dry for eggs to hatch. Thus, despite being a global pest and disease vector, Ae. aegypti mosquitoes are naturally vulnerable to extinction in certain conditions. Such vulnerability should be exploited in vector control programs

Piezo1 channel activation mimics high glucose as a stimulator of insulin release

Glucose and hypotonicity induced cell swelling stimulate insulin release from pancreatic β-cells but the mechanisms are poorly understood. Recently, Piezo1 was identified as a mechanically-activated nonselective Ca2+ permeable cationic channel in a range of mammalian cells. As cell swelling induced insulin release could be through stimulation of Ca2+ permeable stretch activated channels, we hypothesised a role for Piezo1 in cell swelling induced insulin release. Two rat β-cell lines (INS-1 and BRIN-BD11) and freshly-isolated mouse pancreatic islets were studied. Intracellular Ca2+ measurements were performed using the fura-2 Ca2+ indicator dye and ionic current was recorded by whole cell patch-clamp. Piezo1 agonist Yoda1, a competitive antagonist of Yoda1 (Dooku1) and an inactive analogue of Yoda1 (2e) were used as chemical probes. Piezo1 mRNA and insulin secretion were measured by RT-PCR and ELISA respectively. Piezo1 mRNA was detected in both β-cell lines and mouse islets. Yoda1 evoked Ca2+ entry was inhibited by Yoda1 antagonist Dooku1 as well as other Piezo1 inhibitors gadolinium and ruthenium red, and not mimicked by 2e. Yoda1, but not 2e, stimulated Dooku1-sensitive insulin release from β-cells and pancreatic islets. Hypotonicity and high glucose increased intracellular Ca2+ and enhanced Yoda1 Ca2+ influx responses. Yoda1 and hypotonicity induced insulin release were significantly inhibited by Piezo1 specific siRNA. Pancreatic islets from mice with haploinsufficiency of Piezo1 released less insulin upon exposure to Yoda1. The data show that Piezo1 channel agonist induces insulin release from β-cell lines and mouse pancreatic islets suggesting a role for Piezo1 in cell swelling induced insulin release. Hence Piezo1 agonists have the potential to be used as enhancers of insulin release

Unique Transcriptome Signature Distinguishes Patients With Heart Failure With Myopathy

Background People with chronic heart failure (CHF) experience severe skeletal muscle dysfunction, characterized by mitochondrial abnormalities, which exacerbates the primary symptom of exercise intolerance. However, the molecular triggers and characteristics underlying mitochondrial abnormalities caused by CHF remain poorly understood. Methods and Results We recruited 28 patients with CHF caused by reduced ejection fraction and 9 controls. We simultaneously biopsied skeletal muscle from the pectoralis major in the upper limb and from the vastus lateralis in the lower limb. We phenotyped mitochondrial function in permeabilized myofibers from both sites and followed this by complete RNA sequencing to identify novel molecular abnormalities in CHF skeletal muscle. Patients with CHF presented with upper and lower limb skeletal muscle impairments to mitochondrial function that were of a similar deficit and indicative of a myopathy. Mitochondrial abnormalities were strongly correlated to symptoms. Further RNA sequencing revealed a unique transcriptome signature in CHF skeletal muscle characterized by a novel triad of differentially expressed genes related to deficits in energy metabolism including adenosine monophosphate deaminase 3, pyridine nucleotide‐disulphide oxidoreductase domain 2, and lactate dehydrogenase C. Conclusions Our data suggest an upper and lower limb metabolic myopathy that is characterized by a unique transcriptome signature in skeletal muscle of humans with CHF

Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials

Objective Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder. Method Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed. Results Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81). Conclusions This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population

Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signaling Loop

Rationale: In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. Objective: To answer this question, we generated a mouse with endothelial cell (EC)–specific overexpression of the human insulin receptor (hIRECO) using the Tie2 promoter–enhancer. Methods and Results: hIRECO demonstrated significant endothelial dysfunction measured by blunted endothelium-dependent vasorelaxation to acetylcholine, which was normalized by a specific Nox2 NADPH oxidase inhibitor. Insulin-stimulated phosphorylation of protein kinase B was increased in hIRECO EC as was Nox2 NADPH oxidase–dependent generation of superoxide, whereas insulin-stimulated and shear stress–stimulated eNOS activations were blunted. Phosphorylation at the inhibitory residue Y657 of eNOS and expression of proline-rich tyrosine kinase 2 that phosphorylates this residue were significantly higher in hIRECO EC. Inhibition of proline-rich tyrosine kinase 2 improved insulin-induced and shear stress–induced eNOS activation in hIRECO EC. Conclusions: Enhancing insulin sensitivity specifically in EC leads to a paradoxical decline in endothelial function, mediated by increased tyrosine phosphorylation of eNOS and excess Nox2-derived superoxide. Increased EC insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Inhibition of proline-rich tyrosine kinase 2 restores insulin-induced and shear stress–induced NO production. This study demonstrates for the first time that increased endothelial insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide

Restoring Akt1 activity in outgrowth endothelial cells from south asian men rescues vascular reparative potential

Recent data suggest reduced indices of vascular repair in South Asian men, a group at increased risk of cardiovascular events. Outgrowth endothelial cells (OEC) represent an attractive tool to study vascular repair in humans and may offer potential in cell-based repair therapies. We aimed to define and manipulate potential mechanisms of impaired vascular repair in South Asian (SA) men. In vitro and in vivo assays of vascular repair and angiogenesis were performed using OEC derived from SA men and matched European controls, prior defining potentially causal molecular mechanisms. SA OEC exhibited impaired colony formation, migration, and in vitro angiogenesis, associated with decreased expression of the proangiogenic molecules Akt1 and endothelial nitric oxide synthase (eNOS). Transfusion of European OEC into immunodeficient mice after wire-induced femoral artery injury augmented reendothelialization, in contrast with SA OEC and vehicle; SA OEC also failed to promote angiogenesis after induction of hind limb ischemia. Expression of constitutively active Akt1 (E17KAkt), but not green fluorescent protein control, in SA OEC increased in vitro angiogenesis, which was abrogated by a NOS antagonist. Moreover, E17KAkt expressing SA OEC promoted re-endothelialization of wire-injured femoral arteries, and perfusion recovery of ischemic limbs, to a magnitude comparable with nonmanipulated European OEC. Silencing Akt1 in European OEC recapitulated the functional deficits noted in SA OEC. Reduced signaling via the Akt/eNOS axis is causally linked with impaired OEC-mediated vascular repair in South Asian men. These data prove the principle of rescuing marked reparative dysfunction in OEC derived from these men.This work was supported by the British Heart Foundation, London, UK, and the Diabetes Research and Wellness Foundation, Portsmouth, UK

Long-term, high frequency in situ measurements of intertidal mussel bed temperatures using biomimetic sensors

At a proximal level, the physiological impacts of global climate change on ectothermic organisms are manifest as changes in body temperatures. Especially for plants and animals exposed to direct solar radiation, body temperatures can be substantially different from air temperatures. We deployed biomimetic sensors that approximate the thermal characteristics of intertidal mussels at 71 sites worldwide, from 1998-present. Loggers recorded temperatures at 10-30 min intervals nearly continuously at multiple intertidal elevations. Comparisons against direct measurements of mussel tissue temperature indicated errors of similar to 2.0-2.5 degrees C, during daily fluctuations that often exceeded 15 degrees-20 degrees C. Geographic patterns in thermal stress based on biomimetic logger measurements were generally far more complex than anticipated based only on 'habitat-level' measurements of air or sea surface temperature. This unique data set provides an opportunity to link physiological measurements with spatially-and temporally-explicit field observations of body temperature

Cheating the locals: invasive mussels steal and benefit from the cooling effect of indigenous mussels

The indigenous South African mussel Perna perna gapes during periods of aerial exposure to maintain aerobic respiration. This behaviour has no effect on the body temperatures of isolated individuals, but when surrounded by conspecifics, beneficial cooling effects of gaping emerge. It is uncertain, however, whether the presence of the invasive mussel Mytilus galloprovincialis limits the ability of P. perna for collective thermoregulation. We investigated whether varying densities of P. perna and M. galloprovincialis influences the thermal properties of both natural and artificial mussel beds during periods of emersion. Using infrared thermography, body temperatures of P. perna within mixed artificial beds were shown to increase faster and reach higher temperatures than individuals in conspecific beds, indicating that the presence of M. galloprovincialis limits the group cooling effects of gaping. In contrast, body temperatures of M. galloprovincialis within mixed artificial mussel beds increased slower and exhibited lower temperatures than for individuals in beds comprised entirely of M. galloprovincialis. Interestingly, differences in bed temperatures and heating rates were largely dependent on the size of mussels, with beds comprised of larger individuals experiencing less thermal stress irrespective of species composition. The small-scale patterns of thermal stress detected within manipulated beds were not observed within naturally occurring mixed mussel beds. We propose that small-scale differences in topography, size-structure, mussel bed size and the presence of organisms encrusting the mussel shells mask the effects of gaping behaviour within natural mussel beds. Nevertheless, the results from our manipulative experiment indicate that the invasive species M. galloprovincialis steals thermal properties as well as resources from the indigenous mussel P. perna. This may have significant implications for predicting how the co-existence of these two species may change as global temperatures continue to rise

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

<p>Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.</p> <p>Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).</p> <p>Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).</p&gt