Young adults' perspectives on living with kidney failure: a systematic review and thematic synthesis of qualitative studies.

Young adults fare worse than younger adolescents or older adults on a broad range of health indicators. Those with a chronic illness such as renal failure are a particularly vulnerable group, who experience poor outcomes compared with both children and older adults. Understanding how being in receipt of renal replacement therapy (RRT) affects the lives of young adults might help us to better prepare and support these individuals for and on RRT, and improve outcomes. This study aimed to synthesise research describing young adults' experiences of the psychosocial impact of kidney failure and RRT.This article is freely available via Open Access. Click on the Additional Link above to access the full-text

Analysis of Male Pheromones That Accelerate Female Reproductive Organ Development

Male odors can influence a female's reproductive physiology. In the mouse, the odor of male urine results in an early onset of female puberty. Several volatile and protein pheromones have previously been reported to each account for this bioactivity. Here we bioassay inbred BALB/cJ females to study pheromone-accelerated uterine growth, a developmental hallmark of puberty. We evaluate the response of wild-type and mutant mice lacking a specialized sensory transduction channel, TrpC2, and find TrpC2 function to be necessary for pheromone-mediated uterine growth. We analyze the relative effectiveness of pheromones previously identified to accelerate puberty through direct bioassay and find none to significantly accelerate uterine growth in BALB/cJ females. Complementary to this analysis, we have devised a strategy of partial purification of the uterine growth bioactivity from male urine and applied it to purify bioactivity from three different laboratory strains. The biochemical characteristics of the active fraction of all three strains are inconsistent with that of previously known pheromones. When directly analyzed, we are unable to detect previously known pheromones in urine fractions that generate uterine growth. Our analysis indicates that pheromones emitted by males to advance female puberty remain to be identified

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset : protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Rationale Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. Hypothesis In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. Sample size estimates A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24 +/- 6 hours, defined as either >= 33% relative increase or >= 6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. Discussion We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.Peer reviewe

Evidence for Widespread Genomic Methylation in the Migratory Locust, Locusta migratoria (Orthoptera: Acrididae)

The importance of DNA methylation in mammalian and plant systems is well established. In recent years there has been renewed interest in DNA methylation in insects. Accumulating evidence, both from mammals and insects, points towards an emerging role for DNA methylation in the regulation of phenotypic plasticity. The migratory locust (Locusta migratoria) is a model organism for the study of phenotypic plasticity. Despite this, there is little information available about the degree to which the genome is methylated in this species and genes encoding methylation machinery have not been previously identified. We therefore undertook an initial investigation to establish the presence of a functional DNA methylation system in L. migratoria. We found that the migratory locust possesses genes that putatively encode methylation machinery (DNA methyltransferases and a methyl-binding domain protein) and exhibits genomic methylation, some of which appears to be localised to repetitive regions of the genome. We have also identified a distinct group of genes within the L. migratoria genome that appear to have been historically methylated and show some possible functional differentiation. These results will facilitate more detailed research into the functional significance of DNA methylation in locusts

Mechanical thrombectomy for emergent large vessel occlusion: an Australian primary stroke centre workflow analysis

Background: Time to successful reperfusion is a critical prognostic factor for acute ischaemic stroke. Mechanical thrombectomy has become the gold standard treatment for emergent large vessel occlusion stroke. The timely delivery of this highly specialised procedure to patients outside of metropolitan centres presents a dilemma of inequity, with limited workflow data hindering benchmarking and service optimisation. Aims: To analyse key stroke treatment time parameters from a primary stroke centre existing in a regional centre within a hub-and-spoke delivery model in Victoria, Australia. Methods: Retrospective cohort study of patients transferred from a regional primary stroke centre to a metropolitan comprehensive stroke centre for mechanical thrombectomy between July 2016 and December 2018. Time workflow analysis was conducted from symptom onset to primary stroke centre departure. Results: A total of 55 patients was included in this study with an average age of 70.2 years. Median National Institutes of Health Stroke Scale score on admission was 13 (interquartile range (IQR) 7–17). Median pre-hospital time was 68 min (IQR 56–137) and median door-in-door-out time was 120.5 min (IQR 98–150), constituting 36.1% and 63.9% of total median time from symptom onset to primary stroke centre departure (188.5 min) respectively. There were no significant differences across observed cohort characteristics under linear regression analysis. Conclusion: Protracted pre-hospital and primary stroke centre workflow times can delay effective treatment for patients with acute ischaemic stroke in regional areas. A systems-level approach to streamlining processes in these key areas is required to bridge this inequity in best practice care

The advanced imaging-guided approach to acute ischemic stroke in the extended reperfusion time window

Evaluation and treatment of acute ischemic stroke has undergone significant advancement since the 1990s, when acute systemic reperfusion with intravenous alteplase became the first approved method for achieving reperfusion. Until recently, 4.5 h after stroke onset appeared to be the maximum time window in which positive results from thrombolysis can be achieved. However, the advent of advanced imaging modalities, including multimodal magnetic resonance imaging and computed tomography perfusion has allowed clinicians to refine the evaluation of these patients by delineating areas of infarcted tissue, areas of potentially salvageable tissue given timely reperfusion, and areas of benign oligemia. Early work in extending the time window beyond this historical limit of 4.5 h has culminated in four positive trials that demonstrate the benefit of acute mechanical or systemic reperfusion therapy in an extended time window of up to 24 h, using advanced imaging criteria for patient selection. The implications of the success of advanced imaging suggest use of these modalities for disposition decisions and selection of greater numbers of patients for reperfusion but add complexity to individual patient evaluation. Despite this, many questions remain unanswered, including the best choice of thrombolysis agent, whether we can extend the time window further to 24 h, and the optimal combination of mechanical thrombectomy and bridging therapy in the late time window in patients with or without large vessel occlusion