Spreading depolarizations occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an spreading depolarization requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential. In the injured brain, this is difficult because local blood flow is often low and unreactive. In this study, we use a new variant of microdialysis, continuous on-line microdialysis, to observe the effects of spreading depolarizations on brain metabolism. The neurochemical changes are dynamic and take place on the timescale of the passage of an spreading depolarization past the microdialysis probe. Dialysate potassium levels provide an ionic correlate of cellular depolarization and show a clear transient increase. Dialysate glucose levels reflect a balance between local tissue glucose supply and utilisation. These show a clear transient decrease of variable magnitude and duration. Dialysate lactate levels indicate non-oxidative metabolism of glucose and show a transient increase. Preliminary data suggest that the transient changes recover more slowly after the passage of a sequence of multiple spreading depolarizations giving rise to a decrease in basal dialysate glucose and an increase in basal dialysate potassium and lactate levels.

Highlights d Multiple cell compartments can support accumulation of high levels of polyPs d Over 350 transcripts and 100 proteins show mis-regulation with polyP accumulation d Intracellular polyP results in selective signaling via MAPK effectors d Targets of lysine polyphosphorylation change localization with polyP accumulation

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Posterior urethral valves (PUV) are commonest cause of congenital bladder outlet obstruction (BOO) in boys, and of ESRF in childhood. In the 1990s, 1 in 4,000 boys had PUV: 1/3 presented antenatally, 1/3 postnatally in infancy, 1/3 late (>1year). This study aimed to ascertain the proportion presenting antenatally, postnatally and late in a contemporary cohort and to identify any differences between these patient groups. MethodsA national audit (BAPS CASS) of all referrals in the UK of boys diagnosed with suspected or confirmed PUV in a year was conducted. National registration data provided male birthrate. Data presented as number (%), analysed by Mann-Whitney U-test and Chi-square test, with p<0.05 taken as significant.

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OBJECTIVES To determine whether vascular endothelial growth factor A (VEGF) and its receptors are expressed during bladder development in mice when capillaries are forming, and whether exogenous VEGF might enhance the growth of endothelia and other types of bladder cells, using an embryonic organ‐culture model. MATERIALS AND METHODS Whole bladders from wild‐type mice, at embryonic day (E) 14, were grown in serum‐free organ culture in an air/5% CO2 atmosphere; some cultures were supplemented with VEGF and/or with VEGF receptor 1/Fc chimera (VEGFR1/Fc), which blocks VEGF bioactivity. Organs were harvested after 6 days and the expression of VEGF and related molecules assessed using immunohistochemistry. RESULTS VEGF, VEGFR1 and VEGFR2 positive cells were immunodetected in E14 and E18 bladders. Exogenous VEGF increased whole‐organ growth, as assessed by explant areas, total cell numbers, DNA and protein content; proliferation was enhanced, and apoptosis decreased, in urothelium and surrounding tissues. VEGF also increased the proportions of cells expressing endothelial (CD31) and smooth muscle (α smooth muscle actin) markers. VEGFR1/Fc blocked the growth‐enhancing effects of exogenous VEGF. CONCLUSIONS In organ culture, exogenous VEGF not only stimulated embryonic bladder endothelial cells but also strikingly enhanced the growth of the whole organ. Whether the effects of VEGF on diverse bladder cell populations are direct or indirect requires further investigation. The finding that VEGF protein is present in embryonic bladders in vivo raises the possibility that it has similar actions during normal development. The results also illuminate the pathobiology of certain bladder diseases in which VEGF levels have been shown to be increased.

Aim:To determine the efficacy and potential complications of double-J ureteric stents in the treatment of persistent or progressive primary obstructive megaureter in pediatric patients within our institution.Materials and Methods:A retrospective case-note review of all patients with double-J ureteric stents, between 1997 and 2004, was performed. In all, 38 stents were inserted in 31 patients aged between 2 months and 15 years of age. Complications and results of follow-up investigations and the need for follow-up investigations were recorded. Patients were followed up clinically and radiologically for a minimum of 2 years following stent insertion.Results:Endoscopic placement of double-J ureteric stents in childhood is straightforward and complications are uncommon (8/38 insertions). In non-resolving or progressive primary non-refluxing megaureter, double-J ureteric stenting alone is effective with resolution of primary non-refluxing megaureter in 66% of cases (25/38 insertions).Conclusions:Ureteric stenting provides an alternative to early surgery in patients with primary non-refluxing megaureter. The youngest patient in our series was 2 months old at the time of endoscopic ureteric double-J stent insertion. Endoscopic placement of ureteric double-J stents should be considered as a first-line treatment in the management of persistent or progressive non-refluxing megaureter leading to progressive hydronephrosis or pyonephrosis.

Polyphosphates (polyP) are long chains of inorganic phosphates that can be attached to lysine residues of target proteins as a non-enzymatic post-translational modification. This modification, termed polyphosphorylation, may be particularly prevalent in bacterial and fungal species that synthesize and store large quantities of polyP. In this study, we applied a proven screening strategy to evaluate the polyphosphorylation status of over 200 candidate targets in the budding yeast S. cerevisiae. We report 8 new polyphosphorylated proteins that interact genetically and physically with a previously identified network of targets implicated in ribosome biogenesis. The expanded target network includes vacuolar proteins Prb1 and Apl5, whose modification with polyP suggests a model for feedback regulation of polyP synthesis, while raising additional questions regarding the location of polyphosphorylation in vivo.. CC-BY 4.0 International license a certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under