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The energy status of plant cells strongly depends on the energy metabolism in chloroplasts and mitochondria, which are capable of generating ATP either by photosynthetic or oxidative phosphorylation, respectively. Another energy-rich metabolite inside plastids is the glycolytic intermediate phosphoenolpyruvate (PEP). However, chloroplasts and most non-green plastids lack the ability to generate PEP via a complete glycolytic pathway. Hence, PEP import mediated by the plastidic PEP/phosphate translocator or PEP provided by the plastidic enolase are vital for plant growth and development. In contrast to chloroplasts, metabolism in non-green plastids (amyloplasts) of starch-storing tissues strongly depends on both the import of ATP mediated by the plastidic nucleotide transporter NTT and of carbon (glucose 6-phosphate, Glc6P) mediated by the plastidic Glc6P/phosphate translocator (GPT). Both transporters have been shown to co-limit starch biosynthesis in potato plants. In addition, non-photosynthetic plastids as well as chloroplasts during the night rely on the import of energy in the form of ATP via the NTT. During energy starvation such as prolonged darkness, chloroplasts strongly depend on the supply of ATP which can be provided by lipid respiration, a process involving chloroplasts, peroxisomes, and mitochondria and the transport of intermediates, i.e. fatty acids, ATP, citrate, and oxaloacetate across their membranes. The role of transporters involved in the provision of energy-rich metabolites and in pathways supplying plastids with metabolic energy is summarized here.

PurposePhotodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT.MethodsBetween 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113)ResultsMedian follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257).ConclusionNon-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Purpose Radical cystectomy (RC) can be associated with significant blood loss, whereas many patients are presenting with anemia preoperatively. To date, there is a lack of data addressing the impact of preoperative anemia (PA) on survival of patients undergoing RC for urothelial carcinoma of the bladder (UCB). Methods This retrospective multicenter study includes 684 patients with UCB undergoing RC with pelvic lymph node dissection. The median follow-up was 50 (IQR 29,78) months. Anemia was defined in line with the WHO classification (hemoglobin (Hb): male ≤13 g/dL, female ≤12 g/dL) and based on contemporary gender- and age-adjusted classification (Hb: white male aged <60 years: ≤13.7 g/dL; ≥60 years: ≤13.2 g/dL; white female of all ages ≤12.2 g/dL). Univariable and multivariable Cox regression analyses were used to assess the effects of PA on oncological outcomes. Results A total of 269 (39.3 %) and 302 (44.2 %) patients were anemic according to the WHO classification versus contemporary classification. Age, increased ECOG performance status, advanced tumor stages, lymph node metastasis, positive surgical margin and anemia were associated with disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM). In multivariable analysis, anemia was an independent predictor of DR, CSM and ACM (WHO and/or contemporary classification). Blood transfusion was significantly associated with ACM in both classifications of anemia. Conclusions PA is significantly associated with worse oncological outcome in patients undergoing RC. Based on the additional unfavorable influence of blood transfusion, this emphasizes the importance of early diagnosis and correction of anemia and implementation of alternative methods of blood volume management.

Purpose Radical cystectomy (RC) can be associated with significant blood loss. Allogenic blood transfusion (ABT) may alter disease outcome because of a theoretical immunomodulatory effect. We evaluated the effects of ABT on overall survival (OS) and progression-free survival (PFS) of patients undergoing RC for urothelial carcinoma of the bladder (UCB). Materials and methods This is a retrospective single-center study of 350 consecutive patients of a university health center with a median follow-up of 70.1 month. All patients underwent RC and pelvic lymph node dissection. The effect of ABT on OS and PFS was analyzed using univariable and multivariable Cox proportional hazards models. Results The overall ABT rate was 63 % ( n  = 219), with intraoperative blood transfusion and postoperative blood transfusion being performed in 183 patients (52 %) and 99 patients (28 %), respectively. Preoperative anemia was detected in 156 patients (45 %) with median estimated blood loss of 800 ml (IQR: 500–1,200). ABT was associated with significant decrease of OS and PFS in multivariable analyses ( p  < 0.001), whereas patients’ prognosis worsened the more packed red blood cells (PRBC) were transfused ( p  < 0.001). The study is limited in part due to its retrospective design. Conclusions We found that ABT and the number of PRBC transfused are associated with poor prognosis for UCB patients undergoing RC, whereas preoperative anemia had no influence on survival. This emphasizes the importance of surgeon’s awareness for a strict indication for ABT. A prospective study will be necessary to evaluate the independent risks associated with ABT during surgical treatments.

Purpose Rectourinary fistula (RUF) is an uncommon but devastating condition that usually occurs as a complication of surgical treatment or radiotherapy of prostate cancer. Although operative fistula repair remains the most successful treatment, there still is no consensus concerning the management of RUF. We present first experiences and transanal surgical technique using biological mesh for fistula repair after urological intervention. Material and methods From January 2009 to December 2013, four cases of RUF were reported at our university hospital. Fistula occurred after extraperitoneal laparoscopic radical prostatectomy, open radical prostatectomy, and high-intensity focused ultrasound, respectively. All patients were initially treated with transanal Cook Biodesign™ mesh, whereas two patients received reoperation with rectal mucosa advancement flap and gracilis muscle flap interposition, respectively. Mean follow-up was 36 months (range 9–62). Results Fistula diameters ranged from 0.6 to 3.0 cm and were located 5 to 6 cm of anocutaneous line. The time from diagnosis to fistula repair was 3 to 7 weeks. The median operative time for Cook Biodesing™ mesh procedure was 79 min (IQR 60, 98). The initial success rate for biological mesh was 50 % (2/4 patients). Larger fistulae were minimalized successfully and finally closed with reoperation mentioned above. No deterioration of continence was documented. Conclusions Management of rectourinary fistula is still challenging. Using biomaterials for fistula closure seems to be a promising and minimally invasive transanal technique in future. Further analysis including more patients is needed to clarify its exact role in comparison to traditional surgical techniques.

Shock wave lithotripsy (SWL) is the gold standard for the treatment of upper urinary tract stones. Despite being relatively non-invasive, SWL can cause renal hematoma (RHT). The aim of this study was to determine incidence and risk factors for RHT following SWL. 857 patients were included in a prospectively maintained database. The observation period spans from 2007 to 2012. 1,324 procedures were performed due to kidney stones. Treatment protocol included power ramping and shock wave frequency of 60-90 per minute as well as an ultrasound check within 3 days of SWL for all patients. Patients with RHT were analyzed, and treatment characteristics were compared with the complete population in a non-statistical manner due to the low event count. RHTs after SWL, sized between 2.6 × 0.6 cm and 17 × 15 cm, were verified in seven patients (0.53 %). In four patients, the RHT was asymptomatic. Three patients developed pain after SWL treatment due to a RHT. In one patient surgical intervention was necessary due to a symptomatic RHT, the kidney was preserved. The risk of RHT following SWL treatment of kidney stones is about 0.5 %. Clinically relevant or symptomatic RHTs occur in 0.23 %, RHTs requiring surgical intervention are extremely rare. Older age and vascular comorbidities appear to be risk factors for the development of RHT. The technical characteristics of SWL treatment and intake of low-dose acetylsalicylic acid due to an imperative cardiologic indication do not appear to influence the risk. Prospective studies are warranted.[PUBLICATION ABSTRACT]

Purpose To evaluate the possible association between bladder tumor location and the laterality of positive lymph nodes (LN) in a prospectively collected multi-institutional radical cystectomy (RC) series. Methods The study population included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic lymph node dissection in 2011 without neoadjuvant chemotherapy and without distant metastasis. Tumor location was classified as right, left or bilateral and compared to the laterality of positive pelvic LN. A logistic regression model was used to identify predictors of ipsilaterality of lymphatic spread. Using multivariate Cox regression analyses (median follow-up: 25 months), the effect of the laterality of positive LN on cancer-specific mortality (CSM) was estimated. Results Overall, median 18.5 LN [interquartile range (IQR), 11–27] were removed and 3 LN (IQR 1–5) were positive. There was concordance of tumor location and laterality of positive LN in 82% [95% confidence interval (CI), 76–89]. Patients with unilateral tumors ( n  = 78) harbored exclusively ipsilateral positive LN in 67% (95% CI 56–77). No criteria were found to predict ipsilateral positive LN in patients with unilateral tumors. CSM after 3 years in patients with ipsilateral, contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively ( p  = 0.042). However, no significant effect of the laterality of positive pelvic LN on CSM could be confirmed in multivariate analyses. Conclusions Our prospective cohort showed a concordance of tumor location and laterality of LN metastasis in BC at RC without any predictive criteria and without any influence on CSM. It is debatable, whether these findings may contribute to a more individualized patient management.

Potassium is an important macronutrient and the most abundant cation in plants. Because soil mineral conditions can vary, plants must be able to adjust to different nutrient availabilities. Here, we used Affymetrix Genechip microarrays to identify genes responsive to potassium (K+) deprivation in roots of mature Arabidopsis (Arabidopsis thaliana) plants. Unexpectedly, only a few genes were changed in their expression level after 6, 48, and 96 h of K+ starvation even though root K+ content was reduced by approximately 60%. AtHAK5, a potassium transporter gene from the KUP/HAK/KT family, was most consistently and strongly up-regulated in its expression level across 48-h, 96-h, and 7-d K+ deprivation experiments. AtHAK5 promoter-β-glucuronidase and -green fluorescent protein fusions showed AtHAK5 promoter activity in the epidermis and vasculature of K+ deprived roots. Rb+ uptake kinetics in roots of athak5 T-DNA insertion mutants and wild-type plants demonstrated the absence of a major part of an inducible high-affinity $\\text{Rb}^{+}/\\text{K}^{+}$ (Km approximately 1-4 μM) transport system in athak5 plants. In comparative analyses, uptake kinetics of the K+ channel mutant akt1-1 showed that akt1-1 roots are mainly impaired in a major transport mechanism, with an apparent affinity of approximately 0.9 mM $\\text{K}^{+}(Rb^{+})$. Data show adaptation of apparent K+ affinities of Arabidopsis roots when individual K+ transporter genes are disrupted. In addition, the limited transcriptome-wide response to K+ starvation indicates that posttranscriptional mechanisms may play important roles in root adaptation to K+ availability in Arabidopsis. The results demonstrate an in vivo function for AtHAK5 in the inducible high-affinity K+ uptake system in Arabidopsis roots.

Purpose Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. Methods In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. Results cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. Conclusions In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Potassium (K+) is an essential nutrient and the most abundant cation in plants, whereas the closely related ion sodium (Na+) is toxic to most plants at high millimolar concentrations. K+ deficiency and Na+ toxicity are both major constraints to crop production worldwide. K+ counteracts Na+ stress, while Na+, in turn, can to a certain degree alleviate K+ deficiency. Elucidation of the molecular mechanisms of K+ and Na+ transport is pivotal to the understanding – and eventually engineering – of plant K+ nutrition and Na+ sensitivity. Here we provide an overview on plant K+ transporters with particular emphasis on root K+ and Na+ uptake. Plant K+-permeable cation transporters comprise seven families: Shaker-type K+ channels, 'two-pore' K+ channels, cyclic-nucleotidegated channels, putative K+/H+ antiporters, KUP/HAK/KT transporters, HKT transporters, and LCT1. Candidate genes for Na+ transport are the KUP/HAK/KTs, HKTs, CNGCs, and LCT1. Expression in heterologous systems, localization in plants, and genetic disruption in plants will provide insight into the roles of transporter genes in K+ nutrition and Na+ toxicity.