Novel transcriptome networks are associated with adaptation of capsicum fruit development to a light-blocking glasshouse film.

Light-blocking films (LBFs) can contribute to significant energy savings for protected cropping via altering light transmitting, such as UVA, photosynthetically active radiation, blue and red spectra affecting photosynthesis, and capsicum yield. Here, we investigated the effects of LBF on orange color capsicum (O06614, Capsicum annuum L.) fruit transcriptome at 35 (mature green) and 65 (mature ripe) days after pollination (DAP) relative to untreated control in a high-technology glasshouse. The results of targeted metabolites showed that LBF significantly promotes the percentage of lutein but decreased the percentage of zeaxanthin and neoxanthin only at 35 DAP. At 35 DAP, fruits were less impacted by LBF treatment (versus control) with a total of 1,192 differentially expressed genes (DEGs) compared with that at 65 DAP with 2,654 DEGs. Response to stress and response to light stimulus in biological process of Gene Ontology were found in 65-DAP fruits under LBF vs. control, and clustering analysis revealed a predominant role of light receptors and phytohormone signaling transduction as well as starch and sucrose metabolism in LBF adaptation. The light-signaling DEGs, UV light receptor UVR8, transcription factors phytochrome-interacting factor 4 (PIF4), and an E3 ubiquitin ligase (COP1) were significantly downregulated at 65 DAP. Moreover, key DEGs in starch and sucrose metabolism (SUS, SUC, and INV), carotenoid synthesis (PSY2 and BCH1), ascorbic acid biosynthesis (VTC2, AAO, and GME), abscisic acid (ABA) signaling (NCED3, ABA2, AO4, and PYL2/4), and phenylpropanoid biosynthesis (PAL and DFR) are important for the adaptation of 65-DAP fruits to LBF. Our results provide new candidate genes for improving quality traits of low-light adaptation of capsicum in protected cropping.

Light blocking film in a glasshouse impacts Capsicum annuum L. yield differentially across planting season.

High energy costs are a barrier to producing high-quality produce at protected cropping facilities. A potential solution to mitigate high energy costs is film technology, which blocks heat-producing radiation; however, the alteration of the light environment by these films may impact crop yield and quality. Previous studies have assessed the impact of ULR 80 [i.e., light-blocking film (LBF)] on crop yield and photosynthetically active radiation (PAR); however, an assessment of the spectral environment over different seasons is important to understand potential crop impacts through different developmental phases. In this study, two varieties (red and orange) of Capsicum annuum were grown across two crop cycles: one cycle with primary crop growth in the autumn (i.e., autumn experiment [AE]) and the other with primary crop growth in the summer (i.e., summer experiment [SE]). LBF reduced PAR (roof level: 26%-30%, plant canopy level: 8%-25%) and net radiation (36%-66%). LBF also reduced total diffuse PAR (AE: 8%, SE: 15%), but the diffuse fraction of PAR increased by 7% and 9% for AE and SE, respectively, potentially resulting in differential light penetration throughout the canopy across treatments. LBF reduced near-infrared radiation (700 nm-2,500 nm), including far-red (700 nm-780 nm) at mid- and lower-canopy levels. LBF significantly altered light quantity and quality, which determined the amount of time that the crop grew under light-limited (<12 mol m-2 d-1) versus sufficient light conditions. In AE, crops were established and grown under light-limited conditions for 57% of the growing season, whereas in SE, crops were established and grown under sufficient light conditions for 66% of the growing season. Overall, LBF significantly reduced the yield in SE for both varieties (red: 29%; orange: 16%), but not in AE. The light changes in different seasons in response to LBF suggest that planting time is crucial for maximizing fruit yield when grown under a film that reduces light quantity. LBF may be unsuitable for year-round production of capsicum, and additional development of LBF is required for the film to be beneficial for saving energy during production and sustaining good crop yields in protected cropping.

Pharmacokinetics of Teneligliptin in Subjects With Renal Impairment.

The pharmacokinetics of teneligliptin was compared in renally impaired and healthy subjects. Subjects were assigned to one of four groups of eight subjects, according to the stage of disease [mild, moderate, severe or end stage renal disease (ESRD)], while matched healthy subjects were allocated to one of two reference groups. Mild, moderate and severe renal impairment had no effect on maximum plasma concentration (Cmax ) following a single oral dose of 20 mg teneligliptin, as defined in the FDA guideline. AUC0-∞ was increased in all groups relative to the reference group but this was unrelated to the degree of renal impairment. Mean plasma protein binding was <80% in all groups. Overall, teneligliptin was well tolerated by subjects with renal impairment or ESRD. Dialysis is not expected to affect the efficacy or safety of teneligliptin. These results indicate that dose adjustment may not be needed when teneligliptin is administered to subjects with mild, moderate or severe renal impairment or ESRD.

Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry.

BACKGROUND: May 22nd marks the beginning of a Shiga-toxin-producing Escherichia coli (STEC) O104:H4 outbreak in Northern Germany. By its end on 27 July, it had claimed 53 deaths among 2987 STEC and 855 confirmed haemolytic-uraemic syndrome (HUS) cases. METHODS: To describe short-term effectiveness of best supportive care (BSC), therapeutic plasma exchange (TPE) and TPE with eculizumab (TPE-Ecu) in 631 patients with suspected HUS treated in 84 hospitals in Germany, Sweden and the Netherlands using the web-based registry of the DGfN (online since 27 May). RESULTS: Of 631 entries, 491 fulfilled the definition of HUS (median age 46 years; 71% females). The median (inter-quartile range) hospital stay was 22 (14-31) days. Two hundred and eighty-one (57%) patients underwent dialysis and 114 (23%) mechanical ventilation. Fifty-seven patients received BSC, 241 TPE and 193 TPE-Ecu. Treatment strategy was dependent on disease severity (laboratory signs of haemolysis, thrombocytopenia, peak creatinine level, need for dialysis, neurological symptoms, frequency of seizures) which was lower in BSC than in TPE and TPE-Ecu patients. At study endpoint (hospital discharge or death), the median creatinine was lower in BSC [1.1 mg/dL (0.9-1.3)] than in TPE [1.2 mg/dL (1.0-1.5), P < 0.05] and TPE-Ecu [1.4 mg/dL (1.0-2.2), P < 0.001], while need for dialysis was not different between BSC (0.0%, n = 0), TPE (3.7%; n = 9) and TPE-Ecu (4.7%, n = 9). Seizures were absent in BSC and rare in TPE (0.4%; n = 1) and TPE-Ecu (2.6%; n = 5) patients. Total hospital mortality in HUS patients was 4.1% (n = 20) and did not differ significantly between the TPE and TPE-Ecu groups. CONCLUSIONS: Despite frequent renal impairment, advanced neurological disorders and severe respiratory failure, short-term outcome was better than expected when compared with previous reports. Within the limitations of a retrospective registry analysis, our data do not support the notion of a short-term benefit of Ecu in comparison to TPE alone in the treatment of STEC-HUS. A randomized trial comparing BSC, TPE and Ecu seems to be prudent and necessary prior to establishing new treatment guidelines for STEC-HUS.

Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor.

AIM: This study evaluated the effects of impaired renal function on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban (10mg single dose), an oral, direct Factor Xa inhibitor. METHODS: Subjects (n= 32) were stratified based on measured creatinine clearance: healthy controls (≥80ml min(-1) ), mild (50-79mlmin(-1) ), moderate (30-49mlmin(-1) ) and severe impairment (<30mlmin(-1) ). RESULTS: Renal clearance of rivaroxaban decreased with increasing renal impairment. Thus, plasma concentrations increased and area under the plasma concentration-time curve (AUC) LS-mean values were 1.44-fold (90% confidence interval [CI] 1.1, 1.9; mild), 1.52-fold (90% CI 1.2, 2.0; moderate) and 1.64-fold (90% CI 1.2, 2.2; severe impairment) higher than in healthy controls. Corresponding values for the LS-mean of the AUC for prolongation of prothrombin time were 1.33-fold (90% CI 0.92, 1.92; mild), 2.16-fold (90% CI 1.51, 3.10 moderate) and 2.44-fold (90% CI 1.70, 3.49 severe) higher than in healthy subjects, respectively. Likewise, the LS-mean of the AUC for Factor Xa inhibition in subjects with mild renal impairment was 1.50-fold (90% CI 1.07, 2.10) higher than in healthy subjects. In subjects with moderate and severe renal impairment, the increase was 1.86-fold (90% CI 1.34, 2.59) and 2.0-fold (90% CI 1.44, 2.78) higher than in healthy subjects, respectively. CONCLUSIONS: Rivaroxaban clearance is decreased with increasing renal impairment, leading to increased plasma exposure and pharmacodynamic effects, as expected for a partially renally excreted drug. However, the influence of renal function on rivaroxaban clearance was moderate, even in subjects with severe renal impairment.

Benzoate hydroxylation: a measure of oxidative stress in divers.

Hyperoxia may facilitate the formation of reactive oxygen species. Recent experiments indicated signs of oxidative stress after 3.5 h hyperoxic diving. We analyzed in the urine of healthy, 100% O2-breathing male volunteers before and after 45 min seawater diving (170 kPa) or 30 min resting at 280 kPa in a pressure chamber (HBO) for sub-fractions of hydroxybenzoate (HB), monohydroxybenzoate (MHB), and of dihydroxybenzoate (DHB). Measurements were performed by HPLC and electrochemical or UV-detection. Additionally, urinary concentrations of thiobarbituric acid-reactive substances (TBARS) and of creatinine (CREA) were analyzed by standard colorimetric assays. During HBO treatment, TBARS, DHB, 2,4-DHB, and 3,4-DHB increased significantly. MHB and CREA did not change. 2,4- and 3,4-DHB-alterations correlated with changes in TBARS. Diving induced urine dilution and stimulated oxygen consumption. Urinary TBARS and HB rose significantly higher during diving at 170 kPa than during HBO at 280 kPa. A different pattern in urinary sub-fractions of DHB could be observed in divers: 2,6 > 2,3 > 2,5 > 3,4. Changes in 2,6- and 2,5-DHB correlated significantly with alterations in TBARS. 2,6-DHB probably indicated renal oxidant stress similar to previously described animal experiments. It is concluded that analyzing urinary HB may provide a sensitive measure to quantify and qualify oxidant stress in divers.