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Background Little is known about the distribution of posaconazole in brain tissue and CSF. We therefore analysed trough concentrations of posaconazole in paediatric leukaemia patients in non-inflamed CSF. Patients and methods The study included paediatric patients <18 years of age with acute leukaemia in remission who underwent repeat therapeutic lumbar punctures as part of their anti-leukaemia treatment. CSF and blood were obtained 20–24 h after dosing, and posaconazole was measured by LC-MS/MS. Results Six patients (median age: 10 years; range, 6–14) with acute lymphatic (three) or acute myeloid (three) leukaemia were included who received posaconazole gastroresistant tablets at weight-banded doses (five) or the oral solution (one). In contrast to 14 control samples, posaconazole was detectable in all 11 samples of treated patients. CSF concentrations ranged from 8.3 to 42 ng/mL with a median CSF concentration of 13.6 ng/mL. Concurrent serum concentrations were between 965 and 5177 ng/mL with a median of 1716 ng/mL. Conclusions Trough concentrations of posaconazole in the CSF after systemic administration were low but detectable in all subjects. Concurrent serum concentrations were in the target range for prophylaxis and treatment in 100% and 90%, respectively. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES A combined lung and liver transplant in patients with cystic fibrosis (CF) is an uncommon procedure. The goal of this study was to compare long-term outcomes between patients with CF who underwent either a combined lung-liver or a lung-only transplant. METHODS This is a retrospective single-centre study of patients with CF who underwent a lung transplant between January 2005 and May 2020. Since 2006, our preference for a combined lung-liver transplant was to transplant the liver first and then the lung. Outcomes were compared using the Kaplan–Meier analysis and the log-rank test. Median follow-up was 53 (23–97) months. RESULTS During the study period, among 357 patients with CF who underwent a lung transplant, 14 (4%) required a lung-liver transplant whereas 343 (96%) had a lung-only transplant. Lung cold ischaemic time was longer in the lung-liver transplant group, but no patient in this group showed primary graft dysfunction at 72 h after the transplant. Prevalence of anti-human leucocyte antigen donor-specific antibodies was 7.1% vs 13.7% in the lung-liver versus the lung-only transplant group (P  = 0.42). At 5 years, lung graft survival (78% vs 69%) and freedom from chronic lung allograft dysfunction (79% vs 62%) did not differ between the lung-liver versus the lung-only groups (P  = 0.45 and P  = 0.55, respectively). Freedom from lung biopsy-confirmed rejection was significantly higher in patients undergoing a lung-liver transplant (91% vs 50%; P  = 0.027). CONCLUSIONS A lung-liver transplant did not impair lung graft function. The lower prevalence of donor-specific antibodies and the better freedom from lung biopsy-confirmed rejection suggest tolerogenic effects of the liver graft. [ABSTRACT FROM AUTHOR]

Agricultural development is a major threat to global biodiversity, and effective conservation actions are crucial. Physiological repercussions of life alongside human-modified landscapes can undermine adaptable species' health and population viability; however, baseline data are lacking for many wildlife species. We assessed the physiological status of a generalist carnivore, the Malay civet (Viverra tangalunga), persisting within an extensively human-modified system in Sabah, Malaysian Borneo. We characterized hematology and serum biochemistry panels from civets sampled across a mosaic landscape comprising tropical forest fragments and oil palm plantations. Intra-population variation in certain blood parameters were explained by expected biological drivers such as sex, age category and sampling season. Furthermore, we determined several erythrocyte measures, immune cell counts and dietary biochemistry markers significantly varied with proximity to oil palm plantation boundaries. These findings were supported by a case study, whereby blood profiles of GPS collared male civets were contrasted based on their exclusive use of forests or use of oil palm plantations. These data provide robust and valuable first insights into this species' physiological status and suggest agricultural landscapes are impacting the persisting population. [ABSTRACT FROM AUTHOR]

Background: Posaconazole is a recommended option for antifungal prophylaxis in paediatric patients >12 years of age. However, little is known about plasma exposures and safety following administration of the delayed-release tablets (DRTs) in children and adolescents.Methods: In a retrospective observational study, we analysed steady-state trough concentrations of posaconazole in all paediatric patients who had received the DRT formulation between May 2015 and December 2018 for antifungal prophylaxis. Dosing was guided by a published population pharmacokinetic model with weight-based dosing. Drug concentrations in plasma were measured by a validated tandem MS method. Liver function and drug discontinuations due to adverse effects were also assessed.Results: A total of 34 patients (21 male, 13 female; median age 12 years, range 5-17 years; median body weight 43.5 kg, range 16-84 kg) undergoing treatment for haemato-oncological disorders (n=23) or immunosuppression for polyarthritis (n=1) or post-allogeneic HSCT (n=11) received posaconazole DRTs for a median of 70 days (range 9-391 days). The median first steady-state trough plasma concentration following model-derived dosing was 1607 ng/mL (range 501-8485 ng/mL) with trough concentrations being above the dosing target of ≥700 ng/mL in 32/34 patients (94%). Considering all (first and subsequent) trough concentrations, target attainment was 90% (63/70 samples). Posaconazole was well tolerated without adverse event-related discontinuations or breakthrough infections.Conclusions: Administration of posaconazole DRTs to paediatric patients guided by a population pharmacokinetic-derived dosing algorithm resulted in predictable and potentially effective exposures and was well tolerated over prolonged time periods. [ABSTRACT FROM AUTHOR]

As tomato fruit ripen, the wounding-elicited transcriptome and VOC profiles alter. This shift is consistent with a change from protection of developing seeds to attraction of frugivores for seed dispersal.Fleshy fruits develop from an unripe organ that needs to be protected from damage to a ripe organ that attracts frugivores for seed dispersal through production of volatile organic compounds (VOCs). Thus, different responses to wounding damage are predicted. The aim of this study was to discover whether wound-induced changes in the transcriptome and VOC production alter as tomato transitions from unripe to ripe. Transcript changes were analysed 3h post-wounding using microarray analysis in two commercial salad-tomato (Solanum lycopersicum L.) cultivars: Luna Rossa and AVG, chosen for their high aroma production. This was followed by quantitative PCR on Luna Rossa genes involved in VOC biosynthesis and defence responses. VOCs elicited by wounding at different ripening stages were analysed by solid phase micro extraction and gas chromatography–mass spectrometry. Approximately 4000 differentially expressed genes were identified in the cultivar AVG and 2500 in Luna Rossa. In both cultivars the majority of genes were up-regulated and the most affected pathways were metabolism of terpenes, carotenoids, and lipids. Defence-related genes were mostly up-regulated in immature stages of development, whereas expression of genes related to VOCs changed at riper stages. More than 40 VOCs were detected and profiles changed with ripening stage. Thus, both transcriptome and VOC profiles elicited by wounding depend on stage of ripening, indicating a shift from defence to attraction. [ABSTRACT FROM PUBLISHER]

Native to South America, Alstroemeria flowers are known for their colourful tepals, and Alstroemeria hybrids are an important cut flower. However, in common with many commercial cut flowers, virtually all the commercial Alstroemeria hybrids are not scented. The cultivar ‘Sweet Laura’ is one of very few scented commercial Alstroemeria hybrids. Characterization of the volatile emission profile of these cut flowers revealed three major terpene compounds: (E)-caryophyllene, humulene (also known as α-caryophyllene), an ocimene-like compound, and several minor peaks, one of which was identified as myrcene. The profile is completely different from that of the parental scented species A. caryophyllaea. Volatile emission peaked at anthesis in both scented genotypes, coincident in cv. ‘Sweet Laura’ with the maximal expression of a putative terpene synthase gene AlstroTPS. This gene was preferentially expressed in floral tissues of both cv. ‘Sweet Laura’ and A. caryophyllaea. Characterization of the AlstroTPS gene structure from cv. ‘Sweet Laura’ placed it as a member of the class III terpene synthases, and the predicted 567 amino acid sequence placed it into the subfamily TPS-b. The conserved sequences R28(R)X8W and D321DXXD are the putative Mg2+-binding sites, and in vitro assay of AlstroTPS expressed in Escherichia coli revealed that the encoded enzyme possesses myrcene synthase activity, consistent with a role for AlstroTPS in scent production in Alstroemeria cv. ‘Sweet Laura’ flowers. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: Pulmonary retransplantation remains controversial due to the increased morbidity and mortality compared with primary lung transplantation. So far, only few data about paediatric retransplantation are available. We retrospectively analysed our experience with retransplantations in children. Methods: Since 1994, seven pulmonary retransplantations in children were performed at our institution. We analysed pretransplant characteristics, operative parameters as well as the post-transplant outcome of these recipients and compared them to 29 patients who underwent primary lung transplantation during the same period. Results: Indications for retransplantation were bronchiolitis obliterans syndrome in six patients and primary graft failure in one patient. Pretransplant characteristics, perioperative morbidity and mortality were similar in both groups. Hospital mortality was 2/7 (29%) after retransplantation and 6/29 (21%) after primary transplantation (p =0.64). Actuarial 3-year survival was 71% and 60% after redo and primary transplantation, respectively (p =0.50). Development of bronchiolitis obliterans syndrome did not differ between both groups (p =0.99). Conclusions: In our small cohort of paediatric patients, pulmonary retransplantation was associated with an acceptable long-term outcome comparable to primary pulmonary transplantation. This differs from currently available data. However, further long-term studies including more patients and longer follow-up intervals are required. [ABSTRACT FROM AUTHOR]

Nereis succinea and Platynereis dumerilii (Annelida, Polychaeta) are broadcast spawners and reproduce semelparously. The final events in reproduction, swarming and spawning are co-ordinated by sex pheromones. A water-soluble fraction of crude oil, the volatile fraction (C9--C16) of EKO FISK crude oil was found to induce release of gametes in male nereids at levels <0.3 ppm. Using vacuum distillation, column chromatography, preparative GC and GC-MS analysis we showed that C5-alkylated benzenes were most potent in inducing sperm release, of those n-butyl-4-methylbenzene and 1,4-diethyl-2-methylbenzene were found to induce release of gametes at concentrations ≥4 nM. This threshold is lower than those reported for natural pheromones (nereithione: 60 nM, uric acid: 600 nM) but higher than background levels of aromatic compounds of 0.05 nM and below. Other oil fractions showed additional effects, blocking pheromone reception or narcotising and intoxicating animals. Part of these effects could be assigned to naphthalenes at levels down to approx. 320 nM. In the original mixtures, their action was modified or compensated by the presence of gamete release inducing alkylated benzenes. Other highly paralysing substances remained elusive. [ABSTRACT FROM AUTHOR]