Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults ...with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 10
, 10
or up to 10
cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.
Short gut syndrome can lead to type 3 intestinal failure, and nutrition and hydration can only be achieved with parenteral nutrition (PN). While this is a lifesaving intervention, it carries short- ...and long-term complications leading to complex comorbidities, including chronic kidney disease. Through a patient with devastating inflammatory bowel disease's journey, this review article illustrates the effect of short gut and PN on kidney function, focusing on secondary hyperoxaluria and acute precipitants of glomerular filtration. In extensive small bowel resections colon in continuity promotes fluid reabsorption and hydration but predisposes to hyperoxaluria and stone disease through the impaired gut permeability and fat absorption. It is fundamental, therefore, for dietary intervention to maintain nutrition and prevent clinical deterioration (i.e., sarcopenia) but also to limit the progression of renal stone disease. Adaptation of both enteral and parenteral nutrition needs to be individualised, keeping in consideration not only patient comorbidities (short gut and jejunostomy, cirrhosis secondary to PN) but also patients' wishes and lifestyle. A balanced multidisciplinary team (renal physician, gastroenterologist, dietician, clinical biochemist, pharmacist, etc.) plays a core role in managing complex patients, such as the one described in this review, to improve care and overall outcomes.
Potassium (K) and magnesium (Mg) deficiency are common stresses that can impact on grape yield and quality, but their effects on photosynthesis have received little attention. Understanding the ...diffusional and biochemical limitations to photosynthetic constraints will help to guide improvements in cultural practices. Accordingly, the photosynthetic response of Vitis vinifera cvs. Shiraz and Chardonnay to K or Mg deficiency was assessed under hydroponic conditions using miniature low-nutrient-reserve vines. Photosynthesis was at least partly reduced by a decline in stomatal conductance. Light and CO2-saturated photosynthesis, maximum rate of ribulose 1.5 bisphospate (RuBP) carboxylation (Vcmax) and maximum rate of electron transport (Jmax) all decreased under K and Mg deficiency. Likewise, chlorophyll fluorescence and electron transport were lower under both nutrient deficiencies while dark respiration increased. K deficiency drastically reduced shoot biomass in both cultivars, while root biomass was greatly reduced under both Mg and K deficiency. Taken together, these results indicate that the decrease in biomass was likely due to both stomatal and biochemical limitations in photosynthesis. Optimising photosynthesis through adequate nutrition will thus support increases in biomass with carry-on positive effects on crop yields.
The film-forming antitranspirant, di-1-p-menthene, is able to reduce transpiration in a number of crops, potentially resulting in water savings and improved productivity. The success of the response ...is, however, dependent on genotype and environmental factors. We aimed to assess the efficacy of this natural terpene polymer on red raspberry (Rubus idaeus, L.) cv. Tulameen leaf water-use efficiency across a 25–40 °C temperature range under controlled conditions. The film reduced transpiration (E) and was most effective when applied to the lower leaf surface. Leaf net assimilation (A) and stomatal conductance (g) were also curtailed after the application of di-1-p-menthene, and as a consequence intrinsic transpiration efficiency (A/g) and instantaneous transpiration efficiency (ratio of net carbon fixation to water loss, A/E) did not improve. At 40 °C, gas exchange of both treated and untreated leaves was minimal due to stomatal closure. The antitranspirant was effective at reducing water loss from berries, but only at the immature stages when transpiration rates were naturally high. Further studies are required to determine if the antitranspirant, di-1-p-menthene, will offer protection against dehydration across a range of temperatures and if productivity and berry composition will benefit.
IntroductionLiver cirrhosis is a growing global healthcare challenge. Cirrhosis is characterised by severe liver fibrosis, organ dysfunction and complications related to portal hypertension. There ...are no licensed antifibrotic or proregenerative medicines and liver transplantation is a scarce resource. Hepatic macrophages can promote both liver fibrogenesis and fibrosis regression. The safety and feasibility of peripheral infusion of ex vivo matured autologous monocyte-derived macrophages in patients with compensated cirrhosis has been demonstrated.Methods and analysisThe efficacy of autologous macrophage therapy, compared with standard medical care, will be investigated in a cohort of adult patients with compensated cirrhosis in a multicentre, open-label, parallel-group, phase 2, randomised controlled trial. The primary outcome is the change in Model for End-Stage Liver Disease score at 90 days. The trial will provide the first high-quality examination of the efficacy of autologous macrophage therapy in improving liver function, non-invasive fibrosis markers and other clinical outcomes in patients with compensated cirrhosis.Ethics and disseminationThe trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by Scotland A Research Ethics Committee (reference 15/SS/0121), National Health Service Lothian Research and Development department and the Medicine and Health Care Regulatory Agency-UK. Final results will be presented in peer-reviewed journals and at relevant conferences.Trial registration numbersISRCTN10368050 and EudraCT; reference 2015-000963-15
The genus Coelastrum Nägeli (Sphaeropleales; Scenedesmaceae) is a diverse genus of green algae with potential biotechnical applications. A sound understanding of its phylogeny will be a useful tool ...for predicting the distribution of traits that may enhance its utility, and may lead to a better understanding of its evolution and ecology. Here we present the plastome of Coelastrum microporum. Our exemplar was isolated from Gull Lake, Michigan and the complete plastome as assembled was 169,961 bp in length. The plastome contained 104 genes of which 68 were protein-coding genes (CDSs), 27 tRNA genes and three rRNA genes. The GC content of the plastome was 31.2%. The maximum likelihood phylogeny suggested that C. microporum was the sister group to a clade of single exemplars of three other genera in the Scenedesmaceae (Tetradesmus, Pectinodesmus and Coelastrella).
Microcirculatory dysfunction is associated with organ failure, poor response to vasoactive drugs and increased mortality in cirrhosis, but monitoring techniques are not established. We hypothesized ...that the chorioretinal structures of the eye could be visualized as a non-invasive proxy of the systemic microvasculature in cirrhosis and would correlate with renal dysfunction. Optical Coherence Tomography (OCT) was performed to image the retina in
= 55 cirrhosis patients being assessed for liver transplantation. OCT parameters were compared with established cohorts of age- and sex-matched healthy volunteers (HV) and patients with chronic kidney disease (CKD). Retinal thickness, macular volume and choroidal thickness were significantly reduced relative to HV and comparable to CKD patients (macular volume: HV vs. cirrhosis mean difference 0.44 mm
(95% CI 0.26-0.61),
≤ 0.0001). Reduced retinal thickness and macular volume correlated with renal dysfunction in cirrhosis (macular volume vs. MDRD-6 eGFR r = 0.40,
= 0.006). Retinal changes had resolved substantially 6 weeks following transplantation. There was an inverse association between choroidal thickness and circulating markers of endothelial dysfunction (endothelin-1 r = -0.49,
≤ 0.001; von Willebrand factor r = -0.32,
≤ 0.05). Retinal OCT may represent a non-invasive window to the microcirculation in cirrhosis and a dynamic measure of renal and endothelial dysfunction. Validation in different cirrhosis populations is now required.
Oesophageal intraluminal pseudodiverticulosis is a rare benign condition of the oesophageal wall, with not many cases reported in the literature. Usually, patients present with dysphagia and food ...impaction in association with a proximal oesophageal stricture. Pathogenesis of the disease is not yet established; hence, it remains important to raise awareness about this distinctive pathology. Here, we present a case of a 62-year-old male admitted to Aberdeen Royal Infirmary, Scotland, UK, with a history of food bolus. Upper gastrointestinal endoscopy revealed food bolus impaction with underlying oesophageal pseudodiverticulosis in the distal two-thirds of the oesophagus.
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