Explore the vast range of titles available.

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 107, 108 or up to 109 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.

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.

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 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.

IntroductionEnteral nutrition through tube feeding forms part of the established treatment for patients with acute on chronic liver failure (ACLF) who are unable to meet their nutritional demands orally. There are concerns among gastroenterologists that nasogastric tube insertion may provoke upper gastrointestinal bleeding in this patient group, and literature in this field is lacking.MethodsWe retrospectively identified 69 patients with ACLF admitted to our unit between December 2017 and February 2020 who underwent nasogastric feeding (NG) by comparing dietetic and electronic records. Epidemiology data and complications post NG insertion were collected. Multivariate analysis were calculated and a two-tailed p value of ≤0.05 was considered significant.ResultsPatients were predominantly male (n=38, 54%), with alcohol related liver cirrhosis (n=54, 78.3%). Varices were known at time of admission in 28 patients. Four patients (5.8%) were considered to have had gastrointestinal bleeding post NG insertion, defined as new melaena (n=1), haematemesis (n=2), or a fall in haemoglobin accompanied by a urea rise (n=1) within 72 hours. There were no differences in rate of bleeding between patients with pre-existing varices and patients without varices ( p=0.84). In all cases bleeding was managed conservatively without endoscopy, and it had no effect on outcomes (transfusion and mortality). Only elevated INR (p=0.04) was associated with bleeding, with an INR <2 showing a trend to significance for decreased relative risk of bleeding (RR 0.38, 95% CI 0.20-0.76, p=0.09).ConclusionsNG tube insertion in patients with ACLF is safe but carries a small risk of gastrointestinal bleeding, associated with progressively deranged clotting parameters. This should be factored into clinical decision making.Abstract PTH-10 Table 1Patients who experienced an UGIB within 72 hours from NGT insertion UGIB within 72h No UGIB within 72h n N=4 N=65 Age (years) 53.25 ± 14.6 58.2 ± 11.6 0.42 Male, n (%) 3 (75) 1 (25) 0.41 Etiology, n (%) Alcoholic 2 (50) 52 (80) 0.55 Non-Alcoholic 2 (50) 13 (20) Alcohol Consumption 43.7 ±71.8 (0-150) 69.2 ± 89.3 (0-300) 0.62 BMI (kg/m2) 22.6 ± 4.4 (18-28) 24.1 ± 6.1 (14-43) 0.69 INR 2.5 ± 0.5 (1.8-2.8) 2.0 ± 1.0 (1.0-8.2) 0.04 PLT (x109/L) 113 ± 62 (59-189) 156 ± 95 (33-450) 0.43 Varices (%) 2 (50) 26 (40) 0.84 AbbreviationsUGIB, upper gastrointestinal bleed; NGT, nasogastric tube; BMI, body mass index; INR, international normalized ratio; PLT, platelet count; L, litre

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).

IntroductionMost patients with acute lower gastrointestinal bleeding (LGIB) requiring admission to the Aberdeen Royal Infirmary (ARI) are managed under gastroenterology. Before the COVID-19 pandemic, escalation of care was largely to the Medical High Dependency Unit (MHDU), but at the onset of the pandemic, MHDU beds were absorbed into the intensive treatment unit (ITU) as part of critical care re-organisation. In the absence of a validated severity score for LGIB, we retrospectively reviewed patient pathways and survival to understand the impact of critical care restructuring.MethodsAn electronic patient record search over 10 months before and after 31/03/2020, respectively termed ‘pre-pandemic’ and ‘pandemic’, identified unscheduled admissions to ARI with discharge summaries coded with LGIB or unspecified GIB. We used discharge summaries and investigation reports to identify patients with LGIB that warranted investigation or management. Patient demographics, investigations, admitting ward, and outcome were analysed with statistical testing by chi-squared, Wilcoxon rank sum, and general linear models.ResultsThe audit identified 279 admissions, comprising 263 unique patients, with 141 pre-pandemic admissions (50.5%) and 138 admissions (49.5%) in the pandemic timeframe. There were no significant differences in sex, age, or managing specialty between timeframes. No pre-pandemic patients were admitted to ITU and similarly in the pandemic timeframe, no patients were admitted to MHDU. of pre-pandemic admissions, 22 (17%) were admitted to MHDU; of pandemic admissions, 8 (7%) were admitted to ITU. There was a non-statistically significant decrease in lower gastrointestinal endoscopy (40% vs 30%). There were no statistically significant changes in computed tomography mesenteric angiograms, reliance on outpatient investigations or length of stay. Decreased survival at 30 days was associated with documented shock, but not timeframe or critical care setting.ConclusionsPatients with LGIB admitted to the ARI in the 10-month periods before and after 31/03/2020 may have experienced different care due to critical care reorganisation, rapidly increased staffing pressures, and disinclination to perform endoscopy due to concerns about faecal viral shedding relating to the COVID-19 pandemic. Indeed, admission to critical care decreased to less than half of pre-pandemic levels. Despite this, admitting specialties, investigations performed, length of stay, and survival did not significantly change. This suggests that major outcomes are not affected by managing all but the most critically ill patients with LGIB at ward level.

Sepsis of unknown origin can be a difficult scenario whereupon careful balance needs to be struck between managing a deteriorating patient and choosing investigations carefully to uncover the aetiology. This case highlights a 70-year-old man with neutropenic sepsis of an unusual cause that is described on a key image from a CT scan. The patient was treated with medical management in favour of surgery in view of his relative frailty, and he had a good outcome. We expound on key clinical pearls for managing this condition.

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.

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n  = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy ( n  = 27) compared to standard medical care ( n  = 24). The primary endpoint was the difference in baseline to day 90 change in MELD score (ΔMELD) between treatment and control groups (ΔΔMELD). Secondary endpoints included adverse clinical outcomes, non-invasive fibrosis biomarkers and health-related quality of life (HRQoL) at 90 d, 180 d and 360 d. The ΔΔMELD between day 0 and day 90 in the treatment group compared to controls was −0.87 (95% confidence interval: −1.79, 0.0; P  = 0.06); therefore, the primary endpoint was not met. During 360-d follow-up, five of 24 participants in the control group developed a total of 10 severe adverse events, four of which were liver related, and three deaths (two liver related), whereas no liver-related severe adverse events or deaths occurred in the treatment group. Although no differences were observed in biomarkers or HRQoL, exploratory analysis showed anti-inflammatory serum cytokine profiles after macrophage infusion. This study reinforces the safety and potential efficacy of macrophage therapy in cirrhosis, supporting further investigation. Results from the phase 2 MATCH01 clinical trial of autologous monocyte-derived macrophage therapy for liver cirrhosis revealed no liver-related severe adverse events or deaths in the treatment group.