Modelling temperature and fish biomass data to predict annual Scottish farmed salmon, Salmo salar L., losses: Development of an early warning tool.

Losses due to mortality are a serious economic drain on Scottish salmon aquaculture and are a limitation to its sustainable growth. Understanding the changes in losses, and associated drivers, are required to identify risks to sustainable aquaculture. Data on losses were obtained from two open source data sets: monthly losses of biomass 2003-2018 and losses of salmon over production cycles (numbers input minus output harvest) 2002-2016. Monthly loss rates increased, accelerating after 2010, while losses per production cycle displayed no trend. Two modelling frameworks were investigated to produce an early warning tool for managers about potential increases in losses. Both linear regression and beta regression showed that monthly losses related to biomass and minimum winter air temperatures with high precision and low bias. These relationships apply at both the national and regional levels where the beta regression best fit model explain 82 % and 69 % of variation in mortality, some regional differences apply, particularly for the Northern Isles. The lack of trend in losses per production cycle may have been due to shorter production cycles as more salmon were harvested earlier, and possibly increasing losses of larger salmon (which affects biomass but not numbers lost). In the long-term, the models predict that milder winters and increased biomass will be associated with increased mortality, which will need to be managed. In the short-term, given relatively little year-to-year variation in biomass, minimum winter temperature is a powerful early warning of the likely extent of losses in the Scottish salmon farming industry.

Retinoic acid activates p53 in human embryonal carcinoma through retinoid receptor-dependent stimulation of p53 transactivation function.

Although retinoids are known to regulate gene transcription by activating retinoid receptors, the targets of retinoid receptors are largely unknown. This study indicates effective all-trans retinoic acid (RA)-induced differentiation of human embryonal carcinoma cells engages p53. Unexpectedly, RA has been found to activate the transactivation function of p53 in the human embryonal carcinoma cell line, NT2/D1, in a retinoid receptor-dependent manner. A derived RA-resistant line, NT2/D1-R1, is deficient in this activity and is co-resistant to cisplatin. This indicates that RA and cisplatin responses may share a common pathway involving p53 in embryonal carcinomas. RA has no effect on p53 steady-state protein levels in either line. RA enhances endogenous p53 transactivation activity in NT2/D1 but not NT2/D1-R1 cells. In addition, RA induces transactivation activity of a gal4-p53 fusion protein, suggesting that RA activates p53 independent of increasing p53 levels or sequence-specific DNA binding. This activity is absent in retinoic acid receptor gamma (RARgamma)-deficient NT2/D1-R1 cells but can be restored upon co-transfection with specific RARs. Transient transfection of a dominant-negative p53 construct in NT2/D1 cells blocks the RA-mediated transcriptional decline of a differentiation-sensitive reporter plasmid and enhances survival of NT2/D1 cells following cisplatin treatment. Taken together, these findings indicate that RA activates the intrinsic activation function of p53 by a novel mechanism independent of effects on p53 stability or DNA binding and that this activation may be a general mechanism that contributes to RA-mediated G1 arrest.

Retinoic acid promotes ubiquitination and proteolysis of cyclin D1 during induced tumor cell differentiation.

Mechanisms by which differentiation programs engage the cell cycle are poorly understood. This study demonstrates that retinoids promote ubiquitination and degradation of cyclin D1 during retinoid-induced differentiation of human embryonal carcinoma cells. In response to all-trans-retinoic acid (RA) treatment, the human embryonal carcinoma cell line NT2/D1 exhibits a progressive decline in cyclin D1 expression beginning when the cells are committed to differentiate, but before onset of terminal neuronal differentiation. The decrease in cyclin D1 protein is tightly associated with the accumulation of hypophosphorylated forms of the retinoblastoma protein and G(1) arrest. In contrast, retinoic acid receptor gamma-deficient NT2/D1-R1 cells do not growth-arrest or accumulate in G(1) and have persistent cyclin D1 overexpression despite RA treatment. Notably, stable transfection of retinoic acid receptor gamma restores RA-mediated growth suppression and differentiation to NT2/D1-R1 cells and restores the decline of cyclin D1. The proteasome inhibitor LLnL blocks this RA-mediated decline in cyclin D1. RA treatment markedly accelerates ubiquitination of wild-type cyclin D1, but not a cyclin D1 (T286A) mutant. Transient expression of cyclin D1 (T286A) in NT2/D1 cells blocks RA-mediated transcriptional decline of a differentiation-sensitive reporter plasmid and represses induction of immunophenotypic neuronal markers. Taken together, these findings strongly implicate RA-mediated degradation of cyclin D1 as a means of coupling induced differentiation and cell cycle control of human embryonal carcinoma cells.

Lipohyperplasia of ileocecal valve, causing recurrent intussusception.

Lipohyperplasia of the ileocecal valve is a fairly common entity that occasionally behaves as an intestinal tumor, causing obstruction, sometimes with intussusception, or bleeding, which may be acute or chronic. Most often occurring in middle-aged or elderly women, it may be mistaken clinically and radiologically for carcinoma or other neoplasms. Its differentiation is best made by endoscopy, confirmed if possible by biopsy. Differentiation is important, as the treatment is a limited ileal and cecal resection, instead of a blind hemicolectomy. A recent study suggests possible associations with other medical conditions. We describe the clinical and pathological findings of this entity in a patient who had recurrent bouts of intussusception over a period of seven years, causing gastrointestinal symptoms and a palpable mass, eventually requiring surgical treatment.

Silicone synovitis.

Silicone synovitis around a broken silicone elastomer finger joint implant was first described by Aptekar et al in 1974. More recently, it has become apparent that synovitis can result from abraded particles from intact prostheses, which can cause severe damage to adjacent bones and joints. Early recognition of this complication is important because prompt removal of the implant may be necessary to arrest a progressive, destructive process.

Long-standing indolent blastomycosis at internal opening of tracheostomy.

An unusual case of long-standing endotracheal blastomycosis caused recurrent airway obstruction at a tracheostomy site.

Silicone lymphadenopathy and synovitis. Complications of silicone elastomer finger joint prostheses.

We report two complications of silicone elastomer finger joint prostheses. In one patient, the prostheses broke, with silicone particles present in synovium ("detritic synovitis"). In another patient, silicone particles were found in an axillary lymph node five years after insertion of prostheses in the ipsilateral hand (prostheses were intact at the time). Microscopically, silicone particles in synovium and lymph node were identical to particles abraded from a new prosthesis.