Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study.

This is the author accepted manuscript. The final version is available from the American Heart Association via http://dx.doi.org/10.1161/ATVBAHA.115.306460OBJECTIVE: To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography computed tomography. APPROACH: In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using (18)F-fluorodeoxyglucose positron emission tomography computed tomography. RESULTS: Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8-8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (β=0.41, P=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2; P=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL; P<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL; P<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (β=0.53; P=0.02) and vascular inflammation (β=0.48; P=0.02). CONCLUSIONS: Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.JMT is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. JHFR is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trus

Accumulation of natural killer cells after hepatic artery embolisation in the midgut carcinoid syndrome.

Eleven patients with disseminated midgut carcinoid tumour disease were subjected to hepatic artery embolisation. In six patients, lymphocytosis with a predominance of NK cells occurred and the cytotoxic activity of isolated lymphocytes increased. A relation between NK cell accumulation and subsequent radiological and biochemical response was observed, and it is suggested that anti-tumour mechanisms other than ischaemia may contribute to the therapeutic response in these patients

Automatically adjusting light spectrum for optimal short term photosynthetic rate

The use of light emitting diods (LEDs) as greenhouse illumination is increasingly common. When each LED color is individually dimmable both light spectrum and light intensity can be tuned, which opens up for optimisation of photosynthesis through automatic control of light quality and quantity. However, this requires a non-destructive biological growth signal that can be measured fast, remotely and preferably without interacting with the plants. A potential candidate signal is steady-state chlorophyll a fluorescence gain at 740 nm, defined as dF740/dq, i.e. the difference in fluorescence at 740 nm divided by the difference in incident light quanta caused by a (small) change in intensity of each individual LED color in the lamp (Ahlman et al., 2017). By automatically adjusting the spectrum, to aim for equal fluorescence gains for all LED colors (Wik et al., 2014), the instant photosynthetic rate can be optimised given a preset electric power input to the lamp. When implementing such a controller though, constraints on the spectral distribution are needed to minimise a negative impact on plant morphology

Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour

Somatostatin receptor (sstr)-mediated radiation therapy is a new therapeutic modality for neuroendocrine (NE) tumours. High expression of sstr in NE tumours leads to tumour-specific uptake of radiolabelled somatostatin analogues and high absorbed doses. In this study, we present the first optimised radiation therapy via sstr using [177Lu-DOTA0-Tyr3]-octreotate given to nude mice xenografted with the human midgut carcinoid GOT1. The tumours in 22 out of 23 animals given therapeutic amounts showed dose-dependent, rapid complete remission. The diagnostic amount (0.5 MBq [177Lu-DOTA0-Tyr3]-octreotate) did not influence tumour growth and was rapidly excreted. In contrast, the therapeutic amount (30 MBq [177Lu-DOTA0-Tyr3]-octreotate) induced rapid tumour regression and entrapment of 177Lu so that the activity concentration of 177Lu remained high, 7 and 13 days after injection. The entrapment phenomenon increased the absorbed dose to tumours from 1.6 to 4.0 Gy MBq−1 and the tumours in animals treated with 30 MBq received 120 Gy. Therapeutic amounts of [177Lu-DOTA0-Tyr3]-octreotate rapidly induced apoptosis and gradual development of fibrosis in grafted tumours. In conclusion, human midgut carcinoid xenografts can be cured by receptor-mediated radiation therapy by optimising the uptake of radioligand and taking advantage of the favourable change in biokinetics induced by entrapment of radionuclide in the tumours