Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Ultrafast science and development at the Artemis facility

The Artemis facility for ultrafast XUV science is constructed around a high average power carrier-envelope phasestabilised system, which is used to generate tuneable pulses across a wavelength range spanning the UV to the far infrared, few-cycle pulses at 800nm and short pulses of XUV radiation produced through high harmonic generation. The XUV pulses can be delivered to interaction stations for materials science and atomic and molecular physics and chemistry through two vacuum beamlines for broadband XUV or narrow-band tuneable XUV pulses. The novel XUV monochromator provides bandwidth selection and tunability while preserving the pulse duration to within 10 fs. Measurements of the XUV pulse duration using an XUV-pump IR-probe technique demonstrate that the XUV pulselength is below 30 fs for a 28 fs drive laser pulse. The materials science station, which contains a hemispherical electron analyser and five-axis manipulator cooled to 14K, is optimised for photoemission experiments with the XUV. The end-station for atomic and molecular physics and chemistry includes a velocity-map imaging detector and molecular beam source for gas-phase experiments. The facility is now fully operational and open to UK and European users for twenty weeks per year. Some of the key new scientific results obtained on the facility include: the extension of HHG imaging spectroscopy to the mid-infrared; a technique for enhancing the conversion efficiency of the XUV by combining two laser fields with non-harmonically related wavelengths; and observation of D₃⁺ photodissociation in intense laser fields