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

Wearing long pants while working outdoors in the tropics does not yield higher body temperatures

Objective: To compare the thermoregulatory demands of outdoor workers wearing long or knee-length pants while working in situ in a tropical environment.\ud \ud Methods: Fifteen male (35.8 ± 10.5 yr) outdoor Council workers completed their daily occupational duties (construction or gardening) in trials conducted six days apart: once wearing knee-length shorts (SHORTS) and once wearing full-length pants (PANTS). Body mass and hydration were assessed prior to and following each trial with core body (TC) and mean skin temperature (MST; weighted from sites: chest, arm, thigh and calf) assessed at 30-minute intervals throughout each trial.\ud \ud Results: No significant differences between SHORTS and PANTS for TC, maximum TC, heart rate, MST or body mass changes. Skin temperature at the calf was greater for PANTS (33.8 ± 0.4°C) compared to SHORTS (32.9 ± 0.4°C; p<0.05). Hydration assessments identified 36.7% of participants commenced work hypohydrated while the average body mass lost throughout the workday was 2.5 ± 1.5%. Main effects of time were observed for heart rate and MST but no other assessed variable.\ud \ud Conclusion: The additional exposed surface area available for heat exchange when wearing shorts is insufficient to elicit differences in thermoregulatory demands of outdoor employees under the assessed conditions.\ud \ud Implications: These results suggest the use of SHORTS or PANTS can be determined by occupational duty requirements rather than risk of heat-related illness during very-light to moderate workloads completed under warm and humid environmental conditions

PRMT5 is a critical regulator of breast cancer stem cell function via histone methylation and FOXP1 expression..

Breast cancer progression, treatment resistance, and relapse are thought to originate from a small population of tumor cells, breast cancer stem cells (BCSCs). Identification of factors critical for BCSC function is therefore vital for the development of therapies. Here, we identify the arginine methyltransferase PRMT5 as a key in vitro and in vivo regulator of BCSC proliferation and self-renewal and establish FOXP1, a winged helix/forkhead transcription factor, as a critical effector of PRMT5-induced BCSC function. Mechanistically, PRMT5 recruitment to the FOXP1 promoter facilitates H3R2me2s, SET1 recruitment, H3K4me3, and gene expression. Our findings are clinically significant, as PRMT5 depletion within established tumor xenografts or treatment of patient-derived BCSCs with a pre-clinical PRMT5 inhibitor substantially reduces BCSC numbers. Together, our findings highlight the importance of PRMT5 in BCSC maintenance and suggest that small-molecule inhibitors of PRMT5 or downstream targets could be an effective strategy eliminating this cancer-causing population