In ascending not descending colon, ageing impairs cholinergic function.

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon.

Objective: Paediatric Cushing's syndrome (CS) remains a challenge to diagnose and exclude. We assessed the accuracy of 24-hour urinary free cortisol (UFC) determination in children referred for suspected CS. Design: We conducted a retrospective study of paediatric patients referred to our centre with suspected CS between 1982 and 2014. Patients: Of 66 subjects (mean age 12.9 years; range 4.4-16.9), there were 47 cases of CS (29 males), which included Cushing's disease (CD; 39 patients, 25 males), primary pigmented nodular adrenocortical disease (8 patients, 4 males) and 19 ‘controls' (6 males) in whom the diagnosis of CS was excluded. Measurements: The subjects had between one and five 24-hour UFC collections analysed by radioimmunoassay, chemiluminescent immunoassay or liquid chromatography-mass spectrometry. The data were normalised, corrected for body surface area (m²) and assessed using receiver operating characteristic analysis and an independent two-tailed t test. Results: The diagnostic accuracy of 24-hour UFC for CS was excellent (area under the curve 0.98, 95% CI 0.946-1.00, sensitivity 89%, specificity 100%). Conclusions: Twenty-four-hour UFC is a reliable and practical investigation with high diagnostic accuracy for paediatric CS. However, further investigations may be required if the UFC is normal but there is a high diagnostic suspicion of CS.

Background/Aims Several studies have demonstrated an increased prevalence of sleep disorders in patients with psoriatic arthritis (PsA). However, there are few data on the relationship between sleep disturbance and disease activity in PsA. We conducted a cross-sectional study to investigate the prevalence of insomnia symptoms and poor sleep quality in PsA and examine correlation with demographic, clinical and patient-reported outcome measures. Methods Patients were recruited from rheumatology clinics at a single centre. Patients had a diagnosis of PsA, met the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria and were aged ≥ 18 and ≤ 80 years. They had no other confirmed sleep disorder diagnoses. Disease activity was calculated using the cDAPSA (Clinical Disease Activity in PSoriatic Arthritis) score. Disease impact was measured using a pain visual analogue scale (VAS) and the Psoriatic Arthritis Impact of Disease (PsAID)-12 questionnaire and functional impairment was assessed using the health assessment questionnaire (HAQ). We used the Sleep Condition Indicator (SCI) to assess symptoms of Diagnostic and Statistical Manual of Mental Disorders (DSM)-V insomnia disorder (ID). The SCI is a score from 0-30 with lower scores indicating worse subjective sleep. We used the Pittsburgh Sleep Quality Index (PSQI) to assess subjective sleep quality. Relationships between clinical characteristics and sleep disturbance were examined using Pearson’s correlation coefficients and multivariable logistic regression. Results Thirty participants were enrolled in the study, of which 13 were female. Mean (SD) age of participants was 49 (13.5) years. Overall, the prevalence of probable DSM-V ID (SCI score ≤ 16) was 43.33% (13/30) with a mean (SD) SCI score of 6.80 (4.79). Mean (SD) PSQI score was 6.77 (3.22) with 60% (18/30) classified as subjective poor sleepers. Mean (SD) pain VAS, PsAID-12 and HAQ were 33.89 (28.67), 2.97 (2.05) and 46.12 (38.83), respectively. Mean (SD) cDAPSA score was 12.3 (15). A significant correlation was observed between the SCI score and cDAPSA (r=-0.3809, p = 0.038), and SCI and PsAID-12 scores (r=-0.3809, p = 0.033). No correlation was found between SCI score and HAQ, age, pain VAS, or disease duration. Multivariable logistic regression controlling for age found an association between cDAPSA and probable ID (OR:1.098 95%CI:1.014-1.253). This association did not persist once pain level, gender, PsAID-12 and HAQ scores were controlled for. Conclusion This cross-sectional analysis of patients with PsA demonstrates that sleep disturbance is highly prevalent. Symptoms of insomnia in this small cohort were related to higher baseline disease activity and self-reported disease impact. This study is the first to demonstrate these findings and warrants further exploration in a larger sample size with longitudinal data. It would be of interest to understand the relationship between insomnia and disease activity and whether insomnia is responsive to treating PsA to low disease activity levels. Disclosure D. McGagh: None. N.M. McGowan: None. S. Elahi: None. J. MacDonald: None. K.E.A. Saunders: None. L.C. Coates: None.

Summary Objective To determine the expression of the bile acid receptor, farnesoid X (FXR), in human gastric mucosa and investigate correlations between expression and body‐mass index (BMI) and in patients with obesity, with changes in weight and BMI following vertical sleeve gastrectomy (VSG). Methods Human gastric mucosa was obtained from normal/overweight individuals (macroscopically‐normal tissue following surgery for malignancy) or from patients with obesity (VSG). The expression of FXR and its isoforms (FXRα, FXRβ) were examined by quantitative PCR and compared with the G protein‐coupled bile acid receptor, GPBA. In patients with obesity, changes in BMI and weight loss were determined following VSG. Results FXRα was the predominant isoform in normal/overweight individuals. FXR expression was higher in patients with obesity but GPBA receptor expression was unchanged. For those with obesity ( n = 19), no correlation was found between FXR expression and change in Body‐Mass Index (BMI)/month or weight loss/month, taken 3 ± 1 months after surgery, or in BMI or weight at surgery. Conclusions Obesity is associated with increased FXR expression in the gastric mucosa. The findings are preliminary but suggest that this increase in FXR expression is a consequence of obesity, rather than its cause.