Levinholbrook1103

Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). Sodiumorthovanadate We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants.

Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO

), ventilatory threshold (VT), and VO

efficiency (ratio of total work performed to O

consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n=51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t

) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy=13, HTN=9, and HFpEF=12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphSkM may contribute to exercise intolerance in HFpEF.Cyclic AMP-dependent protein kinase A (PKA) and protein phosphatase 1 (PP1) are proteins involved in numerous essential signalling pathways that modulate physiological and pathological functions. Both PP1 and PKA can be inhibited by dopamine- and cAMP-regulated phosphoprotein 32 kD (DARPP-32). Using immunohistochemistry, PKA and PP1 expression was determined in a large primary breast tumour cohort to evaluate associations between clinical outcome and clinicopathological criteria (n > 1100). In addition, mRNA expression of PKA and PP1 subunits was assessed in the METABRIC data set (n = 1980). Low protein expression of PKA was significantly associated with adverse survival of breast cancer patients; interestingly, this relationship was stronger in ER-positive breast cancer patients. PP1 protein expression was not associated with patient survival. PKA and PP1 subunit mRNA was also assessed; PPP1CA, PRKACG and PRKAR1B were associated with breast cancer-specific survival. In patients with high expression of DARPP-32, low expression of PP1 was associated with adverse survival when compared to high expression in the same group. PKA expression and PP1 expression are of significant interest in cancer as they are involved in a wide array of cellular processes, and these data indicate PKA and PP1 may play an important role in patient outcome.

To meet the demands imposed by the continuing growth of the Age-related macular degeneration (AMD) patient population, automation of follow-ups by detecting retinal oedema using deep learning might be a viable approach. However, preparing and labelling data for training is time consuming. In this study, we investigate the feasibility of training a convolutional neural network (CNN) to accurately detect retinal oedema on optical coherence tomography (OCT) images of AMD patients with labels derived directly from clinical treatment decisions, without extensive preprocessing or relabelling.

A total of 50439 OCT images with associated treatment information were retrieved from databases at the Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark between 01.06.2007 and 01.06.2018. A CNN was trained on the retrieved data with the recorded treatment decisions as labels and validated on a subset of the data relabelled by three ophthalmologists to denote presence of oedema.

Moderate inter-grader agreemts might encourage the use of existing clinical databases for development of deep learning based algorithms without labour-intensive preprocessing in the future.

This study aimed to determine the clinical presentation, management and outcomes for patients with ileoanal pouch cancer.

Patients who were diagnosed with ileoanal pouch cancer were identified from our polyposis registry (1978-2019) and operative and referral records (2006-2019). Details of presentation, endoscopic surveillance, cancer staging and management were retrieved from hospital records.

Eighteen patients were identified (12 with ulcerative colitis, one with Crohn's disease, three with familial adenomatous polyposis [FAP], two with dual diagnosis of FAP and inflammatory bowel disease). The median time from pouch formation to cancer diagnosis was 16.5years (range 5-34years) and the median age of the patient at pouch cancer diagnosis was 54years (range 35-71years). Eleven of the 18 patients were undergoing surveillance. Four of five FAP patients developed pouch cancer whilst on surveillance. Eight patients were asymptomatic at the time of pouch cancer diagnosis. Two patients had complete clinical response following chemoradiotherapy. Fourteen patients underwent pouch excision surgery (eight with exenteration). Median survival was 54months; however, only eight patients had outcomes available beyond 24months follow-up.

Pouch cancer can occur in patients despite routine surveillance and without symptoms, and survival is poor. Centralization of 'high-risk' patients who require surveillance is recommended and a low threshold for referral to centres that can provide expert investigation and management is advised.

Pouch cancer can occur in patients despite routine surveillance and without symptoms, and survival is poor. Centralization of 'high-risk' patients who require surveillance is recommended and a low threshold for referral to centres that can provide expert investigation and management is advised.Biology is a data-driven discipline facilitated greatly by computer programming skills. This article describes an introductory experiential programming activity that can be integrated into distance learning environments. Students are asked to develop their own Python programs to identify the nature of alleles linked to disease. This activity effectively engages students in a problem solving exercise that provides an opportunity for application of basic programming skills as well as understanding eukaryotic gene structure. We provide sets of mapped alleles for two well-known genes, CFTR and HFE, as well as a suite of relevant Python programs to achieve these outcomes or allow subsequent exercise modifications.