Implementation of nutritional guidelines in a university hospital monitored by repeated point prevalence surveys

Background/Objectives: Malnutrition is present in 20–50% of hospitalized patients, and nutritional care is a challenge. The aim was to evaluate whether the implementation of a nutritional strategy would influence nutritional care performance in a university hospital. Subjects/Methods: This was a prospective quality improvement program implementing guidelines for nutritional care, with the aim of improving nutritional practice. The Nutrition Risk Screening (NRS) 2002 was used. Point prevalence surveys over 2 years to determine whether nutritional practice had improved. Results: In total, 3604 (70%) of 5183 eligible patients were screened and 1230 (34%) were at nutritional risk. Only 53% of the at-risk patients got nutritional treatment and 5% were seen by a dietician. The proportion of patients screened increased from the first to the eighth point prevalence survey (P=0.012), but not the proportion of patients treated (P=0.66). The four initial screening questions in NRS 2002 identified 92% of the patients not at nutritional risk. Conclusions: Implementation of nutritional guidelines improved the screening performance, but did not increase the proportion of patients who received nutritional treatment. Point prevalence surveys were useful to evaluate nutritional practice in this university hospital. In order to improve practice, we suggest using only the four initial screening questions in NRS 2002 to identify patients not at risk, better education in nutritional care for physicians and nurses, and more dieticians employed. Audit of implementation of guidelines, performed by health authorities, and specific reimbursement for managing nutrition may also improve practice.publishedVersio

Structure-activity relationship of the peptide binding-motif mediating the BRCA2:RAD51 protein-protein interaction

RAD51 is a recombinase involved in the homologous recombination of double-strand breaks in DNA. RAD51 forms oligomers by binding to another molecule of RAD51 via an 'FxxA' motif, and the same recognition sequence is similarly utilised to bind BRCA2. We have tabulated the effects of mutation of this sequence, across a variety of experimental methods and from relevant mutations observed in the clinic. We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X-ray crystallography. Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered.We would like to thank Protein and Nucleic Acid Service at the Department of Biochemistry for peptide synthesis and the X-ray crystallographic and Biophysics facilities for access and support. We thank Diamond Light Source (beamline I02, I03 and I04 proposal MX315), Swiss Light Source (beamline pxIII) and European Synchrotron Radiation Source (beamline ID14.4) for access to and support at beamlines that contributed to the results presented here. This work was funded by a Translational Award from the Wellcome Trust (080083/Z/06/Z)

Soul's Tools

This paper explores the various ways Aristotle refers to and employs “heat and cold” in his embryology. In my view, scholars are too quick to assume that references to heat and cold are references to matter or an animal’s material nature. More commonly, I argue, Aristotle refers to heat and cold as the “tools” of soul. As I understand it, Aristotle is thinking of heat and cold in many contexts as auxiliary causes by which soul activities (primarily “concoction”) are carried out. This, as I argue, is what it means to call them “tools” of soul. An upshot of this investigation is the fuller picture of Aristotle’s conception of efficient causation it provides in general, and the better understanding of the efficient causal operation of an organism’s nature or soul it provides in particular

Signatures of mutational processes in human cancer.

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy

The molecular and cellular origin of human prostate cancer

Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs