Studies in cholesterol metabolism in the animal body

1. Experiments are described whose results indicate that the half-life of serum ¹⁴C-labelled cholesterol in the rat was decreased when the animals had been pre-fed a diet containing unsaturated fat. 2. In most of these experiments there was also an indication that the rate of biosynthesis of cholesterol from acetate was increased when the animals had been pre-fed such a diet. 3. A proposed explanation for these phenomena is that unsaturated fatty acids may combine with cholesterol to form esters which are metabolized more readily than are esters formed with other fatty acids. 4. The isolation of a new Lifschútz chromogen is described. The material was present in human serum and leucocytes and in rat serum, skin and liver. It was shown to be identical with the 3ß-oleyl and linoleyl esters of 7α-hydroxycholesterol. 5. The chemical synthesis of a series of 3ß-acyl esters of 7α-hydroxycholesterol is described in detail, as previously a method has been reported only for the acetyl ester. The physical and chromatographic properties of the esters are tabulated. 6. The synthetic esters were used as substrates for enzymic experiments. The results of these experiments show that the cholesterol esterase system of pancreas was effective for both the hydrolysis and synthesis of the esters, and that of liver for hydrolysis only. 7. The esters were efficiently metabolized to bile acids in vitro. 8. Attempts to produce the synthetic esters either by enzymic oxidation or by autoxidatio of cholesteryl esters were not successful. 9. A description is given of the curious changes undergone by the esters on exposure to ultraviolet light. The resultant changes in structure are discussed. 10. A possible Ale for the naturally occurring esters is suggested, whereby they may form an alternative pathway in the production of bile acids from cholesterol. 11. A hypothesis is described in which it is proposed that the preferential oxidation of certain cholesteryl esters to form esters of 7α-hydroxycholesterol may explain the effect of unsaturated fatty acids on cholesterol turnover

Hypotensive Drugs

Based on a Dissertation read before the Royal Medical Society on Friday, 23rd October 1959.The arterial blood pressure is controlled by the autonomic nervous system.  Information about the level of the arterial pressure is obtained by the stretch receptors of the aortic arch and the carotid sinus.  An increase in pressure is registered as an increase in sensory discharge frequency and vice-versa.  The sensory impulses reach the medulla by the carotid sinus nerves, the cardia-aortic nerves and the vagi. The central nervous mechanisms are such that changes in the arterial pressure evoke compensatory changes in the dynamics of the circulation. A fall in carotidsinus pressure, for example, evokes peripheral arteriolar constriction, an increase in venous tone and an increase in heart rate. Generalised arteriolar constriction increases total peripheral resistance. An increase in venous tone tends to increase the venous tilling pressure and the stroke volume of the heart. The combined increase in stroke volume and heart rate produces a rise in cardiac output, which, together with the increase in peripheral resistance,restores the original arterial pressur

“It's like you’re actually playing as yourself”: Development and preliminary evaluation of ‘Green Acres High’, a serious game-based primary intervention to combat adolescent dating violence

AbstractThis paper provides an overview of the development of ‘Green Acres High’, a serious game-based primary intervention to raise awareness of and change attitudes towards dating violence in adolescents, and an analysis of how adolescents described their experience of playing this game. Transcripts from focus group data were analysed using thematic analysis. The global theme that was developed, Assessment of the game, was represented by two organising themes, Positive assessment: Pedagogical Underpinnings and Negative Assessment: Functionality Limitations and Frustrations. These represented the fact that overall the learning experience was positive based on the pedagogical principles and content that could be embedded in this digital game but that technical issues with the game needed to be addressed as these could impinge on the learning experience of the adolescents. It was seen that using a serious game was a valid and meaningful way for adolescents to learn about dating violence and that this is a viable alternative or adjunct to traditional teaching methods

Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure

Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure.BackgroundResistance to the action of parathyroid hormone (PTH) has been demonstrated in end-stage renal failure and is considered to be important in the pathogenesis of secondary hyperparathyroidism. The mechanism of resistance is unknown. However, altered regulation of cellular PTH/PTH-related protein (PTH/PTHrP) receptor (PTH1R) has been assumed to be important.MethodsWe have used in situ hybridization to examine PTH1R mRNA expression by osteoblasts in human bone and have compared the expression in high- and low-turnover renal bone disease, high-turnover nonrenal bone disease (healing fracture callus and Pagetic bone), and normal bone. Bone biopsies were formalin fixed, ethylenediaminetetraacetic acid decalcified, and paraffin wax embedded. A 1.8kb PTH1R cDNA probe, labeled with 35S, was used, and the hybridization signal was revealed by autoradiography. The density of signal over osteoblasts was quantitated using a semiautomated Leica™ image analysis software package.ResultsThe mean density of PTH1R mRNA signal over osteoblasts in renal high-turnover bone was only 36% of that found in nonrenal high-turnover bone (P < 0.05) and 51% of that found in normal bone (P < 0.05). Osteoblast PTH1R mRNA signal in adynamic bone from individuals with diabetes mellitus was 28% of normal bone (P < 0.05) and 54% of that found in renal high-turnover bone (P < 0.05).ConclusionsThese results demonstrate a down-regulation of osteoblast PTH1R mRNA in end-stage renal failure in comparison to normal and high-turnover bone from otherwise healthy individuals, and provide an insight into the mechanisms of “skeletal resistance” to the actions of PTH

First large-scale study of antimicrobial susceptibility data, and genetic resistance determinants, in Fusobacterium necrophorum highlighting the importance of continuing focused susceptibility trend surveillance

Objectives: The objective of the study was to explore antimicrobial resistance gene determinant, and phenotypic antibiotic susceptibility, data for Fusobacterium necrophorum from a collection of UK strains. In addition, antimicrobial resistance genes detected in publicly available assembled whole genome sequences were investigated for comparison.Methods: Three hundred and eighty five F. necrophorum strains (1982-2019) were revived from cryovials (Prolab). Subsequent to sequencing (Illumina) and quality checking, 374 whole genomes were available for analysis. These genomes, in addition to publicly available assembled F. necrophorum genetic data, were interrogated using BioNumerics (bioMérieux; v 8.1), for the presence of known antimicrobial resistance genes (ARGs). Agar dilution susceptibility results for 313 F. necrophorum isolates (2016-2021) were also examined.Results: The phenotypic antibiotic test data for the 313 contemporary strains demonstrated potential resistance to penicillin, without increased dosing, in only three isolates. Otherwise, all strains were susceptible to ceftriaxone, clindamycin, co-amoxiclav, meropenem, metronidazole, penicillin and piperacillin/tazobactam, using EUCAST (v 11.0) interpretive guidance. The tet(O), tet(M), tet(40), aph(3’)-III, ant(6)-la and blaOXA-85 ARGs were present in publicly available assembled genomes. tet(M), tet(32), erm(A) and erm(B) were found within the UK strains, with correspondingly raised clindamycin and tetracycline minimum inhibitory concentrations.Conclusions: Current antibiotics recommended for the treatment of infections caused by F. necrophorum, including Lemierre’s disease, are likely to be effective in most cases. However, with evidence of potential ARG transmission from oral bacteria, and the detection of a transposon-mediated beta-lactamase resistance determinant in F. necrophorum, surveillance of both phenotypic and genotypic antimicrobial susceptibility trends must continue, and increase.<br/

Moving beyond physical education subject knowledge to develop knowledgeable teachers of the subject

All knowledge is socially constructed, including physical education teachers’ knowledge of their subject. It is acquired from other people either formally and deliberately (e.g. by being taught) or informally and casually (e.g. by interacting with physical education teachers or playing in a sports team). The social aspects of learning appear to be particularly strong in physical education. This has implications for the development of knowledge for teaching, with trainee teachers focusing on the development of subject, and particularly content, knowledge. Focusing on subject knowledge reinforces a traditional view of physical education as it is, not as it might be to meet the needs of young people today. It is argued that attention needs to be given not only to the knowledge, skills and competencies that trainee teachers ought to develop but also to the social aspects of their learning and development and the context in which they learn. Attention also needs to be given to how the ability to think critically can be developed so that trainee teachers can become reflective practitioners able to challenge and, where appropriate, change the teaching of the subject. Only by doing this can the particularly strong socialisation which shapes the values and beliefs of physical education teachers begin to be challenged. However, as the process of developing knowledgeable teachers is ongoing it is also necessary to look beyond teacher training to continuing professional development

Moving beyond physical education subject knowledge to develop knowledgeable teachers of the subject

All knowledge is socially constructed, including physical education teachers’ knowledge of their subject. It is acquired from other people either formally and deliberately (e.g. by being taught) or informally and casually (e.g. by interacting with physical education teachers or playing in a sports team). The social aspects of learning appear to be particularly strong in physical education. This has implications for the development of knowledge for teaching, with trainee teachers focusing on the development of subject, and particularly content, knowledge. Focusing on subject knowledge reinforces a traditional view of physical education as it is, not as it might be to meet the needs of young people today. It is argued that attention needs to be given not only to the knowledge, skills and competencies that trainee teachers ought to develop but also to the social aspects of their learning and development and the context in which they learn. Attention also needs to be given to how the ability to think critically can be developed so that trainee teachers can become reflective practitioners able to challenge and, where appropriate, change the teaching of the subject. Only by doing this can the particularly strong socialisation which shapes the values and beliefs of physical education teachers begin to be challenged. However, as the process of developing knowledgeable teachers is ongoing it is also necessary to look beyond teacher training to continuing professional development

Res Medica, Autumn 1959, Volume 2, Number 1

TABLE OF CONTENTSSYLLABUS FOR THE 223RD SESSIONHYPOTENSIVE DRUGS: G. E. Mawer, B.ScAN OCULIST LOOKS ATENDOCRINE EXOPHTHALMOS: C. R. S. Jackson.M.A., M.D., D.O.M .S., F.R.C.S.E.RES MEDICA THE TREATMENT OF CANCER: John McKendrick,M.B., Ch.B.DOCTORS AND ARTISTS: Professor W. I. C.Morris, F.R.C.S.E.SOME ASPECTS OFRHEUMATIC FEVER: David J. ClarkABDOMINAL PAIN: Geoffrey T. Millar,M.B., Ch.B.TWO HUNDRED YEARS AGO: James A. Gray, M.B..Ch.B

Validation of the modified Fresno Test: assessing physical therapists' evidence based practice knowledge and skills

<p>Abstract</p> <p>Background</p> <p>Health care educators need valid and reliable tools to assess evidence based practice (EBP) knowledge and skills. Such instruments have yet to be developed for use among physical therapists. The Fresno Test (FT) has been validated only among general practitioners and occupational therapists and does not assess integration of research evidence with patient perspectives and clinical expertise. The purpose of this study was to develop and validate a modified FT to assess EBP knowledge and skills relevant to physical therapist (PT) practice.</p> <p>Methods</p> <p>The FT was modified to include PT-specific content and two new questions to assess integration of patient perspectives and clinical expertise with research evidence. An expert panel reviewed the test for content validity. A cross-sectional cohort representing three training levels (EBP-novice students, EBP-trained students, EBP-expert faculty) completed the test. Two blinded raters, not involved in test development, independently scored each test. Construct validity was assessed through analysis of variance for linear trends among known groups. Inter and intra-rater reliability, internal consistency, item discrimination index, item total correlation, and difficulty were analyzed.</p> <p>Results</p> <p>Among 108 participants (31 EBP-novice students, 50 EBP-trained students, and 27 EBP-expert faculty), there was a statistically significant (p < 0.0001) difference in total score corresponding to training level. Total score reliability and psychometric properties of items modified for discipline-specific content were excellent [inter-rater (ICC (2,1)] = 0.91); intra-rater (ICC (2,1)] = 0.95, 0.96)]. Cronbach's α was 0.78. Of the two new items, only one had strong psychometric properties.</p> <p>Conclusions</p> <p>The 13-item modified FT presented here is a valid, reliable assessment of physical therapists' EBP knowledge and skills. One new item assesses integration of patient perspective as part of the EBP model. Educators and researchers may use the 13-item modified FT to evaluate PT EBP curricula and physical therapists' EBP knowledge and skills.</p