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Interprofessional training programs for obstetric emergencies have been introduced for up-skilling birth unit staff in hospitals but not frequently used in training midwives and paramedicine staff for home birth emergency. Practical Obstetric Multiprofessional Training (PROMPT) has previously been described in the home birth setting using in-situ simulation training of home births for midwifery and paramedicine staff. The aim of this study was to evaluate the benefit of the home birth simulation in clinical practice and to explore how the simulation program prepared the midwives for a birth-related emergency in a publicly funded home birth program. Midwives conducting home births, the midwifery educator and the simulated woman in labour (n = 9) attended an interview that explored how the midwives' learning through simulation affected their home birth clinical practice. The simulated woman and the facilitator who conducted the simulation for more than six years were also interviewed to comment on the observed change in performance in simulation. The interview transcripts were thematically analysed. The themes that were identified and agreed upon, were applying learning to clinical practice, learning in teams, valuing realism, facilitating simulation based education and managing variation. In-situ nature of simulation with home birth midwives and paramedical staff facilitated learning transfer and team-based approach to practice. The careful simulation design provided a breadth of experience in emergencies. Applying learning to prepare for clinical emergency situations changed the midwives' approach in managing home births. This provided evidence for a change in behaviour (Level 3 Kirkpatrick's framework) and transfer of learning, leading to changed protocols (Level 4a Kirkpatrick's framework). [ABSTRACT FROM AUTHOR]

Abstract Introduction Non-technical skills (NTS) are fundamental requirements for health professional graduates for safe and competent practice. Technology enhanced simulation, including virtual patients (VPs), is suggested to be effective in developing NTS. Purpose The purpose of this paper is to explore what participants learnt about NTS following interactions with the VPs in the case study. Design Case study methodology was used to explore learning by undergraduate nursing students related to NTS following interactions with VPs. First- (n = 40) and third-year (n = 31) undergraduate nursing students from two universities in Victoria, Australia agreed to participate in focus groups and interviews. These were audio-recorded, transcribed and then underwent framework analysis. A priori codes in the framework used NTS categories including communication, situation awareness, teamwork, decision-making skills, leadership, managing stress and coping with fatigue. Findings Overall, students in both years and universities reported that interactions with VPs developed knowledge and skills across all categories of NTS to varying degrees. Third-year students suggested that interactions with VPs enabled development of knowledge and skills, as well as practise of selected NTS in the clinical setting. Conclusion Interactions with VPs across the curriculum may assist undergraduate nursing students in developing knowledge, skill and practice of NTS categories including communication, situation awareness, teamwork, decision-making skills and duty, advocacy and empathy. [ABSTRACT FROM AUTHOR]

The turnover and metabolism of the individual C apolipoproteins (C-II, C-III1, and C-III2) were studied following the injection of 125I-labeled VLDL into 15 normal and hyperlipoproteinemic subjects. The C apolipoproteins from very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were separated by analytical isoelectric focusing, and subsequent densitometric scanning and radioassay of the stained bands yielded values for specific activity. In 13 of 15 subjects, kinetics of C-II, C-III1, and C-III2 were best described by a one-pool model, whereas two subjects showed biexponential kinetics. The specific activity-time curves for VLDL and HDL were super-imposable, indicating rapid exchange of all C apolipoproteins in hyperlipidemic as well as in normal subjects. In each subject the half-life was similar for C-II, C-III1, and C-III2, which suggests similar synthesis and catabolic mechanisms for each C apolipoprotein. The mass of exchangeable C-II (range 1.0-5.8 mg/kg), C-III1 (2.6-20 mg/kg), and C-III2 (2.0-13 mg/kg) increased with plasma triglyceride concentrations. Values for flux of C-II were 1.0-2.8 mg/d per kg, for C-III1 1.6-5.6 mg/d per kg, and for C-III2 1.2-3.1 mg/d per kg, but they were not related to levels of plasma triglyceride. However the irreversible fractional catabolic rates were inversely related to C apolipoprotein (and triglyceride) mass, suggesting that expansion in C apolipoprotein pool size is related to slower removal, due to the longer residence time of triglyceride-rich VLDL particles in plasma. This was confirmed by similar findings for B apolipoprotein kinetics in VLDL carried out simultaneously.

To determine if plasma lipoproteins interact and therefore possibly regulate intestinal lipoprotein metabolism, we investigated the binding, internalization, and degradation of 125I-labeled low density lipoprotein (LDL) and high density lipoprotein (HDL) by enzyme-dispersed rat intestinal mucosal cells. Both human and rat LDL and HDL were bound, internalized, and degraded in a concentration-dependent manner with calculated half-saturation occurring at approximately 30, 35, 35, and 15 micrograms/ml for human LDL, rat LDL, human HDL, and rat HDL, respectively. Isolated brush border membranes had no saturable or specific binding sites for 125I-labeled HDL or LDL, suggesting that lipoproteins may be bound to receptors on lateral or basal membranes of mucosal cells. Compared with HDL, LDL binding was characterized by a large non-specific component. LDL of human and the rat were not only displaced by excess LDL but at least as effectively by excess HDL of their own species. Labeled HDL was displaced by corresponding unlabeled lipoproteins, but human LDL could produce only minor displacement of human HDL3. ApoE-deficient rat HDL, separated by heparin-Sepharose affinity chromatography also showed highly specific saturable binding to intestinal cells. Thus, apparently two different lipoprotein binding sites exist in intestinal plasma membranes, one recognizing B and/or E apoproteins present in human and rat LDL and rat HDL while another binds human HDL3 and apoE-deficient rat HDL which contain A apoproteins as major components.

The serum cholesterol on ruminant animals rises when supplemental fat is fed in a form that ensures the absorption of long-chain fatty acids. The effects of these fat supplements on cholesterol metabolism have been studied in sheep and goats. The proximal part of the small intestine was the major site of sterol synthesis in sheep. Supplementing the diet with fat significantly enhanced sterolgenesis in the small intestine both in vivo and in vitro, whereas in vitro sterolgenesis appeared to be suppressed in the liver. Increased intestinal sterolgenesis was seen with several varieties of fat, but was greatest when palm oil was fed. The reciprocal findings in the intestine and liver may reflect the increased requirement for cholesterol for the transport of triglyceride in chylomicrons and the secondary inhibiting effect of this cholesterol on sterol synthesis in the liver. Dietary fat supplementation did not alter the excretion of neutral steroids in the feces of goats but did not cause a marked reduction in the excretion of acidic steroids which may have been due to the decreased formation of sterols in the liver. In two lactating goats in which an injection of [14C] cholesterol was followed by daily intraruminal administration of labeled cholesterol, fat supplementation lowered the specific radioactivity of cholesterol in alimentary particles and in milk, being consistent with an increase in intestinally synthesized cholesterol. The hypercholesterolemia that develops in fat-fed ruminants appears to be primarily due to an increased intestinal biosynthesis of cholesterol but may also be partly due to a decreased fecal excretion of bile acids.

There is good evidence that high density lipoprotein (HDL) is involved in the flux of cholesterol into the cells of some organs and out of the cells of other tissues. Because we have previously found that HDL is bound specifically by mucosal cells of the small intestine, we have examined the possibility that this was associated with regulation of cholesterol flux. We have, therefore, compared the specific binding of 125I-labeled HDL3 with cholesterol synthesis in mucosal cells obtained from rats that had been treated to alter intestinal cholesterol metabolism. The rate of sterol synthesis measured in tissue slices, by the incorporation of [3H]water into sterols, was altered up to fivefold by treatment with cholestyramine (to induce bile salt loss), by surformer treatment (to reduce absorption of cholesterol), and by biliary diversion. Yet the capacity of mucosal cells to bind, internalize, and degrade 125I-labeled HDL3 was unchanged. Cholesterol feeding influenced neither the interaction of 125I-labeled HDL3 with cells nor the rate of sterol synthesis. Furthermore, the interactions of 125I-labeled HDL3 with mucosal cells isolated from the proximal and distal halves of the intestine or between the upper and lower villus cells were similar, despite differences in sterol synthesis. These data suggest that, in rat intestine, the specific binding of HDL is not related to sterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect on the plasma cholesterol esters of diets rich in either carbohydrate, chocolate, or safflower oil was studied sequentially in two men. The changes in the cholesterol esters of the major plasma lipoproteins were studied by measuring (a) the distribution of fatty acids in the esters and (b) the distribution of radioactivity among the esters after the administration of cholesterol-4-14C labeled lipoproteins.Similar changes were found in the cholesterol esters of the two major lipoproteins; these changes became apparent within 24 hr after changing diets. Monounsaturated esters predominated with carbohydrate-rich diets. When the chocolate-rich diet was substituted, the proportion of saturated and monounsaturated esters fell and that of cholesteryl linoleate rose. This indicated the utilization of preexisting linoleate in preference to the more saturated fatty acids which abounded in the diet. The substitution of safflower oil led to further increments of cholesteryl linoleate. The possible reasons underlying the preferential incorporation of cholesteryl linoleate in man are discussed.

The formation and transport of hepatic triglyceride fatty acids (TGFA) were studied after intravenous administration of palmitate-1-14C or palmitate-9,10-3H in rabbits pretreated with ethanol or ethionine.Administration of ethanol produced significant hypertriglyceridemia without consistent accumulation of hepatic fat. The isotopic studies suggest that plasma free fatty acids were the major precursors of TGFA in d < 1.006 lipoproteins and that fatty acids synthesized in the liver were not the source of the hypertriglyceridemia in the ethanol-treated animals.Administration of ethionine resulted in an increased concentration of TGFA in the liver, a decreased level of TGFA in d < 1.006 lipoproteins and a very low specific activity in this plasma fraction. These findings suggest that the development of fatty liver after administration of ethionine is in part accompanied by impaired release of TGFA from the liver.

Lymph chylomicrons of widely different fatty acid composition were obtained from donor animals fed either cream and palmitic acid-9,10-H3 or corn oil and linoleic acid-1-C14. The rates of removal of these two types of chylomicrons from the circulation of recipient dogs and rats were determined from the relative rates of removal of the two isotopes and in some cases by changes in the fatty acid composition of the plasma chylomicrons.In intact dogs and rats, the removal of cream chylomicrons was the more rapid. In dogs the H3/C14 ratio in hepatic venous blood was lower than that in femoral venous blood. In livers of rats, there was a greater percentage uptake of radioactivity associated with cream chylomicrons than of that associated with corn oil chylomicrons, but similar amounts were recovered from adipose tissue.When livers of rats were perfused with the two types of chylomicrons, the rate of removal of cream chylomicrons from the perfusate was greater. On the other hand, cream and corn oil chylomicrons were removed in similar amounts when adipose tissue of rats was perfused.

When rat livers were perfused with red cell-albumin solutions containing high concentrations of free fatty acids (FFA), the FFA were very rapidly taken up. Concomitantly, the glyceride content of the liver rose by 25–60% over control values, the absolute increment corresponding roughly to the amount of FFA taken up. The net increase in liver glyceride content was independent of whether palmitate, linoleate, or a combination of the two was used to raise the FFA concentration of the perfusate. The results support the conclusion drawn from earlier in vivo studies that high serum FFA levels can directly contribute to development of fatty liver. When the initial FFA concentration of perfusate was less than l μEq/ml, there was no significant increment in the glyceride content of the perfusate. When the initial FFA concentration of the perfusate was high (2-3 μEq/ml), the glyceride content of the perfusate rose significantly during a 90-min perfusion. The changes in the fatty acid pattern of the glycerides in the liver and in the perfusate indicated that the fatty acid added to the perfusate to raise the FFA concentration to high levels was being preferentially utilized for formation of the new glycerides, but the quantitative effects when perfusing with palmitate alone and linoleate alone differed. Perfusion with palmitate markedly increased the percentage of palmitate in liver glycerides but increased only slightly the percentage of palmitate in the perfusate glycerides. Linoleate had less effect on the fatty acid pattern of the liver glycerides and a greater effect on that of the perfusate glycerides. The differences between the metabolic fates of the two fatty acids are consistent with results of in vivo studies reported previously. Studies of utilization of labeled FFA by liver slices showed that relatively more labeled palmitate was incorporated into glycerides and relatively more linoleate into phospholipids. Incorporation into other lipids and conversion to CO2 were also compared. Livers were perfused with palmitate at low and at high concentration adding palmitate-1-C14 as a tracer. It was shown that high FFA concentrations strongly stimulated conversion to C14O2 and incorporation into glycerides but had a less marked effect on incorporation into phospholipids.

Plasma free fatty acid (FFA) transport in human subjects has been studied during the course of prolonged ingestion of different amounts of glucose. Compared with the fasting state, hypocaloric glucose intake resulted in marked suppression of net transport of FFA with no change in (fractional) turnover rate. There was no further suppression of net transport of FFA when the intake was increased to isocaloric or hypercaloric levels, but there was a significant increase in the (fractional) turnover rate, indicating an enhancement of clearance mechanisms. During the 20–24-hr period of fasting after isocaloric glucose consumption, the (fractional) turnover rate quickly fell to that found in the fasting individual, whereas net transport remained suppressed for much longer. This suggested that ingestion of glucose maintains an influence on lipolysis longer than on esterification. During this period of fasting after glucose administration, the contribution of plasma FFA to circulating triglyceride fatty acids increased with time and was positively and significantly correlated with the changes in the net transport of plasma FFA.

The influence of clofibrate on cholesterol metabolism in patients with hyperlipidemia was studied by means of sterol balance and isotope kinetic techniques and by measurements of flow rates of cholesterol through the biliary tract. Long-term balance studies were carried out on a metabolic ward in 24 patients with all currently recognized types of hyperlipidemia; in five other patients with hypercholesterolemia, pool sizes and turnover rates of cholesterol were defined by compartmental analysis before and after three years' daily administration of the drug.Except in fat-induced hypertriglyceridemia (two patients), clofibrate caused reduced plasma levels of triglycerides and cholesterol in all categories of hyperlipidemia. As a general rule, excretion of cholesterol into bile and feces was significantly increased and fecal bile acid excretion was decreased, regardless of the type of lipoprotein abnormality. Despite a net increase in steroid excretion in most patients with hyperlipidemia, cholesterol synthesis was not increased; indeed, in many patients synthesis appeared to be decreased. While the data obtained in 29 patients were not always consistent, the bulk of the evidence suggests that, in all forms of hyperlipidemia except fat-induced hyperglyceridemia, the drug causes an increased output of cholesterol while simultaneously inhibiting any compensatory increase in cholesterol synthesis. Therefore, it appeared that the increased excretion of steroids was most likely derived from cholesterol stored in tissues. This conclusion was strengthened by finding that long-term administration of the drug can cause marked reduction in body pools of cholesterol.These findings are reflected clinically by resolution of skin and tendon xanthomatosis. However, it is not yet known whether the accumulation of cholesterol in arterial walls that is part of the process of atherogenesis can be inhibited or reversed by the drug.

Increasing body weight appears to alter lipid metabolism in adipose tissue. We have measured the content of lipoprotein lipase and the uptake of chylomicron triglyceride fatty acids in epididymal fat pads of rats of different weights. In order that the results might be expressed in terms of cell numbers, the relationship between the weights of fat pads and the numbers and volumes of fat cells isolated from them was determined.Highly significant correlations were found between fat pad weight and both the number and the volume of the individual adipocytes. In rats weighing from 140 to 350 g, the increase in the size of fat pads was attributable almost equally to increases in cell size and in cell number.Lipoprotein lipase activity was measured in acetone powders of whole fat pads and of isolated fat cell preparations. With both, lipoprotein lipase activity per cell diminished significantly as the weight of fat tissue increased, i.e., larger fat cells contained less enzyme per cell than smaller cells.The uptake of triglyceride fatty acid radioactivity was measured after incubation of fat pads with radiolabeled rat lymph chylomicrons in flasks containing either buffer alone or with added glucose or glucose plus insulin. The addition of glucose and insulin led to a mean increase of 70% in the uptake of radioactivity, but larger adipocytes were stimulated less than smaller cells. This resulted in a significant negative correlation between the weights of fat pads and the uptake of radioactivity. Enlargement of fat cells also led to a diminution in their capacity to esterify fatty acids.

Clinical evidence in oncology argues for the advantages of performing molecular analysis of blood biomarkers to provide information about systemic changes and tumor heterogeneity. Whereas the diagnostic value of cell-free circulating DNA (fcDNA) has successfully been demonstrated in several studies, DNA enclosed in extracellular vesicles (EV) has only recently been described, and its potential diagnostic value is unclear. We established a protocol for separation of EV and fc fractions and tested for presence of mutant BRAFV600E mediating resistance to Vemurafenib and cKITD816V mediating resistance to Imatinib in blood of patients with melanoma and mastocytosis. Our results show that EV contain significantly higher amounts of total DNA as compared to the fc fraction. However, about ten-fold higher copy numbers of the wild type and mutant BRAF and cKIT were detected in the fcDNA fraction supporting its diagnostic value and pointing to differences in fc and EV DNA content. [ABSTRACT FROM AUTHOR]

Background Simulation-based interprofessional education programs can have variable objectives for different participating professional teams. Methods In this study, through a qualitative research design, we report the medical and midwifery students' approach to their learning and attitude towards each other's team, assessed through thematic analysis of independently run focus groups three months after the attendance of the Women's Health Interprofessional Learning Through Simulation program and their respective clinical placements. Results Medical students reported the importance of “learning by doing” through simulation as the key theme. The feedback obtained from midwifery students was focused on “relationship of power” compared with the other discipline. Conclusions Interprofessional learning had a positive influence on the attitude of medical and midwifery students, in spite of the disparity in their background knowledge and experience. IPE competencies are better appreciated at a relatively mature level of clinical practice. Core skills in women's health taught through simulation were found to be helpful by both midwifery and medical students. However, the key learning was about developing respect and a supportive relationship “of equals” with each other. [ABSTRACT FROM AUTHOR]

In cancer, extracellular vesicles (EV) contribute to tumor progression by regulating local and systemic effects. Being released into body fluids, EV may be used in nanomedicine as a valuable source for diagnostic biomarkers. In this work, infrared and Raman spectroscopy were used for comprehensive comparative analysis of cancer versus non-cancer EV and patient screening. Two different EV fractions enriched in exosomes and microvesicles were isolated by differential centrifugation from serum and plasma of cancer and non-cancer patients and from serum and plasma of a healthy donor. The EV fractions were then subjected to drop-coating deposition and drying on calcium fluoride substrates. Reduction of alpha-helix-rich proteins and enhancement of beta-sheet-rich proteins as a cancer-specific blood EV signature was determined, and subsequently this feature was applied for a pilot study aiming to detect prostate cancer in a test cohort of patients with high-grade prostate carcinoma and benign hypoplasia. [ABSTRACT FROM AUTHOR]