Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.

BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions

Decision for reconstructive interventions of the upper limb in individuals with tetraplegia: the effect of treatment characteristics

Objective: To determine the effect of treatment characteristics on the\ud decision for reconstructive interventions for the upper extremities (UE) in\ud subjects with tetraplegia. - \ud Setting: Seven specialized spinal cord injury centres in the Netherlands. - \ud Method: Treatment characteristics for UE reconstructive interventions were\ud determined. Conjoint analysis (CA) was used to determine the contribution\ud and the relative importance of the treatment characteristics on the decision\ud for therapy. Therefore, a number of different treatment scenarios using these\ud characteristics were established. Different pairs of scenarios were presented\ud to subjects who were asked to choose the preferred scenario of each set. - \ud Results: forty nine subjects with tetraplegia with a stable C5, C6 or C7\ud lesion were selected. All treatment characteristics significantly influenced\ud the choice for treatment. Relative importance of treatment characteristics\ud were: intervention type (surgery or surgery with FES implant) 13%, number\ud of operations 15%, in patient rehabilitation period 22%, ambulant\ud rehabilitation period 9%, complication rate 15%, improvement of elbow\ud function 10%, improvement of hand function 15%. In deciding for therapy\ud 40% of the subjects focused on one characteristic. - \ud Conclusion: CA is applicable in Spinal Cord Injury medicine to study the\ud effect of health outcomes and non-health outcomes on the decision for\ud treatment. Non-health outcomes which relate to the intensity of treatment\ud are equally important or even more important than functional outcome in the\ud decision for reconstructive UE surgery in subjects with tetraplegia

Emerging technologies for the management of Type 1 diabetes in pregnancy

Purpose of Review: The purpose of the study is to discuss emerging technologies available in the management of type 1 diabetes in pregnancy. Recent Findings: The latest evidence suggests that continuous glucose monitoring (CGM) should be offered to all women on intensive insulin therapy in early pregnancy. Studies have additionally demonstrated the ability of CGM to help gain insight into specific glucose profiles as they relate to glycaemic targets and pregnancy outcomes. Despite new studies comparing insulin pump therapy to multiple daily injections, its effectiveness in improving glucose and pregnancy outcomes remains unclear. Sensor-integrated insulin delivery (also called artificial pancreas or closed-loop insulin delivery) in pregnancy has been demonstrated to improve time in target and performs well despite the changing insulin demands of pregnancy. Summary: Emerging technologies show promise in the management of type 1 diabetes in pregnancy; however, research must continue to keep up as technology advances. Further research is needed to clarify the role technology can play in optimising glucose control before and during pregnancy as well as to understand which women are candidates for sensor-integrated insulin delivery

‘Trying to pin down jelly’ - exploring intuitive processes in quality assessment for meta-ethnography

Background: Studies that systematically search for and synthesise qualitative research are becoming more evident in health care, and they can make an important contribution to patient care. However, there is still no agreement as to whether, or how we should appraise studies for inclusion. We aimed to explore the intuitive processes that determined the ‘quality’ of qualitative research for inclusion in qualitative research syntheses. We were particularly interested to explore the way that knowledge was constructed. Methods: We used qualitative methods to explore the process of quality appraisal within a team of seven qualitative researchers funded to undertake a meta-ethnography of chronic non-malignant musculoskeletal pain. Team discussions took place monthly between October 2010 and June 2012 and were recorded and transcribed. Data was coded and organised using constant comparative method. The development of our conceptual analysis was both iterative and collaborative. The strength of this team approach to quality came from open and honest discussion, where team members felt free to agree, disagree, or change their position within the safety of the group. Results: We suggest two core facets of quality for inclusion in meta-ethnography - (1) Conceptual clarity; how clearly has the author articulated a concept that facilitates theoretical insight. (2) Interpretive rigour; fundamentally, can the interpretation ‘be trusted?’ Our findings showed that three important categories help the reader to judge interpretive rigour: (ii) What is the context of the interpretation? (ii) How inductive is the interpretation? (iii) Has the researcher challenged their interpretation? Conclusions: We highlight that methods alone do not determine the quality of research for inclusion into a meta-ethnography. The strength of a concept and its capacity to facilitate theoretical insight is integral to meta-ethnography, and arguably to the quality of research. However, we suggest that to be judged ‘good enough’ there also needs to be some assurance that qualitative findings are more than simply anecdotal. Although our conceptual model was developed specifically for meta-ethnography, it may be transferable to other research methodologies

Detecting the orientation of magnetic fields in galaxy clusters

Clusters of galaxies, filled with hot magnetized plasma, are the largest bound objects in existence and an important touchstone in understanding the formation of structures in our Universe. In such clusters, thermal conduction follows field lines, so magnetic fields strongly shape the cluster's thermal history; that some have not since cooled and collapsed is a mystery. In a seemingly unrelated puzzle, recent observations of Virgo cluster spiral galaxies imply ridges of strong, coherent magnetic fields offset from their centre. Here we demonstrate, using three-dimensional magnetohydrodynamical simulations, that such ridges are easily explained by galaxies sweeping up field lines as they orbit inside the cluster. This magnetic drape is then lit up with cosmic rays from the galaxies' stars, generating coherent polarized emission at the galaxies' leading edges. This immediately presents a technique for probing local orientations and characteristic length scales of cluster magnetic fields. The first application of this technique, mapping the field of the Virgo cluster, gives a startling result: outside a central region, the magnetic field is preferentially oriented radially as predicted by the magnetothermal instability. Our results strongly suggest a mechanism for maintaining some clusters in a 'non-cooling-core' state.Comment: 48 pages, 21 figures, revised version to match published article in Nature Physics, high-resolution version available at http://www.cita.utoronto.ca/~pfrommer/Publications/pfrommer-dursi.pd

Parents' experiences of care offered after stillbirth: An international online survey of high and middle-income countries

BACKGROUND: Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high-income and middle-income countries. METHODS: An online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high-income and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high-income and middle-income countries. RESULTS: Over three thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. Fifteen countries had atleast 40 responses. Significant differences in the prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries (MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR = 4.8, 95% CI 4.0-5.9). The widespread occurrence of all nine practices was reported only for The Netherlands. CONCLUSIONS: Bereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making, and follow-up care

Mitochondrial dysfunction resulting from loss of cytochrome c impairs radiation-induced bystander effect

Cytochrome c is a pivotal protein that resides in mitochondria as component of mitochondria respiration and apoptosis initiator. Using murine cells lacking cytochrome c, we showed here that cytochrome c-deficient cells had attenuated reactive oxygen species/nitric oxide and micronuclei induction to radiation-induced bystander signals, indicating cytochrome c is essential for the bystander effect

Phosphate Energy Metabolism During Domoic Acid-Induced Seizures

The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEC recording and in vivo 31 P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of >30-Hz and of 4–5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electro graphic spikes appeared at increasing frequency, pro gressing to high-amplitude (0.1-0.8 mV) continuous sei zure activity (status epilepticus). In ventilated mice, the [ 31 P]NMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was fol lowed by a marked decrease in EEG amplitude that pro gressed rapidly to isoelectric silence. [ 31 P]NMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was ac companied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 ± 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65953/1/j.1528-1157.1993.tb02124.x.pd

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Team Objective Structured Bedside Assessment (TOSBA) as formative assessment in undergraduate Obstetrics and Gynaecology: a cohort study.

BACKGROUND: Team Objective Structured Bedside Assessment (TOSBA) is a learning approach in which a team of medical students undertake a set of structured clinical tasks with real patients in order to reach a diagnosis and formulate a management plan and receive immediate feedback on their performance from a facilitator. TOSBA was introduced as formative assessment to an 8-week undergraduate teaching programme in Obstetrics and Gynaecology (O\u26G) in 2013/14. Each student completed 5 TOSBA sessions during the rotation. The aim of the study was to evaluate TOSBA as a teaching method to provide formative assessment for medical students during their clinical rotation. The research questions were: Does TOSBA improve clinical, communication and/or reasoning skills? Does TOSBA provide quality feedback? METHODS: A prospective cohort study was conducted over a full academic year (2013/14). The study used 2 methods to evaluate TOSBA as a teaching method to provide formative assessment: (1) an online survey of TOSBA at the end of the rotation and (2) a comparison of the student performance in TOSBA with their performance in the final summative examination. RESULTS: During the 2013/14 academic year, 157 students completed the O\u26G programme and the final summative examination . Each student completed the required 5 TOSBA tasks. The response rate to the student survey was 68 % (n = 107/157). Students reported that TOSBA was a beneficial learning experience with a positive impact on clinical, communication and reasoning skills. Students rated the quality of feedback provided by TOSBA as high. Students identified the observation of the performance and feedback of other students within their TOSBA team as key features. High achieving students performed well in both TOSBA and summative assessments. The majority of students who performed poorly in TOSBA subsequently passed the summative assessments (n = 20/21, 95 %). Conversely, the majority of students who failed the summative assessments had satisfactory scores in TOSBA (n = 6/7, 86 %). CONCLUSIONS: TOSBA has a positive impact on the clinical, communication and reasoning skills of medical students through the provision of high-quality feedback. The use of structured pre-defined tasks, the observation of the performance and feedback of other students and the use of real patients are key elements of TOSBA. Avoiding student complacency and providing accurate feedback from TOSBA are on-going challenges