The patient experience of a medical emergency team review: A convergent mixed-methods study.

AIMS: The aim of this study was to explore clinician-patient engagement during, and patient experience of, medical emergency team (MET) reviews. DESIGN: This study involved a convergent mixed-methods design. METHODS: This three-phase study was conducted at two hospitals of one Australian health service. Reviews by the MET were observed for clinician-patient engagement behaviours; medical records were audited to confirm patient demographics and clinical characteristics; and patients who received a MET review were interviewed. Quantitative data were analysed using descriptive statistics, and thematic analysis of qualitative interview data was conducted. RESULTS: In total, 26 MET reviews were observed for 22 patients (median age = 81.5 years and 68.2% females). Between 8 and 13 clinicians and other staff members were present during each review, with a total of 209 clinicians present during the 26 reviews. Clinicians were not observed to speak directly or indirectly to the patient about their care in 38.5% (n = 10/26) of the MET reviews, and 58.3% (n = 56/96) of interventions were performed without explanation. Four themes were identified from the interviews: An unexpected event; A lack of understanding; In good hands, and What happens next? CONCLUSION: Clinician-patient engagement was infrequent during and after MET reviews. Patients experienced surprise from the sudden arrival of clinicians in their room and had poor levels of understanding about the review. However, most patients felt supported and safe. MET reviews are frequent safety-critical events, and this study identified the patient experience of these events. Clinicians should be aware that patients expressed they were surprised and shocked by the review and that an explanation of what was being done by the clinical team was rarely offered. These findings can be used to inform strategies to improve their patient-engagement behaviours and patient-centred care.

Social Isolation and Psychosis: Perspectives from People with Psychosis, Family Caregivers and Mental Health Professionals.

This paper explores the subjective experiences of mental health practitioners, people with psychosis and carers, on social isolation and community integration of people with psychosis. Focus groups and one-to-one interviews with 80 adult participants across three sites in the UK were conducted. Audio recordings were transcribed and analysed using thematic analysis. Participants commented on various aspects that may cause social isolation or enable community integration, including institutional factors (lack of resources, hospitalisation impact), illness symptoms (e.g., paranoia; over-pathologising vs individual choice), stigma (particularly the psychosis label), and the importance of communities that foster agency and embrace change. Hospitalisation maybe be a cause for isolation and psychiatric wards should consider allowing for socialisation as a therapeutic tool. Initiatives should consider the social fabric of our communities, socioeconomic inequalities and stigmatisation. Building communities that are accepting, kind and flexible can create opportunities that could lead to independence from mental health services.

Social transmission of Pavlovian fear: fear-conditioning by-proxy in related female rats.

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing). Individuals can also acquire fear from a social context, such as through observing the fear expression of a conspecific. In the current study, we examined the influence of kinship/familiarity on social transmission of fear in female rats. Rats were housed in triads with either sisters or non-related females. One rat from each cage was fear conditioned to a tone CS+ shock US. On day two, the conditioned rat was returned to the chamber accompanied by one of her cage mates. Both rats were allowed to behave freely, while the tone was played in the absence of the foot-shock. The previously untrained rat is referred to as the fear-conditioned by-proxy (FCbP) animal, as she would freeze based on observations of her cage-mate's response rather than due to direct personal experience with the foot-shock. The third rat served as a cage-mate control. The third day, long-term memory tests to the CS were performed. Consistent with our previous application of this paradigm in male rats (Bruchey et al. in Behav Brain Res 214(1):80-84, 2010), our results revealed that social interactions between the fear conditioned and FCbP rats on day two contribute to freezing displayed by the FCbP rats on day three. In this experiment, prosocial behavior occurring at the termination of the cue on day two was significantly greater between sisters than their non-sister counterparts, and this behavior resulted in increased freezing on day three. Our results suggest that familiarity and/or kinship influences the social transmission of fear in female rats.

Responding to distressed infants: Does mothers' positive versus negative affect matter for infants' behavior and physiology?

How mothers respond to infants' distress has implications for infants' development of self-regulation and social competence. In a sample of 35 mothers and their 4- to 8-month-old infants, we induced infant distress using an arm restraint task and compared infants' observed affect and physiological responses under two conditions, when mothers were instructed to respond with: 1) positive affect and 2) negative affect. Based on theoretical and empirical support, we empirically evaluated two opposing hypotheses. Based on the Mutual Regulation Model and work on affect matching, we predicted that when mothers respond with negative affect versus positive affect, distressed infants' duration of negative affect would be smaller, negative affect would be less intense, and respiratory sinus arrythmia (RSA) withdrawal would be lower. Based on social referencing theory and research, we expected that when mothers respond with positive affect versus negative affect, distressed infants' duration of negative affect would be smaller, negative affect would be less intense, and RSA withdrawal would be lower. We found that when mothers responded to their distressed infants with negative affect versus positive affect, infants spent significantly more time in negative affect, their intensity of expressed negative affect was greater, and their RSA withdrawal was greater, suggesting that mothers' display of mild positive affect when infants are distressed may be helpful for infants. The current findings add to accumulating evidence that mothers' positive relative to negative affective response to their infants' distress can produce observable differences in infants' duration and intensity of negative affect, as well as their physiology. Findings have the potential to inform future research that investigates how mothers can most effectively reduce their infants' distress and intervention that targets the moment-to-moment behaviors in mother-infant reciprocal interactions.

Beneficial network effects of methylene blue in an amnestic model.

Posterior cingulate/retrosplenial cortex (PCC) hypometabolism is a common feature in amnestic mild cognitive impairment and Alzheimer's disease. In rats, PCC hypometabolism induced by mitochondrial dysfunction induces oxidative damage, neurodegeneration and memory deficits. USP methylene blue (MB) is a diaminophenothiazine drug with antioxidant and metabolic-enhancing properties. In rats, MB facilitates memory and prevents neurodegeneration induced by mitochondrial dysfunction. This study tested the memory-enhancing properties of systemic MB in rats that received an infusion of sodium azide, a cytochrome oxidase inhibitor, directly into the PCC. Lesion volumes were estimated with unbiased stereology. MB's network-level mechanism of action was analyzed using graph theory and structural equation modeling based on cytochrome oxidase histochemistry-derived metabolic mapping data. Sodium azide infusions induced PCC hypometabolism and impaired visuospatial memory in a holeboard food-search task. Isolated PCC cytochrome oxidase inhibition disrupted the cingulo-thalamo-hippocampal effective connectivity, decreased the PCC functional networks and created functional redundancy within the thalamus. An intraperitoneal dose of 4 mg/kg MB prevented the memory impairment, reduced the PCC metabolic lesion volume and partially restored the cingulo-thalamo-hippocampal network effects. The effects of MB were dependent upon the local sub-network necessary for memory retrieval. The data support that MB's metabolic-enhancing effects are contingent upon the neural context, and that MB is able to boost coherent and orchestrated adaptations in response to physical alterations to the network involved in visuospatial memory. These results implicate MB as a candidate intervention to improve memory. Because of its neuroprotective properties, MB may have disease-modifying effects in amnestic conditions associated with hypometabolism.

A role for CBFß in maintaining the metastatic phenotype of breast cancer cells.

Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show, using MDA-MB-231 cells as a model, that the plasticity of at least some metastatic breast cancer cells is dependent on the transcriptional co-regulator CBFß. We demonstrate that CBFß is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFß-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells. We subsequently show, using an inducible CBFß system, that the MET can be reversed, thus demonstrating the plasticity of CBFß-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose expression is dependent on CBFß. Finally, we demonstrate that loss of CBFß inhibits the ability of metastatic breast cancer cells to invade bone cell cultures and suppresses their ability to form bone metastases in vivo. Together our findings demonstrate that CBFß can determine the plasticity of the metastatic cancer cell phenotype, suggesting that its regulation in different micro-environments may play a key role in the establishment of metastatic tumours.

Mass survival of birds across the Cretaceous-Tertiary boundary: molecular evidence.

The extent of terrestrial vertebrate extinctions at the end of the Cretaceous is poorly understood, and estimates have ranged from a mass extinction to limited extinctions of specific groups. Molecular and paleontological data demonstrate that modern bird orders started diverging in the Early Cretaceous; at least 22 avian lineages of modern birds cross the Cretaceous-Tertiary boundary. Data for several other terrestrial vertebrate groups indicate a similar pattern of survival and, taken together, favor incremental changes during a Cretaceous diversification of birds and mammals rather than an explosive radiation in the Early Tertiary.

The nature of the last universal common ancestor.

Cytologically, prokaryotes appear simpler and thus evolutionarily 'older' than eukaryotes. In terms of RNA processing, however, prokaryotes are sophisticated and eukaryotes, which retain many features of an RNA-world, appear primitive. The last universal common ancestor may have been mesophilic and could have had many features of the eukaryote genome, but its cytology is unknown.

The brain metabolic enhancer methylene blue improves discrimination learning in rats.

Methylene blue (MB) is a metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of tasks in rats, including inhibitory avoidance, spatial memory (in both normal and metabolically-impaired subjects), object recognition, and habituation to a familiar environment. MB has been also shown to improve memory retention of extinction of fear conditioning in the rat. No experiments have been conducted to determine the effects of MB on more complex learning such as in discrimination tasks that require repeated days of training. This study examined the effects of daily MB on spatial discrimination memory in a baited holeboard maze. Following three days of discrimination training, subjects treated daily with post-training MB (1 mg/kg) reliably discriminated between rewarded (baited) and non-rewarded (unbaited) trials as indicated by a greater number of correct responses on rewarded trials than non-rewarded trials during the last three days of discrimination training. No such discrimination effects were observed in the saline-treated control group during the same training period. To determine whether the memory-enhancing effects of MB are associated with an increase in metabolic energy capacity in the brain, cytochrome c oxidation was measured in brains from rats treated with 1 mg/kg MB or saline for three days. The number of daily injections was chosen based on the behavioral data which revealed group differences three days after the beginning of MB treatment. Brain cytochrome oxidase activity in the MB-treated group was approximately 70% higher than in saline-treated rats. The findings suggest that repeated post-training MB may improve memory consolidation between days of learning by an induction in the enzyme cytochrome oxidase, leading to increased metabolic capacity in brain regions requiring more energy during discrimination learning.

Severe airflow limitation after the unifocalization procedure: clinical and morphological correlates.

BACKGROUND: While unifocalization techniques have improved the treatment options in patients with pulmonary atresia, ventricular septal defect (PA-VSD), and major aortopulmonary collaterals (MAPCAs), severe airflow limitation contributes to significant early postoperative morbidity and mortality. Although this has been attributed to bronchospasm, characteristically it is refractory to bronchodilators, suggesting that other mechanisms may play a role. METHODS AND RESULTS: The clinical course and preoperative angiograms of patients who underwent unifocalization were reviewed. Patients who developed airflow limitation early after surgery underwent fiberoptic bronchoscopy. In addition, the anatomy of the MAPCAs was examined in 14 heart-lung blocks from patients with PA-VSD. Twenty-two procedures were performed in 16 children. Three developed marked airflow limitation early after surgery, necessitating prolonged high-pressure ventilation. Bronchoscopy demonstrated tracheobronchial epithelial necrosis in 2 and signs of tracheobronchial ischemia in the third. Two were successfully extubated after 15 and 16 days, but the third died after 57 days of ventilatory support. Review of the preoperative angiograms demonstrated an extensive peribronchial arterial supply arising from a MAPCA in 1 of the patients who developed severe airway necrosis after unifocalization. This was also obvious in a second patient, but the MAPCA was not included in the unifocalization. In 7 autopsy specimens, MAPCAs contributed to a peribronchial or peritracheal vascular network. Dissection of the distribution of these branches in 2 specimens revealed extensive intrapulmonary peribronchial anastomoses. CONCLUSIONS: Airflow limitation early after unifocalization is related to airway ischemia resulting from interruption of the tracheobronchial blood supply during mobilization of MAPCAs.

Failure of stroke volume augmentation during exercise and dobutamine stress is unrelated to load-independent indexes of right ventricular performance after the Mustard operation.

BACKGROUND: Impaired right ventricular function has been implicated as a cause of reduced maximal exercise capacity after the Mustard operation for transposition of the great arteries. METHODS AND RESULTS: Fourteen asymptomatic survivors of the Mustard operation were studied. Each underwent conventional cardiac catheterization, and after satisfactory hemodynamics were confirmed, load-independent indexes of ventricular function were derived by conductance catheter during dobutamine infusion (0, 5, and 10 microg x kg(-1) x min(-1)). Seven patients also underwent upright exercise testing on a bicycle ergometer with analysis of respiratory gas exchange by continuous mass spectrometry. Accessible pulmonary blood flow was measured at each workload with an automated acetylene rebreathing technique. All patients exercised to a satisfactory end point (respiratory quotient >1.1). Maximum oxygen consumption during exercise was impaired compared with predicted values (mean, 77%; P:<0.02). Both exercise and dobutamine infusion were associated with an increase in cardiac index and heart rate and a reduced stroke volume index response. This was despite significantly improved indexes of myocardial contraction (end-systolic pressure volume relation, P:<0.001), preload recruitable stroke work index (P:<0.01), VA coupling (P:<0.001), and isovolumic relaxation (P:<0.001) during dobutamine infusion. There were no changes observed in end-diastolic pressure-volume relations, but there was failure to augment ventricular filling manifest by absence of change in dV/dt (P:=NS). CONCLUSIONS: The stroke volume response to exercise stress is reduced in patients after the Mustard operation. A similar failure to augment stroke volume occurs during dobutamine stress despite appropriate responses in load-independent indexes of contraction and relaxation. This is due to failure to augment right ventricular filling rates during tachycardia, presumably as a result of impaired AV transport, consequent to the abnormal intra-atrial pathways.

L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery.

BACKGROUND: The increase in pulmonary vascular resistance (PVR) seen in children after cardiopulmonary bypass has been attributed to transient pulmonary endothelial dysfunction (PED). We therefore examined PED in children with congenital heart disease by assessing the L-arginine-nitric oxide (NO) pathway in terms of substrate supplementation (L-arginine [L-Arg]), stimulation of endogenous NO release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery. METHODS AND RESULTS: Ten patients (aged 0.62+/-0.27 years) with pulmonary hypertension undergoing cardiac catheterization who had not had surgery and 10 patients (aged 0.65+/-0.73 years) who had recently undergone cardiopulmonary bypass were examined. All were sedated and paralyzed and received positive-pressure ventilation. Blood samples and pressure measurements were taken from catheters in the pulmonary artery and the pulmonary vein or left atrium. Respiratory mass spectrometry was used to measure oxygen uptake, and cardiac output was determined by the direct Fick method. PVR was calculated during steady state at ventilation with room air, during FIO(2) of 0.65, then during additional intravenous infusion of L-Arg (15 mg. kg(-1). min(-1)) and Sub-P (1 pmol. kg(-1). min(-1)), and finally during inhalation of NO (20 ppm). In preoperative patients, the lack of an additional significant change of PVR with L-Arg, Sub-P, and inhaled NO suggests little preexisting PED. Postoperative PVR was higher, with an additional pulmonary endothelial contribution that was restorable with L-Arg and Sub-P. CONCLUSIONS: Postoperatively, the rise in PVR suggested PED, which was restorable by L-Arg and Sub-P, with no additional effect of inhaled NO. These results may indicate important new treatment strategies for these patients.

Regional ventricular wall motion abnormalities in tricuspid atresia after the Fontan procedure: flawed methodology may lead to a spurious finding of hypokinesia.

We believe that the two-frame method described by Akagi et al. cannot adequately describe the highly abnormal wall motion characteristics of these post-Fontan ventricles, and the systolic hypokinesia they describe may be spurious. Our data show that the predominant abnormality is incoordinate relaxation of the ventricular wall, which in turn prolongs the time constant of relaxation and the isovolumetric relaxation time and leads to reduced early rapid filling. Indeed, it was these abnormalities of diastolic, not systolic, function that were the strongest predictor of poor exercise performance in our study of patients late after the Fontan procedure. We strongly believe that the analysis of ventricular wall motion requires sequential data throughout the cardiac cycle, with well defined reference points concerning the timing of cardiac events, so that misinterpretation can be avoided.

Identification of critical IgG binding epitopes on the neonatal Fc receptor.

The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. FcRn also binds IgG and returns it to the bloodstream, thus protecting IgG from a default degradative pathway. Biosensor assays have been used to characterize the interaction of a soluble form of rat FcRn with IgG, and demonstrate that FcRn dimerization and immobilization are necessary to reproduce in vivo binding characteristics. Here, we report the identification of several FcRn amino acid substitutions that disrupt its affinity for IgG and examine the effect of alteration of residues at the FcRn dimer interface. The role of these amino acids is discussed in the context of the previously reported structures of rat FcRn and a complex of FcRn with the Fc portion of IgG.

Methyl-RNA: an evolutionary bridge between RNA and DNA?

Given the apparent limitation of double-stranded RNA (dsRNA) genomes to about 30 kb, together with the complexity of DNA synthesis, it appears difficult for a dsRNA genome to encode all the information required before the transition from an RNA to a DNA genome. Ribonucleotide reductase itself, which synthesizes deoxyribonucleotides from ribonucleotides, requires complex protein radical chemistry, and RNA world genomes may have reached their limits of coding capacity well before such complex enzymes had evolved. The transition from RNA to DNA thus appears to require intermediate steps, and we suggest that the naturally occurring 2'-O-methylated RNA, with chemical properties intermediate between RNA and DNA, is a suitable candidate.

Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption.

Methylene blue administered post-training improves memory retention in avoidance and appetitive tasks, and restores spatial memory impaired by an inhibitor of cytochrome oxidase. Methylene blue may improve memory retention by increasing brain oxygen utilization. We investigated which doses improve memory without nonspecific behavioral effects, and whether methylene blue enhances brain oxygen consumption. Different doses were evaluated 24 h after administration in wheel running, feeding, open field habituation and object recognition tests. The 1-10 mg/kg methylene blue-treated rats were not different from saline-treated rats in locomotion or feeding behavior. The 50-100 mg/kg doses decreased running wheel behavior. The 4 mg/kg dose improved behavioral habituation and object memory recognition. Dose-dependent effects of methylene blue on brain oxygen consumption revealed that low concentrations increased brain oxygen consumption in vitro and 24 h after in vivo administration. Therefore, methylene blue doses that increase brain oxygen consumption also facilitate memory retention.

Increased aortic blood pressure contributes to potentiated dobutamine inotropic responses after systemic NO synthase inhibition in sheep.

OBJECTIVE: To determine whether inotropic responses to the beta-adrenergic agonist dobutamine are potentiated by systemic inhibition of nitric oxide synthase (NOS) with the L-arginine analogue N omega-nitro-L-arginine (L-NNA), and to establish to what extent any observed responses are related to the increase in aortic blood pressure accompanying systemic NOS inhibition. METHODS: Dobutamine was infused incrementally at rates of 1, 2.5, 5 and 10 micrograms/kg/min in 15 open-chest, anaesthetised ewes before and after inhibition of NO synthesis with i.v. L-NNA (n = 8), or elevation of mean aortic blood pressure to the same extent as attained with NOS inhibition using proximal arterial occlusion (n = 7). RESULTS: By the peak infusion rate, dobutamine increased the maximal rate of rise of left ventricular pressure (LV dP/dtMAX) by 100% (p < 0.001) and reduced LV stroke work by 18% (p < 0.01). L-NNA and arterial occlusion increased resting mean aortic blood pressure by 55 +/- 4 and 51 +/- 3 mmHg respectively. Compared to dobutamine alone, subsequent peak dobutamine-related increases in LV dP/dtMAX were augmented by 76% after L-NNA and by 88% after arterial occlusion (both p < 0.001). Moreover, dobutamine increased LV stroke work by 23% at infusion rates of 1-5 micrograms/kg/min (p < 0.001) after L-NNA, and by 17% at an infusion rate of 1 microgram/kg/min (p < 0.01) after arterial occlusion. CONCLUSIONS: Systemic NOS inhibition potentiates the effects of dobutamine on LV isovolumic and pumping performance in the intact circulation, but this potentiation is in large part related to the increase in arterial blood pressure accompanying NOS inhibition.