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.

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.

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.

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.

Expression of Vesicular Glutamate Transporter 2 (vGluT2) on Large Dense-Core Vesicles within GnRH Neuroterminals of Aging Female Rats.

The pulsatile release of GnRH is crucial for normal reproductive physiology across the life cycle, a process that is regulated by hypothalamic neurotransmitters. GnRH terminals co-express the vesicular glutamate transporter 2 (vGluT2) as a marker of a glutamatergic phenotype. The current study sought to elucidate the relationship between glutamate and GnRH nerve terminals in the median eminence--the site of GnRH release into the portal capillary vasculature. We also determined whether this co-expression may change during reproductive senescence, and if steroid hormones, which affect responsiveness of GnRH neurons to glutamate, may alter the co-expression pattern. Female Sprague-Dawley rats were ovariectomized at young adult, middle-aged and old ages (~4, 11, and 22 months, respectively) and treated four weeks later with sequential vehicle + vehicle (VEH + VEH), estradiol + vehicle (E2 + VEH), or estradiol + progesterone (E2+P4). Rats were perfused 24 hours after the second hormone treatment. Confocal microscopy was used to determine colocalization of GnRH and vGluT2 immunofluorescence in the median eminence. Post-embedding immunogold labeling of GnRH and vGluT2, and a serial electron microscopy (EM) technique were used to determine the cellular interaction between GnRH terminals and glutamate signaling. Confocal analysis showed that GnRH and vGluT2 immunofluorescent puncta were extensively colocalized in the median eminence and that their density declined with age but was unaffected by short-term hormone treatment. EM results showed that vGluT2 immunoreactivity was extensively associated with large dense-core vesicles, suggesting a unique glutamatergic signaling pathway in GnRH terminals. Our results provide novel subcellular information about the intimate relationship between GnRH terminals and glutamate in the median eminence.

Clinical learning experiences of male nursing students in a Bachelor of Nursing programme: Strategies to overcome challenges.

BACKGROUND: Male nursing students are faced with more challenges in the clinical setting than their female counterparts. The ways in which male nurses are viewed and received by nursing staff and patients have an impact on how they perceive themselves and their role in the profession. These perceptions of self have a significant impact on their self-esteem. This study was conducted to explore the clinical learning experiences of male nursing students at a university during their placement in clinical settings in the Western Cape Province, and how these experiences impacted on their self-esteem. OBJECTIVES: To describe the learning experiences of male nursing students during placement in clinical settings, and how these impact on their self-esteem. METHOD: A qualitative, exploratory study was conducted. Purposive sampling was used to select participants. Three focus group (FG) discussions, consisting of six participants per group, were used to collect data. Data analysis was conducted by means of Coliazzi's (1978) seven steps method of qualitative analysis. STUDY FINDINGS: The following three major themes were identified: experiences that related to the constraints in the learning environment, the impact on the self-esteem, and the social support of students working in a female-dominated profession. CONCLUSION: Male nurses should be supported in nursing training, as the rate at which males enter the profession is increasing.

Hypothalamic molecular changes underlying natural reproductive senescence in the female rat.

The role of the hypothalamus in female reproductive senescence is unclear. Here we identified novel molecular neuroendocrine changes during the natural progression from regular reproductive cycles to acyclicity in middle-aged female rats, comparable with the perimenopausal progression in women. Expression of 48 neuroendocrine genes was quantified within three hypothalamic regions: the anteroventral periventricular nucleus, the site of steroid positive feedback onto GnRH neurons; the arcuate nucleus (ARC), the site of negative feedback and pulsatile GnRH release; and the median eminence (ME), the site of GnRH secretion. Surprisingly, the majority of changes occurred in the ARC and ME, with few effects in anteroventral periventricular nucleus. The overall pattern was increased mRNA levels with chronological age and decreases with reproductive cycle status in middle-aged rats. Affected genes included transcription factors (Stat5b, Arnt, Ahr), sex steroid hormone receptors (Esr1, Esr2, Pgr, Ar), steroidogenic enzymes (Sts, Hsd17b8), growth factors (Igf1, Tgfa), and neuropeptides (Kiss1, Tac2, Gnrh1). Bionetwork analysis revealed region-specific correlations between genes and hormones. Immunohistochemical analyses of kisspeptin and estrogen receptor-α in the ARC demonstrated age-related decreases in kisspeptin cell numbers as well as kisspeptin-estrogen receptor-α dual-labeled cells. Taken together, these results identify unexpectedly strong roles for the ME and ARC during reproductive decline and highlight fundamental differences between middle-aged rats with regular cycles and all other groups. Our data provide evidence of decreased excitatory stimulation and altered hormone feedback with aging and suggest novel neuroendocrine pathways that warrant future study. Furthermore, these changes may impact other neuroendocrine systems that undergo functional declines with age.

Lean Six Sigma Applied to Ultrasound Guided Needle Biopsy in the Head and Neck.

OBJECTIVES: (1) Confirm the positive value stream of office-based ultrasound using Lean Six Sigma; (2) demonstrate how ultrasound reduces time to diagnosis, costs, patient inconvenience and travel, exposure to ionizing radiation, intravenous contrast, and laboratory tests. STUDY DESIGN: Case series with historical controls using chart review. SETTING: Tertiary Veterans Administration Hospital (university-affiliated). SUBJECTS AND METHODS: Patients with a consult request or decision for ultrasound guided fine needle aspiration (USFNA) from 2006 to 2012. Process evaluation using Lean Six Sigma methodologies; years study conducted: 2006-2012; outcome measurements: type of diagnostic tests and imaging studies including CT scans with associated radiation exposure, time to preliminary and final cytopathologic diagnosis, episodes of patient travel. RESULTS: Value stream mapping prior to and after implementing office-based ultrasound confirmed the time from consult request or decision for USFNA to completion of the USFNA was reduced from a range of 0 to 286 days requiring a maximum 17 steps to a range of 0 to 48 days, necessitating only a maximum of 9 steps. Office-based USFNA for evaluation of head and neck lesions reduced costs, time to diagnosis, risks and inconvenience to patients, radiation exposure, unnecessary laboratory, and patient complaints while increasing staff satisfaction. In addition, office-based ultrasound also changed the clinical management of specific patients. CONCLUSION: Lean Six Sigma reduces waste and optimizes quality and accuracy in manufacturing. This is the first known application of Lean Six Sigma to office-based USFNA in the evaluation of head and neck lesions. The literature supports the value of office-based ultrasound to patients and health care systems.

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.

The c.7409G>A (p.Cys2470Tyr) Variant of FBN1: Phenotypic Variability across Three Generations.

Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in the fibrillin gene FBN1, which encodes an extracellular matrix glycoprotein. Major features of Marfan syndrome occur in the ocular, cardiovascular, and skeletal systems as well as in the dura mater. Approximately 60% of known disease-causing mutations are missense mutations of single amino acid residues. Effects on the cardiovascular system are classically associated with mutations in exons 24-32 of the 65 FBN1 exons and many, though not all, reports associate missense mutations in exons 59-65 with a mild cardiovascular phenotype. Here we present 5 related individuals among whom a c.7409G>A (p.Cys2470Tyr) missense variant in exon 59 of FBN1 is associated with significant cardiovascular features. The index case also had an apparently de novo 46,XX,del(5)(q33.1q33.3) deletion on chromosome 5. This family demonstrates skeletal, dermatological and neurological features consistent with Marfan syndrome but lacks significant ophthalmological findings to date. These findings suggest that FBN1 C-terminal missense mutations may not confer the ophthalmological features of Marfan syndrome, but they also confer a more significant risk for cardiovascular pathology than that suggested by previous studies. Furthermore, clinical data from this family supports the previously reported association of dural ectasia with C-terminal mutations.

A simple, versatile valve model for use in lumped parameter and one-dimensional cardiovascular models.

Lumped parameter and one-dimensional models of the cardiovascular system generally employ ideal cardiac and/or venous valves that open and close instantaneously. However, under normal or pathological conditions, valves can exhibit complex motions that are mainly determined by the instantaneous difference between upstream and downstream pressures. We present a simple valve model that predicts valve motion on the basis of this pressure difference, and can be used to investigate not only valve pathology, but a wide range of cardiac and vascular factors that are likely to influence valve motion.

Specificity and sensitivity of serum canine pancreatic elastase-1 concentration in the diagnosis of pancreatitis.

The aim of the current study was to determine the sensitivity and specificity of serum canine pancreatic elastase-1 (cPE-1) for the diagnosis of pancreatitis in dogs. The study was prospective, assessing dogs presenting with clinical signs similar to pancreatitis. Sixty-one dogs were recruited (49 with pancreatic disease and 12 with non-pancreatic disease). There was no significant difference in serum cPE-1 between dogs with pancreatic disease and non-pancreatic disease. However, there was a significant difference in serum cPE-1 between severe acute pancreatitis and non-pancreatic disease. A cut-off value for serum cPE-1 > 17.24 ng/ml resulted in sensitivity of 61.4% and specificity of 91.7% for diagnosis of all types of pancreatic disease. The sensitivity rose to 65.85% and 78.26% for the diagnosis of all types of acute pancreatitis and severe acute pancreatitis, respectively. Serum cPE-1 is more sensitive at diagnosing severe acute pancreatitis than chronic or mild acute pancreatitis, and has a high positive likelihood ratio. Dogs with chronic pancreatitis tended to have lower serum cPE-1 concentration, suggesting decreased exocrine function.

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.

Changes in resting energy expenditure in children with congenital heart disease.

OBJECTIVES: The aim of this study was to relate changes in energy expenditure and growth in infants with congenital heart disease (CHD), to the timing of corrective cardiac surgery. METHODS: Prospective cohort study of infants less than 1 year with CHD admitted for cardiac surgery to Royal Children's Hospital, between January to September 2005. Infants were assessed using anthropometry and indirect calorimetry and compared to healthy age-matched controls. RESULTS: Infants (38) underwent corrective (n=25) or palliative (n=13) cardiac surgery either at < or = 10 days or at >10 days. Infants undergoing corrective surgery after 10 days had deficits in z-scores for weight compared with infants undergoing early surgery (-1.15+/-1.02 vs -0.24+/-0.98; CI 95%: -1.736 to -0.085; P<0.05) and height (-1.47+/-1.16 vs -0.12+/-0.66; CI 95%: -2.262 to -0.428; P<0.01). However, 6 months following surgery, weight and height were similar in both groups. Resting energy expenditure was increased before surgery compared to healthy controls (247+/-36 vs 210+/-22 kJ kg(-1 )day(-1); 95% CI: -57.29 to -16.71; P<0.001) however, normalized 1 week following cardiac surgery. Standard equations did not accurately predict measured REE. CONCLUSION: Increased REE observed in infants with CHD normalizes within 1 week following corrective cardiac surgery. Deficits in weight and growth were greater in infants undergoing corrective cardiac surgery>10 days of age compared with infants undergoing surgery in the first 10 days of life.

Population-based study of antenatal detection of congenital heart disease by ultrasound examination.

OBJECTIVES: Ultrasound-based screening is widely employed for the detection of congenital malformations in utero including congenital heart disease (CHD), but there is widespread variability in the efficacy of screening programs. We aimed to evaluate current antenatal detection rates of selected congenital heart defects in Victoria. METHODS: Data were collected from the Victorian Perinatal Data Collection Unit and Birth Defects Registry. There were 631 209 births in Victoria (1993-2002), of which 4897 cases had CHD. Cases included live births, stillbirths and termination of pregnancies because of CHD. We reviewed all cases from 1999 to 2002 with atrioventricular septal defect, simple coarctation of the aorta, double-inlet or -outlet ventricle, hypoplastic left heart syndrome, simple transposition of the great arteries (TGA), tetralogy of Fallot and truncus arteriosus. Outcome measures were antenatal diagnosis, pregnancy outcome and associated malformations. RESULTS: The overall birth prevalence of CHD from 1993 to 2002 in Victoria was 7.8/1000. The antenatal detection rate for the seven selected defects from 1999 to 2002 was 52.8%. All but 4.8% of the cases had an ultrasound examination at > 13 weeks' gestation. Antenatal detection was highest for hypoplastic left heart syndrome (84.6%) and lowest for simple TGA (17.0%). CONCLUSIONS: This study shows wide variation in the antenatal detection rate of CHD in Victoria. The low antenatal detection rate of TGA, a defect that should be detected easily, demonstrates suboptimal routine obstetric anomaly scanning.

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.

SigM-responsive genes of Bacillus subtilis and their promoters.

Promoters of nine Bacillus subtilis genes (bcrC, yacK, ydaH, yfnI, yjbD, ypbG, ypuA, yraA, and ysxA), all responsive to artificially induced increases in the stress-responsive extracytoplasmic function sigma factor, SigM, were mapped by rapid amplification of cDNA ends-PCR. The resulting promoter consensus suggests that overlapping control by SigX or SigW is common.