The costs, barriers and enablers of providing PGY2 placements in general practice in Aotearoa New Zealand: a mixed-methods study.

Introduction Few mandatory community-based attachments for postgraduate year two doctors (PGY2s) in Aotearoa New Zealand are hosted in general practices, due to space, time and remuneration barriers. Aim This study aimed to explore the costs, barriers and enablers to general practices of hosting PGY2s. Methods A cost analysis for four general practices beginning to host PGY2s was undertaken, including time spent supervising and supporting PGY2s, revenue impact including subsidies and cost of providing clinical space. Interviews with these practices and seven experienced PGY2 host practices were conducted and analysed thematically. Results The estimated mean cost of hosting PGY2s excluding room cost was NZ$4907 per 13-week placement (range $890-$9183), increasing to $13 727 per placement (range $5750-$24 715) when room rental was included. Four themes were identified: working within a small business model; a new learning environment for PGY2s; providing positive experiences for the PGY2s; the relationship between practices and district hospitals that employed the PGY2s, including job sizing. Discussion Tension exists between the small business model of general practice and providing positive experiences for PGY2s in a new learning environment. Guidance and support structures for PGY2 hosting should be developed nationally, and communication and cooperation between practices and employing hospitals needs improvement. Out-of-hours work should be included in community-based attachments so PGY2s' remuneration is consistent. General practice teams are willing to be part of creating a sustainable workforce. However, the time taken to host and costs of providing training in primary care are barriers. There is urgent need to increase funding to general practices for hosting PGY2s.

Faculty Entrustment and Resident Entrustability.

Importance: As the surgical education paradigm transitions to entrustable professional activities, a better understanding of the factors associated with resident entrustability are needed. Previous work has demonstrated intraoperative faculty entrustment to be associated with resident entrustability. However, larger studies are needed to understand if this association is present across various surgical training programs. Objective: To assess intraoperative faculty-resident behaviors and determine if faculty entrustment is associated with resident entrustability across 4 university-based surgical training programs. Design, Setting, and Participants: This cross-sectional study was conducted at 4 university-based surgical training programs from October 2018 to May 2022. OpTrust, a validated tool designed to assess both intraoperative faculty entrustment and resident entrustability behaviors independently, was used to assess faculty-resident interactions. A total of 94 faculty and 129 residents were observed. Purposeful sampling was used to create variation in type of operation performed, case difficulty, faculty-resident pairings, faculty experience, and resident training level. Main Outcomes and Measures: Observed resident entrustability scores (scale 1-4, with 4 indicating full entrustability) were compared with reported measures (faculty level, case difficulty, resident postgraduate year [PGY], resident gender, observation month) and observed faculty entrustment scores (scale 1-4, with 4 indicating full entrustment). Path analysis was used to explore direct and indirect effects of the predictors. Associations between resident entrustability and faculty entrustment scores were assessed by pairwise Pearson correlation coefficients. Results: A total of 338 cases were observed. Cases observed were evenly distributed by faculty experience (1-5 years' experience: 67 [20.9%]; 6-14 years' experience: 186 [58%]; ≥15 years' experience: 67 [20.9%]), resident PGY (PGY 1: 28 [8%]; PGY 2: 74 [22%]; PGY 3: 64 [19%]; PGY 4: 40 [12%]; PGY 5: 97 [29%]; ≥PGY 6: 36 [11%]), and resident gender (female: 183 [54%]; male: 154 [46%]). At the univariate level, PGY (mean [SD] resident entrustability score range, 1.44 [0.46] for PGY 1 to 3.24 [0.65] for PGY 6; F = 38.92; P < .001) and faculty entrustment (2.55 [0.86]; R2 = 0.94; P < .001) were significantly associated with resident entrustablity. Path analysis demonstrated that faculty entrustment was associated with resident entrustability and that the association of PGY with resident entrustability was mediated by faculty entrustment at all 4 institutions. Conclusions and Relevance: Faculty entrustment remained associated with resident entrustability across various surgical training programs. These findings suggest that efforts to develop faculty entrustment behaviors may enhance intraoperative teaching and resident progression by promoting resident entrustability.

Faculty perception of resident promotion and prevention associated behaviors in the operating room to facilitate intra-operative learning.

BACKGROUND: Previous work has demonstrated that residents are able to accurately perceive the intraoperative motivational style of faculty. Additionally, alignment of motivational style between residents and faculty has been demonstrated to enhance resident intraoperative autonomy. This study evaluated if faculty perception of resident behaviors aligned with resident self-perception in order to identify ways of enhancing intraoperative learning. METHODS: General surgery residents were asked to complete a self-assessment evaluating their own intraoperative behaviors. Conversely, faculty rated how strongly the residents exhibited these behaviors in the operating room. RESULTS: Of the 10 intraoperative behaviors that were evaluated, eight demonstrated no correlation between resident self-perception and faculty perception of resident behavior. Similarly, inconsistent correlations emerged when behaviors were assessed according to the self-reported gender and race of the resident. CONCLUSION: Faculty are not able to accurately perceive the motivational style of residents. Strategies to improve faculty perception of resident motivational style may enhance intraoperative learning.

Endothelial to mesenchymal transition in the interleukin-1 pathway during aortic aneurysm formation.

OBJECTIVE: Endothelial to mesenchymal transition may represent a key link between inflammatory stress and endothelial dysfunction seen in aortic aneurysm disease. Endothelial to mesenchymal transition is regulated by interleukin-1ß, and previous work has demonstrated an essential role of interleukin-1 signaling in experimental aortic aneurysm models. We hypothesize that endothelial to mesenchymal transition is present in murine aortic aneurysms, and loss of interleukin-1 signaling attenuates this process. METHODS: Murine aortic aneurysms were created in novel CDH5-Cre lineage tracking mice by treating the intact aorta with peri-adventitial elastase. Endothelial to mesenchymal transition transcription factors as well as endothelial and mesenchymal cell markers were analyzed via immunohistochemistry and immunofluorescence (n = 10/group). To determine the role of interleukin-1 signaling, endothelial-specific interleukin-1 receptor 1 knockout and wild-type mice (n = 10/group) were treated with elastase. Additionally, C57/BL6 mice were treated with the interleukin-1 receptor 1 antagonist Anakinra (n = 7) or vehicle (n = 8). RESULTS: Elastase treatment yielded greater aortic dilation compared with controls (elastase 97.0% ± 34.0%; control 5.3% ± 4.8%; P < .001). Genetic deletion of interleukin-1 receptor 1 attenuated aortic dilation (control 126.7% ± 38.7%; interleukin-1 receptor 1 knockout 35.2% ± 14.7%; P < .001), as did pharmacologic inhibition of interleukin-1 receptor 1 with Anakinra (vehicle 146.3% ± 30.1%; Anakinra 63.5% ± 23.3%; P < .001). Elastase treatment resulted in upregulation of endothelial to mesenchymal transition transcription factors (Snail, Slug, Twist, ZNF) and mesenchymal cell markers (S100, alpha smooth muscle actin) and loss of endothelial cell markers (vascular endothelial cadherin, endothelial nitric oxide synthase, von Willebrand factor). These changes were attenuated by interleukin-1 receptor 1 knockout and Anakinra treatment. CONCLUSIONS: Endothelial to mesenchymal transition occurs in aortic aneurysm disease and is attenuated by loss of interleukin-1 signaling. Endothelial dysfunction through endothelial to mesenchymal transition represents a new and novel pathway in understanding aortic aneurysm disease and may be a potential target for future treatment.

Preoperative passive venous pressure-driven cardiac function determines left ventricular assist device outcomes.

BACKGROUND: Right heart output in heart failure can be compensated through increasing systemic venous pressure. We determined whether the magnitude of this "passive cardiac output" can predict LVAD outcomes. METHODS: This was a retrospective review of 383 patients who received a continuous-flow LVAD at the University of Michigan between 2012 and 2021. Pre-LVAD cardiac output driven by venous pressure was determined by dividing right atrial pressure by mean pulmonary artery pressure, multiplied by total cardiac output. Normalization to body surface area led to the passive cardiac index (PasCI). The Youden J statistic was used to identify the PasCI threshold, which predicted LVAD death by 2 years. RESULTS: Increased preoperative PasCI was associated with reduced survival (hazard ratio [HR], 2.27; P < .01), and increased risk of right ventricular failure (RVF) (HR, 3.46; P = .04). Youden analysis showed that a preoperative PasCI ≥0.5 (n = 226) predicted LVAD death (P = .10). Patients with PasCI ≥0.5 had poorer survival (P = .02), with a trend toward more heart failure readmission days (mean, 45.09 ± 67.64 vs 35.13 ± 45.02 days; P = .084) and increased gastrointestinal bleeding (29.2% vs 20.4%; P = .052). Additionally, of the 97 patients who experienced readmissions for heart failure, those with pre-LVAD implantation PasCI ≥0.5 were more likely to have more than 1 readmission (P = .05). CONCLUSIONS: Although right heart output can be augmented by raising venous pressure, this negatively impacts end-organ function and increases heart failure readmission days. Patients with a pre-LVAD PasCI ≥0.5 have worse post-LVAD survival and increased RVF. Using the PasCI metric in isolation or incorporated into a predictive model may improve the management of LVAD candidates with RV dysfunction.

IL-1 in Abdominal Aortic Aneurysms.

Abdominal Aortic Aneurysms (AAA) remain a clinically devastating disease with no effective medical treatment therapy. AAAs are characterized by immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Interleukin-1 (IL-1) has been shown to play role in AAA associated inflammation through immune cell recruitment and activation, endothelial dysfunction, production of reactive oxygen species (ROS), and regulation of transcription factors of additional inflammatory mediators. In this review, we will discuss the principles of IL-1 signaling, its role in AAA specific inflammation, and regulators of IL-1 signaling. Additionally, we will discuss the influence of genetic and pharmacological inhibitors of IL-1 on experimental AAAs. Evidence suggests that IL-1 may prove to be a potential therapeutic target in the management of AAA disease.

The effects of hippocampal and area parahippocampalis lesions on the processing and retention of serial-order behavior, autoshaping, and spatial behavior in pigeons.

We examined the role of the avian hippocampus and area parahippocampalis in serial-order behavior and a variety of other tasks known to be sensitive to hippocampal damage in mammals. Damage to the hippocampus and area parahippocampalis caused impairments in autoshaping and performance on an analogue of a radial-arm maze task, but had no effect on acquisition of 2-item, 3-item, and 4-item serial-order lists. Additionally, the lesions had no effect on the retention of 3-items lists, or on the ability to perform novel derived lists composed of elements from lists they had previously learned. The impairments in autoshaping and spatial behavior are consistent with the findings in mammals. The absence of impairments on the serial-order task may also be consistent once one considers that damage to the hippocampus in mammals seems to affect more internally-organized rather than externally-organized serial-order tasks. Together, the findings support the view that the avian hippocampal complex serves a function very similar to the mammalian hippocampus, a finding that is interesting given that the architecture of the avian hippocampus differs dramatically from that of the mammalian hippocampus.

A 42-Year-Old Man With Shortness of Breath, Fever, and Pleural Effusions.

CASE PRESENTATION: A 42-year-old man with a history of progressive multiple myeloma and chronic kidney disease presented with worsening shortness of breath and fever. He was scheduled for a planned admission for chemotherapy on the day of presentation and had developed these symptoms the night before. He had also developed worsening fatigue but denied any new cough, sputum production, or abdominal pain. The patient had been previously admitted 3 weeks prior for neutropenic fever and colitis during his first cycle of chemotherapy.

The effects of propranolol and clonidine on bone marrow expression of hematopoietic cytokines following trauma and chronic stress.

BACKGROUND: Attenuating post-injury neuroendocrine stress abrogates persistent injury-associated anemia. Our objective was to examine the mechanisms by which propranolol and clonidine modulate this process. We hypothesized that propranolol and clonidine would decrease bone marrow expression of high-mobility group box-1 (HMGB1) and increase expression of stem cell factor (SCF) and B-cell lymphoma-extra large (Bcl-xL). METHODS: Male Sprague-Dawley rats were allocated to naïve control, lung contusion followed by hemorrhagic shock (LCHS), or LCHS plus daily chronic restraint stress (LCHS/CS) ±propranolol, ±clonidine. Day seven bone marrow expression of HMGB1, SCF, and Bcl-xL was assessed by polymerase chain reaction. RESULTS: Following LCHS, HMGB1 was decreased by propranolol (49% decrease, p = 0.012) and clonidine (54% decrease, p < 0.010). SCF was decreased following LCHS/CS, and was increased by propranolol (629% increase, p < 0.001) and clonidine (468% increase, p < 0.001). Bcl-xL was decreased following LCHS/CS, and was increased by propranolol (59% increase, p = 0.006) and clonidine (77% increase, p < 0.001). CONCLUSIONS: Following severe trauma, propranolol and clonidine abrogate persistent injury-associated anemia by modulating bone marrow cytokines, favoring effective erythropoiesis.

Trans-carotid endovascular repair of ascending aortic pseudoaneurysms.

We present an endovascular technique to repair an ascending aortic pseudoaneurysm in a patient with multiple previous sternotomies using access via the right common carotid artery.

Spared motivational modulation of cognitive effort in a maternal immune activation model of schizophrenia risk.

Maternal immune activation (MIA) during gestation is a significant risk factor for development of schizophrenia and other neurodevelopmental diseases. In animal models of this risk factor, MIA during pregnancy can produce offspring that recapitulate certain aspects of the behavioral and neurophysiological impairments seen in schizophrenia. Here, the authors tested the effect of polyinosinic-polycytidylic acid (poly I:C)-induced MIA in a task that explicitly assays the interaction between motivation and cognition. In our paradigm, discrimination accuracy during a sustained-attention task is differentially impacted by environmental cues that signal the probability of reward for accurate performance. Cognition-motivation interactions are implicated in producing functional impairments in patients. Therefore, to the extent that this MIA model recapitulates such impairments, the authors predicted impaired ability of reward-associated signals to modulate cognitive performance in MIA rat offpsring. Adult offspring of dams in which MIA was induced displayed impaired prepulse inhibition relative to controls, verifying a functional effect of poly I:C induction. Despite this deficit, there were no differences between MIA and control rats in any aspects of task learning or performance, including under extinction and reacquisition conditions. These results indicate that MIA spares functioning of some of the cognitive, motivational, and decision-making processes that are impacted in schizophrenia and suggest that MIA as an isolated manipulation does not model the full range and nuance of the cognitive and motivational impairments in the disease. The authors suggest that some aspects of the functional impairment in schizophrenia and other neurodevelopmental diseases may be better modeled using multiple "hit" models of disease risk. (PsycINFO Database Record

Maternal immune activation in rats produces temporal perception impairments in adult offspring analogous to those observed in schizophrenia.

The neurophysiology underlying temporal perception significantly overlaps with areas of dysfunction identified in schizophrenia. Patients commonly exhibit distorted temporal perception, which likely contributes to functional impairments. Thus, study of temporal perception in animal models of the disease may help to understand both cognitive and neurobiological factors involved in functional impairments in patients. As maternal immune activation (MIA) has been shown to be a significant etiological risk factor in development of schizophrenia and other developmental psychiatric diseases, we tested interval timing in a rat model of MIA that has previously been shown to recapitulate several behavioural and neurophysiological impairments observed in the disease. Rats were tested on a temporal-bisection task, in which temporal duration stimuli were categorized as either "short" or "long" by responding to a corresponding lever. Data from this task were modeled to provide estimates of accuracy and sensitivity of temporal perception. Parameter estimates derived from the model fitting showed that MIA rats significantly overestimated the passage of time compared to controls. These results indicate that the MIA rat paradigm recapitulates timing distortions that are phenotypical of schizophrenia. These findings lend further support to the epidemiological validity of this MIA rat model, supporting its relevance for future research into the role of maternal immune activation in producing neurobiological and behavioural impairments in schizophrenia.

Clonidine restores vascular endothelial growth factor expression and improves tissue repair following severe trauma.

BACKGROUND: We hypothesized that clonidine and propranolol would increase VEGF and VEGF-receptor expression and promote lung healing following severe trauma and chronic stress. METHODS: Sprague-Dawley rats were subjected to lung contusion (LC), lung contusion/hemorrhagic shock (LCHS), or lung contusion/hemorrhagic shock/daily restraint stress (LCHS/CS). Clonidine and propranolol were administered daily. On day seven, lung VEGF, VEGFR-1, VEGFR-2, and HMGB1 were assessed by PCR. Lung injury was assessed by light microscopy (*p < 0.05). RESULTS: Clonidine increased VEGF expression following LCHS (43%*) and LCHS/CS (46%*). Clonidine increased VEGFR-1 and R-2 expression following LCHS/CS (203%* and 47%*, respectively). Clonidine decreased HMGB1 and TNF-alpha expression following LCHS/CS (22%* and 58%*, respectively.) Clonidine decreased inflammatory cell infiltration and total Lung Injury Score following LCHS/CS. Propranolol minimally affected VEGF and did not improve lung healing. CONCLUSIONS: Clonidine increased VEGF and VEGF-receptor expression, decreased HMGB1 expression, decreased lung inflammation, and improved lung tissue repair.

Persistent injury-associated anemia: the role of the bone marrow microenvironment.

BACKGROUND: The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. MATERIALS AND METHODS: Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1ß, interleukin-10, stem cell factor, transforming growth factor-ß, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. RESULTS: Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1ß, interleukin-10, stem cell factor, and transforming growth factor-ß) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). CONCLUSIONS: The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia.

Maternal immune activation alters sensitivity to action-outcome contingency in adult rat offspring.

Epidemiological studies have provided convincing evidence for a role of maternal immune activation in the pathogenesis of neurodevelopmental disorders such as autism and schizophrenia. In recent years, several research groups have capitalised on this discovery and developed animal models such as the maternal immune activation (MIA) model that emulates many phenotypes characteristic of disorders such as schizophrenia. In the present series of experiments we used the MIA model to examine motivation, a core component of the negative symptomatology in schizophrenia. Contrary to what we expected, in the progressive ratio task, which assesses an animals' willingness to work for a reward under increasing effort requirements, we found that MIA rats appeared more motivated than controls. Subsequent tests showed that this seemingly enhanced motivation was not due to an overall increase in responding, nor due to enhanced attribution of incentive salience to reward associated responses. Instead, we found that the increased willingness to work exhibited by MIA animals was due to an inability to detect changes in the contingency between their behaviour and the resulting rewarding outcome. With regard to motivation, the experiments reported here are the first to subject the MIA model to a rigorous experimental analysis of behaviour by parsing underlying processes that give rise to the overt symptoms in psychiatric disease.

Medial orbitofrontal cortex modulates associative learning between environmental cues and reward probability.

It has recently been recognized that orbitofrontal cortex has 2 subdivisions that are anatomically and functionally distinct. Most rodent research has focused on the lateral subdivision, leaving the medial subdivision (mOFC) relatively unexplored. We recently showed that inhibiting mOFC neurons eliminated the differential impact of reward probability cues on discrimination accuracy in a sustained attention task. In the present study, we tested whether increasing mOFC neuronal activity in rats would accelerate acquisition of reward contingencies. mOFC neuronal activity was increased using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) method, in which clozapine-N-oxide administration leads to neuronal modulation by acting on synthetic receptors not normally expressed in the rat brain. We predicted that rats with neuronal activation in mOFC would require fewer sessions than controls for acquisition of a task in which visual cues signal the probability of reward for correct discrimination performance. Contrary to this prediction, mOFC neuronal activation impaired task acquisition, suggesting mOFC may play a role in learning relationships between environmental cues and reward probability or for using that information in adaptive decision-making. In addition, disrupted mOFC activity may contribute to psychiatric conditions in which learning associations between environmental cues and reward probability is impaired. (PsycINFO Database Record