Risk estimation in relation to anxiety and depression for low probability negative events.

Foundational cognitive models propose that people with anxiety and depression show risk estimation bias, but most literature does not compute true risk estimation bias by comparing people's subjective risk estimates to their individualized reality (i.e., person-level objective risk). In a diverse community sample (N = 319), we calculated risk estimation bias by comparing people's subjective risk estimates for contracting COVID-19 to their individualized objective risk. Person-level objective risk was consistently low and did not differ across symptom levels, suggesting that for low probability negative events, people with greater symptoms show risk estimation bias that is driven by subjective risk estimates. Greater levels of anxiety, depression, and COVID-specific perseverative cognition separately predicted higher subjective risk estimates. In a model including COVID-specific perseverative cognition alongside anxiety and depression scores, the only significant predictor of subjective risk estimates was COVID-specific perseverative cognition, indicating that symptoms more closely tied to feared outcomes may more strongly influence risk estimation. Finally, subjective risk estimates predicted information-seeking behavior and eating when anxious, but did not significantly predict alcohol or marijuana use, drinking to cope, or information avoidance. Implications for clinical practitioners and future research are discussed.

Trait and situation-specific intolerance of uncertainty predict affective symptoms during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic, a high-uncertainty situation, presents an ideal opportunity to examine how trait intolerance of uncertainty (IU) and situation-specific IU relate to each other and to mental health outcomes. The current longitudinal study examined the unique associations of trait and COVID-specific IU with general distress (anxiety and depression) and pandemic-specific concerns (pandemic stress and vaccine worry). METHODS: A community sample of Florida adults (N = 2152) was surveyed online at three timepoints. They completed measures of trait IU at Wave 1 (April-May 2020) and COVID-specific IU at Wave 2 (May-June 2020). At Wave 3 (December-February 2021), they reported symptoms of depression, anxiety, pandemic stress, and vaccine worry. RESULTS: We used structural equation modeling to test our overall model. Trait IU significantly predicted later COVID-specific IU, however there was no significant effect of trait IU on any outcome measure after accounting for COVID-specific IU. Notably, COVID-specific IU fully mediated the relationship between trait IU and all four symptom measures. LIMITATIONS: There were several limitations of the current study, including the use of a community sample and high participant attrition. CONCLUSIONS: Results suggest that COVID-specific IU predicts mental health outcomes over and above trait IU, extending the existing literature. These findings indicate that uncertainty may be more aversive when it is related to specific distressing situations, providing guidance for developing more specific and individualized interventions. Idiographic treatments which target situation-specific IU may be more efficacious in reducing affective symptoms and related stress during the COVID-19 pandemic or other similar events.

African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer's Disease Measured by pTau181.

Background: Cognitive and functional abilities in individuals with Alzheimer's disease (AD) pathology (ADP) are highly variable. Factors contributing to this variability are not well understood. Previous research indicates that higher educational attainment (EA) correlates with reduced cognitive impairments among those with ADP. While cognitive and functional impairments are correlated, they are distinguishable in their manifestations. Objective: To investigate whether levels of education are associated with functional impairments among those with ADP. Methods: This research involved 410 African American (AA) individuals (Institutional Review Boards 20070307, 01/27/2023) to ascertain whether EA correlates with functional resilience and if this effect varies between APOE ɛ4 carriers and non-carriers. Utilizing EA as a cognitive reserve proxy, CDR-FUNC as a functional difficulties measure, and blood pTau181 as an ADP proxy, the non-parametric Mann-Whitney U test assessed the relationship between EA and CDR-FUNC in individuals with advanced pTau181 levels. Results: The results showed that EA correlated with functional difficulties in AA individuals with high levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (W = 730.5, p = 0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in ɛ4 non-carriers compared to ɛ4 carriers (W = 555.5, p = 0.022). Conclusion: This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele ɛ4.

Diabetes Care and Mental Health During the COVID-19 Pandemic: Perspectives of Adolescents with Diabetes, Parents, and Providers.

This study explored ways in which the COVID-19 pandemic impacted adolescents' diabetes management and psychosocial functioning, and how adolescents, parents, and providers viewed telemedicine. We present data from three studies: (1) a comparison of psychosocial functioning and glycemic levels before and after pandemic onset (n = 120 adolescents; 89% with type 1 diabetes), (2) an online survey of parents about pandemic-related stressors (n = 141), and (3) qualitative interviews with adolescents, parents, and medical providers about the pandemic's impacts on adolescents' diabetes care and mental health (n = 13 parent-adolescent dyads; 7 medical providers). Results suggested some adverse effects, including disrupting routines related to health behaviors and psychosocial functioning and impairing adolescents' quality of life. Despite these challenges, most participants did not endorse significant impacts. Some even noted benefits, such as increased parental supervision of diabetes management that can be leveraged beyond the pandemic. Furthermore, telemedicine offers benefits to continuity of diabetes care but presents challenges to care quality. These findings underscore the varied and unique impacts of the COVID-19 pandemic on adolescents with diabetes.

Blocking CCN2 Reduces Established Bone Loss Induced by Prolonged Intense Loading by Increasing Osteoblast Activity in Rats.

We have an operant model of reaching and grasping in which detrimental bone remodeling is observed rather than beneficial adaptation when rats perform a high-repetition, high-force (HRHF) task long term. Here, adult female Sprague-Dawley rats performed an intense HRHF task for 18 weeks, which we have shown induces radial trabecular bone osteopenia. One cohort was euthanized at this point (to assay the bone changes post task; HRHF-Untreated). Two other cohorts were placed on 6 weeks of rest while being simultaneously treated with either an anti-CCN2 (FG-3019, 40 mg/kg body weight, ip; twice per week; HRHF-Rest/anti-CCN2), or a control IgG (HRHF-Rest/IgG), with the purpose of determining which might improve the trabecular bone decline. Results were compared with food-restricted control rats (FRC). MicroCT analysis of distal metaphysis of radii showed decreased trabecular bone volume fraction (BV/TV) and thickness in HRHF-Untreated rats compared with FRCs; responses improved with HRHF-Rest/anti-CCN2. Rest/IgG also improved trabecular thickness but not BV/TV. Histomorphometry showed that rest with either treatment improved osteoid volume and task-induced increases in osteoclasts. Only the HRHF-Rest/anti-CCN2 treatment improved osteoblast numbers, osteoid width, mineralization, and bone formation rate compared with HRHF-Untreated rats (as well as the latter three attributes compared with HRHF-Rest/IgG rats). Serum ELISA results were in support, showing increased osteocalcin and decreased CTX-1 in HRHF-Rest/anti-CCN2 rats compared with both HRHF-Untreated and HRHF-Rest/IgG rats. These results are highly encouraging for use of anti-CCN2 for therapeutic treatment of bone loss, such as that induced by chronic overuse. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Psychosocial and health stressors during the COVID-19 pandemic and their association with sleep quality.

OBJECTIVE: We investigated how psychosocial and health stressors and related cognitive-affective factors were differentially associated with sleep quality during the early months of the COVID-19 pandemic. METHODS AND MEASURES: Adults living in Florida (n = 2,152) completed a Qualtrics survey in April-May 2020 (Wave 1). Participants (n = 831) were reassessed one month later (Wave 2; May-June 2020). At Wave 1, participants reported their level of physical contact with someone they care about, presence of a pre-existing chronic disease, employment status, loneliness, health worry, and financial distress. At Wave 2, participants rated their quality of sleep and insomnia symptoms. RESULTS: Loneliness, but not health worry or financial distress, directly predicted worse sleep quality. Lack of physical contact was indirectly associated with worse sleep quality via greater levels of loneliness. Further, results showed the presence of a pre-existing chronic disease was associated with both greater health worry and worse sleep quality. CONCLUSION: Loneliness was the sole cognitive-affective predictor of worse sleep quality when controlling for other psychosocial factors. As expected, adults living with a chronic disease reported impaired sleep quality. Understanding the processes influencing sleep quality during a significant time of stress is important for identifying risk factors, informing treatment, and improving sleep health beyond the pandemic.

The astrocytic Na+ -HCO3 - cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.

The interoceptive homeostatic mechanism that controls breathing, blood gases and acid-base balance in response to changes in CO2 /H+ is exquisitely sensitive, with convergent roles proposed for chemosensory brainstem neurons in the retrotrapezoid nucleus (RTN) and their supporting glial cells. For astrocytes, a central role for NBCe1, a Na+ -HCO3 - cotransporter encoded by Slc4a4, has been envisaged in multiple mechanistic models (i.e. underlying enhanced CO2 -induced local extracellular acidification or purinergic signalling). We tested these NBCe1-centric models by using conditional knockout mice in which Slc4a4 was deleted from astrocytes. In GFAP-Cre;Slc4a4fl/fl mice we found diminished expression of Slc4a4 in RTN astrocytes by comparison to control littermates, and a concomitant reduction in NBCe1-mediated current. Despite disrupted NBCe1 function in RTN-adjacent astrocytes from these conditional knockout mice, CO2 -induced activation of RTN neurons or astrocytes in vitro and in vivo, and CO2 -stimulated breathing, were indistinguishable from NBCe1-intact littermates; hypoxia-stimulated breathing and sighs were likewise unaffected. We obtained a more widespread deletion of NBCe1 in brainstem astrocytes by using tamoxifen-treated Aldh1l1-Cre/ERT2;Slc4a4fl/fl mice. Again, there was no difference in effects of CO2 or hypoxia on breathing or on neuron/astrocyte activation in NBCe1-deleted mice. These data indicate that astrocytic NBCe1 is not required for the respiratory responses to these chemoreceptor stimuli in mice, and that any physiologically relevant astrocytic contributions must involve NBCe1-independent mechanisms. KEY POINTS: The electrogenic NBCe1 transporter is proposed to mediate local astrocytic CO2 /H+ sensing that enables excitatory modulation of nearby retrotrapezoid nucleus (RTN) neurons to support chemosensory control of breathing. We used two different Cre mouse lines for cell-specific and/or temporally regulated deletion of the NBCe1 gene (Slc4a4) in astrocytes to test this hypothesis. In both mouse lines, Slc4a4 was depleted from RTN-associated astrocytes but CO2 -induced Fos expression (i.e. cell activation) in RTN neurons and local astrocytes was intact. Likewise, respiratory chemoreflexes evoked by changes in CO2 or O2 were unaffected by loss of astrocytic Slc4a4. These data do not support the previously proposed role for NBCe1 in respiratory chemosensitivity mediated by astrocytes.

Untargeted, High-Resolution Metabolomics in Pediatric Eosinophilic Esophagitis.

BACKGROUND/OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory disease of unclear etiology. The aim of this study was to use untargeted plasma metabolomics to identify metabolic pathway alterations associated with EoE to better understand the pathophysiology. METHODS: This prospective, case-control study included 72 children, aged 1-17 years, undergoing clinically indicated upper endoscopy (14 diagnosed with EoE and 58 controls). Fasting plasma samples were analyzed for metabolomics by high-resolution dual-chromatography mass spectrometry. Analysis was performed on sex-matched groups at a 2:1 ratio. Significant differences among the plasma metabolite features between children with and without EoE were determined using multivariate regression analysis and were annotated with a network-based algorithm. Subsequent pathway enrichment analysis was performed. RESULTS: Patients with EoE had a higher proportion of atopic disease (85.7% vs 50%, P = 0.019) and any allergies (100% vs 57.1%, P = 0.0005). Analysis of the dual chromatography features resulted in a total of 918 metabolites that differentiated EoE and controls. Glycerophospholipid metabolism was significantly enriched with the greatest number of differentiating metabolites and overall pathway enrichment ( P < 0.01). Multiple amino and fatty acid pathways including linoleic acid were also enriched, as well as pyridoxine metabolism ( P < 0.01). CONCLUSIONS: In this pilot study, we found differences in metabolites involved in glycerophospholipid and inflammation pathways in pediatric patients with EoE using untargeted metabolomics, as well as overlap with amino acid metabolome alterations found in atopic disease.

Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans.

BACKGROUND: This study used admixture mapping to prioritize the genetic regions associated with Alzheimer's disease (AD) in African American (AA) individuals, followed by ancestry-aware regression analysis to fine-map the prioritized regions. METHODS: We analyzed 10,271 individuals from 17 different AA datasets. We performed admixture mapping and meta-analyzed the results. We then used regression analysis, adjusting for local ancestry main effects and interactions with genotype, to refine the regions identified from admixture mapping. Finally, we leveraged in silico annotation and differential gene expression data to prioritize AD-related variants and genes. RESULTS: Admixture mapping identified two genome-wide significant loci on chromosomes 17p13.2 (p = 2.2 × 10-5 ) and 18q21.33 (p = 1.2 × 10-5 ). Our fine mapping of the chromosome 17p13.2 and 18q21.33 regions revealed several interesting genes such as the MINK1, KIF1C, and BCL2. DISCUSSION: Our ancestry-aware regression approach showed that AA individuals have a lower risk of AD if they inherited African ancestry admixture block at the 17p13.2 locus. HIGHLIGHTS: We identified two genome-wide significant admixture mapping signals: on chromosomes 17p13.2 and 18q21.33, which are novel in African American (AA) populations. Our ancestry-aware regression approach showed that AA individuals have a lower risk of Alzheimer's disease (AD) if they inherited African ancestry admixture block at the 17p13.2 locus. We found that the overall proportion of African ancestry does not differ between the cases and controls that suggest African genetic ancestry alone is not likely to explain the AD prevalence difference between AA and non-Hispanic White populations.

The relationship between health worry, work distress, and affective symptoms during the COVID-19 pandemic: The mediating role of hopelessness and helplessness.

OBJECTIVES: The COVID-19 pandemic presented both serious health threats and economic hardships, which were reflected in increased rates of mood and anxiety symptoms. We examined two separate distress domains, health worries and work distress, as predictors of mood and anxiety symptoms. Additionally, we considered whether these two domains might be uniquely associated with the development of dysfunctional beliefs, as a proposed mechanism to account for increased symptoms during the pandemic. Two separate models were considered to examine if associations remained stable through the first year of the pandemic. METHODS: Participants (N = 2152) were a representative sample of Florida adults. They completed online surveys at three waves: Wave 1 (April-May 2020), Wave 2 (May-June 2020), and Wave 3 (December-February 2021). Participants completed measures of COVID-19 health worry and work distress, anxiety, and depression. They also reported their level of hopelessness and helplessness (indices of dysfunctional beliefs). RESULTS: In an early pandemic model (Wave 1-Wave 2), health worry directly and indirectly predicted anxiety and depression via dysfunctional beliefs. In contrast, work distress only indirectly predicted both outcomes. In a longer-term model (Wave 2-Wave 3), health worry had direct and indirect effects on downstream anxiety but not depression. Pandemic work distress had no effect on depression or dysfunctional beliefs; however, it was associated with less anxiety. CONCLUSIONS: Although health worry and work distress predicted later symptoms of anxiety and depression, they appeared to operate through different pathways. These findings provide guidance for the development of more effective interventions to reduce the impact of pandemics.

Central respiratory chemoreception.

Brain PCO2 is sensed primarily via changes in [H+]. Small pH changes are detected in the medulla oblongata and trigger breathing adjustments that help maintain arterial PCO2 constant. Larger perturbations of brain CO2/H+, possibly also sensed elsewhere in the CNS, elicit arousal, dyspnea, and stress, and cause additional breathing modifications. The retrotrapezoid nucleus (RTN), a rostral medullary cluster of glutamatergic neurons identified by coexpression of Phoxb and Nmb transcripts, is the lynchpin of the central respiratory chemoreflex. RTN regulates breathing frequency, inspiratory amplitude, and active expiration. It is exquisitely responsive to acidosis in vivo and maintains breathing autorhythmicity during quiet waking, slow-wave sleep, and anesthesia. The RTN response to [H+] is partly an intrinsic neuronal property mediated by proton sensors TASK-2 and GPR4 and partly a paracrine effect mediated by astrocytes and the vasculature. The RTN also receives myriad excitatory or inhibitory synaptic inputs including from [H+]-responsive neurons (e.g., serotonergic). RTN is silenced by moderate hypoxia. RTN inactivity (periodic or sustained) contributes to periodic breathing and, likely, to central sleep apnea. RTN development relies on transcription factors Egr2, Phox2b, Lbx1, and Atoh1. PHOX2B mutations cause congenital central hypoventilation syndrome; they impair RTN development and consequently the central respiratory chemoreflex.

Impact of the COVID-19 pandemic on American College of Surgeons-Accredited Education Institutes & American Society of Anesthesiologists-Simulation Education Network: Opportunities for interdisciplinary collaboration.

BACKGROUND: The COVID-19 pandemic presented challenges for simulation programs including American College of Surgeons Accredited Education Institutes and American Society of Anesthesiologists Simulation Education Network. American College of Surgeons Accredited Education Institutes and American Society of Anesthesiologists Simulation Education Network leadership were surveyed to identify opportunities to enhance patient safety through simulation. METHODS: Between January and June 2021, surveys consisting of 3 targeted domains: (I) Changing practice; (II) Contributions and recognition; and (III) Moving ahead were distributed to 100 American College of Surgeons Accredited Education Institutes and 54 American Society of Anesthesiologists Simulation Education Network centers. Responses were combined and percent frequencies reported. RESULTS: Ninety-six respondents, representing 51 (51%) American College of Surgeons Accredited Education Institutes, 17 (31.5%) American Society of Anesthesiologists Simulation Education Network, and 28 dually accredited centers, completed the survey. Change of practice. Although 20.3% of centers stayed fully operational at the COVID-19 onset, 82% of all centers closed: 32% were closed less than 3 months, 28% were closed 3 to 6 months, 8% were closed 7 to 9 months, and 32% remained closed as of June 6, 2021. Most impacted activities were large-group instruction and team training. Sixty-nine percent of programs converted in-person to virtual programs. Contributions. The top reported innovative contributions included policies (80%), curricula (80%), and scholarly work (74%), Moving ahead. The respondents' top concerns were returning to high-quality training to best address learners' deficiencies and re-engagement of re-directed training programs. When asked "How the American College of Surgeons/American Society of Anesthesiologists Programs could best assist your simulation center goals?" the top responses were "facilitate collaboration" and "publish best practices from this work." CONCLUSION: The Pandemic presented multiple challenges and opportunities for simulation centers. Opportunities included collaboration between American College of Surgeons Accredited Education Institutes and the American Society of Anesthesiologists Simulation Education Network to identify best practices and resources needed to enhance patient safety through simulation.

American College of Surgeons Objective Assessment of Skills in Surgery (ACS OASIS): A Formative Assessment of Junior Residents' Technical Skills.

OBJECTIVE: The objective assessment of technical skills of junior residents is essential in implementing competency-based training and providing specific feedback regarding areas for improvement. An innovative assessment that can be easily implemented by training programs nationwide has been developed by expert surgeon educators under the aegis of the American College of Surgeons (ACS) Division of Education. This assessment, ACS Objective Assessment of Skills in Surgery (ACS OASIS) uses eight stations to address technical skills important for junior residents within the domains of laparoscopic appendectomy, excision of lipoma, central line placement, laparoscopic cholecystectomy, trocar placement, exploratory laparotomy, repair of enterotomy, and tube thoracostomy. The purpose of this study was to implement ACS OASIS at a number of sites to study its psychometric rigor. DESIGN: The ACS OASIS was pre-piloted at two programs to establish feasibility and to gather information regarding implementation. Each skills station was 12 minutes long, and the faculty completed a checklist with 5 to 15 items, and a global assessment scale. The study was then repeated at three pilot sites and included 29 junior residents who were assessed by a total of 44 faculty. Psychometric data for the stations and checklists were collected and analyzed. SETTING: The pre-pilot sites were Geisinger and University of Tennessee Knoxville.Data were gathered from pilot sites that included Wellspan Health, Duke University, and University of California Los Angeles. RESULTS: The mean checklist score for all learners was 76% (IQR of 66%-85%). The average global rating was 3.36 on a 5-point scale with a standard deviation of 0.56. The overall cut score derived using the borderline group method was at 68% with 34% of performances requiring remediation. Using this criterion, the average number of stations that were completed by each learner without need for remediation was five.The station discrimination index ranged from 0.27 to 0.65 (all above the threshold of 0.25), demonstrating solid psychometric characteristics at the station level. The internal-consistency reliability was 0.76 with SEM of 5.8%. The inter-rater reliability (intraclass correlation) was high at 0.73 with general agreement of 79% between the two raters. The station discrimination was at 0.45 (range of 0.27 to 0.65) indicating a high level of differentiation between high and low performers. Using the generalizability theory, the G-coefficient reliability was at 0.72 with the reliability projection flattening after 8 stations. Overall, 75% to 82% the faculty and learners rated ACS OASIS as realistic and beneficial. CONCLUSIONS: ACS OASIS is a psychometrically sound technical skills assessment tool that can provide useful information for feedback to junior residents and support efforts to remediate gaps in performance.

Psychosocial screening in a pediatric diabetes clinic: Adolescents' and mothers' perspectives.

OBJECTIVE: Adolescents with type 1 diabetes (T1D) frequently experience psychosocial concerns, and mental health screening is becoming increasingly common in routine diabetes care. However, little is known about what adolescents or their caregivers think about the role of mental health screening and intervention within the context of comprehensive diabetes care, or how their diabetes care providers should be involved in navigating mental health concerns. This study used qualitative methods to obtain the perspectives of adolescents with T1D and their caregivers regarding these issues. METHODS: Participants were 13 adolescents with T1D (ages 12-19 years; M = 15.1 years; 53.8% female; 61.5% Hispanic/Latinx White) and 13 mothers, recruited from an outpatient pediatric endocrinology clinic in South Florida, who participated in semi-structured interviews via video teleconference. Thematic content analysis was used to evaluate participants' responses. RESULTS: Adolescents and their mothers reported positive experiences with the clinic's psychosocial screening procedures and appreciated meeting with the psychology team during visits. They wanted the clinic to offer more opportunities for peer support. Mothers highlighted barriers to seeking mental health care outside of the clinic and the importance of mental health professionals understanding diabetes. Mothers also wanted the clinic to offer more on-site therapeutic services. DISCUSSION: Study participants valued psychosocial screening and supported addressing mental health as a routine part of diabetes comprehensive care.

Adrenergic C1 neurons monitor arterial blood pressure and determine the sympathetic response to hemorrhage.

Hemorrhage initially triggers a rise in sympathetic nerve activity (SNA) that maintains blood pressure (BP); however, SNA is suppressed following severe blood loss causing hypotension. We hypothesized that adrenergic C1 neurons in the rostral ventrolateral medulla (C1RVLM) drive the increase in SNA during compensated hemorrhage, and a reduction in C1RVLM contributes to hypotension during decompensated hemorrhage. Using fiber photometry, we demonstrate that C1RVLM activity increases during compensated hemorrhage and falls at the onset of decompensated hemorrhage. Using optogenetics combined with direct recordings of SNA, we show that C1RVLM activation mediates the rise in SNA and contributes to BP stability during compensated hemorrhage, whereas a suppression of C1RVLM activity is associated with cardiovascular collapse during decompensated hemorrhage. Notably, re-activating C1RVLM during decompensated hemorrhage restores BP to normal levels. In conclusion, C1 neurons are a nodal point for the sympathetic response to blood loss.

What are the Top Research Priorities in Surgical Simulation and How Can They Be Best Addressed? Results From a Multidisciplinary Consensus Conference.

OBJECTIVES: To define the top priorities in simulation-based surgical education where additional research would have the highest potential to advance the field and develop proposals that would address the identified research priorities. SUMMARY AND BACKGROUND DATA: Simulation has become integral part of surgical training but there are a number of outstanding questions that have slowed advances in this field. METHODS: The Delphi methodology was used to define the top priorities in simulation-based surgical education. A research summit was held with multiple stakeholders under the auspices of the American College of Surgeons Division of Education to develop proposals to address these priorities. RESULTS: Consensus was achieved after the first round of voting on the following 3 most important topics: (1) impact of simulation training on patient safety and outcomes, (2) the value proposition of simulation, and (3) the use of simulation for physician certification and credentialing. Knowledge gaps, challenges and opportunities, and research questions to address these topics were defined by summit participants. CONCLUSIONS: The top 3 priorities in surgical simulation research were defined and project outlines were developed for impactful projects on these topics. Successful completion of such projects is expected to advance the field of simulation-based surgical education.

Rostral ventrolateral medulla, retropontine region and autonomic regulations.

The rostral half of the ventrolateral medulla (RVLM) and adjacent ventrolateral retropontine region (henceforth RVLMRP) have been divided into various sectors by neuroscientists interested in breathing or autonomic regulations. The RVLMRP regulates respiration, glycemia, vigilance and inflammation, in addition to blood pressure. It contains interoceptors that respond to acidification, hypoxia and intracranial pressure and its rostral end contains the retrotrapezoid nucleus (RTN) which is the main central respiratory chemoreceptor. Acid detection by the RTN is an intrinsic property of the principal neurons that is enhanced by paracrine influences from surrounding astrocytes and CO2-dependent vascular constriction. RTN mediates the hypercapnic ventilatory response via complex projections to the respiratory pattern generator (CPG). The RVLM contributes to autonomic response patterns via differential recruitment of several subtypes of adrenergic (C1) and non-adrenergic neurons that directly innervate sympathetic and parasympathetic preganglionic neurons. The RVLM also innervates many brainstem and hypothalamic nuclei that contribute, albeit less directly, to autonomic responses. All lower brainstem noradrenergic clusters including the locus coeruleus are among these targets. Sympathetic tone to the circulatory system is regulated by subsets of presympathetic RVLM neurons whose activity is continuously restrained by the baroreceptors and modulated by the respiratory CPG. The inhibitory input from baroreceptors and the excitatory input from the respiratory CPG originate from neurons located in or close to the rhythm generating region of the respiratory CPG (preBötzinger complex).