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Traumatic stress, particularly during critical developmental periods such as adolescence, has been strongly linked to an increased propensity and severity of aggression. Existing literature underscores that being a victim of abuse can exacerbate aggressive behaviors, with the amygdala playing a pivotal role in mediating these effects. Historically, animal models have demonstrated that traumatic stressors can increase attack behavior, implicating various amygdala nuclei. Building on this foundation, our previous work has highlighted how traumatic stress invokes long-lasting aggression via an excitatory pathway within the posterior ventral medial amygdala (MeApv). In the current study, we sought to further delineate this mechanism by examining the effects of acute social defeat during adolescence on aggressive behaviors and neural activation in mice. Using a common social defeat paradigm, we first established that acute social defeat during late adolescence indeed promotes long-lasting aggression, measured as attack behavior 7 days after the defeat session. Immunolabeling with c-Fos demonstrated that acute social defeat activates the MeApv and ventrolateral aspect of the ventromedial hypothalamus (VmHvl), consistent with our previous studies that used foot shock as an acute stressor. Finally, chemogenetically inhibiting excitatory MeApv neurons during social defeat significantly mitigated the aggression increase without affecting non-aggressive social behavior. These results strongly suggest that the MeApv plays a critical role in the onset of aggression following traumatic social experience, and offer the MeA as a potential target for therapeutic interventions.

Traumatic stress has been shown to contribute to persistent behavioral changes, yet the underlying neural pathways are not fully explored. Structural plasticity, a form of long-lasting neural adaptability, offers a plausible mechanism. To scrutinize this, we used the mGRASP imaging technique to visualize synaptic modifications in a pathway formed between neurons of the posterior ventral segment of the medial amygdala and ventrolateral segment of the ventromedial hypothalamus (MeApv-VmHvl), areas we previously showed to be involved in stress-induced excessive aggression. We subjected mice (7–8 weeks of age) to acute stress through foot shocks, a reliable and reproducible form of traumatic stress, and compared synaptic changes to control animals. Our data revealed an increase in synapse formation within the MeApv-VmHvl pathway post-stress as evidenced by an increase in mGRASP puncta and area. Chemogenetic inhibition of CaMKIIα-expressing neurons in the MeApv during the stressor led to reduced synapse formation, suggesting that the structural changes were driven by excitatory activity. To elucidate the molecular mechanisms, we administered the NMDAR antagonist MK-801, which effectively blocked the stress-induced synaptic changes. These findings suggest a strong link between traumatic stress and enduring structural changes in an MeApv-VmHvl neural pathway. Furthermore, our data point to NMDAR-dependent mechanisms as key contributors to these synaptic changes. This structural plasticity could offer insights into persistent behavioral consequences of traumatic stress, such as symptoms of PTSD and social deficits.

Highlights Amygdala is proposed as site of action for serotonin drugs ameliorating anxiety. Contrary to this, intra-amygdala infusion of SSRIs did not affect social behavior. Similarly, 5-HT 1A , 5-HT 2A , and 5-HT 3 agonism/antagonism in amygdala had no effect. Thus, serotonin effects on social behavior are likely not modulated by amygdala. Serotonin signaling plays critical roles in social and emotional behaviors. Likewise, decades of research demonstrate that the amygdala is a prime modulator of social behavior. Permanent excitotoxic lesions and transient amygdala inactivation consistently increase social behaviors in non-human primates. In rodents, acute systemic administration of drugs that increase serotonin signaling is associated with decreased social interactions. However, in primates, the direct involvement of serotonin signaling in the amygdala, particularly in affiliative social interaction, remains unexplored. Here, we examined the effects of serotonin manipulations within the amygdala on social behavior in eight pairs of familiar male macaques. We microinfused drugs targeting the serotonin system into either the basolateral (BLA) or central (CeA) amygdala and measured changes in social behavior. Surprisingly, the results demonstrated no significant differences in social behavior following the infusion of a selective serotonin reuptake inhibitor, 5-HT 1A agonist or antagonist, 5-HT 2A agonist or antagonist, or 5-HT 3 agonist or antagonist into either the BLA or CeA. These findings suggest that serotonin signaling in the amygdala does not directly contribute to the regulation of social behavior between familiar conspecifics. Future research should explore alternative mechanisms and potential interactions with other brain regions to gain a comprehensive understanding of the complex neural circuitry governing social behavior.

The amygdala and extended amygdala, which includes the bed nucleus of the stria terminalis (BNST), are two areas implicated in the regulation of social behavior. Lesions of the amygdala in nonhuman primates impact various aspects of social behavior including social dominance, aggression, and affiliative behavior. Studies in rodents have shown that the BNST is involved in various social behaviors including aggression, maternal care, mating behavior, and social interaction. The serotonin system has also been implicated in social behavior. Manipulations of serotonin signaling have been shown to impact a variety of social behaviors including aggression, mating behavior, and social interaction. To examine whether serotonin signaling in the primate amygdala plays a role in social behavior we performed focal microinfusions of various serotonergic drugs and measured social behavior in pairs of familiar macaque monkeys. We hypothesized that amygdala infusion of a selective serotonin reuptake inhibitor (SSRI; fluoxetine), 5-HT1A antagonist, 5-HT2A agonist, or 5-HT3 agonist would decrease social behavior and conversely that administration of a 5-HT1A agonist, 5-HT2A antagonist, or 5-HT3 antagonist would increase social behavior. To our surprise we found no effect of any of the serotonin manipulations on social behavior. These results did not support our overarching hypothesis that serotonin signaling in the amygdala regulates social behavior.To further characterize the involvement of the BNST in social behavior we reversibly inactivated the BNST in rhesus macaques and measured the effect on social behavior in dyads. We found that BNST inactivation significantly increased the duration of social contact in pairs of familiar monkeys. This effect was accompanied by a nonsignificant increase in passive contact, and a significant decrease in locomotion. These findings supported our hypothesis that the BNST is a critical modulator of social behavior. Taken together, these studies provide substantial insight to the neural substrates of social behavior in the primate. Future research should focus on dissociating social behavior from other behaviors (i.e. anxiety), examining the effects of circuit level manipulations, and on outlining subnucleus specific functions of the BNST in primates

Introduction150 Nurses from 8 Higher Education Institutes (HEIs) attend placement at Great Ormond Street Hospital (GOSH) at any one time; many of whom will subsequently take employment here once qualified. Supporting student nurse health and well-being is both encouraged and promoted within the NMC; this underpins our practices and the education delivered by the student team here at GOSH.MethodThe undergraduate team at GOSH plan and deliver weekly educational wellbeing sessions in the form of ‘Wellbeing Wednesdays’. Sessions are tailored to the level of learning the student is at; and are delivered using a variety of teaching methods to ensure learning needs are met.The focus is placed on building resilience; developing emotional intelligence; minimising stress; and building on leadership skills. The team additionally provides pastoral support to raise awareness and empower learners to access help from appropriate services.Our intention is to equip learners with the tools needed to manage their health and wellbeing at an early stage, from training through to qualification.ResultsEvaluation and feedback are anonymised and obtained through multiple diverse methods ensuring the inclusion of different generations and groups. Overall teaching evaluation score May-August 2022 is 4.4/5.Wellbeing teaching evaluates positively, with feedback such as: ‘teaching was delivered in a very sensitive way and it was a comfortable environment to learn in’, ‘very informative, was good to be able to have open conversations about topics and share experiences’, ‘participative’, ‘very engaging’.Discussion and ConclusionThe feedback received, evidences that Undergraduate wellbeing education is valuable and impactful. Our purpose is to strengthen the bridge between Student Nurse and Newly Registered Practitioner; the desirable outcome is that they will develop skills and knowledge to take ownership of their wellbeing. We hope that this can prevent cases of burnout, stress and work-related mental health concerns.Instagram@UndergradGOSH

In this study, childhood cardiovascular risk factors including BMI, systolic blood pressure, lipid levels, and smoking were correlated with cardiovascular events in adulthood after a mean follow-up of 35 years. Childhood risk factors and the change in risk score between childhood and adulthood were associated with midlife cardiovascular events.

Autistic people experience higher risk of suicidal ideation (SI) and suicide attempts (SA) compared to non-autistic people, yet there is limited understanding of complex, multilevel factors that drive this disparity. Further, determinants of mental health service receipt among this population are unknown. This study will identify socioecological factors associated with increased risk of SI and SA for autistic people and evaluate determinants of mental health care receipt. This study will link information for individuals aged 12-64 years in healthcare claims data (IBM® MarketScan® Research Database and CMS Medicaid) to publicly available databases containing community and policy factors, thereby creating a unique, multilevel dataset that includes health, demographic, community, and policy information. Machine learning data reduction methods will be applied to reduce the dimensionality prior to nested, multilevel empirical estimation. These techniques will allow for robust identification of clusters of socioecological factors associated with 1) risk of SI and SA and 2) receipt of mental health services (type, dose, delivery modality). Throughout, the research team will partner with an established group of autistic partners to promote community relevance, as well as receive input and guidance from a council of policy and practice advisors. We hypothesize that nested individual (co-occurring conditions, age, sex), community (healthcare availability, social vulnerabilities), and policy factors (state mental health legislation, state Medicaid expansion) will be associated with heightened risk of SI and SA, and that receipt, dose, and delivery of mental health services will be associated with interdependent factors at all three levels. The approach will lead to identification of multilevel clusters of risk and factors that facilitate or impede mental health service delivery. The study team will then engage the community partners, and policy and practice advisors to inform development of recommendations to reduce risk and improve mental health for the autistic population.

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory.

Two poems are presented.

We introduce two validated single (SH) and dual hormone (DH) mathematical models that represent an in-silico virtual patient population (VPP) for type 1 diabetes (T1D). The VPP can be used to evaluate automated insulin and glucagon delivery algorithms, so-called artificial pancreas (AP) algorithms that are currently being used to help people with T1D better manage their glucose levels. We present validation results comparing these virtual patients with true clinical patients undergoing AP control and demonstrate that the virtual patients behave similarly to people with T1D. A single hormone virtual patient population (SH-VPP) was created that is comprised of eight differential equations that describe insulin kinetics, insulin dynamics and carbohydrate absorption. The parameters in this model that represent insulin sensitivity were statistically sampled from a normal distribution to create a population of virtual patients with different levels of insulin sensitivity. A dual hormone virtual patient population (DH-VPP) extended this SH-VPP by incorporating additional equations to represent glucagon kinetics and glucagon dynamics. The DH-VPP is comprised of thirteen differential equations and a parameter representing glucagon sensitivity, which was statistically sampled from a normal distribution to create virtual patients with different levels of glucagon sensitivity. We evaluated the SH-VPP and DH-VPP on a clinical data set of 20 people with T1D who participated in a 3.5-day outpatient AP study. Twenty virtual patients were matched with the 20 clinical patients by total daily insulin requirements and body weight. The identical meals given during the AP study were given to the virtual patients and the identical AP control algorithm that was used to control the glucose of the virtual patients was used on the clinical patients. We compared percent time in target range (70-180 mg/dL), time in hypoglycemia (<70 mg/dL) and time in hyperglycemia (>180 mg/dL) for both the virtual patients and the actual patients. The subjects in the SH-VPP performed similarly vs. the actual patients (time in range: 78.1 ± 5.1% vs. 74.3 ± 8.1%, p = 0.11; time in hypoglycemia: 3.4 ± 1.3% vs. 2.8 ± 1.7%, p = 0.23). The subjects in the DH-VPP also performed similarly vs. the actual patients (time in range: 75.6 ± 5.5% vs. 71.9 ± 10.9%, p = 0.13; time in hypoglycemia: 0.9 ± 0.8% vs. 1.3 ± 1%, p = 0.19). While the VPPs tended to over-estimate the time in range relative to actual patients, the difference was not statistically significant. We have verified that a SH-VPP and a DH-VPP performed comparably with actual patients undergoing AP control using an identical control algorithm. The SH-VPP and DH-VPP may be used as a simulator for pre-evaluation of T1D control algorithms.