Immune activation state modulates infant engram expression across development.

Infantile amnesia is possibly the most ubiquitous form of memory loss in mammals. We investigated how memories are stored in the brain throughout development by integrating engram labeling technology with mouse models of infantile amnesia. Here, we found a phenomenon in which male offspring in maternal immune activation models of autism spectrum disorder do not experience infantile amnesia. Maternal immune activation altered engram ensemble size and dendritic spine plasticity. We rescued the same apparently forgotten infantile memories in neurotypical mice by optogenetically reactivating dentate gyrus engram cells labeled during complex experiences in infancy. Furthermore, we permanently reinstated lost infantile memories by artificially updating the memory engram, demonstrating that infantile amnesia is a reversible process. Our findings suggest not only that infantile amnesia is due to a reversible retrieval deficit in engram expression but also that immune activation during development modulates innate, and reversible, forgetting switches that determine whether infantile amnesia will occur.

Navigating the global IV contrast shortage: The experience of a comprehensive cancer center.

PURPOSE/OBJECTIVE(S): In March 2022, a COVID-19 associated lockdown at an intravenous (IV) contrast production facility resulted in global shortages. We report our experience as a comprehensive cancer center navigating the IV contrast shortage. METHODS: A triage prioritization system was developed to serve as a guideline for ordering clinicians to reduce contrast use. The triage team reviewed all requests and made final determination based on patient history, treatment plan, prior imaging, possible alternative modalities, and competing requests. RESULTS: Our institution performed a median of 194 CT studies per day. Contrast utilization as a percentage of all CTs ordered was approximately 80% prior to the shortage, nadired at 9% during peak shortage, and has since returned to pre-shortage levels. Over the study period, 132 requests were reviewed. Fifty studies (38%) were approved by the team for contrast administration, 56 (42%) were recommended to be performed without contrast, 15 (11%) for a change in modality, and 11 (8%) were felt suitable for delay. There was overall general concordance between the recommendations of the triage team and studies conducted without significant distributional differences (χ2 = 4.004, two-tailed p = 0.2610). CONCLUSION: The concept of resilience involves the development of system-based practices that allow for sustained operations during periods of sudden change, or loss of critical supplies. The effort to optimally allocate limited supply of contrast was an extensive effort across the organization including from senior leadership, IT, radiology, nursing, physicians, and APPs. Concepts from heuristics and behavioral science can aid the conservation of a scarce resource. Decisions made by the team appeared to be sound without any known patient harm associated with a lack of contrast.

Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1ß drives amplified responses in primed astrocytes and neuronal network dysfunction.

Neuroinflammation contributes to Alzheimer's disease (AD) progression. Secondary inflammatory insults trigger delirium and can accelerate cognitive decline. Individual cellular contributors to this vulnerability require elucidation. Using APP/PS1 mice and AD brain, we studied secondary inflammatory insults to investigate hypersensitive responses in microglia, astrocytes, neurons, and human brain tissue. The NLRP3 inflammasome was assembled surrounding amyloid beta, and microglia were primed, facilitating exaggerated interleukin-1ß (IL-1ß) responses to subsequent LPS stimulation. Astrocytes were primed to produce exaggerated chemokine responses to intrahippocampal IL-1ß. Systemic LPS triggered microglial IL-1ß, astrocytic chemokines, IL-6, and acute cognitive dysfunction, whereas IL-1ß disrupted hippocampal gamma rhythm, all selectively in APP/PS1 mice. Brains from AD patients with infection showed elevated IL-1ß and IL-6 levels. Therefore, amyloid leaves the brain vulnerable to secondary inflammation at microglial, astrocytic, neuronal, and cognitive levels, and infection amplifies neuroinflammatory cytokine synthesis in humans. Exacerbation of neuroinflammation to produce deleterious outcomes like delirium and accelerated disease progression merits careful investigation in humans.

Characterizing the Patient Experience of CS/HIPEC Through In-Depth Interviews with Patients: Identification of Key Concepts in the Development of a Patient-Centered Program.

INTRODUCTION: The cytoreduction and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) procedure is complex, involving lengthy preparation and recovery in a heterogeneous patient group. Understanding the patient experience is essential to improving interactions with health professionals that is critical to recovery. OBJECTIVE: This study sought to characterize the early recovery and return to quality of life (at 3 and 6-12 months post-surgery, respectively) in patients having undergone CS/HIPEC, through structured interviews. METHODS: Two sets of interviews were conducted among 20 CS/HIPEC patients. Interviews were uploaded into QSR NVivo 10 qualitative software (QSR International, Australia) and coded by two study personnel. Interview 1 focused on initial treatment decision making and postoperative hospitalization, while interview 2 focused on recovery, supports, and return to quality of life. RESULTS: Among the participants, 60% were female and the mean age was 57 years (range 31-71). Diagnoses included disseminated peritoneal adenomucinosis (n = 6), appendiceal adenocarcinoma (n = 4), colorectal adenocarcinoma (n = 6), goblet cell (n = 2), and mesothelioma (n = 2). The first interview identified common themes of perioperative psychosocial isolation, lack of direction, and the importance of an established support system. Patients requested printed and audiovisual materials focused on addressing expectations. The main findings from the second interview captured patient experiences with longer-term complications, as well as surveillance. CONCLUSION: Focused interviews with patients recently having undergone CS/HIPEC identified key issues that may be addressed in programs to improve the patient experience. These issues were distinctly different in relation to phase of recovery, and patient-centered programs designed with these factors in mind have the potential to enhance the recovery process.