Prefrontal-Amygdala Pathways for Object and Social Value Representation.

This special focus article was prepared to honor the memory of our National Institutes of Health colleague, friend, and mentor Leslie G. Ungerleider, who passed away in December 2020, and is based on a presentation given at a symposium held in her honor at the National Institutes of Health in September 2022. In this article, we describe an extension of Leslie Ungerleider's influential work on the object analyzer pathway in which the inferior temporal visual cortex interacts with the amygdala, and then discuss a broader role for the amygdala in stimulus-outcome associative learning in humans and nonhuman primates. We summarize extant data from our and others' laboratories regarding two distinct frontal-amygdala circuits that subserve nonsocial and social valuation processes. Both neuropsychological and neurophysiological data suggest a role for the OFC in nonsocial valuation and the ACC in social valuation. More recent evidence supports the possibility that the amygdala functions in conjunction with these frontal regions to subserve these distinct, complex valuation processes. We emphasize the dynamic nature of valuation processes and advocate for additional research on amygdala-frontal interactions in these domains.

Trends in End-of-Life Care and Satisfaction Among Veterans Undergoing Surgery.

OBJECTIVE: To examine trends in end-of-life care services and satisfaction among Veterans undergoing any inpatient surgery. SUMMARY BACKGROUND DATA: The Veterans Health Administration has undergone system-wide transformations to improve end-of-life care yet the impacts on end-of-life care services use and family satisfaction are unknown. METHODS: We performed a retrospective, cross-sectional analysis of Veterans who died within 90 days of undergoing inpatient surgery between 01/2010 and 12/2019. Using the Veterans Affairs (VA) Bereaved Family Survey (BFS), we calculated the rates of palliative care and hospice use and examined satisfaction with end-of-life care. After risk and reliability adjustment for each VA hospital, we then performed multivariable linear regression model to identify factors associated with the greatest change. RESULTS: Our cohort consisted of 155,250 patients with a mean age of 73.6 years (standard deviation 11.6). Over the study period, rates of palliative care consultation and hospice use increased more than two-fold (28.1% to 61.1% and 18.9% to 46.9%, respectively) while the rate of BFS excellent overall care score increased from 56.1% to 64.7%. There was wide variation between hospitals in the absolute change in rates of palliative care consultation, hospice use and BFS excellent overall care scores. Rural location and ACGME accreditation were hospital-level factors associated with the greatest changes. CONCLUSIONS: Among Veterans undergoing inpatient surgery, improvements in satisfaction with end-of-life care paralleled increases in end-of-life care service use. Future work is needed to identify actionable hospital-level characteristics that may reduce heterogeneity between VA hospitals and facilitate targeted interventions to improve end-of-life care.

Motor System-Dependent Effects of Amygdala and Ventral Striatum Lesions on Explore-Exploit Behaviors.

Deciding whether to forego immediate rewards or explore new opportunities is a key component of flexible behavior and is critical for the survival of the species. Although previous studies have shown that different cortical and subcortical areas, including the amygdala and ventral striatum (VS), are implicated in representing the immediate (exploitative) and future (explorative) value of choices, the effect of the motor system used to make choices has not been examined. Here, we tested male rhesus macaques with amygdala or VS lesions on two versions of a three-arm bandit task where choices were registered with either a saccade or an arm movement. In both tasks we presented the monkeys with explore-exploit tradeoffs by periodically replacing familiar options with novel options that had unknown reward probabilities. We found that monkeys explored more with saccades but showed better learning with arm movements. VS lesions caused the monkeys to be more explorative with arm movements and less explorative with saccades, although this may have been due to an overall decrease in performance. VS lesions affected the monkeys' ability to learn novel stimulus-reward associations in both tasks, while after amygdala lesions this effect was stronger when choices were made with saccades. Further, on average, VS and amygdala lesions reduced the monkeys' ability to choose better options only when choices were made with a saccade. These results show that learning reward value associations to manage explore-exploit behaviors is motor system dependent and they further define the contributions of amygdala and VS to reinforcement learning.

Transplacental infection by bovine alphaherpesvirus type 1 induces protein expression of COX-2, iNOS and inflammatory cytokines in fetal lungs and placentas.

Bovine alphaherpesvirus type 1 (BoAHV-1) is associated with respiratory and reproductive syndromes. Until present the immunologic mechanisms involved in BoAHV-1 abortion are partially known. We studied key elements of the innate immune response in the placentas and fetal lungs from cattle experimentally-inoculated with BoAHV-1. These tissues were analyzed by histopathology. Furthermore, virus identification was performed by qPCR and the expression of the inflammatory cytokines such as tumor necrosis factor-alpha, interleukin 1-alpha and inflammatory mediators like inducible nitric oxide synthase and cyclooxeganse-2 was evaluated by immunohistochemistry. The viral transplacental infection was confirmed by the detection of BoAHV-1 by qPCR in the placenta and fetal organs, which revealed mild inflammatory lesions. Inducible nitric oxide synthase immunolabelling was high in the lungs of infected fetuses and placentas, as well as for tumor necrosis factor-alpha in the pulmonary parenchyma and cyclooxeganse-2 in fetal annexes. However, the expression of interleukin 1-alpha was weak in these organs. To our knowledge, this is the first study that provides strong evidence of an early immune response to BoAHV-1 infection in the conceptus. Advances in the knowledge of the complex immunological interactions at the feto-maternal unit during BoAHV-1 infection are needed to clarify the pathogenesis of abortion.

"It took so much of the humanness away": Health care professional experiences providing care to dying patients during COVID-19.

COVID-19 has affected healthcare in profound and unprecedented ways, distorting the experiences of patients and healthcare professionals (HCPs) alike. One area that has received little attention is how COVID-19 affected HCPs caring for dying patients. The goal of this study was to examine the experiences of HCPs working with dying patients during the COVID-19 pandemic. Between July 2020-July 2021, we recruited HCPs (N = 25) across Canada. We conducted semi-structured interviews, using a qualitative study design rooted in constructivist grounded theory methodology. The core themes identified were the impact of the pandemic on care utilization, the impact of infection control measures on provision of care, moral distress in the workplace, impact on psychological wellbeing, and adaptive strategies to help HCPs manage emotions and navigate pandemic imposed changes. This is the first Canadian study to qualitatively examine the experiences of HCPs providing care to dying patients during the COVID-19 pandemic. Implications include informing supportive strategies and shaping policies for HCPs providing palliative care.

Neuroticism as a moderator of symptom-related distress and depression in 4 noncancer end-of-life populations.

OBJECTIVES: Neuroticism is a significant predictor of adverse psychological outcomes in patients with cancer. Less is known about how this relationship manifests in those with noncancer illness at the end-of-life (EOL). The objective of this study was to examine the impact of neuroticism as a moderator of physical symptoms and development of depression in patients with amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), end-stage renal disease (ESRD), and frailty in the last 6 months of life. METHODS: We met this objective using secondary data collected in the Dignity and Distress across End-of-Life Populations study. The data included N = 404 patients with ALS (N = 101), COPD (N = 100), ESRD (N = 101), and frailty (N = 102) in the estimated last 6 months of life, with a range of illness-related symptoms, assessed longitudinally at 2 time points. We examined neuroticism as a moderator of illness-related symptoms at Time 1 (∼6 months before death) and depression at Time 2 (∼3 months before death) using ordinary least squares regression. RESULTS: Results revealed that neuroticism significantly moderated the relationship between the following symptoms and depression measured 3 months later: drowsiness, fatigue, shortness of breath, wellbeing (ALS); drowsiness, trouble sleeping, will to live, activity (COPD); constipation (ESRD); and weakness and will to live (frailty). SIGNIFICANCE OF RESULTS: These findings suggest that neuroticism represents a vulnerability factor that either attenuates or amplifies the relationship of specific illness and depressive symptoms in these noncancer illness groups at the EOL. Identifying those high in neuroticism may provide insight into patient populations that require special care at the EOL.

Factors Associated With Improved Pediatric Resuscitative Care in General Emergency Departments.

OBJECTIVES: To describe the quality of pediatric resuscitative care in general emergency departments (GEDs) and to determine hospital-level factors associated with higher quality. METHODS: Prospective observational study of resuscitative care provided to 3 in situ simulated patients (infant seizure, infant sepsis, and child cardiac arrest) by interprofessional GED teams. A composite quality score (CQS) was measured and the association of this score with modifiable and nonmodifiable hospital-level factors was explored. RESULTS: A median CQS of 62.8 of 100 (interquartile range 50.5-71.1) was noted for 287 resuscitation teams from 175 emergency departments. In the unadjusted analyses, a higher score was associated with the modifiable factor of an affiliation with a pediatric academic medical center (PAMC) and the nonmodifiable factors of higher pediatric volume and location in the Northeast and Midwest. In the adjusted analyses, a higher CQS was associated with modifiable factors of an affiliation with a PAMC and the designation of both a nurse and physician pediatric emergency care coordinator, and nonmodifiable factors of higher pediatric volume and location in the Northeast and Midwest. A weak correlation was noted between quality and pediatric readiness scores. CONCLUSIONS: A low quality of pediatric resuscitative care, measured using simulation, was noted across a cohort of GEDs. Hospital factors associated with higher quality included: an affiliation with a PAMC, designation of a pediatric emergency care coordinator, higher pediatric volume, and geographic location. A weak correlation was noted between quality and pediatric readiness scores.

Longitudinal home self-collection of capillary blood using homeRNA correlates interferon and innate viral defense pathways with SARS-CoV-2 viral clearance.

Blood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the immune response in dynamic infections (e.g., respiratory viruses). Here we present an at-home self-collection methodology, homeRNA, to study the host transcriptional response during acute SARS-CoV-2 infections. This method uniquely enables high frequency measurement of the host immune kinetics in non-hospitalized adults during the acute and most dynamic stage of their infection. COVID-19+ and healthy participants self-collected blood every other day for two weeks with daily nasal swabs and symptom surveys to track viral load kinetics and symptom burden, respectively. While healthy uninfected participants showed remarkably stable immune kinetics with no significant dynamic genes, COVID-19+ participants, on the contrary, depicted a robust response with over 418 dynamic genes associated with interferon and innate viral defense pathways. When stratified by vaccination status, we detected distinct response signatures between unvaccinated and breakthrough (vaccinated) infection subgroups; unvaccinated individuals portrayed a response repertoire characterized by higher innate antiviral responses, interferon signaling, and cytotoxic lymphocyte responses while breakthrough infections portrayed lower levels of interferon signaling and enhanced early cell-mediated response. Leveraging cross-platform longitudinal sampling (nasal swabs and blood), we observed that IFI27, a key viral response gene, tracked closely with SARS-CoV-2 viral clearance in individual participants. Taken together, these results demonstrate that at-home sampling can capture key host antiviral responses and facilitate frequent longitudinal sampling to detect transient host immune kinetics during dynamic immune states.

"I Wish There had been Resources": A Photo-Elicitation Study of Rectal Cancer Survivorship Care Needs.

BACKGROUND: Rectal cancer survivors experience unique, prolonged posttherapy symptoms. Previous data indicate that providers are not skilled at identifying the most pertinent rectal cancer survivorship issues. Consequently, survivorship care is incomplete with the majority of rectal cancer survivors reporting at least one unmet posttherapy need. METHODS: This photo-elicitation study combines participant-submitted photographs and minimally structured qualitative interviews to explore one's lived experiences. Twenty rectal cancer survivors from a single tertiary canter provided photographs representative of their life after rectal cancer therapy. The iterative steps informed by inductive thematic analysis were used to analyze the transcribed interviews. RESULTS: Rectal cancer survivors had several recommendations to improve their survivorship care, which fell into three major themes: (1) informational needs (e.g., more details about posttherapy side effects); (2) continued multidisciplinary follow up care (e.g., dietary support); and (3) suggestions for support services (e.g., subsidized bowel altering medications and ostomy supplies). CONCLUSIONS: Rectal cancer survivors desired more detailed and individualized information, access to longitudinal multidisciplinary follow-up care, and resources to ease the burdens of daily life. These needs may be met through the restructuring of rectal cancer survivorship care to include disease surveillance, symptom management, and support services. As screening and therapy continues to improve, providers must continue to screen and to provide services that address the physical and psychosocial needs of rectal cancer survivors.

The Inequitable Experiences of Left-Handed Medical Students in Surgical Education.

PURPOSE: Left-handed medical students contend with unique educational barriers within surgery, such as lack of educational resources, lack of left-handed-specific training, and widespread stigmatization of surgical left-handedness. This study aimed to highlight the surgical experiences of left-handed medical students so educators may be empowered to act with greater care and appreciation of these students' circumstances. METHOD: In this qualitative study, the authors conducted semistructured interviews on surgical experiences during medical school between January 31, 2021, and June 20, 2021, on 31 current surgical residents and fellows from 15 U.S. institutions and 6 surgical specialties. Left-handed trainees were included regardless of their surgical hand dominance. RESULTS: The authors identified 3 themes related to left-handed medical students' surgical experience: (1) disorienting advice from faculty or residents, (2) discouraging right-handed pressures and left-handed stigmatization, and (3) educational wishes of left-handed medical students. Trainees describe dialogues during medical school in which their handedness was directly addressed by residents and faculty with disorienting and nonbeneficial advice. Often trainees were explicitly told which hand to use, neglecting any preferences of the left-handed student. Participants also described possible changes in future surgical clerkships, including normalization of left-handedness, tangible mentorship, or granular and meaningful instruction. CONCLUSIONS: Left-handed medical students encounter unique challenges during their surgical education. These students report being disoriented by the variability of advice provided by mentors, discouraged by how pressured they feel to operate right-handed, and burdened by the need to figure things out by themselves in the absence of adequate left-handed educational resources. Surgical education leadership should detail the unique problems left-handed learners face, impartially elicit the learner's current operative hand preference, take responsibility for their left-handed students, promote acceptance and accommodation strategies of left-handed surgical trainees, and endeavor to improve the breadth of left-handed surgical resources.

Use of animals in dental research: Trends and ethical reflections.

This study aimed to survey and analyze the profile of experimental dental research in animals, verifying its trends. We evaluated studies developed with the use of animals in vivo, published in 10 dental journals with high impact factors, from 2015 to 2020. From 1652 studies retrieved, 594 involved in vivo experimentation on animals and were analyzed further. Rats were the species most used and with the highest mean of animals per study. Ferrets, although presenting the lowest rate of publications, had the second highest mean of animals per study. Periodontics was the dental specialty with the highest number of publications, while oral rehabilitation had the lowest number. The data on the institution responsible for reviewing animal research protocols approval, sample size, anesthesia and analgesia were provided in 93.10%, 83%, 70.54% and 23.74% of studies, respectively. In 53% of studies, euthanasia was specified and anesthetic overdose was the method most used. Over the period analyzed, there was a reduction in animal studies in vivo, and periodontics was the specialty that most used this experimental model. Although most studies mentioned approval by an ethics committee, some publications neglected to mention sample size, anesthesia and euthanasia. The omission of essential information may raise scientific and ethical concerns.

Reactivation and Foetal Infection in Pregnant Heifers Infected with Neospora caninum Live Tachyzoites at Prepubertal Age.

Neospora caninum is recognised for causing cattle abortion, provoking severe economic losses in the livestock industry worldwide. The aim of the present study was to evaluate the reactivation and foetal infection in pregnant heifers inoculated with live N. caninum tachyzoites before puberty. A total of 15 30-month-old pregnant heifers were allocated into four groups: animals inoculated with live tachyzoites of NC-Argentina LP1 isolate before puberty and challenged with live tachyzoites of NC-1 strain at 210 days of gestation (DG) (Group A); animals mock inoculated before puberty and challenged with NC-1 strain at 210 DG (Group B), animals inoculated before puberty but not subsequently challenged (Group C); and noninfected and nonchallenged animals (Group D). The results of this study showed that 100% of animals infected before puberty (Groups A and C) suffered reactivation of the infection at the seventh month of gestation. In addition, in three and two calves from Groups A and C, respectively, congenital infection was confirmed. Interestingly, we provide evidence that the use of live N. caninum tachyzoites in young animals as a strategy to induce protection is neither safe nor effective.

Selective prefrontal-amygdala circuit interactions underlie social and nonsocial valuation in rhesus macaques.

Lesion studies in macaques suggest dissociable functions of the orbitofrontal cortex (OFC) and medial frontal cortex (MFC), with OFC being essential for goal-directed decision making and MFC supporting social cognition. Bilateral amygdala damage results in impairments in both of these domains. There are extensive reciprocal connections between these prefrontal areas and the amygdala; however, it is not known whether the dissociable roles of OFC and MFC depend on functional interactions with the amygdala. To test this possibility, we compared the performance of male rhesus macaques (Macaca mulatta) with crossed surgical disconnection of the amygdala and either MFC (MFC x AMY, n=4) or OFC (OFC x AMY, n=4) to a group of unoperated controls (CON, n=5). All monkeys were assessed for their performance on two tasks to measure: (1) food-retrieval latencies while viewing videos of social and nonsocial stimuli in a test of social interest, and (2) object choices based on current food value using reinforcer devaluation in a test of goal-directed decision making. Compared to the CON group, the MFC x AMY group, but not the OFC x AMY group, showed significantly reduced food-retrieval latencies while viewing videos of conspecifics, indicating reduced social valuation and/or interest. By contrast, on the devaluation task, group OFC x AMY, but not group MFC x AMY, displayed deficits on object choices following changes in food value. These data indicate that the MFC and OFC must functionally interact with the amygdala to support normative social and nonsocial valuation, respectively.Significance StatementAscribing value to conspecifics (social) vs. objects (nonsocial) may be supported by distinct but overlapping brain networks. Here we test whether two nonoverlapping regions of the prefrontal cortex, the medial frontal cortex and the orbitofrontal cortex, must causally interact with the amygdala to sustain social valuation and goal-directed decision making, respectively. We found that these prefrontal-amygdala circuits are functionally dissociable, lending support for the idea that medial frontal and orbital frontal cortex make independent contributions to cognitive appraisals of the environment. These data provide a neural framework for distinct value assignment processes and may enhance our understanding of the cognitive deficits observed following brain injury or in the development of mental health disorders.

It's not fine: A photo-elicitation study of rectal cancer survivors' emotions and coping strategies.

BACKGROUND: Comprehensive cancer care includes supporting the psychological health of survivors who are at high risk of distress. However, little is known about the emotional experiences of rectal cancer survivors specifically. We sought to explore psychological well-being and coping strategies utilized by rectal cancer survivors. METHODS: Twenty rectal cancer survivors shared photographs of their post-treatment experiences. In follow-up interviews, participants discussed photographs' meanings and emotional experiences during their cancer journey. Transcribed interviews were analyzed using iterative steps of inductive thematic analysis. RESULTS: Emotions ranged from sadness to anxiety and fear of cancer recurrence. Coping mechanisms were grouped into 3 categories: (1) seeking support and information; (2) focus on attitudes and perspectives; and (3) distancing strategies. CONCLUSION: Our results highlight the persistent psychological impact of rectal cancer and need for additional support for survivors. Providers may help temper patients' fear of recurrence by explicitly discussing prognosis and risk of recurrence. Although multidisciplinary survivorship clinics are ideal, all cancer care providers and primary care physicians should feel empowered to screen for psychological distress and refer patients to appropriate resources when needed.

Incorporating a Trauma-Informed Care Protocol Into Pediatric Trauma Evaluation: The Pediatric PAUSE Does Not Delay Imaging or Disposition.

OBJECTIVES: Trauma evaluation in the emergency department (ED) can be a stressful event for children. With the goal of minimizing pain, anxiety, and unneeded interventions in stable patients, we implemented the Pediatric PAUSE at our level 1 adult/level 2 pediatric trauma center. The Pediatric PAUSE is a brief protocol performed after the primary survey, which addresses Pain/Privacy, Anxiety/IV Access, Urinary Catheter/Rectal exam/Genital exam, Support from family or staff, and Explain to patient/Engage with PICU team. The aim was to assess whether performing the PAUSE interfered with timeliness of emergent imaging in pediatric patients and their disposition. METHODS: We identified all patients aged 0 to 18 years evaluated as trauma activations at our institution after the Pediatric PAUSE was implemented (October 1, 2016-March 31, 2017) as well as 2 analogous 6-month pre-PAUSE periods. Patient demographics, time to imaging studies, and time to ED disposition were analyzed. RESULTS: One hundred seventy-two patients met the study criteria, with a mean age of 10.9 years and mean injury severity score of 10.6. One hundred fifteen participants (68.5%) were transferred from other hospitals, and 101 (87.8%) had ≥1 imaging study performed before arrival. The Pediatric PAUSE was performed for 41 (25%) of 163 study participants. There was no difference in time to first imaging study in participants for whom the PAUSE was performed (18.4 vs 15.0 minutes, P = 0.09). CONCLUSIONS: The PAUSE is a practice intervention designed to address the psychosocial needs of pediatric trauma patients and their families to help prevent posttraumatic stress symptoms. Implementation did not interfere with the timeliness of first imaging in pediatric trauma patients.