Impact of Psychiatry Clerkship Rotation in Attitudes Towards Mental Illness and Psychiatry as a Career Among Medical Students.

Background: Stigma associated with mental illness (MI) permeates many professions, including healthcare. Recognizing and correcting bias is critical in delivering impartial and beneficial healthcare for all patients. Early educational interventions providing exposure to individuals with MI have shown to be effective at reducing MI stigma. The primary aim of our study was to assess the impact of a psychiatry clerkship on attitudes to MI. A secondary aim was to determine if the psychiatry clerkship influenced medical students' perceptions of psychiatry as a career. Methods: A cohort of third-year medical students in Florida was invited to complete an online survey before and after participating in their first 4-week-long psychiatry clerkship during the 2021-2022 academic year. The voluntary, anonymous survey consisted of the Attitudes to Mental Illness Questionnaire (AMIQ) and a 3-item questionnaire on interest and knowledge in psychiatry. The Wilcoxon Sign-Rank test was used to determine statistical significance (P < .05) for pre- and post-clerkship values. Results: Among 39 invited students, 22 participated before (56.4%), and 23 participated after their psychiatry rotation (59.0%). Overall, there was a statistically significant increase in the perceived level of general interest in psychiatry (P = .027), psychiatry knowledge (P < .001), and career interest in psychiatry (P = .040). There was also a significant decrease in the stigmatized attitude score for depression and self-harm after their psychiatry rotation (P = .042). Finally, the participants initially showed the highest stigmatized attitude score for intravenous drug abuse among the 4 mental illnesses presented, which also included depression and suicidal ideation, alcohol use disorder, and schizophrenia. Conclusion: The findings suggest that a psychiatry clerkship provided a positive exposure to the field, enhanced medical students' overall interest in psychiatry, and positively impacted medical students' attitudes towards MI.

Melatonin in Traumatic Brain Injury and Cognition.

Traumatic brain injury (TBI) is a leading cause of long-term disability and mortality in young adults. The devastating effects of TBI on emotion regulation, executive functioning, and cognition have been well-established, and recent research links TBI as a risk factor for neurodegenerative diseases such as Alzheimer's disease. Despite an increased focus on the long-term cognitive dysfunction associated with TBI, research into potential treatments has not yet generated consistent successful results in human subjects. Many foundational studies have analyzed the cellular and molecular events involved in the inflammatory and healing processes following TBI, enhancing our understanding of the mechanisms that may contribute to the progression of dementia and cognitive decline in these patients. In this review, we will discuss the emergent research on melatonin within the framework of neuroinflammation and oxidative stress resulting from TBI and possibly preventing further sequelae such as Alzheimer's disease. A literature review was conducted using standard search strategies to query the PubMed database. The following search terms were used with qualifiers of various combinations: TBI, traumatic brain injury, melatonin, treatment, dementia, Alzheimer's, cognition, and neurodegeneration. Selected studies included meta-analyses, literature reviews, and randomized controlled trials (RCT) that evaluated melatonin's role as a potential therapy to prevent post-TBI neurodegeneration, specifically the development of dementia and deficits in memory and cognition. Three independent reviewers assessed all articles for eligibility. After assessment for eligibility, 11 total studies were included. Much of the available data on melatonin in TBI has highlighted its significant neuroprotective and antiinflammatory effects, which can be significant in fighting against the neuroinflammatory processes indicated in neurodegeneration. In animal models, immunohistochemistry and histopathology have allowed researchers to study measures of cell injury such as inflammatory cytokines, edema, and markers of oxidative stress. Though the effects of melatonin in TBI appear to be mediated through mostly indirect mechanisms on inflammatory processes, some research has explored potential mechanisms that could be specific to melatonin. Animal model studies support that melatonin treatment after TBI significantly improves cognition and behavioral outcomes. However, clinical studies with human subjects are scarce. Beyond the apparent general antiinflammatory and antioxidant actions of melatonin, a review of the evidence identified some preliminary research that has suggested the significance of melatonin receptors specifically in TBI. While there is some evidence to suggest that melatonin is able to reduce post-TBI cognitive decline as measured by subject performance on memory tasks, there is a lack of longitudinal data on whether melatonin decreases the risk of developing dementia after TBI. Considering melatonin therapy's promising preclinical data, favorable safety profile, and accessibility, further studies are warranted to assess the effects of melatonin as a post-TBI therapy on human subjects.

A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling.

PURPOSE: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer. EXPERIMENTAL DESIGN: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activation were performed on peripheral blood and tumor. RESULTS: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67+) CD4+ and CD8+ T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. CONCLUSIONS: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy. Clin Cancer Res; 22(23); 5729-37. ©2016 AACR.

Somatic mutations in leukocytes infiltrating primary breast cancers.

BACKGROUND: Malignant transformation requires the interaction of cancer cells with their microenvironment, including infiltrating leukocytes. However, somatic mutational studies have focused on alterations in cancer cells, assuming that the microenvironment is genetically normal. Because we hypothesized that this might not be a valid assumption, we performed exome sequencing and targeted sequencing to investigate for the presence of pathogenic mutations in tumor-associated leukocytes in breast cancers. METHODS: We used targeted sequencing and exome sequencing to evaluate the presence of mutations in sorted tumor-infiltrating CD45-positive cells from primary untreated breast cancers. We used high-depth sequencing to determine the presence/absence of the mutations we identified in breast cancer-infiltrating leukocytes in purified tumor cells and in circulating blood cells. RESULTS: Capture-based sequencing of 15 paired tumor-infiltrating leukocytes and matched germline DNA identified variants in known cancer genes in all 15 primary breast cancer patients in our cohort. We validated the presence of mutations identified by targeted sequencing in infiltrating leukocytes through orthogonal exome sequencing. Ten patients harbored alterations previously reported as somatically acquired variants, including in known leukemia genes (DNTM3A, TET2, and BCOR). One of the mutations observed in the tumor-infiltrating leukocytes was also detected in the circulating leukocytes of the same patients at a lower allele frequency than observed in the tumor-infiltrating cells. CONCLUSIONS: Here we show that somatic mutations, including mutations in known cancer genes, are present in the leukocytes infiltrating a subset of primary breast cancers. This observation allows for the possibility that the cancer cells interact with mutant infiltrating leukocytes, which has many potential clinical implications.

The GABAergic system in schizophrenia.

A defect in neurotransmission involving gamma-amino butyric acid (GABA) in schizophrenia was first proposed in the early 1970s. Since that time, a considerable effort has been made to find such a defect in components of the GABAergic system. After a brief introduction focusing on historical perspectives, this paper reviews post-mortem and other biological studies examining the following components of the GABAergic system in schizophrenic subjects: the GABA biosynthetic enzyme, glutamate decarboxylase; free GABA; the GABA transporter; the GABAA, GABAB and benzodiazepine receptors; and the catabolic enzyme GABA transaminase. Additionally, post-mortem studies using morphology or calcium-binding protein to identify GABAergic neurons are also reviewed. Substantial evidence argues for a defect in the GABAergic system of the frontal cortex in schizophrenia which is limited to the parvalbumin-class of GABAergic interneurons.