Rules of Engagement: Implementing Student-Centered Learning in Breast Imaging

In response to changing learner needs, our institution launched a new translational curriculum wherein basic sciences and clinical skills were integrated, longitudinal patient care experiences provided, and earlier opportunities in specialty fields introduced to better inform residency program decisions. Medical students taking the breast imaging elective were enrolled in a breast imaging immersive experience designed to meet the School of Medicine’s core competencies. In focusing the elective on a narrow range of specialized topics and skills, we labeled this experience the Breast Imaging Boot Camp. Outcome data from March 6, 2017, to April 26, 2019, have been analyzed for this report. The modifications made to the elective include: e-mailing a detailed orientation document to students prior to the start of the rotation; assigning students to diagnostic, procedural, and screening roles; the attendance of students at introductory radiology symposia; students’ weekly attendance at institutional multidisciplinary and divisional breast radiologic–pathologic correlation conferences; student self-study assignments using faculty-vetted resources; student participation in breast biopsy simulation and small parts ultrasound laboratories; the development of a student-centric radiology educational website; and student-directed publishing of digital case files. Medical student feedback and course analytics indicated superior course evaluation scores reinforced by narrative feedback. In website domain utilization data, the breast file domain is the most viewed subspecialty domain. The Breast Imaging Boot Camp is a successful curriculum. Its novelty lies in both its integrated approach to medical student core competencies and its clinician educators’ use of today’s student-favored teaching tools

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior

SummaryEscalated aggression can have devastating societal consequences, yet underlying neurobiological mechanisms are poorly understood. Here, we show significantly increased inter-male mouse aggression when neurotransmission is constitutively blocked from either of two subsets of serotonergic, Pet1+ neurons: one identified by dopamine receptor D1(Drd1a)::cre-driven activity perinatally, and the other by Drd2::cre from pre-adolescence onward. Blocking neurotransmission from other Pet1+ neuron subsets of similar size and/or overlapping anatomical domains had no effect on aggression compared with controls, suggesting subtype-specific serotonergic neuron influences on aggression. Using established and novel intersectional genetic tools, we further characterized these subtypes across multiple parameters, showing both overlapping and distinct features in axonal projection targets, gene expression, electrophysiological properties, and effects on non-aggressive behaviors. Notably, Drd2::cre marked 5-HT neurons exhibited D2-dependent inhibitory responses to dopamine in slices, suggesting direct and specific interplay between inhibitory dopaminergic signaling and a serotonergic subpopulation. Thus, we identify specific serotonergic modules that shape aggression

HDAC6 Regulates Glucocorticoid Receptor Signaling in Serotonin Pathways with Critical Impact on Stress Resilience

Genetic variations in certain components of the glucocorticoid receptor (GR) chaperone complex have been associated with the development of stress-related affective disorders and individual variability in therapeutic responses to antidepressants. Mechanisms that link GR chaperoning and stress susceptibility are not well understood. Here, we show that the effects of glucocorticoid hormones on socioaffective behaviors are critically regulated via reversible acetylation of Hsp90, a key component of the GR chaperone complex. We provide pharmacological and genetic evidence indicating that the cytoplasmic lysine deacetylase HDAC6 controls Hsp90 acetylation in the brain, and thereby modulates Hsp90–GR protein–protein interactions, as well as hormone- and stress-induced GR translocation, with a critical impact on GR downstream signaling and behavior. Pet1-Cre-driven deletion of HDAC6 in serotonin neurons, the densest HDAC6-expressing cell group in the mouse brain, dramatically reduced acute anxiogenic effects of the glucocorticoid hormone corticosterone in the open-field, elevated plus maze, and social interaction tests. Serotonin-selective depletion of HDAC6 also blocked the expression of social avoidance in mice exposed to chronic social defeat and concurrently prevented the electrophysiological and morphological changes induced, in serotonin neurons, by this murine model of traumatic stress. Together, these results identify HDAC6 inhibition as a potential new strategy for proresilience and antidepressant interventions through regulation of the Hsp90–GR heterocomplex and focal prevention of GR signaling in serotonin pathways. Our data thus uncover an alternate mechanism by which pan-HDAC inhibitors may regulate stress-related behaviors independently of their action on histones

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Social Stress Alters Inhibitory Synaptic Input to Distinct Subpopulations of Raphe Serotonin Neurons

Anxiety disorders are among the most prevalent psychiatric disorders, yet much is unknown about the underlying mechanisms. The dorsal raphe (DR) is at the crux of the anxiety-inducing effects of uncontrollable stress, a key component of models of anxiety. Though DR serotonin (5-HT) neurons play a prominent role, anxiety-associated changes in the physiology of 5-HT neurons remain poorly understood. A 5-day social defeat model of anxiety produced a multifaceted, anxious phenotype in intruder mice that included increased avoidance behavior in the open field test, increased stress-evoked grooming, and increased bladder and heart weights when compared to control mice. Intruders were further compared to controls using electrophysiology recordings conducted in midbrain slices wherein recordings targeted 5-HT neurons of the ventromedial (vmDR) and lateral wing (lwDR) subfields of the DR. Though defining membrane characteristics of 5-HT neurons were unchanged, γ-aminobutyric-acid-mediated (GABAergic) synaptic regulation of 5-HT neurons was altered in a topographically specific way. In the vmDR of intruders, there was a decrease in the frequency and amplitude of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). However, in the lwDR, there was an increase in the strength of inhibitory signals due to slower sIPSC kinetics. Synaptic changes were selective for GABAergic input, as glutamatergic synaptic input was unchanged in intruders. The distinct inhibitory regulation of DR subfields provides a mechanism for increased 5-HT output in vmDR target regions and decreased 5-HT output in lwDR target regions, divergent responses to uncontrollable stress that have been reported in the literature but were previously poorly understood

Increased Intrinsic Excitability of Lateral Wing Serotonin Neurons of the Dorsal Raphe: A Mechanism for Selective Activation in Stress Circuits

The primary center of serotonin (5-HT) projections to the forebrain is the dorsal raphe nucleus (DR), a region known for its role in the limbic stress response. The ventromedial subregion of the DR (vmDR) has the highest density of 5-HT neurons and is the major target in experiments that involve the DR. However, studies have demonstrated that a variety of stressors induce activation of neurons that is highest in the lateral wing subregion (lwDR) and includes activation of lwDR 5-HT neurons. Despite the functional role that the lwDR is known to play in stress circuits, little is known about lwDR 5-HT neuron physiology. Whole cell patch clamp electrophysiology in mice revealed that lwDR 5-HT cells have active and passive intrinsic membrane properties that make them more excitable than vmDR 5-HT neurons. In addition, lwDR 5-HT neurons demonstrated faster in vitro firing rates. Finally, within the vmDR there was a positive correlation between rostral position and increased excitability, among several other membrane parameters. These results are consistent with stressor induced patterns of activation of 5-HT neurons that includes, in addition to lwDR neurons, a small subset of rostral vmDR neurons. Thus increased intrinsic excitability likely forms a major part of the mechanism underlying the propensity to be activated by a stressor. The membrane properties identified in lwDR recordings may thereby contribute to a unique role of lwDR 5-HT neurons in adaptive responses to stress and in the pathobiology of stress-related mood disorders

Stability in the feeding practices and styles of low-income mothers: questionnaire and observational analyses

Abstract Background During the last two decades, researchers have devoted considerable attention to the role of maternal feeding behaviors, practices, and styles in the development of obesity in young children. Little is known, however, about the consistency of maternal feeding across settings and time. The purpose of this paper was to provide data on this issue by examining the consistency of observed maternal feeding behavior across multiple eating occasions, as well as examine the consistency of observed and self-reported maternal feeding behavior across 18 months. Methods Videotapes from two studies of low-income mothers and their preschool children were coded for feeding practices, dimensions, and styles: a study of 137 low-income, African American and Latina mothers and their children observed during three meals in their homes over a two to three week period, and a study of 138 low-income, Latina mothers observed during a buffet meal in a laboratory setting on two separate occasions 18 months apart. Videotapes from both studies were coded for a wide range of maternal feeding behaviors and strategies. Mothers in the second study also completed three validated, self-report questionnaires on their feeding practices and styles. Results Overall, both observed and self-reported feeding practices and styles showed only moderate levels of stability across meals and over time. Maternal attempts to regulate children’s eating showed more stability across meals and over time than the content of general mealtime conversation. Also, greater stability was found in what mothers were trying to get their children to do during the meals than in the strategies they used to influence child behavior. Self-reports of feeding showed greater stability over time than observational measures. Across meals and across 18 months, the stability of general feeding styles was between 40% and 50%. Conclusions The findings demonstrate that maternal feeding behavior was only moderately stable across meals and over time—that is, feeding behavior varied considerably across situations. The lack of high levels of consistency in feeding behavior suggests that situational factors may play a major role in influencing maternal behavior as well. Family-focused childhood obesity programs should focus not only on helping parents change their feeding practices and styles, but also focus on increasing parents’ sensitivity to situational factors that affect their approach to feeding their children