Inclusive Approaches for Measuring Demographics of Underrepresented Populations in STEM and Biomedical Research Training Programs.

As federal strategic plans prioritize increasing diversity within the biomedical workforce, and STEM training and outreach programs seek to recruit and retain students from historically underrepresented populations, there is a need for interrogation of traditional demographic descriptors and careful consideration of best practices for obtaining demographic data. To accelerate this work, equity-focused researchers and leaders from STEM programs convened to examine approaches for measuring demographic variables. Gender, race/ethnicity, disability, and disadvantaged background were prioritized given their focus by federal funding agencies. Categories of sex minority, sexual (orientation) minority, and gender minority (SSGM) should be included in demographic measures collected by STEM programs, consistent with recommendations from White House Executive Orders and federal reports. Our manuscript offers operationalized phrasing for demographic questions and recommendations for use across student-serving programs. Inclusive demographics permit the identification of individuals who are being excluded, marginalized, or improperly aggregated, increasing capacity to address inequities in biomedical research training. As trainees do not enter training programs with equal access, accommodations, or preparation, inclusive demographic measures can welcome trainees and inform a nuanced set of program outcomes that facilitate research on intersectionality to support the recruitment and retention of underrepresented students in biomedical research.

Interprofessional Near-Peer Mentoring Teams Enhance Cancer Research Training: Sustainable Approaches for Biomedical Workforce Development of Historically Underrepresented Students.

A cancer research training program explored different approaches for staffing their in-person and virtual programs for high school students. The inclusion of undergraduate near-peer mentors had a universal benefit when implemented across in-person and virtual training programs of one- and ten-week durations. Benefits are described for four stakeholder groups: the high school trainees, program staff, scientist partners, and peer mentors themselves. Peer mentors described that their involvement enhanced their own professional development and, for some, drove a new interest in cancer research. Scientist partners described that peer mentors helped translate their work in the virtual environment for high school students. High school trainees reported their sessions with peer mentors to be one of their favorite parts of the program. Interprofessional peer mentors were highly relatable to students and modeled communication and paths in biomedical research. Staff reported that peer mentors supported student engagement during community shadowing sessions, allowing staff to focus on developing the shadowing experiences with partners. The benefit of including peer mentors was substantial from all viewpoints explored. Their intensive inclusion in cancer research training programs supports sustainability and capacity building in biomedical workforce development.

Knight Scholars Program: A Tiered Three-Year Mentored Training Program for Urban and Rural High School High School Students Increases Interest and Self-Efficacy in Interprofessional Cancer Research.

Cancer research training programs build our future biomedical workforce. Training is often centered for students residing close to research institutions, making access more challenging for rural students. A cancer research training program was developed for high school students residing in five geographical regions across Oregon. Training was tiered in duration and intensity across the three years, including a one-week Introduction program and subsequent 10-week summer research training programs (Immersion and Intensive). A total of 60 students participated in in-person and/or virtual training, with Immersion students receiving mentored shadowing experiences in clinical care, public health, and outreach in their home communities. Laboratory rotations at a research-intensive institution enabled students to sample research environments before selecting an area of interest for Intensive training the following summer. Aligning with Self-Determination Theory, the Knight Scholars Program aims to build competence, relatedness, and autonomy of its trainees in biomedical sciences. The program exposed students to a wide range of interprofessional careers and collaborative teams, enabling scholars to envision themselves in various paths. Results show strong gains in interest and research self-efficacy for both Introduction and Immersion scholars, with findings highlighting the importance of representation within mentoring and training efforts.

Thai adaptation and reliability of three versions of the Barratt Impulsiveness Scale (BIS 11, BIS-15, and BIS-Brief).

Long, short, and brief versions of the Barratt Impulsiveness scale (BIS-11, BIS-15, and BIS-Brief) were tested in an adult Thai population. The BIS-11T and BIS-15T were translated, back-translated, and administered to a non-clinical population (n = 305) of native Thai speakers who returned 2 weeks later for re-test. BIS-Brief-T psychometrics were calculated post-hoc. Impulsivity scores were normally distributed for the BIS-11T and BIS-15T, but not BIS-Brief-T. Excellent internal consistency was observed, with Cronbach's alpha coefficients above 0.80 for all translated instruments: BIS-11T (α = 0.86), BIS-15T (α = 0.81), BIS-Brief-T (α = 0.81). A total of 260 participants completed both instruments (85%), with test-retest reliability exceeding r = 0.81. All three instruments were highly correlated (r = 0.83-0.89). Confirmatory factor analysis supports a three factor structure (attention, motor, non-planning) for BIS-15T and two factor structure for BIS-11T. BIS scales can support measurement of a range of impulsivity scores in an adult Thai population, though predictive validity of these scales remains unexplored.

Neuroprotective effects of estrogen and selective estrogen receptor modulators begin at the plasma membrane.

Estrogen is neuroprotective in a large number of models in vivo and in vitro. Its application in hormone replacement therapy has proven to be more complicated, necessitating better understanding of how estrogen signals in the brain. Estrogen binds to estrogen receptors to regulate gene transcription, and activates a number of rapid signaling cascades from the plasma membrane. These rapid signaling cascades have been shown to play important roles in mediating the neuroprotective effects of estrogen. This review covers evidence that understanding and targeting the membrane effects of estrogen has emerged as an important area in the design of novel neuroprotective drugs.

Brain infusion of lipopolysaccharide increases uterine growth as a function of estrogen replacement regimen: suppression of uterine estrogen receptor-alpha by constant, but not pulsed, estrogen replacement.

The effects of estrogen therapy can differ depending on the regimen of estrogen administration. In addition, estrogen can modulate the effects of stressors. To examine the interaction between these systems, we infused adult female rats with lipopolysaccharide (LPS) into the fourth ventricle of the brain for 6 d and compared the effects of constant and pulsed estrogen replacement. Constant, but not pulsed, estrogen treatment reduced estrogen receptor-alpha (ERalpha) protein by 90% in the uterus and increased heat-shock proteins 70 and 90 by 74 and 48%, respectively, whereas progesterone receptor levels increased in all ovariectomized rats receiving estrogen replacement. In contrast to the uterine decline in ERalpha, no changes in ERalpha were observed in the hypothalamus or hippocampus, and ERbeta levels were unchanged in all regions tested. Brain infusion of LPS did not alter these proteins but increased the number of activated microglia in the thalamus and reduced body weight in all rats as well as activated the hypothalamic-pituitary-adrenal axis in ovariectomized rats, as determined by elevations in circulating corticosterone and progesterone. Estrogen treatments did not alter these markers, and no differences were observed in cortical choline acetyltransferase activity or nitrotyrosine for any of the treatment groups. The current study found an unexpected increase in uterine weight in lipopolysaccharide-infused rats treated with constant, but not pulsed, estrogen. This report suggests that constant and pulsed regimens of estrogen administration produce different effects and that stress may be an important factor in the postmenopausal intervention with estrogen.

Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus.

The regimen of estrogen replacement can alter the consequences of estrogen therapy and stressors. To determine the long-term effects and interaction of these systems on the brain and periphery, adult female rats were infused with lipopolysaccharide (LPS) into the fourth ventricle of the brain for 4 weeks, and ovariectomized rats were administered either constant or pulsed regimens of estrogen replacement (17beta-estradiol) until sacrifice at 8 weeks. Constant, but not pulsed, estrogen replacement reduced ERalpha and increased HSP90, HSP70, and PR(B) uterine protein levels. Both estrogen regimens increased ERbeta, HSP27, and PR(A) uterine proteins. Both regimens reduced hypothalamic levels of ERalpha, but not ERbeta, HSP, or PR. No changes were observed in the hippocampus. Long-term brain infusion of LPS activated microglia and reduced body weight, but did not alter corticosterone or nitrotyrosine levels. LPS infusion into intact rats suppressed uterine weight, increased ERalpha and decreased HSP90 in the uterus. LPS did not alter uterine weight in ovariectomized rats treated with constant or pulsed estrogen. Together, these data suggest the timing of estrogen replacement and neuroinflammatory stressors can profoundly affect uterine and hypothalamic steroid receptor expression and may be important parameters to consider in the post-menopausal intervention with estrogen.

Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience.

After a spatial behavioral experience, hippocampal CA1 pyramidal cells express the activity-regulated, immediate early gene Arc in an environment-specific manner, and in similar proportions ( 40%) to cells exhibiting electrophysiologically recorded place fields under similar conditions. Theoretical accounts of the function of the fascia dentata suggest that it plays a role in pattern separation during encoding. The hypothesis that the dentate gyrus (DG) uses a sparse, and thus more orthogonal, coding scheme has been supported by the observation that, while granule cells do exhibit place fields, most are silent in a given environment. To quantify the degree of sparsity of DG coding and its corresponding ability to generate distinct environmental representations, behaviorally induced Arc expression was assessed using in situ hybridization coupled with confocal microscopy. The proportion of Arc(+) cells in the "upper blade" of the fascia dentata (i.e., the portion that abuts CA1) increased in an environment-specific fashion, approximately 4-fold above cage-control activity, after behavioral exploration. Surprisingly, cells in the lower blade of the fascia dentata, which are capable of expressing Arc following electrical stimulation, exhibited virtually no behaviorally-induced Arc expression. This difference was confirmed using "line scan" analyses, which also revealed no patterns or gradients of activity along the upper blade of the DG. The expression of Arc in the upper blade was quantitatively similar after exploring familiar or novel environments. When animals explored two different environments, separated by 20 min, a new group of cells responded to the second environment, whereas two separated experiences in the same environment did not activate a new set of granular cells. Thus, granule cells generate distinct codes for different environments. These findings suggest differential contribution of upper and lower blade neurons to plastic networks and confirm the hypothesis that the DG uses sparse coding that may facilitate orthogonalization of information.

Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning.

Estrogen modulates learning and memory in ovariectomized and naturally cycling female rats, especially in tasks using spatial learning and navigation. Estrogen also modulates cholinergic function in various forebrain structures. Past studies have shown positive correlations between hippocampal ACh output and performance on hippocampus-dependent tasks. The present study examined whether estradiol replacement would potentiate hippocampal ACh release during place learning. In vivo microdialysis and HPLC were used to measure extracellular ACh levels in the hippocampus of ovariectomized female rats that had received s.c. injections of 17beta-estradiol (10 microg) or sesame oil (vehicle treatment) 48 and 24h prior to training on a place task. Estrogen did not alter baseline levels of extracellular ACh in the hippocampus. During training, hippocampal ACh increased in ovariectomized rats regardless of estrogen status. However, while estradiol did not enhance learning in this experiment, estradiol significantly potentiated the increase in hippocampal ACh release seen during place training. This represents the first demonstration of on-line assessment of ACh output in hippocampus during learning in female rats and suggests that estrogen-dependent modulation of ACh release during training might control activation of different neural systems used during learning.

Long-term estrogen therapy worsens the behavioral and neuropathological consequences of chronic brain inflammation.

Alzheimer's disease (AD) is accompanied by chronic neuroinflammation and occurs with greater incidence in postmenopausal women. The increased incidence may be delayed by estrogen replacement therapy (ERT). The authors investigated the interaction of chronic ERT and lipopolysaccharide (LPS)-induced neuroinflammation in the female rat. Ovariectomy did not impair water maze performance; however, addition of chronic ERT or neuroinflammation resulted in an impairment that became exacerbated by the simultaneous occurrence of both conditions. Chronic LPS activated microglia, which was not reduced by ERT. Intact females receiving LPS infusion were not impaired in the water maze and had significantly fewer activated microglia. Results suggest that chronic ERT in postmenopausal women may exacerbate the memory impairment induced by the chronic neuroinflammation associated with AD.

Galanin peptide levels in hippocampus and cortex of galanin-overexpressing transgenic mice evaluated for cognitive performance.

Galanin-overexpressing transgenic mice (GAL-tg) generated on a dopamine beta-hydroxylase promoter were previously shown to express high levels of galanin mRNA in the locus coeruleus, and to perform poorly on challenging cognitive tasks. The present study employed radioimmunoassay to quantitate the level of galanin peptide overexpression in two brain regions relevant to learning and memory, the hippocampus and cerebral cortex. Approximately 4-fold higher levels of galanin were detected in the hippocampus of GAL-tg as compared to WT. Approximately 10-fold higher levels of galanin were detected in the frontal cortex of GAL-tg as compared to WT. A second cohort of GAL-tg and WT again showed high levels of galanin overexpression in GAL-tg as compared to WT in both brain regions. Correlation analyses were conducted between galanin peptide concentrations and behavioral scores on four learning and memory tasks: the Morris water maze, social transmission of food preference, standard delay fear conditioning, and trace fear conditioning. While some significant correlations were detected, neither hippocampal nor cortical galanin levels in the two cohorts of GAL-tg consistently correlated with performance across these diverse cognitive tasks. Several interpretations of these findings are discussed, including the possibility that a threshold level of galanin overexpression is sufficient to impair performance on learning and memory tasks in mice.