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.

Jointly modelling longitudinally measured urinary human chorionic gonadotrophin and early pregnancy outcomes.

Human chorionic gonadotrophin (hCG) is largely used to confirm pregnancy. Yet evidence shows that longitudinal hCG profiles are distinguishable between healthy and failing pregnancies. We retrospectively fitted a joint longitudinal-survival model to data from 127 (85 healthy and 42 failing pregnancies) US women, aged 18-45, who were attempting to conceive, to quantify the association between longitudinally measured urinary hCG and early miscarriage. Using subject-specific predictions, obtained uniquely from the joint model, we investigated the plausibility of adaptively monitoring early pregnancy outcomes based on updating hCG measurements. Volunteers collected daily early morning urine samples for their menstrual cycle and up to 28 days post day of missed period. The longitudinal submodel for log hCG included a random intercept and slope and fixed linear and quadratic time terms. The survival submodel included maternal age and cycle length covariates. Unit increases in log hCG corresponded to a 63.9% (HR 0.36, 95% CI 0.16, 0.47) decrease in the risk of miscarriage, confirming a strong association between hCG and miscarriage. Outputted conditional survival probabilities gave individualised risk estimates for the early pregnancy outcomes in the short term. However, longer term monitoring would require a larger sample size and prospectively followed up data, focusing on emerging extensions to the joint model, which allow assessment of the specificity and sensitivity.

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.

What do babies eat? Evaluation of a food frequency questionnaire to assess the diets of infants aged 6 months.

OBJECTIVE: To evaluate the relative validity of a food frequency questionnaire (FFQ) for assessing nutrient intakes in 6-month-old infants. DESIGN AND SETTING: The FFQ was developed to assess the diets of infants born to women in the Southampton Women's Survey (SWS), a population-based survey of young women and their offspring. The energy and nutrient intakes obtained from an interviewer-administered FFQ were compared with those obtained from a 4-day weighed diary. SUBJECTS AND METHODS: A sub-sample of 50 infants aged 6 months from the SWS had their diets assessed by both methods. The FFQ recorded the frequencies and amounts of milks, baby foods, regular foods and drinks consumed by the infants over the previous seven days. The diaries recorded the weights of all foods and drinks consumed by the infants on four separate days within 15 days following FFQ completion. RESULTS: Spearman rank correlation coefficients for intakes of energy, macronutrients and 18 micronutrients, determined by the two methods, ranged from r = 0.39 to 0.86; adjustment for energy intake tended to increase the correlation coefficients, range r(a) = 0.55 to 0.89. Bland-Altman statistics showed that mean differences between methods were in the range of -12.5% to +12.5% except for vitamin B12 (-18.9%). CONCLUSION: Although there were differences in absolute energy and nutrient intakes between methods, Spearman rank correlation coefficients indicated reasonable agreement in the ranking of intakes. The interviewer-administered FFQ is a useful tool for assessing energy and nutrient intakes of healthy infants aged about 6 months.

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.

Detection of Louping ill virus in clinical specimens from mammals and birds using TaqMan RT-PCR.

The identification of Louping ill virus (LIV) in clinical specimens has been routinely achieved by virus isolation using susceptible pig kidney cells and subsequent serological analysis. While this method is sensitive and detects infectious virus, it is relatively labour intensive and time-consuming. In view of the veterinary and potential medical importance of LIV, a rapid and precise detection method for routine use that employs the TaqMan reverse transcription polymerase chain reaction (RT-PCR) has been developed to detect LIV RNA extracted from field samples. The TaqMan assay was evaluated against virus isolation using 22 cell culture grown LIV isolates, which had previously been partially characterised by sequencing, and material from 63 suspect field cases. Histopathological and/or serological reports were available for 39 of the suspect cases, providing additional diagnostic information to evaluate the results obtained from the TaqMan RT-PCR assay. The TaqMan assay was as sensitive as the cell culture infectious virus assay currently used and had the advantage that it was able to detect LIV in clinical specimens from which infectious virus could not be isolated possibly due to the presence of high levels of LIV antibody.

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.

Advances in the nutrition of preterm infants.

The greatly improved survival rate of infants born both preterm and low birth weight (LBW) has led to the subsequent growth and development of these infants becoming an important focus for research. Preterm infants begin life with, or acquire as a result of their prematurity, greater morbidity than term born babies, growth deficits, an increased risk of developmental delay and an increased risk of later adult diseases compared with appropriate for gestational age (AGA) term born babies. Research in recent decades has confirmed that there are marked differences in the nutritional requirements of preterm LBW infants compared with their AGA term born counterparts, both in the neonatal period and probably for all of infancy. In addition to the increased requirement for energy and protein, preterm LBW infants demonstrate a greatly increased requirement for some of the mineral elements, particularly iron, zinc and calcium, when compared with the needs of term AGA infants. In the UK, feeding practices for preterm infants in neonatal units and throughout infancy after hospital discharge are variable and many questions remain as to the optimal nutritional regimen for preterm LBW infants (and for subgroups of these infants) at different stages of infancy. There is some concern that the 2002 World Health Organization recommendations on infant feeding may be applied to all infants, including preterm infants, without consideration of their special nutritional needs, which may further compromise their growth and development. A brief résumé of the work of prominent researchers in the field of preterm infant nutrition in the UK, notably Lucas, Cooke and Fewtrell, is included in the review, together with information from papers published by the authors of the review. The review concludes with a summary of the generally accepted recommendations on feeding preterm LBW infants after hospital discharge and information on some practical help available to the parents of these children and to health workers in the field.

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.

Weaning preterm infants: a randomised controlled trial.

OBJECTIVE: To assess the effect on growth and iron status in preterm infants of a specially devised weaning strategy compared with current best practices in infant feeding. The preterm weaning strategy recommended the early onset of weaning and the use of foods with a higher energy and protein content than standard milk formula, and foods that are rich sources of iron and zinc. SUBJECTS AND DESIGN: In a blinded, controlled study, 68 preterm infants (mean (SD) birth weight 1470 (430) g and mean (SD) gestational age 31.3 (2.9) weeks) were randomised to either the preterm weaning strategy group (n = 37) or a current best practice control group (n = 31), from hospital discharge until 1 year gestation corrected age (GCA). MAIN OUTCOME MEASURES: Weight, supine length, occipitofrontal head circumference, and intakes of energy, protein, and minerals were determined at 0, 6, and 12 months GCA. Levels of haemoglobin, serum iron, and serum ferritin were assayed at 0 and 6 months GCA. RESULTS: Significant positive effects of treatment included: greater increase in standard deviation length scores and length growth velocity; increased intake of energy, protein, and carbohydrate at 6 months GCA and iron at 12 months GCA; increased haemoglobin and serum iron levels at 6 months GCA. CONCLUSIONS: The preterm weaning strategy significantly influenced dietary intakes with consequent beneficial effects on growth in length and iron status. This strategy should be adopted as the basis of feeding guidelines for preterm infants after hospital discharge.

Weaning of infants.

The WHO 2001 global recommendation is a one size fits all approach to weaning, an approach which may not take sufficient account of the special needs of some infants and fails to allow for the different problems encountered in the industrialised nations compared with economically developing countries. For the healthy normal birth weight full term infant born in an industrialised country, current research supports the benefit of exclusive breast milk feeding until 4-6 months. Evidence of harm through introducing solid food to these infants earlier than this is weak. Infants should be managed individually according to their needs.

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.

The disposition of saquinavir in normal and P-glycoprotein deficient mice, rats, and in cultured cells.

Protease inhibitors are very effective in treating patients infected with HIV. However, many drugs in this class penetrate poorly into the central nervous system (CNS) and may permit this site to be a sanctuary from which resistant virus can emerge. Previous studies have shown that the protease inhibitor saquinavir (SQV) interacts with the multidrug transport system, P-glycoprotein (P-gp), expressed in epithelial cells in the gut mucosa and at the blood-brain barrier, and thus might affect both the oral absorption and the penetration of SQV into the CNS. To determine whether SQV is a substrate for P-gp, its uptake was determined in cancer cells, which do (Dx5) and do not (MES-SA) express P-gp. The distribution of SQV between brain tissue and plasma was also investigated in rats and in normal and P-gp-deficient mdr1a(-/-) mice. The distribution ratio of SQV in plasma:brain:cerebrospinal fluid was approximately 100:10:0.2 in rats. The accumulation of SQV was enhanced in MES-SA cells (P-gp-negative) versus Dx5 cells (P-gp-positive). Bolus i.v. injection of [(14)C]SQV (2 and 5 mg/kg) into mdr1a(-/-) and normal mice (n = 3 or 4) resulted in 3-fold higher radioactivity in brains from mdr1a(-/-) mice. Similarly, oral administration of [(14)C]SQV (500 mg/kg) resulted in a 5-fold increase in systemic exposure and a 10-fold increase in brain levels in mdr1a(-/-) mice. These data demonstrate that saquinavir is a substrate for P-gp and that this transport system may play a role in limiting oral absorption and CNS exposure to this protease inhibitor.