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Background: Xenon is a general anesthetic with neuroprotective properties. Xenon inhibition at the glycine-binding site of the N-Methyl-D-aspartate (NMDA) receptor mediates xenon neuroprotection against ischemic injury in vitro. Here we identify specific amino acids important for xenon binding to the NMDA receptor, with the aim of finding silent mutations that eliminate xenon binding but leave normal receptor function intact.Methods: Site-directed mutagenesis was used to mutate specific amino-acids in the GluN1 subunit of rat NMDA receptors. Mutant GluN1/GluN2A receptors were expressed in HEK 293 cells and were assessed functionally using patch-clamp electrophysiology. The responses of the mutant receptors to glycine and anesthetics were determined.Results: Mutation of phenylalanine 758 to an aromatic tryptophan or tyrosine left glycine affinity unchanged, but eliminated xenon binding without affecting the binding of sevoflurane or isoflurane.Conclusions: These findings confirm xenon binds to the glycine site of the GluN1 subunit of the NMDA receptor and indicate that interactions between xenon and the aromatic ring of the phenylalanine 758 residue are important for xenon binding. Our most important finding is that we have identified two mutations, F758W and F758Y, that eliminate xenon binding to the NMDA receptor glycine site without changing the glycine affinity of the receptor or the binding of volatile anesthetics. The identification of these selective mutations will allow knock-in animals to be used to dissect the mechanism(s) of xenon's neuroprotective and anesthetic properties in vivo. [ABSTRACT FROM AUTHOR]

Pyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long-term potentiation of stratum radiatum synapses. CA2 neurons express high levels of several known and potential regulators of metabotropic glutamate receptor (mGluR)-dependent signaling including Striatal-Enriched Tyrosine Phosphatase (STEP) and several Regulator of G-protein Signaling (RGS) proteins, yet the functions of these proteins in regulating mGluR-dependent synaptic plasticity in CA2 are completely unknown. Thus, the aim of this study was to examine mGluR-dependent synaptic depression and to determine whether STEP and the RGS proteins RGS4 and RGS14 are involved. Using whole cell voltage-clamp recordings from mouse pyramidal cells, we found that mGluR agonist-induced long-term depression (mGluR-LTD) is more pronounced in CA2 compared with that observed in CA1. This mGluR-LTD in CA2 was found to be protein synthesis and STEP dependent, suggesting that CA2 mGluR-LTD shares mechanistic processes with those seen in CA1, but in addition, RGS14, but not RGS4, was essential for mGluR-LTD in CA2. In addition, we found that exogenous application of STEP could rescue mGluR-LTD in RGS14 KO slices. Supporting a role for CA2 synaptic plasticity in social cognition, we found that RGS14 KO mice had impaired social recognition memory as assessed in a social discrimination task. These results highlight possible roles for mGluRs, RGS14, and STEP in CA2-dependent behaviors, perhaps by biasing the dominant form of synaptic plasticity away from LTP and toward LTD in CA2., (© 2023 The Authors. Hippocampus published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

When the outcome of a choice is less favorable than expected, humans and animals typically shift to an alternate choice option on subsequent trials. Several lines of evidence indicate that this "lose-shift" responding is an innate sensorimotor response strategy that is normally suppressed by executive function. Therefore, the lose-shift response provides a covert gauge of cognitive control over choice mechanisms. We report here that the spatial position, rather than visual features, of choice targets drives the lose-shift effect. Furthermore, the ability to inhibit lose-shift responding to gain reward is different among male and female habitual cannabis users. Increased self-reported cannabis use was concordant with suppressed response flexibility and an increased tendency to lose-shift in women, which reduced performance in a choice task in which random responding is the optimal strategy. On the other hand, increased cannabis use in men was concordant with reduced reliance on spatial cues during decision-making, and had no impact on the number of correct responses. These data (63,600 trials from 106 participants) provide strong evidence that spatial-motor processing is an important component of economic decision-making, and that its governance by executive systems is different in men and women who use cannabis frequently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Banks, Bennett, Sekuler and Gruber.)

Studying the physiological properties of specific synapses in the brain, and how they undergo plastic changes, is a key challenge in modern neuroscience. Traditional in vitro electrophysiological techniques use electrical stimulation to evoke synaptic transmission. A major drawback of this method is its nonspecific nature; all axons in the region of the stimulating electrode will be activated, making it difficult to attribute an effect to a particular afferent connection. This issue can be overcome by replacing electrical stimulation with optogenetic-based stimulation. We describe a method for combining optogenetics with in vitro patch-clamp recordings. This is a powerful tool for the study of both basal synaptic transmission and synaptic plasticity of precise anatomically defined synaptic connections and is applicable to almost any pathway in the brain. Here, we describe the preparation and handling of a viral vector encoding channelrhodopsin protein for surgical injection into a pre-synaptic region of interest (medial prefrontal cortex) in the rodent brain and making of acute slices of downstream target regions (lateral entorhinal cortex). A detailed procedure for combining patch-clamp recordings with synaptic activation by light stimulation to study short- and long-term synaptic plasticity is also presented. We discuss examples of experiments that achieve pathway- and cell-specificity by combining optogenetics and Cre-dependent cell labeling. Finally, histological confirmation of the pre-synaptic region of interest is described along with biocytin labeling of the post-synaptic cell, to allow further identification of the precise location and cell type.

The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting. Furthermore, LRFN2 associates with AMPA receptors and knockdown of LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and attenuated hippocampal long-term potentiation. Overall, our study provides an additional mechanism by which SNX27 can control AMPA receptor-mediated synaptic transmission and plasticity indirectly through the sorting of LRFN2 and offers molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions., Competing Interests: KM, PB, FH, RC, TC, AE, KH, PL, BC, ZB, JH, KW, PC No competing interests declared, (© 2021, McMillan et al.)

In this review we consider the various roles played by N-methyl-d-aspartate receptors (NMDARs) located on pyramidal neurones in medial prefrontal cortex (mPFC). We focus on recent data from our lab that has investigated how NMDARs contribute to ongoing synaptic transmission in a frequency dependent manner, the plasticity of NMDARs and how this impacts their contribution to synaptic transmission, and finally consider how NMDARs contribute to plasticity induced by synchronous activation of two separate inputs to mPFC., (Copyright © 2021. Published by Elsevier Ltd.)

The nucleus reuniens and rhomboid nuclei of the thalamus (ReRh) are reciprocally connected to a range of higher order cortices including hippocampus (HPC) and medial prefrontal cortex (mPFC). The physiological function of ReRh is well predicted by requirement for interactions between mPFC and HPC, including associative recognition memory, spatial navigation, and working memory. Although anatomical and electrophysiological evidence suggests ReRh makes excitatory synapses in mPFC there is little data on the physiological properties of these projections, or whether ReRh and HPC target overlapping cell populations and, if so, how they interact. We demonstrate in ex vivo mPFC slices that ReRh and HPC afferent inputs converge onto more than two-thirds of layer 5 pyramidal neurons, show that ReRh, but not HPC, undergoes marked short-term plasticity during theta frequency transmission, and that HPC, but not ReRh, afferents are subject to neuromodulation by acetylcholine acting via muscarinic receptor M2. Finally, we demonstrate that pairing HPC followed by ReRh (but not pairing ReRh followed by HPC) at theta frequency induces associative, NMDA receptor dependent synaptic plasticity in both inputs to mPFC. These data provide vital physiological phenotypes of the synapses of this circuit and provide a novel mechanism for HPC-ReRh-mPFC encoding., (© The Author(s) 2021. Published by Oxford University Press.)

Saturated soil paste extracts indicate soluble ions in soil pore water that are available to vegetation. As such, they are thought to accurately describe the relationship between soil and groundwater salinity. To test this assumption, soil and groundwater samples were collected from 575 monitoring wells in saline regions of the Western Canadian Sedimentary Basin (WCSB). Samples were analyzed for electrical conductivity (EC) and Cl - , Na + , Ca 2+ , Mg 2+ , K + , SO 42- , and HCO - 3 content. We compared groundwater ionic concentrations to paste extracts derived from matching soils, finding that differences from in situ soil porosity cause saturated pastes to underestimate groundwater salinity. Therefore, we provide pedotransfer functions for accurately calculating groundwater quality from soil data. In addition, we discuss the effects of porosity and soil composition on the saturated paste method, as measured through hydraulic conductivity, saturation percent, and sample lithology. Groundwater salinity may also influence further leaching of salts from soil. As produced water (NaCl brine) spills are common across the sulfate-rich soils of the WCSB, we considered the effects of NaCl on leaching of other ions, finding that influx of Na + into groundwater is associated with increased sulfate leaching from soil. Therefore, considering the secondary effects of produced water on groundwater quality is essential to spill management.

The propensity of animals to shift choices immediately after unexpectedly poor reinforcement outcomes is a pervasive strategy across species and tasks. We report here on the memory supporting such lose-shift responding in humans, assessed using a binary choice task in which random responding is the optimal strategy. Participants exhibited little lose-shift responding when fully attending to the task, but this increased by 30%-40% in participants that performed with additional cognitive load that is known to tax executive systems. Lose-shift responding in the cognitively loaded adults persisted throughout the testing session, despite being a sub-optimal strategy, but was less likely as the time increased between reinforcement and the subsequent choice. Furthermore, children (5-9 years old) without load performed similarly to the cognitively loaded adults. This effect disappeared in older children aged 11-13 years old. These data provide evidence supporting our hypothesis that lose-shift responding is a default and reflexive strategy in the mammalian brain, likely mediated by a decaying memory trace, and is normally suppressed by executive systems. Reducing the efficacy of executive control by cognitive load (adults) or underdevelopment (children) increases its prevalence. It may therefore be an important component to consider when interpreting choice data, and may serve as an objective behavioral assay of executive function in humans that is easy to measure.

Gambling studies have described a "near-miss effect" wherein the experience of almost winning increases gambling persistence. The near-miss has been proposed to inflate the value of preceding actions through its perceptual similarity to wins. We demonstrate here, however, that it acts as a conditioned stimulus to positively or negatively influence valuation, dependent on reward expectation and cognitive engagement. When subjects are asked to choose between two simulated slot machines, near-misses increase valuation of machines with a low payout rate, whereas they decrease valuation of high payout machines. This contextual effect impairs decisions and persists regardless of manipulations to outcome feedback or financial incentive provided for good performance. It is consistent with proposals that near-misses cause frustration when wins are expected, and we propose that it increases choice stochasticity and overrides avoidance of low-valued options. Intriguingly, the near-miss effect disappears when subjects are required to explicitly value machines by placing bets, rather than choosing between them. We propose that this task increases cognitive engagement and recruits participation of brain regions involved in cognitive processing, causing inhibition of otherwise dominant systems of decision-making. Our results reveal that only implicit, rather than explicit strategies of decision-making are affected by near-misses, and that the brain can fluidly shift between these strategies according to task demands.

Some of the outstanding questions in neuroscience today are aimed at understanding the cellular and network mechanisms responsible for learned behaviours. Being able to identify and subsequently manipulate those specific neurones previously activated in a behavioural episode is key to this endeavour. A number of different methods have now been developed that enable this to be achieved. In this article, we highlight the Daun02-daunorubicin method of disrupting neuronal activity. Despite the fact that the Daun02-daunorubicin method has been used for a number of years and has been applied across a number of different experimental systems, the mechanism by which Daun02-daunorubicin disrupts neuronal activity is not clear. In this article, we summarise some of the advances that have been made by using this technology and we discuss potential mechanisms by which Daun02-daunorubicin disrupts neuronal function., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2017.)

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

Purpose: Despite the Institute of Medicine's (IOM) 2005 recommendation, few care organizations have instituted standard survivorship care plans (SCPs). Low health literacy and low English proficiency are important factors to consider in SCP development. Our study aimed to identify information needs and survivorship care plan preferences of low literacy, multi-lingual patients to support the transition from oncology to primary care and ongoing learning in survivorship., Methods: We conducted focus groups in five languages with African American, Latina, Russian, Filipina, White, and Chinese medically underserved breast cancer patients. Topics explored included the transition to primary care, access to information, knowledge of treatment history, and perspectives on SCPs., Results: Analysis of focus group data identified three themes: 1) the need for information and education on the transition between "active treatment" and "survivorship"; 2) information needed (and often not obtained) from providers; and 3) perspectives on SCP content and delivery., Conclusions: Our data point to the need to develop a process as well as written information for medically underserved breast cancer patients. An SCP document will not replace direct communication with providers about treatment, symptom management and transition, a communication that is missing in participating safety-net patients' experiences of cancer care. Women turned to peer support and community-based organizations in the absence of information from providers., Implications for Cancer Survivors: "Clear and effective" communication of survivorship care for safety-net patients requires dedicated staff trained to address wide-ranging information needs and uncertainties., Competing Interests: The authors have declared that no competing interests exist.

Functional connectivity between the hippocampus and prefrontal cortex (PFC) is essential for associative recognition memory and working memory. Disruption of hippocampal-PFC synchrony occurs in schizophrenia, which is characterized by hypofunction of NMDA receptor (NMDAR)-mediated transmission. We demonstrate that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of hippocampal-PFC NMDAR-mediated synaptic transmission. We show that dopamine-dependent LTD of NMDAR-mediated transmission profoundly disrupts normal synaptic transmission between hippocampus and PFC. These results show how dopaminergic activation induces long-term hypofunction of NMDARs, which can contribute to disordered functional connectivity, a characteristic that is a hallmark of psychiatric disorders such as schizophrenia.

A large body of data from human and animal studies using psychological, recording, imaging, and lesion techniques indicates that recognition memory involves at least two separable processes: familiarity discrimination and recollection. Familiarity discrimination for individual visual stimuli seems to be effected by a system centred on the perirhinal cortex of the temporal lobe. The fundamental change that encodes prior occurrence within the perirhinal cortex is a reduction in the responses of neurones when a stimulus is repeated. Neuronal network modelling indicates that a system based on such a change in responsiveness is potentially highly efficient in information theoretic terms. A review is given of findings indicating that perirhinal cortex acts as a storage site for recognition memory of objects and that such storage depends upon processes producing synaptic weakening., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Learning is widely believed to involve synaptic plasticity, employing mechanisms such as those used in long-term potentiation (LTP) and long-term depression (LTD). In this chapter, we will review work on mechanisms of synaptic plasticity in perirhinal cortex in vitro and relate these findings to studies underlying recognition memory in vivo. We describe how antagonism of different glutamate and acetylcholine receptors, inhibition of nitric oxide synthase, inhibition of CREB phosphorylation, and interfering with glutamate AMPA receptor internalization can produce deficits in synaptic plasticity in vitro. Inhibition of each of these different mechanisms in vivo also results in recognition memory deficits. Therefore, we provide strong evidence that synaptic plastic mechanisms are necessary for the information processing and storage that underlies object recognition memory., (© 2014 Elsevier Inc. All rights reserved.)

Work is reviewed that relates recognition memory to studies of synaptic plasticity mechanisms in perirhinal and prefrontal cortices. The aim is to consider evidence that perirhinal cortex and medial prefrontal cortex store rather than merely transmit information necessary for recognition memory and, if so, to consider what mechanisms are potentially available within these cortices for producing such storage through synaptic change. Interventions with known actions on plasticity mechanisms are reviewed in relation to their effects on recognition memory processes. These interventions importantly include those involving antagonism of glutamatergic and cholinergic receptors but also inhibition of plasticity consolidation and expression mechanisms. It is concluded that there is strong evidence that perirhinal cortex is involved in information storage necessary for object recognition memory and, moreover, that such storage involves synaptic weakening mechanisms including the removal of AMPA glutamate receptors from synapses. There is good evidence that medial prefrontal cortex is necessary for associative and temporal order recognition memory and that this cortex expresses plasticity mechanisms that potentially allow the storage of information. However, the case for medial prefrontal cortex acting as a store requires further support., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: Ten years after diagnosis, women diagnosed with breast cancer at age 50 or younger were assessed to determine whether quality of life (QOL) problems found at five years persisted. We predicted that QOL in the physical and social domains would be poorer, but improvements would be found in the psychological domain., Methods: We re-interviewed 312 women, who had been interviewed at their five year anniversary and remained cancer free, on their QOL in three domains (physical, social, and psychological). Comparisons between their 5- and 10-year reports were performed using paired t-tests for numeric variables and McNemar's test for categorical variables. Multiple regression analysis was used to model change from 5 to 10 years in each QOL domain, given the level of QOL at 5 years., Results: The women's mean age was 55, 60% were college graduates, 79% had a partner, and 27% were non-Euro-American. Ten years after diagnosis they reported poorer general health (p<0.0001) and physical well-being (p = 0.001), less sexual activity (p = 0.009), and more chronic conditions (p<0.0001) than at 5 years. Relationships were found between: (1) the number of chronic conditions at 5 years and decreased physical, social, and psychological well-being at 10 years; and (2) a smaller social network at 5 years and poorer social functioning at 10 years., Conclusions: Certain aspects of both physical and social QOL worsened over time. The remaining question is whether these changes can be attributed to the late effects of treatment or to normal effects of aging., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Today, the 5-year relative survival rate for cancer is 65% and there are 10.5 million survivors. The largest group of survivors are those of breast cancer. Reductions in mortality are occurring at a greater rate for women under age 50 at diagnosis than among older women., Aims: Our goal was to design a socio-educational intervention for 5-year survivors aged 50 or younger at diagnosis and test the hypotheses that women in the intervention group would show greater improvement than controls with respect to (1) knowledge of breast cancer, its treatment, and long-term health concerns; (2) lifestyle habits (i.e., exercise and diet); and (3) communication with family and physicians., Methods: Using a randomized controlled trial with a pre-post design, 404 women who were 5 years from diagnosis and cancer-free (response rate 54%) were randomly assigned to an intervention or delayed intervention (control) group and were assessed at pre-test (baseline) and 6 months later (96% retention). The intervention consisted of three 6-h workshops over a 3 month period. Four series of workshops were held at different geographical areas in the greater San Francisco Bay Area. The workshops included activities and information to promote physical, social, emotional, and spiritual well-being. The intervention design was based on findings from focus groups and a survey of 185 cancer-free 5-year survivors that assessed changes since the early months after diagnosis in physical, social, emotional, and spiritual concerns (response rate 73%)., Results: Consistent with our first hypothesis, at post-test, women in the intervention group, on average, had greater knowledge regarding breast cancer, its treatment, and their own future health than did those in the control group (p = 0.015). Hypothesis 2 was partially supported as women in the intervention group were more likely than the control group to report an increased amount of physical activity (p = 0.036), but not significant dietary changes. Social support was related to increased self report of physical activity. With the exception of the last series of workshops, the intervention group did not report improved communications with family, friends, and physicians (hypothesis 3)., Conclusions: A short-term intervention can affect knowledge levels and physical activity but not diet or communication in the family., Implications for Cancer Survivors: The intervention was related to greater knowledge related to breast cancer, and increased report of physical activity. The program was not related to changes in reported diet or family communication.

Background: Many African American men have two major risk factors for prostate cancer. By ethnicity alone, they have twice the risk of Euro-American men of developing prostate cancer. Having a family history (brother or father with prostate cancer) also doubles their risk. The major hypotheses tested in this study are that men with a family history perceive their risk to be higher, are more worried about getting prostate cancer, and are more likely to have used cancer screening tests than men without such a history., Methods: A sample of 208 African American men, ages 40 to 74 years, were recruited through relatives or friends whose prostate cancer diagnosis was reported to the California Cancer Registry during the years 1997 to 2001 and from churches and African American social groups. Following a screening interview to determine eligibility, 88 men with self-reported, first-degree family history of prostate cancer and 120 without such history were interviewed by telephone. Logistic regression was used to create models of perceived risk, prostate cancer worries, receipt of a digital rectal exam, and/or prostate-specific antigen (PSA) testing., Results: Men with a self-reported family history of prostate cancer did not perceive their risk as higher than men without a family history, nor did they report more cancer worries. They were more likely to report having a recent PSA test, but not a digital rectal exam. Having a higher than average perceived risk was associated with younger age, a college education, and lower mental well-being, and reporting more prostate cancer worries and being more likely to have had a recent PSA test., Conclusions: Although there continues to be controversy about PSA testing, these data suggest that African American men at above-average risk are inclined to be screened.

Purpose: The purpose of this study was to determine the frequency of body image and sexual problems in the first months after treatment among women diagnosed with breast cancer at age 50 or younger., Background: Breast cancer treatment may have severe effects on the bodies of younger women. Surgical treatment may be disfiguring, chemotherapy may cause abrupt menopause, and hormone replacement is not recommended., Methods: A multi-ethnic population-based sample of 549 women aged 22-50 who were married or in a stable unmarried relationship were interviewed within seven months of diagnosis with in situ, local, or regional breast cancer., Results: Body image and sexual problems were experienced by a substantial proportion of women in the early months after diagnosis. Half of the 546 women experienced two or more body image problems some of the time (33%), or at least one problem much of the time (17%). Among sexually active women, greater body image problems were associated with mastectomy and possible reconstruction, hair loss from chemotherapy, concern with weight gain or loss, poorer mental health, lower self-esteem, and partner's difficulty understanding one's feelings. Among the 360 sexually active women, half (52%) reported having a little problem in two or more areas of sexual functioning (24%), or a definite or serious problem in at least one area (28%). Greater sexual problems were associated with vaginal dryness, poorer mental health, being married, partner's difficulty understanding one's feelings, and more body image problems, and there were significant ethnic differences in reported severity., Conclusions: Difficulties related to sexuality and sexual functioning were common and occurred soon after surgical and adjuvant treatment. Addressing these problems is essential to improve the quality of life of young women with breast cancer.

Background: Women under age 50, a quarter of all cases of breast cancer, are especially vulnerable to physical and psychosocial late effects of their treatment due to having more aggressive treatment and their relative youth., Methods: In person interviews were conducted with the population-based sample: 185 women who were under 50 at diagnosis and were cancer-free 5 years later. Quality of life in the physical, psychological, social, and spiritual domains was assessed and compared with results obtained a few months after diagnosis., Results: Five years after diagnosis, 92% rated their health as good or excellent, and only 10% said their health had been getting worse. Between baseline and 5 years, there were significant improvements in surgical symptoms, body image, worry about the future, patient-physician communication, intrusiveness of treatment, and all of the SF-36 measures except for general health. There were significant decreases in emotional support and the size of one's social network. More women were now menopausal (75% due to treatment) and there were fewer children at home. There were no significant changes in employment status, marital/partner status, sexual activity, sexual problems, self-esteem, and attendance at religious services or frequency of prayer. In multivariate models, a greater increase in physical quality of life was associated with reporting fewer chronic conditions, being employed, having been treated by chemotherapy and fewer had no children under age 18 living at home. A greater increase in mental quality of life was associated with fewer chronic conditions and a smaller decrease in emotional support., Conclusions: Five years after diagnosis, young breast cancer survivors who remained cancer-free enjoyed good health and improved quality of life. Nonetheless, physical, social, and psychological concerns must be addressed so that young breast cancer survivors will continue to be resilient as they age., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: There is little ethnic diversity at the doctoral level among researchers in cancer control. The Minority Training Program in Cancer Control Research is designed to encourage underrepresented master's level health science students to pursue doctoral training and careers in research., Methods: Program components include an annual 5-day summer institute, internships, and doctoral incentive awards. Intention to pursue doctoral training is measured before and after participation. Doctoral applications and enrollment are tracked through annual surveys., Results: Seventy students participated during the first three years, 1999-2001. Intention to apply increased significantly for each class (year one, p %lt; 0.001; year two, p = 0.042; year three, p = 0.006). Thirty-one percent of participants have either enrolled in doctoral programs (n= 10) or report plans to apply in the next one to two years (n = 9). Over half of these students indicated that the MTPCCR had a positive influence on their plans., Conclusions: A targeted training program encourages under-represented students to pursue doctoral degrees and thus has the potential to increase ethnic diversity in public health research.