␤-Site APP-cleaving enzyme 1 (BACE1) is required for the penultimate cleavage of the amyloid-␤ precursor protein (APP) leading to the generation of amyloid-␤ peptides that is central to the pathogenesis of Alzheimer's disease. In addition to its role in endoproteolysis of APP, BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) and influences the myelination of central and peripheral axons. Although NRG1 has been genetically linked to schizophrenia and NRG1 ؉/؊ mice exhibit a number of schizophrenia-like behavioral traits, it is not known whether altered BACE1-dependent NRG1 signaling can cause similar behavioral abnormalities. To test this hypothesis, we analyze the behaviors considered to be rodent analogs of clinical features of schizophrenia in BACE1 ؊/؊ mice with impaired processing of NRG1. We demonstrate that BACE1 ؊/؊ mice exhibit deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic psychostimulant (MK-801), cognitive impairments, and deficits in social recognition. Importantly, some of these manifestations were responsive to treatment with clozapine, an atypical antipsychotic drug. Moreover, although the total amount of ErbB4, a receptor for NRG1 was not changed, binding of ErbB4 with postsynaptic density protein 95 (PSD95) was significantly reduced in the brains of BACE1 ؊/؊ mice. Consistent with the role of ErbB4 in spine morphology and synaptic function, BACE1 ؊/؊ mice displayed reduced spine density in hippocampal pyramidal neurons. Collectively, our findings suggest that alterations in BACE1-dependent NRG1/ErbB4 signaling may participate in the pathogenesis of schizophrenia and related psychiatric disorders.clozapine ͉ dizocilpine ͉ neuregulin ͉ prepulse inhibition ͉ spine density B ACE1 (␤-site APP-cleaving enzyme 1), is the rate-limiting enzyme that makes the initial cleavage of the amyloid-␤ (A␤) precursor protein (APP) and, in concert with ␥-secretase, gives rise to the plaque-forming ␤-amyloid peptides in Alzheimer's disease (AD) (1). Deletion of BACE1 prevents the formation of A␤ in vitro and in vivo and the cognitive abnormalities in mouse models of A␤ amyloidosis. These findings strongly support BACE1 as an attractive therapeutic target for AD (1-3). In addition to APP, a number of other putative substrates for BACE1 have been identified, suggesting that BACE1 has multiple physiological functions (2). For example, recent studies indicate that BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) (4, 5), a ligand for members of the ErbB family of receptor-tyrosine kinases. This signaling pathway have numerous roles in CNS development and functions, including synapse formation, plasticity, neuronal migration, myelination of central and peripheral axons, and the regulation of neurotransmitter expression and function (6, 7). In addition to these physiological functions, NRG1 is one of the first genes that has been linked to an increased risk of schizophrenia (8). The disease-associated single-nucleotide polymor...

Context-Multiple complex symptoms from cancer treatment can interfere with functioning.Objectives-To evaluate the efficacy of an "energy and sleep enhancement" (EASE) intervention to relieve fatigue and sleep disturbance and improve health-related functional status.Methods-Individuals receiving chemotherapy were randomized to the EASE (n = 153) or a control intervention (n = 139). The EASE intervention included information and behavioral skills taught by an oncology nurse in three telephone sessions. The primary outcomes of fatigue, sleep disturbance and functional status were measured before chemotherapy, Day 4 after first treatment (baseline) and 43-46 or 57-60 days later (follow-up) depending on chemotherapy cycle length.Results-The sample was primarily female (82%) and non-Hispanic white (89%) with mean age of 53.9 years. Fatigue and patient-reported sleep disturbance were elevated in both groups at baseline and follow-up. Actigraphy revealed total sleep time was almost eight hours and sleep percent was over 85% for both groups at both time points (normal range). Physical functioning was diminished and at the same level as a sample with serious illness. Mental functioning was in normal range. A repeated measures analysis of variance revealed no statistically significant groupby-time effects for fatigue, sleep disturbance, or functional status. Unemployed individuals showed greater benefit from the EASE intervention, reporting less pain and symptom interference.Conclusion-Potential explanations include high variability and/or floor effect for fatigue; incorrect timing of measures; insufficient amount or dose of the intervention; and confounding effects of gender. Future research should consider screening for symptom severity and tailoring interventions.

Goals of Work To characterize sleep quality and quantity prior to and in the first 3 nights after initial chemotherapy for breast cancer. Patients and Methods Secondary analysis of data from two separate randomized clinical trials (RCT) of behavioral interventions to improve fatigue and sleep. Patients came from two comprehensive cancer centers, three clinical cancer centers, and 10 community clinics in five states. Participants were women with stage I-IIIA breast cancer treated with anthracycline and/or cyclophosphamide based regimens. Main Results Baseline data from each RCT were used in the analysis. Sixty-five percent of women self-reported poor sleep in the month preceding chemotherapy using the Pittsburgh Sleep Quality Index (PSQI) score >5. Three nights of actigraphy data indicated a wide range of sleep experience with an average of 10 awakenings and time (minutes) awake after sleep onset (WASO-M) averaging 61 minutes per night. The first night’s sleep was the worst. There was no statistically significant relationship between self-reported poor sleep and sleep measures obtained by actigraphy. Women with poor sleep at baseline (global PSQI >5) had significantly lower (p<.001) physical (MOS PCS) and mental (MOS MCS) health status. However neither the PCS nor MCS was associated with any of the average actigraphy sleep parameters or Night 1 parameters in the aggregated sample. Increasing age was also associated with poorer sleep. Conclusions A high percent of women with breast cancer begin chemotherapy with disturbed sleep and the initial nights after chemotherapy are characterized by sleep fragmentation that disrupts sleep maintenance. Interventions should focus on strategies to decrease the number and duration of night awakenings. Further research is needed to identify predictors of poor sleep during this time.

Gall et al. (2005) developed a framework for spirituality by adapting and applying the transactional model of stress and coping, which is an interactive and fluid process spurred by a stressor involving spiritual appraisal, person factors, spiritual connections, spiritual coping behavior, and meaning-making impacting well-being. The components of the framework are examined through five cancer survivor narratives. The results showed that the components of the framework were experienced by the survivors, for example, various spiritual problem-solving styles were used, indication of spiritual connections to nature, others, and the transcendent. Meaning-making was common as they faced the life-threatening disease which often altered their worldview. The spirituality of the participants is reflected in the spiritual framework and the framework embraces these survivor experiences. This study has limitations due to its qualitative nature and small sample size.

Purpose This paper aims to review existing literature on distance library services for individuals with disabilities with a specific focus on deaf and hard of hearing (D/HH) users and provide strategies for creating an online library that is accessible to this community. Design/methodology/approach The authors reviewed articles covering distance library services for D/HH users and then identified specific parts of the Web Content Accessibility Guidelines (WCAG) 2.0 that are applicable to the D/HH community. By using the literature, strategies for developing and purchasing accessible electronic library resources are presented. Findings While there is a breadth of literature focused on creating accessible resources for online libraries, there is a gap when it comes to D/HH users. Libraries can cater to this community by providing text-based alternatives for all library instructional materials and working closely with vendors to ensure that library databases are accessible. Practical implications The authors present strategies for creating and converting electronic resources and services that are accessible to D/HH users. Originality/value This paper fills a gap in literature by addressing fully online library services for users with disabilities with a particular focus on meeting the needs of D/HH users in a distance-learning environment.