Thalamocortical Projections Are Significantly Impaired in the R6/2 Mouse Model of Huntington's Disease.

As Huntington's disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL; motor) and ventral posteromedial nucleus (VPM; somatosensory) thalamic neurons in ex vivo brain slices of R6/2 and wild-type (WT) mice revealed that cells in both thalamic nuclei of R6/2 mice exhibited significant differences in passive and active cell membrane properties (smaller cell membrane capacitances, faster decay time constants and increased input resistances) compared with WT cells. Although only cells in the VPM of symptomatic R6/2 mice had more depolarized resting membrane potentials compared with WTs, cells in both nuclei displayed increased excitability in symptomatic, but not presymptomatic, R6/2 mice. Optical activation of VAL and VPM terminals elicited smaller magnitude current responses in cortical pyramidal neurons (CPNs) in both motor cortex (M1CTX) and somatosensory barrel cortex (BCTX) of symptomatic R6/2 mice compared with CPNs in WT mice. Furthermore, we observed a decrease in the frequency of thalamocortical excitatory quantal events in R6/2 BCTX CPNs, with no genotype-dependent differences in AMPA:NMDA response amplitude ratios. These data suggest there is a decrease in the transmission of thalamocortical information that is likely because of impaired neurotransmitter release.

Greater Average Meal Planning Frequency Predicts Greater Weight Loss Outcomes in a Worksite-Based Behavioral Weight Loss Program.

BACKGROUND: Planning in behavioral weight loss (BWL) programs helps participants enact changes in eating and exercise, although the direct impact on weight loss is unclear. PURPOSE: To examine how meal and exercise planning frequencies change in a BWL program and their relations to weight loss outcomes. METHODS: Participants (N = 139) in a 40 week worksite-based BWL program completed a questionnaire regarding meal and exercise planning frequency at Weeks 0, 10, 20, 30, and 40 and were weighed weekly. Growth curve models were used to determine trajectories in meal and exercise planning frequency and to assess the role of an individual's average meal and exercise planning (between-person effect) and individual variation in planning (within-person effect) on body mass index (BMI). RESULTS: The best-fitting model, a linear random effect with a quadratic fixed-effect model, demonstrated that meal and exercise planning frequency increased over the course of the program with slowing growth rates. Between participants, higher average meal planning frequency (B = -0.029, t = -3.60), but not exercise planning frequency, was associated with greater weight loss. Within participants, exercise planning, but not meal planning, predicted a higher than expected BMI (B = 3.17, t = 4.21). CONCLUSIONS: Frequent meal planning should be emphasized as a continued, as opposed to intermittent, goal in BWL programs to enhance weight loss. Average exercise planning frequency does not impact weight loss in BWL programs; however, acute increases in exercise planning frequency may be a popular coping strategy during a weight loss setback or, alternatively, may lead to increased calorie consumption and weight gain.

CREB controls cortical circuit plasticity and functional recovery after stroke.

Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with the hM4Di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue, demonstrating that by manipulating the activity of CREB-transfected neurons it is possible to turn off and on stroke recovery. CREB transfection enhances remapping of injured somatosensory and motor circuits, and induces the formation of new connections within these circuits. CREB is a central molecular node in the circuit responses after stroke that lead to recovery from motor deficits.

Barriers and facilitators to self-management of asthma in adolescents: An interview study to inform development of a novel intervention.

BACKGROUND AND OBJECTIVE: Despite literature that spans twenty years describing the barriers to asthma self-management in adolescents, successful, clinically based interventions to address this important issue are lacking. Given the limitations of some of the previous studies, we conducted a study that aimed to gain a broader insight into barriers and facilitators to self-management of asthma by adolescents, not just adherence to treatment, and triangulated their views with those of their parents and healthcare professionals. METHODS: Focus groups and interviews were conducted separately for 28 adolescents with asthma aged 12-18 years, 14 healthcare professionals and 12 parents. Focus groups and interviews were audio-recorded, and transcripts from each participant group were analysed separately using inductive thematic analysis. We triangulated the three perspectives by comparing themes that had emerged from each analysis. RESULTS: Adolescents', parents' and healthcare professionals' views were summarized into ten related themes that included forgetting and routines, knowledge, embarrassment and confidence, communication with healthcare professionals, triggers, support at school, apathy and taking responsibility. We found that adolescents, parents and healthcare professionals raised similar barriers and facilitators to self-management and our results provide further validation for previous studies. CONCLUSION AND CLINICAL RELEVANCE: Our study highlights that healthcare professionals may need to consider a range of psychological and contextual issues influencing adolescents' ability to effectively self-manage their asthma, in particular, how they implement treatment routines and the understanding that adolescents have of their condition and treatments. Crucially, healthcare professionals need to consider how this information is communicated and ensure they facilitate open, inclusive, two-way consultations. From this more comprehensive understanding, we have developed interventional strategies that healthcare professionals can utilize to empower adolescents to improve their asthma self-management.

On the same page: a novel interprofessional model of patient-centered perinatal consultation visits.

OBJECTIVE: To plan and implement an interprofessional collaborative care clinic for women in midwifery care needing a consultation with a maternal-fetal medicine specialist. STUDY DESIGN: A community-engaged design was used to develop a new model of collaborative perinatal consultation, which was tested with 50 women. Participant perinatal outcomes and semistructured interviews with 15 women (analyzed using qualitative descriptive analysis) and clinic providers were used to evaluate the model. RESULTS: Participant perinatal outcomes following a simultaneous consultation visit involving a nurse-midwife and maternal-fetal medicine specialist were similar to practice and hospital averages. Women's comments on their experience were positive and had the theme 'on the same page' with six subcategories: clarity, communication, collaboration, planning, validation and 'above and beyond'. Providers also were pleased with the model. CONCLUSION: A simultaneous consultation involving the woman, a nurse-midwife and a maternal-fetal medicine specialist improved communication and satisfaction among women and providers.

Executive function and sleep problems in childhood epilepsy.

Pediatric epilepsy has been reported to be associated with both sleep problems and cognitive deficits. In turn, in healthy children, poorer sleep has been associated with deficits in cognitive functioning. We hypothesized that poor sleep in childhood epilepsy may contribute to cognitive deficits. Using actigraphy, we objectively measured the sleep of children with epilepsy alongside that of healthy controls. In contrast to previous reports, we did not find any differences in objectively measured sleep between children with epilepsy and healthy controls. However, significant deficits in cognitive functioning were demonstrated that were not explained by differences in sleep.

Graveyards - special landfills.

Graveyards have been a matter of controversial debate for many years in terms of the risk they pose to the environment. However, literature data are inconclusive and there are no systematic studies available from modern graveyards with special reference to soil found in the vicinity of the coffin. To our knowledge, the present study is the first to systematically investigate a comprehensive exhumation series (involving 40 graves) in order to determine burial-related changes in matter and element content. Human burials lead to the accumulation of certain elements, with higher than normal levels of N, C, Zn, Ba, Ca and Na being observed in soils below coffins. Decomposition material inside coffins has much higher levels of heavy metals and alkaline elements than the surrounding soil. However, the major problem observed was the large quantity of synthetic bedding material which is more likely to lead to the formation of adipocere under the moist conditions given. Adipocere formation, which is the result of the anaerobic bacterial hydrolysis of fat, is known to interrupt the natural decomposition process and delay the post-mortem release of elements. We assume that once the inhumed matter has completely decomposed, much higher than normal levels of pollutants will be released into and have an ecological effect on the soil and water environment.

Use of human chorionic gonadotropin in a male Pacific walrus (Odobenus rosmarus divergens) to induce rut and achieve a pregnancy in a nulliparous female.

Walrus in US zoos have a very low reproductive rate of 11 births in 80 years, and little is known about Pacific walrus (Odobenus rosmarus divergens) reproductive biology. To address this, we initiated a program in which detailed biological data were recorded on captive walrus. As part of a 7-year study, 1 male and 1 female 16-year-old captive Pacific walrus were carefully monitored with weekly serum hormone analysis, daily glans penis smears for spermatozoa, and abdominal ultrasound for pregnancy. The female ovulated once annually from late December through mid-January and then exhibited 9 months of sustained elevated progesterone. This nonconceptive estrous cycle profile is consistent with reports from wild walrus females. In contrast, the male's seasonal rut routinely occurred in late February through May with a serum testosterone peak in March. This profile differed from the reported adult male cycle in wild walrus of November through March. During the period of the female's ovulation, the male had nadir testosterone levels and was consistently azoospermic. Likewise, during the male's spermatogenic rut in the spring, the female was anovulatory with elevated progesterone. On this basis, the male was treated for 14 weeks with human chorionic gonadotropin (hCG) in an attempt to increase testosterone levels in synchrony with the female's annual ovulation. The treatment successfully induced rut characterized by sustained elevated serum testosterone levels and production of spermatozoa. The male and female successfully bred, and the female became pregnant. Upon discontinuation of hCG treatment, the male resumed baseline testosterone levels. We theorize that the lack of synchronization of rut and ovulatory cycles is a primary reason for reproductive failure in these captive walrus.

Humor as aggression: effects of motivation on hostility expressed in humor appreciation.

In 4 studies, the authors examined the hypothesis that relative to primed autonomy motivation, primed control would increase enjoyment of hostile (compared with nonhostile) humor as assessed by self-reported enjoyment and aversiveness and by nonverbal behavior. Results confirmed the hypothesis. Furthermore, initial state hostility moderated the effect such that high-hostility participants who were primed with control motivation especially enjoyed hostile humor. The 2 final studies showed that the effect was mediated by implicit aggression such that the combination of high initial state hostility and control priming led to implicit aggression, which in turn resulted in hostile humor enjoyment. Results are interpreted in terms of the effects of autonomy versus control motivation on intrapersonal self-regulatory processes, which influence interpersonal functioning.

An hour less sleep is a risk factor for childhood conduct problems.

BACKGROUND: There is emerging evidence that sleep problems in childhood may have enduring consequences. Studies using parental and objective sleep measurement suggest that sleep difficulties in children may be associated with behavioural problems. However, the findings using objective sleep measures are inconsistent and it is not clear what aspects of sleep quality are associated with daytime behavioural difficulties. The aim of this paper is to identify which behavioural symptoms are best predicted by actigraphic sleep measures in a general population sample of school-aged children aged 6-11 years. METHODS: Actigraphy was used to measure sleep in 91 typically developing children aged 6-11 years for 6 days. Parents completed the Strengths and Difficulties Questionnaire (SDQ). A series of multivariate linear regression models were computed to analyse the effects of sleep on SDQ subscales. RESULTS: Sleep did not predict emotional symptoms or hyperactivity. After controlling for age and gender, sleep accounted for 18% of the variance in conduct problems. Only actual sleep time in minutes made a significant contribution to the model. CONCLUSIONS: A child who sleeps 1 h less than the average child may be at risk of conduct problems. Clinicians should consider routinely screening for sleep difficulties when assessing children with conduct problems.

Autonomy and control in dyads: effects on interaction quality and joint creative performance.

Two studies examined interaction quality and joint performance on two creative tasks in unacquainted dyads primed for autonomy or control orientations. It was hypothesized that autonomy-primed dyads would interact more constructively, experience more positive mood, and engage the task more readily, and as a result these dyads would perform better. To test this, Study 1 primed orientation and explored verbal creative performance on the Remote Associates Task (RAT). In Study 2, dyads were primed with autonomy and control orientation and videotaped during two joint creative tasks, one verbal (RAT) and one nonverbal (charades). Videotapes were coded for behavioral indicators of closeness and task engagement. Results showed that autonomy-primed dyads felt closer, were more emotionally and cognitively attuned, provided empathy and encouragement to partners, and performed more effectively. The effects of primed autonomy on creative performance were mediated by interpersonal quality, mood, and joint engagement.

The cost of self-protection: threat response and performance as a function of autonomous and controlled motivations.

Seventy-seven undergraduates, primed for autonomous or controlled motivation, were videotaped and physiologically monitored during a stressful interview and subsequent speech. Interview videotapes were coded for behavioral measures of threat response; speech videotapes were coded for performance. It was hypothesized that relative to controlled motivation, autonomous motivation would decrease interview threat response and enhance speech performance, and that threat response would mediate the effect of motivation on performance. Results support the prediction across measures of verbal, paralinguistic, smiling, vocal fundamental frequency, and cardiovascular response. Autonomously primed participants continued to show less cardiovascular threat throughout the later speech and gave better speeches. Finally, speech performance was mediated by interview threat response. Results demonstrate that relative to controlled motivation, autonomous motivation lowers threat response, which enhances performance.

Attentional processes and meditation.

Visual attentional processing was examined in adult meditators and non-meditators on behavioral measures of change blindness, concentration, perspective-shifting, selective attention, and sustained inattentional blindness. Results showed that meditators (1) noticed more changes in flickering scenes and noticed them more quickly, (2) counted more accurately in a challenging concentration task, (3) identified a greater number of alternative perspectives in multiple perspectives images, and (4) showed less interference from invalid cues in a visual selective attention task, but (5) did not differ on a measure of sustained inattentional blindness. Together, results show that regular meditation is associated with more accurate, efficient, and flexible visual attentional processing across diverse tasks that have high face validity outside of the laboratory. Furthermore, effects were assessed in a context separate from actual meditation practice, suggesting that meditators' better visual attention is not just immediate, but extends to contexts separate from meditation practice.

The moderating role of autonomy and control on the benefits of written emotion expression.

Two studies examined the hypothesis that relative to control motivation, autonomy motivation is associated with effective written expression and regulation, leading to positive emotional, physical, and cognitive outcomes over time. Participants viewed a Hiroshima-Nagasaki documentary in each of two sessions. Study 1 showed that dispositionally autonomous participants, particularly those who expressed, had positive well-being, energy, and memory after the second viewing. Study 2 explored benefits of situational motivation by priming autonomy and control. Results showed that dispositionally controlled individuals received the same benefits as autonomous individuals only when primed with autonomy and encouraged to express. Coding of writing content revealed that the benefits of autonomy were mediated by nondefensive and effective emotional processing, as reflected in greater use of self-referencing and cognitive mechanism words and lower use of concrete words. Results support the expectation that autonomy relates to effective expression and emotion regulation, leading to positive functioning over time.

Segmentation of touching cell nuclei using gradient flow tracking.

Reliable cell nuclei segmentation is an important yet unresolved problem in biological imaging studies. This paper presents a novel computerized method for robust cell nuclei segmentation based on gradient flow tracking. This method is composed of three key steps: (1) generate a diffused gradient vector flow field; (2) perform a gradient flow tracking procedure to attract points to the basin of a sink; and (3) separate the image into small regions, each containing one nucleus and nearby peripheral background, and perform local adaptive thresholding in each small region to extract the cell nucleus from the background. To show the generality of the proposed method, we report the validation and experimental results using microscopic image data sets from three research labs, with both over-segmentation and under-segmentation rates below 3%. In particular, this method is able to segment closely juxtaposed or clustered cell nuclei, with high sensitivity and specificity in different situations.

Cyclin D1 polymorphism and expression in patients with squamous cell carcinoma of the head and neck.

We have previously reported that the cyclin D1 (CCND1) GG870 genotype was associated with poorly differentiated tumors and reduced disease-free interval in patients with squamous cell carcinoma of the head and neck (SCCHN). We have now examined the association of this and a second CCND1 polymorphism with gene expression and outcome in SCCHN patients. Analysis of a CCND1 G/C1722 polymorphism revealed that CCND1 CC1722 genotype was associated with poorly differentiated tumors [P = 0.005; odds ratio (OR), 5.7; 95% CI, 1.7 to 19.2), and reduced disease-free interval (P = 0.003; Hazard Ratio (HR), 7.3; 95% CI, 1.1 to 27.2.) independently from the influence of CCND1 GG870 genotype. Patients whose tumors were negative for cyclin D1 were associated with reduced disease-free interval (P = 0.028; HR, 4.1; 95% CI, 1.4 to 14.2). Although G/C1722 genotypes were not associated with expression, we found a significant trend between reduced expression of cyclin D1 in patients with the CCND1 GG870 genotype (P = 0.04). Splicing of CCND1 mRNA in head and neck tissues was modulated by CCND1 A/G870 alleles, thus CCND1 transcript a was spliced equally from CCND1 A870 and G870 alleles, whereas CCND1 transcript b was spliced mainly from the CCND1 A870 allele. Our analysis has also identified differences in cyclin D1 genotype and protein expression and the pathogenesis of SCCHN in males and females. Thus, CCND1 CC1722 genotype was more common in female patients (P = 0.019; OR, 3.3; 95% CI, 1.3 to 10) and cyclin D1 expression was more frequent (chi-square1, 3.96; P = 0.046) and at higher levels (P = 0.004) in tumors from female patients. In summary, our data show that the two CCND1 polymorphic sites are independently associated with tumor biology and clinical outcome. CCND1 A/G870 alleles affect gene expression in head and neck tissues. We also provide preliminary evidence that the molecular genetics of SCCHN development may be influenced by patient gender.

Energy for living with cancer: preliminary findings of a cancer rehabilitation group intervention study.

PURPOSE/OBJECTIVES: To evaluate the acceptability and efficacy of a rehabilitation group intervention for people with cancer experiencing cancer-related fatigue (CRF) and examine the effects of the program on CRF distress. quality of life (QOL), and depression. DESIGN: Prospective, pre-/post-test intervention. SETTING: An outpatient area of a 551 -bed tertiary-care community hospital in the southeastern United States. SAMPLE: 20 participants have completed the program in four different groups. The preliminary mean age was 63.6 (range = 38-86). These participants had six different types of cancers, and 15 patients were receiving some form of cancer therapy during their participation in the program. METHODS: After providing informed consent participants completed the Cancer-Related Fatigue Distress Scale, the Center for Epidemiological Studies-Depression, the Functional Living Index-Cancer, and a demographic Information form. The intervention consists of eight weekly, 90-minute sessions with educational and sharing components. At the eighth session, participants were asked to complete the three instruments plus a program evaluation. MAIN RESEARCH VARIABLES: CRF distress, depression, QOL. FINDINGS: Preliminary results indicate that the program provided information, support, and management strategies for CRF. The mean for the program evaluations overall was 9.8 (0-10 scale, range = 9-10). Statistically significant differences were found for pre- and post-test fatigue distress and QOL scores. CONCLUSIONS: Preliminary findings indicate that this intervention is appropriate and beneficial for patients with cancer experiencing fatigue, even for those patients who are very debilitated. IMPLICATIONS FOR NURSING PRACTICE: The program can be used as a rehabilitation program to help people with cancer to manage the sequelae of their illness and treatments.

Zebrafish lunatic fringe demarcates segmental boundaries.

Cell interactions involving Notch signaling are required for the demarcation of tissue boundaries in both invertebrate and vertebrate development. Members of the Fringe gene family encode beta-1,3 N-acetyl-glucosaminyltransferases that function to refine the spatial localization of Notch-receptor signaling to tissue boundaries. In this paper we describe the isolation and characterization of the zebrafish (Danio rerio) homologue of the lunatic fringe gene (lfng). Zebrafish lfng is generally expressed in equivalent structures to those reported for the homologous chick and mouse genes. These sites include expression along the A-P axis of the neural tube, within the lateral plate mesoderm, in the presomitic mesoderm and the somites and in specific rhombomeres of the hindbrain; however, within these general expression domains species-specific differences in lfng expression exist. In mouse, Lfng is expressed in odd-numbered rhombomeres, whereas in zebrafish, expression occurs in even-numbered rhombomeres. In contrast to reports in both mouse and chicken embryos showing a kinematic cyclical expression of Lfng mRNA in the presomitic paraxial mesoderm, we find no evidence for a cyclic pattern of expression for the zebrafish lfng gene; instead, the zebrafish lfng is expressed in two static stripes within the presomitic mesoderm. Nevertheless, in zebrafish mutants affecting the correct formation of segment boundaries in the hindbrain and somites, lfng expression is aberrant or lost.

Evaluating patient distress from cancer-related fatigue: an instrument development study.

PURPOSE/OBJECTIVES: To develop a clinically useful and psychometrically sound tool for the measurement of the distress from fatigue in patients with cancer. DESIGN: Instrument development of a numeric rating scale to assess cancer-related fatigue (CRF) distress. SETTING: A comprehensive cancer center and a Veterans Administration hospital. SAMPLE: The interview sample consisted of 17 adults with cancer experiencing CRF. The sample for instrument testing consisted of 221 adults with cancer. Twenty-nine different types of cancers were among the diagnoses. Seventy-eight percent of the participants were receiving some form of cancer treatment. The mean age was 60. METHODS: The Cancer-Related Fatigue Distress Scale (CRFDS) was developed from 23 in-depth audiotaped interviews with patients experiencing CRF. Krippendorff's content analysis procedures were used for interview analysis. Twenty-three items were generated. Five cancer survivors assessed content validity. Factor analysis was used to assess construct validity, and coefficient alpha was used to estimate the reliability of the CRFDS. FINDINGS: Factor analysis resulted in all items loading on one factor, indicating a single scale. The coefficient alpha was 0.98 after the elimination of three items. CONCLUSIONS: The CRFDS has strong content validity, high reliability, and very good construct validity. IMPLICATIONS FOR NURSING PRACTICE: The CRFDS is a clinically useful and psychometrically sound tool for the measurement of CRF distress. This tool is clinically useful because of its brevity (20 items), clear instructions that required no training to use, and a readability score at the third-grade level.

Control of her1 expression during zebrafish somitogenesis by a delta-dependent oscillator and an independent wave-front activity.

Somitogenesis has been linked both to a molecular clock that controls the oscillation of gene expression in the presomitic mesoderm (PSM) and to Notch pathway signaling. The oscillator, or clock, is thought to create a prepattern of stripes of gene expression that regulates the activity of the Notch pathway that subsequently directs somite border formation. Here, we report that the zebrafish gene after eight (aei) that is required for both somitogenesis and neurogenesis encodes the Notch ligand DeltaD. Additional analysis revealed that stripes of her1 expression oscillate within the PSM and that aei/DeltaD signaling is required for this oscillation. aei/DeltaD expression does not oscillate, indicating that the activity of the Notch pathway upstream of her1 may function within the oscillator itself. Moreover, we found that her1 stripes are expressed in the anlage of consecutive somites, indicating that its expression pattern is not pair-rule. Analysis of her1 expression in aei/DeltaD, fused somites (fss), and aei;fss embryos uncovered a wave-front activity that is capable of continually inducing her1 expression de novo in the anterior PSM in the absence of the oscillation of her1. The wave-front activity, in reference to the clock and wave-front model, is defined as such because it interacts with the oscillator-derived pattern in the anterior PSM and is required for somite morphogenesis. This wave-front activity is blocked in embryos mutant for fss but not aei/DeltaD. Thus, our analysis indicates that the smooth sequence of formation, refinement, and fading of her1 stripes in the PSM is governed by two separate activities.