Summary This review examined the efficacy of cognitive behavior therapy for insomnia (CBT-I) in people diagnosed with cancer. Studies were identified through November 2014 using multiple databases, ...clinical trial records, and bibliography searches. Inclusion was limited to randomized controlled trials of CBT-I conducted in individuals with a cancer diagnosis who had clinically relevant insomnia. The primary outcome variable was sleep efficiency (SE) as measured by sleep diary. Eight studies including data from 752 cancer survivors met inclusion criteria. CBT-I resulted in a 15.5% improvement in SE relative to control conditions (6.1%) from pre- to post-intervention, with a medium effect size (ES: d = 0.53). Overall, sleep latency was reduced by 22 min with an ES of d = 0.43, compared to a reduction of 8 min in the control conditions. Wake after sleep onset was reduced by 30 min with an ES of d = 0.41, compared to 13 min in the control conditions. Large effect sizes were observed for self-reported insomnia severity ( d = 0.77) for those patients who received CBT-I, representing a clinically relevant eight point reduction. Effects were durable up to 6 mo. The quality of the evidence supports a strong recommendation for the use of CBT-I among cancer survivors.
H-Ras, K-Ras, and N-Ras are small GTPases that are important in the control of cell proliferation, differentiation, and survival, and their mutants occur frequently in human cancers. The G-domain, ...which catalyzes GTP hydrolysis and mediates downstream signaling, is 95% conserved between the Ras isoforms. Because of their very high sequence identity, biochemical studies done on H-Ras have been considered representative of all three Ras proteins. We show here that this is not a valid assumption. Using enzyme kinetic assays under identical conditions, we observed clear differences between the three isoforms in intrinsic catalysis of GTP by Ras in the absence and presence of the Ras-binding domain (RBD) of the c-Raf kinase protein (Raf-RBD). Given their identical active sites, isoform G-domain differences must be allosteric in origin, due to remote isoform-specific residues that affect conformational states. We present the crystal structure of N-Ras bound to a GTP analogue and interpret the kinetic data in terms of structural features specific for H-, K-, and N-Ras.
The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features.
Microarray gene expression profiling was done on ...285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results.
Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends.
Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.
Purpose
Cancer-related fatigue (CRF) is a common and distressing symptom that can persist after cancer treatment has concluded. Bright light therapy has shown preliminary efficacy in reducing CRF, ...but its impact on other psychosocial factors is unclear. The purpose was to examine the impact of a 1-month light therapy intervention on fatigue, mood, and quality of life in cancer survivors with fatigue.
Methods
This 4-week blinded randomized controlled trial recruited cancer survivors who met diagnostic criteria for CRF. Participants were randomly assigned to receive a light therapy device that produced either bright white light (BWL; intervention) or dim red light (DRL; active control). Participants were instructed to use the device daily for 30 min upon waking for 28 days. The primary outcome, fatigue, was assessed weekly. Secondary outcomes assessed pre- and post-intervention included mood, depressive symptoms, and quality of life.
Results
A total of 81 participants were randomly assigned to receive BWL (
n
= 42) or DRL (
n
= 39). Analyses revealed a group-by-time interaction for fatigue (
p
= .034), wherein the BWL condition reported a 17% greater reduction in fatigue than those in the DRL condition (between group
d
= .30). There were also significant improvements over time for both groups on measures of mood, depressive symptoms, and quality of life (
p
’s < .01).
Conclusions
BWL was associated with greater improvements in fatigue and both groups displayed improvements on secondary psychosocial outcomes.
Implications for cancer survivors
These findings, along with previous reports of light therapy for CRF, support the use of this intervention to improve fatigue in cancer survivors.
Background
Irritable bowel syndrome (IBS) is a functional disorder of the lower gastrointestinal (GI) tract affected by stress, which may benefit from a biopsychosocial treatment approach such as ...mindfulness-based stress reduction (MBSR).
Purpose
A treatment as usual (TAU) wait-list controlled trial was conducted in Calgary, Canada to investigate the impact of MBSR on IBS symptoms. It was hypothesized that MBSR patients would experience greater reduction in overall IBS symptom severity and self-reported symptoms of stress relative to control patients.
Method
Ninety patients diagnosed with IBS using the Rome III criteria were randomized to either an immediate MBSR program (
n
= 43) or to wait for the next available program (
n
= 47). Patients completed IBS symptom severity, stress, mood, quality of life (QOL), and spirituality scales pre- and post-intervention or waiting period and at 6-month follow-up. Intent-to-treat linear mixed model analyses for repeated measures were conducted, followed by completers analyses.
Results
While both groups exhibited a decrease in IBS symptom severity scores over time, the improvement in the MBSR group was greater than the controls and was clinically meaningful, with symptom severity decreasing from constantly to occasionally present. Pre- to post-intervention dropout rates of 44 and 23 % for the MBSR and control groups, respectively, were observed. At 6-month follow-up, the MBSR group maintained a clinically meaningful improvement in overall IBS symptoms compared to the wait-list group, who also improved marginally, resulting in no statistically significant differences between groups at follow-up. Improvements in overall mood, QOL, and spirituality were observed for both groups over time.
Conclusions
The results of this trial provide preliminary evidence for the feasibility and efficacy of a mindfulness intervention for the reduction of IBS symptom severity and symptoms of stress and the maintenance of these improvements at 6 months post-intervention. Attention and self-monitoring and/or anticipation of MBSR participation may account for smaller improvements observed in TAU patients.
Individuals with cancer are disproportionately affected by sleep disturbance and insomnia relative to the general population. These problems can be a consequence of the psychological, behavioral, and ...physical effects of a cancer diagnosis and treatment. Insomnia often persists for years and, when combined with already high levels of cancer-related distress, may place cancer survivors at a higher risk of future physical and mental health problems and poorer quality of life. The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I), a non-pharmacological treatment that incorporates cognitive and behavior-change techniques and targets dysfunctional attitudes, beliefs, and habits involving sleep. This article presents a comprehensive review of the literature examining the efficacy of CBT-I on sleep and psychological outcomes in cancer patients and survivors. The search revealed 12 studies (four uncontrolled, eight controlled) that evaluated the effects of CBT-I in cancer patients or survivors. Results suggest that CBT-I is associated with statistically and clinically significant improvements in subjective sleep outcomes in patients with cancer. CBT-I may also improve mood, fatigue, and overall quality of life, and can be successfully delivered through a variety of treatment modalities, making it possible to reach a broader range of patients who may not have access to more traditional programs. Future research in this area should focus on the translation of evidence into clinical practice in order to increase awareness and access to effective insomnia treatment in cancer care.
The ubiquitous Stille coupling reaction utilizes Sn−C bonds and is of great utility to organic chemists. Unlike the B−C bonds used in the Miyaura−Suzuki coupling reaction, which are readily obtained ...via direct borylation of C−H bonds, routes to organotin compounds via direct C−H bond functionalization are lacking. Here we report that the nickel-catalyzed reaction of fluorinated arenes and pyridines with vinyl stannanes does not provide the expected vinyl compounds via C−F activation but rather provides new Sn−C bonds via C−H functionalization with the loss of ethylene. This mechanism provides a new unanticipated methodology for the direct conversion of C−H bonds to carbon−heteroatom bonds.
Abstract
Background
Research pairing ecological momentary assessment (EMA) methodology and ambulatory cortisol during daily life is still rare, as is careful testing of the within-person associations ...between stress, affect, and cortisol. Using a circumplex approach, we considered both valence and arousal components of affect.
Purpose
To examine the within-person covariation of momentary cortisol with momentary perceived stress, affective valence, and affective arousal in everyday life.
Methods
115 working adults (Mage = 41.2; 76% women; 76% white) completed six EMA surveys per day over 3 days. Each assessment included reports of perceived stress and affect (used to construct indicators of affective valence and arousal), followed by a saliva sample (from which cortisol was assessed). Multi-level models were used to examine the momentary associations between perceived stress, affective valence, affective arousal, and cortisol.
Results
Moments characterized by higher perceived stress were associated with higher cortisol (p = .036). Affective valence covaried with cortisol (p = .003) such that more positive valence was associated with lower cortisol and more negative valence with higher cortisol. Momentary affective arousal was not related to cortisol (p = .131). When all predictors were tested in the same model, only valence remained a significant predictor of cortisol (p = .047).
Conclusion
Momentary perceived stress and affective valence, but not affective arousal, were associated with naturalistic cortisol. Cortisol was more robustly associated with affective valence than perceived stress or affective arousal. These findings extend our understanding of how moments of stress and particular characteristics of affective states (i.e., valence but not arousal) may “get under the skin” in daily life.
In everyday life, moments of more stress and negatively valenced moods, but not higher arousal moods, were associated with higher levels of cortisol.
The mechanisms of the C–F activation reactions of 2,3,5,6-tetrafluoropyridine and pentafluoropyridine with the phenanthrene adduct (PEt3)2Ni(η2-C14H10) and Ni(PEt3)4 as sources of (PEt3)2Ni were ...investigated. The activation of 2,3,5,6-tetrafluoropyridine proceeds via the mononuclear adduct (PEt3)2Ni(η2-2,3,5,6-C5F4HN) (3) in equilibrium with the C–H activation product, trans-(PEt3)2NiH(2,3,5,6-C5F4N) (2). The C–F activation reaction occurs by concerted oxidative addition, as judged by the observation of cis-(PEt3)2NiF(3,5,6-C5F3HN) (4), as an intermediate to trans-(PEt3)2NiF(3,5,6-C5F3HN) (1). The dinuclear adduct (PEt3)2Ni2(μ-η2 :η2-2,3,5,6-C5F4HN) (5) was not observed. Pentafluoropyridine reacted with the phenanthrene adduct (PEt3)2Ni(η2-C14H10) to provide the mononuclear adduct (PEt3)2Ni(η2-C5F5N) (6) and the dinuclear adduct (PEt3)2Ni2(μ-η2 :η2-C5F5N) (11). A (PEt3)2Ni adduct of the C–F activation product, (PEt3)2Niη2-3,4,5,6-C5F4N-2-NiF(PEt3)2 (10), and the double C–F activation product trans-(PEt3)2NiF2(3,4,5-C5F3N) (9) were also assigned by NMR spectroscopy. Complex 10 was a precursor to both trans-(PEt3)2NiF(3,4,5,6-C5F4N) (7) and 9. The rate of formation of trans-(PEt3)2NiF(3,4,5,6-C5F4N) (7) is not first order with respect to the concentration of 6. The EPR spectrum of (PEt3)2Ni(η2-C14H10) and pentafluoropyridine, in a toluene solution that was frozen in N2(l) during reaction at −40 °C, revealed signals consistent with the speculative formulation (PEt3)2Ni(2-C5F4N). These results suggest that pathways other than concerted oxidative addition or phosphine-assisted pathways arising from 6 are required to account for the unusual selectivity of the C–F activation of pentafluoropyridine by the (PEt3)2Ni fragment.
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