Objective: The purpose of this study was to test the efficacy of a cancer parenting program for child rearing mothers with breast cancer, the Enhancing Connections Program. Primary goals were to decrease maternal depressed mood and anxiety, improve parenting quality, parenting skills and confidence, and enhance the child's behavioral-emotional adjustment to maternal breast cancer. Method: A total of 176 mothers diagnosed within 6 months with Stage 0 to Stage III breast cancer and their 8- to 12-year-old child were recruited from medical providers in 6 states: Washington, California, Pennsylvania, Minnesota, Arizona, and Indiana. After consenting and obtaining baseline measures, study participants were randomized into experimental or control groups. Experimental mothers received 5, 1-hr educational counseling sessions at 2-week intervals; controls received a booklet and phone call on communicating and supporting their child about the mother's cancer. Outcomes were assessed at 2 and 12 months. Results: Compared to controls, at 2 months experimental mothers significantly improved on depressed mood and parenting skills; experimental children improved on behavioral-emotional adjustment: total behavior problems, externalizing problems, and anxiety/depressed mood significantly declined. At 1 year, experimental children remained significantly less depressed than controls on both mother- and child-reported measures. The intervention failed to significantly affect parenting self-efficacy or maternal anxiety. Conclusions: The Enhancing Connections Program benefitted mothers and children in specific areas and warrants refinement and further testing. Public Health Significance Statement: The clinical trial results show that a brief intervention to mothers with breast cancer can significantly reduce the burden of cancer on both the child and the ill parent. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Mindfulness-based stress reduction (MBSR) reduces symptoms of depression, anxiety, and fear of recurrence among breast cancer (BC) survivors. However, the effects of MBSR (BC) on telomere length (TL) and telomerase activity (TA), known markers of cellular aging, psychological stress, and disease risk, are not known. This randomized, wait-listed, controlled study, nested within a larger trial, investigated the effects of MBSR (BC) on TL and TA. BC patients (142) with Stages 0-III cancer who had completed adjuvant treatment with radiation and/or chemotherapy at least 2 weeks prior to enrollment and within 2 years of completion of treatment with lumpectomy and/or mastectomy were randomly assigned to either a 6-week MBSR for BC program or a usual care. Assessments of TA and TL were obtained along with psychological measurements at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) program. The mean age of 142 participants was 55.3 years; 72% were non-Hispanic White; 78% had Stage I or II cancer; and 36% received both chemotherapy and radiation. In analyses adjusted for baseline TA and psychological status, TA increased steadily over 12 weeks in the MBSR(BC) group (approximately 17%) compared to essentially no increase in the control group (approximately 3%, p < .01). In contrast, no between-group difference was observed for TL (p = .92). These results provide preliminary evidence that MBSR(BC) increases TA in peripheral blood mononuclear cells from BC patients and have implications for understanding how MBSR(BC) may extend cell longevity at the cellular level.
This randomized controlled trial was conducted to examine immune recovery following breast cancer (BC) therapy and evaluate the effect of mindfulness-based stress reduction therapy (MBSR) on immune recovery with emphasis on lymphocyte subsets, T cell activation, and production of T-helper 1 (Th1; interferon [IFN]-?) and T-helper 2 (Th2; interleukin-4 [IL-4]) cytokines.
To investigate prevalence and severity of symptoms and symptom clustering in breast cancer survivors who attended MBSR(BC). Women were randomly assigned into MBSR(BC) or Usual Care (UC). Eligible women were ? 21 years, had been diagnosed with breast cancer and completed treatment within 18 months of enrollment. Symptoms and interference with daily living were measured pre- and post-MBSR(BC) using the M.D. Anderson Symptom Inventory. Symptoms were reported as highly prevalent but severity was low. Fatigue was the most frequently reported and severe symptom among groups. Symptoms clustered into 3 groups and improved in both groups. At baseline, both MBSR(BC) and the control groups showed similar mean symptom severity and interference; however, after the 6-week post-intervention, the MBSR(BC) group showed statistically-significant reduction for fatigue and disturbed sleep (P < 0.01) and improved symptom interference items, compared to the control group. For the between-group comparisons, 11 of 13 symptoms and 5 of 6 interference items had lower means in the MBSR(BC) condition than the control condition. These results suggest that MBSR(BC) modestly decreases fatigue and sleep disturbances, but has a greater effect on the degree to which symptoms interfere with many facets of life. Although these results are preliminary, MBSR intervention post-treatment may effectively reduce fatigue and related interference in QOL of breast cancer survivors.
Dynamic psychotherapy of psychosis works through gradually diminishing terror, replacing this with a clearer and shared understanding of the patients life history, its traumas and its strengths. It is diametrically opposed to our current push for efficiency and an assumption of an underlying brain disorder that responds to our current medications. Over the course of a long treatment, this patient became a scholar of psychoanalytic contributions to understanding psychosis and is now a philosopher of this field, developing an understanding of anorexia psychosis. She draws on the writings of Freud, Bion, Lacan, and Julian Jaynes, placing the core of psychosis not in primary process but in a preceding, non-self phase of development. She relates this individual development to the history of human development.
JMJD6 is a Jumonji C domain-containing hydroxylase. JMJD6 binds alpha-ketoglutarate and iron and has been characterized as either a histone arginine demethylase or U2AF65 lysyl hydroxylase. Here, we describe the structures of JMJD6 with and without alpha-ketoglutarate, which revealed a novel substrate binding groove and two positively charged surfaces. The structures also contain a stack of aromatic residues located near the active center. The side chain of one residue within this stack assumed different conformations in the two structures. Interestingly, JMJD6 bound efficiently to single-stranded RNA, but not to single-stranded DNA, double-stranded RNA, or double-stranded DNA. These structural features and truncation analysis of JMJD6 suggest that JMJD6 may bind and modify single-stand RNA rather than the previously reported peptide substrates.
Blood glucose control can be time-consuming and difficult to achieve. We hypothesized that a computerized system to obtain glucose control would enable faster "time to target" and produce less variability in blood glucose levels.
Community-based participatory research (CBPR) is a method to improve environmental quality in communities primarily inhabited by minorities or low-income families. The Buffalo Lupus Project was a CBPR partnership formed to explore the relationship between a local waste site and high rates of lupus. The "Behind the Fence" Community Environmental Forum Theater project was able to successfully funnel the results of scientific research and ongoing activities to the community by utilizing a Forum Theater approach, image-making techniques, an interactive workshop, and energetic public performance. Filming of project activities will expand the reach of that original performance and provide other communities with a potential model for similar efforts.
This retrospective analysis defined and described patterns and predictors of weight change during treatment in children with acute lymphocytic leukemia (ALL) with high-risk features who received treatment on Childrens Cancer Group protocol CCG 1961.
This pilot study aimed to determine the feasibility of providing massage to children with cancer to reduce symptoms in children and anxiety in parents. Twenty-three children/parent dyads were enrolled; 17 completed all data points. Children with cancer, ages 1 to 18 years, received at least 2 identical cycles of chemotherapy, and one parent, participated in the 2-period crossover design in which 4 weekly massage sessions alternated with 4 weekly quiet-time control sessions. Changes in relaxation (heart and respiratory rates, blood pressure, and salivary cortisol level) and symptoms (pain, nausea, anxiety, and fatigue) were assessed in children; anxiety and fatigue were measured in parents. Massage was more effective than quiet time at reducing heart rate in children, anxiety in children less than age 14 years, and parent anxiety. There were no significant changes in blood pressure, cortisol, pain, nausea, or fatigue. Children reported that massage helped them feel better, lessened their anxiety and worries, and had longer lasting effects than quiet time. Massage in children with cancer is feasible and appears to decrease anxiety in parents and younger children.
The objective of this survey is to determine the frequency, reasons, and factors influencing use of complementary and alternative medicine (CAM) in general and specialty pediatrics within the same geographic area. Of the 281 surveys completed, CAM use was higher in children with epilepsy (61.9%), cancer (59%), asthma (50.7%), and sickle cell disease (47.4%) than in general pediatrics (36%). Children most often used prayer (60.5%), massage (27.9%), specialty vitamins (27.2%), chiropractic care (25.9%), and dietary supplements (21.8%). Parents who used CAM for themselves (68.7%) were more likely to access CAM for their child. Most parents (62.6%) disclosed some or all of their childs use of CAM to providers. This study confirms that within the same geographic region, children with chronic and life-threatening illness use more CAM therapies than children seen in primary care clinics. Children with cancer use CAM for different reasons than children with non-life-threatening illnesses.
Considerable morbidity persists among survivors of breast cancer (BC) including high levels of psychological stress, anxiety, depression, fear of recurrence, and physical symptoms including pain, fatigue, and sleep disturbances, and impaired quality of life. Effective interventions are needed during this difficult transitional period.
Immunological adjuvants, such as bacterial LPS, increase the mRNA levels of the IkB-related NF-kappaB transcriptional transactivator, Bcl-3, in activated T cells. Adjuvants also increase the life expectancy of activated T cells, as does over-expression of Bcl-3, suggesting that Bcl-3 is part of the pathway whereby adjuvants affect T cell lifespans. However, previous reports, confirmed here, show that adjuvants also increase the life expectancies of Bcl-3-deficient T cells, making Bcl-3s role and effects in adjuvant-induced survival uncertain. To investigate the functions of Bcl-3 further, here we confirm the adjuvant-induced expression of Bcl-3 mRNA and show Bcl-3 induction at the protein level. Bcl-3 was expressed in mice via a transgene driven by the human CD2 promoter. Like other protective events, over-expression of Bcl-3 slows T cell activation very early in T cell responses to antigen, both in vitro and in vivo. This property was intrinsic to the T cells over-expressing the Bcl-3 and did not require Bcl-3 expression by other cells such as antigen-presenting cells.
An alphabeta T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral alphabeta T cells to recognize MHC is at least partly determined by MHC-dependent thymic selection, by which an immature T cell survives only if its TCR can recognize self MHC. This process may allow MHC-reactive TCRs to be selected from a repertoire with completely random and unbiased specificities. However, analysis of thymocytes before positive selection indicated that TCR proteins might have a predetermined ability to bind MHC. Here we show that specific germline-encoded amino acids in the TCR promote generic MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2beta to Ala reduced development of the entire TCR repertoire. Altogether, these results show that thymic selection is controlled by germline-encoded MHC contact points in the alphabeta TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this built-in specificity.
Virtually all T cell development and functions depend on its antigen receptor. The T cell receptor (TCR) is a multi-protein complex, comprised of a ligand binding module and a signal transmission module. The signal transmission module includes proteins from CD3 family (CD3epsilon, CD3delta, CD3gamma) as well as the zeta chain protein. The CD3 proteins have a short extracellular stalk connecting their Ig-like domains to their transmembrane regions. These stalks contain a highly evolutionarily conserved CXXC motif, whose function is unknown. To understand the function of these two conserved cysteines, we generated mice that lacked endogenous CD3epsilon but expressed a transgenic CD3epsilon molecule in which these cysteines were mutated to serines. Our results show that the mutated CD3epsilon could incorporate into the TCR complex and rescue surface TCR expression in CD3epsilon null mice. In the CD3epsilon mutant mice, all stages of T cell development and activation that are TCR-dependent were impaired, but not eliminated, including activation of mature naïve T cells with the MHCII presented superantigen, staphylococcal enterotoxin B, or with a strong TCR cross-linking antibody specific for either TCR-Cbeta or CD3epsilon. These results argue against a simple aggregation model for TCR signaling and suggest that the stalks of the CD3 proteins may be critical in transmitting part of the activation signal directly through the membrane.
Ikaros is important in the development and maintenance of the lymphoid system, functioning in part by associating with chromatin-remodeling complexes. We have studied the functions of Ikaros in the transition from pre-T cell to the CD4(+) CD8(+) thymocyte using an Ikaros null CD4(-) CD8(-) mouse thymoma cell line (JE131). We demonstrate that this cell line carries a single functional TCR ? gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry nonfunctional rearrangements on both alleles of their TCR ? loci. Retroviral reintroduction of Ikaros dramatically increased the rate of transcription in the ? locus and TCR V?/J? recombination resulting in the appearance of many new ??TCR(+) cells. The process is RAG dependent, requires switch/sucrose nonfermentable chromatin-remodeling complexes and is coincident with the binding of Ikaros to the TCR ? enhancer. Furthermore, knockdown of Mi2/nucleosome remodeling and deacetylase complexes increased the frequency of TCR ? rearrangement. Our data suggest that Ikaros controls V?/J? recombination in T cells by controlling access of the transcription and recombination machinery to the TCR ? loci. The JE131 cell line should prove to be a very useful tool for studying the molecular details of this and other processes involved in the pre-T cell to ??TCR(+) CD4(+) CD8(+) thymocyte transition.
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