Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21.

Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.

Nursing's leaky pipeline: Barriers to a diverse nursing workforce.

BACKGROUND: Nursing educational programs have been charged with increasing the diversity of the nursing workforce; however, this depends on having a diverse and qualified applicant pool to select from. PURPOSE: To determine the effects of student losses over time on nursing program diversity. DESIGN AND METHODS: Descriptive longitudinal study. Progression of all students from a single university enrolled as pre-nursing majors from 2012 to 2016 (N = 2498) was tracked over seven key checkpoints during a seven-year time period. RESULTS: Slightly more than half of the students (57%) were lost prior to nursing program application, which occurred at the end of the sophomore year. Losses were higher for minority students (70%), those requiring remedial coursework (65%), and first-generation students (62%). Older students, those with a prior degree, and those who started in another major were more likely to persist through some, but not all, of the checkpoints. CONCLUSIONS: Pre-nursing program losses significantly decreased the diversity of the remaining nursing applicant pool, particularly for African American students. Losses were highest during the freshman level Anatomy and Physiology course. Nursing education programs need to develop early intervention programs to support diverse students during the critical pre-nursing period to increase the diversity of the nursing workforce.

Humor and Laughter May Influence Health IV. Humor and Immune Function.

This is the final article in a four part series reviewing the influence of humor and laughter on physiological and psychological well-being. This final article reviews the evidence for the effect of sense of humor, exposure to a humor stimulus and laughter on various immune system components, with a focus on the effects of laughter on natural killer cell cytotoxicity.

Selective binding of sterol regulatory element-binding protein isoforms and co-regulatory proteins to promoters for lipid metabolic genes in liver.

Mice were subjected to different dietary manipulations to selectively alter expression of hepatic sterol regulatory element-binding protein 1 (SREBP-1) or SREBP-2. mRNA levels for key target genes were measured and compared with the direct binding of SREBP-1 and -2 to the associated promoters using isoform specific antibodies in chromatin immunoprecipitation studies. A diet supplemented with Zetia (ezetimibe) and lovastatin increased and decreased nuclear SREBP-2 and SREBP-1, respectively, whereas a fasting/refeeding protocol dramatically altered SREBP-1 but had modest effects on SREBP-2 levels. Binding of both SREBP-1 and -2 increased on promoters for 3-hydroxy-3-methylglutaryl-CoA reductase, fatty-acid synthase, and squalene synthase in livers of Zetia/lovastatin-treated mice despite the decline in total SREBP-1 protein. In contrast, only SREBP-2 binding was increased for the low density lipoprotein receptor promoter. Decreased SREBP-1 binding during fasting and a dramatic increase upon refeeding indicates that the lipogenic "overshoot" for fatty-acid synthase gene expression known to occur during high carbohydrate refeeding can be attributed to a similar overshoot in SREBP-1 binding. SREBP co-regulatory protein recruitment was also increased/decreased in parallel with associated changes in SREBP binding, and there were clear distinctions for different promoters in response to the dietary manipulations. Taken together, these studies reveal that there are alternative molecular mechanisms for activating SREBP target genes in response to the different dietary challenges of Zetia/lovastatin versus fasting/refeeding. This underscores the mechanistic flexibility that has evolved at the individual gene/promoter level to maintain metabolic homeostasis in response to shifting nutritional states and environmental fluctuations.

Humor and Laughter May Influence Health: III. Laughter and Health Outcomes.

This is part three of a four-part series reviewing the evidence on how humor influences physiological and psychological well-being. The first article included basic background information, definitions and a review of the theoretical underpinnings for this area of research. The second article discussed use of humor as a complementary therapy within various clinical samples, as well as evidence concerning how a sense of humor influences physiological and psychological wellbeing. This third article examines how laughter influences health outcomes; including muscle tension, cardio-respiratory functioning and various stress physiology measures.

Immune responses to guided imagery during breast cancer treatment.

BACKGROUND: The use of relaxation and guided imagery to reduce stress and improve immune function has great potential benefits for patients with breast cancer. METHODS: This pilot study used a pretest-posttest experimental design with 28 breast cancer patients, aged 25 to 75 years, with the diagnosis of stage 0, 1, or 2 breast cancer. The experimental group received a relaxation and guided imagery intervention and the control group received standard care. The effects of the intervention on immune function were measured by natural killer (NK) cell cytotoxicity and IL-2-activated NK cell activity prior to surgery and 4 weeks postsurgery. NK cell activity was measured using a 15-hr incubation chromium release assay. Cytotoxicity of NK cells was measured against chromium-labeled K-562 target cells. IL-2 was used to enhance reactivity of NK cells against tumor cells. After incubation for 15 hr, cytotoxicity was measured through the release of radioactive chromium. RESULTS: Significant differences between groups were found at 4 weeks postsurgery. T-tests showed increased NK cell cytotoxicity for the intervention group at 100:1, 50:1, and 25:1 effector cell: target cell ratios (E:T) (p < .01 to p < .05) and increased activation for IL-2 at 100:1, 50:1, 25:1, and 12.5:1 (E:T) (p < .01 to p < .05) for the intervention group as compared to the control group. DISCUSSION: These findings suggest that a relaxation intervention such as guided imagery could have an effect on NK cell cytotoxicity and NK cell cytotoxicity after activation with IL-2 in patients undergoing surgery for breast cancer.

Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase.

We discovered a nuclear receptor element in the FAS promoter consisting of an inverted repeat spaced by one nucleotide (IR-1) and located 21 bases downstream of a direct repeat sequenced by 4 nucleotides (DR-4) oxysterol liver X receptor response element. An IR-1 is present in promoters of several genes of bile acid and lipid homeostasis and binds farnesoid X receptor/retinoid X receptor (FXR/RXR) heterodimers to mediate bile acid-dependent transcription. We show that FXR/RXRalpha specifically binds to the FAS IR-1 and that the FAS promoter is activated approximately 10-fold by the addition of a synthetic FXR agonist in transient transfection assays. We also demonstrate that endogenous FXR binds directly to the murine FAS promoter in the hepatic genome using a tissue-based chromatin immunoprecipitation procedure. Furthermore, we show that feeding wild-type mice a chow diet supplemented with the natural FXR agonist chenodeoxycholic acid results in a significant induction of FAS mRNA expression. Thus, we have identified a novel IR-1 in the FAS promoter and demonstrate that it mediates FXR/bile acid regulation of the FAS gene. These findings provide the first evidence for direct regulation of lipogenesis by bile acids and also provide a mechanistic rationale for previously unexplained observations regarding bile acid control of FAS expression.

Humor and Laughter May Influence Health: II. Complementary Therapies and Humor in a Clinical Population.

Our results support a connection between sense of humor and self-reported physical health, however, it is difficult to determine the relationship to any specific disease process. Whereas relationships between sense of humor and self-reported measures of physical well-being appear to be supported, more research is required to determine interrelationships between sense of humor and well-being.

Humor and laughter may influence health. I. History and background.

Articles in both the lay and professional literature have extolled the virtues of humor, many giving the impression that the health benefits of humor are well documented by the scientific and medical community. The concept that humor or laughter can be therapeutic goes back to biblical times and this belief has received varying levels of support from the scientific community at different points in its history. Current research indicates that using humor is well accepted by the public and is frequently used as a coping mechanism. However, the scientific evidence of the benefits of using humor on various health related outcomes still leaves many questions unanswered.

Relief of symptoms, side effects, and psychological distress through use of complementary and alternative medicine in women with breast cancer.

PURPOSE/OBJECTIVES: To identify use of complementary and alternative medicine (CAM) for relief of symptoms and side effects among women diagnosed with breast cancer and to identify demographic and clinical factors associated with the use of CAM in these patients. DESIGN: A descriptive, cross-sectional survey. SETTING: Clinics and community groups in the Tampa Bay area and community groups in a rural midwestern area. SAMPLE: A convenience sample of 105 predominantly Caucasian women (mean age = 59 years) with a diagnosis of breast cancer was recruited from the Tampa Bay area and a rural midwestern area. METHODS: The instrument used to gather the data was the Use of Complementary Therapies Survey. The reasons for choosing 33 individual CAM treatments were tabulated. The frequency of use was calculated according to four reasons: (a) to reduce physical symptoms or side effects, (b) to reduce psychological distress, (c) to gain a feeling of control over treatment, or (d) because of dissatisfaction with traditional medical care. Least-squares regression models were fit to identify independent demographic and clinical predictors of CAM therapy use. MAIN RESEARCH VARIABLES: Use of CAM for relief of physical and psychological distress. FINDINGS: Patients used all categories of CAM therapies to reduce physical symptoms and side effects. The most frequently cited reason for use of CAM was to reduce the symptom of psychological distress, whereas the lowest frequency of CAM use was because of dissatisfaction with traditional medical care. Traditional and ethnic medicines frequently were used to reduce physical symptoms and side effects, followed by diet and nutritional supplements. The most frequently used CAM therapy category cited for gaining a feeling of control over treatment was use of diet and nutritional supplements. Previous chemotherapy and having more than a high school education were associated with more frequent use of diet and nutritional supplements and stress-reducing techniques. CONCLUSIONS: Frequency of specific use according to type of CAM was higher and more specific than reported in other studies. Patients who had undergone chemotherapy were most likely to use CAM. IMPLICATIONS FOR NURSING: Oncology nurses are in a key position to identify which symptoms or side effects patients are experiencing and which CAM therapies may be helpful to relieve patients' symptoms related to treatment and psychological distress related to their cancer.

A monoclonal antibody that binds anionic phospholipids on tumor blood vessels enhances the antitumor effect of docetaxel on human breast tumors in mice.

Anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of viable vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. We recently raised an IgG monoclonal antibody, 3G4, which binds to anionic phospholipids in a beta2-glycoprotein I-dependent manner. It inhibited tumor growth in a variety of rodent tumor models by stimulating antibody-dependent cellular cytotoxicity toward tumor vessels. In the present study, we tested the hypothesis that docetaxel, which is known to have antivascular effects on tumors, might induce exposure of anionic phospholipids on tumor vasculature and, thus, enhance the antitumor activity of 3G4. Treatment of human umbilical vascular endothelial cells with subtoxic concentrations of docetaxel (20 pmol/L) in vitro caused anionic phospholipids to be externalized without inducing apoptosis. Docetaxel treatment of mice increased the percentage of tumor vessels that expose anionic phospholipids from 35% to 60%. No induction of phosphatidylserine was observed on vessels in normal tissues even after systemic treatment with docetaxel. Treatment of mice bearing orthotopic MDA-MB-435 human breast tumors with 3G4 plus docetaxel inhibited tumor growth by 93%. Treatment of mice bearing disseminated MDA-MB-435 tumors with 3G4 plus docetaxel reduced the average number of tumor colonies in the lungs by 93% and half the animals did not develop tumors. In both tumor models, the antitumor effect of the combination was statistically superior (P < 0.01) to that of docetaxel or 3G4 alone. Combination therapy reduced the tumor vessel density and plasma volume in tumors to a greater extent than did the individual drugs. The combination therapy was no more toxic to the mice than was docetaxel alone. These results indicate that, as an adjuvant therapy, 3G4 could enhance the therapeutic efficacy of docetaxel in breast cancer patients.

Identifying barriers to psychosocial spiritual care at the end of life: a physician group study.

OBJECTIVE: The recent literature addresses the need to improve care for dying patients. The purpose of this study was to identify barriers to the psychosocial spiritual care of these patients by their physicians. Psychosocial spiritual care is defined as aspects of care concerning patient emotional state, social support and relationships, and spiritual well-being. The study was an exploratory means for generating hypotheses and identifying directions for interventions, research, and training in care for the dying. DESIGN AND PARTICIPANTS: The study used a qualitative group discussion format. Seventeen physicians at a university-based health sciences center representing 10 areas of medical specialty--including internal medicine, oncology, pediatrics, and geriatrics met in two groups for 20 75-minute discussion sessions over the course of one year. Discussions were recorded, analyzed, and categorized. RESULTS: Barriers to psychosocial spiritual care were grouped into three domains and seven themes. The cultural domain included the themes of training, selection, medical practice environment, and debt/delay. Participants believed that medical selection and training combine to marginalize psychosocial spiritual approaches to patient care, while the practice environment and debt/delay augment emotional isolation and dampen idealism. The organizational domain included the themes of dissatisfaction and time/business. Physicians indicated that the current reimbursement climate and time pressures contribute to dissatisfaction and the tendency to avoid patient psychosocial spiritual issues. The clinical domain included the theme of communication. Physicians were concerned about their ability to communicate nonmedical issues effectively and manage the patient s reactions and needs in the psychosocial spiritual arena. CONCLUSIONS: This study suggests that research and educational approaches to improving the psychosocial spiritual care of the dying by physicians should address barriers at the cultural, organizational, and clinical levels. Suggestions for interventions at various levels are offered.

Design and testing of the use of a complementary and alternative therapies survey in women with breast cancer.

PURPOSE/OBJECTIVES: To design and test a reliable and valid instrument to determine the frequency of use of complementary and alternative medicine (CAM) therapies among women diagnosed with breast cancer. DESIGN: A descriptive cross-sectional survey. SETTING: Women were recruited from the southeastern area and a rural midwestern area of the United States. SAMPLE: 105 predominantly Caucasian women (mean= 59 years of age) with a diagnosis of breast cancer. METHODS: The Use of Complementary and Alternative Therapies Survey was designed with a content validity index, and reliability was determined with the coefficient alpha. Exploratory factor analysis using a principal components analysis identified primary components (factors) embedded within the survey. Frequency of CAM therapy use was calculated for 33 individual therapies listed on the survey and among three survey-defined subscales of CAM therapies (i.e., diet and nutritional supplements, stress-reducing techniques, and traditional and ethnic medicines). MAIN RESEARCH VARIABLES: Psychometric properties of an instrument to assess frequency of use of CAM among women with breast cancer. FINDINGS: The reported prevalence of use of the individual CAM therapies varied considerably. The coefficient alpha estimate for the total survey was 0.86. Estimates for the individual hypothesized subscales were 0.67 for diet and nutritional supplements, 0.79 for stress-reducing techniques, and 0.80 for traditional and ethnic medicines. The principal components analysis resulted in a two-factor solution with nine items that loaded heavily and uniquely on a factor conceptualized as stress and anxiety reduction and six items that loaded heavily and uniquely on a factor conceptualized as dietary and physical manipulation. The remaining five items (vitamins and minerals, prayer and spiritual healing, massage, reflexology, and aromatherapy) indicated moderate loadings on factors one and two and, thus, were interpreted as equivocal items. CONCLUSIONS: Preliminary data indicated that the instrument is reliable and valid. Additional work is needed to improve the range of items and to test the instrument with other populations. IMPLICATIONS FOR NURSING: Use of CAM by women with breast cancer is believed to be increasing. However, limited data exist on the frequency and predictors of its use in this patient population; therefore, reliable and valid instruments are needed to determine use. If nurses can determine which CAM therapies women are employing, nurses can educate patients with breast cancer on the safe use of these therapies.

The effect of mirthful laughter on stress and natural killer cell activity.

CONTEXT: A recent survey of rural Midwestern cancer patients revealed that humor was one of the most frequently used complementary therapies. Psychoneuroimmunology research suggests that, in addition to its established psychological benefits, humor may have physiological effects on immune functioning. OBJECTIVE: To determine the effect of laughter on self-reported stress and natural killer cell activity. DESIGN: Randomized, pre-post test with comparison group. SETTING: Indiana State University Sycamore Nursing Center, which is a nurse-managed community health clinic in a mid-sized, Midwestern city. PARTICIPANTS: 33 healthy adult women. INTERVENTION: Experimental subjects viewed a humorous video while subjects in the distraction control group viewed a tourism video. MAIN OUTCOME MEASURES: Self-reported stress and arousal (Stress Arousal Check List), mirthful laughter (Humor Response Scale), and immune function (chromium release natural killer [NK] cell cytotoxicity assay). RESULTS: Stress decreased for subjects in the humor group, compared with those in the distraction group (U32 = 215.5; P = .004). Amount of mirthful laughter correlated with postintervention stress measures for persons in the humor group (r16 = -.655; P = .004). Subjects who scored greater than 25 on the humor response scale had increased immune function postintervention (t16 = 2.52 P = .037) and compared with the remaining participants (t32 = 32.1; P = .04). Humor response scale scores correlated with changes in NK cell activity (r16 = .744; P = 001). CONCLUSION: Laughter may reduce stress and improve NK cell activity. As low NK cell activity is linked to decreased disease resistance and increased morbidity in persons with cancer and HIV disease, laughter may be a useful cognitive-behavioral intervention.

Frequency of use of complementary and alternative medicine in women with breast cancer.

PURPOSE/OBJECTIVES: To estimate the frequency of use of complementary and alternative medicine (CAM) therapies among women diagnosed with breast cancer and to identify demographic and clinical factors associated with CAM use in these patients. DESIGN: A descriptive, cross-sectional survey. SAMPLE: A convenience sample of 105 predominantly Caucasian women (mean age = 59 years) with a diagnosis of breast cancer was recruited from the Tampa Bay area and a rural midwestern area. METHODS: Utilizing the "Use of Complementary Therapies Survey," frequency of CAM use was calculated for 33 individual therapies listed on the survey and among three survey-defined subscales of CAM therapies (i.e., diet and nutritional supplements, stress-reducing techniques, and traditional and ethnic medicines). MAIN RESEARCH VARIABLES: Use of CAM therapies and types of treatment in women with breast cancer. FINDINGS: Among diet and nutritional supplements, 64% of all participants reported regular use of vitamins and minerals and 33% regularly used antioxidants, herbs, and health foods. Among stress-reducing techniques, 49% of all participants regularly used prayer and spiritual healing, followed by support groups (37%) and humor or laughter therapy (21%). Traditional and ethnic medicine therapies rarely were used with the exception of massage, which 27% of all participants used at least once after diagnosis. More frequent CAM use was observed among study participants who had undergone previous chemotherapy treatment and those with more than a high school education. Also, being less satisfied with their primary physician was associated with patients' more frequent CAM use. CONCLUSIONS: CAM use is increasing among women with breast cancer, and frequency of specific use according to type of CAM is higher than what has been reported in other studies. Use increased in patients who had undergone chemotherapy and in those with a high school education. IMPLICATIONS FOR NURSING: Oncology nurses are in a key position to identify what treatments patients are using and implement CAM therapies that can be helpful to relieve patient symptoms related to treatment and psychological distress.