Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice.

Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.

PT-VWD posing diagnostic and therapeutic challenges - small case series.

Despite the increased worldwide awareness, over the last decade, of the platelet-type von Willebrand Disease (PT-VWD), many uncertainties remain around this rare platelet bleeding disorder. This report aims to correctly identify and study the phenotype of new patients and highlights the diagnostic and therapeutic challenges this disease remains to pose. We describe four PT-VWD cases confirmed by genetic analysis in which either the diagnosis and/or the treatment posed challenge. We provide the details of the clinical presentation, laboratory analysis, and the treatment and the responses in each case. We show that in addition to type 2B VWD, PT-VWD can be misdiagnosed as idiopathic thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, and unexplained gestational thrombocytopenia. The disease can be diagnosed as early as 1 year of age and with phenotypically normal parents. Bleeding in some patients can be managed successfully using Humate P and DDAVP combined with tranexamic acid with no significant thrombocytopenia. We provide for the first time an evidence of an efficient response to rFVIIa in PT-VWD. Anaphylactic reaction to VWF preparations may be related to PT-VWD and the development of HLA antibodies is not uncommon. Progressive thrombocytopenia with normal VWF levels can be seen with PT-VWD and the platelet count was normalized at 2.5 weeks postpartum in one case. We conclude that these studies represent a record of clinical observations/interventions that help improve diagnoses/management of PT-VWD, highlight the variations in age and clinical presentations, laboratory diagnostic approaches, the importance of genetic testing for accurate diagnosis and consideration of therapeutic alternatives.

The effects of psychoeducation and telephone counseling on the adjustment of women with early-stage breast cancer.

BACKGROUND: Throughout the illness trajectory, women with breast cancer experience issues that are related to physical, emotional, and social adjustment. Despite a general consensus that state-of-the-art treatment for breast cancer should include educational and counseling interventions to reduce illness or treatment-related symptoms, there are few prospective, theoretically based, phase-specific randomized, controlled trials that have evaluated the effectiveness of such interventions in promoting adjustment. PURPOSE: The aim of this study is to examine the physical, emotional, and social adjustment of women with early-stage breast cancer who received psychoeducation by videotapes, telephone counseling, or psychoeducation plus telephone counseling as interventions that address the specific needs of women during the diagnostic, postsurgery, adjuvant therapy, and ongoing recovery phases of breast cancer. DESIGN: Primary data from a randomized controlled clinical trial. SETTING: Three major medical centers and one community hospital in New York City. METHODS: A total of 249 patients were randomly assigned to either the control group receiving usual care or to one of the three intervention groups. The interventions were administered at the diagnostic, postsurgery, adjuvant therapy, and ongoing recovery phases. Analyses were based on a mixed model analysis of variance. MAIN RESEARCH VARIABLES AND MEASUREMENT: Physical adjustment was measured by the side effects incidence and severity subscales of the Breast Cancer Treatment Response Inventory (BCTRI) and the overall health status score of the Self-Rated Health Subscale of the Multilevel Assessment Instrument. Emotional adjustment was measured using the psychological well-being subscale of the Profile of Adaptation to Life Clinical Scale and the side effect distress subscale of BCTRI. Social adjustment was measured by the domestic, vocational, and social environments subscales of the Psychosocial Adjustment to Illness Scale. FINDINGS: Patients in all groups showed improvement over time in overall health, psychological well-being, and social adjustment. There were no significant group differences in physical adjustment, as measured by side effect incidence, severity, or overall health. There was poorer emotional adjustment over time in the usual care (control) group as compared to the intervention groups on the measure of side effect distress. For the telephone counseling group, there was a marked decline in psychological well-being from the adjuvant therapy phase through the ongoing recovery phase. There were no significant group differences in the dimensions of social adjustment. CONCLUSION: The longitudinal design of this study has captured the dynamic process of adjustment to breast cancer, which in some aspects and at various phases has been different for the control and intervention groups. Although patients who received the study interventions improved in adjustment, the overall conclusion regarding physical, emotional, and social adjustment is that usual care, which was the standard of care for women in both the usual care (control) and intervention groups, supported their adjustment to breast cancer, with or without additional interventions. IMPLICATIONS FOR NURSING: The results are important to evidence-based practice and the determination of the efficacy and cost-effectiveness of interventions in improving patient outcomes. There is a need to further examine adjustment issues that continue during the ongoing recovery phase. KEY POINTS: Psychoeducation by videotapes and telephone counseling decreased side effect distress and side effect severity and increased psychological well-being during the adjuvant therapy phase. All patients in the control and intervention groups improved in adjustment. Adjustment issues are still present in the ongoing recovery phase.

Sinomenine inhibits microglial activation by Aß and confers neuroprotection.

BACKGROUND: Neuroinflammation is an important contributor to the development of neurodegenerative diseases, including Alzheimer's disease. Thus, there is a keen interest in identifying compounds, especially from herbal sources, that can inhibit neuroinflammation. Amyloid-ß (Aß) is a major component of the amyloid plaques present in the brains of Alzheimer's disease patients. Here, we examined whether sinomenine, present in a Chinese medicinal plant, prevents oligomeric Aß-induced microglial activation and confers protection against neurotoxicity. METHODS: Oligomeric amyloid-ß was prepared from Aß(1-42). Intracellular reactive oxygen species production was determined using the dye 2',7'-dichlorodihydrofluorescin diacetate. Nitric oxide level was assessed using the Griess reagent. Flow cytometry was used to examine the levels of inflammatory molecules. BV2-conditioned medium was used to treat hippocampal cell line (HT22) and primary hippocampal cells in indirect toxicity experiments. Toxicity was assessed using MTT reduction and TUNEL assays. RESULTS: We found that sinomenine prevents the oligomeric Aß-induced increase in levels of reactive oxygen species and nitric oxide in BV2 microglial cells. In addition, sinomenine reduces levels of Aß-induced inflammatory molecules. Furthermore, sinomenine protects hippocampal HT22 cells as well as primary hippocampal cells from indirect toxicity mediated by Aß-treated microglial cells, but has no effect on Aß-induced direct toxicity to HT22 cells. Finally, we found that conditioned medium from Aß-treated BV2 cells contains increased levels of nitric oxide and inflammatory molecules, but the levels of these molecules are reduced by sinomenine. CONCLUSIONS: Sinomenine prevents oligomeric Aß-induced microglial activation, and confers protection against indirect neurotoxicity to hippocampal cells. These results raise the possibility that sinomenine may have therapeutic potential for the treatment of Alzheimer's diseases as well as other diseases that involve neuroinflammation.

Breast cancer: education, counseling, and adjustment among patients and partners: a randomized clinical trial.

BACKGROUND: Although various forms of psychoeducation and counseling interventions have been examined among patients with a variety of diagnoses, the unique contribution of phase-specific psychoeducation and telephone counseling (TC) to the ongoing process of adjustment has not been explored among patients with breast cancer and their partners. OBJECTIVE: To conduct a randomized controlled clinical trial of phase-specific evidence-based psychoeducation and TC interventions to enhance emotional, physical, and social adjustments in patients with breast cancer and their partners. METHODS: A purposive sample of 249 patient-partner dyads were assigned randomly to one of four groups: (a) control group receiving disease management (DM), (b) standardized psychoeducation (SE), (c) TC, or (d) standardized psychoeducation plus telephone counseling (SE + TC). Data were collected at baseline, diagnostic, postsurgery, adjuvant therapy, and ongoing recovery phases measuring emotional, physical, and social adjustments. RESULTS: Patients showed poorer adjustment over time in the DM group relative to those receiving interventions on selected measures of emotional adjustment. All patients showed improvement over time in overall health and adjustment in social and vocational environments. Partners in all groups exhibited improvement over time for measures of adjustment in the social environment but no changes in psychological well-being or overall health. Partners in the TC group had poorer scores on physical symptoms compared with the SE + TC group and poorer vocational scores compared with the DM group. DISCUSSION: Findings from this study provide preliminary support for the value of phase-specific SE and TC interventions to enhance selected adjustment outcomes for patients with breast cancer and their partners.