Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R.

The phosphoinositide 3-kinase (PI3K) signaling cascade is a key mediator of cellular growth, survival and metabolism and is frequently subverted in human cancer. The gene encoding for the alpha catalytic subunit of PI3K (PIK3CA) is mutated and/or amplified in ∼30% of breast cancers. Mutations in either the kinase domain (H1047R) or the helical domain (E545K) are most common and result in a constitutively active enzyme with oncogenic capacity. PIK3CA(H1047R) was previously demonstrated to induce tumors in transgenic mouse models; however, it was not known whether overexpression of PIK3CA(E545K) is sufficient to induce mammary tumors and whether tumor initiation by these two types of mutants differs. Here, we demonstrate that expression of PIK3CA(E545K) in the mouse mammary gland induces heterogenous mammary carcinomas but with a longer latency than PIK3CA(H1047R)-expressing mice. Our results suggest that the helical domain mutant PIK3CA(E545K) is a less potent inducer of mammary tumors due to less efficient activation of downstream Akt signaling

Prophylactic Acupuncture Treatment during Chemotherapy in Patients with Breast Cancer – Results of a Qualitative Study nested in a Randomized Pragmatic Trial

Background: In a randomized controlled trial, compared with standard care alone in breast cancer, acupuncture as a prophylactic treatment did not show better quality of life or fewer side effects of chemotherapy (NCT01727362 [clinicaltrials.gov]). The aim of the qualitative part of this mixed methods study was to better understand the subjective perspectives of the patients regarding quality of life during chemotherapy and the perceived effects of acupuncture. Methods: In a nested retrospective qualitative study, semi-structured telephone interviews were conducted with 5 responders and 5 non-responders (defined by the outcome of the primary parameter FACT-B) who were randomly selected from both study arms. The interviews were digitally recorded, pseudonymized, transcribed, and then deductively and inductively analyzed according to Qualitative Content Analysis using MAXQDA® software. Results: A total of 20 patients were included in the qualitative part of the study. In both groups, most women stated that their quality of life was surprisingly better than what they had expected before starting the chemotherapy. All patients of the acupuncture group experienced the acupuncture treatments as relaxing and beneficial, mentioning a friendly setting, and empathic attitude of the therapist. Most of these patients stated that the acupuncture treatment reduced chemotherapy-induced side effects. The patients reported that acupuncture was supportive for coping with the disease in a salutogenic way. For all patients, finding strategies to cope with life-threatening cancer and the side effects of chemotherapy was essential, for example, keeping a positive attitude toward life, selecting social contacts, and staying active as much as possible. Conclusions: Patients in the acupuncture group reported positive effects on psychological and physical well-being after receiving the study intervention. For all patients, having coping strategies for cancer seemed to be more important than reducing side effects. Therefore, further studies should focus more on coping strategies and reducing acute side effects

Experiences and Perceived Effects of Rosary Praying: A Qualitative Study

The aim of this study is to explore experiences and perceived effects of the Rosary on issues around health and well-being, as well as on spirituality and religiosity. A qualitative study was conducted interviewing ten Roman Catholic German adults who regularly practiced the Rosary prayer. As a result of using a tangible prayer cord and from the rhythmic repetition of prayers, the participants described experiencing stability, peace and a contemplative connection with the Divine, with Mary as a guide and mediator before God. Praying the Rosary was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness and devotion

Acupuncture in Seasonal Allergic Rhinitis (ACUSAR) - Design and Protocol of a Randomised Controlled Multi-Centre Trial

Background: We report on the study design and protocol of a randomised controlled trial (Acupuncture in Seasonal Allergic Rhinitis, ACUSAR) that investigates the efficacy of acupuncture in the treatment of seasonal allergic rhinitis (SAR). Objective: To investigate whether acupuncture is non-inferior or superior to (a) penetrating sham acupuncture and (b) rescue medication in the treatment of SAR. Design: 3-armed, randomised controlled multi-centre trial with a total follow-up time of 16 weeks in the 1st year and 8 weeks in the 2nd year. Setting: 41 physicians in 37 out-patient units in Germany specialised in acupuncture treatment. Patients: 400 seasonal allergic rhinitis patients with clinical symptoms and test-positive (skin-prick test and/or specific IgE) to both birch and grass pollen. Interventions: Patients will be randomised in a 2:1:1 ratio to one of three groups: (a) semi-standardised acupuncture plus rescue medication (cetirizine); (b) penetrating sham acupuncture at non-acupuncture points plus rescue medication; or (c) rescue medication alone for 8 weeks (standard treatment group). Acupuncture and sham acupuncture will consist of 12 treatments per patient over 8 weeks. Main Outcome Measures: Average means of the Rhinitis Quality of Life Questionnaire (RQLQ) overall score and the Rescue Medication Score (RMS) between weeks 6 and 8 in the first year, adjusted for baseline values. Outlook: The results of this trial available in 2011 will have a major impact on the decision of whether acupuncture should be considered as a therapeutic option in the treatment of SAR

Efficacy of Injections with Disci/Rhus Toxicodendron Compositum for Chronic Low Back Pain – A Randomized Placebo-Controlled Trial

The effectiveness of injection therapy for low-back pain is still debatable. We compared the efficacy of local injections of the homeopathic preparation Disci/Rhus toxicodendron compositum (verum) with placebo injections and with no treatment in patients with chronic low back pain.In a randomized controlled partly double blind multicenter trial patients with chronic low back pain from 9 German outpatient clinics were enrolled and randomly allocated in a 1∶1∶1 ratio to receive subcutaneous injections (verum or placebo) into painful sites on the lower back over 12 treatment sessions within eight weeks, or no treatment (rescue pain medication with paracetamol or NSAIDs). All trial personnel and participants were masked to treatment allocation. The primary outcome measure was the average pain intensity over the last seven days on a visual analogue scale (0-100 mm, 0 = no pain, 100 = worst imaginable pain) after eight weeks. Follow-up was 26 weeks. Primary analysis was by intention to treat. Between August 2007 and June 2008, 150 patients were randomly allocated to three groups (51 verum, 48 placebo and 51 no treatment). The mean baseline-adjusted low back pain intensity at week eight was: verum group 37.0 mm (97.5% CI 25.3;48.8), no treatment group 53.0 (41.8;64.2), and placebo group 41.8 (30.1;53.6). The verum was significantly superior to no treatment (P = 0.001), but not to placebo (P = 0.350). No significant side effects were reported.The homeopathic preparation was not superior to placebo. Compared to no treatment injections resulted in significant and clinical relevant chronic back pain relief.ClinicalTrials.gov NCT00567736

Self-care strategies for medical students: an uncontrolled mixed-methods evaluation of a mind-body-medicine group course

Background High stress during medical education and its detrimental effects on student health is well documented. This exploratory evaluation study assesses a 10-week Mind-Body-Medicine student course, created to promote student self-care at Charité Universitätsmedizin Berlin, Germany. Methods During 2012–2019, uncontrolled quantitative and qualitative data were gathered from 112 student participants. Outcomes including changes in perceived stress (PSS), mindfulness (FMI/MAAS), self-reflection (GRAS), self-efficacy (GSE), empathy (SPF), and health-related quality of life (SF-12) were measured between the first (T0) and last sessions (T1). Qualitative data were obtained in focus groups at course completion and triangulated with quantitative data. Results Quantitative outcomes showed decreases in perceived stress and increased self-efficacy, mindfulness, self-reflection, and empathy. In focus groups, students reported greater abilities to self-regulate stressful experiences, personal growth and new insights into integrative medicine. Triangulation grounded these effects of MBM practice in its social context, creating an interdependent dynamic between experiences of self and others. Conclusion After completing an MBM course, students reported reduced perceived stress, increased self-efficacy, mindfulness, empathy and positive engagement with integrative concepts of doctor–patient relationships. Further research with larger randomized confirmatory studies is needed to validate these benefits

PBMCs transcriptome profiles identified breed-specific transcriptome signatures for PRRSV vaccination in German Landrace and Pietrain pigs

Porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting the swine industry worldwide. Genetic variation in host immunity has been considered as one of the potential determinants to improve the immunocompetence, thereby resistance to PRRS. Therefore, the present study aimed to investigate the breed difference in innate immune response to PRRSV vaccination between German Landrace (DL) and Pietrain (Pi) pigs. We analyzed microarray-based transcriptome profiles of peripheral blood mononuclear cells (PBMCs) collected before (0 h) and 24 h after PRRSV vaccination from purebred DL and Pi pigs with three biological replicates. In total 4,269 transcripts were identified to be differentially expressed in PBMCs in at least any of four tested contrast pairs (i.e. DL-24h vs. DL-0h, Pi-24h vs. Pi-0h, DL-0h vs. Pi-0h and DL-24h vs. Pi-24h). The number of vaccine-induced differentially expressed genes (DEGs) was much higher (2,459) in DL pigs than that of Pi pigs (291). After 24 h of PRRSV vaccination, 1,046 genes were differentially expressed in PMBCs of DL pigs compared to that of Pi (DL-24h vs. Pi-24h), indicating the breed differences in vaccine responsiveness. The top biological pathways significantly affected by DEGs of both breeds were linked to immune response functions. The network enrichment analysis identified ADAM17, STAT1, MMS19, RPA2, BAD, UCHL5 and APC as potential regulatory genes for the functional network of PRRSV vaccine response specific for DL; while FOXO3, IRF2, ADRBK1, FHL3, PPP2CB and NCOA6 were found to be the most potential hubs of Pi specific transcriptome network. In conclusion, our data provided insights of breed-specific host transcriptome responses to PRRSV vaccination which might contribute in better understanding of PPRS resistance in pigs