A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome.

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele. Consequently, only the maternally inherited UBE3A gene is expressed in mature neurons. AS occurs due to deletions of the maternal 15q11 - 13 region, paternal uniparental disomy (UPD), imprinting center defects, mutations in the maternal UBE3A gene, or other unknown genetic malfunctions that result in a silenced maternal UBE3A gene in the specific imprinted regions of the brain.ResultsA potential treatment strategy for AS is to increase methylation of UBE3A-ATS to promote expression of the paternal UBE3A gene and thus ameliorate the clinical phenotypes of AS. We treated two sets of male identical twins with class I deletions with a 1 year treatment trial of either betaine and folic acid versus placebo. We found no statistically significant changes in the clinical parameters tested at the end of the 1 year trial, nor did we find any significant adverse events.ConclusionsThis study tested the hypothesis that by increasing the methylation of the UBE3A-antisense transcript in Angelman syndrome to promote expression of the silenced paternal UBE3A gene we may ameliorate the clinical phenotypes of AS. We treated two sets of identical twins with placebo versus betaine and folic acid. Although this study represented a novel approach to treating Angelman syndrome, the differences in the developmental testing results was not significant. This paper also discusses the value of monozygotic twin studies in minimizing confounding variables and its utility in conducting small treatment studies.Trial registrationNCT00348933 . Registered 6 July 2006

Leukotriene B4 enhances the generation of proinflammatory microRNAs to promote MyD88-dependent macrophage activation

MicroRNAs are known to control TLR activation in phagocytes. We have shown that leukotriene (LT) B4 (LTB4) positively regulates macrophage MyD88 expression by decreasing suppressor of cytokine signaling-1 (SOCS-1) mRNA stability. In this study, we investigated the possibility that LTB4 control of MyD88 expression involves the generation of microRNAs. Our data show that LTB4, via its receptor B leukotriene receptor 1 (BLT1) and Gαi signaling, increased macrophage expression of inflammatory microRNAs, including miR-155, miR-146b, and miR-125b. LTB4-mediated miR-155 generation was attributable to activating protein-1 activation. Furthermore, macrophage transfection with antagomirs against miR-155 and miR-146b prevented both the LTB4-mediated decrease in SOCS-1 and increase in MyD88. Transfection with miR-155 and miR-146b mimics decreased SOCS-1 levels, increased MyD88 expression, and restored TLR4 responsiveness in both wild type and LT-deficient macrophages. To our knowledge, our data unveil a heretofore unrecognized role for the GPCR BLT1 in controlling expression of microRNAs that regulate MyD88-dependent activation of macrophages

The Emperor Penguin is Bigger Than You Think and Other Science (Science, Part II)

pp. 20-2

Report on Anti-Oppression staff training

Philadelphia Folklore Project, AFS Consultancy GrantIn 2014, the Philadelphia Folklore Project completed a 4-year-long leadership transition. After 27 years at the helm, the Founding Director stepped down and the organization welcomed the next Director and two new senior staff members. Currently, staff includes two long-time PFP staffers (10 years and 4 years) and two new-to-PFP senior staff members. The transition was a landmark moment for the organization. The moment was full of important questions about PFP’s identity, community, sustainability, mission, and vision. Over this first year, the new staff worked together on best understanding and relating to the mission of the organization and on a shared vision for PFP and for the city of Philadelphia. Supported by a grant from the American Folklore Society, the Philadelphia Folklore Project worked with Jenna Peters Golden, Anti-Oppression Resource Training Alliance (http//:aorta.coop), on planning and teambuilding

EP4 and EP2 Receptor Activation of Protein Kinase A by Prostaglandin E 2 Impairs Macrophage Phagocytosis of Clostridium sordellii

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102186/1/aji12153.pd

Between stigma and pink positivity: women’s perceptions of social interactions during and after breast cancer treatment

This study explores women’s perceptions of social interaction during and after their treatment for early stage breast cancer. Analysis of interviews with 24 women between 6 months-29 years post-diagnosis, reveals that interactions can be influenced by conflicting public discourses surrounding breast cancer. For example, there is the continuing association of cancer with death and the resulting potential for a stigmatised identity (Goffman, 1963). In contrast is the ultra-positive discourse around cancer survivorship, with breast cancer in particular being associated with pink campaigning and a push towards positive thinking. Participants described ‘managing’ conversations during treatment; sometimes playing down their ‘private’ suffering and presenting a positive (‘public’) image rather than risk alienating support. After treatment they were encouraged to move on and get back to ‘normal’. Whilst other breast cancer patients/survivors were often good sources of support, there was also a danger of assuming that all experiences will be the same. We present data to illustrate that women often present ‘public’ accounts which are driven by an expectation of positivity and fear of stigmatization at all stages of breast cancer treatment and beyond

Student Perception of the Impact of Audience Response Software in a Team-Based Learning Self-Care Course

Objectives: Evidence evaluating audience response systems (ARS) used in team-based learning (TBL) compared to traditional classes is limited. The objectives of this study are to evaluate student perceptions of the technology and compare students’ assessment of technology with their performance. Method: TBL was implemented in the required self-care course (PP2120: Introduction to Pharmaceutical Care: Non-prescription drugs) at St. Louis College of Pharmacy, and an audience response system was implemented in Fall 2015. At the conclusion of the course, a web-based survey was administered to students. Results: Of the 29 students who successfully completed the course, 23 (79%) completed the survey. Student response to the audience response technology was generally favorable. Of the students who responded “somewhat agree” and “strongly agree” to questions related to ARS, 87% were more actively involved in the case, 96% felt the visual responses made understanding easier, and 91% felt the ARS would be useful in other courses in the curriculum. Student performance in the course was analyzed by Pearson correlation and was positively correlated with students who self-reported as technology enthusiasts (0.509, p=0.016) and early adopters of technology (0.601, p=0.004). Implications: This is the first study to measure the impact of ARS with TBL implementation in a self-care course. ARS data can be used to help implement TBL in pharmacy school curricula and further research can be performed to link student adoption of technology to performance in courses that implement ARS

Interactions of allergens and irritants in susceptible populations in producing lung dysfunction: implications for future research.

Environmental agents, when applied in combination or sequentially, can induce a wide variety of adverse health effects in humans. To determine the effects of sequential allergen challenge and acid exposure on human bronchial epithelial cell function, we subjected normal, nonallergic control and ragweed-allergic individuals to bronchoscopic segmental ragweed challenge in vivo. We harvested bronchial epithelial cells by brush biopsy both before challenge and 24 hr after challenge and exposed cells to an acid stress in vitro (pH 5 for 3 hr), followed by a 1-hr recovery period at normal pH. In normal, nonallergic subjects, segmental allergen challenge produced no effects on ciliary activity; pH 5 exposure produced reduced ciliary activity (a decrease in the percent of the initially active area), with significant recovery after cells were returned to a normal pH. Ciliary activity from allergic subjects was also inhibited by pH 5 exposure; however, activity was not recovered when cells were placed in medium of normal pH. Ciliary activity in allergics who developed a stress response postantigen challenge, as determined by an induction of the 27 kDa stress (heat shock) protein, displayed no ciliary dysfunction when exposed to a pH 5 stress. In this case, a stress sufficient to provoke a heat shock (stress) protein (HSP) response (but not one that produced more severe lung injury and did not provoke an HSP response) protected cells from a subsequent acid stress. Because of our observations and recent findings reported in the literature, we suggest that in order to define the wide variety of health effects of environmental agents, control as well as at-risk populations should be studied and the ability to define potentially beneficial as well as detrimental effects should be built into the experimental design. Inclusion of different and novel end points also should be considered

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Inhibition of protein translation as a novel mechanism for prostaglandin E2 regulation of cell functions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154239/1/fsb2028001008.pd