Regulation of Pancreatic microRNA-7 Expression

Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer, which is important for pancreas development. Differentiation of endocrine cells is controlled by a network of pancreatic transcription factors including Ngn3 and NeuroD/Beta2. However, how specific miRNAs are intertwined into this transcriptional network is not well understood. Here, we characterize the regulation of microRNA-7 (miR-7) by endocrine-specific transcription factors. Our data reveal that three independent miR-7 genes are coexpressed in the pancreas. We have identified conserved blocks upstream of pre-miR-7a-2 and pre-miR-7b and demonstrated by functional assays that they possess promoter activity, which is increased by the expression of NeuroD/Beta2. These data suggest that the endocrine specificity of miR-7 expression is governed by transcriptional mechanisms and involves members of the pancreatic endocrine network of transcription factors

Quality of informed consent for invasive procedures

Abstract Objective. To assess quality of informed consent among patients undergoing procedures and patient's preferences about decision-making. Design. Cross-sectional survey of hospitalized patients about informed consent before surgery or other procedures. Preference for decision-making was elicited in hospitalized and ambulatory patients. Setting. Large academic general hospital and 10 general clinics, over the years 2002 -04. Intervention. Data of initial survey were presented at staff meetings, recommending asking patients to restate what was explained to them. Main outcome measures. Rate of patient's recall for explanations on risks and alternative options; rate of patients preferring shared, autonomous and paternalistic modes of decision-making; degree of satisfaction from the decision-making. Results. Half of the patients did not recall receiving explanations about risks and two-third did not remember discussion of alternative options. The intervention failed, ,10% of patients being asked to re-state what was explained to them. Expectations about decision varied: 60% favored shared decision, nearly 20% preferred autonomous decision and the remainder wanted physicians to make decisions. Satisfaction was rated as good or very good by 80% of patients. Conclusions. Most patients do not remember receiving explanations about risks or alternatives for procedures, and physicians resist attempts to improve informed consent. Tools should be developed to measure the quality of consent. Since patients significantly differ in their preferred mode of decision-making, the informed consent should be patient-specific. Keywords: informed consent, quality of care Informed consent of patients undergoing procedures is important not only for ethical and legal reasons [1] but also for the quality of care: patient's understanding allows cooperation, improves results and satisfaction and also helps preventing errors Since the informed consent is culture-dependent and we were unaware of clinical research on its implementation in our country, we set about to evaluate some aspects of this process at our institution. Rather than looking at the quantity of information remembered by patients, we wished to look at some qualitative aspects of this exchange: Was the patient satisfied with decision-making? Could the patient recall any mention of risks or alternatives? Had she or he wished to receive more information? What is the preferred mode of decision-making: autonomous, shared or paternalistic? Had the patient signed an informed consent? Had she or he been asked to repeat the explanations? Although the necessary legal requirements for informed consent have been reviewed in great detail [15], we were more interested in examining and framing the issues from the viewpoint of quality of care. We prospectively surveyed patients surrounding invasive procedures, exploring gaps between perceived and preferred modes of decision, attempting to construct a basis for a standard for the quality of the informed consent. Address reprint requests to: Maye

Open Design: Contributions, Solutions, Processes and Projects

Open design is a catchall term for various on- and offline design and making activities. It can be used to describe a type of design process that allows for (is open to) the participation of anybody (novice or professional) in the collaborative development of something. As well as this, it can mean the distribution and unrestricted use of design blueprints and documentation for the use by others. In this paper, the authors highlight various aspects of open and collaborative design and argue for the use of new terms that address what is open and when. A range of design projects and online platforms that have open attributes are then explored, whereby these terms are applied. In terms of design, the focus is specifically on the design of physical things rather than graphical, software or system design

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke

The rhetoric of the ineffable : awakening in Judaism, Christianity and Zen

textThis dissertation rhetorically analyzes the ways in which ineffable moments of awakening are constructed in the context of three religions: Judaism, Christianity, and Zen. Close textual analysis revealed that awakening is constructed differently in all three religions and that ineffability itself assumed different meanings in all cases. The conventional understanding of language as arbitrary and as based on human convention does not apply to Hebrew which takes itself to be a sacred language. Words are understood in this tradition as creative elements that convey more than trivial information and the term ineffability does not occupy much thought in Judaism. Christianity is grounded in a representative model of language and equates words with mortality and temporality. Awakening is constructed ontologically as moments in which textuality and corporality are transcended and one merges with the infinite divine. Zen is cautious about the ways in which language constructs the illusion of distinct identities, but ineffability is not constructed as an ontological concept in this tradition. Awakening is understood as beyond all words. The tropes recognized in the Jewish construction of awakening are metonymy, dialogue, differences, juxtapositions, particularities, haunting, and intertextuality. In Christianity, the dominant tropes are allegory, typology, metaphors, substitution, replacement and abstraction. Awakening is modeled after the resurrection of Jesus and is understood as a dramatic and ineffable event. The dominant rhetorical moves in Zen are suchness, nonsense, and paradoxes. Differences are also found between the construction of subjectivity, the perception of time, aesthetics, the linguistic model and ineffability. Judaism views itself as an architecture of time, but this time is not linear and is instead understood by the qualitative moments of the events. Awakening maintains the reverberations of past events into the present, but present moments are given significant attention. In Christianity, man is understood as grounded in space and progressing on a linear axis of time from birth towards his telos. Ineffability is constructed spatially and the event of awakening divides life into before and after. Zen attempts to deconstruct time and views it as sunyata, or “emptiness”.Communication Studie

Total antioxidant activity (TAA) of bell pepper during prolonged storage on low temperature

Bell pepper (Capsicum annum L.) is a vegetable known for its antioxidant content, highly important for its nutritional values. The total antioxidant activity (TAA) of pepper fruits is measured by TEAC (Trolox equivalent antioxidant capacity). This assay measures both the hydrophilic (HAA) (vitamin C) and lipophilic (LAA)(carotenoids and vitamin E) contents based on the total radical scavenging capacity and the ability of a scaverenge the stable ABTS radical (ABTS + ) described by Vinocur and Rodov (2006). Fruit were cleaned and disinfected with hot water by rinsing and brushing (HWRB) at 55°C as it is described by Fallik et all ., (1999). Tap water wash was served as control. Fruit were stored at 2°C or 7°C during 3 weeks plus 3 days at 20°C (shelf life simulation). TAA in red bell pepper, immediately after harvest, was 4.29 (0.74 lipophilic and 3,55 hydrophilic) mol TE/g fr.wt. After 3 weeks storage at 2°C, TAA in pepper with cold wash treatment was 4.14 and 3.97 TEAC mol TE/g fr.wt. in HWRB treatment. After 3weeks +3days shelf life on 20°C TAA slowly growing up and obtained content of 5.24 in cold wash and 5.16 TEAC mol TE/g fr.wt. in HWRB. This is mainly due to changes in the lipophilic activity-LAA (treatment with cold water-1.79 and 1.81 mol TE/g fr.wt. in HWRB, comparing with 0.74 mol TE/g fr.wt. on beginning of storage). Hydrophilic antioxidant activity-HAA remains practically unchanged. In fruit, stored at 7°C, pepper ripeness has been associated with carotenoids accumulation especially after shelf life, TAA was 5.33 TEAC ( LAA 2.03) mol TE/g fr.wt

Smoking quit rates among patients receiving pharmacotherapy who received general practitioner counselling versus intensive counselling: a retrospective cohort study

Abstract Background Behavioral treatments can augment the success of pharmacotherapy in smoking cessation. The aim of this study was to compare smoking quit rates between patients receiving individual counseling with their general practitioner during office visits or intensive counselling with behavioral support, both augmented by varenicline. Methods A nationwide retrospective cohort study conducted in a large Healthcare Maintenance Organization in Israel. We selected randomly patients who filled a prescription for varenicline and received either individual consulting by their general practitioner or intensive counselling with behavioural support, and asked them to answer a questionnaire. The outcome variables were smoking cessation 26–52 weeks following the beginning of treatment and satisfaction with the process. Results 870 patients were contacted and 604 agreed to participate (a response rate of 69%); 301 patients in the general practitioner group, 300 in the intensive counselling group and 3 were excluded due to missing date. The quit rate was 36.5% in the general practitioner group and 42.3% in the intensive counselling group (P = 0.147). In a logistic regression analysis, controlling for age, gender, socioeconomic status, ischemic heart disease, chronic obstructive pulmonary disease, pack years and duration of varenicline consumption, the adjusted OR for quitting in the general practitioner group was 0.79 (95% CI 0.56,1.13). The adjusted OR was higher in the group with the highest socioeconomic status at 2.06 (1.39,3.07) and a longer period of varenicline consumption at 1.30 (1.15,1.47). Age, gender and cigarette pack-years were not associated with quit rate. In the general practitioner group 68% were satisfied with the process, while 19% were not. In the intensive counselling group 64% were satisfied and 14% were not (P = 0.007). Conclusion We did not detect a statistically significant difference in smoking quit rates, though there was a trend towards higher quit rates with intensive counselling