OR14-3OPIOID SUBSTITUTION TREATMENT: FROM LAW TO CLINICAL PRACTICE AND VICE VERSA

Background. On the edge of the >, the Neuchatel Institute of Health Law compared regulations for opioid substitution treatment (OST) in Switzerland, France, Canada, Belgium and Tunisia. Most standards described appear to be linked to a historic repressive framework. Reference to the right to health as defined by the Committee on Economic, Social and Cultural Rights (general comment 14), appear to be absent or unclear. We present the rational for creating an interdisciplinary panel from the concerned countries, in order to prepare recommendations about how a regulative system of OST should be based on scientific evidence and right to health. Method. Following a literature review identifying barriers to best practice from an addiction medicine point of view, a DELFI technique will identify the domains requiring removal or implementation of regulations, as a priority. Results and Conclusion. Based on the report of comparative law cited above, following areas need to be considered: access to care and free choice to treatment; the articulation of different laws; conditions for authorisation; concerned substances and products; personal conditions posed to patients and professionals; requirements and limitations surrounding substitution treatment itself; the terms of ending or interruption; the protection of personal dat

Expression, Processing, and Localization of PmpD of Chlamydia trachomatis Serovar L2 during the Chlamydial Developmental Cycle

BACKGROUND: While families of polymorphic membrane protein (pmp) genes have been identified in several Chlamydia species, their function remains mostly unknown. These proteins are of great interest, however, because of their location in the outer membrane and possible role in chlamydial virulence. METHODOLOGY/PRINCIPAL FINDING: We analyzed the relative transcription of the pmpD gene, a member of the pmp gene family in C. trachomatis serovar L2, and its protein product translation and processing during the chlamydial developmental cycle. By real-time reverse transcription polymerase chain reaction, the pmpD gene was found to be upregulated at 16 to 24 four hours after infection. Using polyclonal antibodies generated against the predicted passenger domain of PmpD, we demonstrated that it is initially localized on the surface of reticulate bodies, followed by its secretion outside Chlamydia starting at 24 hours after infection. In elementary bodies, we found a approximately 157 kDa PmpD only inside the cell. Both events, the upregulation of pmpD gene transcription and PmpD protein processing and secretion, are coincidental with the period of replication and differentiation of RBs into EBs. We also demonstrated that, in the presence of penicillin, the cleavage and secretion of the putative passenger domain was suppressed. CONCLUSION/SIGNIFICANCE: Our results are in agreement with the general concept that PmpD is an autotransporter protein which is post-translationally processed and secreted in the form of the putative passenger domain outside Chlamydia at mid- to- late point after infection, coinciding with the development of RBs into EBs

Work-life conflicts and health among Swiss physicians--in comparison with other university graduates and with the general Swiss working population

QUESTION UNDER STUDY: The present study aimed to compare the prevalence of work-life conflicts and the health status of physicians, with a representative sample of university graduates as well as with a representative sample of the general Swiss working population. Furthermore, it aimed to analyse whether work-life conflicts correlate with the health of physicians, as it does in the general working population. METHODS: The present cross-sectional study analysed data from 2007 originating from the SwissMedCareer Study (a prospective cohort study of physicians who graduated in 2001; n = 543) and the Swiss Household Panel (a representative Swiss survey on living and working conditions; university graduates of the same age range: n = 172, general working population of the same age range: n = 670). Data were analysed with Chi2 tests, correlations and logistic regressions. RESULTS: Physicians reported strong time-based as well as strain-based work-life conflicts more frequently than university graduates and the general working population. Significantly more physicians reported "moderate" to "very poor" health than the other two samples. Surprisingly, on the other side of the scale ("very good" health), physicians outnumbered the other samples too. Strong associations between work-life conflict and self-rated health as well as various health complaints were found for physicians. CONCLUSION: The high prevalence of work-life conflicts may explain the comparably high prevalence of poor self-rated health in the physicians' sample

The relevance of ERTS-1 data to the state of Ohio

There are no author-identified significant results in this report

Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure

The serotonin receptor 2C plays a central role in mood and appetite control. It undergoes pre-mRNA editing as well as alternative splicing. The RNA editing suggests that the pre-mRNA forms a stable secondary structure in vivo. To identify substances that promote alternative exons inclusion, we set up a high-throughput screen and identified pyrvinium pamoate as a drug-promoting exon inclusion without editing. Circular dichroism spectroscopy indicates that pyrvinium pamoate binds directly to the pre-mRNA and changes its structure. SHAPE (selective 2\u27-hydroxyl acylation analysed by primer extension) assays show that part of the regulated 5\u27-splice site forms intramolecular base pairs that are removed by this structural change, which likely allows splice site recognition and exon inclusion. Genome-wide analyses show that pyrvinium pamoate regulates \u3e300 alternative exons that form secondary structures enriched in A-U base pairs. Our data demonstrate that alternative splicing of structured pre-mRNAs can be regulated by small molecules that directly bind to the RNA, which is reminiscent to an RNA riboswitch

Changing trends in end-stage renal disease patients with diabetes.

Worldwide, diabetes has become the most common cause of end-stage renal disease (ESRD), yet Swiss data are largely lacking. This observational study examined ESRD patients with diabetes mellitus (ESRD-DM) at end of 2009 and 2014. The prevalence and characteristics of ESRD-DM patients were collected in all dialysis facilities in the Canton of Vaud of Switzerland in 2009 and in 2014, and the 5-year mortality rate was assessed. A total of 107 and 140 ESRD-DM patients underwent dialysis at end of 2009 and 2014, respectively. Within the 5-year period a total of 167 incidental ESRD-DM patients required dialysis, corresponding to an estimated incidental rate of 0.84/1000 person-years in the diabetic population. In 2009, all patients with ESRD-DM underwent haemodialysis, decreasing to 96.2% in 2014, with 3.8% on peritoneal dialysis. Age, sex, body mass index, type of diabetes, duration of diabetes, cause of ESRD, dialysis duration, dialysis frequency, vascular access, and glycosylated haemoglobin levels did not differ between 2009 and 2014. In 2014, macrovascular comorbidity was reported more often than in 2009, but not amputations. Haemoglobin level decreased significantly from 117.9 g/l to 112.3 g/l. Calcium-containing phosphate binder and angiotensin-converting enzyme inhibitor use significantly decreased, whereas iron therapy significantly increased with time. The 5-year mortality rate was 61.7%. Five-year survivors were significantly younger and had a higher body mass index. The growing prevalence of ESRD-DM emphasises that prevention of chronic kidney disease and its progression should be a public health priority in Switzerland

The unidentified TeV source (TeVJ2032+4130) and surrounding field: Final HEGRA IACT-System results

The unidentified TeV source in Cygnus is now confirmed by follow-up observations from 2002 with the HEGRA stereoscopic system of Cherenkov Telescopes. Using all data (1999 to 2002) we confirm this new source as steady in flux over the four years of data taking, extended with radius 6.2 arcmin (+-1.2 arcmin (stat) +-0.9 arcmin (sys)) and exhibiting a hard spectrum with photon index -1.9. It is located in the direction of the dense OB stellar association, Cygnus OB2. Its integral flux above energies E>1 TeV amounts to \~5% of the Crab assuming a Gaussian profile for the intrinsic source morphology. There is no obvious counterpart at radio, optical nor X-ray energies, leaving TeVJ2032+4130 presently unidentified. Observational parameters of this source are updated here and some astrophysical discussion is provided. Also included are upper limits for a number of other interesting sources in the FoV, including the famous microquasar Cygnus X-3.Comment: 7 pages, 3 figures. Accepted for publication in Astronomy & Astrophysic