Understanding management of poorly controlled pain in community-dwelling analgesic users: a qualitative study.

Background Chronic pain is a prevalent and debilitating condition for many people. Globally it is the greatest contributor to years lived with disability. Management often includes pharmacotherapy and pharmacists are therefore well placed to contribute to chronic pain management. Objective To explore chronic pain management in community-dwelling analgesic users with poorly controlled pain and investigate potential barriers to adequate pain management. Setting Regional Victoria, Australia. Method A descriptive qualitative approach was used. People who had been prescribed an analgesic for at least 6 months and reported an average pain score over the last week of 4 or more out of 10 were interviewed about their pain management. Interviews followed a semi-structured interview guide. Thematic analysis of the data was undertaken followed by participant validation of the key themes. Main outcome measure Experience of chronic pain management. Results Three female and eight male people, aged between 34 and 77 years were interviewed. The study demonstrated that there was a diverse range of issues relating to chronic pain management that fitted into seven major themes: impact of pain on life, invisibility of pain, issues associated with healthcare professionals, general medication issues, attitude towards taking analgesics, medication adherence, and attitude towards other treatment options. Chronic pain had dramatically altered the lives of all participants and their families as they came to accept and learn to live with the pain they experienced. The main barrier to adequate pain management was the invisibility of pain, which resulted in health professionals undertreating the pain reported by participants. Participants desire to take as few analgesics as possible, the reluctance of GPs to prescribe opioids and healthcare professionals focus on misuse also contributed to poor pain management. Conclusion Participants were able to accept high levels of pain while minimizing analgesic use. The two main barriers to adequate pain management were the invisibility of pain, which resulted in health professionals not treating the pain reported by the participant and the perception of participants that analgesics should not need to be taken regularly in adequate doses for the rest of their lives.

Transgene expression produced by biolistic-mediated, site-specific gene integration is consistently inherited by the subsequent generations.

The efficient production of stable transgenic plants is important for both crop improvement and functional genomics. Site-specific integration of foreign genes into a designated genomic position is an attractive tool for minimizing expression variability between transgenic lines. Here, we studied the utility of a Cre-mediated, site-specific integration approach, facilitated by particle bombardment, for streamlining the production of stable transgenic plants, using rice as a model species. Using this method, we generated 18 different transgenic lines containing a precise integration of a single copy of beta-glucuronidase gene (gusA) into a designated genomic location. Eleven of these lines contained no illegitimate integration in the background (single-copy lines), and seven contained illegitimate integrations in addition to the site-specific integration (multicopy lines). We monitored gusA expression in these lines up to three to four successive generations. Each of the single-copy lines expressed the gusA gene at consistent levels and nearly doubled the expression level in the homozygous state. In contrast, multicopy lines displayed expression variation and gene silencing. In about half of the multicopy lines, however, expression of the site-specific integration locus could be reactivated and stabilized on segregation of the illegitimate integrations, whereas, in the remaining half, expression could not be restored, as they contained genetically linked illegitimate integrations. This study demonstrates that biolistic-mediated, site-specific gene integration is an efficient and reliable tool for streamlining the production of stable transgenic plants.

Cre-mediated site-specific gene integration for consistent transgene expression in rice.

To minimize expression variability amongst transgenic lines, we have utilized the strategy of Cre/lox-mediated site-specific gene integration. This method allows the precise integration of a transgene in a lox site previously placed in the genome. Using the biolistic method for DNA delivery, we have generated several site-specific integrant lines, derived from three different target lines. About 80% of the selected lines contain precise integration of the gusA reporter gene and fall into two categories: single-copy (SC) lines that contain site-specific integration without additional random integrations, and multicopy (MC) lines that contain random integrations in addition to the site-specific integration. The expression of the gusA gene was studied in callus cells and regenerated plants. The isogenic SC lines displayed significantly lower expression variation, whereas much higher expression variation was observed in MC lines. Furthermore, stable inheritance of the gusA gene was observed in T1 plants derived from a subset of SC lines. This demonstrates that consistent gene expression can be obtained in rice by Cre-mediated site-specific integration.