Touch-stimulation increases host-seeking behavior in Steinernema Carpocapsae.

Previous research demonstrated that Steinernema carpocapsae infective juveniles (IJs) exposed to a host cuticle were more attracted toward certain host-associated volatile odors. We wanted to test the specificity of attraction that results from exposure to host cuticle. Host recognition behavior was analyzed after stimulating IJs by allowing them to physically interact with Galleria mellonella cuticles. The subsequent behavioral response and the proportion of the population participating in chemotaxis to multiple host odors were measured. We found that exposure to host cuticles resulted in a significantly higher percentage of the population participating in host-seeking behavior, with threefold more nematodes participating in chemotaxis. We tested whether exposure to live or dead host cuticle resulted in a different response and found that a higher percentage of IJs exposed to a live host cuticle participated in chemotaxis than IJs exposed to a dead host cuticle, but that IJs exposed to a dead host demonstrated significantly higher participation than was observed for non-stimulated IJs. To test whether the increase in IJ participation in host-seeking behaviors after exposure to a live host cuticle was specific, we exposed stimulated IJs to a known repulsive odor, a neutral odor, and two predicted attractants. We found that stimulation of IJs through physical contact with a host cuticle induces a specific enhancement of host-seeking behavior to host-specific odors rather than a general increased chemotactic response to all volatile stimuli. However, the nematodes displayed an enhanced response to multiple host-specific odors. Future work should focus on the mechanism through which contact with live host cuticle stimulates increased behavioral response.Previous research demonstrated that Steinernema carpocapsae infective juveniles (IJs) exposed to a host cuticle were more attracted toward certain host-associated volatile odors. We wanted to test the specificity of attraction that results from exposure to host cuticle. Host recognition behavior was analyzed after stimulating IJs by allowing them to physically interact with Galleria mellonella cuticles. The subsequent behavioral response and the proportion of the population participating in chemotaxis to multiple host odors were measured. We found that exposure to host cuticles resulted in a significantly higher percentage of the population participating in host-seeking behavior, with threefold more nematodes participating in chemotaxis. We tested whether exposure to live or dead host cuticle resulted in a different response and found that a higher percentage of IJs exposed to a live host cuticle participated in chemotaxis than IJs exposed to a dead host cuticle, but that IJs exposed to a dead host demonstrated significantly higher participation than was observed for non-stimulated IJs. To test whether the increase in IJ participation in host-seeking behaviors after exposure to a live host cuticle was specific, we exposed stimulated IJs to a known repulsive odor, a neutral odor, and two predicted attractants. We found that stimulation of IJs through physical contact with a host cuticle induces a specific enhancement of host-seeking behavior to host-specific odors rather than a general increased chemotactic response to all volatile stimuli. However, the nematodes displayed an enhanced response to multiple host-specific odors. Future work should focus on the mechanism through which contact with live host cuticle stimulates increased behavioral response.

Mapping the Pax6 3' untranslated region microRNA regulatory landscape.

BACKGROUND: PAX6 is a homeodomain transcription factor that acts in a highly dosage-sensitive manner to regulate the development and function of the eyes, nose, central nervous system, gut, and endocrine pancreas. Several individual microRNAs (miRNA) have been implicated in regulating PAX6 in different cellular contexts, but a more general view of how they contribute to the fine-tuning and homeostasis of PAX6 is poorly understood. RESULTS: Here, a comprehensive analysis of the Pax6 3' untranslated region was performed to map potential miRNA recognition elements and served as a backdrop for miRNA expression profiling experiments to identify potential cell/tissue-specific miRNA codes. Pax6 3'UTR pull-down studies identified a cohort of miRNA interactors in pancreatic αTC1-6 cells that, based on the spacing of their recognition sites in the Pax6 3'UTR, revealed 3 clusters where cooperative miRNA regulation may occur. Some of these interacting miRNAs have been implicated in α cell function but have not previously been linked to Pax6 function and may therefore represent novel PAX6 regulators. CONCLUSIONS: These findings reveal a regulatory landscape upon which miRNAs may participate in the developmental control, fine-tuning and/or homeostasis of PAX6 levels.

Overcoming the translational roadblocks: a cancer care and research model.

There are many challenges to the process of translating the knowledge gained in the laboratory into new clinical approaches that can meet the needs of patients, clinicians and the wider community. We describe here an initiative that has borrowed concepts and principles from participatory research to produce a new process embedded in a cancer center aiming to facilitate translational research and overcome the three translational roadblocks. The centre-wide project named Personal Response Determinants in Cancer Therapy (PREDICT) operates with the support of the centre's leadership, staff, volunteers and patients to contribute to current and future cancer research successes. We describe the different phases of the project, the current structure and lessons learned during its evolution, highlighting how PREDICT contributes to translational research and its linkage to participatory research concepts. Despite the contextualized nature of the PREDICT initiative, we believe that the framework developed for the project has the potential to help other clinical centers to overcome the translational research roadblocks.

Individual investigator profiles of biospecimen use in cancer research.

BACKGROUND: Establishing targets for case accrual is an important component of a strategic plan for a biobank. We have previously assessed overall patterns of biospecimen use in cancer research publications in selected journals. Here we extend this analysis to consider patterns of biospecimen use in relation to cancer research programs developed by individual investigators. METHODS: We selected three individual cancer research investigators whose independent research programs began circa 1986, have been characterized by extensive use of human tumor biospecimens, and have primarily involved translational research in the areas of breast, lung, and ovarian cancer. We analyzed biospecimen and data usage in their career publications categorized by numbers, type, and format, and accompanying annotating data in terms of conformance with BRISQ reporting and ethics related criteria. RESULTS: Biospecimens were used in 313/474 (66%) of publications analyzed. The average number of biospecimens used by these research programs increased six-fold from less than 1000 in 2001-2003 to greater than 6000 in 2010-2012, and the average cohort sizes per article also increased from approximately 50 to 200 cases per study over the same period in most biospecimen categories (p<0.05). The relative proportions of different formats of biospecimens used has varied significantly and continues to change with the emergence of digital biospecimen derived data. In these three translational research programs, BRISQ elements relating to 'Biobank' categories were significantly less well reported for biospecimens used in publications than data corresponding to 'Clinical chart' categories (p<0001). CONCLUSIONS: This study shows that overall use of biospecimens in cancer research has increased significantly and that dynamic variation in the relative use of different biospecimen formats has also occurred. This study also confirms our previous findings on patterns of biospecimen use and also those concerning incomplete reporting of relevant data elements that has not improved in the past decade.

Significant inconsistency among pediatric oncologists in the use of the neutropenic diet.

BACKGROUND: The role of the neutropenic diet in the development of infections in oncology and stem cell transplant (SCT) patients is controversial. There is no data on the use of the neutropenic diet among pediatric oncologists. METHODS: A self-administered electronic survey was sent to 1,639 pediatric oncologists at 198 institutions who are members of Children's Oncology Group. A pediatric dietitian and pediatric oncologists developed, pretested, and modified the survey for item clarification. RESULTS: Five hundred fifty-seven physicians (34%) responded representing 174 (87%) of the 198 member institutions. More than half of respondents (57%) report implementing the neutropenic diet at their facility. In a multivariate analysis, being a stem cell transplant (SCT) center was the only significant factor associated with implementing a neutropenic diet (OR: 6.06, 95% CI, 2.88-12.738, P < 0.001) after controlling for years in practice, gender, center size, and academic versus private practice. Among physicians who implemented a neutropenic diet, absolute neutrophil count was the trigger for initiating the diet in oncology patients (72%) while admission and start of preparative regimen was used for SCT patients (84%). The majority of respondents (82%) stop the neutropenic diet when oncology patients are no longer neutropenic while the practice varied significantly with SCT patients. Providers at the same institution were not consistent with implementation of the diet, patient populations placed on the neutropenic diet and parameters for initiation, discontinuation of the diet and specific food restrictions. CONCLUSION: The implementation of the neutropenic diet by pediatric oncologists remains quite variable even among those at the same institution.

Permission to contact (PTC)--a strategy to enhance patient engagement in translational research.

UNLABELLED: Improving patient recruitment and consent to participate in clinical studies is an important issue. The process of consent involves three steps: patient referral for contact, the preliminary interview to determine patient interest, and the informed consent discussion. We hypothesized that putting the first step of the consent process into a 'Permission to Contact' (PTC) platform would improve patient engagement, would improve the efficiency of the other steps of the process, and would be acceptable to diverse patient groups. METHODS: To test this hypothesis, four PTC platforms were established in three types of outpatient health clinics (cancer, cardiac, maternal health) in different British Columbia health centers. Each began as a research project where clinic personnel were engaged, clinic flow processes were mapped, and a design for each PTC was derived by consensus. All patients at these clinics were asked for 'permission to be contacted for future research purposes.' Patient approach and permission response rates were assessed and operational costs were estimated. RESULTS: Overall permission rates were high for all projects, but ranged from 94% of 'cancer' patients to 80% of 'congenital heart' patients who were approached (p<0.0001). Sustainability was demonstrated by stable enrollment levels after several years, and ongoing costs averaged $25 (range $12-$39) for each 'permission' across all four platforms. CONCLUSIONS: A PTC platform is a feasible mechanism to engage patients in research programs such as biobanking. It is well supported by clinic staff and receives high engagement and acceptance from patients. Patient-approach rates vary in different clinics, likely due to both clinic and PTC process factors, but this strategy provides an efficient means of engaging patients in research and sets the stage for enhanced enrollment into translational research programs.

Impact of a Permission to Contact (PTC) platform on biobank enrollment and efficiency.

The consent process involves three steps; referral for contact, preliminary interview, and informed consent discussion. We propose that the efficiency and frequency of the consent process for individual biobank related projects increases when the referral for contact is conducted by an independent "Permission to Contact" (PTC) platform within a health research organization. A PTC platform established at our center in 2007 obtains "permission to be contacted about future cancer research" from approximately 1200 patients annually. With ethics board approval, the British Columbia (BC) Cancer Agency's Tumour Tissue Repository (TTR) deployed a post-procedure consent protocol designed to obtain initial referrals from the PTC platform. This protocol was initially deployed for breast and gastrointestinal (GI) cancer patients (48% of patients), and later expanded as an option for all patients. We examined the impact on biobank accrual over a 4-year period spanning implementation of the post-procedure protocol. Within the first 2 years, while deploying an existing pre-procedure consent protocol, the TTR received, on average, 38.5 referrals/month, and consented 36.5 patients/month. Over the next 24 months, referral and consent rates increased to 68.5/month and 45.6/month, respectively, while operating both pre-procedure and post-procedure protocols. This represents a significant increase in overall referrals (1.78 fold) and consented patients (1.25 fold). For breast and GI cancer patients, referrals and consents, increased even further (2.4 and 1.6 fold, respectively). Overall, the consented/declined/unknown decision rates in the first period were 95.3%/1.2%/3.5% (n=918 approached patients), while rates in the second period were 86%/2.3%/11.7% (n=1272 approached patients). Overall, consent process costs fell by 14% per case. Patient engagement can be positively influenced by connecting a biobank with a PTC platform enhancing efficiency in obtaining consent, which is a key determinant of tumor biobank costs.