Expression of an alternate splice form of Bmi-1 in multiple myeloma

The concept of “tumor stem cells” has garnered much attention in the last few years. Tumor stem cells are believed to exist among a heterogeneous group of cells that constitute a tumor. These tumor stem cells often express genes that are important for stem cell function, cell division, and maintenance of pluripotent state in stem cells. Stem cell or stem cell maintenance genes such as SALL 4 and Bmi-1 are often seen in these cancer cells and contribute to self-renewing divisions and cancer cell survival. In particular, high expression of Bmi-1 (B lymphoma mouse Moloney leukemia virus insertion region), a member of the polycomb family of transcription factors, is often associated with poor prognosis in cancers. Our laboratory has shown the existence of an alternatively spliced Bmi-1 RNA and protein in multiple myeloma cells. The purpose of this research project is to understand the effect of an alternate splice form of Bmi-1 protein on cell cycle and apoptosis in multiple myeloma cells. To understand the effect of this alternate Bmi-1 protein, I first compared the growth rate of different myeloma cell lines and correlated that with the expression of the wild-type Bmi-1 and the alternatively spliced Bmi-1 form. I performed time course experiments and counted the cell numbers in each cell line at various time points. My results show that the myeloma cell lines, which highly express the alternate form of Bmi-1, grew faster than the myeloma cell lines, which mostly express the wild-type form of Bmi-1. Currently I am performing RT-PCR and western blot analysis to confirm the existence of the alternatively spliced Bmi-1 protein. I plan to isolate and sequence the alternatively spliced form of Bmi-1. I also plan to determine the effect of knocking-down Bmi-1 expression on cell cycle and apoptosis by incorporating inducible shRNA viral constructs targeted against Bmi-1 RNA in myeloma cells

Effectiveness of a Faculty Development Program in Fostering Interprofessional Education Competencies

AbstractBackground: To determine the effectiveness of a faculty development program offered to clinical faculty in fostering interprofessional education competencies.Methods and Findings: A pre-post randomized control group design was used in which only one of two cohorts of clinical faculty received an interprofessional educational intervention. Both cohorts then facilitated case-based interprofessional education sessions for student learners. A variety of outcome measures were used to assess differences between groups in terms of knowledge, skills, and attitudes related to interprofessional education and practice. No significant differences were noted between the control and intervention groups.Conclusions: The use of a pre-post randomized control group design to measure effectiveness of an educational intervention should be considered to demonstrate the impact of educational interventions

Genome-wide mouse embryonic stem cell regulatory network self-organisation : a big data CoSMoS computational modelling approach.

The principal barrier to gaining understanding of embryonic stem (ES) cell regulatory networks is their complexity. Reductionist approaches overlook much of the complexity inherent in these networks and treat the ES cell regulatory system as more or less equivalent to the sum of its component parts, studying them in relative isolation. However, as we learn more about regulatory components it becomes increasingly difficult to integrate complex layers of knowledge and to develop more refined understanding. We seek better control of the complexity inherent in non-equilibrium ES cell regulatory networks undergoing lineage specification by developing computer simulations of self-organisation using the CoSMoS approach. Simulation, together with the hypothesis that lineage computation occurs at the edge of chaos, should allow us to investigate the driving of gradual accumulation of network complexity 'from the bottom up'. Here, we present the first step in this design process: use of the CoSMoS approach to develop a highly abstracted model and simulation of regulatory network activity driven by just single pluripotent transcription factors (TF), but at genome-wide scales. We investigate three TFs in isolation: Oct4, Nanog and Sox2, central elements of the core pluripotent network of mouse embryonic stem cells. This provides a suitable basis for future modelling of multiple interacting TFs

Positive family connections : co-producing a virtual group programme for family carers of children with learning disabilities or who are autistic

Purpose This paper aims to outline the process of developing a new co-produced virtual group support programme called Positive Family Connections (PFC) aimed at family carers of children with a learning disability, or who are autistic, aged between 8 and 13 years. Design/methodology/approach Development process: family carers were recruited to develop PFC prior to a feasibility randomised controlled trial being conducted (not reported in this paper). The programme was positively oriented and family systems-focused. PFC was developed by family carers, along with the research team, and designed to be delivered by family carer facilitators. The development process included several meetings to design the format and content of the programme. An initial pilot was then delivered and further amendments made to the programme in response to the pilot participants’ feedback. Findings The programme: the co-produced PFC programme involved attending six weekly sessions on Zoom; each 2-h session focused on different themes (e.g. communication and activities). Research limitations/implications Reflections on the co-production process: key ingredients of co-production included ensuring clarity on roles, positive communication and understanding of the family carers’ situation and utilising the varied skills family carers can bring to research and practise. Originality/value This is the first family systems-focused programme that the authors know of, that has been co-produced with family carers and solely delivered virtually by trained family carer facilitators from the outset

[Study Protocol] Palliative long-term abdominal drains versus repeated drainage in individuals with untreatable ascites due to advanced cirrhosis: study protocol for a feasibility randomised controlled trial

Background: UK deaths due to chronic liver diseases such as cirrhosis have quadrupled over the last 40 years, making this condition now the third most common cause of premature death. Most patients with advanced cirrhosis (end–stage liver disease, [ESLD]) develop ascites. This is often managed with diuretics, but if refractory then the fluid is drained from the peritoneal cavity every 10-14 days by large volume paracentesis (LVP), a procedure requiring hospital admissions. As the life expectancy of patients with ESLD and refractory ascites (if ineligible for liver transplantation) is on average ≤ 6 months, frequent hospital visits are inappropriate from a palliative perspective. One alternative is long-term abdominal drains (LTAD), used successfully in patients whose ascites is due to malignancy. Although inserted in hospital, these drains allow ascites management outside of a hospital setting. LTAD have not been formally evaluated in patients with refractory ascites due to ESLD. Methods: Due to uncertainty about appropriate outcome measures and whether patients with ESLD would wish or be able to participate in a study, a feasibility randomised controlled trial (RCT) was designed. Patients were consulted on trial design. We plan to recruit 48 patients with refractory ascites and randomise them (1:1) to either a) LTAD or b) current standard of care (LVP) for 12 weeks. Outcomes of interest include acceptability of LTAD to patients, carers and healthcare professionals as well as recruitment and retention rates. Palliative care Outcome Scale (IPOS), the Short Form Liver Disease Quality of Life (SF-LDQOL), the EuroQol (EQ-5D) and carer (Zarit Burden Interview [ZBI-12]) reported outcomes will also be assessed. Preliminary data on cost effectiveness will be collected and patients and healthcare professionals will be interviewed about their experience of the trial with a view to identifying barriers to recruitment. Discussion: LTAD could potentially improve end-of-life care in patients with refractory ascites due to ESLD by improving symptom control, reducing hospital visits and enabling some self-management. Our trial is designed to see if such patients can be recruited, as well as informing the design of a subsequent definitive trial. Trial registration: ISRCTN30697116, date assigned: 07/10/201