Qualitative Researcher Reflexivity: A Follow-Up Study with Female Sexual Assault Survivors

Motivated by researcher reflexivity, the author sought to learn from participants about the sensitive, ethical issues of the qualitative research process. The current study followed up with eight women who had previously participated in an interview-based study about sexual assault disclosure. Multiple sources of qualitative data were triangulated, including interviews, follow-up interviews, interviews from the original study, and participant checks. Phenomenological analysis yielded five themes: (a) Meaning of Participation, (b) Trust in the Researcher, (c) Connection with the Other Participants, (d) Changing Comfort, and (e) Recommendations to Increase Participants’ Comfort. Based on these results, recommendations are provided for researchers conducting reflexive qualitative research practices

Activity disengagement: Understanding challenges and opportunities for reengagement

Although maintaining engagement in activities has a positive influence on our health and wellbeing as we age, many programs that serve older adults struggle with getting participation in the programs they offer. This study sought to explore activity disengagement among older adults in a senior housing community and identify the challenges and opportunities for reengagement with the aim of informing future intervention development and testing. Fifty-one adults over the age of 60 participated in structured interviews. Findings highlighted that many older adults have activities patterns that are not optimal for health. Many reasons given for disengaging in activities (e.g., no opportunity) were surprising given that participants lived in a setting where a variety of programs were offered. Programs need to more purposively address social challenges to participating in activities and consider a more person-centered approach when developing interventions for the older adults they serve

Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients.

Capecitabine is commonly used in treating breast cancer; however, therapeutic response varies among patients and there is no clinically validated model to predict individual outcomes. Here, we investigated whether drug sensitivity quantified in ex vivo patients' blood-derived cell lines can predict response to capecitabine in vivo. Lymphoblastoid cell lines (LCLs) were established from a cohort of metastatic breast cancer patients (n = 53) who were prospectively monitored during treatment with single agent capecitabine at 2000 mg/m2/day. LCLs were treated with increasing concentrations of 5'-DFUR, a major capecitabine metabolite, to assess patients' ex vivo sensitivity to this drug. Subsequently, ex vivo phenotype was compared to observed patient disease response and drug induced-toxicities. We acquired an independent cohort of breast cancer cell lines and LCLs derived from the same donors from ATCC, compared their sensitivity to 5'-DFUR. As seen in the patient population, we observed large inter-individual variability in response to 5'-DFUR treatment in patient-derived LCLs. Patients whose LCLs were more sensitive to 5'-DFUR had a significantly longer median progression free survival (9-month vs 6-month, log rank p-value = 0.017). In addition, this significant positive correlation for 5'-DFUR sensitivity was replicated in an independent cohort of 8 breast cancer cell lines and LCLs derived from the same donor. Our data suggests that at least a portion of the individual sensitivity to capecitabine is shared between germline tissue and tumor tissue. It also supports the utility of patient-derived LCLs as a predictive model for capecitabine treatment efficacy in breast cancer patients

A novel series of positive modulators of the AMPA receptor : discovery and structure based hit-to-lead studies

Starting from an HTS derived hit 1, application of biostructural data facilitated rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first demonstration of how structure based drug design can be exploited in an optimization program for a glutamate receptor

Outcomes of Cardiovascular Disease Risk Factor Screening and Referrals in a Family Planning Clinic

Background: Cardiovascular disease (CVD) screening in Title X settings can identify low-income women at risk of future chronic disease. This study examines follow-up related to newly identified CVD risk factors in a Title X setting

Screening Low-Income Women of Reproductive Age for Cardiovascular Disease Risk Factors

Identifying and treating chronic diseases, their precursors, and other cardiovascular disease (CVD) risk factors during family planning visits may improve long-term health and reproductive outcomes among low-income women. A cross-sectional study design was used to describe the prevalence of chronic diseases (hypertension, high cholesterol, and diabetes), their precursors (pre-hypertension, borderline high cholesterol, and pre-diabetes), and related CVD risk factors (such as obesity, smoking, and physical inactivity) among low-income women of reproductive age

Molecular Networks in FGF Signaling: Flotillin-1 and Cbl-Associated Protein Compete for the Binding to Fibroblast Growth Factor Receptor Substrate 2

Fibroblast growth factor receptor substrate 2 (FRS2α) is a signaling adaptor protein that regulates downstream signaling of many receptor tyrosine kinases. During signal transduction, FRS2 can be both tyrosine and threonine phosphorylated and forms signaling complexes with other adaptor proteins and tyrosine phosphatases. We have here identified flotillin-1 and the cbl-associated protein/ponsin (CAP) as novel interaction partners of FRS2. Flotillin-1 binds to the phosphotyrosine binding domain (PTB) of FRS2 and competes for the binding with the fibroblast growth factor receptor. Flotillin-1 knockdown results in increased Tyr phosphorylation of FRS2, in line with the inhibition of ERK activity in the absence of flotillin-1. CAP directly interacts with FRS2 by means of its sorbin homology (SoHo) domain, which has previously been shown to interact with flotillin-1. In addition, the third SH3 domain in CAP binds to FRS2. Due to the overlapping binding domains, CAP and flotillin-1 appear to compete for the binding to FRS2. Thus, our results reveal a novel signaling network containing FRS2, CAP and flotillin-1, whose successive interactions are most likely required to regulate receptor tyrosine kinase signaling, especially the mitogen activated protein kinase pathway