Facilitated Peer Group Mentoring for Underrepresented Biomedical Researchers: Facilitators' Experiences and Implications for Dissemination of a Curriculum.

Peer group mentoring facilitated by senior faculty represents an effective approach. However, for underrepresented biomedical researchers, access to senior faculty from underrepresented racial/ethnic groups is limited. We explored motivations, benefits, and challenges for facilitators enrolled to deploy an intervention in the context of a randomized controlled trial that tested two peer group mentoring strategies for underrepresented early career researchers.

Catalyzing communities of research rigour champions.

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science.

Implementation and Evaluation of a National Well-Being Curriculum for KL2 Scholars.

The study aimed to pilot test a well-being curriculum for KL2 scholars to be used across the Clinical and Translational Science Award consortium. Between November 2022, and May 2023, 36 KL2 scholars from 25 hubs participated in the program. The General Well-Being Index for U.

A Feasibility Study of a Physical and Occupational Therapy-Led and Parent-Administered Program to Improve Parent Mental Health and Infant Development.

Aims: Extremely premature birth puts infants at high risk for developmental delay and results in parent anxiety and depression. The primary objective of this study was to characterize feasibility and acceptability of a therapist-led, parent-administered therapy and massage program designed to support parent mental health and infant development.

Methods: A single cohort of 25 dyads - parents (24 mothers, 1 father) and extremely preterm (<28 wk gestation) infants - participated in the intervention.

The Virtual CTSA Visiting Scholar Program to Support Early-Stage Clinical and Translational Researchers: Implementation and Outcomes.

In addition to restrictions on conducting research, COVID-19-related travel bans and scientific meeting cancellations have negatively affected scholars in the Clinical and Translational Science Award (CTSA) Mentored Career Development Award (KL2) program. In response, a national virtual visiting scholar program was developed to provide opportunity for KL2 scholars to be virtual visiting professors at another CTSA hub, meet faculty and scholars, and expand networks and build collaborations. This article describes the design and short-term outcomes of the virtual CTSA Visiting Scholar Program.

Immediate impact of the COVID-19 pandemic on CTSA TL1 and KL2 training and career development.

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write.

Personalized training pathways for translational science trainees: Building on a framework of knowledge, skills, and abilities across the translational science spectrum.

Background: In order to conduct translational science, scientists must combine domain-specific expertise with knowledge on how to identify and cross translational hurdles, and insights on positioning discoveries for the next translational stage. Expert educators from the Clinical and Translational Science Awards (CTSA) Consortium identified 97 knowledge, skills, and abilities (KSAs) important to include in training programs for translational scientists. To assist educators and trainees to use these KSAs, a conceptual model called "Personalized Pathways" was developed that prioritizes KSAs based on trainee background, research area, or phenotype, and expertise on the research team.

A model for developing, evaluating, and disseminating best practices in education and training.

With the shift toward team-based translational science came recognition that existing strategies for training individual investigators and retaining them in the biomedical workforce would be inadequate. To support this shift, it is important to: develop innovative strategies to educate and train diverse members of research teams; evaluate those programs; and disseminate best practices broadly. We have developed a four-phase model to facilitate the development, evaluation, and widespread dissemination of innovative strategies to train the biomedical research workforce.

Clinical and translational scientist career success: metrics for evaluation.

Despite the increased emphasis on formal training in clinical and translational research and the growth in the number and scope of training programs over the past decade, the impact of training on research productivity and career success has yet to be fully evaluated at the institutional level. In this article, the Education Evaluation Working Group of the Clinical and Translational Science Award Consortium introduces selected metrics and methods associated with the assessment of key factors that affect research career success. The goals in providing this information are to encourage more consistent data collection across training sites, to foster more rigorous and systematic exploration of factors associated with career success, and to help address previously identified difficulties in program evaluation.

Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine.

Background: We previously established furanocoumarins as mediators of the interaction between grapefruit juice (GFJ) and the model CYP3A4 substrate felodipine in healthy volunteers using a GFJ devoid of furanocoumarins. It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates.

Objective: The effects of furanocoumarin-free GFJ on drug disposition were further characterized by using the dual CYP3A4/P-glycoprotein substrate cyclosporine.

The Environmental Polymorphisms Registry: a DNA resource to study genetic susceptibility loci.

The National Institute of Environmental Health Sciences is establishing a DNA repository named the Environmental Polymorphisms Registry (EPR). The goal is to recruit 20,000 subjects from the greater Research Triangle Park region of North Carolina and collect a sample of each subject's DNA for genetic study. Personal information is obtained from each EPR subject and linked to their sample in coded form.

The influence of CYP3A5 expression on the extent of hepatic CYP3A inhibition is substrate-dependent: an in vitro-in vivo evaluation.

Despite several studies suggesting that CYP3A5 expression can influence the extent of hepatic CYP3A-mediated inhibition, a systematic in vitro-in vivo evaluation of this potential clinically important issue has not been reported. Using representative probes from two distinct CYP3A substrate subgroups (midazolam, erythromycin), the inhibitory potency of fluconazole was evaluated in pooled human liver microsomes (HLM) with a low or high specific CYP3A5 content, in recombinant CYP3A enzymes (rCYP3A), and in healthy volunteers lacking or carrying the CYP3A5(*)1 allele. Fluconazole was a slightly more potent inhibitor of CYP3A activity in CYP3A5-HLM than in CYP3A5+ HLM with midazolam (K(i) of 15 and 25 microM, respectively) but not with erythromycin (IC(50) of 70 and 54 microM, respectively).

Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response.

Unlabelled: The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy.

Factors that influence the timing of spontaneous labor at term.

Objective: Whether pre-term birth culminates as a result of a de novo pathologic process or is more simply early activation of physiologic mechanisms is unknown. Exploration of the onset of labor in term women with classical risk factors for early delivery might provide insights into the mechanisms leading to pre-term birth. This study examines whether sociodemographic factors known to increase the risk of pre-term birth also affect the length of term gestations.

A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction.

Background: Grapefruit juice (GFJ) enhances the systemic exposure of numerous CYP3A4 drug substrates, including felodipine, by inhibiting intestinal (but not hepatic) first-pass metabolism. Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice, but their contribution to the GFJ effect in vivo remains unclear.

Objective: To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction, a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine.

Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5.

Objective: Saquinavir, a widely prescribed human immunodeficiency virus 1 protease inhibitor, has a low and variable oral bioavailability that has been attributed to extensive first-pass extraction mediated by hepatic or intestinal cytochrome P450 (CYP) 3A4 and intestinal P-glycoprotein (P-gp). The polymorphic CYP3A5 has also been shown to influence the saquinavir metabolite/parent urinary ratio, suggesting a role for CYP3A5.

Methods: Twenty healthy subjects received a single oral dose of saquinavir (600 mg) with water (control) and, on a separate occasion, with Seville orange juice (a selective intestinal CYP3A4/5 inhibitor).

Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?

Aims: To evaluate the antimalarial agent quinine as a potential in vivo probe for hepatic cytochrome P450 (CYP) 3A4 activity.

Methods: Ten healthy adult volunteers received, by randomized crossover design, either a single oral dose of quinine sulphate (600 mg) alone, or quinine sulphate (600 mg) plus the CYP3A4 inhibitor troleandomycin (TAO; 500 mg every 8 h). Plasma and urine samples were collected before quinine administration, and up to 48 h thereafter, then analysed by h.