The role of Patient and public involvement (PPI) in pre-clinical spinal cord research: An interview study.

BACKGROUND: Patient and public involvement in research (PPI) has many benefits including increasing relevance and impact. While using PPI in clinical research is now an established practice, the involvement of patients and the public in pre-clinical research, which takes place in a laboratory setting, has been less frequently described and presents specific challenges. This study aimed to explore the perspectives of seriously injured rugby players' who live with a spinal cord injury on PPI in pre-clinical research. METHODS: Semi-structured interviews were conducted via telephone with 11 seriously injured rugby players living with spinal cord injury on the island of Ireland. A purposive sampling approach was used to identify participants. Selected individuals were invited to take part via gatekeeper in a charitable organisation that supports seriously injured rugby players. Interviews were transcribed verbatim and analysed thematically. FINDINGS: Six themes were identified during analysis: 'appreciating potential benefits of PPI despite limited knowledge', 'the informed perspectives of people living with spinal cord injury can improve pre-clinical research relevance', 'making pre-clinical research more accessible reduces the potential for misunderstandings to occur', 'barriers to involvement include disinterest, accessibility issues, and fear of losing hope if results are negative', 'personal contact and dialogue helps people feel valued in pre-clinical research, and 'PPI can facilitate effective dissemination of pre-clinical research as desired by people living with spinal cord injury.' CONCLUSION: People affected by spinal cord injury in this study desire further involvement in pre-clinical spinal cord injury research through dialogue and contact with researchers. Sharing experiences of spinal cord injury can form the basis of PPI for pre-clinical spinal cord injury research.

Profiling of vaginal Lactobacillus jensenii isolated from preterm and full-term pregnancies reveals strain-specific factors relating to host interaction.

Each year, 15 million infants are born preterm (<37 weeks gestation), representing the leading cause of mortality for children under the age of five. Whilst there is no single cause, factors such as maternal genetics, environmental interactions, and the vaginal microbiome have been associated with an increased risk of preterm birth. Previous studies show that a vaginal microbiota dominated by Lactobacillus is, in contrast to communities containing a mixture of genera, associated with full-term birth. However, this binary principle does not fully consider more nuanced interactions between bacterial strains and the host. Here, through a combination of analyses involving genome-sequenced isolates and strain-resolved metagenomics, we identify that L. jensenii strains from preterm pregnancies are phylogenetically distinct from strains from full-term pregnancies. Detailed analysis reveals several genetic signatures that distinguish preterm birth strains, including genes predicted to be involved in cell wall synthesis, and lactate and acetate metabolism. Notably, we identify a distinct gene cluster involved in cell surface protein synthesis in our preterm strains, and profiling the prevalence of this gene cluster in publicly available genomes revealed it to be predominantly present in the preterm-associated clade. This study contributes to the ongoing search for molecular biomarkers linked to preterm birth and opens up new avenues for exploring strain-level variations and mechanisms that may contribute to preterm birth.

Applying Patient and Public Involvement in preclinical research: A co-created scoping review.

BACKGROUND: Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence-based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects. METHODS: A scoping review was conducted to search the literature in Medline (PubMed), EMBASE, CINAHL, PsycInfo and Web of Science Core Collection to identify applied examples of preclinical PPI. Two independent reviewers conducted study selection and data extraction separately. Data were extracted relating to PPI in terms of (i) rationale and aims, (ii) approach used, (iii) benefits and challenges, (iv) impact and evaluation and (v) learning opportunities for preclinical PPI. Findings were reviewed collaboratively by PPI contributors and the research team to identify principles that could be applied to other projects. RESULTS: Nine studies were included in the final review with the majority of included studies reporting PPI to improve the relevance of their research, using approaches such as PPI advisory panels and workshops. Researchers report several benefits and challenges, although evidence of formal evaluation is limited. CONCLUSION: Although currently there are few examples of preclinical research studies reporting empirical PPI activity, their findings may support those aiming to use PPI in preclinical research. Through collaborative analysis of the scoping review findings, several principles were developed that may be useful for other preclinical researchers. PATIENT OR PUBLIC CONTRIBUTION: This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5-year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers and PPI facilitators collaborated as co-authors on the conceptualization, execution and writing of this review, including refining the findings into the set of principles reported here.

Biomimetic Scaffolds for Spinal Cord Applications Exhibit Stiffness-Dependent Immunomodulatory and Neurotrophic Characteristics.

After spinal cord injury (SCI), tissue engineering scaffolds offer a potential bridge for regeneration across the lesion and support repair through proregenerative signaling. Ideal biomaterial scaffolds that mimic the physicochemical properties of native tissue have the potential to provide innate trophic signaling while also minimizing damaging inflammation. To address this challenge, taking cues from the spinal cord's structure, the proregenerative signaling capabilities of native cord components are compared in vitro. A synergistic mix of collagen-IV and fibronectin (Coll-IV/Fn) is found to optimally enhance axonal extension from neuronal cell lines (SHSY-5Y and NSC-34) and induce morphological features typical of quiescent astrocytes. This optimal composition is incorporated into hyaluronic acid scaffolds with aligned pore architectures but varying stiffnesses (0.8-3 kPa). Scaffolds with biomimetic mechanical properties (<1 kPa), functionalized with Coll-IV/Fn, not only modulate primary astrocyte behavior but also stimulate the production of anti-inflammatory cytokine IL-10 in a stiffness-dependent manner. Seeded SHSY-5Y neurons generate distributed neuronal networks, while softer biomimetic scaffolds promote axonal outgrowth in an ex vivo model of axonal regrowth. These results indicate that the interaction of stiffness and biomaterial composition plays an essential role in vitro in generating repair-critical cellular responses and demonstrates the potential of biomimetic scaffold design.

Alcohol use in an academic medical school environment: A UC San Diego Healer Education Assessment and Referral (HEAR) Report.

BACKGROUND: Medical students and physicians in training and in practice are at risk for excessive alcohol use and abuse, potentially impacting the affected individuals as well as their family members, trainees, and patients. However, several roadblocks to care, including stigma, often keep them from seeking treatment. METHODS: We analyzed data from anonymous questionnaires completed by medical students, house staff, and faculty from 2009 to 2014 as part of a depression awareness and suicide prevention program at a state-supported medical school in the United States. The authors explored associations between self-reported "drinking too much" and depression, suicidal ideation, substance use, intense affective states, and mental health treatment. RESULTS: Approximately one-fifth of the respondents reported "drinking too much." "Drinking too much" was associated with more severe depression and impairment, past suicide attempts and current suicidal ideation, intense affective states, and other substance use. Those who were "drinking too much" were more likely than others to accept referrals for mental health treatment through the anonymous interactive screening program, suggesting that this program may be effective in skirting the stigma barrier for accessing mental health care for this at-risk population. CONCLUSIONS: The self-reported prevalence of "drinking too much" among medical students, house staff, and faculty is high and associated with negative mental health outcomes. Targeted, anonymous screenings may identify at-risk individuals and provide mental health care referrals to those in need.

Listening to depression and suicide risk in medical students: the Healer Education Assessment and Referral (HEAR) Program.

OBJECTIVE: A growing body of literature documents high rates of burnout, depression, and suicidal ideation among physicians and medical students. Barriers to seeking mental health treatment in this group include concerns about time, stigma, confidentiality, and potential career impact. The authors describe a 4-year trial of the Healer Education Assessment and Referral (HEAR) program, designed to increase mental health services utilization (MHSU) and decrease suicide risk (SR) as assessed by an Interactive Screening Program (ISP)at one US medical school. METHODS: Over a 4-year period, medical students were engaged in face-to-face, campus-wide, educational group programs and were invited to complete an individual, online, and anonymous survey. This survey contained the 9-item Patient Health Questionnaire (PHQ-9) scale to assess depression and items to identify suicidal thoughts and behaviors, substance use, distressing emotional states, and the use of mental health treatment. Students who engaged in this ISP by corresponding electronically with a counselor after completing the survey were assessed and when indicated, referred to further treatment. RESULTS: The HEAR program was delivered to 1,008 medical students. Thirty-four percent (343/1,008) completed the online screening portion. Almost 8 % of respondents met the criteria for high/significant SR upon analysis of the completed screens. Ten out of 13 of the students with SR who dialogued with a counselor were not already receiving mental health treatment, indicating that this anonymous ISP identified a high proportion of an untreated, at risk, and potentially suicidal population. MHSU among medical students who completed the survey was 11.5 % in year 1 and 15.0 % by year 4. SR among medical students was 8.8 % in year 1 and 6.2 % in year 4 as assessed by the ISP. CONCLUSIONS: This novel interventional program identified at risk, potentially suicidal medical students at one institution. Based on this single-site experience, we suggest that future multisite studies incorporate a comparison group, acquire baseline (prematriculation) data regarding MHSU and SR, and use an individualized yet anonymous identification system to measure changes in individual participants' mental health status over time.

The suicide prevention and depression awareness program at the University of California, San Diego School of Medicine.

To address physician depression and suicide at one U.S. medical school, a faculty committee launched a Suicide Prevention and Depression Awareness Program in 2009 whose focus is medical students', residents', and faculty physicians' mental health. The program consists of a two-pronged approach: (1) screening, assessment, and referral and (2) education. The screening process is anonymous, confidential, and Web based, using customized software created by the American Foundation for Suicide Prevention. The educational component consists of a medical-school-wide campaign including Grand Rounds on physician burnout, depression, and suicide as well as similar sessions geared toward trainees. The authors document the process of developing and implementing the program, including the program's origins and goals, their critical decision-making processes, and successes and challenges of the program's first year.Of the 2,860 medical students, housestaff, and faculty who received the e-mail invitation in the first year, 374 individuals (13%) completed screens, 101/374 (27%) met criteria for significant risk for depression or suicide, and 48/374 (13%) received referrals for mental health evaluation and treatment. The program provided 29 Grand Rounds and other presentations during the first year.This may be the first program that aims to increase awareness of depression and to destigmatize help-seeking in order to prevent suicide and whose target population includes the full panoply of medical school constituents: students, residents, and faculty physicians. The program was well received in its first year, and while demonstrating the prevention of suicides is difficult, the authors are encouraged by the program's results thus far.