Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide. Fourteen programmes participated in this study. Eight programmes operated 24 h/7 days, resulting in a lower median postmortem interval (time between death and start of the autopsy, 4 h) compared with those operating during working hours (9 h). Most programmes (n = 10) succeeded in collecting all samples within a median of 12 h after death. A large number of tumour sites were sampled during each autopsy (median 15.5 per patient). The median number of samples collected per patient was 58, including different processing methods for tumour samples but also non-tumour tissues and liquid biopsies. Unique biological insights derived from these samples included metastatic progression, treatment resistance, disease heterogeneity, tumour dormancy, interactions with the tumour micro-environment, and tumour representation in liquid biopsies. Tumour patient-derived xenograft (PDX) or organoid (PDO) models were additionally established, allowing for drug discovery and treatment sensitivity assays. Apart from the opportunities and achievements, we also present the challenges related with postmortem sample collections and strategies to overcome them, based on the shared experience of these 14 programmes. Through this work, we hope to increase the transparency of postmortem tissue donation, to encourage and aid the creation of new programmes, and to foster collaborations on these unique sample collections. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The long-term effectiveness of a personality-targeted substance use prevention program on aggression from adolescence to early adulthood.

BACKGROUND: Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20. METHODS: In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12-15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering. RESULTS: Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = -0.42; 95% confidence interval [CI] -0.64 to -0.20; p < 0.001), reactive aggression (b = -0.22; 95% CI 0.35 to -0.10; p = 0.001), and proactive aggression (b = -0.14; 95% CI -0.23 to -0.05; p = 0.002) was greater for the Preventure group compared to the control group. CONCLUSIONS: The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Engineering xylose induction in Vibrio natriegens for biomanufacturing applications.

Xylose is an abundant, inexpensive and readily available carbohydrate common in minimally processed feedstocks such as seaweed and algae. While a wide variety of marine microbes have evolved to utilize seaweed and algae, only a few currently have the requisite characteristics and genetic engineering tools necessary to entertain the use of these underutilized feedstocks. The rapidly growing Gram-negative halophilic bacterium Vibrio natriegens is one such chassis. In this study, we engineered and tested xylose induction in V. natriegens as a tool for scalable bioproduction applications. First, we created a sensing construct based on the xylose operon from Escherichia coli MG1665 and measured its activity using a fluorescent reporter and identified that cellular import plays a key role in induction strength and that expression required the XylR transcription factor. Next, we identified that select deletions of the promoter region enhance gene expression, limiting the effect of carbohydrate repression when xylose is used as an inducer in the presence of industrially relevant carbon sources. Lastly, we used the optimized constructs to produce the biopolymer melanin using seawater mimetic media. One of these formulations utilized a nori-based seaweed extract as an inducer and demonstrated melanin yields comparable to previously optimized methods using a more traditional and costly inducer. Together, the results demonstrate that engineering xylose induction in V. natriegens can provide an effective and lower cost option for timed biosynthesis in scalable biomanufacturing applications using renewable feedstocks.

Firearm businesses as partners in suicide prevention: a cross-sectional study of the Gun Shop Project in Colorado, USA.

BACKGROUND: The Gun Shop Project aims to reduce firearm suicide and is widely implemented in the USA, yet little is known about the core firearm business practices and behaviours that might contribute to preventing firearm suicide. METHODS: Owners or managers of all firearm businesses identified as participants in Colorado's Gun Shop Project were invited to respond to a questionnaire. Data collection occurred from March to May 2021. Analyses included unweighted descriptive statistics with CIs and Pearson χ2 tests for categorical associations. RESULTS: 54 firearm businesses participated (response rate: 28%). Under half reported practices that are Gun Shop Project core aspects (range: 14%-45%). 22% of businesses frequently engaged customers on the importance of safe firearm storage in suicide prevention while 26% had denied a firearm sale and 14% had assisted with temporary secure storage in the past year with customers perceived to be in suicidal crisis. However, high proportions reported willingness to engage in these behaviours if a customer was in crisis: 74% were willing to refuse a sale of a firearm or ammunition, 70% were willing to discuss temporary secure storage options and 70% were willing to direct customers to mental health services. CONCLUSIONS: This study suggests that efforts to continue educating and involving firearm businesses may have an impact on the adoption of organisational suicide prevention practices and behaviours. Ongoing efforts are needed to understand core components of Gun Shop Project to inform standardised recommendations for effective firearm business practices that prevent firearm suicide.

Improved Resolution and Image Quality of Musculoskeletal Magnetic Resonance Imaging using Deep Learning-based Denoising Reconstruction: A Prospective Clinical Study.

OBJECTIVE: To prospectively evaluate a deep learning-based denoising reconstruction (DLR) for improved resolution and image quality in musculoskeletal (MSK) magnetic resonance imaging (MRI). METHODS: Images from 137 contrast-weighted sequences in 40 MSK patients were evaluated. Each sequence was performed twice, first with the routine parameters and reconstructed with a routine reconstruction filter (REF), then with higher resolution and reconstructed with DLR, and with three conventional reconstruction filters (NL2, GA43, GA53). The five reconstructions (REF, DLR, NL2, GA43, and GA53) were de-identified, randomized, and blindly reviewed by three MSK radiologists using eight scoring criteria and a forced ranking. Quantitative SNR, CNR, and structure's full width at half maximum (FWHM) for resolution assessment were measured and compared. To account for repeated measures, Generalized Estimating Equations (GEE) with Bonferroni adjustment was used to compare the reader's scores, SNR, CNR, and FWHM between DLR vs. NL2, GA43, GA53, and REF. RESULTS: Compared to the routine REF images, the resolution was improved by 47.61% with DLR from 0.39 ± 0.15 mm2 to 0.20 ± 0.06 mm2 (p < 0.001). Per-sequence average scan time was shortened by 7.93% with DLR from 165.58 ± 21.86 s to 152.45 ± 25.65 s (p < 0.001). Based on the average scores, DLR images were rated significantly higher in all image quality criteria and the forced ranking (p < 0.001). CONCLUSION: This prospective clinical evaluation demonstrated that DLR allows approximately two times finer resolution and improved image quality compared to the standard-of-care images.

Regulatory Intensity on Private Forestland and its Relationship with State Characteristics in the United States.

Though the federal government impacts private forest management across the United States through legislation such as the Clean Water Act, state-level regulations applied to private forest landowners vary remarkably. Despite this diversity of policies, little is known about how variations in regulatory intensity (defined here as number of forestry regulations) correlate with state-level political and socioeconomic characteristics. In this study, we use a quantitative approach to explore the intensity of regulation on forest practices impacting private landowners across all 50 states. We quantified intensity by tabulating the number of regulated forest practices, then used a quasi-Poisson regression to estimate the relationship between regulatory intensity and state-level characteristics, including forestland ownership types, the economic importance of the forest industry, and measures of state environmentalism. Results indicated a positive association between regulatory intensity and the percent of private corporate land, environmental voting records of elected officials, and direct democracy. Foresters and landowners may learn from these relationships, consider how to influence different policies, and build or achieve greater levels of public trust. This study starts to help us explain why state-level forestry policies differ, not just how they differ.

Improving Data-Driven Decision Making for Primary Prevention: Providing Data Interpretation Resources to Schools and Communities in Colorado.

Communities are increasingly interested in primary prevention efforts to reduce health inequities. However, few communities can access local data on social determinants of health and many do not have the skills or training to interpret data to inform decision making on appropriate strategies that impact social determinants of health. A population-based youth health survey administered to middle and high school students, such as exists in most states in the United States, can assess health behaviors and risk and protective factors. The schools and school districts that participate are provided with reports of results and data interpretation resources that support their understanding of risk and protective factors to inform local decision making and action. Other states can similarly provide local data and resources on risk and protective factors to help communities collaborate on primary prevention efforts that achieve health equity.

Clinician perspectives on patient-centered conversations about weight management with patients with early breast cancer.

BACKGROUND: The aim of this study is to gather detailed insights from breast cancer (BC) clinicians on how to have patient-centered conversations about weight and weight management with women diagnosed with early BC. A high body mass index (BMI) is a risk factor for female BC, and many women diagnosed with BC experience unhealthy weight gain after their primary treatment. The oncology team has the opportunity to discuss the importance of healthy weight for BC prognosis and survival. METHODS: The sample of community-based BC clinicians included the following: three Black clinicians, three White clinicians, and two clinicians who were neither Black nor White; six females and two males; and six MDs and two physician assistants or nurse practitioners. Semistructured telephone interviews were conducted with these clinicians regarding their experience with and insights into having healthy weight conversations during routine clinic visits. RESULTS: Clinicians noted that weight-related conversations should focus less on BMI and weight loss and more on "healthy behavior." Clinicians looked for cues from their patients as to when they were ready for "healthy weight" counseling, receptive to diet/nutrition counseling and referrals, and ready to attempt behavioral change. Clinicians noted that encouraging physical activity could be especially challenging with patients accustomed to a sedentary lifestyle. CONCLUSIONS: Clinic-based conversations about healthy weight are likely to be most productive for both patients and their treating oncologists during the post-primary treatment phase when patients are most receptive to behavioral change that enhances their prognosis and survival.

Employee Cardiometabolic Risk Following a Cluster-Randomized Workplace Intervention From the Work, Family and Health Network, 2009-2013.

Objectives. To examine whether workplace interventions to increase workplace flexibility and supervisor support and decrease work-family conflict can reduce cardiometabolic risk. Methods. We randomly assigned employees from information technology (n = 555) and long-term care (n = 973) industries in the United States to the Work, Family and Health Network intervention or usual practice (we collected the data 2009-2013). We calculated a validated cardiometabolic risk score (CRS) based on resting blood pressure, HbA1c (glycated hemoglobin), HDL (high-density lipoprotein) and total cholesterol, height and weight (body mass index), and tobacco consumption. We compared changes in baseline CRS to 12-month follow-up. Results. There was no significant main effect on CRS associated with the intervention in either industry. However, significant interaction effects revealed that the intervention improved CRS at the 12-month follow-up among intervention participants in both industries with a higher baseline CRS. Age also moderated intervention effects: older employees had significantly larger reductions in CRS at 12 months than did younger employees. Conclusions. The intervention benefited employee health by reducing CRS equivalent to 5 to 10 years of age-related changes for those with a higher baseline CRS and for older employees. Trial Registration. ClinicalTrials.gov Identifier: NCT02050204. (Am J Public Health. 2023;113(12):1322-1331. https://doi.org/10.2105/AJPH.2023.307413).

Comparative Analysis of Palliative Care Needs Identified in Inpatient Rehabilitation and Skilled Nursing Facilities by Multidisciplinary Team Members.

OBJECTIVE: Assess access to, need for, and beliefs surrounding specialized palliative care (PC). DESIGN: Observational, comparative analysis needs assessment survey. SETTING: Four inpatient rehabilitation facilities (IRFs) or skilled nursing facilities with long-term care (SNFs/LTC) that provide subacute rehabilitation within 1 tertiary care system. PARTICIPANTS: Allied health professionals, physicians, nursing, case managers, social workers, spiritual care (n=198). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Frequency of patient needs, attitudes about current systems, individual beliefs, and barriers to PC. Confidence in management, communicating, and navigating primary PC competencies among clinical pathway employees. RESULTS: Of 198 respondents, 37% said PC was available at their facility. Those in IRF reported higher frequencies of grief/unmet spiritual needs of patients compared with SNF/LTC (P≤.001). Conversely, SNF/LTC reported higher frequencies of agitation, poor appetite, and end-of-life care (P≤.003). Respondents in SNF/LTC felt more confident managing end-of-life care, explaining what hospice and PC are and appropriateness for referral to each, discussing advance directives, determining appropriate decision-makers, and navigating ethical decisions than in IRFs (P≤.007). SNF/LTC participants reported higher effectiveness of their current system involving PC and ease of hospice transition compared with IRFs (P≤.008). A majority agreed that PC does not take away patient hope, could prevent recurrent hospitalizations, improve symptom management, communication, and patient and family satisfaction. The most common reported barriers to PC consultation were (1) attitudes and beliefs of staff or patients and families, (2) system issues with access, cost, or prognosis communication, and (3) lack of understanding of PC role. CONCLUSIONS: A gap exists in PC access in IRF and SNF/LTC despite patient needs and staff beliefs. Future studies should focus on identifying which patients should be referred to PC in the post-acute setting and what outcomes can be used as a guide to meet the needs of this growing area of practice.

Harm reduction in undergraduate and graduate medical education: a systematic scoping review.

BACKGROUND: Substance use increasingly contributes to early morbidity and mortality, which necessitates greater preparation of the healthcare workforce to mitigate its harm. The purpose of this systematic scoping review is to: 1) review published curricula on harm reduction for substance use implemented by undergraduate (UME) and graduate medical education (GME) in the United States and Canada, 2) develop a framework to describe a comprehensive approach to harm reduction medical education, and 3) propose additional content topics for future consideration. METHODS: PubMed, Scopus, ERIC: Education Resources Information Center (Ovid), and MedEdPORTAL were searched. Studies included any English language curricula about harm reduction within UME or GME in the United States or Canada from 1993 until Nov 22, 2021. Two authors independently reviewed and screened records for data extraction. Data were analyzed on trainee population, curricula objectives, format, content, and evaluation. RESULTS: Twenty-three articles describing 19 distinct educational programs across the United States were included in the final sample, most of which created their own curricula (n = 17). Data on educational content were categorized by content and approach. Most programs (85%) focused on introductory substance use knowledge and skills without an understanding of harm reduction principles. Based on our synthesis of the educational content in these curricula, we iteratively developed a Harm Reduction Educational Spectrum (HRES) framework to describe curricula and identified 17 discrete content topics grouped into 6 themes based on their reliance on harm reduction principles. CONCLUSIONS: Harm reduction is under-represented in published medical curricula. Because the drug supply market changes rapidly, the content of medical curricula may be quickly outmoded thus curricula that include foundational knowledge of harm reduction principles may be more enduring. Students should be grounded in harm reduction principles to develop the advanced skills necessary to reduce the physical harm associated with drugs while still simultaneously recognizing the possibility of patients' ongoing substance use. We present the Harm Reduction Educational Spectrum as a new framework to guide future healthcare workforce development and to ultimately provide the highest-quality care for patients who use drugs.

Comparison of Lateral versus Medial Entry Femoral Traction Pin Complication Rates.

Distal femoral skeletal traction is a common procedure for the stabilization of fractures of the pelvis, acetabulum, and femur following trauma. Femoral traction pins are traditionally inserted via medial-to-lateral (MTL) entry to accurately direct the pin away from the medial neurovascular bundle. Alternatively, cadaveric studies have demonstrated low risk to the neurovascular bundle using a lateral-to-medial (LTM) approach. The purpose of this study was to compare the incidence of complications of LTM and MTL femoral traction pin placement at a single institution. This was a retrospective review of patients from the orthopaedic consult registry at a academic Level I Trauma Center. We identified 233 LTM femoral traction pin procedures in 231 patients and 29 MTL pin procedures in 29 patients. The two pin placement techniques were compared with respect to complications, specifically the incidence of neurovascular injury, cellulitis, septic arthritis, osteomyelitis, and heterotopic ossification after femoral traction pin placement. Two complications were reported. One patient developed heterotopic ossification along the pin tract after LTM traction pin placement. Another patient developed septic arthritis after LTM pin placement, likely attributable to retrograde intramedullary nailing of his open femur fracture rather than his traction pin. There were no reports of neurovascular injury, cellulitis, or osteomyelitis associated with pin placement. The complication rate was 0.9% for LTM group and 0.0% for MTL group (p = 0.616). LTM femoral traction pin placement is a safe procedure with a similarly low complication rate compared with traditional MTL placement when the limb is positioned in neutral alignment. (Journal of Surgical Orthopaedic Advances 32(4):259-262, 2023).

Burnout and Commitment to Primary Care: Lessons From the Early Impacts of COVID-19 on the Workplace Stress of Primary Care Practice Teams.

PURPOSE: The COVID-19 pandemic has dramatically affected all areas of health care. Primary care practices are on the front lines for patients seeking health care during this period. Understanding clinical and administrative staff members' strategies for managing the broad-ranging changes to primary care service delivery is important for the support of workforce well-being, burnout, and commitment to primary care. METHODS: Thirty-three staff members from 8 practices within a single health care system completed short, semistructured interviews from May 11, 2020 to July 20, 2020. Interviews were coded using a combination of conventional and directed content analysis. RESULTS: Themes emerged from the data that mapped onto the Job Demands-Control-Social Support model. Participants reported that every aspect of primary care service delivery needed to be adapted for COVID-19, which increased their job demands significantly. Several also described pride in their development of new skills, and in most interviews, they expressed that the experience brought staff together. Staff engaged in active cognitive reframing of events during the interviews as they coped with increased workplace stress. However, as the pandemic changed from an acute stress event to a chronic stressor, staff were more likely to indicate signs of burnout. CONCLUSIONS: Primary care teams absorbed tremendous burdens during COVID-19 but also found that some stress was offset by increased support from management and colleagues, belief in their own necessity, and new development opportunities. Considering high prepandemic strain levels, the ability of primary care teams to persist under these conditions might erode as the crisis becomes an enduring challenge.

Selective personality-targeted prevention of suicidal ideation in young adolescents: post hoc analysis of data collected in a cluster randomised controlled trial.

OBJECTIVE: To assess the efficacy of a selective, personality-targeted intervention for reducing suicidal ideation in adolescents. DESIGN: Post hoc analysis of survey data collected in the Climate and Preventure (CAP) study, a cluster randomised controlled trial that compared strategies for reducing alcohol misuse by adolescents, 2012-2015. SETTING, PARTICIPANTS: Year 8 students at 16 New South Wales non-government schools and one Victorian non-government school. INTERVENTION: Preventure, a selective, personality-targeted intervention designed to help adolescents with personality risk factors for alcohol misuse, comprising two 90-minute sessions, one week apart. For our post hoc analysis, we combined data from the two CAP trial groups in which Preventure was offered (the Preventure and the Preventure/Climate Schools [a non-selective prevention strategy] groups) as the intervention group; and data from the two groups in which Preventure was not offered (usual health education only [control] and Climate Schools groups) as the control group. MAIN OUTCOME MEASURE: Difference between post hoc control and intervention groups in the change in proportions of students reporting suicidal ideation during the preceding six months (single item of Brief Symptom Inventory depression subscale) over three years. RESULTS: A total of 1636 students (mean age at baseline, 13.3 years; standard deviation, 0.5 years) were included in our analysis, of whom 1087 (66%) completed the suicidal ideation item in the three-year follow-up assessment. The post hoc control group included 755 students (nine schools), the intervention group 881 students (eight schools). After adjusting for nesting of students in schools and sex, reporting of suicidal ideation by students who had received Preventure had declined over three years, compared with the control group (per year: adjusted odds ratio, 0.80; 95% CI, 0.66-0.97). CONCLUSION: Personality-targeted selective prevention during early secondary school can have a lasting impact on suicidal ideation during adolescence. TRIAL REGISTRATION (CAP STUDY ONLY): Australian and New Zealand Clinical Trials Registry, ACTRN12612000026820 (prospective).

Perspectives of older women with early breast cancer on telemedicine during post-primary treatment.

PURPOSE: Telemedicine has the potential to lessen healthcare burden of older patients due to frequent appointments, physical disabilities, and reliance on caretakers. To benefit from telemedicine, patients must have the capacity and willingness to engage with technology. This study aimed to better understand the telemedicine experiences of older women with non-metastatic breast cancer regarding visit convenience, completeness, and interpersonal satisfaction. METHODS: Semi-structured interviews were conducted in a convenience sample of women age 65+, post-primary treatment for stage I-III breast cancer, who had received in-person outpatient care at a cancer center in urban North Carolina before a telemedicine appointment occurring after March 2020. Patients were interviewed about their perceptions of telemedicine (telephone, video) as compared to in-person visits. Audio files of interviews were transcribed and analyzed for themes and subthemes established a priori in the interview protocol. RESULTS: Fifteen patients (telephone = 5, video = 10) were consented and interviewed July-October 2021, mean age 74. Thirteen participants reported they preferred a hybrid care model that included telemedicine care over in-person care alone. COVID-19, physical disability, and transportation burden were the most common factors for telemedicine preference. Comfort with familiar face-to-face interactions and having a physical exam were common factors for in-person appointment preference. In-person appointment was favored early in the post-primary treatment phase; telemedicine was more acceptable when relationships were well-established and patients were farther out from diagnosis. CONCLUSIONS: Patient-provider discussions about appointment modality should take into account newness of diagnosis, patient familiarity with the care team, travel burden, and necessity of physical exam.

Associations of childhood emotional and physical neglect with mental health and substance use in young adults.

BACKGROUND: Childhood neglect is a risk factor for subsequent mental health problems. However, research on the unique contribution of emotional and physical subtypes of neglect is lacking. Importantly, if emotional and physical neglect have different impacts on mental health, they must be examined separately to understand how to prevent and treat their effects. OBJECTIVE: This study aimed to examine associations of emotional and physical neglect with depression, anxiety, stress, alcohol and drug use in 18- to 20-year-olds. METHODS: Participants (N = 569, mean age = 18.9, 70% female) responded in an online survey to questions on childhood emotional and physical neglect, childhood abuse, symptoms of depression, anxiety and stress, and alcohol and drug use and problems. Procedures were approved by the University of Sydney Human Ethics Committee. Hierarchical linear regressions were performed, controlling for socio-demographic characteristics and other adverse childhood experiences. RESULTS: Combined neglect was associated with depression (B = 2.895, p < 0.001), anxiety (B = 1.572, p = 0.003) and stress (B = 1.781, p = 0.001). However, a second model entering emotional and physical neglect as separate exposures revealed emotional neglect was driving this association with depression (B = 2.884, p < 0.001), anxiety (B = 1.627, p = 0.001) and stress (B = 1.776, p = 0.001), and that physical neglect was not associated with any outcome. Neither emotional nor physical neglect were associated with alcohol or drug use. CONCLUSION: Emotional neglect is a risk factor for mental health problems in early adulthood. Research that combines emotional and physical neglect into a single exposure may be obscuring relationships with mental health. Mental health prevention and treatment must screen for, and address, emotional neglect.

A Failure to Guide: Patient Experiences within a State-Run Cannabis Program in Pennsylvania, United States.

INTRODUCTION: Medical cannabis has been available for purchase in dispensaries in Pennsylvania, United States since April 2018. Patients wanting to access medical cannabis must receive certification from physicians for a limited number of physical and psychological conditions. Despite increasing numbers of patients using cannabis in the United States, little is known about the patient experience during certification and entry into state-regulated cannabis programs and how and if they are guided by health care professionals and dispensary staff. Through focus group discussions, we sought to capture patient perspectives of certification, cannabis acquisition and cannabis use. METHODS: Twenty-seven Pennsylvania participants took part in 7 virtual focus groups from June to July 2020. Participants were recruited statewide from the community, medical settings, and dispensaries. RESULTS: Focus group results indicate that while the medical cannabis program is functional, policymakers and the medical community have failed to meaningfully integrate cannabis into the health care system. Participants expressed frustration around two central themes: there was no overarching education about medical use of cannabis and there was little consistency and availability for people once they found a suitable product, resulting in inadequate symptom relief and exorbitant out of pocket costs to pursue cannabis use as an adjuvant therapeutic. Participants noted a siloed experience between the certification process, accessing dispensaries, and receiving ongoing medical care. The lack of integrated care required high levels of self-reliance and experimentation with medical cannabis for participants. CONCLUSION: We recommend that cannabis be better integrated into medical care for patients with qualifying conditions.

Client Outreach in Los Angeles County's Assisted Outpatient Treatment Program: Strategies and Barriers to Engagement.

Purpose: Assisted Outpatient Treatment (AOT) programs can compel treatment-refusing individuals to participate in mental health treatment via civil court order. In California's AOT programs, individuals first must be offered 30 days of outreach services and can accept services voluntarily. This study examines the use of outreach strategies in an AOT program with the potential for voluntary or involuntary enrollment. Methods: Outreach staff completed a survey in which they reported and rated outreach strategies and barriers to treatment for 487 AOT-referred individuals. Results: Outreach staff reported using a broad array of strategies to persuade and engage clients. Supportive and persuasive strategies were most common. More coercive strategies, including court order, were used when needed. More clients enrolled voluntarily (39.4%) than involuntarily (7.2%). Conclusions: Outreach, coupled with the strategic used of potential court involvement, can lead to voluntary enrollment of treatment-refusing individuals with many, often severe, barriers to engaging in outpatient treatment.

Base-pairing interactions between substrate RNA and H/ACA guide RNA modulate the kinetics of pseudouridylation, but not the affinity of substrate binding by H/ACA small nucleolar ribonucleoproteins.

H/ACA small nucleolar ribonucleoproteins (snoRNPs) pseudouridylate RNA in eukaryotes and archaea. They target many RNAs site-specifically through base-pairing interactions between H/ACA guide and substrate RNA. Besides ribosomal RNA (rRNA) and small nuclear RNA (snRNA), H/ACA snoRNPs are thought to also modify messenger RNA (mRNA) with potential impacts on gene expression. However, the base pairing between known target RNAs and H/ACA guide RNAs varies widely in nature, and therefore the rules governing substrate RNA selection are still not fully understood. To provide quantitative insight into substrate RNA recognition, we systematically altered the sequence of a substrate RNA target by the Saccharomyces cerevisiae H/ACA guide RNA snR34. Time courses measuring pseudouridine formation revealed a gradual decrease in the initial velocity of pseudouridylation upon reducing the number of base pairs between substrate and guide RNA. Changing or inserting nucleotides close to the target uridine severely impairs pseudouridine formation. Interestingly, filter binding experiments show that all substrate RNA variants bind to H/ACA snoRNPs with nanomolar affinity. Next, we showed that binding of inactive, near-cognate RNAs to H/ACA snoRNPs does not inhibit their activity for cognate RNAs, presumably because near-cognate RNAs dissociate rapidly. We discuss that the modulation of initial velocities by the base-pairing strength might affect the order and efficiency of pseudouridylation in rRNA during ribosome biogenesis. Moreover, the binding of H/ACA snoRNPs to near-cognate RNAs may be a mechanism to search for cognate target sites. Together, our data provide critical information to aid in the prediction of productive H/ACA guide-substrate RNA pairs.

Drawing up a collaborative contract: Amino acid cross-feeding between interspecies bacterial pairs.

Synthetic microbial communities have the potential to enable new platforms for bioproduction of biofuels and biopharmaceuticals. However, using engineered communities is often assumed to be difficult because of anticipated challenges in establishing and controlling community composition. Cross-feeding between microbial auxotrophs has the potential to facilitate coculture growth and stability through a mutualistic ecological interaction. We assessed cross-feeding between 13 Escherichia coli amino acid auxotrophs paired with a leucine auxotroph of Bacillus megaterium. We developed a minimal medium capable of supporting the growth of both bacteria and used the media to study coculture growth of the 13 interspecies pairs of auxotrophs in batch and continuous culture, as well as on semi-solid media. In batch culture, 8 of 13 pairs of auxotrophs were observed to grow in coculture. We developed a new metric to quantify the impact of cross-feeding on coculture growth. Six pairs also showed long-term stability in continuous culture, where coculture growth at different dilution rates highlighted differences in cross-feeding amongst the pairs. Finally, we found that cross-feeding-dependent growth on semi-solid media is highly stringent and enables identification of the most efficient pairs. These results demonstrate that cross-feeding is a viable approach for controlling community composition within diverse synthetic communities.