Financial barriers and facilitators to secure firearm and medication storage among veterans with elevated suicide risk: a qualitative study.

OBJECTIVE: To explore financial barriers and facilitators to promoting secure firearm and medication storage among patients at risk for suicide. METHODS: Veterans seeking care in Veterans Affairs emergency care settings (N=28) participated in qualitative interviews on barriers and facilitators to adopting secure firearm and medication storage behaviours. Thematic analysis with inductive and iterative coding was used to identify themes pertaining to financial barriers and facilitators. Interviews were double-coded for reliability. RESULTS: We identified four themes-two related to financial barriers and two to financial facilitators. Barrier-related themes included: (1) the high cost of firearms and medications made owners less likely to dispose of medications, relinquish ownership of firearms or pursue out-of-home storage for firearms; (2) the high cost of out-of-home storage and preferred locking devices were barriers to secure storage. Facilitator-related themes included: (1) no-cost services or locking devices may help motivate secure firearm and medication storage and (2) preferences varied for no-cost locking devices versus coupons for devices. CONCLUSIONS: Addressing financial barriers and leveraging financial facilitators may motivate secure storage of lethal means, which could enhance suicide prevention efforts.

Measures of anxiety, depression and stress in the antenatal and perinatal period following a stillbirth or neonatal death: a multicentre cohort study.

BACKGROUND: The grief associated with the death of a baby is enduring, however most women embark on another pregnancy, many in less than a year following their loss. Symptoms of anxiety and depression are reported to be increased in pregnancies after perinatal death, although effect on maternal stress is less clear. Variation between individual studies may result from differences in gestation at sampling, the questionnaire used and the type of antecedent perinatal death. We aimed to describe quantitative measures of anxiety, depression, stress and quality of life at different timepoints in pregnancies after perinatal death and in the early postnatal period. METHODS: Women recruited from three sites in the North-West of England. Women were asked to participate if a previous pregnancy had ended in a perinatal death. Participants completed validated measures of psychological state (Cambridge Worry Score, Edinburgh Postnatal Depression Score (EPDS), Generalized Anxiety Disorder 7-item score) and health status (EQ-5D-5L™ and EQ5D-Visual Analogue Scale) at three time points, approximately 15 weeks' and 32 weeks' gestation and 6 weeks postnatally. A sample of hair was taken at approximately 36 weeks' gestation for measurement of hair cortisol in a subgroup of women. The hair sample was divided into samples from each trimester and cortisol measured by ELISA. RESULTS: In total 112 women participated in the study. Measures of anxiety and depressive symptoms decreased from the highest levels at 15 weeks' gestation to 6-weeks postnatal (for example mean GAD-7: 15 weeks 8.2 ± 5.5, 6 weeks postnatal 4.4 ± 5.0, p<0.001). Hair cortisol levels fell in a similar profile to anxiety and depression symptoms (p<0.05). In contrast, the median EQ-5D index, measuring health status was 0.768 at 15 weeks' gestation (Interquartile range (IQR) 0.684-0.879), 0.696 at 32 weeks' (IQR 0.637-0.768) and 0.89 (0.760-1.00) at 6 weeks postnatal. There was a negative relationship between EPDS and perceived health status. CONCLUSIONS: This study demonstrated heightened anxiety and depressive symptoms and elevated cortisol levels in women in pregnancies after a stillbirth or neonatal death which decrease as pregnancy progresses. Further studies are needed to determine optimal care for women to address these negative psychological consequences.

Sleep Quality Moderates the Relationship between Anxiety Sensitivity and PTSD Symptoms in Combat-exposed Veterans.

Objective/Background: Posttraumatic stress disorder (PTSD) and related conditions (e.g., depression) are common in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) veterans. High anxiety sensitivity (AS), defined as fear of anxiety and anxiety-related consequences, is related to greater PTSD and depressive symptoms; however, few studies have identified possible modifiers of these associations. The current study examined the moderating role of sleep quality in the associations between AS and PTSD and depressive symptoms. Participants: Participants were 155 OEF/OIF/OND community veterans ages 21-40 (12.3% women). Methods: Participants completed a semi-structured clinical interview for DSM-IV PTSD symptoms (Clinician Administered PTSD Scale; CAPS) and self-report measures of anxiety sensitivity (Anxiety Sensitivity Index), sleep quality (Pittsburgh Sleep Quality Index global score; PSQI), and depressive symptoms (Beck Depression Inventory-II; BDI-II). Results: Results of hierarchical linear regression models indicated that the main effects of AS and global PSQI score were significantly associated with greater PTSD and depressive symptoms (both with sleep items removed), above and beyond the covariates of trauma load and military rank. Sleep quality moderated the relationship between AS and PTSD symptoms (but not depressive symptoms), such that greater AS was associated with greater PTSD symptoms for individuals with good sleep quality, but not poor sleep quality. Conclusions: Sleep quality and AS account for unique variance in PTSD and depressive symptoms in combat-exposed veterans. AS may be less relevant to understanding risk for PTSD among combat-exposed veterans experiencing poor sleep quality.

A Methodological Approach for Evaluating the Enterprise Community Healthy Start Program in Rural Georgia: An Analysis Using Linked PRAMS, Birth Records and Program Data.

INTRODUCTION: Community Healthy Start program evaluations are often limited by a lack of robust data and rigorous study designs. This study describes an enhanced methodological approach using local program data linked with existing population-level datasets for external comparison to evaluate the Enterprise Community Healthy Start (ECHS) program in two rural Georgia counties and presents results from the evaluation. METHODS: ECHS program data were linked to birth records and the Pregnancy Risk Assessment Monitoring System (PRAMS) for 869 women who delivered a live birth in Burke and McDuffie counties from 2010 to 2011. Multivariate logistic regressions with and without propensity score methods modeled the association between ECHS participation and maternal health indicators and pregnancy outcomes. RESULTS: 107 ECHS participants and 726 non-participants responded to PRAMS and met eligibility criteria. Compared with non-participants, ECHS participants were younger, completed fewer years of education, and were more likely to be non-Hispanic Black, unmarried, insured with Medicaid, participating in WIC, and having an unintended pregnancy. Models with and without propensity score weighting derived similar results: there was a positive association between ECHS participation and receiving adequate or adequate plus prenatal care (p < 0.05); no statistically significant associations were observed between ECHS participation and any other health behaviors, health care access and utilization measures or pregnancy outcomes. DISCUSSION: Rigorous evaluation of a local Healthy Start program using linked PRAMS and birth records with a population-based external comparison group and propensity score methods is an enhanced and feasible approach that can be applied in other local and state jurisdictions.

Piloting of the Just Say Know prevention program: a psychoeducational approach to translating the neuroscience of addiction to youth.

BACKGROUND: Substance use during adolescence can have a number of negative consequences and interfere with normal brain development. Given limited time and resources, brief group- and school-based prevention programs are an efficient strategy for educating youth about the effects of substance use on health outcomes. OBJECTIVES: To determine if a science-based, interactive substance prevention program could improve student knowledge and influence students' attitudes toward future substance use behaviors. METHODS: The Just Say Know program was given to 1,594 middle and high school students. The facilitator engaged students in an interactive, hour-long session covering brain basics and effects of substance use. Students completed an eight-item pre- and post-knowledge-based test to measure learning outcomes along with feedback questions about youths' attitudes toward substance use and the program. RESULTS: After the program, 94% of students reported that it provided helpful information; 92% reported it may influence their approach to substance use, with 76% specifying that they would delay or cut back on substance use. Knowledge-based test performance increased by 78%, with high schoolers displaying significantly higher scores than middle schoolers, but both showing similar improvements in scores. Students who reported higher levels of friends' substance use had smaller improvements from pre- to posttest. CONCLUSION: Results suggest Just Say Know, a scientifically-based prevention program, is effective in increasing adolescents' program based-knowledge, has the potential to affect youths' attitudes toward substance use, and is well-received. These findings provide preliminary evidence that a cost-effective, neuroscience-informed group prevention program might reduce or delay adolescents' future substance use.

Site-Specific Protein Photochemical Covalent Attachment to Carbon Nanotube Side Walls and Its Electronic Impact on Single Molecule Function.

Functional integration of proteins with carbon-based nanomaterials such as nanotubes holds great promise in emerging electronic and optoelectronic applications. Control over protein attachment poses a major challenge for consistent and useful device fabrication, especially when utilizing single/few molecule properties. Here, we exploit genetically encoded phenyl azide photochemistry to define the direct covalent attachment of four different proteins, including the fluorescent protein GFP and a ß-lactamase binding protein (BBP), to carbon nanotube side walls. AFM showed that on attachment BBP could still recognize and bind additional protein components. Single molecule fluorescence revealed that on attachment to SWCNTs function was retained and there was feedback to GFP in terms of fluorescence intensity and improved resistance to photobleaching; GFP is fluorescent for much longer on attachment. The site of attachment proved important in terms of electronic impact on GFP function, with the attachment site furthest from the chromophore having the larger effect on fluorescence. Our approach provides a versatile and general method for generating intimate protein-CNT hybrid bioconjugates. It can be potentially applied to any protein of choice; the attachment position and thus interface characteristics with the CNT can easily be changed by simply placing the phenyl azide chemistry at different residues by gene mutagenesis. Thus, our approach will allow consistent construction and modulate functional coupling through changing the protein attachment position.

A mixed-methods evaluation of continuous electronic fetal monitoring for an extended period.

INTRODUCTION: Continuous fetal monitoring is used to objectively record the fetal heart rate and fetal activity over an extended period of time; however, its feasibility and acceptability to women is currently unknown. The study addressed the hypothesis that continuous fetal monitoring is feasible and acceptable to pregnant women. MATERIAL AND METHODS: Pregnant participants (n = 22) were monitored using a continuous fetal electrocardiography device, the Monica AN24. Signal quality, duration of recording and cardiotocography findings were correlated with maternal and fetal factors. Participants' change in anxiety before and after monitoring was assessed using validated questionnaires. Participants' experiences were explored through a questionnaire (n = 20) and semi-structured interview (n = 13). RESULTS: Recordings were successfully obtained in 19 of the 22 participants (86.3%). The mean recording quality of fetal heart rate was 69.0% (range 17.4%-99.4%) and maternal heart rate was 99.0% (90.9%-100.0%). Recording quality was positively correlated with gestational age (P = 0.05) and negatively correlated with uterine activity and maternal movement (P < 0.001). Overall, participants were satisfied with their experience of continuous fetal monitoring; 30% considered it preferable to intermittent monitoring. Continuous fetal monitoring did not significantly increase maternal anxiety, with a trend towards a reduction in Pregnancy Specific Anxiety score (P = 0.07). Qualitative analysis grouped women's responses into three themes: (a) reassurance and anxiety, (b) the physical device and (c) future developments in continuous fetal monitoring. CONCLUSIONS: Continuous fetal monitoring is a feasible and acceptable form of monitoring to pregnant women although further practical improvements could be incorporated. Further research is required to assess the ability of continuous fetal monitoring to detect fetal compromise.

Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid production in plants.

Terpenoids, compounds found in all domains of life, represent the largest class of natural products with essential roles in their hosts. All terpenoids originate from the five-carbon building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which can be derived from the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways. The absence of two components of the MVA pathway from archaeal genomes led to the discovery of an alternative MVA pathway with isopentenyl phosphate kinase (IPK) catalyzing the final step, the formation of IPP. Despite the fact that plants contain the complete classical MVA pathway, IPK homologs were identified in every sequenced green plant genome. Here, we show that IPK is indeed a member of the plant terpenoid metabolic network. It is localized in the cytosol and is coexpressed with MVA pathway and downstream terpenoid network genes. In planta, IPK acts in parallel with the MVA pathway and plays an important role in regulating the formation of both MVA and MEP pathway-derived terpenoid compounds by controlling the ratio of IP/DMAP to IPP/DMAPP. IP and DMAP can also competitively inhibit farnesyl diphosphate synthase. Moreover, we discovered a metabolically available carbon source for terpenoid formation in plants that is accessible via IPK overexpression. This metabolite reactivation approach offers new strategies for metabolic engineering of terpenoid production.

Impulsivity and Comorbid PTSD and Binge Drinking.

OBJECTIVE: Trauma exposure is common, with estimates of 28% to 90% of adults reporting at least one traumatic event over their lifetime. Those exposed to traumatic events are at risk for alcohol misuse (i.e., binge drinking), posttraumatic stress disorder (PTSD), or both. A potential underlying mechanism for this comorbidity is increased impulsivity-the tendency to act rashly. Little work to date has examined the impact of different impulsogenic traits on this comorbidity. METHODS: This study (n = 162) investigated trauma-exposed young adults (aged 21-30) who had endorsed a lifetime interpersonal trauma. In addition, three impulsogenic traits (motor, nonplanning, and attentional) were measured. RESULTS: Over and above the covariates for age, gender, race, and traumatic events, greater attentional impulsivity was associated with greater likelihood of meeting criteria for PTSD and binge drinking, compared to meeting criteria for PTSD, binge drinking, or neither. Neither nonplanning impulsivity nor motor impulsivity exerted unique effects. CONCLUSIONS: Young adults who report difficulty attending to immediate stimuli within their environment may be unable to think about and/or process the traumatic event, potentially increasing risk for PTSD and maladaptive coping skills to manage this distress (e.g., alcohol misuse, binge drinking).

Pathogen roid rage: cholesterol utilization by Mycobacterium tuberculosis.

The ability of science and medicine to control the pathogen Mycobacterium tuberculosis (Mtb) requires an understanding of the complex host environment within which it resides. Pathological and biological evidence overwhelmingly demonstrate how the mammalian steroid cholesterol is present throughout the course of infection. Better understanding Mtb requires a more complete understanding of how it utilizes molecules like cholesterol in this environment to sustain the infection of the host. Cholesterol uptake, catabolism and broader utilization are important for maintenance of the pathogen in the host and it has been experimentally validated to contribute to virulence and pathogenesis. Cholesterol is catabolized by at least three distinct sub-pathways, two for the ring system and one for the side chain, yielding dozens of steroid intermediates with varying biochemical properties. Our ability to control this worldwide infectious agent requires a greater knowledge of how Mtb uses cholesterol to its advantage throughout the course of infection. Herein, the current state of knowledge of cholesterol metabolism by Mtb is reviewed from a biochemical perspective with a focus on the metabolic genes and pathways responsible for cholesterol steroid catabolism.

Perinatal program evaluations: methods, impacts, and future goals.

The objective of this methodology note is to examine perinatal program evaluation methods as they relate to the life course health development model (LCHD) and risk reduction for poor birth outcomes. We searched PubMed, CDC, ERIC, and a list from the Association of Maternal and Child Health Programs (AMCHP) to identify sources. We included reports from theory, methodology, program reports, and instruments, as well as reviews of Healthy Start Programs and home visiting. Because our review focused upon evaluation methods we did not include reports that described the Healthy Start Program. The LCHD model demonstrates the non-linear relationships among epigenetic factors and environmental interactions, intentionality or worldview within a values framework, health practices, and observed outcomes in a lifelong developmental health trajectory. The maternal epigenetic and social environment during fetal development sets the stage for the infant's lifelong developmental arc. The LCHD model provides a framework to study challenging maternal child health problems. Research that tracks the long term maternal-infant health developmental trajectory is facilitated by multiple, linked public record systems. Two instruments, the life skills progression instrument and the prenatal risk overview are theoretically consistent with the LCHD and can be adapted for local or population-based use. A figure is included to demonstrate a method of reducing interaction among variables by sample definition. Both in-place local programs and tests of best practices in community-based research are needed to reduce unacceptably high infant mortality. Studies that follow published reporting standards strengthen evidence.

Improving Ethnocultural Empathy in Healthcare Students through a Targeted Intervention.

Students in training to become future healthcare providers must be trained not only how to provide quality care but also how to effectively communicate with patients, regardless of the patient's cultural background. Poor communication between provider and patient when racial or ethnic backgrounds differ between patient and provider is a relevant factor in suboptimal healthcare services to ethnic minorities. This pilot study was conducted to examine changes in the scores on the Scale of Ethnocultural Empathy (SEE)for first year nursing (n = 40) and dental students (n = 42)following an intervention. Participants completed an anonymous online survey that included the SEE, a validated measure of empathy toward people with racial and ethnic backgrounds different from one's own prior to the intervention (baseline), immediately following the intervention workshop (post-test) and one month following the workshop (follow-up). Results showed statistically significant increases from baseline to post-intervention on the SEE (p < .05), and these gains were maintained at follow-up. This study is the first to examine whether an intervention specifically designed to improve students' understanding of racial groups discordant from their own actually improves empathy and communication. Results from this pilot study support that controlled trials are warranted.

Stream denitrification across biomes and its response to anthropogenic nitrate loading.

Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing more bioavailable nitrogen to enter groundwater and surface waters. Large-scale nitrogen budgets show that an average of about 20-25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins, indicating that substantial sinks for nitrogen must exist in the landscape. Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification. Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in-stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.

Maternal health literacy progression among rural perinatal women.

This research examined changes in maternal health literacy progression among 106 low income, high risk, rural perinatal African American and White women who received home visits by Registered Nurse Case Managers through the Enterprise Community Healthy Start Program. Maternal health literacy progression would enable women to better address intermediate factors in their lives that impacted birth outcomes, and ultimately infant mortality (Lu and Halfon in Mater Child Health J 7(1):13-30, 2003; Sharma et al. in J Natl Med Assoc 86(11):857-860, 1994). The Life Skills Progression Instrument (LSP) (Wollesen and Peifer, in Life skills progression. An outcome and intervention planning instrument for use with families at risk. Paul H. Brookes Publishing Co., Baltimore, 2006) measured changes in behaviors that represented intermediate factors in birth outcomes. Maternal Health Care Literacy (LSP/M-HCL) was a woman's use of information, critical thinking and health care services; Maternal Self Care Literacy (LSP/M-SCL) was a woman's management of personal and child health at home (Smith and Moore in Health literacy and depression in the context of home visitation. Mater Child Health J, 2011). Adequacy was set at a score of (≥4). Among 106 women in the study initial scores were inadequate (<4) on LSP/M-HCL (83 %), and on LSP/M-SCL (30 %). Significant positive changes were noted in maternal health literacy progression from the initial prenatal assessment to the first (p < .01) postpartum assessment and to the final (p < .01) postpartum assessment using McNemar's test of gain scores. Numeric comparison of first and last gain scores indicated women's scores progressed (LSP/M-HCL; p < .0001) and (LSP/M-SCL; p < .0001). Elevated depression scores were most frequent among women with <4 LSP/M-HCL and/or <4 LSP/M-SCL. Visit notes indicated lack or loss of relationship with the father of the baby and intimate partner discord contributed to higher depression scores.

Nitrous oxide emission from denitrification in stream and river networks.

Nitrous oxide (N(2)O) is a potent greenhouse gas that contributes to climate change and stratospheric ozone destruction. Anthropogenic nitrogen (N) loading to river networks is a potentially important source of N(2)O via microbial denitrification that converts N to N(2)O and dinitrogen (N(2)). The fraction of denitrified N that escapes as N(2)O rather than N(2) (i.e., the N(2)O yield) is an important determinant of how much N(2)O is produced by river networks, but little is known about the N(2)O yield in flowing waters. Here, we present the results of whole-stream (15)N-tracer additions conducted in 72 headwater streams draining multiple land-use types across the United States. We found that stream denitrification produces N(2)O at rates that increase with stream water nitrate (NO(3)(-)) concentrations, but that <1% of denitrified N is converted to N(2)O. Unlike some previous studies, we found no relationship between the N(2)O yield and stream water NO(3)(-). We suggest that increased stream NO(3)(-) loading stimulates denitrification and concomitant N(2)O production, but does not increase the N(2)O yield. In our study, most streams were sources of N(2)O to the atmosphere and the highest emission rates were observed in streams draining urban basins. Using a global river network model, we estimate that microbial N transformations (e.g., denitrification and nitrification) convert at least 0.68 Tg·y(-1) of anthropogenic N inputs to N(2)O in river networks, equivalent to 10% of the global anthropogenic N(2)O emission rate. This estimate of stream and river N(2)O emissions is three times greater than estimated by the Intergovernmental Panel on Climate Change.

The potential utility of drinking motive questions to screen at-risk drinking in socially anxious patients.

BACKGROUND: Drinking motives are thought to be important mediators of the relationship between social anxiety and alcohol use. This project evaluates whether specific drinking motives accurately reflect alcohol dependence. If so, brief questions about drinking motives could serve as valuable alcohol screening tools with socially anxious patients. METHODS: This investigation was a secondary analysis of an existing data set of 83 subjects with social anxiety disorder and at-risk alcohol use. The relationship between Drinking Motives Questionnaire (DMQ-R-5) subscales and alcohol dependence was evaluated. RESULTS: Coping-Depression was the only subscale that contributed to the unique prediction of a diagnosis of alcohol dependence. Additionally, two items (i.e. "to cheer up when you're in a bad mood" and "to forget painful memories") predicted a diagnosis of alcohol dependence above and beyond their association with each other. CONCLUSIONS: Among patients with social anxiety, two specific questions on the DMQ-R-5 could provide a useful screen for health professionals to predict alcohol dependence. It may be fruitful to specifically target the motives of "to cheer up when you're in a bad mood" and "to forget painful memories" when providing advice during brief interventions.

Pilot Perceptions of Wire Strikes in Agricultural Aviation Operations.

INTRODUCTION: Agricultural aircraft operations are associated with unique challenges. In particular, these include maintaining awareness of obstacles associated with flight at very low altitudes. Wire strikes are a common cause of accidents in these operations.METHODS: Focus groups were completed during the 2022 Ag Aviation Expo hosted by the National Agricultural Aviation Association with pilots who had experienced wire-strike events (N = 22). The researchers coded the transcripts using a human factors framework.RESULTS: Notably, unplanned "trim passes" were a key stage of flight during wire-strike events. Cognitive risk factors that may have affected their performance included situation awareness, decision-making choices, and pressure to perform. Over half of subjects reported being aware of the wire before collision. Possible prevention strategies include not spraying the field due to safety risks, paying better attention to where they were in the field, and avoiding deviation from the planned route.DISCUSSION: Wire-strike events often occur due to momentary lapses in attention, even when the pilot is already aware of the wire. This study shows that targeted approaches to prevent wire strikes in agricultural aviation operations require addressing a number of cognitive risks and human factors, rather than implementing increased preflight surveillance. These results have implications for preventing future wire-strike accidents based directly on pilot perceptions, both within agricultural operations and general aviation more broadly.Baumgartner HM, DiDomenica R, Hu PT, Thomas S. Pilot perceptions of wire strikes in agricultural aviation operations. Aerosp Med Hum Perform. 2024; 95(6):305-312.

Patients' Perspectives on Medication-Related Suicide Prevention Interventions Delivered in Emergency Settings.

OBJECTIVE: Encouraging patients at risk for suicide to reduce access to potentially lethal medications and drugs is a key component of evidence-based suicide prevention. However, little research has been done to inform interventions for reducing intentional self-harm. METHODS: Semistructured interviews were conducted with 28 U.S. veterans who sought emergency care from the Veterans Health Administration between 2021 and 2023 to explore veterans' perspectives on medication-related interventions, including opinions on intervention components (e.g., medication return envelopes). Matrix analysis was used to aggregate data into categories, which were predefined by using constructs from the health belief model (e.g., perceived benefits). RESULTS: The participating veterans generally endorsed interventions as acceptable and were particularly supportive of distributing medication return envelopes. However, they often conceptualized these efforts as steps to prevent unintentional overdose or theft-not necessarily to prevent suicide-and rarely indicated that such interventions were appropriate for themselves. Across the interviews, participants identified important facilitators to care, such as ensuring that interventions were convenient and accounted for the perceived cost of disposing medications. Perspectives on engaging family or friends in interventions were mixed. The importance of the interventions was more readily acknowledged among participants with previous opioid use exposure-perspectives that appeared to stem from lived experiences. CONCLUSIONS: This study contributes important foundational knowledge that can be used to inform research and clinical initiatives aimed at preventing medication- and drug-related suicides.

A community-based mentoring scheme for pregnant and parenting adolescents in Sierra Leone: Protocol for a hybrid pilot cluster randomised controlled trial.

BACKGROUND: Sierra Leone has a very high maternal mortality rate, and this burden falls heavily on adolescents, a particularly vulnerable group; this is usually driven by poverty, lack of education and employment opportunities. In 2017, a local grassroots organisation, Lifeline Nehemiah Projects, developed a community-based mentoring intervention '2YoungLives' (2YLs) for adolescent girls in Eastern Freetown. We aim to formally assess the feasibility and implementation of the 2YL mentorship scheme in new communities in Sierra Leone. METHODS: A hybrid type 2 pilot cluster randomised controlled trial of the 2YL mentoring scheme in urban and rural communities living around twelve peripheral health units (PHU) across five districts in Sierra Leone. Clusters will be matched into pairs and randomisation will be determined by computer-generated random numbers via a secure web-based system hosted by MedSciNet. All under-eighteen adolescents identified as pregnant in the community and/or the PHU are included. Feasibility (recruitment, retention, and attrition rates; data collection and completeness; sample calculation) and primary clinical outcome data (composite of maternal deaths, stillbirths, neonatal deaths) will be collected. A mixed-methods process evaluation will explore implementation outcomes, mechanisms of change, contextual factors, experiences of care, and health and wellbeing. A concurrent cost-consequence analysis will be undertaken. Main trial analysis will be pragmatic, by intention to treat, and a complementary per protocol analysis will also be included. DISCUSSION: Improving health and wellbeing for adolescent girls (including sexual and reproductive health) remains a top priority in Sierra Leone indicated by several government policies targeted to this group, in which maternal and infant mortality are still persistently high. Supporting these girls and facilitating their wellbeing is imperative, along with sensitisation of communities, strengthening of youth friendly services and collaboration with stakeholders at all levels (government, regional, community, family). We believe 2YL supports the global holistic agenda to integrate and implement interventions across health, education, and social systems in order to protect, nurture, and support the health and development potential of every adolescent girl, and thus become a model of good practice for adolescent pregnancy, to be adopted more widely in Sierra Leone and elsewhere. TRIAL REGISTRATION: ISRCTN registry ISRCTN32414369. Prospectively registered on 14/03/2022.

Shrinking the FadE proteome of Mycobacterium tuberculosis: insights into cholesterol metabolism through identification of an α2ß2 heterotetrameric acyl coenzyme A dehydrogenase family.

The ability of the pathogen Mycobacterium tuberculosis to metabolize steroids like cholesterol and the roles that these compounds play in the virulence and pathogenesis of this organism are increasingly evident. Here, we demonstrate through experiments and bioinformatic analysis the existence of an architecturally distinct subfamily of acyl coenzyme A (acyl-CoA) dehydrogenase (ACAD) enzymes that are α2ß2 heterotetramers with two active sites. These enzymes are encoded by two adjacent ACAD (fadE) genes that are regulated by cholesterol. FadE26-FadE27 catalyzes the dehydrogenation of 3ß-hydroxy-chol-5-en-24-oyl-CoA, an analog of the 5-carbon side chain cholesterol degradation intermediate. Genes encoding the α2ß2 heterotetrameric ACAD structures are present in multiple regions of the M. tuberculosis genome, and subsets of these genes are regulated by four different transcriptional repressors or activators: KstR1 (also known as KstR), KstR2, Mce3R, and SigE. Homologous ACAD gene pairs are found in other Actinobacteria, as well as Proteobacteria. Their structures and genomic locations suggest that the α2ß2 heterotetrameric structural motif has evolved to enable catalysis of dehydrogenation of steroid- or polycyclic-CoA substrates and that they function in four subpathways of cholesterol metabolism.