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Abstract Objective Distinct dominant mutations in the calcium‐permeable ion channel TRPV4 (transient receptor potential vanilloid 4) typically cause nonoverlapping diseases of either the neuromuscular or skeletal systems. However, accumulating evidence suggests that some patients develop mixed phenotypes that include elements of both neuromuscular and skeletal disease. We sought to define the genetic and clinical features of these patients. Methods We report a 2‐year‐old with a novel R616G mutation in TRPV4 with a severe neuropathy phenotype and bilateral vocal cord paralysis. Interestingly, a different substitution at the same residue, R616Q, has been reported in families with isolated skeletal dysplasia. To gain insight into clinical features and potential genetic determinants of mixed phenotypes, we perform in‐depth analysis of previously reported patients along with functional and structural assessment of selected mutations. Results We describe a wide range of neuromuscular and skeletal manifestations and highlight specific mutations that are more frequently associated with overlap syndromes. We find that mutations causing severe, mixed phenotypes have an earlier age of onset and result in more marked elevations of intracellular calcium, increased cytotoxicity, and reduced sensitivity to TRPV4 antagonism. Structural analysis of the two mutations with the most dramatic gain of ion channel function suggests that these mutants likely cause constitutive channel opening through disruption of the TRPV4 S5 transmembrane domain. Interpretation These findings demonstrate that the degree of baseline calcium elevation correlates with development of mixed phenotypes and sensitivity to pharmacologic channel inhibition, observations that will be critical for the design of future clinical trials for TRPV4 channelopathies.

Abstract Layers of genome organization are becoming increasingly better characterized, but less is known about how these structures respond to perturbation or shape changes. Low-salt swelling of isolated chromatin fibers or nuclei has been used for decades to investigate the structural properties of chromatin. But, visible changes in chromatin appearance have not been linked to known building blocks of genome structure or features along the genome sequence. We combine low-salt swelling of isolated nuclei with genome-wide chromosome conformation capture (Hi-C) and imaging approaches to probe the effects of chromatin extension genome-wide. Photoconverted patterns on nuclei during expansion and contraction indicate that global genome structure is preserved after dramatic nuclear volume swelling, suggesting a highly elastic chromosome topology. Hi-C experiments before, during, and after nuclear swelling show changes in average contact probabilities at short length scales, reflecting the extension of the local chromatin fiber. But, surprisingly, during this large increase in nuclear volume, there is a striking maintenance of loops, TADs, active and inactive compartments, and chromosome territories. Subtle differences after expansion are observed, suggesting that the local chromatin state, protein interactions, and location in the nucleus can affect how strongly a given structure is maintained under stress. From these observations, we propose that genome topology is robust to extension of the chromatin fiber and isotropic shape change, and that this elasticity may be beneficial in physiological circumstances of changes in nuclear size and volume.

Bonefishes are a nearshore species targeted by non-commercial anglers and subsistence fishers in the Central and South Pacific islands. Among the bonefish species in the Indo-Pacific region, Albula glossodonta are known to have one of the widest geographic ranges, from the Red Sea to the Central Pacific, but it is unknown how dispersive A. glossodonta are between geographically isolated islands. Volunteer anglers collected A. glossodonta fin clips from the main Hawaiian Islands in the North Pacific, Anaa Atoll in the South Pacific, and intermediate Kiritimati Island (Line Islands) to assess the scale of dispersal and population structure within the Pacific Ocean. Population genomics was conducted based on 208 individuals and 7225 SNPs. Although adult A. glossodonta exhibit strong site fidelity, genomic results show no population differentiation between Oahu and Maui in Hawai‘i. Bonefishes exhibit significant population structure between Anaa and Hawai‘i (FST = 0.096), with intermediate Kiritimati comprising admixed fishes. A lengthy larval duration likely promotes connectivity between Pacific islands. Regional management regimes may be most appropriate for a species with this level of dispersal.

The sharing of genome sequences in online data repositories allows for large scale analyses of specific genes or gene families. This can result in the detection of novel gene subtypes as well as the development of improved detection methods. Here, we used publicly available WGS data to detect a novel Stx subtype, Stx2n in two clinical E. coli strains isolated in the USA. During this process, additional Stx2 subtypes were detected; six Stx2j, one Stx2m strain, and one Stx2o, were all analyzed for variability from the originally described subtypes. Complete genome sequences were assembled from short- or long-read sequencing and analyzed for serotype, and ST types. The WGS data from Stx2n- and Stx2o-producing STEC strains were further analyzed for virulence genes pro-phage analysis and phage insertion sites. Nucleotide and amino acid maximum parsimony trees showed expected clustering of the previously described subtypes and a clear separation of the novel Stx2n subtype. WGS data were used to design OMNI PCR primers for the detection of all known stx1 (283 bp amplicon), stx2 (400 bp amplicon), intimin encoded by eae (221 bp amplicon), and stx2f (438 bp amplicon) subtypes. These primers were tested in three different laboratories, using standard reference strains. An analysis of the complete genome sequence showed variability in serogroup, virulence genes, and ST type, and Stx2 pro-phages showed variability in size, gene composition, and phage insertion sites. The strains with Stx2j, Stx2m, Stx2n, and Stx2o showed toxicity to Vero cells. Stx2j carrying strain, 2012C-4221, was induced when grown with sub-inhibitory concentrations of ciprofloxacin, and toxicity was detected. Taken together, these data highlight the need to reinforce genomic surveillance to identify the emergence of potential new Stx2 or Stx1 variants. The importance of this surveillance has a paramount impact on public health. Per our description in this study, we suggest that 2017C-4317 be designated as the Stx2n type-strain.

This study explored the feasibility of using fish skin bandages as a therapeutic option for third-degree skin burns. Following the California wildfires, clinical observations of animals with third-degree skin burns demonstrated increased comfort levels and reduced pain when treated with tilapia fish skin. Despite the promises of this therapy, there are few studies explaining the healing mechanisms behind the application of tilapia fish skin. In this study, mice with third-degree burns were treated with either a hydrocolloid adhesive bandage (control) (n = 16) or fish skin (n = 16) 7 days post-burn. Mice were subjected to histologic, hematologic, molecular, and gross evaluation at days 7, 16, and 28 post-burn. The fish skin offered no benefit to overall wound closure compared to hydrocolloids. Additionally, we detected no difference between fish skin and control treatments in regard to hypermetabolism or hematologic values. However, the fish skin groups exhibited 2 times more vascularization and 2 times higher expression of antimicrobial defensin peptide in comparison to controls. Proteomic analysis of the fish skin revealed the presence of antimicrobial peptides. Collectively, these data suggest that fish skin can serve as an innovative and cost-effective therapeutic alternative for burn victims to facilitate vascularization and reduce bacterial infection.

Canada Warblers ( Cardellina canadensis ) are small Neotropical migrants whose populations are declining across most of their range. Understanding factors limiting Canada Warbler populations requires knowledge of population ecology across the full annual cycle, including migratory pathways and over-winter locations. Light-level geolocator tags have offered unprecedented insight into migratory ecology for many species, but previous studies suggest that geolocators may influence apparent return rates. We sought to determine if geolocators influence apparent return rates of adult male Canada Warblers breeding in West Virginia, USA. In 2020, we deployed geolocators on 32 birds and color banded an additional 78 birds without geolocators. The following year, 13 of 32 (40.6%) geolocator birds and 37 of 78 (47.4%) color-banded birds were detected with no significant difference in apparent return rates between groups (χ² = 0.19, p = 0.66). Although further evaluation of additional groups will be valuable, the lack of significant effect on adult male Canada Warblers suggests that the slightly lower return rate does not preclude the use of geolocators as a tool to assess the migration ecology of this small songbird of conservation concern.

Recycling aluminium is essential for a circular economy, reducing the energy required and greenhouse gas emissions compared to extraction from virgin ore. A ‘Twitch’ waste stream is a mix of shredded wrought and cast aluminium. Wrought must be separated before recycling to prevent contamination from the impurities present in the cast. In this paper, we demonstrate magnetic induction spectroscopy (MIS) to classify wrought from cast aluminium. MIS measures the scattering of an oscillating magnetic field to characterise a material. The conductivity difference between cast and wrought makes it a promising choice for MIS. We first show how wrought can be classified on a laboratory system with 89.66% recovery and 94.96% purity. We then implement the first industrial MIS material recovery solution for sorting Twitch, combining our sensors with a commercial-scale separator system. The industrial system did not reflect the laboratory results. The analysis found three areas of reduced performance: (1) metal pieces correctly classified by one sensor were misclassified by adjacent sensors that only captured part of the metal; (2) the metal surface facing the sensor can produce different classification results; and (3) the choice of machine learning algorithm is significant with artificial neural networks producing the best results on unseen data.

Using data from the National Longitudinal Transition Study 2 (NLTS2), we examined risk and protective factors associated with post-secondary outcomes among youth with emotional and behavioral disorders (EBD). Results indicate that, compared to their male peers, females with EBD demonstrated higher levels of social and behavioral skills and higher grades. We also discovered discrepancies between teacher reports and female students' self-reports of academic, social, and behavioral competencies, suggesting females with EBD underestimate their own skills or that teachers are not fully aware of these students' areas of difficulty. We discuss implications of these results related to existing prevention and intervention strategies for females with EBD.

In this article, the authors describe the complexity of special education teacher (SET) shortage, how shortage undermines equal educational opportunity, and strategies that school districts and state and federal governments have used to combat them. The authors consider the economic consequences of shortage and describe how school budgets are burdened by turnover and, in some cases, litigation. The authors consider specific aspects of SET shortages, including the problems of staffing high-poverty urban and rural schools, recruiting and retaining teachers of color, and staffing alternative educational placements. The authors then consider more general factors related to shortage, including the valence of teaching as a profession, attrition, working conditions, and compensation. The authors describe how broad policy-based interventions, such as federal spending on personnel preparation and alternative route entrées to teaching, have largely failed to remedy SET shortage. Finally, the authors posit that SET shortage cannot be addressed successfully without improving working conditions and differentiating compensation for shortage area teachers and teachers working with struggling students. Although special education cannot achieve such sweeping change alone, the time seems ripe for moving forward on this important agenda.

EmrE transporter effluxes cationic substrates across lipid membranes in a pH-coupled manner. Here, the authors solve the structure of ligand-bound EmrE at high pH by NMR, with insights into the transport mechanism.

Abstract Background Many law enforcement agencies across the United States equip their officers with the life-saving drug naloxone to reverse the effects of an opioid overdose. Although officers can be effectively trained to administer naloxone, and hundreds of law enforcement agencies carry naloxone to reverse overdoses, little is known about what happens on scene during an overdose call for service from an officer’s perspective, including what officers perceive their duties and responsibilities to be as the incident evolves. Methods The qualitative study examined officers’ experiences with overdose response, their perceived roles, and what happens on scene before, during, and after an overdose incident. In-person interviews were conducted with 17 officers in four diverse law enforcement agencies in the United States between January and May 2020. Results Following an overdose, the officers described that overdose victims are required to go to a hospital or they are taken to jail. Officers also described their duties on scene during and after naloxone administration, including searching the belongings of the person who overdosed and seizing any drug paraphernalia. Conclusion These findings point to a pressing need for rethinking standard operating procedures for law enforcement in these situations so that the intentions of Good Samaritan Laws are upheld and people get the assistance they need without being deterred from asking for future help.

AbstractUsing individual differences approaches, a growing body of literature finds positive associations between musicality and language-related abilities, complementing prior findings of links between musical training and language skills. Despite these associations, musicality has been often overlooked in mainstream models of individual differences in language acquisition and development. To better understand the biological basis of these individual differences, we propose the Musical Abilities, Pleiotropy, Language, and Environment (MAPLE) framework. This novel integrative framework posits that musical and language-related abilities likely share some common genetic architecture (i.e., genetic pleiotropy) in addition to some degree of overlapping neural endophenotypes, and genetic influences on musically and linguistically enriched environments. Drawing upon recent advances in genomic methodologies for unraveling pleiotropy, we outline testable predictions for future research on language development and how its underlying neurobiological substrates may be supported by genetic pleiotropy with musicality. In support of the MAPLE framework, we review and discuss findings from over seventy behavioral and neural studies, highlighting that musicality is robustly associated with individual differences in a range of speech-language skills required for communication and development. These include speech perception-in-noise, prosodic perception, morphosyntactic skills, phonological skills, reading skills, and aspects of second/foreign language learning. Overall, the current work provides a clear agenda and framework for studying musicality-language links using individual differences approaches, with an emphasis on leveraging advances in the genomics of complex musicality and language traits.

Abstract Hepatitis C virus (HCV) contributes to liver-related morbidity and mortality throughout Africa despite effective antivirals. HCV is endemic in the Democratic Republic of the Congo (DRC) but data on HCV/HIV co-infection in pregnancy is limited. We estimated the prevalence of and risk factors for HCV/HIV co-infection among pregnant women in the Kinshasa province of the DRC. This cross-sectional study was conducted as a sub-study of an ongoing randomized trial to assess continuous quality improvement interventions (CQI) for prevention of mother-to-child transmission (PMTCT) of HIV (CQI-PMTCT study, NCT03048669). HIV-infected women in the CQI-PMTCT cohort were tested for HCV, and risk factors were evaluated using logistic regression. The prevalence of HCV/HIV co-infection among Congolese women was 0.83% (95% CI 0.43-1.23). Women who tested positive for HCV were younger, more likely to live in urban areas, and more likely to test positive during pregnancy versus postpartum. HCV-positive women had significantly higher odds of infection with hepatitis B virus (HBV) (aOR 13.87 [3.29,58.6]). An inverse relationship was noted between HCV infection and the overall capacity of the health facility as measured by the service readiness index (SRI) (aOR:0.92 [0.86,0.98] per unit increase). Women who presented to rural, for-profit and PEPFAR-funded health facilities were more likely to test positive for HCV. In summary, this study identified that the prevalence of HCV/HIV co-infection was

Changes in gonadal hormones during puberty are thought to potentiate adolescents’ social re-orientation away from caregivers and towards peers. This study investigated the effect of testosterone on neural processing of emotional (vocal) stimuli by unfamiliar peers vs. parents, in transgender boys receiving exogenous testosterone as a gender-affirming hormone (GAH+) or not (GAH-). During fMRI, youth heard angry and happy vocal expressions spoken by their caregiver and an unfamiliar teenager. Youth also self-reported on closeness with friends and parents. Whole-brain analyses (controlling for age) revealed that GAH+ youth showed blunted neural response to caregivers’ angry voices—and heightened response to unfamiliar teenage angry voices—in the anterior cingulate cortex. This pattern was reversed in GAH- youth, who also showed greater response to happy unfamiliar teenager vs. happy caregiver voices in this region. Blunted ACC response to angry caregiver voices—a pattern characteristic of GAH+ youth—was associated with greater relative closeness with friends over parents, which could index more “advanced” social re-orientation. Consistent with models of adolescent neurodevelopment, increases in testosterone during adolescence may shift the valuation of caregiver vs. peer emotional cues in a brain region associated with processing affective information.

We determined weights for a multi-criteria tool for assessing the relative merits of clinical-trial research proposals, and investigated whether the weights vary across relevant stakeholder groups. A cross-sectional, adaptive discrete choice experiment using 1000minds online software was administered to consumers, researchers and funders affiliated with the Australian Clinical Trials Alliance (ACTA). We identified weights for four criteria-Appropriateness, Significance, Relevance, Feasibility-and their levels, representing their relative importance, so that research proposals can be scored between 0% (nil or very low merit) and 100% (very high merit). From 220 complete survey responses, the most important criterion was Appropriateness (adjusted for differences between stakeholder groups, mean weight 28.9%) and the least important was Feasibility (adjusted mean weight 19.5%). Consumers tended to weight Relevance more highly (2.7% points difference) and Feasibility less highly (3.1% points difference) than researchers. The research or grant writing experience of researchers or consumers was not associated with the weights. A multi-criteria tool for evaluating research proposals that reflects stakeholders' preferences was created. The tool can be used to assess the relative merits of clinical trial research proposals and rank them, to help identify the best proposals for funding.

Abstract Background: The COVID-19 pandemic has disproportionally affected traditionally marginalized groups. Both the Delta and Omicron variants raised concern amongst public health officials due to potentially higher infectivity rates and disease severity than prior variants. This study sought to compare disease severity between adults infected with the Omicron variant and adults infected with the Delta variant who presented to the Emergency Department at an academic, safety-net hospital in Virginia. Methods: This retrospective cohort study used electronic medical record data of patients who presented to the Emergency Department and received a positive SARS-CoV-2 test between September 1, 2021, and January 31, 2022. Positive tests were stratified by genotypic variant through whole genome sequencing. Participants with the Omicron variant were propensity scores matched with individuals with the Delta variant. Results: Among 500 Delta and 500 Omicron participants, 279 propensity score-matched pairs were identified. Participants were predominantly unvaccinated, with medical comorbidities, and self-identified as Black. Individuals infected with the Delta variant had more severe disease compared to those with the Omicron variant, regardless of vaccination status. Patients with kidney, liver, and respiratory disease, as well as cancer, are at higher risk for severe disease. Patients with 2 doses of COVID-19 immunization trended toward less severe disease. Conclusions: Overall, these data further support the literature regarding the disproportionate effects of the COVID-19 pandemic on vulnerable patient populations – such as those with limited access to care, people of color, and those with chronic medical conditions – and can be used to inform public health interventions.

IntroductionDevelopmental disabilities and neuromotor delay adversely affect long-term neuromuscular function and quality of life. Current evidence suggests that early therapeutic intervention reduces the severity of motor delay by harnessing neuroplastic potential during infancy. To date, most early therapeutic intervention trials are of limited duration and do not begin soon after birth and thus do not take full advantage of early neuroplasticity. The Corbett Ryan-Northwestern-Shirley Ryan AbilityLab-Lurie Children's Infant Early Detection, Intervention and Prevention Project (Project Corbett Ryan) is a multi-site longitudinal randomized controlled trial to evaluate the efficacy of an evidence-based physical therapy intervention initiated in the neonatal intensive care unit (NICU) and continuing to 12 months of age (corrected when applicable). The study integrates five key principles: active learning, environmental enrichment, caregiver engagement, a strengths-based approach, and high dosage (ClinicalTrials.gov identifier NCT05568264).MethodsWe will recruit 192 infants at risk for neuromotor delay who were admitted to the NICU. Infants will be randomized to either a standard-of-care group or an intervention group; infants in both groups will have access to standard-of-care services. The intervention is initiated in the NICU and continues in the infant's home until 12 months of age. Participants will receive twice-weekly physical therapy sessions and caregiver-guided daily activities, assigned by the therapist, targeting collaboratively identified goals. We will use various standardized clinical assessments (General Movement Assessment; Bayley Scales of Infant and Toddler Development, 4th Edition (Bayley-4); Test of Infant Motor Performance; Pediatric Quality of Life Inventory Family Impact Module; Alberta Infant Motor Scale; Neurological, Sensory, Motor, Developmental Assessment; Hammersmith Infant Neurological Examination) as well as novel technology-based tools (wearable sensors, video-based pose estimation) to evaluate neuromotor status and development throughout the course of the study. The primary outcome is the Bayley-4 motor score at 12 months; we will compare scores in infants receiving the intervention vs. standard-of-care therapy.

Understanding metabolism in the pathogen Candida glabrata is key to identifying new targets for antifungals. The thiamine biosynthetic (THI) pathway is partially defective in C. glabrata, but the transcription factor CgPdc2 upregulates some thiamine biosynthetic and transport genes. One of these genes encodes a recently evolved thiamine pyrophosphatase (CgPMU3) that is critical for accessing external thiamine. Here, we demonstrate that CgPdc2 primarily regulates THI genes. In Saccharomyces cerevisiae, Pdc2 regulates both THI and pyruvate decarboxylase (PDC) genes, with PDC proteins being a major thiamine sink. Deletion of PDC2 is lethal in S. cerevisiae in standard growth conditions, but not in C. glabrata. We uncover cryptic cis elements in C. glabrata PDC promoters that still allow for regulation by ScPdc2, even when that regulation is not apparent in C. glabrata. C. glabrata lacks Thi2, and it is likely that inclusion of Thi2 into transcriptional regulation in S. cerevisiae allows for a more complex regulation pattern and regulation of THI and PDC genes. We present evidence that Pdc2 functions independent of Thi2 and Thi3 in both species. The C-terminal activation domain of Pdc2 is intrinsically disordered and critical for species differences. Truncation of the disordered domains leads to a gradual loss of activity. Through a series of cross species complementation assays of transcription, we suggest that there are multiple Pdc2-containing complexes, and C. glabrata appears to have the simplest requirement set for THI genes, except for CgPMU3. CgPMU3 has different cis requirements, but still requires Pdc2 and Thi3 to be upregulated by thiamine starvation. We identify the minimal region sufficient for thiamine regulation in CgTHI20, CgPMU3, and ScPDC5 promoters. Defining the cis and trans requirements for THI promoters should lead to an understanding of how to interrupt their upregulation and provide targets in metabolism for antifungals.

We need novel strategies to target the complexity of cancer and, particularly, of metastatic disease. As an example of this complexity, certain tissues are particularly hospitable environments for metastases, whereas others do not contain fertile microenvironments to support cancer cell growth. Continuing evidence that the extracellular matrix (ECM) of tissues is one of a host of factors necessary to support cancer cell growth at both primary and secondary tissue sites is emerging. Research on cancer metastasis has largely been focused on the molecular adaptations of tumor cells in various cytokine and growth factor environments on 2-dimensional tissue culture polystyrene plates. Intravital imaging, conversely, has transformed our ability to watch, in real time, tumor cell invasion, intravasation, extravasation, and growth. Because the interstitial ECM that supports all cells in the tumor microenvironment changes over time scales outside the possible window of typical intravital imaging, bioengineers are continuously developing both simple and sophisticated in vitro controlled environments to study tumor (and other) cell interactions with this matrix. In this perspective, we focus on the cellular unit responsible for upholding the pathologic homeostasis of tumor-bearing organs, cancer-associated fibroblasts (CAFs), and their self-generated ECM. The latter, together with tumoral and other cell secreted factors, constitute the “tumor matrisome”. We share the challenges and opportunities for modeling this dynamic CAF/ECM unit, the tools and techniques available, and how the tumor matrisome is remodeled (e.g., via ECM proteases). We posit that increasing information on tumor matrisome dynamics may lead the field to alternative strategies for personalized medicine outside genomics.

Previously, we reviewed 1052 randomized-controlled trial abstracts presented at the American Society of Anesthesiologists annual meetings from 2001-2004. We found significant positive publication bias in the period examined, with the odds ratio for abstracts with positive results proceeding to journal publication over those with null results being 2.01 [95% confidence interval: 1.52, 2.66; P < 0.001]. Mandatory trial registration was introduced in 2005 as a required standard for publication. We sought to examine whether mandatory trial registration has decreased publication bias in the anesthesia and perioperative medicine literature. We reviewed all abstracts from the 2010-2016 American Society of Anesthesiologists meetings that reported on randomized-controlled trials in humans. We scored the result of each abstract as positive or null according to a priori definitions. We systematically searched for any subsequent publication of the studies and calculated the odds ratio for journal publication, comparing positive vs null studies. We compared the odds ratio from the 2010-2016 abstracts (post-mandatory trial registration) with the odds ratio from the 2001-2004 abstracts (pre-mandatory trial registration) as a ratio of odds ratios. We defined a 33% decrease in the odds ratio as significant, corresponding to a new odds ratio of 1.33. We reviewed 9789 abstracts; 1049 met inclusion criteria as randomized-controlled trials, with 542 (51.7%) of the abstracts going on to publication. The odds ratio for abstracts with positive results proceeding to journal publication was 1.28 [95% CI: 0.97, 1.67; P = 0.076]. With adjustment for sample size and abstract quality, the difference in publication rate between positive and null abstracts was statistically significant (odds ratio 1.34; 95% CI: 1.02, 1.76; P = 0.037). The ratio of odds ratios, comparing the odds ratio from the 2010-2016 abstracts (post-mandatory trial registration) to the odds ratio from the 2001-2004 abstracts (pre-mandatory trial registration), was 0.63 (95% CI: 0.43, 0.93); P = 0.021). We present the first study in the anesthesia and perioperative medicine literature that examines and compares publication bias over two discrete periods of time, prior to and after the implementation of mandatory trial registration. Our results suggest that the amount of publication bias has decreased markedly following implementation of mandatory trial registration. However, some positive publication bias in the anesthesia and perioperative medicine literature remains.

BackgroundMental health problems, such as behavioural and emotional problems, are prevalent in children. These problems can have long lasting, detrimental effects on the child, their parents and society. Most children with a mental health problem do not receive professional help. Those that do get help can face long wait times. While waiting, parents want to learn how they can help their child. To address this need, we co-designed a new website to help parents find ways of helping their child's mental health problem while waiting to get specialist help.ObjectivesTo assess the acceptability and feasibility of a new co-designed website, FindWays, through a pilot randomised controlled trial. The protocol is registered with ISRCTN (ISRCTN64605513).MethodsThis study will recruit up to 60 parents of children aged two-twelve years old referred to a paediatrician for behavioural and/or emotional problems. Participants will be randomly allocated by computer generated number sequence to either the intervention or control group. Intervention group participants will receive access to the FindWays website to help them manage their child's mental health problem while they wait to see the paediatrician. Acceptability and feasibility will be assessed over the 4-month intervention through mixed methods including: recruitment, adherence, retention, net promoter score (quantitative measures) and semi-structured interviews to gain an in-depth understanding of parents' experience and potential adverse effects (qualitative measure). Secondary outcomes measured by parent survey at 4-months post randomisation include child mental health, parent mental health, impact of the child's mental health problem on their functioning and family, and health service use and associated costs.ResultsRecruitment commenced June 2022 with publication expected in October 2023.ConclusionThis study will provide novel data on the acceptability and feasibility of a new website co-designed with parents to help them find ways of managing their child's behaviour and emotions.

Abstract Invasive non‐native species (INNS) are recognized as a major threat to island biodiversity, ecosystems, and economies globally. Preventing high‐risk INNS from being introduced is the most cost‐effective way to avoid their adverse impacts. We applied a horizon scanning approach to identify potentially INNS in the United Kingdom Overseas Territories (OTs), ranging from Antarctica to the Caribbean, and from the Pacific to the Atlantic. High‐risk species were identified according to their potential for arrival, establishment, and likely impacts on biodiversity and ecosystem function, economies, and human health. Across OTs, 231 taxa were included on high‐risk lists. The highest ranking species were the Asian green mussel (Perna viridis), little fire ant (Wasmannia auropunctata), brown rat (Rattus norvegicus), and mesquite tree (Prosopis juliflora). Shipping containers were identified as the introduction pathway associated with the most species. The shared high‐risk species and pathways identified provide a guide for other remote islands and archipelagos to focus ongoing biosecurity and surveillance aimed at preventing future incursions.

Hippocampal subfields (HCsf) are brain regions important for memory function that are vulnerable to decline with amnestic mild cognitive impairment (aMCI), which is often a preclinical stage of Alzheimer’s disease. Studies in aMCI patients often assess HCsf tissue integrity using measures of volume, which has little specificity to microstructure and pathology. We use magnetic resonance elastography (MRE) to examine the viscoelastic mechanical properties of HCsf tissue, which is related to structural integrity, and sensitively detect differences in older adults with aMCI compared to an age-matched control group. Group comparisons revealed HCsf viscoelasticity is differentially affected in aMCI, with CA1-CA2 and DG-CA3 exhibiting lower stiffness and CA1-CA2 exhibiting higher damping ratio, both indicating poorer tissue integrity in aMCI. Including HCsf stiffness in a logistic regression improves classification of aMCI beyond measures of volume alone. Additionally, lower DG-CA3 stiffness predicted aMCI status regardless of DG-CA3 volume. These findings showcase the benefit of using MRE in detecting subtle pathological tissue changes in individuals with aMCI via the HCsf particularly affected in the disease.

BackgroundHeated tobacco products (also called 'heat-not-burn' products) heat tobacco at temperatures below that of combustion, causing nicotine and other compounds to aerosolise. One such product, IQOS from Philip Morris International, is being marketed internationally with claims of harm reduction. We sought to determine whether exposure to IQOS aerosol impairs arterial flow-mediated dilation (FMD), a measure of vascular endothelial function that is impaired by tobacco smoke.MethodsWe exposed anaesthetised rats (n=8/group) via nose cone to IQOS aerosol from single HeatSticks, mainstream smoke from single Marlboro Red cigarettes or clean air for a series of consecutive 30 s cycles over 1.5-5 min. Each cycle consisted of 15 or 5 s of exposure followed by removal from the nose cone. We measured pre-exposure and postexposure FMD, and postexposure serum nicotine and cotinine.ResultsFMD was impaired comparably by ten 15 s exposures and ten 5 s exposures to IQOS aerosol and to cigarette smoke, but not by clean air. Serum nicotine levels were similar to plasma levels after humans have smoked one cigarette, confirming that exposure conditions had real-world relevance. Postexposure nicotine levels were ~4.5-fold higher in rats exposed to IQOS than to cigarettes, despite nicotine being measured in the IQOS aerosol at ~63% the amount measured in smoke. When IQOS exposure was briefer, leading to comparable serum nicotine levels to the cigarette group, FMD was still comparably impaired.ConclusionsAcute exposures to IQOS aerosol impairs FMD in rats. IQOS use does not necessarily avoid the adverse cardiovascular effects of smoking cigarettes.

BackgroundNew electronic heated tobacco products are being introduced in the global market and are gaining popularity. In 2016, Philip Morris International, Inc. (PMI) submitted a modified risk tobacco product (MRTP) application to the Food and Drug Administration (FDA) to market IQOS in the USA with claims of reduced exposure and reduced risk.MethodsWe examined PMI's MRTP application, specifically sections on aerosol chemistry and human exposure assessment, to assess the validity of PMI's claims of reduced exposure and risk.FindingsPMI reported levels for only 40 of 93 harmful and potentially harmful constituents (HPHCs) on FDA's HPHC list in IQOS mainstream aerosol. All substances in PMI's list of 58 constituents (PMI-58) were lower in IQOS emissions compared with mainstream smoke of 3R4F reference cigarettes. However, levels of 56 other constituents, which are not included in the PMI-58 list or FDA's list of HPHCs, were higher in IQOS emissions; 22 were >200% higher and seven were >1000% higher than in 3R4F reference cigarette smoke. PMI's studies also show significantly lower systemic exposure to some HPHCs from use of IQOS compared with smoking combustible cigarettes.ConclusionPMI's data appear to support PMI's claim that IQOS reduces exposure to HPHCs. However, PMI's data also show significantly higher levels of several substances that are not recognised as HPHCs by the FDA in IQOS emissions compared with combustible cigarette smoke. The impact of these substances on the overall toxicity or harm of IQOS is not known.

BackgroundSecondhand smoke (SHS) in US casinos is common, but little is known about the residue of tobacco smoke pollutants left behind in dust and on surfaces, commonly referred to as thirdhand smoke (THS). We examined SHS and THS pollution and exposure before and during a casino smoking ban and after smoking resumed.MethodsA casino was visited nine times over a 15-month period to collect dust, surface and air samples in eight locations. Finger wipe and urine samples were collected from non-smoking confederates before and after a 4-hour casino visit. Samples were analysed for markers of SHS and THS pollution and exposure.ResultsExceptionally high levels of THS were found in dust and on surfaces. Although the smoking ban led to immediate improvements in air quality, surface nicotine levels were unchanged and remained very high for the first month of the smoking ban. Surface nicotine decreased by 90% after 1 month (P

Electric-field-controlled magnetism can boost energy efficiency in widespread applications. However, technologically, this effect is facing important challenges: mechanical failure in strain-mediated piezoelectric/magnetostrictive devices, dearth of room-temperature multiferroics, or stringent thickness limitations in electrically charged metallic films. Voltage-driven ionic motion (magneto-ionics) circumvents most of these drawbacks while exhibiting interesting magnetoelectric phenomena. Nevertheless, magneto-ionics typically requires heat treatments and multicomponent heterostructures. Here we report on the electrolyte-gated and defect-mediated O and Co transport in a Co3O4 single layer which allows for room-temperature voltage-controlled ON-OFF ferromagnetism (magnetic switch) via internal reduction/oxidation processes. Negative voltages partially reduce Co3O4 to Co (ferromagnetism: ON), resulting in graded films including Co- and O-rich areas. Positive bias oxidizes Co back to Co3O4 (paramagnetism: OFF). This electric-field-induced atomic-scale reconfiguration process is compositionally, structurally, and magnetically reversible and self-sustained, since no oxygen source other than the Co3O4 itself is required. This process could lead to electric-field-controlled device concepts for spintronics.

Control of materials through custom design of ionic distributions represents a powerful new approach to develop future technologies ranging from spintronic logic and memory devices to energy storage. Perovskites have shown particular promise for ionic devices due to their high ion mobility and sensitivity to chemical stoichiometry. In this work, we demonstrate a solid-state approach to control of ionic distributions in (La,Sr)CoO3 thin films. Depositing a Gd capping layer on the perovskite film, oxygen is controllably extracted from the structure, up to 0.5 O/u.c. throughout the entire 36-nm thickness. Commensurate with the oxygen extraction, the Co valence state and saturation magnetization show a smooth continuous variation. In contrast, magnetoresistance measurements show no change in the magnetic anisotropy and a rapid increase in the resistivity over the same range of oxygen stoichiometry. These results suggest significant phase separation, with metallic ferromagnetic regions and oxygen-deficient, insulating, nonferromagnetic regions, forming percolated networks. Indeed, x-ray diffraction identifies oxygen-vacancy ordering, including transformation to a brownmillerite crystal structure. The unexpected transformation to the brownmillerite phase at ambient temperature is further confirmed by high-resolution scanning transmission electron microscopy which shows significant structural - and correspondingly chemical - phase separation. This work demonstrates room-temperature ionic control of magnetism, electrical resistivity, and crystalline structure in a 36-nm-thick film, presenting opportunities for ionic devices that leverage multiple material functionalities.

Background: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.Methods: This report presents the results from a method performance study involving 11 laboratories from 6 countries that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two additional blank urine samples fortified with pure nicotine, cotinine, and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography/tandem mass spectrometry.Results: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools, the mean bias observed was < + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results.Conclusions: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine.Impact: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1083-90. ©2018 AACR.

Standard and targeted cancer therapies for late-stage cancer patients almost universally fail due to tumor heterogeneity/plasticity and intrinsic or acquired drug resistance. We used the telomerase substrate nucleoside precursor, 6-thio-2'-deoxyguanosine (6-thio-dG), to target telomerase-expressing non-small cell lung cancer cells resistant to EGFR-inhibitors and commonly used chemotherapy combinations. Colony formation assays, human xenografts as well as syngeneic and genetically engineered immune competent mouse models of lung cancer were used to test the effect of 6-thio-dG on targeted therapy- and chemotherapy-resistant lung cancer human cells and mouse models. We observed that erlotinib-, paclitaxel/carboplatin-, and gemcitabine/cisplatin-resistant cells were highly sensitive to 6-thio-dG in cell culture and in mouse models. 6-thio-dG, with a known mechanism of action, is a potential novel therapeutic approach to prolong disease control of therapy-resistant lung cancer patients with minimal toxicities.

Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and cross-linking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with comonomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic comonomer elicited the highest FBR. Lowering the hydrogel modulus (165 to 3 kPa), or PC content (20 to 0 wt %), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.

Although aberrant EGFR signaling is widespread in cancer, EGFR inhibition is effective only in a subset of non-small cell lung cancer (NSCLC) with EGFR activating mutations. A majority of NSCLCs express EGFR wild type (EGFRwt) and do not respond to EGFR inhibition. TNF is a major mediator of inflammation-induced cancer. We find that a rapid increase in TNF level is a universal adaptive response to EGFR inhibition in NSCLC, regardless of EGFR status. EGFR signaling actively suppresses TNF mRNA levels by inducing expression of miR-21, resulting in decreased TNF mRNA stability. Conversely, EGFR inhibition results in loss of miR-21 and increased TNF mRNA stability. In addition, TNF-induced NF-κB activation leads to increased TNF transcription in a feed-forward loop. Inhibition of TNF signaling renders EGFRwt-expressing NSCLC cell lines and an EGFRwt patient-derived xenograft (PDX) model highly sensitive to EGFR inhibition. In EGFR-mutant oncogene-addicted cells, blocking TNF enhances the effectiveness of EGFR inhibition. EGFR plus TNF inhibition is also effective in NSCLC with acquired resistance to EGFR inhibition. We suggest concomitant EGFR and TNF inhibition as a potentially new treatment approach that could be beneficial for a majority of lung cancer patients.

Background: Many adolescents are exposed to tobacco smoke, from either active smoking (CS) or secondhand smoke (SHS) exposure. Tobacco-specific biomarkers of exposure include cotinine (detects use in past 2-4 days) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; detects use for a month or longer). NNAL is expected to detect more intermittent tobacco exposure. We compared NNAL and cotinine as biomarkers of exposure to tobacco in urban adolescents and determined the optimal NNAL cutoff point to distinguish CS from SHS exposure.Methods: Surplus urine samples, collected from 466 adolescents attending pediatric well or urgent care visits at Zuckerberg San Francisco General Hospital in 2013 to 2014, were assayed for cotinine and NNAL.Results: Ninety-four percent of adolescents had measurable levels of NNAL compared with 87% for cotinine. The optimal NNAL cutoff point to distinguish CS from SHS was 9.6 pg/mL by latent class or 14.4 pg/mL by receiver-operating characteristic analysis. Cotinine and NNAL were strongly correlated, but the correlation slopes differed for active versus SHS-exposed adolescents. Among nonsmokers, NNAL levels were significantly higher in African American (median, 3.3 pg/mL) compared with other groups (0.9-1.9 pg/mL), suggesting greater exposure to SHS.Conclusions: Urine NNAL screening finds a large majority (94%) of urban adolescents are exposed to tobacco. African Americans are exposed to higher levels of SHS than other ethnic/racial groups.Impact: SHS is associated with significant medical morbidity in adolescents. Routine biochemical screening with NNAL or cotinine detects high prevalence of SHS exposure and should be considered as a tool to reduce SHS exposure in high-risk populations. Cancer Epidemiol Biomarkers Prev; 27(3); 254-61. ©2018 AACR.

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk.

Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility, and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell-type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell-type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell-type-specific chromatin accessibility.

Microbial communities are important for the health of mucosal tissues. Traditional culture and gene sequencing have demonstrated bacterial populations on the conjunctiva. However, it remains unclear if the cornea, a transparent tissue critical for vision, also hosts a microbiome. Corneas of wild-type, IL-1R (-/-) and MyD88 (-/-) C57BL/6 mice were imaged after labeling with alkyne-functionalized D-alanine (alkDala), a probe that only incorporates into the peptidoglycan of metabolically active bacteria. Fluorescence in situ hybridization (FISH) was also used to detect viable bacteria. AlkDala labeling was rarely observed on healthy corneas. In contrast, adjacent conjunctivae harbored filamentous alkDala-positive forms, that also labeled with DMN-Tre, a Corynebacterineae-specific probe. FISH confirmed the absence of viable bacteria on healthy corneas, which also cleared deliberately inoculated bacteria within 24 h. Differing from wild-type, both IL-1R (-/-) and MyD88 (-/-) corneas harbored numerous alkDala-labeled bacteria, a result abrogated by topical antibiotics. IL-1R (-/-) corneas were impermeable to fluorescein suggesting that bacterial colonization did not reflect decreased epithelial integrity. Thus, in contrast to the conjunctiva and other mucosal surfaces, healthy murine corneas host very few viable bacteria, and this constitutive state requires the IL-1R and MyD88. While this study cannot exclude the presence of fungi, viruses, or non-viable or dormant bacteria, the data suggest that healthy murine corneas do not host a resident viable bacterial community, or microbiome, the absence of which could have important implications for understanding the homeostasis of this tissue.

Abstract The need for sustainable agricultural practices to meet the food, feed, and fuel demands of a growing global population while reducing detrimental environmental impacts has driven research in multi‐faceted approaches to agricultural sustainability. Perennial cropping systems and microbial biofertilizer supplements are two emerging strategies to increase agricultural sustainability that are studied in tandem for the first time in this study. During the establishment phase of a perennial switchgrass stand in SW Montana, USA, we supplemented synthetic fertilization with a nitrogen‐fixing cyanobacterial biofertilizer (CBF) and were able to maintain aboveground crop productivity in comparison to a synthetic only (urea) fertilizer treatment. Soil chemical analysis conducted at the end of the growing season revealed that late‐season nitrogen availability in CBF‐supplemented field plots increased relative to urea‐only plots. High‐throughput sequencing of bacterial/archaeal and fungal communities suggested fine‐scale responses of the microbial community and sensitivity to fertilization among arbuscular mycorrhizal fungi, Planctomycetes, Proteobacteria, and Actinobacteria. Given their critical role in plant productivity and soil nutrient cycling, soil microbiome monitoring is vital to understand the impacts of implementation of alternative agricultural practices on soil health.

Abstract Background Malignant melanoma in dogs is considered to be largely resistant to conventional chemotherapy, although responses to carboplatin have been documented. Invasion and early metastasis are common features of certain melanoma subtypes that contribute to tumour progression despite aggressive local and systemic therapy. Upregulation of the PI3K/AKT/mTOR pathway has been observed in canine malignant melanoma and may represent a potential target for therapy. Rapamycin (sirolimus) and everolimus are commercially available small molecule inhibitors that target mTOR and therefore may have anticancer activity in canine melanoma. It was hypothesized that there is synergism between rapamycin or everolimus and platinum chemotherapy, and that combination drug treatment would inhibit target/downstream proteins involved in cell viability/proliferation and increase cell death in canine melanoma cells. It was further hypothesized that rapamycin or everolimus would impact metabolism by reducing glycolysis in these cells. Four canine melanoma cell lines were treated in vitro with rapamycin and everolimus as sole treatment or combined with carboplatin. Cell viability, apoptosis, target modulation, and glycolytic metabolism were evaluated by crystal violet colourimetric assay, Annexin V/PI flow cytometry, western blotting, and Seahorse bioanalyzer, respectively. Results When combined with carboplatin chemotherapy, rapamycin or everolimus treatment was overall synergistic in reducing cell viability. Carboplatin-induced apoptosis was noted at 72 h after treatment compared to the vehicle control. Levels of phosphorylated mTOR were reduced by rapamycin and everolimus in all four cell lines, but activation of the downstream protein p70S6K was not consistently reduced by treatment in two of the cell lines. Both mTOR inhibitors decreased the extracellular acidification rate of canine melanoma cells, indicating reduced cancer cell glycolytic activity. Conclusions Inhibition of mTOR by rapalogs, such as rapamycin and everolimus combined with carboplatin chemotherapy may have activity in canine melanoma. Future mechanistic investigation is warranted, including in vivo assessment of this combination therapy.

Suicide is the most common cause of death in male resident physicians and the second most common cause of death in resident physicians overall. Physicians also experience high rates of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and burnout. These conditions frequently develop during medical school, and threaten not only physicians but the patients they care for. A 30-year-old medical student presented to our clinic with a history of treatment-resistant depression (TRD), generalized anxiety disorder (GAD), PTSD, and 5 years of daily suicidal ideation. Previous treatments included therapy, lifestyle modifications, and various combinations of six antidepressants. These interventions had little effect on the patient’s mental health. The patient was treated at our clinic with an 8-month regimen of IV ketamine infusions and ketamine-assisted psychotherapy (KAP). The patient achieved remission from suicidality and PTSD within 1 month; and TRD and GAD within 7 months. The patient’s Patient Health Questionnaire (PHQ-9) score decreased from 25 (severe depression) to 1 (not depressed). These findings suggest that ketamine and KAP may represent effective interventions for mental health applications in healthcare professionals. The patient made the unique decision to attempt to type narrative journals during four of his ketamine infusions (doses ranged from 1.8 to 2.1 mg/kg/h IV). The patient successfully typed detailed journals throughout each 1-h ketamine infusion. To our knowledge, these journals represent the first independently typed, first-person, real-time narratives of ketamine-induced non ordinary states of consciousness. The transcripts of these journals may provide useful insights for clinicians, particularly in the context of KAP.

Procedures in life sciences research laboratories often require chemicals and plasticware that are costly, toxic or pose a risk to the environment. Therefore, sustainable alternatives would be of interest, provided that they generate suitable data quality. Coomassie blue and silver staining are the most widely used methods for detecting proteins following electrophoresis in the laboratory. However, their use presents challenges in terms of safety and waste management. In the current study, aqueous extracts were prepared from a series of common food species and evaluated as alternative stains for protein detection. Beets, blueberries, purple cabbage, raspberries and strawberries were employed to stain identical proteins separated under the same conditions in electrophoresis gels. Extracts of the first two species resulted in protein bands that were detectable through visible light transillumination, whereas extracts from all five species generated specific protein bands under ultraviolet light. The raspberry-derived extract was selected for further study based on the brightness of the fluorescent protein bands and minimal background staining. For both bovine serum albumin and lysozyme at 2.5 μg and 0.5 μg protein per band, the mean signal intensities obtained with raspberry extract staining were just below half of those obtained with Coomassie blue. Furthermore, the mean intensities using raspberry extract were equivalent to those obtained using Coomassie blue in the detection of 0.1 μg protein. Therefore, raspberry could be used to produce an effective stain for the routine laboratory analysis of proteins.

Traditional family planning research has excluded Black and Latinx leaders, and little is known about medication abortion (MA) among racial/ethnic minorities, although it is an increasingly vital reproductive health service, particularly after the fall of Roe v. Wade. Reproductive justice (RJ) community-based organisation (CBO) SisterLove led a study on Black and Latinx women’s MA perceptions and experiences in Georgia. From April 2019 to December 2020, we conducted key informant interviews with 20 abortion providers and CBO leaders and 32 in-depth interviews and 6 focus groups (n = 30) with Black and Latinx women. We analysed data thematically using a team-based, iterative approach of coding, memo-ing, and discussion. Participants described multilevel barriers to and strategies for MA access, wishing that “the process had a bit more humanity … [it] should be more holistic.” Barriers included (1) sociocultural factors (intersectional oppression, intersectional stigma, and medical experimentation); (2) national and state policies; (3) clinic- and provider-related factors (lack of diverse clinic staff, long waiting times); and (4) individual-level factors (lack of knowledge and social support). Suggested solutions included (1) social media campaigns and story-sharing; (2) RJ-based policy advocacy; (3) diversifying clinic staff, offering flexible scheduling and fees, community integration of abortion, and RJ abortion funds; and (4) social support (including abortion doulas) and comprehensive sex education. Findings suggest that equitable MA access for Black and Latinx communities in the post-Roe era will require multi-level intervention, informed by community-led evidence production; holistic, de-medicalised, and human rights-based care models; and intersectional RJ policy advocacy.