Community infant safe sleep and breastfeeding promotion and population level-outcomes: A mixed methods study.

PROBLEM: In the U.S., sudden unexpected infant deaths due to accidental suffocation and strangulation in bed are increasing. Though breastfeeding is a protective factor against sudden unexpected infant death, motivations to breastfeed often couple with unsafe infant sleep practices. Racial/ethnic disparities are present in sudden unexpected infant death, accidental suffocation and strangulation in bed, and breastfeeding. BACKGROUND: Promoting infant safe sleep and breastfeeding through community-level initiatives could address disparities in related outcomes. AIM: Investigate the relationship between community-level strategies and associated state-level outcomes for infant safe sleep and breastfeeding. METHODS: We employed an intervention mixed methods framework and exploratory sequential design. The qualitative component entailed a hermeneutical phenomenological framework to analyze key informant interview data from seven U.S. community-level providers participating in a practice improvement initiative. The quantitative component entailed descriptively analyzing infant safe sleep and breastfeeding indicators from the 2019 Pregnancy Risk Assessment Monitoring System and Ohio Pregnancy Assessment Survey. Qualitative and quantitative data were linked through embedded integration. FINDINGS: We identified two mixed insights: gaps in promotion and outcomes, and persistent disparities between infant safe sleep and breastfeeding promotion and outcomes. DISCUSSION: Our findings indicate conversational approaches could improve infant safe sleep and breastfeeding promotion, outcomes, and relative disparities. We find that community collaboration is needed to address organizational capacity limitations in promoting infant safe sleep and breastfeeding. CONCLUSION: Community-level organizations and providers should consider tailoring program offerings and care delivery to include conversational approaches and community collaboration to promote infant safe sleep and breastfeeding and decrease relative disparities in outcomes.

Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.

Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood. Here we show that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed from the cell surface during apoptosis. This process is mediated by the ADAM10 sheddase, the activity of which is associated with XKR8-catalyzed flipping of phosphatidylserine to the outer leaflet of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins as an enzymatically-modulatable barrier to efferocytosis. Together these findings demonstrate a glycocalyx regulatory pathway with implications for therapeutic intervention in the clearance of normal and transformed apoptotic T cells.

A collaborative approach to designing an online nutrition education program for people with multiple sclerosis.

PURPOSE: People with multiple sclerosis (pwMS) want disease-specific dietary advice to reduce the confusion around diet. This study used co-design principles to develop an online nutrition education program for pwMS. METHODS: Mixed-methods (multiphase sequential design). Phase 1: online survey (n = 114 pwMS) to explore preferred content and characteristics of a nutrition program and develop a draft program. Phase 2: feedback on the draft program from stakeholders (two meetings; n = 10 pwMS and multiple sclerosis (MS) health professionals) and pwMS (two workshops; n = 6) to produce a full program prototype. Phase 3: cognitive interviews (n = 8 pwMS plus 1 spouse) to explore acceptability and ease of comprehension of one module of the program, analysed using deductive content analysis. RESULTS: Preferred topics were included in the program, which were further developed with consumer feedback. Cognitive interviews produced four themes: (1) positive and targeted messaging to motivate behaviour change; (2) "not enough evidence" is not good enough; (3) expert advice builds in credibility; and (4) engaging and appropriate online design elements are crucial. CONCLUSIONS: Positive language appears to improve motivation to make healthy dietary changes and engagement with evidence-based nutrition resources. To ensure acceptability, health professionals can use co-design to engage consumers when developing resources for pwMS.IMPLICATIONS FOR REHABILITATIONCo-designed nutrition education programs can help people achieve high-quality diets in line with recommendations, but very few programs exist for people with multiple sclerosis (MS), and none were co-designedThe participatory research in this study was instrumental in ensuring that important information regarding program acceptability was identifiedCo-design can ensure that the language is appropriate for the target audience, and positive language appeared to improve motivation in people with MS to engage with the online nutrition education programWhere practical and feasible, health professionals should collaborate with MS consumers when developing resources, and use positive, empowering language.

Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens.

Chemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local or global structural distortion. This is of particular importance when the protein in question requires a high degree of structural conservation for inducing a biological outcome such as the elicitation of antibodies to conformationally sensitive epitopes. The HIV-1 envelope glycoprotein (Env) trimer is metastable and shifts between different conformational states, complicating its use as a vaccine antigen. Here we have used the hetero-bifunctional zero-length reagent 1-Ethyl-3-(3-Dimethylaminopropyl)-Carbodiimide (EDC) to cross-link two soluble Env trimers, selected well-folded trimer species using antibody affinity, and transferred this process to good manufacturing practice (GMP) for experimental medicine use. Cross-linking enhanced trimer stability to biophysical and enzyme attack. Cryo-EM analysis revealed that cross-linking retained the overall structure with root-mean-square deviations (RMSDs) between unmodified and cross-linked Env trimers of 0.4-0.5 Å. Despite this negligible distortion of global trimer structure, we identified individual inter-subunit, intra-subunit, and intra-protomer cross-links. Antigenicity and immunogenicity of the trimers were selectively modified by cross-linking, with cross-linked ConS retaining bnAb binding more consistently than ConM. Thus, the EDC cross-linking process improves trimer stability whilst maintaining protein folding, and is readily transferred to GMP, consistent with the more general use of this approach in protein-based vaccine design.

mTOR Regulation of N-Myc Downstream Regulated 1 (NDRG1) Phosphorylation in Clear Cell Renal Cell Carcinoma.

The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected clear cell renal cell carcinoma (ccRCC) relative to pair-matched normal renal tissue. Using a proteomic array, we found N-Myc Downstream Regulated 1 (NDRG1) showed the greatest increase (3.3-fold) in phosphorylation (on Thr346) in ccRCC. This was associated with an increase in total NDRG1. RICTOR is a required subunit in mTORC2, and its knockdown decreased total and phospho-NDRG1 (Thr346) but not NDRG1 mRNA. The dual mTORC1/2 inhibitor, Torin 2, significantly reduced (by ~100%) phospho-NDRG1 (Thr346). Rapamycin is a selective mTORC1 inhibitor that had no effect on the levels of total NDRG1 or phospho-NDRG1 (Thr346). The reduction in phospho-NDRG1 (Thr346) due to the inhibition of mTORC2 corresponded with a decrease in the percentage of live cells, which was correlated with an increase in apoptosis. Rapamycin had no effect on ccRCC cell viability. Collectively, these data show that mTORC2 mediates the phosphorylation of NDRG1 (Thr346) in ccRCC. We hypothesize that RICTOR and mTORC2-mediated phosphorylation of NDRG1 (Thr346) promotes the viability of ccRCC cells.

The risk of all-cause mortality associated with anxiety: a retrospective cohort study using 'The Health Improvement Network' database.

BACKGROUND: Anxiety is a prevalent condition with a substantial associated burden of morbidity. Previous literature investigating effects of anxiety on mortality rates has found conflicting results. This is in part due to inadequate consideration of comorbid depression as a confounder and analysing sub-types of anxiety together. The objective of this study was to compare mortality risks in people diagnosed with anxiety. METHODS: We undertook a retrospective cohort study using the 'The Health Improvement Network' database (a UK primary care dataset) between 1st January 2005 to 1st January 2018. 345 903 patients with anxiety (exposed group) were matched to 691 449 unexposed patients. Cox regression analyses were used to adjusted hazard ratios (HRs) for mortality risk. RESULTS: During the study period 18 962 patients (5·5%) died in the exposed group compared to 32 288 (4·7%) in the unexposed group. This translated into a crude HR for all of 1·14 (95% CI 1·12 - 1·16), which remained significant after adjustment for key co-variates (including depression) giving a final HR of 1·05 (95% CI 1·03 - 1·07). When broken down by sub-type of anxiety (10·3% (35, 581) had phobias, 82·7% (385,882) has 'other' types, and 7·0% (24,262) had stress related anxiety) there were markedly different effect sizes. The adjusted model for the stress-related anxiety sub-type demonstrated a HR of 0·88 (95% CI 0·80 - 0·97). Conversely, the HR was increased in 'other' sub-types to 1·07 (95% CI 1·05 - 1·09) and non-significant in phobia types of anxiety. CONCLUSION: A complex relationship is found between anxiety and mortality. The presence of anxiety slightly increased the risk of death, but this risk varies depending on the type of anxiety diagnosed.

Pre-eclampsia is associated with complement pathway activation in the maternal and fetal circulation, and placental tissue.

OBJECTIVES: Pre-eclampsia (PE) is a leading cause of obstetric morbidity, with no definitive therapy other than delivery. We aimed to compare complement markers in maternal and fetal circulation, and placental tissue, between women with PE and healthy pregnant controls. STUDY DESIGN: Maternal and umbilical cord blood was tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue for C3d, C4d, C9 and C1q, from women with PE (n = 34) and healthy pregnant controls (n = 33). Maternal properdin and Ba tests were repeated in a separate validation cohort (PE n = 35; healthy pregnant controls n = 35). MAIN OUTCOME MEASURES: Complement concentrations in maternal and umbilical cord blood, and placental immunohistochemical complement deposition. RESULTS: Women with PE had significantly lower concentrations of properdin (mean: 4828 vs 6877 ng/ml, p < 0.001) and C4 (mean: 0.20 vs 0.31 g/l, p < 0.001), and higher Ba (median: 150 vs 113 ng/ml, p = 0.012), compared to controls. After controlling for gestational age at blood draw, average properdin concentration was 1945 ng/ml lower in PE vs controls (95 % CI: 1487-2402, p < 0.001). Of the cord blood markers assessed, only Ba differed significantly between PE and controls (median: 337 vs 233 ng/ml, p = 0.004). C4d staining of the syncytiotrophoblast membrane was increased in PE vs controls (median immunoreactivity score 3 vs 0, p < 0.001). Maternal properdin and C4 were significantly negatively correlated with placental C4d staining. CONCLUSIONS: Our data confirm excessive placental complement deposition associated with significant concurrent changes in maternal and fetal circulating complement biomarkers in PE. Inhibition of complement activation is a potential therapeutic target.

Pregnant Latinas' perspectives on pursuing expanded carrier screening: "It is better to know than not".

With the advance of genetic technologies, the use of expanded carrier screening (ECS) in the prenatal setting is growing. ECS tests for a wide range of inherited genetic disorders regardless of racial/ethnic background and family history. Latinxs are an important ECS stakeholder group as they are the largest minority group with the highest fertility rate in the United States. Yet, the Latinx population has, to date, been underrepresented and understudied in genetics/genomics research. We conducted a study to explore the knowledge and perspectives of pregnant Latinas regarding ECS in which descriptive statistics and content analysis were used to analyze the data. Thirty-two pregnant Latinas - mostly of low educational levels (no education beyond high school) and with less than $20,000 annual household income living in rural areas were surveyed, provided with education about ECS, and interviewed. Participants were found to possess limited knowledge about ECS prior to being interviewed. Most (68.8%), however, expressed interest in pursuing ECS following the educational component that explained ECS. Their interest was mainly driven by the desire to know their baby's chance of developing a genetic disorder, the low risk of ECS procedures for both pregnant Latinas and their fetus, and the opportunity to better prepare for raising a child with a genetic condition. Our findings contribute to the limited research in the genetics/genomics field by providing in-depth insights into the perspectives of pregnant Latinas regarding ECS. Obstetric providers and genetic counselors should provide culturally appropriate education and counseling to empower pregnant Latinas to make informed decisions about the use of ECS.

Community-based approaches to infant safe sleep and breastfeeding promotion: a qualitative study.

BACKGROUND: In the U.S., sudden unexpected infant deaths (SUID) due to accidental suffocation and strangulation in bed (ASSB) are increasing, with disparities by race/ethnicity. While breastfeeding is a protective factor against infant mortality, racial/ethnic disparities are present in its uptake, and motivations to breastfeed are also often coupled with non-recommended infant sleep practices that are associated with infant sleep deaths. Combining infant safe sleep (ISS) and breastfeeding promotion on the community level presents opportunities to address racial/ethnic disparities and associated socioeconomic, cultural, and psychosocial influences. METHODS: We completed a descriptive qualitative hermeneutical phenomenology using thematic analysis of focus group data. We examined the phenomenon of community-level providers promoting ISS and breastfeeding in communities vulnerable to ISS and breastfeeding disparities. We asked eighteen informants participating in a national quality improvement collaborative about i.) areas requiring additional support to meet community needs around ISS and breastfeeding, and ii.) recommendations on tools to improve their work promoting ISS and breastfeeding. RESULTS: We identified four themes: i.) education and dissemination, ii.) relationship building and social support, iii.) working with clients' personal circumstances and considerations, and iv.) tools and systems. CONCLUSIONS: Our findings support embedding risk-mitigation approaches in ISS education; relationship building between providers, clients, and peers; and the provision of ISS and breastfeeding supportive material resources with educational opportunities. These findings may be used to inform community-level provider approaches to ISS and breastfeeding promotion.

Maternity Care Clinicians' Experiences Promoting Infant Safe Sleep and Breastfeeding During the COVID-19 Pandemic.

OBJECTIVE: To explore the phenomenon of clinicians' perceptions and experiences of promoting infant safe sleep (ISS) and breastfeeding during the COVID-19 pandemic. DESIGN: Descriptive qualitative hermeneutical phenomenology of key informant interviews conducted as part of a quality improvement initiative. SETTING: Maternity care services of 10 U.S. hospitals from April through September 2020. PARTICIPANTS: Ten hospital teams, including 29 clinicians. INTERVENTION: Participants were part of a national quality improvement intervention focused on promoting ISS and breastfeeding. Participants were asked about challenges and opportunities promoting ISS and breastfeeding during the pandemic. RESULTS: We identified four themes summarizing the experiences and perceptions of clinicians promoting ISS and breastfeeding in the COVID-19 pandemic: Strain on Clinicians Related to Hospital Policies, Coordination, and Capacity; Effects of Isolation for Parentsin Labor and Delivery; ReevaluatingOutpatient Follow-Up Care andSupport; and AdoptingShared Decision-Makingaround ISS andBreastfeeding. CONCLUSIONS: Our results support the need for physical and psychosocial care to reduce crisis-related burnout for clinicians to encourage the continued provision of ISS and breastfeeding education, particularly while navigating capacity constraints. Our findings also suggest that clinicians perceived that parents may require additional support to enhance potentially limited ISS and breastfeeding education. These findings may be used to inform approaches to parental and clinician maternity care support in future public health crises.

Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.

Nutrition Education Programs for Adults with Neurological Diseases Are Lacking: A Scoping Review.

The nutrition recommendation for most common neurological diseases is to follow national dietary guidelines. This is to mitigate malnutrition, reduce the risk of diet-related diseases, and to help manage some common symptoms, including constipation. Nutrition education programs can support people in adhering to guidelines; hence the aim of this scoping review was to explore what programs have been implemented for adults with neurological diseases. We conducted this review according to a published a priori protocol. From 2555 articles screened, 13 were included (dementia n = 6; multiple sclerosis n = 4; stroke survivors n = 2; Parkinson's n = 1). There were no programs for epilepsy, Huntington's, and motor neurone disease. Program duration and number of sessions varied widely; however, weekly delivery was most common. Just over half were delivered by dietitians. Most did not report using a behavior change theory. Commonly used behavior change techniques were instruction on how to perform a behavior, credible source, and behavioral practice/rehearsal. Evidence of nutrition education programs for adults with neurological diseases is lacking. Of those that are published, many do not meet best practice principles for nutrition education regarding delivery, educator characteristics, and evaluation. More programs aligning with best practice principles are needed to assess characteristics that lead to behavior change.

High thermostability improves neutralizing antibody responses induced by native-like HIV-1 envelope trimers.

Soluble HIV-1 envelope glycoprotein (Env) immunogens are a prime constituent of candidate vaccines designed to induce broadly neutralizing antibodies. Several lines of evidence suggest that enhancing Env immunogen thermostability can improve neutralizing antibody (NAb) responses. Here, we generated BG505 SOSIP.v9 trimers, which displayed virtually no reactivity with non-neutralizing antibodies and showed increased global and epitope thermostability, compared to previous BG505 SOSIP versions. Chemical crosslinking of BG505 SOSIP.v9 further increased the melting temperature to 91.3 °C, which is almost 25 °C higher than that of the prototype SOSIP.664 trimer. Next, we compared the immunogenicity of a palette of BG505-based SOSIP trimers with a gradient of thermostabilities in rabbits. We also included SOSIP.v9 proteins in which a strain-specific immunodominant epitope was masked by glycans to redirect the NAb response to other subdominant epitopes. We found that increased trimer thermostability correlated with increased potency and consistency of the autologous NAb response. Furthermore, glycan masking steered the NAb response to subdominant epitopes without decreasing the potency of the autologous NAb response. In summary, SOSIP.v9 trimers and their glycan masked versions represent an improved platform for HIV-1 Env based vaccination strategies.

An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Multivariate Uncertainty in Deep Learning.

Deep learning has the potential to dramatically impact navigation and tracking state estimation problems critical to autonomous vehicles and robotics. Measurement uncertainties in state estimation systems based on Kalman and other Bayes filters are typically assumed to be a fixed covariance matrix. This assumption is risky, particularly for "black box" deep learning models, in which uncertainty can vary dramatically and unexpectedly. Accurate quantification of multivariate uncertainty will allow for the full potential of deep learning to be used more safely and reliably in these applications. We show how to model multivariate uncertainty for regression problems with neural networks, incorporating both aleatoric and epistemic sources of heteroscedastic uncertainty. We train a deep uncertainty covariance matrix model in two ways: directly using a multivariate Gaussian density loss function and indirectly using end-to-end training through a Kalman filter. We experimentally show in a visual tracking problem the large impact that accurate multivariate uncertainty quantification can have on the Kalman filter performance for both in-domain and out-of-domain evaluation data. We additionally show, in a challenging visual odometry problem, how end-to-end filter training can allow uncertainty predictions to compensate for filter weaknesses.

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques.

There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

The RNA sensor MDA5 detects SARS-CoV-2 infection.

Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection. We report that the cytosolic RNA sensor MDA5 was required for type I and III IFN induction in the lung cancer cell line Calu-3 upon SARS-CoV-2 infection. Type I and III IFN induction further required MAVS and IRF3. In contrast, induction of IL6 and TNF was independent of the MDA5-MAVS-IRF3 axis in this setting. We further found that SARS-CoV-2 infection inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 as a cellular sensor for SARS-CoV-2 infection that induced type I and III IFNs.

Systematic review: Automated vehicles and services for people with disabilities.

People with disabilities face many travel barriers. Autonomous vehicles and services may be one solution. The purpose of this project was to conduct a systematic review of the grey and scientific literature on autonomous vehicles for people with disabilities. Scientific evidence (n = 35) was limited to four observational studies with a very low level of evidence, qualitative studies, reviews, design and model reports, and policy proposals. Literature on older adults was most prevalent. Grey literature (n = 37) spanned a variety of media and sources and focuses on a variety of disability and impairment types. Results highlight opportunities and barriers to accessible and usable AVs and services, outline research gaps to set a future research agenda, and identify implications for policy and knowledge translation. People with disabilities are a diverse group, and accessible and usable design solutions will therefore need to be tailored to each group's needs, circumstances, and preferences. Future research in diverse disability groups should include more participatory action design and engineering studies and higher quality, prospective experimental studies to evaluate outcomes of accessible and usable AV technology. Studies will need to address not only all vehicle features but also the entire travel journey.

The Adipose Tissue-Derived Secretome (ADS) in Obesity Uniquely Induces L-Type Amino Acid Transporter 1 (LAT1) and mTOR Signaling in Estrogen-Receptor-Positive Breast Cancer Cells.

Obesity increases the risk of postmenopausal breast cancer (BC). This risk is mediated by obesity-induced changes in the adipose-derived secretome (ADS). The pathogenesis of BC in obesity is stimulated by mTOR hyperactivity. In obesity, leucine might support mTOR hyperactivity. Leucine uptake by BC cells is through L-Type Amino Acid Transporter 1 (LAT1). Our objective was to link obesity-ADS induction of LAT1 to the induction of mTOR signaling. Lean- and obese-ADS were obtained from lean and obese mice, respectively. Breast ADS was obtained from BC patients. Estrogen-receptor-positive BC cells were stimulated with ADS. LAT1 activity was determined by uptake of 3H-leucine. The LAT1/CD98 complex, and mTOR signaling were assayed by Western blot. The LAT1 antagonists, BCH and JPH203, were used to inhibit LAT1. Cell migration and invasion were measured by Transwell assays. The results showed obese-ADS-induced LAT1 activity by increasing transporter affinity for leucine. Consistent with this mechanism, LAT1 and CD98 expression were unchanged. Induction of mTOR by obese-ADS was inhibited by LAT1 antagonists. Breast ADS from patients with BMIs > 30 stimulated BC cell migration and invasiveness. Collectively, our findings show that obese-ADS induction of LAT1 supports mTOR hyperactivity in luminal BC cells.