Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

The ATP-Binding Cassette Gene ABCF1 Functions as an E2 Ubiquitin-Conjugating Enzyme Controlling Macrophage Polarization to Dampen Lethal Septic Shock.

Sepsis is a bi-phasic inflammatory disease that threatens approximately 30 million lives and claims over 14 million annually, yet little is known regarding the molecular switches and pathways that regulate this disease. Here, we have described ABCF1, an ATP-Binding Cassette (ABC) family member protein, which possesses an E2 ubiquitin enzyme activity, through which it controls the Lipopolysaccharide (LPS)- Toll-like Receptor-4 (TLR4) mediated gram-negative insult by targeting key proteins for K63-polyubiquitination. Ubiquitination by ABCF1 shifts the inflammatory profile from an early phase MyD88-dependent to a late phase TRIF-dependent signaling pathway, thereby regulating TLR4 endocytosis and modulating macrophage polarization from M1 to M2 phase. Physiologically, ABCF1 regulates the shift from the inflammatory phase of sepsis to the endotoxin tolerance phase, and modulates cytokine storm and interferon-ß (IFN-ß)-dependent production by the immunotherapeutic mediator, SIRT1. Consequently, ABCF1 controls sepsis induced mortality by repressing hypotension-induced renal circulatory dysfunction.

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma.

Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.

The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ.

Twinkle is the ring-shaped replicative helicase within the human mitochondria with high homology to bacteriophage T7 gp4 helicase-primase. Unlike many orthologs of Twinkle, the N-terminal domain (NTD) of human Twinkle has lost its primase activity through evolutionarily acquired mutations. The NTD has no demonstrated activity thus far; its role has remained unclear. Here, we biochemically characterize the isolated NTD and C-terminal domain (CTD) with linker to decipher their contributions to full-length Twinkle activities. This novel CTD construct hydrolyzes ATP, has weak DNA unwinding activity, and assists DNA polymerase γ (Polγ)-catalyzed strand-displacement synthesis on short replication forks. However, CTD fails to promote multikilobase length product formation by Polγ in rolling-circle DNA synthesis. Thus, CTD retains all the motor functions but struggles to implement them for processive translocation. We show that NTD has DNA-binding activity, and its presence stabilizes Twinkle oligomerization. CTD oligomerizes on its own, but the loss of NTD results in heterogeneously sized oligomeric species. The CTD also exhibits weaker and salt-sensitive DNA binding compared with full-length Twinkle. Based on these results, we propose that NTD directly contributes to DNA binding and holds the DNA in place behind the central channel of the CTD like a "doorstop," preventing helicase slippages and sustaining processive unwinding. Consistent with this model, mitochondrial single-stranded DNA-binding protein (mtSSB) compensate for the NTD loss and partially restore kilobase length DNA synthesis by CTD and Polγ. The implications of our studies are foundational for understanding the mechanisms of disease-causing Twinkle mutants that lie in the NTD.

Transcriptional network analysis of peripheral blood leukocyte subsets in multiple sclerosis identifies a pathogenic role for a cytotoxicity-associated gene network in myeloid cells.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting predominantly adults. It is a complex disease associated with both environmental and genetic risk factors. Although over 230 risk single-nucleotide polymorphisms have been associated with MS, all are common human variants. The mechanisms by which they increase the risk of MS, however, remain elusive. We hypothesized that a complex genetic phenotype such as MS could be driven by coordinated expression of genes controlled by transcriptional regulatory networks. We, therefore, constructed a gene coexpression network from microarray expression analyses of five purified peripheral blood leukocyte subsets of 76 patients with relapsing remitting MS and 104 healthy controls. These analyses identified a major network (or module) of expressed genes associated with MS that play key roles in cell-mediated cytotoxicity which was downregulated in monocytes of patients with MS. Manipulation of the module gene expression was achieved in vitro through small interfering RNA gene knockdown of identified drivers. In a mouse model, network gene knockdown modulated the autoimmune inflammatory MS model disease-experimental autoimmune encephalomyelitis. This research implicates a cytotoxicity-associated gene network in myeloid cells in the pathogenesis of MS.

Outcome measures in pediatric chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. METHODS: This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. RESULTS: Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. DISCUSSION: Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.

Predicting higher child BMI z-score and obesity incidence in Malaysia: a longitudinal analysis of a dynamic cohort study.

BACKGROUND: To target public health obesity prevention, we need to predict who might become obese i.e. predictors of increasing Body Mass Index (BMI) or obesity incidence. Predictors of incidence may be distinct from more well-studied predictors of prevalence, therefore we explored parent, child and sociodemographic predictors of child/adolescent BMI z-score and obesity incidence over 5 years in Malaysia. METHODS: The South East Asia Community Observatory in Segamat, Malaysia, provided longitudinal data on children and their parents (n = 1767). Children were aged 6-14 years at baseline (2013-14) and followed up 5 years later. Linear multilevel models estimated associations with child BMI z-score at follow-up, adjusting for baseline BMI z-score and potential confounders. Predictors included parent cardiometabolic health (overweight/obesity, central obesity, hypertension, hyperglycaemia), and socio-demographics (ethnicity, employment, education). Logistic multilevel models explored predictors of obesity incidence. RESULTS: Higher baseline BMI z-score predicted higher follow-up BMI z-score both in childhood to late adolescence (0.60; 95% CI: 0.55, 0.65) and early to late adolescence (0.76; 95% CI: 0.70, 0.82). There was inconsistent evidence of association between child BMI z-score at follow-up with parent cardiometabolic risk factors independent of baseline child BMI z-score. For example, maternal obesity, but not overweight, predicted a higher BMI z-score in childhood to early adolescence (overweight: 0.16; 95% CI: -0.03, 0.36, obesity: 0.41; 95% CI: 0.20, 0.61), and paternal overweight, but not obesity, predicted a higher BMI z-score in early to late adolescence (overweight: 0.22; 95% CI: 0.01, 0.43, obesity: 0.16; 95% CI: -0.10, 0.41). Parental obesity consistently predicted five-year obesity incidence in early to late adolescence, but not childhood to early adolescence. An adolescent without obesity at baseline with parents with obesity, had 3-4 times greater odds of developing obesity during follow-up (incidence OR = 3.38 (95% CI: 1.14-9.98, mother) and OR = 4.37 (95% CI 1.34-14.27, father) respectively). CONCLUSIONS: Having a higher BMI z-score at baseline was a stronger predictor of a higher BMI z-score at follow-up than any parental or sociodemographic factor. Targeting prevention efforts based on parent or sociodemographic factors is unwarranted but early childhood remains a key period for universal obesity prevention.

CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa.

BACKGROUND: Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. OBJECTIVES: We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324. METHODS: Biopsy and peripheral blood samples were taken from participants of two studies: 2018.206, a noninterventional research study of systemic and dermal neutrophils and inflammatory markers in patients with neutrophilic skin diseases, and CSL324_1001 (ACTRN12616000846426), a single-dose ascending and repeated dose, randomized, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy adult subjects. Ex vivo experiments were performed, including neutrophil enumeration and immunophenotyping, migration, receptor occupancy and transcriptome analysis. RESULTS: The number of cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) was significantly higher in HS lesions compared with biopsies from healthy donors (HDs) (P < 0.0001 and P = 0.0223, respectively). In peripheral blood samples, mean neutrophil counts were significantly higher in patients with HS than in HDs (2.98 vs. 1.60 × 109 L-1, respectively; P = 8.8 × 10-4). Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher mean CXCR1 on the surface of neutrophils in patients with HS (24453.20 vs. 20798.47 for HD; P = 0.03). G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from patients with HS compared with HDs (mean 6.61 vs. 3.84 pg mL-1, respectively; P = 0.013). Administration of CSL324 inhibited G-CSF-induced transcriptional changes in HDs, similar to those observed in the HS cohort, as highlighted by expression changes in genes related to neutrophil migratory capacity. CONCLUSIONS: Data suggest that neutrophils contribute to HS pathophysiology and that neutrophils are increased in lesions due to an increase in G-CSF-driven migration. CSL324 counteracted G-CSF-induced transcriptomic changes and blocked neutrophil migration by reducing cell-surface levels of chemokine receptors.

Characteristics of Individuals Seen as Sources of Social Support in Populations at Increased Risk for HIV.

Access to social support from one's social network can serve as a protective factor against HIV infection; however, research exploring the availability of support in diverse populations that include high proportions of people at increased risk for HIV and the characteristics of network members associated with access to such support is limited. Multi-level dyadic analyses of social network data collected from women at risk for HIV and their network members reveal which individual and relationship characteristics of network members are associated with providing emotional, material, and/or health informational support. Results indicate that access to all three types of support was associated with a network member being a friend, a member of a participant's 'core' group, someone whose opinion matters to the respondent, and the respondent trusting them. These findings have implications for interventions designed to increase access to support among individuals at risk for HIV.

Protocol to evaluate the effectiveness and cost-effectiveness of an environmental nutrition and physical activity intervention in nurseries (Nutrition and Physical Activity Self Assessment for Child Care - NAP SACC UK): a multicentre cluster randomised controlled trial.

BACKGROUND: One in seven UK children have obesity when starting school, with higher prevalence associated with deprivation. Most pre-school children do not meet UK recommendations for physical activity and nutrition. Formal childcare settings provide opportunities to deliver interventions to improve nutritional quality and physical activity to the majority of 3-4-year-olds. The nutrition and physical activity self-assessment for childcare (NAP SACC) intervention has demonstrated effectiveness in the USA with high acceptability in the UK. The study aims to evaluate the effectiveness and cost-effectiveness of the NAP SACC UK intervention to increase physical activity, reduce sedentary time and improve nutritional intake. METHODS: Multi-centre cluster RCT with process and economic evaluation. Participants are children aged 2 years or over, attending UK early years settings (nurseries) for ≥ 12 h/week or ≥ 15 h/week during term time and their parents, and staff at participating nurseries. The 12-month intervention involves nursery managers working with a Partner (public health practitioner) to self-assess policies and practices relating to physical activity and nutrition; nursery staff attending one physical activity and one nutrition training workshop and setting goals to be achieved within 6 months. The Partner provides support and reviews progress. Nursery staff receive a further workshop and new goals are set, with Partner support for a further 6 months. The comparator is usual practice. Up to 56 nurseries will be stratified by area and randomly allocated to intervention or comparator arm with minimisation of differences in level of deprivation. PRIMARY OUTCOMES: accelerometer-assessed mean total activity time on nursery days and average total energy (kcal) intake per eating occasion of lunch and morning/afternoon snacks consumed within nurseries. SECONDARY OUTCOMES: accelerometer-assessed mean daily minutes of moderate-to-vigorous physical activity and sedentary time per nursery day, total physical activity on nursery days compared to non-nursery days, average serving size of lunch and morning/afternoon snacks in nursery per day, average percentage of core and non-core food in lunch and morning/afternoon snacks, zBMI, proportion of children who are overweight/obese and child quality-of-life. A process evaluation will examine fidelity, acceptability, sustainability and context. An economic evaluation will compare costs and consequences from the perspective of the local government, nursery and parents. TRIAL REGISTRATION: ISRCTN33134697, 31/10/2019.

Snacking and anxiety during the coronavirus disease (COVID-19) pandemic: A prospective cohort study.

Anxiety and snacking increased during the initial coronavirus disease 2019 (COVID-19) lockdowns, but it remains unknown whether this change in snacking persisted and if it related to anxiety levels. We used prospective data to examine changes in snacking frequency from t1 (eased restrictions in England in May-June 2020) to t2 (national lockdown in December 2020-March 2021), the association of anxiety (assessed by the Generalised Anxiety Disorder-7 questionnaire at t1) with the snacking change, and the mediating and moderating effects of disinhibition and flexible restraint (assessed by the Three Factor Eating Questionnaire in 2016-17). Analyses including 2128 adults (mean age 28.4 y) residing in England from the Avon Longitudinal Study of Parents and Children showed that snacking frequency increased over time (mean change 1.23 (95% CI 0.81, 1.65) snacks/wk). Linear regressions of snacking adjusted for sociodemographic covariates showed that having clinical levels of generalised anxiety at t1, versus not, was associated with 1.22 (95% CI 0.07, 2.37) more snacks/wk at t2. Disinhibition partially mediated the association between Generalised Anxiety Disorder and snacking (ßindirect = 0.15, 95% CI 0.01, 0.32), while there was no evidence that flexible restraint moderated the association (ß = 0.05, 95% CI -0.57, 0.66). Our longitudinal findings highlight a detrimental anxiety-snacking association partly operating via disinhibition, suggesting future research could target mitigating anxiety and disinhibited eating behaviours to benefit diet-related outcomes following the pandemic.

Ultrasound shear wave elastography in pediatric stricturing small bowel Crohn disease: correlation with histology and second harmonic imaging microscopy.

BACKGROUND: Preclinical animal as well as small exploratory ex vivo and in vivo human studies have suggested that bowel wall shear wave speed (SWS) measurements may be a noninvasive biomarker of intestinal damage. OBJECTIVE: To evaluate the relationships between bowel wall stiffness, measured using ultrasound shear wave elastography (SWE), and intestinal fibrosis and smooth muscle hypertrophy as determined by (1) histology and (2) second harmonic imaging microscopy (SHIM) in surgically resected ileal strictures from pediatric Crohn disease patients. MATERIALS AND METHODS: Nineteen pediatric Crohn disease patients with symptomatic ileal strictures underwent research ultrasound examinations before surgical resection between December 2017 and September 2020. Two-dimensional SWE was performed through the area of the most severe stenosis, with measurements obtained from the bowel wall at the 9:00, 12:00 and 3:00 o'clock locations with 0%, 10% and 20% abdominal strain. Overall right lower quadrant stiffness also was documented. Median bowel wall and overall right lower quadrant SWS measurements were correlated with bowel wall histological scores of inflammation, fibrosis and smooth muscle proliferation as well as SHIM collagen signal. RESULTS: Diagnostic ultrasound SWE imaging was obtained from 18 participants. The median age was 16.8 years. There were negative correlations between histological mucosal active inflammation and both bowel wall SWS with 10% abdominal strain (r=-0.50, P = 0.04) and overall right lower quadrant SWS with 20% abdominal strain (r=-0.69, P = 0.002). There were positive correlations between histological muscularis propria inner layer smooth muscle hypertrophy and both median bowel wall SWS with 10% abdominal strain (r = 0.72, P = 0.002) and overall right lower quadrant SWS with 20% abdominal strain (r = 0.71, P = 0.002). There were no associations between ultrasound stiffness metrics and bowel wall SHIM collagen measurements. CONCLUSION: Bowel wall and overall right lower quadrant ultrasound stiffness measurements correlate with mucosal active inflammation and muscularis propria smooth muscle hypertrophy in pediatric stricturing ileal Crohn disease, but not with intestinal fibrosis.

The presence, action, and influence of bystanders who witness sexual harassment against medical students.

PURPOSE: Sexual harassment (SH) is a widespread problem in academia, with a disproportionate impact on female medical students and those who experience marginalization via multiple systems of oppression (e.g. racism, heterosexism). Bystander intervention education is a potential approach which frames violence as a community issue where all members have a role to play in response and prevention. This study assessed the presence and influence of bystanders in SH situations for students at two medical schools. MATERIALS AND METHODS: Data came from a larger U.S. campus climate study administered online in 2019 and 2020. The sample included 584 students who responded to validated survey questions about sexual harassment experiences, bystander behavior, disclosure, perceptions of the university response to SH, and demographics. RESULTS: More than one-third of respondents experienced some form of SH by a faculty/staff member. Bystanders were present for more than half of these incidents, yet they rarely intervened. When bystanders intervened, people were more likely to disclose an incident than not. CONCLUSIONS: The results indicate that there are many missed opportunities for intervention and given the profound impact that SH has on the well-being of medical students, continued work is needed to determine effective intervention and prevention methods.[Box: see text].

Influence of sampling frequency and estimation method on phosphorus load uncertainty in the Western Lake Erie Basin, Ohio, USA.

Accurate estimates of nutrient loads are necessary to identify critical source areas and quantify the impact of management practices on pollutant export. Previous studies have investigated nutrient load estimate uncertainty, but they often focus on nutrient loads estimated using an interpolation method for large-scale watersheds with short-term datasets. The study objective was to quantify uncertainty in soluble reactive phosphorus (SRP), total phosphorus (TP), and suspended solids (SS) load estimates from two small (<103 km2) agricultural watersheds in the western Lake Erie Basin resulting from different sampling frequencies. Each watershed had high temporal resolution datasets of discharge (15 min) and nutrient concentration (1 to 3 samples per day) collected over a 30-year period (1990-2020). Firstly, SRP, TP, and SS loads were calculated using the high temporal resolution datasets, which was assumed as "true loads". Secondly, the high temporal concentration data were decomposed to semiweekly, weekly, biweekly, and monthly sampling and annual loads were estimated using four common load estimation methods to assess the effect of sampling frequency and load estimation method on load estimate error. Across the four different methods, the composite method had the lowest relative root mean square and absolute bias, but the rectangular interpolation method was the most precise. However, even with semiweekly sampling, the composite method resulted in an unacceptable level of precision (average imprecision = 39 %), while the interpolation method resulted in an unacceptable bias (average absolute bias = 16 %). Because neither method could provide acceptable accuracy and precision at the lowest decrease in sampling (e.t. semiweekly sampling), continued daily sampling is recommended in these watersheds.

The impact of religiousness and beliefs about mental illness on help-seeking behaviors of Muslim Americans.

BACKGROUND: In addition to the typical challenges of daily life, Muslim Americans have experienced high levels of stress and clinical disorders relating to discrimination from the 9/11 attacks and ongoing political stigma. Despite mounting mental health concerns, Muslim Americans have encountered multifaceted barriers to accessing mental health services and remain underserved. AIMS: This study sought to explore the relationship between religiousness and beliefs about mental illness among Muslim Americans to predict their clinical help-seeking attitudes. MATERIALS AND METHODS: The present study gathered a nationwide sample of Muslim Americans through online data collection to assess how the relationship between religiousness and help-seeking was mediated by acculturation and biomedical beliefs about mental illness. RESULTS: Analyses found that Islamic religiousness and biomedical beliefs predicted more openness to mental health treatment. Additional analyses found that integration with mainstream culture was correlated with higher confidence in services. DISCUSSION: The findings of this study provide clinicians a nuanced understanding of how biological beliefs about mental illness may align with Islamic spiritual values and foster culturally responsive communication and healthcare. Barriers to treatment may be addressed for males and other underserved demographics through integrated treatment that recognizes their understandings of health, illness, and treatment. CONCLUSION: Overall, results of the study provide support for recognizing religion along with demographic background as a cultural consideration to enhance treatment efficacy.

Someone you can count on: Examining the mediating effect of social support on economic abuse and depression.

The aim of this study was to examine whether social support mediated the relationship between economic abuse, a form of intimate partner violence, and mental health, specifically depression, among pregnant women. This cross-sectional study used a sample of 193 pregnant women living in the United States who participated in an online Qualtrics panel survey in January 2021. Hayes Process Macro was used to assess a mediation model. Economic abuse was associated with increased odds of depressive sympto ms and fewer perceived social supports. Social support mediated the relationship between economic abuse and depression. Implications for research, policy, and practice are discussed. Notably, research focused on economic abuse and efforts to respond to it need to pay particularly close attention to the role that social supports may play in survivor's overall well-being, as well as the impact that economic abuse may have on survivors' perceptions of social support. This may be particularly true for pregnant women experiencing economic abuse for whom social support-related interventions have yielded positive health outcomes.

Community Gardens: A Catalyst for Community Change.

Community gardens are increasing in popularity and are associated with extensive physical and mental health benefits, increased access to fresh produce, and increased social connections. However, evidence is primarily from research in urban and school settings, and little is known about the role of community gardens in rural settings as part of policy, systems, and environmental (PSE) changes to promote health. This study explores the implementation of community gardens as part of an obesity prevention project, titled Healthier Together (HT), in five rural Georgia counties with limited food access and high obesity prevalence (>40%) using a mixed-methods research design that included data from project records, a community survey, interviews, and focus groups with county coalition members. Nineteen community gardens were implemented across five counties, 89% distributed produce direct to consumers, and 50% were integrated into the food system. Few (8.3%) of the survey respondents (n = 265) identified gardens as a food source, but 21.9% reported using an HT garden in the past year. Themes emerging from interviews (n = 39) and five focus groups suggested community gardens were a catalyst for broader community health change by increasing awareness of the value and absence of healthy food and generating excitement for future PSE initiatives to more comprehensively address food and physical activity access. Practitioners should consider placement of rural community gardens to optimize access to and distribution of produce as well as communication and marketing strategies to increase engagement and leverage gardens as gateways for PSE approaches to improve rural health.

Who Can I Ask? Who Would I Tell? An Egocentric Network Analysis Among a Sample of Women At-Risk to Explore Anticipated Advice Seeking and Disclosure Around Pre-exposure Prophylaxis (PrEP).

Pre-Exposure Prophylaxis (PrEP) health campaigns invite women to talk with their provider, partner, and peers about PrEP, though they do not offer specific guidance about who and how to engage. This study uses egocentric network methods in a sample of women at risk for HIV to understand what characteristics of women (egos), their networks, and network members (alters) were associated with anticipated PrEP advice-seeking and anticipated PrEP disclosure. Multivariable generalized linear mixed models revealed that women often consider close, supportive, and trusted network members as PrEP discussants while ego-level, network-level, and cross-level interactions depict the complexity of anticipated network activation. Findings highlight the importance of considering women at risk for HIV in a broader social context. Anticipated advice-seeking and disclosure related to PrEP were associated but distinct forms of network activation, which highlights the need to develop specific recommendations about who and how women should engage with their networks around PrEP.

The More You Know: Sexual Knowledge as a Predictor of Sexual Well-Being.

The World Health Organization (WHO), defines sexual well-being as a multifaceted construct, consisting of more than absence of disease or experiences of pleasure. Further, the WHO suggests that sexual knowledge should contribute to sexual well-being. We examined the relationship between personal sexual knowledge-knowing one's individual sexual preferences-and sexual health knowledge-awareness of reproduction, contraception, and diseases-and sexual well-being, comprised of sexual satisfaction, assertiveness, and competence in a sample of 484 emerging adults. Personal sexual knowledge but not sexual health knowledge, was a significant predictor of sexual well-being. Further, this relationship was moderated by gender (stronger for women) but not prior sex education.

Prospective association between a Mediterranean-style dietary score in childhood and cardiometabolic risk in young adults from the ALSPAC birth cohort.

PURPOSE: To investigate the prospective association between a children's relative Mediterranean-style diet score (C-rMED) in childhood and a Cardiometabolic Risk (CMR) score in adolescence/young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: A C-rMED was calculated at 7, 10 and 13 years from diet diary data. Anthropometric and biochemical data at 17 (N = 1940) and 24 years (N = 1961) were used to calculate CMR scores (sum of sex-specific log-transformed z-scores from triacylglycerol, HDL cholesterol, LDL cholesterol, mean arterial blood pressure, homeostatic model assessment of insulin resistance (HOMA-IR) and fat mass index (FMI)). Adjusted logistic regression models examined associations between C-rMED (categorical and 2-unit increments) and a high CMR score (≥ 80th percentile) and individual CMR components (≥ 80th percentile). RESULTS: A high C-rMED at 13 was associated with a 32% (OR 0.68 (95% CI: 0.49, 0.94)) decreased adjusted odds of having a high CMR score at 24 years, compared to participants with a low C-rMED. No associations were evident at other ages. Tracking of the C-rMED across the three ages showed a stronger negative association between C-rMED and CMR at 24 years when children had at least two high C-rMED scores from 7 to 13 years (adjusted OR: 0.49, 95% CI: 0.29, 0.85), compared to all low scores. FMI and HOMA-IR were the main CMR components contributing to this association. CONCLUSION: Higher Mediterranean-style diet scores in early adolescence were associated with a better CMR profile in young adults (24 year olds). This underscores the importance of establishing healthy eating habits early in life for future cardiometabolic health.