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BackgroundDiscrimination is a recognized psychosocial stressor that has been linked to various negative health outcomes. This study explored the impact of discrimination on gut health, specifically focusing on microbiome changes, predicted metagenomic differences, transcriptomic profiles, and the potential for using a multi-omic approach to predict discrimination to identify discrimination status for an individual. Methods: We conducted a comprehensive investigation involving male and premenopausal female participants, using the Everyday Discrimination Scale to classify them into either high or low discrimination. Multiple questionnaires were administered to evaluate participants’ physiological, psychological, and perceived stressors. Two diet questionnaires were also administered. Stool samples were collected for microbiome analysis and RNA sequencing. Microbial composition changes were analyzed using the Shannon index and Chao1 richness estimator for alpha diversity and the Aitchison distance metric for beta diversity. Differential abundance was evaluated using MaAsLin2, followed by metatranscriptomics sequencing and annotation. A multi-omic approach utilizing random forest was used to assess the predictability of discrimination.ResultsThe study results showed that high discrimination was linked to higher gut microbiome species richness (Chao1, p = 0.02) and significant beta diversity differences (p = 0.04). Prevotella and Ruminococcaceae were both less abundant in the high discrimination group. High discrimination participants also reported higher levels of depression, anxiety, perceived stress, early life adversity, visceral sensitivity, and neuroticism than those in the low discrimination group. Gene expression analysis revealed distinctive patterns, with significant changes in genes associated with environmental sensing (two-component system) and metabolic pathways. In a plot comparing gene transcription to DNA content, certain genes showed higher expression levels in participants who experienced both high and low levels of discrimination. Our random forest classifier demonstrated the capability to accurately differentiate individuals with high and low discrimination in our training cohort (AUC = 0.91).ConclusionThese findings illuminate the substantial impact of discrimination on gut health, encompassing microbiome composition, gene expression, and functional pathways. These findings suggest that discrimination is associated with internal biological changes that can be associated with negative health outcomes, opening research to examine novel pathways that can be used to mitigate the negative health effects of discrimination.

Higher education institutions can play an essential role in preparing students to participate in movements for just and sustainable food systems change. For the past two decades, many United States land-grant universities (LGUs) have developed food systems education (FSE) courses. This study examined the extent to which FSE courses employ four capacities deemed crucial by the FSE literature: multidimensional approaches, interdisciplinarity, centering equity, and training students to take action in food systems. The syllabi of 171 undergraduate courses at 20 LGUs were obtained by contacting instructors, and their course descriptions and learning outcomes were analyzed. This subset of LGUs were identified from the membership list of the Menus of Change University Research Collaborative (MCURC), a nationwide network of colleges using campus dining halls and classrooms as living laboratories for food systems change. Most course descriptions and learning outcomes exhibited multidimensional approaches and interdisciplinarity. However, many failed to incorporate teaching content and practices that help students critically examine equity and social justice issues in food systems, or engage in transformative change. LGUs have both the resources and urgent responsibility to empower students to be part of movements to transform unjust, unsustainable food systems. The findings of this study, and an accompanying open-access syllabus website, aim to accelerate the development of FSE curricula that prepare students to change food systems.

Objective: To help inform decisions regarding the equitable implementation of obesity interventions, we examined whether interventions were equitably reaching the most vulnerable communities, identified communities that received fewer interventions than expected, and estimated the effect of ‘dose’ of interventions on obesity prevalence. Methods: We created a database to identify and characterize obesity-related interventions implemented in Los Angeles County from 2005 to 2015 linked to community-level sociodemographic and obesity prevalence data. We ran generalized linear models with a Gamma distribution and log link to determine if interventions were directed toward vulnerable communities and to identify communities that received fewer interventions than expected. We ran fixed-effects models to estimate the association between obesity prevalence and intervention strategy count among preschool-aged children enrolled in the Special Supplemental Nutrition Assistance Program for Women Infants and Children. Results: We found that interventions targeted vulnerable communities with high poverty rates and percentages of minority residents. The small cluster of communities that received fewer interventions than expected tended to have poor socioeconomic profiles. Communities which received more intervention strategies saw greater declines in obesity prevalence (β = -0.023; 95 % CI: −0.031, −0.016). Conclusions: It is important to determine if interventions are equitably reaching vulnerable populations as resources to tackle childhood obesity become available. Evaluating the population impact of multiple interventions implemented simultaneously presents methodological challenges in measuring intervention dose and identifying cost-effective strategies. Addressing these challenges must be an important research priority as community-wide interventions involve multiple intervention strategies to reduce health disparities.

Abstract Background The field of the commercial determinants of health (CDOH) refers to the commercial products, pathways and practices that may affect health. The field is growing rapidly, as evidenced by the WHO programme on the economic and commercial determinants of health and a rise in researcher and funder interest. Systematic reviews (SRs) and evidence synthesis more generally will be crucial tools in the evolution of CDOH as a field. Such reviews can draw on existing methodological guidance, though there are areas where existing methods are likely to differ, and there is no overarching guidance on the conduct of CDOH-focussed systematic reviews, or guidance on the specific methodological and conceptual challenges. Methods/results CODES provides guidance on the conduct of systematic reviews focussed on CDOH, from shaping the review question with input from stakeholders, to disseminating the review. Existing guidance was used to identify key stages and to provide a structure for the guidance. The writing group included experience in systematic reviews and other forms of evidence synthesis, and in equity and CDOH research (both primary research and systematic reviews). Conclusions This guidance highlights the special methodological and other considerations for CDOH reviews, including equity considerations, and pointers to areas for future methodological and guideline development. It should contribute to the reliability and utility of CDOH reviews and help stimulate the production of reviews in this growing field.

Cyclin‐dependent kinases (CDKs), together with their cyclin partners, are the master cell cycle regulators. Remarkably, the cyclin family was extended to include atypical cyclins, characterized by distinctive structural features, but their partner CDKs remain elusive. Here, we conducted a yeast two‐hybrid screen to identify new atypical cyclin–CDK complexes. We identified 10 new complexes, including a complex between CDK6 and cyclin I (CCNI), which was found to be active against retinoblastoma protein. CCNI upregulation increased the proliferation of breast cancer cells in vitro and in vivo, with a magnitude similar to that seen upon cyclin D upregulation, an effect that was abrogated by CDK6 silencing or palbociclib treatment. In line with these findings, CCNI downregulation led to a decrease in cell number and a reduction in the percentage of cells reaching S phase. Finally, CCNI upregulation correlated with the high expression of E2F target genes in large panels of cancer cell lines and tissue samples from breast cancer patients. In conclusion, we unveil CCNI as a new player in the pathways that activate CDK6, enriching the wiring of cell cycle control.

Abstract Background The aim of this study was to critically analyse information concerning the relationship between alcohol and food consumption provided via alcohol industry (AI) funded and non-AI-funded health-oriented websites, to determine the role it plays within the alcohol information space, and how this serves the interests of the disseminating organisations. Methods Information on food as a harm reduction measure while drinking alcohol was extracted from 15 AI websites and websites of AI-funded corporate social responsibility (CSR) organisations. As a comparison group, non-AI-funded health websites were also searched (n = 16 websites with food and alcohol-related content). Information was included from webpage content and associated downloadable documents. Critical discourse analysis (CDA) was adopted to allow the texts analysed to be situated within the broader political and social context. Analysis was carried out iteratively, involving continuous comparison within and between websites. Discursive themes were identified by three researchers. Identified discursive elements were discussed to reach a consensus, and a final coding framework was then developed. “Tone” analysis was used to assess whether the overall tone within individual websites was considered to be pro-alcohol consumption, neutral or discouraging of alcohol consumption. Results There were some commonalities across AI and non-AI-funded websites, whereby both appeared to normalise alcohol consumption and to encourage use of food as a measure to enable sustained drinking, to avoid drinking in a way that results in short-term harms, and to prevent or “cure” a hangover. The fact that both AI-funded and non-AI-funded organisations shared many of these narratives is particularly concerning. However, a discourse of food and alcohol that served to promote “moderate” drinking as beneficial to health was used exclusively by AI-funded organisations, focusing on special occasions and individual-blaming. Conclusions Alcohol consumption, including heavy and harmful consumption, is frequently normalised within the online information space. Emphasising food consumption with alcohol may have the effect of supporting consumers to drink for longer periods of time. Health professionals and independent health organisations should review the information they provide in light of our findings and challenge why AI-funded organisations, with a major conflict of interest, and a history of health misinformation, are often given the responsibility for disseminating health information to the public.

Abstract Background There is an extensive body of research demonstrating that trade and globalisation can have wide-ranging implications for health. Robust governance is key to ensuring that health, social justice and sustainability are key considerations within trade policy, and that health risks from trade are effectively mitigated and benefits are maximised. The UK’s departure from the EU provides a rare opportunity to examine a context where trade governance arrangements are being created anew, and to explore the consequences of governance choices and structures for health and social justice. Despite its importance to public health, there has been no systematic analysis of the implications of UK trade policy governance. We therefore conducted an analysis of the governance of the UK’s trade policy from a public health and social justice perspective. Results Several arrangements required for good governance appear to have been implemented – information provision, public consultation, accountability to Parliament, and strengthening of civil service capacity. However, our detailed analyses of these pillars of governance identified significant weaknesses in each of these areas. Conclusion The establishment of a new trade policy agenda calls for robust systems of governance. However, our analysis demonstrates that, despite decades of mounting evidence on the health and equity impacts of trade and the importance of strong systems of governance, the UK government has largely ignored this evidence and failed to galvanise the opportunity to include public health and equity considerations and strengthen democratic involvement in trade policy. This underscores the point that the evidence alone will not guarantee that health and justice are prioritised. Rather, we need strong systems of governance everywhere that can help seize the health benefits of international trade and minimise its detrimental impacts. A failure to strengthen governance risks poor policy design and implementation, with unintended and inequitable distribution of harms, and ‘on-paper’ commitments to health, social justice, and democracy unfulfilled in practice. Although the detailed findings relate to the situation in the UK, the issues raised are, we believe, of wider relevance for those with an interest of governing for health in the area of international trade.

Pregnant women have been ubiquitously exposed to pyrethroid pesticides. Previous studies, mainly based on third trimester measurements of maternal urinary pyrethroid metabolites, have reported inconsistent findings in the effects of prenatal pyrethroid exposure on children's neurodevelopmental outcomes. The purpose of this study was to clarify if pyrethroid exposure during the entire three trimesters of pregnancy may be associated with deleterious effects on infant neurodevelopmental status, particularly at a high dosage of exposure. We measured maternal urinary concentrations of pyrethroid metabolites in all trimesters of pregnancy and assessed children’s neurodevelopment at one year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multiple linear regression models were used to estimate the effects of metabolites (3-PBA, 4 F-3-PBA, cis-DBCA) in each trimester on BSID-III composite scores. Logistic regression analyses were applied to predict developmental delay vs non-delayed status (cut-off composite score of below 80 for developmental delay) based on the maternal levels of pyrethroid metabolites. In the first, second and third trimesters of pregnancy, the detection rates of pyrethroid metabolites were 94.7%, 90.7%, and 89.0%; the 50th percentiles of exposure level were 0.24 μg/g, 0.24 μg/g and 0.21 μg/g for 3-PBA, 0.14 μg/g, 0.17 μg/g and 0.15 μg/g for 4 F-3PBA, 0.21 μg/g, 0.25 μg/g and 0.19 μg/g for cis-DBCA respectively. In the second trimester, 3-PBA was inversely associated with Cognition and Language scores [β = −3.34 (95% CI = −6.11, −0.57) and β = −2.90 (95% CI = −5.20, −0.61), respectively], and significantly increased the risk of Cognition and Language developmental delay [OR= 1.64 (95% CI = 1.03, 2.62) and OR = 1.52 (95% CI = 1.06, 2.19), respectively]; cis-DBCA was inversely associated with Adaptive Behavior scores [β = −0.73 (95% CI = −1.27, −0.19)], and significantly increased the risk of Adaptive Behavior developmental delay [OR= 1.11 (95% CI = 1.02, 1.21)]. When the maternal levels of pyrethroid metabolites were stratified into the regression models according to the 90th percentile of exposure, in the first trimester, Cognition and Motor scores were inversely associated with higher cis-DBCA [β = −7.19 (95% CI = −12.97, −1.41) and β = −8.20 (95% CI = −13.35, −3.05), respectively], Language scores were inversely associated with higher 3-PBA [β = −6.01 (95% CI = −10.96, −1.06)]; in the second trimester, Cognition scores were inversely associated with higher cis-DBCA [β = −6.64 (95% CI = −12.51, −0.76)], Language scores were inversely associated with higher 3-PBA [β = −5.17 (95% CI = −10.07, −0.27)] and cis-DBCA [β = −5.40 (95% CI = −10.28, −0.52)]. We concluded that pyrethroid exposure in the first and second trimesters was associated with poorer infants neurodevelopmental outcomes at one year of age, and these effects were particularly pronounced at high levels of pyrethroid exposure.

Abstract Background Food packages provided by the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) were revised in 2009 to better align them with the Dietary Guidelines for Americans. This study was conducted to evaluate whether the effect of the food package change on childhood obesity varied by the food environment in the neighborhoods where WIC-participating children live. Methods Administrative data from participating children in Los Angeles County, California (2003–2016) were merged with geocoded food vendor information by neighborhood of residence. Obesity risk at age 4 was compared between children receiving old (2003–2009) and new (2010–2016) WIC food packages using sex-stratified Poisson regression models, with interaction terms between WIC package and neighborhood density (number per square mile) of healthy and unhealthy food outlets. Results The new food package was associated with a significant decrease in obesity risk. Among boys, the new food package was associated with 8 to 18% lower obesity risk at all healthy and unhealthy food outlet densities, and the association was not modified by neighborhood food outlet density. Among girls, the association of the new food package with obesity risk was protective in neighborhoods with high healthy and low unhealthy food outlet densities, and adverse in neighborhoods with high unhealthy and low healthy food outlet densities. The effect of the new food package among girls was modified by unhealthy food outlet density, with significantly smaller (p-value = 0.004) decreases in obesity risk observed in neighborhoods with higher unhealthy food outlet density. Conclusions The impact of the food package change was modified by the neighborhood food environment among girls only. Future policy changes should incorporate consideration of ways to mitigate potentially inequitable geographic distribution of the health benefits of policy changes.

Abstract Background The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) changed the food packages provided to its participants in 2009, to better align them with the Dietary Guidelines for Americans. Previous research found that the 2009 WIC food package change was associated with reduced obesity risk, particularly among breastfed infants but also among those who were never breastfed. The objective of this study was to determine if the new child food package introduced in 2009, including more produce and whole grains for 1–4-year old children, was associated with healthier growth trajectories and reduced obesity risk at age 4 years among children who were exclusively formula fed during infancy. Methods Administrative data on WIC-participating children in Los Angeles County, 2003–2016, were used (N = 74,871), including repeated measures of weight and length (or height); child’s age, gender, and race/ethnicity; maternal education and language; and family poverty. Gender-stratified spline mixed models were used to examine weight-for-height z-score (WHZ) growth trajectories from 0 to 4 years and Poisson regression models were used to assess obesity (BMI-for-age > 95th percentile) at age 4. The main independent variable was duration of receipt (dose) of the new child package, categorized as 0, > 0 to

Background and aim For decades, corporations such as the tobacco and fossil fuel industries have used youth education programmes and schools to disseminate discourses, ideas and values favourable to their positions, and to pre-empt regulation that threatens profits. However, there is no systematic research into alcohol industry-funded youth education programmes. This article serves to address this important gap in the literature. Methods Using a discourse theoretical approach informed by poststructural discourse theory and critical discourse analysis, we analysed teaching materials from three school-based youth education initiatives which focus on alcohol consumption and health harms: Drinkaware for Education, The Smashed Project (funded by Diageo), and Talk About Alcohol (Alcohol Education Trust). These materials, some of which are disseminated internationally, are provided to schools through intermediary bodies in receipt of alcohol industry funding. Findings The analysis found that these materials drew from and presented discourses of personal responsibility, moderate alcohol consumption, and involved a narrowing of the problem definition and causes. The locus of the problem is located by the discourses within individuals including youth, with causes of youth alcohol consumption repeatedly presented as peer pressure and ‘poor choices’, with little or no mention of alcohol industry marketing or other practices. All programmes promoted familiarisation and normalisation of alcohol as a ‘normal’ adult consumer product which children must learn about and master how to use responsibly when older. The discourses constructed in these materials closely align with those of other alcohol industry corporate social responsibility discourses which employ selective presentation of harms, including misinformation about cancer, and ambiguous terms such as “responsible drinking”. Furthermore, the role of alcohol price, availability and access, and the impacts of alcohol and the industry on inequities were not articulated within the discourses. The research was limited to an analysis of teaching materials and further research is needed to explore their impact on youth, teachers and wider discourses and social norms. Conclusion Alcohol industry-sponsored youth education programmes serve industry interests and promote moderate consumption while purportedly educating children about harms and influences of alcohol use. There are considerable conflicts of interest in the delivery of alcohol education programmes funded by the alcohol industry and intermediary bodies in receipt of such funding. Alcohol education materials should be developed independent from industry, including funding, and should empower children and young people to understand and think critically about alcohol, including harms and drivers of consumption, and effective interventions needed to protect them and others from alcohol-related harms. Independent organisations can use this analysis to critique their materials to strengthen alignment with meeting student and public health interests. The ongoing exposure of children and young people to such conflicted and misleading materials needs urgent attention from policymakers, practitioners, teachers and parents, and resources dependent on industry support should cease being used in schools.

We are in the midst of an unprecedented public and planetary health crisis. A major driver of this crisis is the current nutrition transition—a product of globalization and powerful multinational food corporations promoting industrial agriculture and the consumption of environmentally destructive and unhealthy ultra-processed and other foods. This has led to unhealthy food environments and a pandemic of diet-related noncommunicable diseases, as well as negative impacts on the biophysical environment, biodiversity, climate, and economic equity. Among migrants from the global south to the global north, this nutrition transition is often visible as dietary acculturation. Yet some communities are defying the transition through selective resistance to globalization by recreating their traditional foods in their new home, and seeking crop species and varieties customarily used in their preparation. These communities include Zapotec migrants from the Central Valleys of the southern Mexican state of Oaxaca living in greater Los Angeles, California. Focusing on the traditional and culturally emblematic beverage tejate, we review data from our research and the literature to outline key questions about the role of traditional foods in addressing the public and planetary health crisis. We conclude that to answer these questions, a transnational collaborative research partnership between community members and scientists is needed. This could reorient public and planetary health work to be more equitable, participatory, and effective by supporting a positive role for traditional foods and minimizing their harms.

Background: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides nutrition assistance to half of infants born in the United States. The nationally representative WIC Infants and Toddler Feeding Practices Study-2 (ITFPS-2) reported a caloric deficit at 7 months among infants receiving WIC mixed feeding packages, suggesting these infants may be at risk for growth deceleration/faltering.Methods: Longitudinal administrative data collected prospectively from WIC participants in Southern California between 2010 and 2019 were used (n = 16,255). Infant lengths and weights were used to calculate weight-for-length (WLZ), weight-for-age (WAZ) and length-for-age (LAZ) z-scores at different time points. Growth deceleration/faltering was determined at 9, 12, 18, and 24 months by the change in z-score from the last measurement taken ≤ 6 months of age. Infant feeding was categorized by the food package (breastfeeding, mixed feeding, and formula feeding) infants received from WIC at 7 months. Poisson regression models were used to evaluate the association between WIC infant package at 7 months and deceleration/faltering at 9, 12, 18, and 24 months.Results: The proportion of infants displaying decelerated/faltering growth was low for all infant food package groups. Receiving the WIC mixed feeding package at 7 months of age was not associated with WLZ, WAZ, and LAZ deceleration/faltering growth.Conclusions: Growth deceleration/faltering rates were very low among WIC participating children in Southern California, highlighting the critical role of nutrition assistance in supporting adequate growth in early childhood.

Despite high rates of housing-cost burden in the United States, little is known regarding its impact on childhood obesity. In this article, we determine whether low-income 2–5-year-olds living in housing-cost burdened households are more likely to be obese and examine the potential moderators and behavioral and psychosocial mediators of this relationship. We used data from a triennial survey (2011, 2014) of a random sample of Los Angeles County participants of the Special Supplemental Nutrition Program for Women, Infants and Children (n = 2307). Logistic regression was used to examine the association between child's obesity status (Body Mass Index for age and sex ≥ 95th percentile) and severe housing-cost burden (finding it very difficult to pay for housing). Mother's depressive symptoms and child's diet and screen time were tested for mediation. We found that 16% of children lived in severe housing-cost burdened households. Severe housing-cost burden was associated with an increase in the odds of childhood obesity [aOR (95%CI) = 1.33 (1.00, 1.78)] and household size moderated this relationship. Child's diet and screen time and mother's depressive symptoms were not mediators. Given the high and vacillating rates of early childhood obesity and the increasing burden of housing costs in low-income populations, there is an urgency to better understand the role of housing-cost burden in epidemiologic investigations of early childhood obesity. Keywords: Pediatric obesity, Housing, Poverty, WIC

Background: Signet ring cell carcinoma (SRCC) is a distinct malignancy occurring across the tubular gastrointestinal tract (tGIT). We comprehensively examined the outcomes of patients diagnosed with SRCC across tGIT. Methods: SRCC and not-otherwise-specified adenocarcinoma (NOS) patients reported to the National Cancer Database from 2004 to 2015 were included. Baseline characteristics, outcomes and site-specific adjusted hazard ratios (aHR) derived from Cox models of SRCC patients were compared to those of NOS patients. Overall survival (OS) was primary endpoint. Results: A total of 41,686 SRCC (4.6%) and 871,373 NOS patients (95.4%) were included. SRCC patients were younger (63.1 ± 14.7 vs. 67.0 ± 13.4 y, p

Protein kinases (PKs) are established gameplayers in biological signalling pathways, and a large body of evidence points to their dysregulation in diseases, in particular cancer, where rewiring of PK networks occurs frequently. Fluorescent biosensors constitute attractive tools for probing biomolecules and monitoring dynamic processes in complex samples. A wide variety of genetically encoded and synthetic biosensors have been tailored to report on PK activities over the last decade, enabling interrogation of their function and insight into their behaviour in physiopathological settings. These optical tools can further be used to highlight enzymatic alterations associated with the disease, thereby providing precious functional information which cannot be obtained through conventional genetic, transcriptomic or proteomic approaches. This review focuses on fluorescent peptide biosensors, recent developments and strategies that make them attractive tools to profile PK activities for biomedical and diagnostic purposes, as well as insights into the challenges and opportunities brought by this unique toolbox of chemical probes.

CDK5/p25 kinase plays a major role in neuronal functions, and is hyperactivated in several human cancers including glioblastoma and neurodegenerative pathologies such as Alzheimer's and Parkinson's. CDK5 therefore constitutes an attractive pharmacological target. Since the successful discovery and development of Roscovitine, several ATP-competitive inhibitors of CDK5 and peptide inhibitors of CDK5/p25 interface have been developed. However, these compounds suffer limitations associated with their mechanism of action and nature, thereby calling for alternative targeting strategies. To date, few allosteric inhibitors have been developed for successful targeting of protein kinases. Indeed, although this latter class of inhibitors are believed to be more selective than compounds targeting the active site, they have proven extremely difficult to identify in high throughput screens. By implementing a fluorescent biosensor that discriminates against ATP-pocket binding compounds to screen for allosteric inhibitors that target conformational activation of CDK5, we have identified a novel family of quinazolinones. Characterization of these hits and several of their derivatives revealed their inhibitory potential toward CDK5 kinase activity in vitro and to inhibit glioblastoma cell proliferation. The quinazolinone derivatives described in this study are the first small molecules reported to target CDK5 at a site other than the ATP pocket, thereby constituting attractive leads for glioblastoma therapeutics and providing therapeutic perspectives for neurodegenerative diseases. These compounds offer alternatives to conventional ATP-competitive inhibitors or peptides targeting CDK5/p25 interface with the potential of bypassing their limitations.

Abstract Background Immigrants to the United States are usually healthier than their U.S.-born counterparts, yet the health of immigrants declines with duration of stay in the U.S. This pattern is often seen for numerous health problems such as obesity, and is usually attributed to acculturation (the adoption of “American” behaviors and norms). However, an alternative explanation is secular trends, given that rates of obesity have been rising globally. Few studies of immigrants are designed to distinguish the effects of acculturation versus secular trends, in part because most studies of immigrants are cross-sectional, lack baseline data prior to migration, and do not have a comparison group of non-migrants in the country of origin. This paper describes the Health of Philippine Emigrants Study (HoPES), a study designed to address many of these limitations. Methods HoPES is a dual-cohort, longitudinal, transnational study. The first cohort consisted of Filipinos migrating to the United States (n = 832). The second cohort consisted of non-migrant Filipinos who planned to remain in the Philippines (n = 805). Baseline data were collected from both cohorts in 2017 in the Philippines, with follow-up data collection planned over 3 years in either the U.S. for the migrant cohort or the Philippines for the non-migrant cohort. At baseline, interviewers administered semi-structured questionnaires that assessed demographic characteristics, diet, physical activity, stress, and immigration experiences. Interviewers also measured weight, height, waist and hip circumferences, blood pressure, and collected dried blood spot samples. Discussion Migrants enrolled in the study appear to be representative of recent Filipino migrants to the U.S. Additionally, migrant and non-migrant study participants are comparable on several characteristics that we attempted to balance at baseline, including age, gender, and education. HoPES is a unique study that approximates a natural experiment from which to study the effects of immigration on obesity and other health problems. A number of innovative methodological strategies were pursued to expand the boundaries of current immigrant health research. Key to accomplishing this research was investment in building collaborative relationships with stakeholders across the U.S. and the Philippines with shared interest in the health of migrants.

Abstract Background Longitudinal invariance is a perquisite for a valid comparison of oral health-related quality of life (OHRQoL) scores over time. Item response theory (IRT) models can assess measurement invariance and allow better estimation of the associations between predictors and latent construct. By extending IRT models, this study aimed to investigate the longitudinal invariance of the two 8-item short forms of the Child Perception Questionnaire (CPQ11–14) regression short form (RSF:8) and item-impact short form (ISF:8) and identify factors associated with adolescents’ OHRQoL and its change. Methods All students from S1 and S2 (equivalent to US grades 6 and 7) who were born in April 1997 and May 1997 (at age 12) from 45 randomly selected secondary schools were invited to participate in this study and followed up after 3 years. Data on the CPQ11–14 RSF:8 and CPQ11–14 ISF:8, demographics, oral health behavior and status were collected. Explanatory graded response models were fitted to both short forms of the CPQ11–14 data for assessing longitudinal invariance and factors associated with OHRQoL. The Bayesian estimation method – Monte Carlo Markov Chain (MCMC) with Gibbs sampling was adopted for parameter estimation and the credible intervals were used for inference. Results Data from 649 children at age 12 at baseline and 415 children at age 15 at follow up were analyzed. For the 12 years old children, healthier oral health behavior, better gum status, families with both parents employed and parents’ education level were found to be associated with better OHRQoL. Four items among the 2 short forms lacked longitudinal invariance. With statistical adjustment of longitudinal invariance, OHRQoL were found improved in general over the 3 years but no predictor was associated with OHRQoL in follow-up. For those with decreased family income, their OHRQoL had worsened over 3 years. Conclusions IRT explanatory analysis enables a more valid identification of the factors associated with OHRQoL and its changes over time. It provides important information to oral healthcare researchers and policymakers.

Adoptive cancer immunotherapy using chimeric antigen receptor (CAR) engineered T-cells holds great promise, although several obstacles hinder the efficient generation of cell products under good manufacturing practice (GMP). Patients are often immune compromised, rendering it challenging to produce sufficient numbers of gene-modified cells. Manufacturing protocols are labour intensive and frequently involve one or more open processing steps, leading to increased risk of contamination. We set out to develop a simplified process to generate autologous gamma retrovirus-transduced T-cells for clinical evaluation in patients with head and neck cancer. T-cells were engineered to co-express a panErbB-specific CAR (T1E28z) and a chimeric cytokine receptor (4αβ) that permits their selective expansion in response to interleukin (IL)-4. Using peripheral blood as starting material, sterile culture procedures were conducted in gas-permeable bags under static conditions. Pre-aliquoted medium and cytokines, bespoke connector devices and sterile welding/sealing were used to maximise the use of closed manufacturing steps. Reproducible IL-4-dependent expansion and enrichment of CAR-engineered T-cells under GMP was achieved, both from patients and healthy donors. We also describe the development and approach taken to validate a panel of monitoring and critical release assays, which provide objective data on cell product quality.

Marine sediments host diverse actinomycetes that serve as a source of new natural products to combat infectious diseases and cancer. Here, we report the biodiversity, bioactivities against ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and ovarian cancer, and metabolites variation among culturable actinomycetes isolated from the marine sediments of Visayan Sea, Philippines. We identified 15 Streptomyces species based on a 16S rRNA gene sequence analysis. The crude extracts of 10 Streptomyces species have inhibited the growth of ESKAPE pathogens with minimum inhibitory concentration (MIC) values ranging from 0.312 mg/mL to 20 mg/mL depending on the strain and pathogens targeted. Additionally, ten crude extracts have antiproliferative activity against A2780 human ovarian carcinoma at 2 mg/mL. To highlight, we observed that four phylogenetically identical Streptomyces albogriseolus strains demonstrated variation in antibiotic and anticancer activities. These strains harbored type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes in their genomes, implying that their bioactivity is independent of the polymerase chain reaction (PCR)-detected bio-synthetic gene clusters (BGCs) in this study. Metabolite profiling revealed that the taxonomically identical strains produced core and strain-specific metabolites. Thus, the chemical diversity among these strains influences the variation observed in their biological activities. This study expanded our knowledge on the potential of marine-derived Streptomyces residing from the unexplored regions of the Visayan Sea as a source of small molecules against ESKAPE pathogens and cancer. It also highlights that Streptomyces species strains produce unique strain-specific secondary metabolites; thus, offering new chemical space for natural product discovery.

Carbon-based molecules could prove useful in terahertz and optical devices controlled by pure spin currents. Here, conversely, the authors use spin currents to probe molecular dynamics and enhance the optical response of a fullerene layer, enabling hybrid magneto-molecular optoelectronic devices.

Abstract Domain walls in ferromagnetic nanowires are potential building-blocks of future technologies such as racetrack memories, in which data encoded in the domain walls are transported using spin-polarised currents. However, the development of energy-efficient devices has been hampered by the high current densities needed to initiate domain wall motion. We show here that a remarkable reduction in the critical current density can be achieved for in-plane magnetised coupled domain walls in CoFe/Ru/CoFe synthetic ferrimagnet tracks. The antiferromagnetic exchange coupling between the layers leads to simple Néel wall structures, imaged using photoemission electron and Lorentz transmission electron microscopy, with a width of only ~100 nm. The measured critical current density to set these walls in motion, detected using magnetotransport measurements, is 1.0 × 1011 Am−2, almost an order of magnitude lower than in a ferromagnetically coupled control sample. Theoretical modelling indicates that this is due to nonadiabatic driving of anisotropically coupled walls, a mechanism that can be used to design efficient domain-wall devices.

Abstract Background Participation in the Supplemental Nutrition Assistance Program (SNAP) has been linked to an increased risk of obesity, but not much is known about the mechanisms behind this association. The objective of this study was to determine if the neighborhood density of unhealthy food outlets modifies the association between obesity and participation in SNAP. Methods Data comes from the first wave of the Los Angeles Family and Neighborhood Survey; included are a subsample of adults (18+ years) who were SNAP participants or eligible non-participants (N = 1,176). We carried out multilevel analyses with obesity (BMI ≥ 30 Kg/m2), SNAP participation, and the neighborhood density of unhealthy food outlets as dependent, independent and modifying variables, respectively, controlling for age, gender, race/ethnicity, marital status, working status, mental health, and neighborhood poverty. Results SNAP participants had double the odds of obesity compared to eligible non-participants (OR = 2.02; 95%CI = 1.44-2.83). However, the neighborhood density of unhealthy food outlets did not modify this association. Conclusions SNAP participation was associated with higher odds of obesity in our primarily Hispanic sample in Los Angeles County, with no effect modification found for the unhealthy portion of the food environment. More research is needed with additional food environment measures to confirm our null findings. Additional research is needed to elucidate the mechanisms linking SNAP participation and obesity as they remain unclear.

Probing the dynamic activities of protein kinases in real-time in living cells constitutes a major challenge that requires specific and sensitive tools tailored to meet the particular demands associated with cellular imaging. The development of genetically-encoded and synthetic fluorescent biosensors has provided means of monitoring protein kinase activities in a non-invasive fashion in their native cellular environment with high spatial and temporal resolution. Here, we review existing technologies to probe different dynamic features of protein kinases and discuss limitations where new developments are required to implement more performant tools, in particular with respect to infrared and near-infrared fluorescent probes and strategies which enable improved signal-to-noise ratio and controlled activation of probes.

Experiences of discrimination are associated with adverse health outcomes, including obesity. However, the mechanisms by which discrimination leads to obesity remain unclear. Utilizing multi-omics analyses of neuroimaging and fecal metabolites, we investigated the impact of discrimination exposure on brain reactivity to food images and associated dysregulations in the brain-gut-microbiome system. We show that discrimination is associated with increased food-cue reactivity in frontal-striatal regions involved in reward, motivation and executive control; altered glutamate-pathway metabolites involved in oxidative stress and inflammation as well as preference for unhealthy foods. Associations between discrimination-related brain and gut signatures were skewed towards unhealthy sweet foods after adjusting for age, diet, body mass index, race and socioeconomic status. Discrimination, as a stressor, may contribute to enhanced food-cue reactivity and brain-gut-microbiome disruptions that can promote unhealthy eating behaviors, leading to increased risk for obesity. Treatments that normalize these alterations may benefit individuals who experience discrimination-related stress.

Oropharyngeal tularemia was identified as the cause of a die-off in captured wild prairie dogs at a commercial exotic animal facility in Texas. From this point source, Francisella tularensis–infected prairie dogs were traced to animals distributed to the Czech Republic and to a Texas pet shop. F. tularensis culture isolates were recovered tissue specimens from 63 prairie dogs, including one each from the secondary distribution sites. Molecular and biochemical subtyping indicated that all isolates were F. tularensis subsp. holarctica (Type B). Microagglutination assays detected antibodies against F. tularensis, with titers as great as 1:4,096 in some live animals. All seropositive animals remained culture positive, suggesting that prairie dogs may act as chronic carriers of F. tularensis. These findings demonstrate the need for additional studies of tularemia in prairie dogs, given the seriousness of the resulting disease, the fact that prairie dogs are sold commercially as pets, and the risk for pet-to-human transmission.

A tularemia outbreak, caused by Francisella tularensis type B, occurred among wild-caught, commercially traded prairie dogs. F. tularensis microagglutination titers in one exposed person indicated recent infection. These findings represent the first evidence for prairie-dog-to-human tularemia transmission and demonstrate potential human health risks of the exotic pet trade.

We conducted a serosurvey of landscapers to determine if they were at increased risk for exposure to Francisella tularensis and to determine risk factors for infection. In Martha’s Vineyard, Massachusetts, landscapers (n=132) were tested for anti–F. tularensis antibody and completed a questionnaire. For comparison, serum samples from three groups of nonlandscaper Martha’s Vineyard residents (n=103, 99, and 108) were tested. Twelve landscapers (9.1%) were seropositive, compared with one person total from the comparison groups (prevalence ratio 9.0; 95% confidence interval 1.2 to 68.1; p=0.02). Of landscapers who used a power blower, 15% were seropositive, compared to 2% who did not use a power blower (prevalence ratio 9.2; 95% confidence interval 1.2 to 69.0; p=0.02). Seropositive landscapers worked more hours per week mowing and weed-whacking and mowed more lawns per week than their seronegative counterparts. Health-care workers in tularemia-endemic areas should consider tularemia as a diagnosis for landscapers with a febrile illness.

A total of 420 rodents in China were examined for Francisella tularensis by polymerase chain reaction. The infection rates were 4.76% in total, and 11.65%, 10.00%, 6.56%, 1.77%, and 0% in Jilin, Xinjiang, Heilongjiang, Inner Mongolia, and Zhejiang, respectively. Sequence analysis showed that all the detected agents belonged to F. tularensis subsp. holarctica.

BackgroundThis study examines how neighborhood socioeconomic status (nSES) and ethnic composition are associated with breast cancer risk for Asian American women.MethodsWe linked individual level data from a population-based case-control study of breast cancer among Asian American women with neighborhood level data in the Greater San Francisco Bay Area (cases: n = 118, controls: n = 390). Multivariable logistic regression models examined the association between nSES, ethnic composition, and odds of having breast cancer.ResultsAsian American women living in neighborhoods with high nSES and high ethnic composition had the highest odds of breast cancer, compared to those living in neighborhoods with high nSES and low ethnic composition (OR = 0.34, 95% CI [0.16-0.75]) or in neighborhoods with low nSES and high ethnic composition (OR = 0.37, 95% CI [0.17-0.83]).DiscussionNeighborhood socioeconomic and ethnic contexts are associated with breast cancer for Asian American women. We discuss explanations and avenues for future research.

During neurogenesis, mitotic progenitor cells lining the ventricles of the embryonic mouse brain undergo their final rounds of cell division, giving rise to a wide spectrum of postmitotic neurons and glia1,2. The link between developmental lineage and cell-type diversity remains an open question. Here we used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during mouse forebrain development. We quantified clonal divergence and convergence across all major cell classes postnatally, and found diverse types of GABAergic neuron that share a common lineage. Divergence of GABAergic clones occurred during embryogenesis upon cell-cycle exit, suggesting that differentiation into subtypes is initiated as a lineage-dependent process at the progenitor cell level.

Studies of migration and health focus on a "healthy migrant effect" whereby migrants are healthier than individuals not migrating. Health selection remains the popular explanation of this phenomenon. However, studies are mixed on whether selection occurs and typically examine migrants post-departure. This study used a novel pre-migration dataset to identify which health and social domains differ between migrants and their non-migrant counterparts and their contribution to explaining variance in self-rated health by migrant status at pre-migration and 1-year later. Data were used from the baseline and 1-year follow-up of the Health of Philippine Emigrants Study (HoPES). We used multivariable ordinary least squares regression to examine differences in self-rated health between migrants to the U.S. and a comparable group of non-migrants at baseline (premigration) and one year later, accounting for seven domains: physical health, mental health, health behavior, demographics, socioeconomic factors and healthcare utilization, psychosocial factors, and social desirability. A migrant advantage was present for self-rated health at baseline and 1-year. Accounting for all domains, migrants reported better self-rated health compared to non-migrants both at baseline (β = 0.32; 95% CI = 0.22, 0.43) and at 1-year (β = 0.28; 95% CI = 0.10, 0.46). Migrant status, health behavior, and mental health accounted for most of the variance in self-rated health both at baseline and 1-year follow-up. This analysis provides evidence of migrant health selection and nuanced understanding to what is being captured by self-rated health in studies of migrant health that should be considered in future research.

BackgroundThis study examines how neighborhood socioeconomic status (nSES) and ethnic composition are associated with breast cancer risk for Asian American women.MethodsWe linked individual level data from a population-based case-control study of breast cancer among Asian American women with neighborhood level data in the Greater San Francisco Bay Area (cases: n = 118, controls: n = 390). Multivariable logistic regression models examined the association between nSES, ethnic composition, and odds of having breast cancer.ResultsAsian American women living in neighborhoods with high nSES and high ethnic composition had the highest odds of breast cancer, compared to those living in neighborhoods with high nSES and low ethnic composition (OR = 0.34, 95% CI [0.16-0.75]) or in neighborhoods with low nSES and high ethnic composition (OR = 0.37, 95% CI [0.17-0.83]).DiscussionNeighborhood socioeconomic and ethnic contexts are associated with breast cancer for Asian American women. We discuss explanations and avenues for future research.