Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility.

STUDY QUESTION: In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)? SUMMARY ANSWER: In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples. WHAT IS KNOWN ALREADY: ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples. STUDY DESIGN, SIZE, DURATION: This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively). LIMITATIONS, REASONS FOR CAUTION: Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons. WIDER IMPLICATIONS OF THE FINDINGS: The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study, and no authors reported conflicting interests. TRIAL REGISTRATION NUMBER: NCT04866524 (clinicaltrials.gov).

A novel multi-stage enrichment workflow and comprehensive characterization for HEK293F-derived extracellular vesicles.

Extracellular vesicles (EVs) are emerging as a promising drug delivery vehicle as they are biocompatible and capable of targeted delivery. However, clinical translation of EVs remains challenging due to the lack of standardized and scalable manufacturing protocols to consistently isolate small EVs (sEVs) with both high yield and high purity. The heterogenous nature of sEVs leading to unknown composition of biocargos causes further pushback due to safety concerns. In order to address these issues, we developed a robust quality-controlled multi-stage process to produce and isolate sEVs from human embryonic kidney HEK293F cells. We then compared different 2-step and 3-step workflows for eliminating protein impurities and cell-free nucleic acids to meet acceptable limits of regulatory authorities. Our results showed that sEV production was maximized when HEK293F cells were grown at high-density stationary phase in semi-continuous culture. The novel 3-step workflow combining tangential flow filtration, sucrose-cushion ultracentrifugation and bind-elute size-exclusion chromatography outperformed other methods in sEV purity while still preserved high yield and particle integrity. The purified HEK293F-derived sEVs were thoroughly characterized for identity including sub-population analysis, content profiling including proteomics and miRNA sequencing, and demonstrated excellent preclinical safety profile in both in-vitro and in-vivo testing. Our rigorous enrichment workflow and comprehensive characterization will help advance the development of EVs, particularly HEK293F-derived sEVs, to be safe and reliable drug carriers for therapeutic applications.

Perception of having children through surrogacy in individuals with MRKH in Vietnam: a qualitative study.

Introduction: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is rare condition that has a negative impact on quality of life because affected women lack a uterus and vagina, and are therefore unable to engage in sexual intercourse and experience natural pregnancy. This study evaluated perceptions of surrogacy in Vietnamese women with MRKH who have started families. Method: Women with MRKH who had undergone successful vaginal reconstruction, were married, and had started families participated in a semi-structured, in-depth, one-on-one online video interview with an experienced female psychologist. Open-ended questions were used to encourage participants to express their perceptions of surrogacy; prominent themes were discussed, compared, and combined. Results: Twenty women (mean age 31 years) agreed to participate. Key themes identified from interviews were the importance of having genetic offspring, consideration of surrogacy as a preferred solution to infertility, the barriers to surrogacy in Vietnam, lack of reproductive information and counselling, individuals concealing their health condition, the impact of religion on the possibility of surrogacy, the economic cost of surrogacy, and the difficulty in finding a surrogate under the restrictions imposed by Vietnamese law. Discussion: Based on the perceptions of women from MRKH from Vietnam, there is an opportunity to improve how infertility is managed in these people, including information about surrogacy. These data show that individuals with MRKH should be provided with information about the possibility of surrogacy, encouraged to be open and seek support, and be managed by a multidisciplinary team that includes psychological support; the provision of economic support for fertility treatments in women with MRKH should also be considered.

Clinical factors associated with unexpected poor or suboptimal response in Poseidon criteria patients.

RESEARCH QUESTION: What clinical factors are associated with 'unexpected' poor or suboptimal responses to IVF ovarian stimulation per POSEIDON's criteria, and which AMH and AFC threshold values distinguish this population? DESIGN: Tri-centre retrospective cohort study (2015-2017) involving first-time IVF and ICSI cycles with conventional ovarian stimulation (≥150 IU/day of FSH). Eligibility criteria included sufficient ovarian reserve markers according to POSEIDON's classification (AMH ≥1.2 ng/ml; AFC ≥5). Ovarian response categories were poor (<4 oocytes), suboptimal (4-9 oocytes) and normal (≥9 oocytes). Primary outcomes included clinical factors associated with an unexpected poor or suboptimal response to conventional ovarian stimulation using logistic regression analyses, and the threshold values of AMH and AFC predicting increased risk of such responses using ROC curves. RESULTS: A total of 7625 patients met the inclusion criteria: 204 (9.3%) were poor and 1998 (90.7%) were suboptimal responders. Logistic regression identified significant clinical predictors for a poor or suboptimal response, including AFC, AMH, total gonadotrophin dose, gonadotrophin type and trigger type (P ≤ 0.02). The ROC curves indicated that AMH 2.87 ng/ml (AUC 0.740) and AFC 12 (AUC 0.826) were the threshold values predicting a poor or suboptimal response; AMH 2.17 ng/ml (AUC 0.741) and AFC 9 (AUC 0.835) predicted a poor response; and AMH 2.97 ng/ml (AUC 0.722) and AFC 12 (AUC 0.801) predicted a suboptimal response. CONCLUSIONS: The threshold values of AMH and AFC predicting 'unexpected' poor or suboptimal response were higher than expected. These findings have critical implications for tailoring IVF stimulation regimens and dosages.

Perspective: Promoting Healthy Aging through Nutrition: A Research Centers Collaborative Network Workshop Report.

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as "older" and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop's themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.

Significance of serum AMH and antral follicle count discrepancy for the prediction of ovarian stimulation response in Poseidon criteria patients.

PURPOSE: To determine the risk of not being a poor responder in ovarian stimulation (OS) for in vitro fertilization (IVF) when ovarian reserve markers are discordant-one falling within Poseidon's criteria normal range (e.g., anti-Müllerian hormone (AMH) ≥ 1.2 ng/mL or antral follicle count (AFC) ≥ 5), and the other in the poor ovarian reserve range. METHODS: A tri-center retrospective cohort study (2015-2017) involving women with discordant AMH and AFC values undergoing their first IVF/ICSI cycle using conventional OS (cOS, ≥ 150 IU/day of follicle-stimulating hormone). Discordant serum AMH and AFC values were defined according to Poseidon's criteria (AMH < 1.2 ng/mL and AFC ≥ 5 or AMH ≥ 1.2 ng/mL and AFC < 5). Poor ovarian response (POR) was < 4 retrieved oocytes. Receiver operating characteristic (ROC) curves were used to determine AMH and AFC cut-offs for non-POR. Logistic regression analysis evaluated factors associated with non-POR. RESULTS: Out of 8797 patients who underwent assessment with both AMH and AFC, 1172 (13.3%) exhibited discordant values. Of these, 854 (72.9%) had ≥ 4 oocytes retrieved. Within this group, 726 (85.0%) had "low" AMH values, whereas 128 (15.0%) had "low" AFCs. An AFC of 6 had 77% sensitivity and 52% specificity (AUC = 0.700), while AMH of 1.19 ng/mL had 31% sensitivity and 85% specificity (AUC = 0.492) for non-POR. AFC and the use of recombinant gonadotropins were positive predictors of non-POR. CONCLUSIONS: When serum AMH is < 1.19 ng/mL, but AFC is ≥ 6, there is a moderate likelihood of a non-POR during stimulation. Conversely, if AFC is < 5 but serum AMH is ≥ 1.19 ng/mL, the chances of non-POR are low. Among patients with discordant markers, AFC emerges as the primary predictor of oocyte yield.

Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection.

Background: Biomarker testing has gradually become standard of care in precision oncology to help physicians select optimal treatment for patients. Compared to single-gene or small gene panel testing, comprehensive genomic profiling (CGP) has emerged as a more time- and tissue-efficient method. This study demonstrated in-depth analytical validation of K-4CARE, a CGP assay that integrates circulating tumor DNA (ctDNA) tracking for residual cancer surveillance. Methods: The assay utilized a panel of 473 cancer-relevant genes with a total length of 1.7 Mb. Reference standards were used to evaluate limit of detection (LOD), concordance, sensitivity, specificity and precision of the assay to detect single nucleotide variants (SNVs), small insertion/deletions (Indels), gene amplification and fusion, microsatellite instability (MSI) and tumor mutational burden (TMB). The assay was then benchmarked against orthogonal methods using 155 clinical samples from 10 cancer types. In selected cancers, top tumor-derived somatic mutations, as ranked by our proprietary algorithm, were used to detect ctDNA in the plasma. Results: For detection of somatic SNVs and Indels, gene fusion and amplification, the assay had sensitivity of >99%, 94% and >99% respectively, and specificity of >99%. Detection of germline variants also achieved sensitivity and specificity of >99%. For TMB measurement, the correlation coefficient between whole-exome sequencing and our targeted panel was 97%. MSI analysis when benchmarked against polymerase chain reaction method showed sensitivity of 94% and specificity of >99%. The concordance between our assay and the TruSight Oncology 500 assay for detection of somatic variants, TMB and MSI measurement was 100%, 89%, and 98% respectively. When CGP-informed mutations were used to personalize ctDNA tracking, the detection rate of ctDNA in liquid biopsy was 79%, and clinical utility in cancer surveillance was demonstrated in 2 case studies. Conclusion: K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients.

Making Oneself "Fit": Community Perspectives on Disaggregated Race and Ethnicity Data Collection and Reporting in Healthcare Settings.

Patient race/ethnicity data collection in most U.S. health systems abide by federal standards, determined by the federal Office of Management and Budget. Yet, decades of research show that reliance on these categories alone limits understanding of within-group health disparities, systematically erasing key groups from health data. Because granular race/ethnicity data is complex and patients may be hesitant to disclose this personal information, it is important for health leaders to consider community perspectives when making decisions about race/ethnicity data procedures. As such, this study uses community focus groups to understand: (1) how individuals representing different racial/ethnic identities perceive the collection of race/ethnicity in healthcare settings; (2) differences in opinions between disaggregated race/ethnicity data collection instruments and those using federal standards; and (3) recommended practices for collecting race/ethnicity from patients. Participants self-selected into 13 focus groups and one key informant interview based on the race/ethnicity with which they most closely identified. Audio recordings from these groups were transcribed and evaluated using thematic content analysis. Among the 83 total participants in this study, there was a strong preference for more flexible and specific options for self-identifying race/ethnicity in healthcare settings. Participants also felt comfortable disclosing granular race/ethnicity to health providers but expressed discomfort with disclosing this information for other purposes. Recommendations for healthcare leaders include ensuring patients receive detailed communication about race/ethnicity data use and purpose, allowing multiple category selection, keeping the list of disaggregated response options short so as to not overwhelm patients, and providing a free text option to ensure inclusivity.

An update on the current indications for in vitro maturation.

PURPOSE OF REVIEW: In vitro maturation has become a significant component of modern assisted reproductive techniques. Published data have been supported for the safety and effectiveness of in vitro maturation treatment. In recent years, potential indications for in vitro maturation (IVM) have been a topic of interest and investigation. RECENT FINDINGS: Significant improvements in technique enhancement and data publication for evaluating the efficacy of IVM have been achieved. Recent studies have shown that IVM could offer several advantages over in vitro fertilization. Currently, there are growing indications for IVM beyond the commonly mentioned indication of infertile women with polycystic ovary syndrome. Additionally, some potential candidates might have significant advantages for IVM, such as women diagnosed with gonadotropin resistance ovary syndrome or those seeking fertility preservation. With a better understanding of IVM, from basic science to clinical practice, it can be applied safely, effectively, and affordably to a broader range of patients, making it a more accessible and patient-friendly option. SUMMARY: Despite the possibly acknowledged limitations, the potential of in vitro maturation cannot be denied. As this technique becomes increasingly accessible to patients and more continuous efforts are dedicated to advancing this technique, the impact of in vitro maturation is expected.

Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos.

BACKGROUND: Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds for synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial to standardize cost-effective methods to produce highly pure ASC-sEVs. METHODS: Human ASCs were expanded in serum-free media with different compositions to first optimize the sEV production. ASC-sEVs from different batches were then purified using tangential flow filtration and sucrose cushion ultracentrifugation, followed by extensive characterization for identity and content profiling including proteomics, lipidomics and miRNA sequencing. ASC-sEVs were further loaded with nicotinamide riboside (NR) and resveratrol by sonication-incubation method. The therapeutic effect of ASC-sEVs and loaded ASC-sEVs was tested on human keratinocyte cell line HaCaT exposed to UVB by measuring reactive oxygen species (ROS). The loaded ASC-sEVs were later applied on the hand skin of three volunteers once a day for 8 weeks and skin analysis was performed every 2 weeks. RESULTS: Our standardized workflow produced ASC-sEVs with high yield, high purity and with stable characteristics and consistent biocargo among different batches. The most abundant subpopulations in ASC-sEVs were CD63+ (∼30%) and CD81+ -CD63+ (∼35%). Purified ASC-sEVs could be loaded with NR and resveratrol at the optimized loading efficiency of ∼20%. In UVB-exposed HaCaT cells, loaded ASC-sEVs could reduce ROS by 38.3%, higher than the sEVs (13.3%) or compounds (18.5%) individually. In human trial, application of loaded ASC-sEVs after 8 weeks substantially improved skin texture, increased skin hydration and elasticity by 104% and reduced mean pore volume by 51%. CONCLUSIONS: This study demonstrated a robust protocol to produce ASC-sEVs and exogenously load them with natural compounds. The loaded ASC-sEVs exhibited synergistic effects of both sEVs and anti-aging compounds in photoaging protection and skin rejuvenation.

Embryological and clinical outcomes in couples with severe male factor infertility versus normozoospermia.

OBJECTIVE: This study evaluated embryological and clinical outcomes in couples with severe male factor infertility versus those with normozoospermia undergoing ICSI and in vitro fertilisation. METHODS: This multicentre, retrospective cohort study included all couples who had undergone autologous ICSI cycles at My Duc Hospital and My Duc Phu Nhuan Hospital in Vietnam between January 2018 and January 2021 (female age < 35 years and males with severe male factor or normozoospermia based on the World Health Organization 2010 criteria). The primary outcome was the cumulative live birth rate after the first ICSI cycle. RESULTS: A total of 1296 couples were included, including 648 with severe male factor infertility and 648 with normozoospermia. The number of two pronuclei zygotes, embryos, and frozen embryos was significantly lower in couples with severe male factor infertility compared with normozoospermia (p < 0.05). In contrast, there were no significant differences between the two groups with respect to cumulative pregnancy outcomes, including the live birth rate, and secondary outcomes including clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate. CONCLUSION: Severe male factor infertility appeared to have an impact on the fertilisation and early developmental potential of embryos, but sperm quality did not affect cumulative clinical fertility outcomes.

A fresh start for IVM: capacitating the oocyte for development using pre-IVM.

BACKGROUND: While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices. OBJECTIVE AND RATIONALE: The objectives of this review are to examine the major scientific advances in ovarian biology with a unique focus on the development of pre-IVM methodologies, to provide an insight into biphasic IVM procedures, and to report on outcomes from animal and clinical human data, including safety data. The potential future impact of biphasic IVM on ART practice is discussed. SEARCH METHODS: Peer review original and review articles were selected from PubMed and Web of Science searches for this narrative review. Searches were performed using the following keywords: oocyte IVM, pre-IVM, biphasic IVM, CAPA-IVM, hCG-triggered/primed IVM, natural cycle IVF/M, ex-vivo IVM, OTO-IVM, oocyte maturation, meiotic competence, oocyte developmental competence, oocyte capacitation, follicle size, cumulus cell (CC), granulosa cell, COC, gap-junction communication, trans-zonal process, cAMP and IVM, cGMP and IVM, CNP and IVM, EGF-like peptide and IVM, minimal stimulation ART, PCOS. OUTCOMES: Minimizing gonadotrophin use means IVM oocytes will be collected from small antral (pre-dominant) follicles containing oocytes that are still developing. Standard IVM yields suboptimal clinical outcomes using such oocytes, whereas pre-IVM aims to continue the oocyte's development ex vivo, prior to IVM. Pre-IVM achieves this by eliciting profound cellular changes in the oocyte's CCs, which continue to meet the oocyte's developmental needs during the pre-IVM phase. The literature contains 25 years of animal research on various pre-IVM and biphasic IVM procedures, which serves as a large knowledge base for new approaches to human IVM. A pre-IVM procedure based on c-type natriuretic peptide (named 'capacitation-IVM' (CAPA-IVM)) has undergone pre-clinical human safety and efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF. WIDER IMPLICATIONS: Over many decades, improvements in clinical IVM have been gradual and incremental but there has likely been a turning of the tide in the past few years, with landmark discoveries in animal oocyte biology finally making their way into clinical practice leading to improved outcomes for patients. Demonstration of favorable clinical results with CAPA-IVM, as the first clinically tested biphasic IVM system, has led to renewed interest in IVM as an alternative, low-intervention, low-cost, safe, patient-friendly ART approach, and especially for patients with PCOS. The same new approach is being used as part of fertility preservation in patients with cancer and holds promise for social oocyte freezing.

Epigenetic variation in neonatal tissues in infants conceived using capacitation-in vitro maturation vs. in vitro fertilization.

OBJECTIVE: To investigate alterations of the global DNA methylation profile in placenta, cord blood, and neonatal buccal smears in infants conceived using in vitro maturation (IVM) with a prematuration step (capacitation-IVM [CAPA-IVM]) vs. in vitro fertilization (IVF). DESIGN: Analysis of data from the offspring of participants in a randomized controlled trial. SETTING: Private clinic. PATIENTS: Forty-six women with polycystic ovary syndrome and/or high antral follicle count and their offspring (58 newborns). INTERVENTION(S): Women with polycystic ovary syndrome and/or a high antral follicle count participating in the clinical trial were randomized to undergo CAPA-IVM or conventional IVF. MAIN OUTCOME MEASURE(S): At delivery, biological samples including cord blood, placental tissue, and a neonatal buccal smear were collected. Genome-wide DNA methylation was determined using the Illumina Infinium MethylationEPIC BeadChip. Variability in methylation was also considered, and mean variances for the two treatment categories were compared. RESULTS: In neonatal buccal smears, there were no significant differences between the CAPA-IVM and conventional IVF groups on the basis of the CpG probe after linear regression analysis using a significant cut-off of false-discovery rate <0.05 and |Δß|≥0.05. In cord blood, only one CpG site showed a significant gain of methylation in the CAPA-IVM group. In the placenta, CAPA-IVM was significantly associated with changes in methylation at five CpG sites. Significantly more variable DNA methylation was found in five probes in the placenta, 54 in cord blood, and two in buccal smears after IVM of oocytes. In cord blood samples, 20 CpG sites had more variable methylation in the conventional IVF vs. IVM group. Isolated CpG sites showing differences in methylation in cord blood were not associated with changes in gene expression of the overlapping genes. CONCLUSION(S): Capacitation-IVM appeared to be associated with only a small amount of epigenetic variation in cord blood, placental tissue, and neonate buccal smears. CLINICAL TRIAL REGISTRATION NUMBER: NCT03405701 (www. CLINICALTRIALS: gov).

Turning the Health Equity Lens to Diversity in Asian American Health Profiles.

The monolithic misrepresentation of Asian American (AsAm) populations has maintained assumptions that AsAm people are not burdened by health disparities and social and economic inequities. However, the story is more nuanced. We critically review AsAm health research to present knowledge of AsAm health profiles from the past two decades and present findings and opportunities across three topical domains: (a) general descriptive knowledge, (b) factors affecting health care uptake, and (c) effective interventions. Much of the literature emphasized underutilization of health care services; low knowledge and awareness among AsAms about health-related risk factors, prevention, diagnosis, and treatment; inadequate efforts by health systems to improve language access, provider-patient communication, and trust; and the critical roles of community- and faith-based organizations and leaders in health promotion initiatives. Future opportunities for AsAm health research will require adoption of and significant investment in community-engaged research infrastructure to increase representation, funding, and research innovation for AsAm communities.

Dairy product consumption and lung cancer risk: A prospective analysis.

BACKGROUND & AIM: Current evidence on prospective associations between dairy product, dairy fat and lactose intakes and lung cancer risk is limited and inconsistent. We conducted a prospective analysis of associations of lung cancer risk with dairy product intakes in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. METHODS: Pre-diagnostic dairy product intake was assessed through a validated Diet History Questionnaire. All incident lung cancer cases were pathologically verified. Multivariable Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations of lung cancer risk with intakes of total, full-fat, low-fat dairy, fermented or non-fermented dairy products; milk fat content preference; and intakes of total and saturated fats and lactose from dairy products. RESULTS: Among 101,709 adults (mean age of 65.5 years), a total of 1583 lung cancer cases were identified during 1,167,239 person-years of follow up. Mean total dairy product intake was 156 g/1000 kilocalories (kcal), including 20 g/1000 kcal from fermented dairy products. Total dairy intake was not associated with lung cancer risk (HR [95% CI] = 1.03 [0.89-1.18]) comparing the highest quartile with the lowest. Fermented dairy intake was inversely associated with lung cancer risk (0.85 [0.72-0.99]). In contrast, there were no statistically significant associations with low-fat, full-fat or non-fermented dairy product intakes. The preference of whole milk when consuming milk as beverage was associated with a higher risk of lung cancer than the preference of <0.5% fat milk (1.24 [1.03-1.49]). Total fat, saturated fat and lactose intakes from dairy products each were not associated with lung cancer risk. CONCLUSIONS: Our results suggest an inverse association of lung cancer risk with fermented dairy intake and a positive association with the whole milk preference in a US population. Future studies exploring underlying molecular mechanisms are warranted.

Identifying opportunities for collective action around community nutrition programming through participatory systems science.

PURPOSE: To apply principles of group model building (GMB), a participatory systems science approach, to identify barriers and opportunities for collective impact around nutrition programming to reduce cancer risk for immigrant communities in an urban environment. METHODS: We convened four in-person workshops applying GMB with nine community partners to generate causal loop diagrams (CLDs)-a visual representation of hypothesized causal relationships between variables and feedback structures within a system. GMB workshops prompted participants to collaboratively identify programmatic goals and challenges related to (1) community gardening, (2) nutrition education, (3) food assistance programs, and (4) community-supported agriculture. Participants then attended a plenary session to integrate findings from all workshops and identify cross-cutting ideas for collective action. RESULTS: Several multilevel barriers to nutrition programming emerged: (1) food policies center the diets and practices of White Americans and inhibit culturally tailored food guidelines and funding for culturally appropriate nutrition education; (2) the lack of culturally tailored nutrition education in communities is a missed opportunity for fostering pride in immigrant food culture and sustainment of traditional food practices; and (3) the limited availability of traditional ethnic produce in food assistance programs serving historically marginalized immigrant communities increases food waste and worsens food insecurity. CONCLUSION: Emergent themes coalesced around the need to embed cultural tailoring into all levels of the food system, while also considering other characteristics of communities being reached (e.g., language needs). These efforts require coordinated actions related to food policy and advocacy, to better institutionalize these practices within the nutrition space.