Borderline Association Research Articles

Relationship Between Plasma Homocysteine and Bone Density, Lean Mass, Muscle Strength and Physical Function in 1480 Middle-Aged and Older Adults: Data from NHANES

Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models. Plasma homocysteine (fluorescence immunoassay) was used as the exposure and bone mineral density (BMD; dual-energy X-ray absorptiometry; DXA), lean mass (DXA), knee extensor strength (isokinetic dynamometer; newtons) and gait speed (m/s) were used as outcomes. Regression models were adjusted for confounders (age, sex, race/Hispanic origin, height, fat mass %, physical activity, smoking status, alcohol intakes, cardiovascular disease, diabetes, cancer and vitamin B12). All models accounted for complex survey design by using sampling weights provided by NHANES. 1480 adults (median age: 64 years [IQR: 56, 73]; 50.3% men) were included. In multivariable models, homocysteine was inversely associated with knee extensor strength (β = 0.98, 95% CI 0.96, 0.99, p = 0.012) and gait speed (β = 0.85, 95% CI 0.78, 0.94, p = 0.003) and borderline inversely associated with femur BMD (β = 0.84, 95% CI 0.69, 1.03, p = 0.086). In the sub-group analysis of older adults (≥ 65 years), homocysteine was inversely associated with gait speed and femur BMD (p < 0.05) and the slope for knee extensor strength and whole-body BMD were in the same direction. No significant associations were observed between homocysteine and total or appendicular lean mass in the full or sub-group analysis. We found inverse associations between plasma homocysteine and muscle strength/physical function, and borderline significant inverse associations for femur BMD.

High COX-2 immunostaining in papillary thyroid carcinoma is associated with adverse survival outcomes.

Thyroid carcinoma is one of the most common malignancies worldwide. More than 70%-80% are papillary thyroid carcinoma (PTC). Many factors influence the PTC pathway of development such as genetic mutations, growth factors, and radiation. More biological understanding of the genetic and molecular pathways is needed in PTC to determine tumor behavior, and initial clinical assessment. Investigate the relation of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters to assess whether immunostaining results have prognostic significance. Retrospective study SETTING: Pathology department, tertiary care center METHODS: Records of PTC were retrieved and tissue microarrays were constructed. Tissue sections were stained using anti-human COX-2 monoclonal antibody. Immunostaining results were recorded and analysed. Relationship of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters. 139 tissue samples from 139 patients RESULTS: High versus low COX-2 immunostaining showed no significant differences for most clinicopathological parameters. However, high COX-2 immunostaining showed borderline association with tumor multifocality (P=.05), lower overall (log-rank=8.739 and P=.003), and disease-free survival (log-rank=7.033, P=.008). The study showed a positive association of high COX-2 immunostaining with lower survival outcomes in PTC. COX-2 immunostaining could be a potential prognostic factor for survival in PTC. Additional molecular and clinical investigations are needed for further understanding the molecular pathways of COX-2 in PTC and the feasibility of using inhibitors of COX-2 as adjuvant therapy along with current chemotherapy. Relatively low number of PTC variants, and no testing of other thyroid carcinomas. None.

Chronic metformin intake and gastric cancer: A pooled analysis within the Stomach cancer Pooling (StoP) Project

IntroductionThe association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC. MethodsData from three studies of the StoP Project with available information on metformin intake were analyzed.Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model.The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials. ResultsThe OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants’ characteristics or when restricting the analyses to those with a history of diabetes.The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake. ConclusionsThe results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.

Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort

Abstract Background Acrylamide is classified as a probable human carcinogen by the IARC but epidemiological evidence on the carcinogenicity of acrylamide from dietary sources is limited. This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort. Methods This prospective cohort study included 80,597 French women (mean [SD] age at baseline: 40.8 [14] years) during a mean (SD) follow-up of 8.8 (2.3) years. Acrylamide intake was evaluated using repeated 24h dietary records (n = 5.5 [SD 3.0]), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal and post-menopausal) were assessed by Cox hazard models adjusted for known risk factors. Results The mean (SD) dietary acrylamide intake was 30.1 (21.9) µg/d (main contributors: coffee, potato fries and chips, pastries and cakes, and bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between acrylamide intake and breast cancer risk overall (HRQ4 vs Q1= 1.21 [95% CI: 1.00-1.47]) and a positive association was observed with premenopausal cancer (HRQ4 vs Q1= 1.40 [95% CI: 1.04-1.88]). Restricted cubic spline analyses suggested evidence for non-linearity of these associations, with higher HR for intermediate (Q2) and high (Q4) exposures. Receptor-specific analyses revealed a positive association with estrogen receptor-positive breast cancer, which represented 86% of total cancer cases. Acrylamide intake was not associated with post-menopausal breast cancer. Conclusions Results from this large prospective cohort study suggest the potential deleterious role of dietary acrylamide in breast cancer etiology, especially in premenopausal women, and provide new insights that should encourage further mitigation strategies to reduce the content of acrylamide in food. Key messages

Maternal androgens and autism spectrum disorder in the MARBLES prospective cohort study

BackgroundMaternal hormonal risk factors for autism spectrum disorder (ASD) in offspring could intersect genetic and environmental risk factors. ObjectivesThis analysis explored ASD risk in association with maternal testosterone, androstenedione, and dehydroepiandrosterone (DHEA) measured in first, second, and third trimesters of pregnancy. MethodsMARBLES is a prospective pregnancy cohort study based at the MIND Institute in Northern California that enrolls mothers who have at least one child previously diagnosed with ASD and are expecting, or planning to have another child. At 36 months the younger sibling is clinically classified as having ASD, or as non-typically developing (Non-TD), or typically developing (TD). Maternal androgens during pregnancy were measured in serum samples from 196 mothers. Multivariable logistic regression models estimated risk of ASD and Non-TD in offspring compared to TD, in relation to the log-transformed maternal androgen concentrations, at each trimester. ResultsNon-significant associations were observed, and borderline significant associations were only observed in some stratified unadjusted models. Second trimester maternal testosterone was non-significantly associated with ASD in female offspring, although not after adjustment, aRR 1.54 (95% CI 0.71, 3.33), and second trimester maternal DHEA was non-significantly associated with non-TD in male offspring, again not after adjustment, aRR 0.50 (95% CI 0.21, 1.21). Secondary analysis suggested that third trimester androgen concentrations in mothers with male offspring had significant or near significant associations with their child’s Social Responsiveness Scale score. ConclusionNo significant associations were found between maternal androgen concentrations and risk of ASD or Non-TD in the child.

Screening for novel risk factors related to high myopia using machine learning

BackgroundHigh myopia-related complications have become a major cause of irreversible vision loss. Evaluating the association between potential factors and high myopia can provide insights into pathophysiologic mechanisms and further intervention targets for myopia progression.MethodParticipants aged 12–25 years from National Health and Nutrition Examination Survey 2001–2006 were selected for the analysis. Myopia was defined as spherical equivalent (sum of spherical error and half of the cylindrical error) of any eyes ≤-0.5 diopters. High myopia was defined as the spherical equivalent of any eye ≤ − 5.00 diopters. Essential variables were selected by Random Forest algorithm and verified by multivariable logistic regression.ResultsA total of 7,033 participants and 74 potential factors, including demographic (4 factors), physical examination (6 factors), nutritional and serological (45 factors), immunological (9 variables), and past medical history factors (10 factors), were included into the analysis. Random Forest algorithm found that several anthropometric, nutritional, and serological factors were associated with high myopia. Combined with multivariable logistic regression, high levels of serum vitamin A was significantly associated with an increased prevalence of high myopia (adjusted odd ratio = 1.46 for 1 µmol/L increment, 95% confidence interval [CI] 1.01–2.10). Furthermore, we found that neither C-reactive protein nor asthma increased the risk and severity of myopia.ConclusionHigh levels of serum vitamin A was seemingly associated with an increased prevalence of high myopia. This borderline significant association should be interpreted with caution because the potential increased type I error after the multiple testing. It still needs further investigation regarding the mechanism underlying this association. Neither C-reactive protein nor asthma increased the risk and severity of myopia.

A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.

The majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the NEBL (rs2359536), PCDH15 (rs10763170) and CDK8 (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population. Genotype and allele frequencies were determined in 570 cases and in 546 controls. The CDK8 rs17083838 minor allele (A allele) was significantly associated with sporadic pituitary adenomas, under an additive (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.19–2.50, p = 0.004) and dominant (OR 1.82, 95% CI 1.24–2.68, p = 0.002) inheritance model. The NEBL rs2359536 and PCDH15 rs10763170 variants were not associated with the overall risk for the disease, although a borderline significant association was observed between the PCDH15 rs10763170 minor allele (T allele) and somatotrophinomas (dominant model, OR 1.55, 95% CI 1.02–2.35, p = 0.035). These findings suggest that the CDK8 rs17083838 variant, and possibly the PCDH15 rs10763170 variant, may increase susceptibility to sporadic pituitary adenomas in the Portuguese population.

S1349 Utility of LAD Score for Treatment Response Assessment and Recurrence Monitoring in Patients With Hepatocellular Carcinoma

Introduction: The GALAD score, which incorporates the biomarkers AFP, AFP-L3% and DCP, has excellent performance for detection of hepatocellular carcinoma (HCC). However, its accuracy in treatment response assessment and recurrence prediction are unknown. We aimed to evaluate the accuracy of these biomarkers in predicting the presence of post-treatment viable tumor and HCC recurrence. Methods: We identified patients with cirrhosis or chronic hepatitis B infection who underwent curative surgical or locoregional treatment (Y-90, TACE, ablation) for HCC between May 2019 to May 2022, with GALAD labs obtained greater than 1 month post-treatment. Because the study cohort already has known HCC, we removed the demographic factors to calculate a score based solely on the biomarkers (the “LAD” score). The LAD score is calculated from the following formula: .04×(AFP-L3) +2.34×log(AFP)+1.33×log(DCP). Evidence of viable tumor was determined by imaging, biopsy, or liver explant pathology after transplant. Patients with non-viable tumor on initial post-treatment imaging were further analyzed for tumor recurrence. The sensitivity and specificity of the LAD score in predicting tumor viability were calculated. The optimal receiver operating characteristic (ROC) curve was used to calculate the cutoff for the LAD score. Results: A total of 78 patients (97 treatments) with surveillance imaging and biomarkers were analyzed. The number of treatments per patient ranged between 1 and 3 (mean 1.2). Mean age at time of HCC detection was 67 years, and a third of patients were female. The most common treatment modality was TACE (48.6%), followed by Y-90 (29.9%), ablation (16.5%), and resection (7.2%). About a third of cases (34.0%) had a viable tumor on initial post treatment images. The optimal LAD cutoff was calculated at 2.23, yielding a sensitivity and specificity of 87.4% and 60.9% for detection of viable tumors, respectively. After median follow up of 21.3 months, 11 cases (17.2%) developed recurrent HCC (mean time to recurrence 3.5 months) among cases with post-treatment non-viable tumor. A total of 7 recurrence cases (64%) had a positive LAD score at negative post-treatment surveillance images. Positive LAD score had a borderline association with recurrence (HR 3.17; 95%CI [0.92, 10.92], p = 0.067). Conclusion: LAD score is increased in most HCC patients with post-treatment viable tumors, suggesting its utility for post treatment response assessment. It might provide risk stratification for HCC recurrence.Figure 1.: Incidence of HCC Recurrence in LAD Positive vs Negative Cases

Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort

Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited. This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status. This prospective cohort study included 80,597 French females (mean±SD age at baseline: 40.8±14 y) during a mean±SD follow-up of 8.8±2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n±SD=5.5±3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). The mean±SD dietary acrylamide intake was 30.1±21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer. Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.

Psychosocial stress accompanied by an unhealthy eating behavior is associated with abdominal obesity in Korean adults: A community-based prospective cohort study.

Psychosocial stress is recognized as a potential modulator of eating behavior. Psychosocial stress also constitutes an independent risk factor for the development of non-communicable diseases. This study examined the gender-stratified associations between perceived stress, eating behavior, and abdominal obesity in 4,411 adults aged 40–69 years during a 10-year follow-up of the Korean Genome and Epidemiology Study (KoGES). Psychosocial stress was evaluated using the Psychosocial Wellbeing Index Short Form (PWI-SF), and eating behavior was analyzed with a focus on the dietary variety score (DVS). The Cox's proportional hazard model was used to examine the risk of abdominal obesity according to stress levels. Higher stress levels were associated with lower DVS in women. Lower DVS scores were positively associated with the consumption of grains and refined grains but was negatively associated with the consumption of fruits. The DVS was not significantly associated with stress levels among men. Prospectively, the highest tertile of grains and refined grains consumption showed an increased risk of abdominal obesity compared to the lowest tertile in women (HR: 1.36, 95% CI: 1.04–1.78, p < 0.05; HR: 1.28, 95% CI: 1.03–1.59, p < 0.05, respectively). By contrast, in all participants, the highest tertile of fruits consumption decreased the risk of abdominal obesity compared to the lowest tertile (men, HR: 0.56, 95% CI: 0.45–0.70, p < 0.01; women, HR: 0.51, 95% CI: 0.40–0.65, p < 0.01). Furthermore, high stress levels showed a borderline significant association with the risk of abdominal obesity only in women (HR: 1.27, 95% CI: 1.00–1.59, p < 0.05). These findings suggested that psychosocial stress might contribute to abdominal obesity by interacting with eating behavior represented by a low DVS. The approach to consume a diet with a high DVS might help decrease the risk of abdominal obesity among people in stressful environments.

Imaging-based body fat depots and new-onset atrial fibrillation in general population: a prospective cohort study

BackgroundObesity is a well-established risk factor for atrial fibrillation (AF). Whether body fat depots differentially associate with AF development remains unknown.MethodsIn the prospective population-based Rotterdam Study, body composition was assessed using dual-energy X-ray absorptiometry (DXA) and liver and epicardial fat using computed tomography (CT). A body composition score was constructed by adding tertile scores of each fat depot. Principal component analysis was conducted to identify potential body fat distribution patterns. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (HR; 95% CI) per 1-standard deviation increase in corresponding fat depots to enable comparisons.ResultsOver a median follow-up of 9.6 and 8.6 years, 395 (11.4%) and 172 (8.0%) AF cases were ascertained in the DXA and the CT analyses, respectively. After adjustments for cardiovascular risk factors, absolute fat mass (HR; 95% CI 1.33; 1.05–1.68), gynoid fat mass (HR; 95% CI 1.36; 1.12–1.65), epicardial fat mass (HR; 95% CI 1.27; 1.09-1.48), and android-to-gynoid fat ratio (HR; 95% CI 0.81; 0.70-0.94) were independently associated with new-onset AF. After further adjustment for lean mass, associations between fat mass (HR; 95% CI 1.17; 1.04-1.32), gynoid fat mass (HR; 95% CI 1.21; 1.08–1.37), and android-to-gynoid fat ratio (HR; 95% CI 0.84; 0.72–0.97) remained statistically significant. Larger body fat score was associated with a higher AF risk (HR; 95% CI 1.10; 1.02–1.20). Borderline significant association was found between a subcutaneous fat predominant pattern with AF onset (HR; 95% CI 1.21; 0.98–1.49).ConclusionsVarious body fat depots were associated with new-onset AF. Total fat mass and gynoid fat mass were independently associated with AF after adjustment for body size. The inverse association between android-to-gynoid fat ratio with AF presents a novel finding. A significant dose-response relationship between body fat accumulation and AF was observed. Our results underscore the predominant role of subcutaneous fat on AF development among a middle-aged and elderly population.Graphical abstractAssociations betw2een body fat depots, fat distribution and new-onset atrial fibrillation. Abbreviations: AF, atrial fibrillation.

Urban exposome and stroke incidence across Europe

Background and Aim: Multiple environmental factors of urban environments may influence cardiovascular health, however their complex interplay has scarcely been studied. Within the EXPANSE project, we evaluated the association between multiple urban exposures and stroke incidence across Europe. Methods: We will conduct a meta-analysis including 3 population-based cohorts (from Sweden, Netherlands, Germany) and 6 administrative cohorts (from Greece, Rome, Catalonia, Switzerland, Sweden, Netherlands). Participants were followed-up until incident stroke, death, migration, disappearance or end of study period. We estimated multiple long-term exposures at residential addresses from different domains: ambient air pollution (nitrogen dioxide, particulate matter &amp;#x3c;2.5m, black carbon, ozone), built environment (green and blue spaces, impervious surface) and meteorology (mean and standard deviation temperatures during summer and winter). Associations between environmental exposures and incident stroke were estimated in single and multiple-exposure Cox proportional hazard models, and Principal Component Analyses (PCA) derived prototypes for exposures domain (i.e built environment). Results: Preliminary results from Sweden (N=19,247), from single and multiple exposures, indicate associations between increased levels of NDVI and reduced incident stroke (hazard ratio (HR) per 0.1 units = 0.92, 95%CI 0.85; 0.99). The first component of each domain in the PCA explained more than 60% of the variability. The built environment domain (capturing high levels of green spaces and low levels of impervious surface) showed a borderline association with incident stroke (HR per interquartile range of the component = 0.92, 95%CI 0.83; 1.01). We also found a suggestive association between air pollution and increased stroke incidence. Conclusions: In preliminary results in Sweden, we found a suggestion for independent effects of green space and air pollution on incident stroke. Further analyses on the other cohorts are ongoing. Keywords: stroke, urban exposome, meta-analysis, air pollution, green space, temperature, blue space.

Association of sleep duration and insomnia with metabolic syndrome and its components in the Women’s Health Initiative

BackgroundEpidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women’s Health Initiative (WHI).MethodsThe study included postmenopausal women (ages 50–79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated.ResultsIn cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12–2.04), while sleep duration of 8- < 9 h was associated with waist circumference > 88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01–1.40 and OR = 1.23; 95%CI 1.05–1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99–1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03–1.34 and OR = 1.17; 95%CI 1.02–1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01–1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08–2.03).ConclusionsAmong postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.

Circulating plasma phospholipid fatty acid levels and breast cancer risk in the Cancer Prevention Study-II Nutrition Cohort.

Prospective studies that objectively measure circulating levels of fatty acids are needed to clarify their role in the etiology of breast cancer. Thirty-eight phospholipid fatty acids were measured using gas chromatograph in the plasma fraction of blood samples collected prospectively from 2718 postmenopausal women (905 breast cancer cases) enrolled in the Cancer Prevention Study II Nutrition Cohort. Associations of 28 fatty acids that passed quality control metrics (modeled as per 1-SD increase) with breast cancer risk were assessed using multiple variable conditional logistic regression models to compute odds ratios (OR) and 95% confidence intervals (CI). The false discovery rate (q value) was computed to account for multiple comparisons. Myristic acid levels were positively associated with breast cancer risk (OR, 1.17, 95% CI: 1.07-1.28; q value=0.03). Borderline associations were also found for palmitoleic acid (OR, 1.14, 95% CI: 1.04-1.24) and desaturation index16 (OR, 1.10, 95% CI: 1.01-1.20) at nominal P values (<.03) (q values>0.05). These findings suggest that higher circulating levels of myristic acid, sourced from dietary intake of palm kernel oils along with increased de novo synthesis of fatty acids, may increase breast cancer risk. Additional studies are needed to investigate de novo synthesis of fatty acid in breast cancer tissues.

Macro-Determinants of NEET: An Ecological Study at the Country Level of Analysis for the Period 1997–2020

The aim of the present study was to examine macro-determinants of the Not Engaged in Employment, Education or Training (NEET) rate with the country as the unit of analysis. Data from 40 countries were extracted from the Organisation for Economic Co-operation and Development (OECD) database. Linear mixed models were used to examine associations between the NEET rate and gross domestic product (GDP), population density, life expectancy, social spending, homicide rate, part-time employment, poverty, social inequality (GINI index), and education spending. As part of a sensitivity analysis, the analysis was repeated using open data from the World Bank Group. GDP and social spending were uniquely associated with the NEET rate after controlling for the effects of other factors. Social inequality, poverty, and education spending showed borderline significant associations with the NEET rate. The findings of the present ecological study showed associations between environmentally unfavourable conditions or harshness and the NEET rate at the country level and may inform appropriate policy measures to contain and promote a decrease in the NEET rate.

Association of Fish and Omega-3 Fatty Acid Intake with Carotid Intima-Media Thickness in Middle-Aged to Elderly Japanese Men and Women: The Toon Health Study.

Fish and omega-3 fatty acid consumption is known to be beneficial for cardiometabolic health. However, the related evidence for individuals with a relatively higher intake of fish or omega-3 unsaturated fatty acids, e.g., Japanese individuals, is scarce. Therefore, this study aimed to examine the association of fish and omega-3 fatty acid intakes with the carotid intima-media thickness (C-IMT) in the Japanese population. In total, 1803 Japanese men and women aged 30–84 years without a history of myocardial infarction or angina pectoris were included in the study. The fish and omega-3 fatty acid intakes were estimated using food frequency questionnaires. The C-IMT was measured using ultrasound imaging, and the participants were classified into three groups: normal, moderate (1.1 to 1.4 mm of maximum C-IMT), and severely increased C-IMT (≥1.5 mm). Multinomial logistic regression models were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI) of the presence of moderately and severely increased C-IMT. The omega-3 fatty acid intake was shown to be associated with lower odds of severely increased C-IMT. The multivariable-adjusted OR (95%CI) was 0.55 (0.31–0.97; p for trend = 0.04). We also found a borderline significant negative association between fish intake and the presence of severely increased C-IMT. In conclusion, omega-3 fatty acid intake might protect against the development of atherosclerosis in the Japanese population.

Associations between pre- and postnatal antibiotic exposures and early allergic outcomes: A population-based birth cohort study.

BackgroundEarly life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre‐ and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months.MethodsWe included 1387 mother–child dyads from the prospective, population‐based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web‐based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician‐diagnosed asthma; parents (n = 1025) reported physician‐diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions.ResultsPrenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01–3.26) but not in the adjusted analyses (aOR 1.58, 0.82–3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95–2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47–3.11), asthma (aOR 2.35, 1.32–4.19), and eczema (aOR 1.49, 1.07–2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25–0.83) but not with food allergy nor sensitization to inhalants.ConclusionPre‐ and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.

Vitamin D status in pregnancy and childhood associates with intelligence quotient at age 7 years: An Odense child cohort study.

Animal studies indicate a key role for vitamin D in brain development and function, but observational studies in humans only suggests a borderline positive association between prenatal vitamin D exposure and cognitive development in the offspring. Knowledge gaps include insights in exposure time window and differences by sex for the association. We aimed to investigate the association between blood concentrations of serum 25-hydroxyvitamin D measured at four different time points and intelligence quotient score at the age of 7 years, including analyses spilt by child sex. In Odense child cohort, we included 1404 mother-child pairs with serum 25-hydroxyvitamin D data from early pregnancy to age 7 years. Full-scale intelligence quotient was assessed with Wechsler Intelligence Scale for Children - fifth edition. Associations were adjusted for maternal education, pre-pregnancy body mass index, gestational age, sex and head circumference. Subanalyses stratified by sex were performed. The median (interquartile range) serum 25-hydroxyvitamin D in cord was 45.88 (31.15-61.08) nmol/L; early pregnancy, 66.45 (51.29-78.74); late pregnancy, 79.13 (59.69-97.31); 7 years, 66.29 (53.45-80.23) nmol/L. The mean (standard deviation) full-scale intelligence quotient was 99.44 (11.98). In adjusted analyses, cord serum 25-hydroxyvitamin D < 50 nmol/L was associated with 2.2 points lower full-scale intelligence quotient compared to the reference (50-75 nmol/L) in boys, β = -2.2; 95% confidence interval = [-4.3, -0.1], p = 0.039. The same association with full-scale intelligence quotient was found for early pregnancy serum 25-hydroxyvitamin D, β = -2.5 [-4.6, -0.3], p = 0.025, primarily driven by an association in boys, β = -4.0 [-7.2, -0.8], p = 0.015; and for serum 25-hydroxyvitamin D at 7 years in girls, β = -3.0 [-6.0, -0.1], p = 0.042. In this cohort, serum 25-hydroxyvitamin D < 50 nmol/L in both early gestation and cord blood in boys and current serum 25-hydroxyvitamin D < 50 nmol/L in girls were independent risk factors for two to four points lower full-scale intelligence quotient at the age of 7 years. Vulnerability to hypovitaminosis D, especially in pregnancy, may relate to child sex.

Electrocardiographic and cardiometabolic risk markers of left ventricular diastolic dysfunction in physically active adults: CHIEF heart study.

AimThis study was aimed to investigate the association of cardiometabolic and ECG markers with left ventricular diastolic dysfunction (LVDD) in physically active Asian young adults, which has not been clarified in prior studies.Methods and resultsA total of 2,019 men aged 18–43 years were included from the military in Taiwan. All the subjects underwent anthropometric, hemodynamic, and blood metabolic marker measurements. Physical fitness was investigated by time for a 3,000-m run. LVDD was defined by presence of either one of the three echocardiographic criteria: (1) mitral inflow E/A ratio < 0.8 with a peak E velocity of > 50 cm/s, (2) tissue Doppler lateral mitral annulus e′ <10 cm/s, and (3) E/e′ ratio > 14. Multiple logistic regressions with adjustments for age, physical fitness, and pulse rate were conducted to determine the association of cardiometabolic and ECG markers with LVDD. The prevalence of LVDD was estimated to be 4.16% (N = 84). Of the cardiometabolic markers, central obesity, defined as waist circumference ≥ 90 cm, was the only independent marker of LVDD [odds ratio (OR) and 95% confidence interval: 2.97 (1.63–5.41)]. There were no association for hypertension, prediabetes, and dyslipidemia. Of the ECG markers, left atrial enlargement and incomplete right bundle branch block/intraventricular conduction delay were the independent ECG markers of LVDD [OR: 2.98 (1.28–6.94) and 1.94 (1.09–3.47), respectively]. There was borderline association for Cornell-based left ventricular hypertrophy and inferior T wave inversion [OR: 1.94 (0.97–3.63) and 2.44 (0.98–6.08), respectively].ConclusionIn the physically active Asian young male adults, central obesity and some ECG markers for left heart abnormalities were useful to identify LVDD.

Biomarker Dynamics and Long-Term Treatment Outcomes in Breast Cancer Patients with Residual Cancer Burden after Neoadjuvant Therapy.

A residual cancer burden after neoadjuvant therapy (NAT) for breast cancer (BC) is associated with worse treatment outcomes compared to patients who achieved pathologic complete remission. This single-institutional retrospective study of 767 consecutive patients, including 468 patients with assessable residual cancer burden (aRCB) after NAT, with a median follow-up of 36 months, evaluated the biomarkers assessed before NAT from a biopsy and after NAT from a surgical specimen, their dynamics, and effect on long-term outcomes in specific breast cancer subtypes. The leading focus was on proliferation index Ki-67, which was significantly altered by NAT in all BC subtypes (p < 0.001 for HER2 positive and luminal A/B HER2 negative and p = 0.001 for TNBC). Multivariable analysis showed pre-NAT and post-NAT Ki-67 as independent predictors of survival outcomes for luminal A/B HER2 negative subtype. For TNBC, post-NAT Ki-67 was significant alone, and, for HER2 positive, the only borderline association of pre-NAT Ki-67 was observed in relation to the overall survival. Steroid and HER2 receptors were re-assessed just in a portion of the patients with aRCB. The concordance of both assessments was 92.9% for ER status, 80.1% for PR, and 92.2% for HER2. In conclusion, these real-world data of a consecutive cohort confirmed the importance of biomarkers assessment in patients with aRCB, and the need to consider specific BC subtypes when interpreting their influence on prognosis.