Significant Dose-response Relationship Research Articles

Does a Hip Muscle Activation Home Exercise Program Change Movement Patterns on the Forward Step-Down Test?

Poor knee biomechanics contribute to knee joint injuries. Neuromuscular control over knee position is partially derived from the hip. It is unknown whether isolated activation training of the gluteal muscles improves lower-extremity frontal plane mechanics. This study examined if a home-based hip muscle activation program improves performance on the Forward Step-Down Test as well as increases surface electromyography (sEMG) activation of the gluteal muscles. The study utilized a single-group repeated-measures design. Thirty-five participants (24 females, mean age = 23.17 [SD 1.36] years) completed an 8-week hip muscle activation program. The Forward Step-Down Test score and sEMG of gluteus maximus and medius were assessed preintervention and postintervention. Forward Step-Down Test scores improved significantly from preintervention (Mdn = 3.5) to postintervention (Mdn = 3.0, T = 109, P = .010, r = .31.), but this result did not meet clinical significance. sEMG analysis revealed a significant increase in mean gluteus maximus activation (P = .028, d = 1.19). No significant dose-response relationship existed between compliance and the Forward Step-Down Test scores or sEMG results. A home-based hip activation program increases gluteus maximus activation without clinically significant changes in frontal plane movement quality. Future studies may find clinical relevance by adding motor learning to the activation training program to improve functional muscle use.

Association between Copper Exposure and Cognitive Function: A Cross-Sectional Study in a County, Guangxi, China.

There has been growing attention to the impact of copper exposure on cognitive function; however, current research on the specific information regarding urinary copper and cognitive function is limited, particularly detailed analyses in the Chinese adult population. This study aimed to explore the association between copper exposure and cognitive function in a cross-sectional design. A total of 2617 participants in a county, Guangxi Zhuang Autonomous Region (Guangxi), China, were included. The mini-mental state examination (MMSE) was used to assess cognitive function, and inductively coupled plasma mass spectrometry was used to measure urinary metal levels. Spearman's rank correlation was used to analyze the correlation between urinary copper levels and various cognitive function assessment indices. After adjusting for potential confounders, binary logistic regression was used to explore the association between urinary copper levels and the risk of cognitive impairment (CI) as revealed by MMSE, and restricted cubic spline regression was further used to explore the dose-response relationship. The results showed a negative correlation between urinary copper levels and orientation, attention and calculation, memory, language ability, and MMSE total scores (P < 0.05). Compared with the low copper exposure group, the high exposure group showed a 58.5% increased risk of CI (OR = 1.585, 95%CI: 1.125 to 2.235, P = 0.008). A significant linear dose-response relationship was observed between urinary copper levels and the risk of CI (P overall = 0.045, P nonlinearity = 0.081). Our findings suggest that higher copper exposure may be associated with CI in the population of a county, Guangxi, China.

624 A Retrospective Review of Blood Pressure Variability (BPV) and Abdominal Aortic Aneurysm (AAA)

Abstract Background Abdominal aortic aneurysms (AAA) rupture risk increases with expansion. Understanding of factors influencing AAA growth are crucial to reduce the risk of rupture. Blood pressure (BP) is considered a contributor to AAA formation, but the association with AAA growth remains unclear. Blood pressure variability (BPV) has emerged as an important cardiovascular risk factor, yet its relationship with AAA growth has not been investigated. Method A retrospective review of 90 patients participating in a multi-centre AAA growth study (NCT05376514) was conducted. Mean growth (mm/yr) was calculated from first and most recent duplex ultrasound scans. Outpatient BP readings between scans were used to calculate BPV defined as the standard deviation (SD) of systolic and diastolic values. Patients were stratified into high and low BPV groups and again into tertiles. Mann-whitney U and unpaired T-tests were used for group comparisons, Kruskall-Wallis to assess for a dose-response relationship between tertiles of BPV. Multiple regression analysis examined variable impact on growth. Results High diastolic BPV was associated with a faster growth rate (2.05 mm/yr [IQR= 1.00 – 3.00]) vs low diastolic BPV (1.44 mm/ yr ([IQR= 0.475-2.00]p=0.036) with a significant dose-response relationship between the lowest and highest BPV tertiles (p= 0.019). DBPV was a significant predictor of AAA growth in the multiple regression model for tertile classification (p=0.016). There was no association between systolic BPV and faster AAA growth rates. Conclusions There was a significant association between higher diastolic blood pressure variability and AAA growth. DBPV may be an important risk stratification tool.

Associations of oxidative balance score with hyperuricemia and gout among American adults: a population-based study.

The current study aimed to assess the relationships between oxidative balance score (OBS) and OBS subclasses (dietary and lifestyle OBS) with risks of hyperuricemia (HUA) and gout among American adults. Participants in the National Health and Nutrition Examination Survey from 2007 to 2018 were initially recruited and then the final sample was restricted to adults without missing values about serum uric acid, gout, OBS, and covariates. Rao-Scott adjusted chi-square test and analysis of variance were utilized to compare the baseline characteristics in adults of different quartiles of OBS, while the weighted stepped logistic regression models were used to explore the associations of overall, dietary, and lifestyle OBS with the risks of HUA and gout. Weighted restricted cubic spline analyses were conducted to explore the nonlinear dose-response associations. The final sample consisted of 22,705 participants aged 20 years and older, which was representative of approximately 197.3 million non-institutionalized American adults. HUA and gout prevalence decreased with OBS quartiles. Compared with adults in the first quartile of OBS, those in the second (OR: 0.85, 95% CI: 0.72-0.99), third (OR: 0.71, 95% CI: 0.58-0.85), and fourth (OR: 0.48, 95% CI: 0.38-0.61) quartiles of OBS had reduced risks of hyperuricemia. Similarly, adults in the second (OR: 0.70, 95% CI: 0.51-0.97) quartile of OBS was associated with lower gout risk in comparison to adults in the lowest quartile. Regarding OBS subclasses, dietary and lifestyle OBS were both negatively correlated with the risk of HUA, and only higher lifestyle OBS was significantly associated with lower gout risk. Furthermore, the subgroup analyses and interaction effects also substantiated similar effects. Significant nonlinear dose-response relationships were observed between overall, dietary, and lifestyle OBS with HUA risk as well as that of lifestyle OBS with gout risk. This study strongly suggests the significant negative associations of OBS with HUA and gout in American adults and provides a dietary and lifestyle guideline to reduce the risks.

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis.

Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM). This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS. The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%. SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

The association of cortisol, testosterone, and cortisol/testosterone ratio with stroke: A cross-sectional study

AimsWe aimed to investigate the association between serum cortisol, testosterone, and cortisol/testosterone (C/T) ratio and stroke. Materials and methodsA total of 6157 subjects were included in this study. The serum levels of cortisol and testosterone were determined by liquid chromatography-tandem mass spectrometry method. The relationships of serum cortisol, testosterone, and C/T ratio levels with the odds ratios (ORs) of stroke were calculated using logistic regression analysis. The dose-response associations between serum cortisol, testosterone, and C/T ratio levels with stroke estimated by restricted cubic splines. ResultsAfter adjusting for multiple variables, serum testosterone levels were negactively associated with stroke in males (per 1 unit, odds ratio (OR) = 0.83, 95 % confidence interval (CI): 0.70, 0.97). The serum C/T ratio is positively associated with stroke in both males and females (OR = 1.16, 95 % CI:1.04,1.34 in males and OR = 1.15, 95 % CI:1.02,1.31 in females). Restricted cubic splines showed a significant linear dose-response relationship between testosterone and C/T ratio and stroke in males (P for overall association <0.05, P for nonlinearity >0.05). ConclusionOur study findings show that serum testosterone levels are negatively correlated with stroke in males; meanwhile, serum C/T ratio is positively correlated with stroke in both males and females.

Lung cancer among patients with secondhand smoke exposure: A systematic review.

e22506 Background: Smoking tobacco is recognized as the leading cause of lung cancer. However, it is imperative to note that 10–15% of lung cancer patients have no history of smoking, and that lung cancer remains the leading cause of cancer deaths among non-smokers. Since passive smokers are exposed to many carcinogenic compounds in the exhaled smoke, it is naturally plausible that secondhand smoking (SHS) is a risk factor for lung cancer. However, current USPSTF screening guidelines for lung cancer with low dose CT (LDCT) do not include patients exposed to SHS. We performed a systematic review to highlight SHS as an etiology of lung cancer and insights for inclusion in cancer screening criteria. Methods: We utilized the PubMed, Medline, Science Direct, and ClinicalTrials.gov databases to search for relevant literature using keywords ('low Dose CT,' 'secondhand smoke,' 'lung cancer'). The search strategy was designed to ensure a comprehensive retrieval of pertinent literature, minimizing the possibility of omitting articles due to insignificant spelling and/or semantic variations. Eligible studies had to be published between 2010 and 2023 and focused on examining the effect of SHS in populations at risk of lung cancer or those undergoing lung cancer screening. Articles not available in English were excluded from this systematic review. In total, 239 relevant articles were retrieved from all databases, narrowing down to 14 articles after the initial screening and further reducing to 4 articles after the second round of screening. Results: Three of the four articles included in our systemic review were conducted in Asia. A study by He et al. showed a substantial increase in the relative risk of lung cancer among SHS (RR 2.00; 95% CI, 0.62-6.40), with significant dose-response relationships between cumulative SHS exposure at home and work and the increased risk of cause-specific and total mortality. Another observational study on the use of LDCT in Japan has interestingly shown a shifting landscape of lung cancer demographics, with 49.6% of patients identified as never-smokers and 70.0% of the never-smoker lung cancer patients having SHS exposure. Secondhand smoking has also been reported to increase the risk of pulmonary nodules (HR 1.17; 95% CI, 1.01-1.35) and pulmonary emphysema (OR 13.6; 95% CI, 1.70-106.1) in those with moderate-to-high SHS exposure, which was the population where lung cancer was more prevalent. Conclusions: Our findings suggest a critical gap in current healthcare recommendations, specifically addressing the absence of guidelines for LDCT screening in individuals with moderate-to-high SHS exposure despite established evidence linking SHS to a significant increase in the risk of lung cancer development. More studies are needed to formulate evidence-based guidelines for lung cancer screening and detection in this population, given the expected mortality reduction benefit.

Dose-response association of obesity and risk of mental health among tehranian residents: result of a cross-sectional study

BackgroundObesity and mental health issues are two of the most prevalent global public health issues for a significant portion of people. The purpose of this study was to investigate the relationship between obesity indicators and mental health in Tehran-dwelling Iranian adults.MethodsWe conducted a cross-sectional study on healthy Iranian adults using a convenience sampling technique. The short form of the Depression Anxiety and Stress Scale (DASS-21) was used to measure the outcome, and independent variables included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI), and a body shape index (ABSI). The relationship between obesity and mental health was investigated using a multivariate logistic regression model. The non-linear dose-response relationships were evaluated using restricted cubic splines (RCS) with three knots. The Benjamini-Hochberg procedure was used to adjust for multiple testing.ResultsIn our study of 434 participants, females made up 52% of the participants, with a mean age of 38.57 years. In all, 54.6%, 53.9%, and 56.6% were classified as having anxiety, depression, and stress respectively. Logistic regression analysis showed that the odds of mental health components including anxiety, depression, or stress was not significantly different across the tertiles of the obesity indicators. We observed a significant dose-response relationship between BAI and ABSI and the risk of anxiety (PBenjamini-Hochberg 0.028 > Pdose-response 0.023) and stress (PBenjamini-Hochberg 0.028 > Pdose-response 0.003) but not depression (PBenjamini-Hochberg 0.014 < Pdose-response 0.018). The lowest risk for anxiety was observed in people with a BAI of 28% and ABSI equal to 0.079. The risk of stress seemed to increase beyond an ABSI of 0.086.ConclusionOur findings showed no direct linear association between obesity indices and anxiety. However, a dose-response relationship was observed between BAI and ABSI and the risk of anxiety and stress, indicating the need for further investigation.

The dose-response relationship between physical activity and the risk of death from pneumonia in middle-aged and older adults: A meta-analysis.

Deaths from COVID-19 are concentrated in older adults, and studies have reported that physical activity (PA) can reduce the risk of death from pneumonia. Eight cohort studies and 2 case-control studies were included according to the inclusion and exclusion criteria established in this meta-analysis study followed the PRISMA guideline, 8 cohort studies and 2 case-control studies were finally included. Then, the research objects in these studies were classified to further study the dose-response relationship and non-dose-response relationship. The highest dose of PA reduced the risk of death by 59% (risk ratio = 0.41; 95% confidence interval: 0.23-0.58) compared with the lowest dose of PA in middle-aged and elderly people. Furthermore, when the PA level was <10 m/wk, the risk of death from pneumonia was reduced by 6% every 4.5 MET-h/wk increase. At a PA level > 10 m/wk, the risk of death from pneumonia increased by 5% every 4.5 MET-h/wk increase. At a PA level > 30 m/wk, PA is a risk factor for pneumonia-related death in middle-aged and elderly people. This meta-analysis showed that PA was associated with a reduced risk of dying from pneumonia in middle-aged and older adults, and that there was a significant nonlinear negative dose-response relationship between PA levels and the risk of dying from pneumonia. Therefore, moderate exercise was recommended.

Exploring the Link Between Exogenous Thyroid Hormones and Dementia Symptoms: A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System.

A growing body of evidence indicates a strong association between exogenous thyroid hormone (ETH) and brain health. Establishing the potential relationship between ETH therapy and dementia symptoms is crucial for patients with thyroid disorders. In this study, we investigate the potential association between ETH therapy and dementia symptoms by exploring the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis (DPA) was conducted using postmarketing data from the FAERS repository (Q1 2004 to Q4 2023). Cases of dementia symptoms associated with ETH therapy were identified and analyzed through DPA using reporting odds ratios and information component methods. Dose and time-to-onset analyses were performed to assess the association between ETH therapy and dementia symptoms. A total of 9889 cases of ETH-associated symptoms were identified in the FAERS database. Dementia accounted for a consistent proportion of adverse drug reactions each year (3.4%-6.3%). The DPA indicated an association between ETH therapy and dementia symptoms, which remained significant even across sex, age, and indications. The median time-to-onset of dementia symptoms was 7.5 days, and the median treatment time was 40.5 days. No significant dose-response relationship was observed. This study provides evidence for a link between ETH therapy and dementia. Clinicians are therefore advised to exercise vigilance, conduct comprehensive monitoring, and consider individualized dosing to mitigate potential reactions to ETH drug administration.

Association of systemic chronic inflammation during pregnancy in different periods and its trajectories with preterm birth.

Systemic chronic inflammation (SCI) is a prevalent characteristic observed in various diseases originating from different tissues, while the association of SCI with preterm birth (PTB) remains uncertain. This study aimed to analyze the association between a nonspecific biomarker of SCI and PTB, while also exploring the trajectories of SCI in pregnant women at risk of PTB. The study used data from the Electronic Medical Record System (EMRS) of a hospital in Zhejiang, China and 9226 pregnant women were included. The duration of pregnancy was categorized into four distinct periods: the first, early-second, late-second, and third trimester. Latent class trajectory modeling (LCTM) was used to identify the trajectories of SCI during pregnancy. The elevated WBC counts in the late-second (OR=1.14, 95% CI: 1.06-1.23) and third (OR=1.16, 95% CI: 1.09-1.24) trimester were both positively associated with an evaluated risk of PTB. Moreover, significant dose-response relationships were observed. There were three distinct SCI trajectories found: progressing SCI (2.89%), high SCI (7.13%), and low SCI (89.98%). Pregnant women with progressive SCI had the highest risk of PTB (OR=3.03, 95% CI: 1.47-6.25). In conclusion, elevated SCI after 23weeks was a risk factor for PTB in healthy women, even if the SCI indicator was within normal range. Pregnant women with progressive SCI during pregnancy had the highest risk of PTB.

Association Between Adverse Childhood Experiences and Academic Performance Among Children and Adolescents: A Global Meta-Analysis.

This study was conducted to quantify the association of adverse childhood experiences (ACEs) and the academic performance of children and adolescents. The literature was systematically searched in six electronic databases, and a meta-analysis was conducted. Twenty studies with a total of 1,196,631 children and adolescents from five countries were included. Meta-analysis showed that ACE score was positively associated with poor academic achievement, grade repetition, and special education support. Compared with children and adolescents without any ACE, those with one or more ACE had a significantly higher risk of poor academic achievement (pooled odds ratio [OR]: 1.45, 95% confidence interval [CI] [1.13, 1.85], I2 = 82.6%) and grade repetition (pooled OR: 1.36, 95% CI [1.29, 1.43], I2 = 71.0%). Moreover, all types of ACEs were positively associated with poor academic achievement and grade repetition. In addition, there was a significant dose-response relationship between the ACE score and the risk of poor academic achievement. This study supported that ACE had a significant impact on the academic performance of children and adolescents. Based on these findings, we recommend that early screening of ACEs for children and adolescent is critical and appropriate support and prevention in education should be developed for those with ACEs. Further studies are needed to further explore the long-term effect of ACEs on education and its gender differences.

Toxoplasma gondii suppresses proliferation and migration of breast cancer cells by regulating their transcriptome

BackgroundBreast cancer is the most common cancer in women worldwide. Toxoplasma gondii (T. gondii) has shown anticancer activity in breast cancer mouse models, and exerted beneficial effect on the survival of breast cancer patients, but the mechanism was unclear.MethodsThe effect of tachyzoites of T. gondii (RH and ME49 strains) on human breast cancer cells (MCF-7 and MDA-MB-231 cells) proliferation and migration was assessed using cell growth curve and wound healing assays. Dual RNA-seq was performed for T. gondii-infected and non-infected cells to determine the differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–Protein Interaction Networks analysis (PPI) were performed to explore the related signaling pathway and hub genes. Hub genes were validated using the Kaplan–Meier plotter database, and Pathogen Host Interaction (PHI-base) database. The results were verified by qRT-PCR.ResultsThe tachyzoites of T. gondii decreased the expression of Ki67 and increased the expression of E-cadherin, resulting in suppressing the proliferation and migration of infected human breast cancer cells. The inhibitory effect of T. gondii on breast cancer cells showed a significant dose–response relationship. Compared with the control group, 2321 genes were transcriptionally regulated in MCF-7 cells infected with T. gondii, while 169 genes were transcriptionally regulated in infected MDA-MB-231 cells. Among these genes, 698 genes in infected MCF-7 cells and 67 genes in infected MDA-MB-231 cells were validated by the publicly available database. GO and KEGG analyses suggested that several pathways were involved in anticancer function of T. gondii, such as ribosome, interleukin-17 signaling, coronavirus disease pathway, and breast cancer pathway. BRCA1, MYC and IL-6 were identified as the top three hub genes in infected-breast cancer cells based on the connectivity of PPI analysis. In addition, after interacting with breast cancer cells, the expression of ROP16 and ROP18 in T. gondii increased, while the expression of crt, TgIST, GRA15, GRA24 and MIC13 decreased.ConclusionsT. gondii transcriptionally regulates several signaling pathways by altering the hub genes such as BRCA1, MYC and IL-6, which can inhibit the breast tumor growth and migration, hinting at a potential therapeutic strategy.

Acute Toxicity of the Lampricide 4-Nitro-3-(trifluoromethyl)phenol to the Mussel (Obovaria subrotunda), Its Host (Percina maculata), and a Surrogate Mussel Species (Obovaria olivaria).

The risk of lampricide applications (such as 4-nitro-3-[trifluoromethyl]phenol [TFM]) to nontarget fauna continues to be a concern within the Great Lakes Fishery Commission Sea Lamprey Control Program, especially among imperiled aquatic species-such as native freshwater mussels. The Grand River (Ohio, USA) is routinely treated for larval sea lampreys (Petromyzon marinus), and this river contains populations of the federally threatened mussel Obovaria subrotunda. Given this spatial overlap, information on the sensitivity of O. subrotunda to TFM is needed. Our objectives were to assess the toxicity of TFM to (1) adult Obovaria olivaria (a surrogate for O. subrotunda), (2) glochidial larvae of O. olivaria and O. subrotunda, (3) juveniles of O. olivaria and O. subrotunda, and (4) adult Percina maculata (host for O. subrotunda glochidia). In acute toxicity tests, TFM was not toxic to glochidia and adult mussels at exposure concentrations that exceed typical treatment rates. Although significant dose-response relationships were observed in hosts and juveniles, survival was ≥95% (Percina maculata), ≥93% (O. olivaria), and ≥74% (O. subrotunda) at typical treatment rates. However, the steep slope of these dose-response relationships indicates that an approximately 20% difference in the treatment level can result in nearly an order of magnitude difference in survival. Collectively, these data indicate that routine sea lamprey control operations are unlikely to acutely affect these species or their host. However, given that many mussel species are long-lived (30-100 years), the risks posed by lampricide treatments in the Great Lakes would be further informed by research on the potential long-term effects of lampricides on imperiled species. Environ Toxicol Chem 2024;43:1423-1430. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou–Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose–response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

A preliminary understanding of the relationship between synthetic phenolic antioxidants and early pregnancy loss: Uncovering the potential molecular mechanisms

Mounting evidence suggests that environmental pollutants may affect reproductive health, potentially leading to adverse outcomes like pregnancy loss. However, it remains unclear whether exposure to synthetic phenolic antioxidants (SPAs) correlates with early pregnancy loss (EPL). This study explores SPA exposure's link to EPL and its potential molecular mechanisms. From 2021 to 2022, 265 early pregnant women (136 serum and 129 villus samples) with and without EPL were enrolled. We quantified 17 SPAs in serum and chorionic villus, with AO1010, AO3114, BHT, AO2246, and BHT-Q frequently being detected, suggesting their ability to cross the placental barrier. AO1135 showed a positive relationship with EPL in sera, indicating a significant monotonic dose-response relationship (p-trend <0.001). BHT-Q exhibited a similar relationship with EPL in villi. Inhibitory effects of BHT-Q on estradiol (E2) were observed. Molecular docking revealed SPA-protein interactions involved in E2 synthesis. SPA-induced EPL might occur with specific serum levels of AO1135 and certain villus levels of AO1010, BHT-Q, and AO2246. BHT-Q emerges as a potential biomarker for assessing EPL risk. This study provides insights into understanding of the exposure to SPAs and potential adverse outcomes in pregnant women.

Ozone risk assessment of common cypress (Cupressus sempervirens L.) clones and effects of Seiridium cardinale infection

Cupressus sempervirens is a relevant species in the Mediterranean for its cultural, economic and landscape value. This species is threatened by Seiridium cardinale, the causal agent of the cypress canker disease (CCD). The effects of biotic stressors on O3 risk assessment are unknown and a comprehensive O3 risk assessment in C. sempervirens is missing. To fill these gaps, two clones of C. sempervirens, one resistant (Clone R) and one susceptible to CCD (Clone S), were subjected to three levels of O3 (Ambient Air - AA; 1.5 × AA; 2.0 × AA) for two consecutive years in an O3-free-air controlled exposure facility and artificially inoculated with S. cardinale. Both the exposure- (AOT40) and flux-based (PODy) indices were tested. We found that PODy performed better than AOT40 to assess O3 effects on biomass and the critical level for a 4% biomass loss was 2.51 mmol/m2 POD2. However, significant O3 dose-response relationships were not found for the inoculated cypresses because the combination of middle level O3 (1.5 × AA) and inoculation stimulated a biomass growth in Clone S as hormetic response. Moreover, we found a different inter-clonal response to both stressors with a statistically significant reduction of total and belowground biomass following O3, and lower root biomass in Clone S than in Clone R following pathogen infection. In summary, Clone R was more resistant to O3, and inoculation altered O3 risk via an hormetic effect on biomass. These results warrant further studies on how biotic stressors affect O3 responses and risk assessment.

Ultra-Processed Food Consumption and Long-Term Risk of Irritable Bowel Syndrome: A Large-Scale Prospective Cohort Study

The considerable disease burden of irritable bowel syndrome (IBS) has coincided with the increase of ultraprocessed food (UPF) consumption over the past few decades. However, epidemiologic evidence is lacking. We aimed to examine the long-term risk of IBS associated with UPF consumption in a large-scale prospective cohort. Participants who completed 24-hour dietary recalls during 2009 to 2012 from the UK Biobank, and free of IBS, celiac disease, inflammatory bowel disease, and any cancer at baseline, were included (N= 178,711; 53.1% female). UPF consumption was defined according to the NOVA food classification system, expressed as a percentage of UPF content in the total diet intake (as grams per day). The primary outcome was incident IBS. A Cox proportional hazard model was performed to estimate associated risk. The mean UPF consumption was 21.0% (SD, 11.0%) of the total diet. During a median of 11.3 years of follow-up evaluation, 2690 incident IBS cases were identified. An 8% higher risk of IBS (hazard ratio, 1.08; 95% CI, 1.04-1.12) was associated with each 10% increment of UPF consumption. Compared with the lowest quartile of UPF consumption, the highest quartile wasassociated with a significantly increased risk of incident IBS (hazard ratio, 1.19; 95% CI, 1.07-1.33; Ptrend < .001). Subgroup analyses by age, sex, body mass index, smoking, and alcohol drinking status also showed similar results, except for the never/previous drinking subgroup. Further sensitivity analyses confirmed the positive association with a higher UPF consumption. Our findings provide evidence that a higher UPF consumption is associated with an increased risk of incident IBS, with a significant dose-response relationship.

Associations between dietary inflammatory index and stroke risk: based on NHANES 2005–2018

The dietary inflammatory index (DII) is a measure of the inflammatory potential of the diet and is closely associated with insulin resistance (IR) and stroke. And IR may play an important role in the development of stroke. Therefore, this study aimed to evaluate the relationship between DII and stroke risk while delving into the potential role of IR in this association. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, performing weighted univariate analyses, logistic regression, and mediation analyses. At baseline, 3.89% of participants developed stroke, and we observed stroke patients exhibited higher DII scores. After adjusting for covariates, compared to participants in the first quartile of DII scores, those in the third quartile and fourth quartile had increased odds of experiencing a stroke (OR: 1.78, 95% CI: 1.18–2.68) and (OR: 1.70, 95% CI: 1.16–2.50), respectively. Moreover, a significant dose–response relationship was observed (P-trend < 0.05). However, there was no observed interaction between DII and homeostatic model assessment-IR (HOMA-IR) concerning stroke risk, and HOMA-IR did not mediate the association between DII and stroke. In summary, our study elucidated the significant association between DII and stroke risk, independent of IR. This insight suggests that an anti-inflammatory diet may serve as an effective strategy for stroke prevention.

Systemic inflammation indices as hematological biomarkers of inflammatory response in non-silicotic workers exposed to respirable silica dust

This cross-sectional study was performed to assess whether systemic inflammatory indices, including systemic inflammation response index (SIRI), systemic immune‑inflammation index (SII), and aggregate index of systemic inflammation (AISI), can be considered as possible inflammatory markers in silica-exposed workers with no diagnosis of silicosis. We studied 371 non-silicotic workers exposed to respirable silica dust (RSD) and 1422 reference workers. The workers’ exposure to RSD were assessed and the inflammatory indices were compared between subgroups of the exposed workers based on the severity and duration of exposure. Correlations between inflammatory indices and the pulmonary function parameters were investigated. Also, the receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off values of the SII, SIRI, and AISI. Significant dose–response relationships were observed between duration of exposure and all indices except monocytes and LMR. No significant interaction was observed between duration of exposure to RSD and smoking. Borderline significant correlations were observed between AISI and SIRI with forced expiratory volume (FEV1) and FEV1 to forced vital capacity (FVC) ratio. Higher AUCs were obtained for SII and AISI, respectively. The cut-off values for these biomarkers to be considered abnormal were > 348.48 for SII, > 183.78 for AISI, and > 0.768 for SIRI. Overall, the present study showed for the first time, that SII, AISI, and SIRI might be considered as available, easy-to-obtain, and non-expensive markers of inflammation in non-silicotic workers with a long duration of exposure to RSD who are at risk of developing silicosis in subsequent years.