Synergistic Association Research Articles

Synergistic association between underweight and type 2 diabetes on the development of laryngeal cancer: a national population-based retrospective cohort study

BackgroundAlthough cigarette smoking is the most significant risk factor for laryngeal cancer, other risk factors might also be associated with the development of laryngeal cancer. We investigated whether underweight and type 2 diabetes are associated with laryngeal cancer in a Korean population.MethodsA total of 9,957,059 participants (≥20 years) without prior history of cancer who underwent a National Health Insurance Service health checkup in 2009 were followed up until December 31, 2018. Newly diagnosed laryngeal cancer was identified using claim data, and underweight was defined as body mass index (BMI) < 18.5 kg/m2. A Cox proportional-hazards models with multivariable adjustment were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs).ResultsDuring the median follow-up period of 8.3 years, 3504 cases of laryngeal cancer occurred. Underweight was associated with increased risk of laryngeal cancer after adjusting for potential confounders (HR: 1.43, 95% CI: 1.22–1.69) compared to those who were not underweight. Underweight and type 2 diabetes were synergistically associated with higher risk of laryngeal cancer (HR: 2.33, 95% CI: 1.54–3.51), compared to those without either condition. This relationship was stronger in those with an age < 65 years (HR: 3.33, 95% CI: 1.88–5.87) and alcohol consumption (HR: 2.72, 95% CI: 1.64–4.53).ConclusionsThese results suggest that underweight may be a significant risk factor for laryngeal cancer and that underweight and type 2 diabetes might synergistically increase the risk of laryngeal cancer.

Synergistic Associations of Depressive Symptoms and Executive Functions With Longitudinal Trajectories of Diabetes Biomarkers Among Urban-Dwelling Adults Without Diabetes.

Depressive symptoms and executive functions (EFs) have recently emerged as novel risk factors for type 2 diabetes, but it is unknown if these factors interact to influence diabetes pathophysiology across the life span. We examined the synergistic associations of depressive symptoms and EFs with longitudinal trajectories of diabetes diagnostic criteria among middle-aged and older adults without diabetes. Participants were 1257 African American and White, urban-dwelling adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were assessed up to three times over a 13-year period (2004-2017). At baseline, participants completed the Center for Epidemiological Studies-Depression scale and measures of EFs-Trail Making Test Part B, verbal fluency, and Digit Span Backward-for a composite EFs score, and provided blood samples at each follow-up for glycated hemoglobin and fasting serum glucose. A total of 155 and 220 individuals developed diabetes or prediabetes at wave 3 and wave 4, respectively. Linear mixed-effects regression models adjusting for sociodemographic factors, diabetes risk factors, and antidepressant medications revealed significant three-way interactions of Center for Epidemiological Studies-Depression, EFs, and age on change in glycated hemoglobin (b = -0.0001, p = .005) and in fasting serum glucose (b = -0.0004, p < .001), such that among individuals with lower but not higher EFs, elevated depressive symptoms were associated with steeper age-related increases in diabetes biomarkers over time. Depressive symptoms and lower EFs may interactively accelerate trajectories of key diagnostic criteria, thereby increasing the risk for earlier diabetes incidence. Identifying individuals in this high-risk group may be an important clinical priority for earlier intervention, which has the promise of preventing or delaying this debilitating disease.

Explorations on risk profiles for overweight and obesity in 9501 preschool-aged children

BackgroundChildhood obesity places a major burden on global public health. We aimed to identify and characterize potential factors, both individually and jointly, in association with overweight and obesity in Chinese preschool-aged children. MethodsWe cross-sectionally recruited 9501 preschool-aged children from 30 kindergartens in Beijing and Tangshan. Overweight and obesity are defined according to the World Health Organization (WHO), International Obesity Task Force (IOTF), and China criteria. ResultsAfter multivariable adjustment, eating speed, sleep duration, birthweight, and paternal body mass index (BMI) were consistently and significantly associated with childhood overweight and obesity under three growth criteria at a significance level of 5%. Additional fast food intake frequency, maternal BMI, gestational weight gain (GWG) and maternal pre-pregnancy BMI were significant factors for overweight (WHO criteria) and obesity (both IOTF and China criteria). Importantly, there were significant interactions between parental obesity and eating speed for childhood obesity. Finally, for practical reasons, risk nomogram models were constructed for childhood overweight and obesity based on significant factors under each criterion, with good prediction accuracy. ConclusionOur findings indicated a synergistic association of lifestyle, fetal and neonatal, and family-related factors with the risk of experiencing overweight and obesity among preschool-aged children.

Synergistic Association With Root Endophytic Fungi Improves Morpho-Physiological and Biochemical Responses of Chenopodium quinoa to Salt Stress

Symbiotic associations with microbes can contribute to mitigating abiotic environmental stress in plants. In this study, we investigated individual and interactive effects of two root endophytic fungal species on physiological and biochemical mechanisms of the crop Chenopodium quinoa in response to salinity. Fungal endophytes (FE) Talaromyces minioluteus and Penicillium murcianum, isolated from quinoa plants that occur naturally in the Atacama Desert, were used for endophyte inoculation. A greenhouse experiment was developed using four plant groups: (1) plants inoculated with T. minioluteus (E1+), (2) plants inoculated with P. murcianum (E2+), (3) plants inoculated with both fungal species (E1E2+), and (4) non-inoculated plants (E-). Plants from each group were then assigned to either salt (300 mM) or control (no salt) treatments. Differences in morphological traits, photosynthesis, stomatal conductance, transpiration, superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase, (POD), phenylalanine ammonia-lyase (PAL), phenolic content, and lipid peroxidation between plant groups under each treatment were examined. We found that both endophyte species significantly improved morphological and physiological traits, including plant height, number of shoots, photosynthesis, stomatal conductance, and transpiration, in C. quinoa in response to salt, but optimal physiological responses were observed in E1E2+ plants. Under saline conditions, endophyte inoculation improved SOD, APX, and POD activity by over 50%, and phenolic content by approximately 30%, with optimal enzymatic responses again observed in E1E2+ plants. Lipid peroxidation was significantly lower in inoculated plants than in non-inoculated plants. Results demonstrate that both endophyte species enhanced the ability of C. quinoa to cope with salt stress by improving antioxidative enzyme and non-enzyme systems. In general, both FE species interacting in tandem yielded better morphological, physiological, and biochemical responses to salinity in quinoa than inoculation by a single species in isolation. Our study highlights the importance of stress-adapted FE as a biological agent for mitigating abiotic stress in crop plants.

Methylprednisolone, venous thromboembolism, and association with heparin to 30\xa0days in hospital survival in severe Covid-19 pneumonia

BackgroundMortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival.MethodsThis was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk.ResultsIn 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335).ConclusionMethylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

Adverse associations of different obesity measures and the interactions with long-term exposure to air pollutants with prevalent type 2 diabetes mellitus: The Henan Rural Cohort study

BackgroundObesity and ambient air pollution are independent risk factors of type 2 diabetes mellitus (T2DM), however, the evidence regarding their joint associations on T2DM was sparsely studied in low-middle income countries. MethodsA total of 38,841 participants were selected from Henan Rural Cohort study which was carried out during 2015–2017. Obesity was identified by body mass index (BMI), WC (waist circumstance), WHR (waist-to-hip ratio), WHtR (waist-to-height ratio), BFP (body fat percent), and VFI (visceral fat index). Three-year averaged-concentrations of NO2, PM1, PM2.5, and PM10 were assessed by using the method of spatiotemporal model incorporated into the satellites data. The independent associations of obesity indicators and exposure to air pollutants on fasting blood glucose (FBG) and T2DM were assessed by generalized linear and logistic regression model, respectively, and their interaction associations on T2DM were quantified by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). ResultsPositive associations of six obesity measures and four air pollutants with FBG levels and prevalent T2DM were observed. Obese participants measured by BMI plus high exposure to NO2, PM1, PM2.5 and PM10 were related to a 2.96-fold (2.66–3.29), 2.87-fold (2.58–3.20), 2.98-fold (2.67–3.32) and 3.01-fold (2.70–3.35) increased risk for prevalent T2DM, respectively; similarity of joint associations of the other obesity measures and air pollutants on T2DM were observed. The additive associations of different obesity measures and air pollutants with prevalent T2DM were further found. ConclusionsThe synergistic associations of obesity and air pollutants on FBG levels and prevalent T2DM were observed, indicating that obese participants were at high risk for prevalent T2DM in highly polluted rural regions.

Neighborhood and Individual Socioeconomic Disadvantage and Survival Among Patients With Nonmetastatic Common Cancers

Disadvantaged neighborhood-level and individual-level socioeconomic status (SES) have each been associated with suboptimal cancer care and inferior outcomes. However, independent or synergistic associations between neighborhood and individual socioeconomic disadvantage have not been fully examined, and prior studies using simplistic neighborhood SES measures may not comprehensively assess multiple aspects of neighborhood SES. To investigate the associations of neighborhood SES (using a validated comprehensive composite measure) and individual SES with survival among patients with nonmetastatic common cancers. This prospective, population-based cohort study was derived from the Surveillance, Epidemiology, and End Results-Medicare database from January 1, 2008, through December 31, 2011, with follow-up ending on December 31, 2017. Participants included older patients (≥65 years) with breast, prostate, lung, or colorectal cancer. Neighborhood SES was measured using the area deprivation index (ADI; quintiles), a validated comprehensive composite measure of neighborhood SES. Individual SES was assessed by Medicare-Medicaid dual eligibility (yes vs no), a reliable indicator for patient-level low income. The primary outcome was overall mortality, and the secondary outcome was cancer-specific mortality. Hazard ratios (HRs) for the associations of ADI and dual eligibility with overall and cancer-specific mortality were estimated via Cox proportional hazards regression. Statistical analyses were conducted from January 23 to April 15, 2021. A total of 96 978 patients were analyzed, including 25 968 with breast, 35 150 with prostate, 16 684 with lung, and 19 176 with colorectal cancer. Median age at diagnosis was 76 years (IQR, 71-81 years) for breast cancer, 73 years (IQR, 70-77 years) for prostate cancer, 76 years (IQR, 71-81 years) for lung cancer, and 78 years (IQR, 72-84 years) for colorectal cancer. Among lung and colorectal cancer patients, 8412 (50.4%) and 10 486 (54.7%), respectively, were female. The proportion of non-Hispanic White individuals among breast cancer patients was 83.7% (n = 21 725); prostate cancer, 76.8% (n = 27 001); lung cancer, 83.5% (n = 13 926); and colorectal cancer, 81.1% (n = 15 557). Neighborhood-level and individual-level SES were independently associated with overall mortality, and no interactions were detected. Compared with the most affluent neighborhoods (ADI quintile 1), living in the most disadvantaged neighborhoods (ADI quintile 5) was associated with higher risk of overall mortality (breast: HR, 1.34; 95% CI, 1.26-1.43; prostate: HR, 1.51; 95% CI, 1.42-1.62; lung: HR, 1.21; 95% CI, 1.14-1.28; and colorectal: HR, 1.24; 95% CI, 1.17-1.32). Individual socioeconomic disadvantage (dual eligibility) was associated with higher risk of overall mortality (breast: HR, 1.22; 95% CI, 1.15-1.29; prostate: HR, 1.29; 95% CI, 1.21-1.38; lung: HR, 1.14; 95% CI, 1.09-1.20; and colorectal: HR, 1.23; 95% CI, 1.17-1.29). A similar pattern was observed for cancer-specific mortality. In this cohort study, neighborhood-level deprivation was associated with worse survival among patients with nonmetastatic breast, prostate, lung, and colorectal cancer, even after accounting for individual SES. These findings suggest that, in order to improve cancer outcomes and reduce health disparities, policies for ongoing investments in low-resource neighborhoods and low-income households are needed.

Gait Speed and Grip Strength Are Predictors of Cognitive Decline and Dementia in Older Individuals.

Lower gait speed and grip strength are common in older adults. However, the results of lower motor function on cognitive outcomes have been mixed. We examined the longitudinal association between baseline slow gait speed and weak grip strength, alone and in combination, with risk of incident dementia or cognitive decline in a cohort of older adults. Participants (n=19,114) aged 70 and over (65 if U.S. minority) without documented evidence of dementia, significant cognitive impairment, physical disability or previous cardiovascular disease at baseline, were recruited from community settings. Incident dementia was adjudicated by an expert panel using DSM-IV criteria. Incident cognitive decline was defined as a persistent intra-individual decline in score of >1.5 SD from baseline on any of the cognitive tests. Using cox proportional hazard models, slow gait speed at baseline was associated with an increased risk of dementia (63%) and cognitive decline (43%), over a median 4.7 years. Weak grip strength was not as strong a predictor, but was also associated with risk (43% and 11%, respectively). Both outcomes showed higher risk for dementia than cognitive decline. There was no gender-specific interaction. When considered together (adjusted for one another), gait speed and grip strength were both independently associated with cognitive decline and dementia. The synergistic association of these physical measures, each of which is readily administered in the clinic or home, serve as effective early markers of increasing risk of cognitive decline and incident dementia and thus, should be considered for routine health assessments for older adults.

High-performance hydrophobic magnetic hydrotalcite for selective treatment of oily wastewater

ABSTRACT Oil emulsified in water is one of the most difficult mixtures to treat due to the good stability of emulsions, so there is a growing demand for more efficient methods for separating immiscible oil/water mixtures. In this context, the focus of this study was to obtain an adsorbent for the selective treatment of a simulated oily wastewater. To this aim, a modified hydrotalcite sample with hydrophobic and magnetic characteristics was prepared and characterized. Initially, the effect of sodium dodecyl sulfate (SDS) amount on the adsorbent characteristics was evaluated (266–800 mgSDS g−1 LDH). The hydrophobic hydrotalcite (LDH-SDS) containing 533 mgSDS g−1 LDH (LDH-SDS2) presented a higher interlayer space where the surfactant molecules were arranged perpendicular to the lamellae, allowing better access to the hydrotalcite pores and facilitating the selective adsorption of oil compounds. Moreover, the synergistic association of hydrophobic properties with super-wetting and effective adhesion oil to Fe3O4 favoured the selective adsorption of the simulated oily wastewater onto the hydrophobic and magnetic hydrotalcite (LDH-MSDS), facilitating the post-treatment separation. The kinetic analysis demonstrated that the adsorption equilibrium was attained in 120 min and the pseudo-second order model was the most suitable for predicting the removal of total organic carbon (TOC) from the simulated oily wastewater. The Langmuir model described very well the equilibrium experimental data, with a maximum adsorption capacity for TOC removal using LDH-MSDS of 659.9 mg g−1. Therefore, the modified hydrotalcite prepared in this study showed intrinsic characteristics that make it a promising adsorbent for the selective treatment of oily wastewaters.

Copper stimulation on methane-supported perchlorate reduction in a membrane biofilm reactor

The present study demonstrated that the perchlorate reduction rate in a methane-based membrane biofilm reactor was significantly enhanced from 14.4 to 25.6 mg-Cl/L/d by increasing copper concentration in the feeding medium from 1 to 10 μM, indicating a stimulatory effect of copper on the methane-supported perchlorate reduction process. Batch tests further confirmed that the increased copper concentration enhanced both methane oxidation and perchlorate reduction rates, which was supported by an increasing trend of functional genes (pmoA for methanotrophs and pcrA for specific perchlorate reducers) abundances through quantitative polymerase chain reaction (qPCR). Both 16S rRNA gene sequencing and functional genes (pmoA and pcrA) sequencing jointly revealed that the biofilm supplied with a higher copper concentration exhibited a more diverse microbial community. The methane-supported perchlorate reduction was accomplished through a synergistic association of methanotrophs (Methylocystis, Methylomonas, and Methylocystaceae) and perchlorate reducers (Dechloromonas, Azospira, Magnetospirillum, and Denitratisoma). Acetate may function as the key syntrophic linkage between methanotrophs and perchlorate reducers. It was proposed that the increased copper concentration improved the activity of particulate methane monooxygenase (pMMO) for methane oxidation or promoted the biosynthesis of intracellular carbon storage compounds polyhydroxybutyrate (PHB) in methanotrophs for generating more acetate available for perchlorate reduction.

Algal consortia based metal detoxification of municipal wastewater: Implication on photosynthetic performance, lipid production, and defense responses

The present investigation was carried out to assess the competence of artificially engineered microalgal consortia i.e. consortia 1 (Scenedesmus vacuolatus + Chlorococcum humicola), consortia 2 (Tetradesmus sp. + Scenedesmus vacuolatus), and consortia 3 (Chlorococcum humicola + Scenedesmus vacuolatus + Tetradesmus sp.) for municipal wastewater treatment and lipid production under laboratory conditions. The purpose of the present study was to screen the competent microalgae consortia based on wastewater remediation, photosynthetic performance, and antioxidant defense responses. The outcome based on nutrient reutilization (78.98–98%), metal detoxification (50–94%), and biomass production (1.43–1.65 folds) reflected greater adaptability and tolerance of consortia 2 against different concentrations of wastewater. The photosynthetic performance parameters such as active photosystem II reaction centre, the quantum yield, and photosynthetic performance index were increased by 1.20–2.35 folds in consortia 2 after treatment with different concentrations of wastewater. Additionally, Fourier transform infrared spectroscopy peak showed at 1750 cm−1 confirmed neutral lipid accumulation in consortia 2 at 100% concentration of wastewater. The measurement of oxidative stress markers such as thiobarbituric acid reactive species and hydrogen peroxide showed considerable decline in consortia 2 as compared to consortia 1 and 3. Interestingly, increased non–enzymatic (1.02–2.44 folds) and enzymatic antioxidant (1.05–4.14 folds) activity in consortia 2 reflected that oxidative stress was attenuated by the amplified activity of ascorbic acid, proline, cysteine, superoxide dismutase, catalase, and glutathione reductase. Overall, photosynthetic performance, lipid production, and antioxidants activity represented that the consortia 2 can be effectively used for sustainable wastewater treatment and lipid production. Thus, the synergistic association of two microalgae may be the superior and neoteric paradigm with multilevel benefits such as sustainable nutrient resource utilization, metal detoxification, and lipid production.

Pseudomonas mediated nutritional and growth promotional activities for sustainable food security.

Numerous microbial communities show synergistic and antagonistic interactions among themselves, resulting in benefit and harm to either or both the associated members. The association holds accountability for nutrients recycling and energy drift, resulting in the availability of macronutrients unavailable and insoluble forms of rhizospheric nutrients, crucial for vital processes in plants, e.g., act as co-factors of various phyto-enzyme and redox mediators. Plant growth promoting rhizobacteria are known to enhance plant growth by increasing these macronutrients availability during their plant root colonization. In comparison to any other genera, Pseudomonas is the most favored bioinoculant due to its significant properties in both plant growth and phytopathogen control during its synergistic association with the host plant. These properties include siderophore production, phosphate solubilization, nitrogen fixation, phenazines, antibiotics, and induced systemic resistance carried out by various Pseudomonas species like Pseudomonas fluorescens, Pseudomonas putida, and Pseudomonas syringae. The association of Pseudomonas with crop plants procures several secretory and electron-based feedback mechanisms in order to regulate the plant growth and phytopathogen control activities through the secretion of several phytohormones (auxins, gibberellins, Indole-3-acetic acid), secondary metabolites (flavonoids) and enzymes (aminocyclopropane-1-carboxylate, phenylalanine ammonia-lyase). Ecologically significant applications of Pseudomonas in biocontrol and bioaugmentation are crucial for maintaining food security.

Synergistic association of endophytic fungi enhances tolerance, growth, and heavy metal uptake of Alocasia calidora in landfill contaminated soil

The present research is designed to determine the influence of inoculation of a consortium of indigenous filamentous fungi on the modulation of Alocasia calidora growth attributes and biochemical responses and to investigate the tolerance, uptake, and translocation of multiple metals under multi-metal contamination. The results revealed increased activity of soil enzymes: urease (EC 3.5.1.5), acid phosphatase (EC 3.1.3.2), invertase (EC 3.2.1.26), and dehydrogenase in the fungi supplemented soil. The inoculation of A. calidora with a consortium of fungi enhanced substantially the shoots and roots growth through improved production of chlorophyll and carotenoids. The upregulated activity of antioxidant enzymes (peroxidase (EC 1.11.1.7), catalase (EC 1.11.1.6), and ascorbate peroxidase (EC 1.11.1.11)) was equally monitored in the fungi inoculated A. calidora. Various metabolites which aided the metal tolerance, growth, and accumulation were determined in the plant (Tryptophan (L-tryptophan), Indole-acrylic acid (Indole-3-acrylic acid), 5,7,2′,3′-Tetrahydroxyflavone, 5,2-Dihydroxyflavone, Scutellarein-6-glucoside, tripeptides, S-(4-Nitrobenzyl) glutathione). Chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were significantly accumulated in the shoots of inoculated A. calidora (P < 0.05), while, the accumulated iron (Fe, 1203.00 mg/kg), Pb (347.51 mg/kg), and Zn (523.02 mg/kg) in the roots of inoculated A. calidora were also higher than those of the control A. calidora. It is presumed that inoculation of A. calidora with fungal organisms can be utilized as an effective strategy for enhancing the tolerance, growth, and metal removal from polluted soils.

Early pregnancy exposure to metal mixture and birth outcomes - A prospective study in Project Viva.

Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. To estimate individual and joint effects of metal mixture components on birth outcomes. We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n=729) and head circumference (n=791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3g (95% CI: -79.9, 29.3), 47.9g (95% CI: -98.0, 2.1), and 72.2g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18cm (95% CI: -0.35, -0.02), 0.10cm (95% CI: -0.25, 0.04), 0.03cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.

PSXVI-26 Using synchrotron/globar techniques to reveal synergistic and interactive association between molecular structures and nutrient supply in enzymatic and thermal treated oat tissue and whole grain

Abstract As an advanced technique, synchrotron radiation-based microspectroscopy SR-FTIRM has been a rapid, direct, non-destructive and non-invasive bioanalytical method. Globar molecular spectroscopic technique -attenuated total reflectance-ATR-FTIR spectroscopy will be used. For this research, feed type CDC Nasser, forage type CDC haymaker, and milling types CDC Arborg and Summit with three consecutive years are studied. There are three treatments for oat samples: Treatment 1, steam pressure processing alone; Treatment 2, adding innovative fibrolytic enzyme; Treatment 3, steam pressure processing plus fibrolytic enzyme. Each treatment combination has three replications. The objectives of this research are to detect the molecular structure spectral features of processed oat endosperm tissues at a molecular and cellular level in relation to chemical profiles, protein and carbohydrate fractions, energy profiles, degradation kinetics, intestinal digestibility, microbial protein production and true nutrient supply of whole oat grains. This research reveals the interactive association between induced molecular structure changes and nutrient properties and true nutrient supply. This research is also to increase economic returns to oat producers and related dairy industries through efficient utilization of feed-type or milling type of oat grains.

Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study.

Aims/IntroductionWe aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes.Materials and MethodsA cross‐sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m2. Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor‐α receptor 1 (sTNFαR1), and high‐sensitivity C‐reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined.ResultsDKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006).ConclusionsUnder an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.

P48.09 Body Mass Index Predicts Benefit From Adding Metformin to EGFR-TKIs in Patients With Lung Adenocarcinoma: Subanalysis From an RCT

Evidence regarding the synergistic association between EGFR-TKIs and metformin has been controversial, with conflicting results from phase II clinical trials performed in different populations. The reasons for the discrepancies could be related to differences in the populations studied in each single-country trial. Interestingly, one factor which was not evaluated in either trial was whether the benefit from metformin was dependent on body mass index (BMI) or baseline glucose uptake by the tumor through PET-CT-FDG.

Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease.

Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH). Participants of the Helsinki Small Vessel Disease Study (n=152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single-leg stance, timed up-and-go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant-evaluated IADL, but not on self-evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance. The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.

Synergistic associations of visual and self-reported hearing acuity with low handgrip strength in older adults: a population-based cross-sectional study

BackgroundIt is unclear whether visual and hearing acuity are independently or synergistically associated with muscle strength. We aimed to examine the associations of visual and self-reported hearing acuity with low handgrip strength and the additive interaction between visual and hearing acuity on low handgrip strength in people over 60 years.MethodData of 3,075 individuals aged over 60 years from the 2017 and 2018 Korea National Health and Nutrition Examination Survey were used for this cross-sectional study. Low handgrip strength was defined based on the 20th percentile of the study population (< 30.4 kg for male and < 17.7 kg for female). Visual and self-reported hearing acuity were each divided into three categories: good, moderate, and impaired. Multiple logistic regression and relative excess risk due to interaction (RERI) were performed.ResultsOf the 3,075 participants, 993 (32.3 %) demonstrated low handgrip strength. Low handgrip strength was more prevalent in participants with moderate (adjusted odds ratio [AOR] = 1.54, 95 % confidence interval [CI] = 1.12–2.12) and impaired visual acuity (AOR = 2.00, 95 % CI = 1.34–2.96). Both moderate and impaired self-reported hearing acuity were significantly associated with low handgrip strength (moderate: AOR = 1.25, 95 % CI = 1.01–1.55; impaired: AOR = 1.66, 95 % CI = 1.15–2.38). The more severe the sensory function decline, the higher the association with muscle weakness. Moreover, combined sensory impairments were associated with deteriorating low handgrip strength (AOR = 8.38), with significantly strong additive interactions (RERI = 2.61, 95 % CI = 2.52–2.70).ConclusionsAwareness is needed regarding the risk of reduced muscle strength in individuals with moderate and impaired sensory function. Older people with sensory function decline in clinical settings may benefit from programs such as exercise prescription to prevent muscle weakness.

Synergistic association of hyperuricemia and hyperhomocysteinemia with chronic kidney disease in middle-aged adults and the elderly population.

Chronic kidney disease (CKD) is a major global public health issue. Both hyperhomocysteinemia (HHcy) and hyperuricemia are independent risk factors for CKD. In this study, we evaluated the association of HHcy and hyperuricemia with CKD in the middle-aged and elderly populations in Taiwan.In this cross-sectional study, we collected the data of 5910 patients aged ≥50 years after their self-paid health examination at a single medical center. Homocysteine (Hcy) levels were divided into 4 quartiles (Q1, <8.2; Q2, 8.2–9.8; Q3, 9.9–11.7; and Q4, >11.7 μM/L). Renal function was determined using the Chronic Kidney Disease Epidemiology Collaboration equation. Patients were considered to have CKD if their estimated glomerular filtration rate was < 60 mL/min/1.73 m2.The prevalence of CKD significantly increased with the quartiles of uric acid (UA) and Hcy. In multiple logistic regression analysis, the odds ratios (ORs) of CKD increased with the quartiles of Hcy, independent of UA. There was 22.9 in Q4 in the normal serum UA group and 18.3 in the hyperuricemia group compared with Q1 of Hcy. Both hyperuricemia (OR 2.9) and Q4 of Hcy (OR 8.1) were significant independent risk factors for CKD. Furthermore, hyperuricemia and HHcy had significant synergistic association (synergy index, 1.7) with CKD.The ORs of CKD increased with the quartiles of Hcy, independent of hyperuricemia. Hyperuricemia and HHcy had synergistic association with CKD.