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Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. Results: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (−0.16 [−0.20, −0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile −0.12 [−0.18, −0.050]; −0.16 [−0.23, −0.09]; −0.11 [−0.18, −0.05], respectively) than those with average genetic susceptibility. Conclusions: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion The impact of smoking on ulcerative colitis (UC) among Asian populations is controversial, and interactions between genetic factors and smoking are not well studied. We evaluated the association between smoking and UC and assessed interactions between smoking and family history.Using the National Health Insurance database, we identified 5.5 million individuals from 2002 to 2019 with information on familial relationships and smoking history. Cox proportional hazard regression was used to examine the association between UC and current/former smoking and estimate familial risk. Interactions between family history and smoking were assessed on an additive scale using relative excess risk due to interaction (RERI).Current smoking was associated with a decreased risk of disease (hazard ratio [HR] 0.53 95% CI 0.49–0.56), whereas former smoking was associated with an increased risk (HR 1.62 95% CI 1.53–1.71), compared to nonsmokers. Familial risk was HR 7.51 (95% CI 6.68–8.48). The protective effect of current smoking was more pronounced among those with a family history, as their combined effect was lower than the sum of their individual risks (HR 4.37 vs. 7.55), whereas the harmful effect of former smoking was more prominent among this group, and their combined effect exceeded the sum of their individual effects (HR 10.20 vs. 8.57), indicating statistically significant interactions (RERI current: −3.18 95% CI −4.89 to −1.47; former: 1.63 95% CI −1.00–4.25).The effects of smoking on UC do not appear to differ between Asian and Western populations. Possible gene‐smoking interactions were observed but in opposing directions for current/former smoking. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa poses a serious threat in healthcare settings. This bacterium can develop resistance to many antibiotics, rendering even last-resort treatments ineffective. Additionally, it forms protective biofilms that shield it from the immune system, making infection treatment challenging. This study investigated the susceptibility of five clinically isolated strains of the test bacteria to a combination of ciprofloxacin and cuminaldehyde. Cuminaldehyde (a natural phytochemical) and ciprofloxacin (an antibiotic) were separately found to show antimicrobial effect against test organism. However, the combination of selected compounds showed an additive effect in their microbial growth inhibitory activity. The mentioned compounds at their sub-MIC doses subjected to test whether they could show any extent of biofilm inhibition or disintegration property against the clinical strains of P. aeruginosa. The chosen concentrations of the compounds demonstrated significant antibiofilm activity against all the tested clinical strains. Additionally, it was observed that the compounds not only accumulated reactive oxygen species (ROS) but also enhanced the cell membrane permeability of the clinical strains. These findings suggest that the combination of ciprofloxacin and cuminaldehyde could explore new directions in fighting P. aeruginosa-linked infections. [ABSTRACT FROM AUTHOR]

Abstract Limited studies have been conducted on the interaction of smoking and abdominal obesity on the risk of pre-diabetes mellitus (PDM) among rural adults in southwest China. The data was obtained from a cross-sectional survey conducted using a two stage random sampling method around Rongchang district in ChongQing municipality southwest of China in 2022. A total of 3,017 participants aged 40 to 79 years old were included in the study. Multivariate logistic regression analyses were performed to evaluate the associated risk factors for PDM, and the effect of multiplicative and additive interactions between smoking and abdominal obesity were also assessed by indicators including the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP) and the synergy index (SI). We found that the prevalence of PDM in participants was 38.98% with an average age of (62.14 ± 11.13) years. Following adjustments for confounding variables, current smoking (OR = 1.26, 95%CI:1.04–1.52) and abdominal obesity (OR = 1.4, 95%CI:1.18–1.66) were significantly linked to an elevated risk of PDM. The multiplicative interaction analyses demonstrated that current smoking exhibited a positive association with PDM (OR = 1.32, 95%CI:1.01–1.71), while a similar association was not observed in the case of abdominal obesity with PDM (OR = 1.15, 95%CI:0.94–1.4). A significant additive interaction was observed between current smoking and abdominal obesity in terms of PDM risk (OR = 3.56, 95% CI: 2.54–4.98). The RERI = 2.09(0.95–3.24), indicating a coexisting risk attributable to additive interaction; the AP = 0.59(0.43–0.75), indicating that 59% of all PDM individuals exposed to both risk factors could be attributed to the synergistic effect of current smoking and abdominal obesity; the SI = 5.51(2.15–14.1), suggesting that the synergistic risk between current smoking and abdominal obesity was 5.51times greater than the sum of effects observed in individuals exposed to a single factor alone. The prevalence of PDM in Rongchang, potentially indicating a higher future incidence of diabetes mellitus. It is noteworthy that smoking and abdominal obesity exhibit a positive synergistic effect on the risk of PDM.

Abstract Background The NLRP3 inflammasome, a pivotal mechanism regulating inflammatory responses and featuring the pyrin domain containing 3 (NLRP3) within the NOD-like receptor family, is widely recognized as a central pathogenic factor in cardiovascular diseases. The present study endeavors to delve into the correlation and potential interplay between the rs10754558 polymorphism of NLRP3 and the predisposition to hypertension among the Chinese adult population. Methods All the participants who came from a community in Bengbu, China were investigated by being interviewed with a questionnaire. Overall, 354 paired case–control participants were analyzed. Genomic DNA was extracted from 5ml venous blood using the Tiangen DNA extraction kit. The rs10754558 polymorphism of the NLRP3 gene was genotyped by TaqMan allelic discrimination real-time PCR.The association between the rs10754558 polymorphism and hypertension risk was investigated by a logistic regression analysis. Furthermore, an additive interaction analysis was conducted using related indicators, including the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). Results Participants carrying the GG genotype were more likely to develop hypertension than participants carrying the CC genotype (adjusted odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.33–3.52). A significant additive interaction between the NLRP3 polymorphism and obesity status concerning the risk of hypertension was observed, as estimated by all indicators: RERI (1.12, 95% CI: 0.70–1.5), AP (0.34, 95% CI: 0.14–0.53), and SI (1.92, 95% CI: 1.03–3.59). The values of RERI (1.74, 95% CI: 0.37–3.11), AP (0.46, 95% CI: 0.21–0.70), and SI (2.62, 95% CI: 1.18–5.83) showed that a significant interaction between the rs10754558 polymorphism and a family history of hypertension. Conclusions Our findings indicate a significant association between the NLRP3 rs10754558 polymorphism and the risk of hypertension in Chinese adults. Moreover, a notable additive interaction emerges between NLRP3 polymorphisms and obesity status, further amplifying the risk of hypertension.

Abstract Background Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF). Methods A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (

Background: The NLRP3 inflammasome, a pivotal mechanism regulating inflammatory responses and featuring the pyrin domain containing 3 (NLRP3) within the NOD-like receptor family, is widely recognized as a central pathogenic factor in cardiovascular diseases. The present study endeavors to delve into the correlation and potential interplay between the rs10754558 polymorphism of NLRP3 and the predisposition to hypertension among the Chinese adult population. Methods: All the participants who came from a community in Bengbu, China were investigated by being interviewed with a questionnaire. Overall, 354 paired case–control participants were analyzed. Genomic DNA was extracted from 5ml venous blood using the Tiangen DNA extraction kit. The rs10754558 polymorphism of the NLRP3 gene was genotyped by TaqMan allelic discrimination real-time PCR.The association between the rs10754558 polymorphism and hypertension risk was investigated by a logistic regression analysis. Furthermore, an additive interaction analysis was conducted using related indicators, including the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). Results: Participants carrying the GG genotype were more likely to develop hypertension than participants carrying the CC genotype (adjusted odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.33–3.52). A significant additive interaction between the NLRP3 polymorphism and obesity status concerning the risk of hypertension was observed, as estimated by all indicators: RERI (1.12, 95% CI: 0.70–1.5), AP (0.34, 95% CI: 0.14–0.53), and SI (1.92, 95% CI: 1.03–3.59). The values of RERI (1.74, 95% CI: 0.37–3.11), AP (0.46, 95% CI: 0.21–0.70), and SI (2.62, 95% CI: 1.18–5.83) showed that a significant interaction between the rs10754558 polymorphism and a family history of hypertension. Conclusions: Our findings indicate a significant association between the NLRP3 rs10754558 polymorphism and the risk of hypertension in Chinese adults. Moreover, a notable additive interaction emerges between NLRP3 polymorphisms and obesity status, further amplifying the risk of hypertension. [ABSTRACT FROM AUTHOR]

Adsorptive polymer additives have been reported to improve the retention capacity of oil films under hydrodynamic lubrication and to reduce friction under boundary lubrication. These effects are believed to result from the formation of a polymer adsorption film on the surface that acts as a lubricious coating. Polymer adsorption films have become dominant in nanometer-order microscopic gaps. However, their mechanical properties are difficult to quantify. This hinders the development of polymer additives. In our previous study, we successfully measured the shear viscoelasticity of lubricants (base oils) sheared in nanogaps using an originally developed measurement method called the fiber wobbling method (FWM). In this study, we measured the shear viscoelasticity of polymer-added lubricants in nanogaps by using FWM. In addition, we developed a heating stage in the FWM to quantify the temperature dependence of shear viscoelasticity in nanogaps. As a result, the viscosity index improved and elasticity was observed in the nanogap, where the polymer adsorption film was dominant. Furthermore, our results indicated that the elasticity of the adsorbed polymer film originated from entropic elasticity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to explore, on an additive scale, the combined effect of the association between insulin resistance (IR), chronic low-grade inflammation (CLGI) and vitamin D deficiency (VDD) on the risk of type 2 Diabetes Mellitus (T2DM). Methods: This is a cohort study, including 1484 non-diabetic subjects, followed for a period of four years. 25 hydroxy-vitamin D (25OHD), hypersensitive C-reactive protein (HsCRP) and triglyceride-glucose index were assessed. Based on VDD and CLGI, the population was subdivided into 4 exposure groups. Analysis was performed both in the case of IR and without IR. Cox proportional regression and additive interaction were applied to explore cumulative effects of exposure. Results: At follow-up, 162 newly diagnosed cases of T2DM were identified. TYG index (RR = 4.0[2.8–5.6]), HsCRP (RR = 1.6 [1.4–1.7]) and 25OHD (RR = 0.96 [0.39–0.98]) were all significantly associated with the risk of T2DM (p < 0.01). The highest excess risk was recorded in patients cumulating simultaneously IR, CLGI and VDD (RR= 8.4[3.6–19.8], p < 0.0001). The additive interaction was significant, the excess risk linked to the interaction RERI = 10.5[1.43–19.7], the proportion attributable to the combined effect: AP = 0.61[0.37–0.85], and the interaction was synergistic: synergy index: 2.8[1.42–5.69]. Conclusion: Baseline levels of TYG index, 25OHD and HsCRP are strongly predictive of future T2DM, and their joint effects are additive and synergistic. Interventional studies are therefore warranted in order to evaluate whether vitamin D supplementation, combined with appropriate anti-inflammatory therapies, is effective as a preventive strategy to reduce the risk of T2DM. [ABSTRACT FROM AUTHOR]

Background: Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF). Methods: A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (< 25.0 kg/m2), overweight (25.0–29.9 kg/m2), and obesity (≥ 30.0 kg/m2). Genetic risk for each outcome was defined as low (lowest tertile), intermediate (second tertile), and high (highest tertile) using polygenic risk score. The joint associations of BMI categories and genetic risk with incident CVD were investigated using Cox proportional hazard models. Additionally, additive interactions were evaluated. Results: Among the 496,851 participants, 270,726 (54.5%) were female, with a mean (SD) age was 56.5 (8.1) years. Over a median follow-up (IQR) of 12.4 (11.5–13.1) years, 102,131 (22.9%) participants developed HTN, 26,301 (5.4%) developed AF, 32,222 (6.9%) developed CHD, 10,684 (2.2%) developed stroke, and 13,304 (2.7%) developed HF. Compared with the normal weight with low genetic risk, the obesity with high genetic risk had the highest risk of CVD: HTN (HR: 3.96; 95%CI: 3.84–4.09), AF (HR: 3.60; 95%CI: 3.38–3.83), CHD (HR: 2.76; 95%CI: 2.61–2.91), stroke (HR: 1.44; 95%CI: 1.31–1.57), and HF (HR: 2.47; 95%CI: 2.27–2.69). There were significant additive interactions between BMI categories and genetic risk for HTN, AF, and CHD, with relative excess risk of 0.53 (95%CI: 0.43–0.62), 0.67 (95%CI: 0.51–0.83), and 0.37 (95%CI: 0.25–0.49), respectively. Conclusions: BMI and genetic factors jointly and interactively contribute to incident CVD, especially among participants with high genetic risk. These findings have public health implications for identifying populations more likely to have cardiovascular benefit from weight loss interventions. [ABSTRACT FROM AUTHOR]

IntroductionThe present study aimed to examine the additive interaction of family medical history of cardiovascular disease (CVD) and self-reported hypertension and diabetes on the diagnosis of CVD among older adults aged 45 years and above in India. A family medical history of CVD in individuals with hypertension and diabetes could identify a subpopulation with a higher risk of CVD.MethodsThe study used the data from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017–2018). The total sample size for the study was 58,734 older adults aged 45 years and above. An additive model was applied to determine the additive interaction effect of the family medical history of CVD with hypertension and diabetes on the diagnosis of CVD by calculating three different measures of additive interaction: the relative excess risk due to interaction (RERI), attribution proportion due to interaction (AP), and synergy index (S).ResultsThe prevalence of CVD was higher among hypertensive individuals with a family medical history of CVD (18.6%) than individuals without the coexistence of family medical history of CVD and hypertension (4.7%), and hypertensive individuals without family medical history of CVD (11.3%). On the other hand, the prevalence of CVD was higher among individuals with diabetes and family history of CVD (20.5%) than individuals without the coexistence of family history of CVD and diabetes (5.0%). Individuals with parental and sibling medical history had two times higher odds of having chronic heart diseases and strokes, respectively than those without parental and sibling history. In the adjusted model, RERI, AP, and S for CVD were 2.30 (95% CI: 0.87–3.74), 35% (0.35; 95% CI: 0.20–0.51), and 1.71 (95% CI: 1.27–2.28) respectively, demonstrating significant positive interaction between family medical history and hypertension on the diagnosis of cardiovascular diseases.ConclusionsThe present study revealed that in the additive model, the interaction effects of family medical history and hypertension were significantly positive on cardiovascular diseases even after adjustment with potential confounding factors. Therefore, it is crucial to consider the presence of family medical history of CVD among individuals with hypertension and diabetes measured in research and clinical practice.

Background and Objectives: In the context of disease prevention, interaction on an additive scale is commonly assessed to determine synergistic effects between exposures. While the "Relative Excess Risk due to Interaction" represents the main measure of additive interaction between risk factors, in this study we aimed to extend this approach to assess additive interaction between factors known to prevent the event's occurrence, such as medical interventions and drugs. Materials and Methods: We introduced and described the "Relative Risk Reduction due to Interaction" (RRRI) as a key measure to assess additive interactions between preventive factors, such as therapeutic interventions and drug combinations. For RRRI values closer to 1, the combination of exposures has a greater impact on reducing the event risk due to their interaction. As a purely illustrative example, we re-evaluated a previous investigation of the synergistic effect between statins and blood pressure-lowering drugs in preventing major adverse cardiovascular events (MACE). Moreover, simulation studies were used to empirically evaluate the performance of a robust Poisson regression model to estimate RRRI across different scenarios. Results: In our example, the drug combination revealed a positive additive interaction in further reducing MACE risk (RRRI > 0), even if not statistically significant. This result is more straightforward to interpret as compared to the original one based on the RERI. Additionally, our simulations highlighted the importance of large sample sizes for detecting significant interaction effects. Conclusion: We recommend RRRI as the main measure to be considered when exploring additive interaction effects between protective exposures, such as the investigation of synergistic effects between drug combinations or preventive treatments. [ABSTRACT FROM AUTHOR]

Evening-type and insomnia symptoms are significantly related to each other and independently associated with depressive symptoms, yet few studies have examined the potential interaction between these two conditions. Therefore, we aimed to examine the associations of evening-type and insomnia symptoms with depressive symptoms among Chinese youths, with a specific focus on the joint effects of the two conditions on depressive symptoms. Participants aged between 12 and 25 were invited to participate in an online survey from December 15, 2022, to May 26, 2023. Multivariate logistic regression models and additive interaction models were used to examine the independent and joint effects of chronotypes and insomnia symptoms on depressive symptoms, respectively. Of the 6145 eligible youths, the prevalence of evening-type and insomnia symptoms were 24.9 % and 29.6 %, respectively. Both evening-type (adjusted OR, [AdjOR]: 3.21, 95 % CI: 2.80–3.67) and insomnia symptoms (AdjOR: 10.53, 95 % CI: 9.14–12.12) were associated with an increased risk of depressive symptoms. In addition, the additive interaction models showed that there is an enhanced risk of depression related to interaction between evening-type and insomnia symptoms (relative excess risk due to interaction, [RERI]: 11.66, 95 % CI: 7.21–16.11). The present study provided additional evidence demonstrating the presence of interaction between evening-type and insomnia symptoms, which can lead to a higher risk of depressive symptoms. Our findings argue the need for addressing both sleep and circadian factors in the management of depressive symptoms in young people. • Insomnia symptoms and evening-type are prevalent in young people. • Both insomnia symptoms and evening-type are independent risk factors of depressive symptoms. • There is a greater combined impact of insomnia symptoms and evening-type on depression (synergistic effect) than the mere sum of their individual effect. • Addressing both insomnia and circadian problems may be beneficial for managing depressive symptoms in young people. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions. Aims: We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia. Method: Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression. Results: In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61–0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35–1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17–0.31). Conclusions: High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention. [ABSTRACT FROM AUTHOR]

Background: To prospectively assess the individual and joint effects of birth weight and the life’s essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life. Methods: In 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids. Results: Low birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02–1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71–11.15), P

BackgroundCombining genetic risk factors and plasma fatty acids (FAs) can be used as an effective method of precision medicine to prevent hypertension risk.MethodsA total of 195,250 participants in the UK Biobank cohort were included in this study from 2006–2010. Polygenic risk scores (PRSs) were calculated for hypertension using single-nucleotide polymorphisms (SNPs). Concentrations of plasma FAs, including polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs), were tested by nuclear magnetic resonance. The Cox model was used to test for the main effects of PRS, different plasma FAs and their joint effects on hypertension. Relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP) were used to test the additive interaction.ResultsPlasma PUFAs, n-3 PUFAs, MUFAs and SFAs were related to the risk of hypertension (PUFAs: HR, 0.878; 95% CI, 0.868–0.888; MUFAs: HR, 1.13; 95% CI, 1.123–1.150; SFAs: HR, 1.086; 95% CI, 1.074–1.098; n-3 PUFAs: HR, 0.984; 95% CI, 0.973–0.995). Moreover, an additive interaction was found between PRS and plasma FAs, which could contribute to an approximately 10–18% risk of hypertension, and the associations between high plasma MUFAs and a high PRS of hypertension were the strongest positive [RERI: 0.178 (95% CI: 0.062, 0.294), AP: 0.079 (95% CI: 0.027, 0.130)].ConclusionIncreased plasma MUFAs or SFAs and decreased plasma PUFAs or n-3 PUFAs were associated with hypertension risk, especially among people at high genetic risk.

Abstract Background The present study aimed to estimate the additive interaction of family history of diabetes and hypertension on the diagnosis of diabetes among individuals aged 45 years and above in India. The coexistence of these two exposures may act synergistically on the risk of diabetes, leading to adverse health outcomes. Methods The study utilized the data from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017–2018). The total sample size for the current study was 58,612 individuals aged 45 years and above. Multivariable logistic regression models were employed to determine the individual and joint effect of a family history of diabetes with hypertension on diabetes. An additive model was applied to assess the interaction effect of the family medical history of diabetes with hypertension on the diagnosis of diabetes by calculating three different measures of additive interaction such as the relative excess risk due to interaction (RERI), attribution proportion due to interaction (AP), and synergy index (S). Results The prevalence of diabetes was three times higher among individuals with family history of diabetes (27.8% vs. 9.2%) than those without family history. Individuals with family history of diabetes (AOR: 2.47, CI: 2.11 2.89) had 2.47 times higher odds of having diabetes than those without family history. The prevalence of diabetes was significantly higher among individuals with hypertension and family history of diabetes (46.6%, 95% CI: 39.7–53.6) than those without the coexistence of family history of diabetes and hypertension (9.9%, 95% CI: 9.5–10.4), individuals with hypertension and without a family history of diabetes (22.7%, 95% CI: 21.2–24.2), and individuals with family history of diabetes and without hypertension (16.5%, 95% CI: 14.5–18.7). Moreover, the adjusted odds ratio (AOR) of the joint effect between family medical history of diabetes and hypertension on diabetes was 9.28 (95% CI: 7.51–11.46). In the adjusted model, the RERI, AP, and S for diabetes were 3.5 (95% CI: 1.52–5.47), 37% (0.37; 95% CI: 0.22–0.51), and 1.69 (95% CI: 1.31–2.18) respectively, which indicates that there is a significant positive interaction between family history of diabetes and hypertension on the diagnosis of diabetes. The study findings on interaction effects further demonstrate consistent results for two models of hypertension (self-reported hypertension and hypertensive individuals receiving medication) even after adjustment with potential confounding factors on diabetes (self-reported diabetes and individuals with diabetes receiving medication). Conclusions The study findings strongly suggest that the interaction of family history of diabetes with hypertension has a positive and significant effect on the risk of diabetes even after adjustment with potential confounding factors. Furthermore, the findings indicate a synergistic effect, emphasizing the importance of considering both family medical history of diabetes and hypertension when assessing diabetes risk and designing preventive strategies or interventions.

AbstractObjectiveMethodsResultsConclusionsTo examine a potential synergistic effect of history of childhood adversity and COVID-19 pandemic exposure on the association with mental health concerns in undergraduate students. Participants: We used U-Flourish Survey data from 2019 (pre-pandemic) and 2020 (during-pandemic) first-year cohorts (n = 3,149) identified at entry to a major Canadian University.Interactions between childhood adversity (physical and sexual abuse, and peer bullying) and COVID-19 pandemic exposure regarding mental health concern (depressive and anxiety symptoms, suicidality, and non-suicidal self-harm) were examined on an additive scale.We found a positive additive interaction between physical abuse and pandemic exposure in relation to suicidality (combined effect was greater than additive effect (risk difference 0.54 vs. 0.36)). Conversely, less than additive interactions between peer bullying and pandemic regarding depression and anxiety were observed.Childhood adversities have diverse reactions to adult stressor depending on the nature of the childhood adversity and the mental health outcomes. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to estimate the additive interaction of family history of diabetes and hypertension on the diagnosis of diabetes among individuals aged 45 years and above in India. The coexistence of these two exposures may act synergistically on the risk of diabetes, leading to adverse health outcomes. Methods: The study utilized the data from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017–2018). The total sample size for the current study was 58,612 individuals aged 45 years and above. Multivariable logistic regression models were employed to determine the individual and joint effect of a family history of diabetes with hypertension on diabetes. An additive model was applied to assess the interaction effect of the family medical history of diabetes with hypertension on the diagnosis of diabetes by calculating three different measures of additive interaction such as the relative excess risk due to interaction (RERI), attribution proportion due to interaction (AP), and synergy index (S). Results: The prevalence of diabetes was three times higher among individuals with family history of diabetes (27.8% vs. 9.2%) than those without family history. Individuals with family history of diabetes (AOR: 2.47, CI: 2.11 2.89) had 2.47 times higher odds of having diabetes than those without family history. The prevalence of diabetes was significantly higher among individuals with hypertension and family history of diabetes (46.6%, 95% CI: 39.7–53.6) than those without the coexistence of family history of diabetes and hypertension (9.9%, 95% CI: 9.5–10.4), individuals with hypertension and without a family history of diabetes (22.7%, 95% CI: 21.2–24.2), and individuals with family history of diabetes and without hypertension (16.5%, 95% CI: 14.5–18.7). Moreover, the adjusted odds ratio (AOR) of the joint effect between family medical history of diabetes and hypertension on diabetes was 9.28 (95% CI: 7.51–11.46). In the adjusted model, the RERI, AP, and S for diabetes were 3.5 (95% CI: 1.52–5.47), 37% (0.37; 95% CI: 0.22–0.51), and 1.69 (95% CI: 1.31–2.18) respectively, which indicates that there is a significant positive interaction between family history of diabetes and hypertension on the diagnosis of diabetes. The study findings on interaction effects further demonstrate consistent results for two models of hypertension (self-reported hypertension and hypertensive individuals receiving medication) even after adjustment with potential confounding factors on diabetes (self-reported diabetes and individuals with diabetes receiving medication). Conclusions: The study findings strongly suggest that the interaction of family history of diabetes with hypertension has a positive and significant effect on the risk of diabetes even after adjustment with potential confounding factors. Furthermore, the findings indicate a synergistic effect, emphasizing the importance of considering both family medical history of diabetes and hypertension when assessing diabetes risk and designing preventive strategies or interventions. [ABSTRACT FROM AUTHOR]

Background: Previous research on the association between serum albumin (ALB) and venous thromboembolism (VTE) has produced inconclusive results. The polygenic risk score is constructed from a set of independent risk variants associated with a disorder, enabling the identification of a larger fraction of the population at comparable or greater disease risk. It is still unknown whether ALB and genetic factors jointly contribute to the incidence of VTE. Objectives: The present study aimed to explore ALB, genetic susceptibility, and the risk of VTE. Methods: The present investigation was an analysis of prospectively collected data from UK Biobank, a population-based, longitudinal cohort. Cox proportional models were used to calculate hazard ratios and 95% CIs for VTE. The Kaplan–Meier curve was utilized to visualize the cumulative risk of VTE according to different serum ALB levels, and the restricted cubic spline model was leveraged to explore the exposure–response relationship among ALB levels and VTE risk. Results: During median follow-up of 13.5 years, 11,502 cases with VTE were diagnosed among 417,113 participants in the UK Biobank. The lower ALB levels were associated with a higher risk for VTE. Individuals with both a high genetic risk and lowest ALB level had the highest risk of VTE (hazard ratio, 3.89; 95% CI, 3.41-4.43), compared with those with low genetic risk and highest ALB level. The positive joint effects of low ALB and polygenic risk score increased the risk of VTE in individuals with high genetic risk. This study excluded non-European patients and primarily focused on the European population, which may limit the generalizability of the findings. Conclusion: Low serum ALB levels were linked to an increased risk of VTE, which was in accordance with a linear dose–response relationship. There was a positive additive effect of ALB and genetic susceptibility on the risk of VTE. ALB could serve as a biomarker for predicting the risk of VTE.

AbstractBackground The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. The study aimed to prospectively assess the interactions and joint effects of birthweight and genetic risk levels on gastrointestinal cancer incidence in adulthood.Methods A total of 254,997 participants were included in the UK Biobank study. We used multivariate restricted cubic splines and Cox regression models to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the association between birthweight and gastrointestinal cancer risk, then constructed a polygenic risk score (PRS) to assess its interaction and joint effect with birthweight on the development of gastrointestinal cancer.Results We documented 2512 incident cases during a median follow-up of 8.88 years. Compare with participants reporting a normal birthweight (2.5–4.5 kg), multivariable-adjusted HR of gastrointestinal cancer incidence for participants with high birthweight (≥4.5 kg) was 1.17 (95%CI: 1.01–1.36). Such association was remarkably observed in pancreatic cancer, with an HR of 1.82 (95%CI: 1.26–2.64). No statistically significant association was observed between low birth weight and gastrointestinal cancers. Participants with high birthweight and high PRS had the highest risk of gastrointestinal cancer (HR: 2.95, 95%CI: 2.19–3.96).Conclusion Our findings highlight that high birthweight is associated with a higher incidence of gastrointestinal cancer, especially for pancreatic cancer. Benefits would be obtained from birthweight control, particularly for individuals with a high genetic risk.KEY MESSAGESThe epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce.This cohort study of 254,997 adults in the United Kingdom found an association of high birthweight with the incidence of gastrointestinal cancer, especially for pancreatic cancer, and also found that participants with high birthweight and high polygenic risk score had the highest risk of gastrointestinal cancer.Our data suggests a possible effect of in utero or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk.

Abstract Background Previous studies have identified that socioeconomic status (SES) and obesity are associated with hypertension. However, their interaction on hypertension risk has not yet been assessed. Methods The study used data from 6,069 Tibetan residents in Chengguan District in Lhasa, the Chinese Tibetan autonomous region’s capital, based on a cohort study conducted from May 2018 to September 2019 in five provinces in southwest China. We used logistic regression models to assess the complex relations of SES and obesity with hypertension. Results Compared with individuals of high SES, low and moderate SES were positively associated with high risk of hypertension. SES and obesity have significant additive interaction on hypertension (general obesity by BMI: RERI = 1.33, P

Recently, dietary inflammatory index (DII) has been introduced as a significant risk factor for MS. We examined the interaction between dietary inflammatory index and some formerly demonstrated key risk factors of multiple sclerosis (MS). We conducted a population-based incident case–control study of 547 MS cases and 1057 controls. Multiplicative and additive interaction were assessed using interaction term in the logistic regression model and synergy index (SI), respectively. Additive interaction was detected between DII and drug abuse (SI = 2.58; 95% CI: 1.14–5.82), gender (SI = 2.00; 95% CI: 1.39–2.87) and history of depression (SI = 1.68; 95% CI: 1.04–2.72) on the risk scale. The risk of MS in drug abusers with DII ≥ 0 was 10.4-times higher than that in non-drug abusers with DII < 0 (OR = 10.4, 95% CI: 5.12–21.02, P < 0.001). We also found that women with DII ≥ 0 had a 9.2 times larger risk compared with the men with DII < 0(OR = 9.2, 95% CI: 6.3–13.5, P < 0.001). Similarly, the risk of MS was remarkably higher in those with a history of depression and DII >0 (OR = 7.6, 95% CI: 5.1–11.5, P < 0.001). There was no evidence of multiplicative interaction between DII and the other risk factors of MS on the risk scale. We identified additive interaction between DII and drug abuse, gender and history of depression on MS. Further studies are needed to understand the underlying mechanisms of these detected interactions. [ABSTRACT FROM AUTHOR]

Background The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. Methods To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. Results Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 1.15, P  =   0.028]. A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 (95% CI, 7.01–17.94)], but not in the CKB. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P  <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk. Conclusions Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic and complex severe psychiatric disorder. Male and female are different in their risks for schizophrenia for the biologic and sociocultural reasons. Homocysteine (Hcy), Cysteine (Cys), and methionine (Met) play important roles in metabolism, and the three amino acids may also be involved in pathogenesis of schizophrenia. This study aimed to test the associations between sulfur-containing amino acid blood levels and risk of schizophrenia, evaluating the different risk in male and female. We organized a case-control study on 876 individuals with schizophrenia and 913 age- and sex-matched healthy subjects as control group. The concentrations of Hcy, Cys and Met were measured by liquid chromatography-tandem mass spectrometry technology. Subsequently, restricted cubic spline was applied to explore full-range associations of these amino acids with schizophrenia. Interactions between levels of the three amino acids and sex on additive scale were also tested. Hcy levels at ≤29 μmol/L were associated with sharply increased risk of schizophrenia, inversely, Met was associated with sharply decreased risk of schizophrenia at levels ≤22 μmol/L. Increased Cys levels were associated with decreased risk of schizophrenia. Almost inverse associations were observed between Cys/Hcy and Met/Hcy ratios and schizophrenia. Significant synergistic interactions between levels of all the three amino acids and sex were discovered on an additive scale. Our study suggests a close association between sulfur-containing amino acids and schizophrenia with different risk in male and female. Future studies are demanded to clarify the pathogenic role of Hcy, Cys and Met in schizophrenia. [ABSTRACT FROM AUTHOR]

The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. The study aimed to prospectively assess the interactions and joint effects of birthweight and genetic risk levels on gastrointestinal cancer incidence in adulthood. A total of 254,997 participants were included in the UK Biobank study. We used multivariate restricted cubic splines and Cox regression models to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the association between birthweight and gastrointestinal cancer risk, then constructed a polygenic risk score (PRS) to assess its interaction and joint effect with birthweight on the development of gastrointestinal cancer. We documented 2512 incident cases during a median follow-up of 8.88 years. Compare with participants reporting a normal birthweight (2.5–4.5 kg), multivariable-adjusted HR of gastrointestinal cancer incidence for participants with high birthweight (≥4.5 kg) was 1.17 (95%CI: 1.01–1.36). Such association was remarkably observed in pancreatic cancer, with an HR of 1.82 (95%CI: 1.26–2.64). No statistically significant association was observed between low birth weight and gastrointestinal cancers. Participants with high birthweight and high PRS had the highest risk of gastrointestinal cancer (HR: 2.95, 95%CI: 2.19–3.96). Our findings highlight that high birthweight is associated with a higher incidence of gastrointestinal cancer, especially for pancreatic cancer. Benefits would be obtained from birthweight control, particularly for individuals with a high genetic risk. The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. This cohort study of 254,997 adults in the United Kingdom found an association of high birthweight with the incidence of gastrointestinal cancer, especially for pancreatic cancer, and also found that participants with high birthweight and high polygenic risk score had the highest risk of gastrointestinal cancer. Our data suggests a possible effect of in utero or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk. [ABSTRACT FROM AUTHOR]

Background and Objectives: In the context of disease prevention, interaction on an additive scale is commonly assessed to determine synergistic effects between exposures. While the “Relative Excess Risk due to Interaction” represents the main measure of additive interaction between risk factors, in this study we aimed to extend this approach to assess additive interaction between factors known to prevent the event’s occurrence, such as medical interventions and drugs. Materials and Methods: We introduced and described the “Relative Risk Reduction due to Interaction” (RRRI) as a key measure to assess additive interactions between preventive factors, such as therapeutic interventions and drug combinations. For RRRI values closer to 1, the combination of exposures has a greater impact on reducing the event risk due to their interaction. As a purely illustrative example, we re-evaluated a previous investigation of the synergistic effect between statins and blood pressure-lowering drugs in preventing major adverse cardiovascular events (MACE). Moreover, simulation studies were used to empirically evaluate the performance of a robust Poisson regression model to estimate RRRI across different scenarios. Results: In our example, the drug combination revealed a positive additive interaction in further reducing MACE risk (RRRI > 0), even if not statistically significant. This result is more straightforward to interpret as compared to the original one based on the RERI. Additionally, our simulations highlighted the importance of large sample sizes for detecting significant interaction effects. Conclusion: We recommend RRRI as the main measure to be considered when exploring additive interaction effects between protective exposures, such as the investigation of synergistic effects between drug combinations or preventive treatments.

Household air pollution (HAP) is associated with the development of lung cancer, yet few studies investigated the exposure patterns and joint associations with tobacco smoking. In our study, we included 224 189 urban participants from China Kadoorie Biobank (CKB), 3288 of which diagnosed with lung cancer during the follow‐up. Exposure to four HAP sources (solid fuels for cooking/heating/stove and environmental tobacco smoke exposure) was assessed at baseline. Distinct HAP patterns and their associations with lung cancer were examined through latent class analysis (LCA) and multivariable Cox regression. A total of 76.1% of the participants reported regular cooking and 52.2% reported winter heating, of which 9% and 24.7% used solid fuels, respectively. Solid fuel heating increased lung cancer risk (Hazards ratio [HR]: 1.25, 95% confidence interval [CI]: 1.08‐1.46). LCA identified three HAP patterns; the "clean fuel cooking and solid fuel heating" pattern significantly increased lung cancer risk (HR: 1.25, 95% CI: 1.10‐1.41), compared to low HAP pattern. An additive interaction was observed between heavy smoking and "clean fuel cooking and solid fuel heating" (relative excess risk [RERI]: 1.32, 95% CI: 0.29‐2.47, attributable proportion [AP]: 0.23, 95% CI: 0.06‐0.36). Cases resulting from solid fuel account for ~4% of total cases (population attribute fraction [PAF]overall: 4.31%, 95% CI: 2.16%‐6.47%, PAFever smokers: 4.38%, 95% CI: 1.54%‐7.23%). Our results suggest that in urban China, solid fuel heating increased the risk of lung cancer, particularly among heavy smokers. The whole population could benefit from cleaner indoor air quality by reducing using solid fuels, especially smokers. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. Methods Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002–2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). Results Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. Conclusion Our findings indicate the possibility of an interaction between RA-associated genes and smoking. [ABSTRACT FROM AUTHOR]

Yan-Yan Zhao,1,&ast; Chun Wang,1,&ast; Wei-Xiao Wang,2 Li-Mei Han,1 Caiyun Zhang,2 Jiao-Yang Yu,3 Wei Chen,2 Chun-Mei Hu1,4 1Department of Tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China; 2Clinical Research Center, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China; 3Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, 710069, People’s Republic of China; 4The Clinical Infectious Disease Center of Nanjing, Nanjing, 210003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chen; Chun-Mei Hu, Email njyy039@njucm.edu.cn; njyy003@njucm.edu.cnBackground: Drug-resistant tuberculosis (TB) is an emerging threat to public health worldwide. Antimicrobial peptide (AMP) is a promising solution to solve the antimicrobial resistance crisis. The apolipoprotein E mimetic peptide COG1410 has been confirmed to simultaneously have neuroprotective, anti-inflammatory, and antibacterial activity. However, whether it is effective to inhibit growth of mycobacteria has not been investigated yet.Methods: The peptide COG1410 was synthesized with conventional solid-phase peptide synthesis and qualified by HPLC and mass spectrometry. Micro-dilution method was used to determine the minimal inhibitory concentration. A time-kill assay was used to determine the bactericidal dynamics of antimicrobial peptide and relative antibiotics. Static biofilm formation was conducted in 24-well plate and the biofilm was separated from planktonic cells and collected. The mechanism of action of COG1410 was explored by TEM observation and ATP leak assay. The localization of COG1410 was observed by confocal laser scan microscopy. The drug–drug interaction was determined by a checkerboard assay.Results: COG1410 was a potent bactericidal agent against M. smegmatis in vitro and within the macrophages with MIC 16 μg/mL, but invalid against M. abscess and M. tuberculosis. A time-kill assay showed that COG1410 killed M. smegmatis as potent as clarithromycin, but faster than LL-37, another short synthetic cationic peptide. 1× MIC COG1410 almost reduced 90% biofilm formation of M. smegmatis. Additionally, COG1410 was able to penetrate the cell membrane of macrophage and inhibit intracellular M. smegmatis growth. TEM observation and ATP leak assay found that COG1410 disrupted cell membrane and caused release of cell contents. Confocal fluorescence microscopy showed that FITC-COG1410 aggregated around cell membrane instead of entering the cytoplasm. Although COG1410 had relative high cytotoxicity, it exhibited strong additive interaction with regular anti-TB antibiotics, which reduced the working concentration of COG1410 and expanding safety window. After 30 passages, there was no induced drug resistance for COG1410.Conclusion: COG1410 was a novel and potent AMP against M. smegmatis by disrupting the integrity of cell membrane.Keywords: antimicrobial peptide, COG1410, Mycobacterium smegmatis, additive interaction

This study aimed to explore the relationship between body mass index (BMI) and abdominal obesity and the risk of airflow obstruction, based on the data from the 2007–2012 National Health and Nutrition Survey (NHANES). Logistic regression was applied to assess the relationships between BMI or abdominal obesity and the risk of airflow obstruction by the fixed ratio method and the lower limit of normal (LLN) method. We further used the restricted cubic splines with 3 knots located at the 5th, 50th, and 95th percentiles of the distribution to evaluate the dose-response relationship. A total of 12,865 individuals aged 20–80 years old were included. In the fixed ratio method, underweight was positively correlated with the risk of airflow obstruction, and overweight and obesity were negatively correlated with the risk of airflow obstruction. In the LLN method, the results were consistent with the fixed ratio method. Abdominal obesity was positively associated with the risk of airflow obstruction only in the fixed ratio method (OR: 1.41, 95% CI: 1.04–1.90). There was an additive interaction between underweight and smoking on airflow obstruction in both methods. Abdominal obesity and smoking had additive interactions in the LLN method. Dose-response analysis indicated that there was a non-linear trend between BMI and the risk of airflow obstruction (Pfor nonlinearity < 0.01). Our study suggested that underweight and abdominal obesity were associated with the increased risk of airflow obstruction, and overweight and general obesity were associated with the decreased risk of airflow obstruction.

Context: Population-based studies on the familial aggregation of Graves disease (GD) are scarce and gene-environment interactions are not wellstudied. Objective: We evaluated the familial aggregation of GD and assessed interactions between family history and smoking. Methods: Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 5 524 403 individuals with first-degree relatives (FDRs). Familial risk was calculated using hazard ratios (HRs), comparing the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using relative excess risk due to interaction (RERI). Results: The HR among individuals with affected FDRs was 3.39 (95% CI, 3.30-3.48) compared with those without affected FDR, and among individuals with affected twin, brother, sister, father, and mother, the HRs were 36.53 (23.85-53.54), 5.26 (4.89-5.66), 4.12 (3.88-4.38), 3.34 (3.16- 3.54), and 2.63 (2.53-2.74), respectively. Individuals with both a positive family history and smoking had an increased risk of disease (HR 4.68) with statistically significant interaction (RERI 0.94; 95% CI, 0.74-1.19). Heavy smokers with a positive family history showed a nearly 6-fold increased risk, which was higher than moderate smoking, suggesting a dose-response interaction pattern. Current smoking also showed a statistically significant interaction with family history (RERI 0.52; 95% CI, 0.22-0.82), while this was not observed for former smoking. Conclusion: A gene-environment interaction can be suggested between smoking and GD-associated genetic factors, which diminishes after smoking cessation. Smokers with a positive family history should be considered a high-risk group and smoking cessation should be advised. [ABSTRACT FROM AUTHOR]

We present all the partial wave descriptions of the nucleon–nucleus system by proposing a new additive phenomenological potential with emphasis on off-energy-shell scattering. For most of the general treatment of the physical processes, the off-shell transition matrices are most expedient quantities because they carry as much information as the potential. As the off-shell Jost solution is an indispensable ingredient for deriving transition matrices, we initially construct this function by taking into account the ordinary differential equation method. Finally, we execute certain tests on our expressions with respect to various limiting conditions and present numerical results using the MATLAB programme. Numerical results are in sensible conformity with the previous works. [ABSTRACT FROM AUTHOR]

Background & Aims: Physical activity, sedentary behaviour, and genetic variants have been associated with the nonalcoholic fatty liver disease (NAFLD). However, whether and how the degree of healthy activity patterns may modify the impact of genetic susceptibility on NAFLD remains unknown. Methods: Behaviour activity factors were determined according to total physical activity (TPA) and sedentary time. The polygenic risk score (PRS) was calculated by variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Cox regression was used to analyse the associations of genetic and behaviour activity factors with incident NAFLD in the UK Biobank (N = 338 087). Results: During a median follow‐up of 12.4 years, 3201 incident NAFLD cases were ascertained. Analyses of TPA and sedentary time simultaneously showed a dose–response association with the risk of NAFLD (ptrend <.001). The association of behaviour activity patterns with NAFLD varied by genetic variants. Of the subjects with high genetic risk, we observed a null protective effect of moderate or high TPA on NAFLD risk, while sitting less than three hours a day significantly decreased the risk of NAFLD (p = 3.50 × 10−4). The high genetic risk of NAFLD can also be offset by the combination of moderate physical activity and shorter sedentary time. Moreover, the high genetic risk group has the greatest reduction of 10‐year absolute risk (6.95 per 1000 person‐years) if reaching both healthy activities. Conclusions: Moderate‐to‐high physical activity and favourable sedentary behaviour may be lifestyle modifications in preventing NAFLD, which could offset the harmful effect of predisposing genetic factors. [ABSTRACT FROM AUTHOR]

As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case-control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10-4 ). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46-0.60) compared to 0.71 (95%CI = 0.66-0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1-5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene-environment analysis in ovarian cancer.

Background: The prevalence of gestational diabetes mellitus (GDM) and advanced maternal age (AMA, = 35 years) has shown an increasing trend worldwide. This study aimed to evaluate the risk of pregnancy outcomes among younger (20-34 years) and older (= 35 years) women with GDM and further analyze the epidemiologic interaction of GDM and AMA on these outcomes. Methods: This historical cohort study included 105 683 singleton pregnant women aged 20 years or older between January 2012 and December 2015 in China. Stratified by maternal age, the associations between GDM and pregnancy outcomes were analyzed by performing logistic regression. Epidemiologic interactions were assessed by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) with their 95% confidence intervals (95%CIs). Results: Among younger women, individuals with GDM had a higher risk of all maternal outcomes, preterm birth (relative risk [RR] 1.67, 95%CI 1.50-1.85), low birthweight (RR 1.24, 95%CI 1.09-1.41), large for gestational age (RR 1.51, 95%CI 1.40-1.63), macrosomia (RR 1.54, 95%CI 1.31-1.79), and fetal distress (RR 1.56, 95%CI 1.37-1.77) than those without GDM. Among older women, GDM increased the risk of gestational hypertension (RR 2.17, 95%CI 1.65-2.83), preeclampsia (RR 2.30, 95%CI 1.81-2.93), polyhydramnios (RR 3.46, 95%CI 2.01-5.96), cesarean delivery (RR 1.18, 95%CI 1.10-1.25), preterm birth (RR 1.35, 95%CI 1.14-1.60), large for gestational age (RR 1.40, 95%CI 1.23-1.60), macrosomia (RR 1.65, 95%CI 1.28-2.14) and fetal distress (RR 1.46, 95%CI 1.12-1.90). Additive interactions of GDM and AMA on polyhydramnios and preeclampsia were found, with RERI of 3.11 (95%CI 0.05-6.16) and 1.43 (95%CI 0.09-2.77), AP of 0.51 (95%CI 0.22-0.80) and 0.27 (95%CI 0.07-0.46), and SI of 2.59 (95%CI 1.17-5.77) and 1.49 (95%CI 1.07-2.07), respectively. Conclusion: GDM is an independent risk factor for multiple adverse pregnancy outcomes, and may exert additive interactions with AMA on the risk of polyhydramnios and preeclampsia. [ABSTRACT FROM AUTHOR]

To examine the independent and interactive associations of being bullied and non-suicidal self-injury (NSSI) with suicidal behaviors (suicidal ideation, suicidal plan, and suicidal attempt) among junior and senior high school students in China. A cross-sectional study was conducted in 4 cities from November 2017 to January 2018 and a total of 18,900 students were enrolled in this study. Being bullied, NSSI and suicidal behaviors were measured by self-reported questionnaires. Analyses were conducted with Chi-square tests, multivariable logistic regression, and additive interaction models. Results showed that the prevalence of suicidal ideation, suicidal plan, and suicidal attempt was 26.4%, 13.2% and 5.2%, respectively. Being bullied was significantly associated with suicidal ideation (OR = 2.35, 95% CI: 2.17–2.55), suicidal plan (OR = 2.25, 95% CI: 2.03–2.48) and suicidal attempt (OR = 2.27, 95% CI: 1.96–2.62). NSSI was significantly positively correlated with suicidal ideation (OR = 3.92, 95% CI: 3.64–4.21), suicidal plan (OR = 3.72, 95% CI: 3.39–4.08) and suicidal attempt (OR = 3.29, 95% CI: 2.86–3.79). Additive interaction models indicated that NSSI was associated with an increase in the risk of suicidal behaviors among adolescents being bullied than those not being bullied. Namely, additive interactions of NSSI and being bullied on suicidal behaviors were found. The NSSI and being bullied have synergistic effects, and co-victimization, rather than single. Meanwhile, considering the perpetrator is critical to intervening suicidal behaviors in adolescence. Ideally, intervention programs should take action from multiple aspects according to different types of factors, including individual level, social environment and institution. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the associations of social jetlag and insomnia symptoms with depressive symptoms among adolescents. A total of 37,871 junior high students completed an online survey between May 24th and Jun 5th, 2022. Insomnia symptoms were assessed by three items based on the Diagnostic and Statistical Manual of Mental Disorders criteria. Social jetlag and depressive symptoms were evaluated by the Munich Chronotype Questionnaire and the Patient Health Questionnaire, respectively. Restricted cubic splines were used to explore the relationship between social jetlag and depressive symptoms. Joint effects of social jetlag and insomnia symptoms on depressive symptoms were estimated using additive interaction models. The prevalence of depressive symptoms was 13.1%. Depressive symptoms were more common in adolescents with social jetlag ≥2 h (OR: 1.51, 95% CI: 1.39–1.65) and insomnia symptoms (OR: 6.91, 95% CI: 6.41–7.44). There was a J-shaped relationship between social jetlag and depressive symptoms when we took social jetlag as a continuous variable. Moreover, a positive additive interaction of social jetlag ≥2 h and insomnia symptoms on depressive symptoms was found in female adolescents (RERI: 2.30, 95% CI: 0.11–4.49). Our findings suggested that social jetlag ≥2 h and insomnia are related to the occurrence of depressive symptoms in adolescents. Their coexistence additively enhances the strength of the association with depressive symptoms. Early screening and intervention for insomnia, as well as methods to reduce social jetlag, should be comprised as part of preventive strategies for depression in adolescents. • A representative sample of Chinese adolescents was used. • Social jetlag ≥2 h and insomnia were associated with a higher risk of depression. • A significant J-shaped relationship between social jetlag and depression was observed. • Joint effects of social jetlag ≥2 h and insomnia on depression were found in females. • Intervention for sleep-wake patterns and insomnia is needed to prevent depression. [ABSTRACT FROM AUTHOR]

Toxicity testing is an important tool for risk assessment of sediment contamination in estuaries. However, there has been a predominant focus on fitness parameters as toxic endpoints and on crustaceans as test organisms, while effects at the sub-organismal level and on other benthic taxa have received less attention. Also, interactions between sediment contamination and natural stressors such as oxygen are often neglected in traditional toxicity tests. Here we conducted a toxicity test of sediments from the Elbe and Oder (Odra) estuaries under three weeks of continuous and intermittent oxygenation, using biomarkers in an annelid, the ragworm Hediste diversicolor. Contaminated sediments affected worm survival and some biomarkers of antioxidant defense, electrophilic stress, and energy status with response ratios of above 20%. Toxic effects were most pronounced in sediments from the upper Elbe estuary, which contained high levels of heavy metals and organic chemicals. Oxygen regimes hardly changed the sediment effects, suggesting the robustness of the biomarker-based toxicity test with ragworms. • Sediments from the Elbe and Oder estuaries contaminated with various chemicals. • Sediment toxicity tested under continuous and intermittent oxygenation. • Ragworm survival and several biomarkers affected by contaminated sediments. • Toxic effects frequently observed in sediments from the upper Elbe estuary. • Sediment toxicity largely independent of oxygen regimes. [ABSTRACT FROM AUTHOR]

Abstract Background The kakaritsuke-yakuzaishi system (henceforth, the family pharmacist system) which provides more health services than those by general pharmaceutical practice, was implemented in Japan in April 2016. To distribute medical resources and medical care expenditures appropriately, identifying the possible major beneficiaries of this system is essential. By analyzing administrative claims data through this retrospective cohort study, we identified modifiers of the potential benefits of the system. Further, we integrated the identified modifiers into a scoring system that indicates the possible benefitting subpopulations. Methods We obtained data about individuals under 75 years old routinely using community pharmacies in Japan from the JMDC database. We classified the individuals as users or non-users. We used claims related to “choufukutouyaku-sougosayoutou-boushi-kasan (additional therapeutic duplication and drug interaction [TDDI] prevention fees)” filed between April 2018 and March 2020, which indicate that individuals’ prescriptions were modified to adjust leftover drugs or to avoid TDDI as indicators of potential benefit. We estimated adjusted absolute risk differences and 95% confidence intervals for product terms using multiple generalized linear regression models. We included the factors whose 95% confidence interval lower limits did not reach 0 in the multiple logistic regression models for developing a scoring system. Results The eligible cohort included 162,340 individuals (1,214 users and 161,126 non-users). The leftover drugs adjustment significantly increased for individuals prescribed antidepressants. However, as only one modifier was identified, we did not develop a scoring system for the leftover drugs adjustment. For TDDI prevention, the following factors were included in the scoring system: being female, being prescribed ≥ 6 drug types, using ≥ 2 medical institutions, and being prescribed proton pump inhibitors, antibiotics, probiotics, or traditional Japanese herbal medicines. The developed scoring system for TDDI prevention scored “female” and “traditional Japanese herbal medicines prescription” factors higher than other factors. Conclusions Individuals who are female or prescribed traditional Japanese herbal medicines, or antidepressants may benefit significantly from the family pharmacist system.

Background: The prevalence of allergic rhinitis (AR) has been increasing steadily worldwide, especially in countries with increasing industrialization such as China. However, available evidence regarding AR prevalence among Chinese adults is scarce and limited to regional data collected in earlier years. We therefore aimed to provide a more recent and robust estimate of AR prevalence using a nationwide representative cross-sectional study in China. Methods: Data of 184 326 participants aged 18 years or older were obtained from the China Chronic Disease and Risk Factor Surveillance conducted in 2018–2019. AR was determined by self-reported sneezing, nasal itching, obstruction, or rhinorrhea symptoms for at least 1 h in the absence of a cold or flu within the last 12 months. Multivariable logistic model was used to examine the risk factors of AR, and a possible non-linear relationship was further tested by restricted cubic spline. Potential additive interactions of risk factors with sex, residence, and geographic region were assessed by relative excess risk due to interaction (RERI). Results: The weighted prevalence of AR was 8.1% (95% confidence interval [CI], 7.4%–8.7%), of whom 23.7% (95% CI, 21.3%–26.0%) were aware of their diagnosis. Increased odds of AR were associated with younger age, men, living in urban area or north region, more education, smoking, underweight, and higher income. Despite the nonsignificant linear trend, the spline regression demonstrated a non-linear association between AR and sleep duration, with higher odds at both ends. Additionally, the observed associations were generally stronger among men and people living in urban area and north region, with significant RERI ranging from 0.07 (95% CI, 0.00–0.14) to 0.40 (95% CI, 0.12–0.67). Conclusions: AR is prevalent in China and the associated factors and interactions are helpful to design targeted preventive strategies towards certain subpopulations. The low awareness of AR calls for a national effort on AR screening.