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The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with ßFLI→SBP = 0.081, P < 0.001 versus ßSBP→FLI = 0.020, P = 0.031; ßFLI→DBP = 0.082, P < 0.001 versus ßDBP→FLI = -0.006, P = 0.480 for CEMC, and ßFLI→SBP = 0.057, P < 0.001 versus ßSBP→FLI = -0.001, P = 0.727; ßFLI→DBP = 0.061, P < 0.001, versus ßDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

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BACKGROUND: Parenting stress has long been proposed as a major risk factor for child maltreatment. However, there is a lack of evidence from existing studies on the temporal sequence to establish a causal relationship. This study aims to examine bidirectional temporal relationships between parenting stress and child maltreatment. METHODS: Longitudinal data from two different sources were analysed: a pre-post study of an online parenting programme conducted across six countries - the ePLH Evaluation Study, and a prospective cohort study in the United States - LONGSCAN. Cross-lagged panel model on parenting stress and child maltreatment was used in each dataset. RESULTS: Based on repeatedly measured data of 484 caregivers in the ePLH study across five time points (every two weeks), we found that parenting stress at an earlier time point predicted later child maltreatment (IRR = 1.14, 95 % CI: 1.10,1.18). In addition, the occurrence of child maltreatment was associated with higher subsequent short-term parenting stress (IRR = 1.04, 95 % CI: 1.01,1.08) and thus could form a vicious circle. In the LONGSCAN analysis with 772 caregivers who were followed up from child age of 6 to child age of 16, we also found parenting stress at an earlier time point predicted later child maltreatment (ß = 0.11, 95 % CI: 0.01,0.20), but did not observe an association between child maltreatment and subsequent long-term parenting stress. LIMITATIONS: Potential information bias on the measurements. CONCLUSIONS: This study provides evidence for a bidirectional temporal relationship between parenting stress and child maltreatment, which should be considered in parenting intervention programmes.

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BACKGROUND AND AIM: Previous studies have demonstrated an association between SUA and dyslipidemia. This study aims to explore the temporal relationship between SUA and dyslipidemia. METHODS AND RESULTS: Based on the Beijing Health Management Cohort conducted from 2013 to 2018, the data of a physical examination population was collected, including a total of 6630 study subjects. Cross-lagged panel analysis was employed to examine the temporal relationship between elevated SUA levels and dyslipidemia, indicated by either elevated TG or decreased HDL-C. The path coefficient and the 95 % CI from baseline TG to follow-up SUA were as follows: in the general population, men, women, and people with BMI ≥25 kg/m2were 0.027 (0.008-0.045), 0.024 (0.001-0.048), 0.032 (0.001-0.063) and 0.033 (0.006-0.059) (P < 0.05); however, the path coefficient from baseline SUA to follow-up TG and the 95 % CI were not statistically significant. Furthermore, the path coefficients and 95 % CIs between elevated SUA and decreased HDL-C were not statistically significant, both in the general population and in populations stratified by gender and BMI. CONCLUSIONS: We found a temporal relationship from elevated TG to elevated SUA in the general population and the populations stratified by gender and BMI (≥25 kg/m2). However, we did not observe a reverse relationship from elevated SUA to elevated TG. Additionally, we did not find a temporal relationship between decreased HDL-C and elevated SUA in both the general population and the stratified populations.

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INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by recurrent episodes of pain. This study aimed to describe the temporal daily relationships between sleep and pain in adolescents with SLE. METHOD: Twenty-three adolescents with SLE recruited from a pediatric hospital wore actigraphy and completed diaries. Generalized estimating equation models were used. RESULTS: On average, evening pain negatively predicted subsequent sleep quality that night, and, on average, sleep quality negatively predicted morning pain. Shorter total sleep time significantly predicted higher morning pain (95% confidence intervals [CI], -0.38 to -0.03, p = .02), whereas sleep efficiency and sleep quality were not significantly associated with morning pain (95% CI, -0.03 to 0.03; 95% CI, -0.08 to 0.06, respectively). Subsequent evening pain did not predict daily nighttime sleep DISCUSSION: Our findings suggest that sleep is a target for pain interventions to include among adolescents with SLE.

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Schema therapy is an effective treatment for personality disorders (PDs). The theory of schema therapy assumes that the decrease of global psychological distress is mediated by change in Early Maladaptive Schemas. The few studies that have investigated a temporal relationship have produced contradictory results. This study examined the temporal relationship between changes in Early Maladaptive Schemas and global psychological distress in Group Schema Therapy (GST) for patients with personality disorders.Assessments were made of 115 patients at baseline, after 20, 40 and after 60 sessions of treatment. We used the Young Schema Questionnaire (YSQ) to measure the severity of Early Maladaptive Schemas and the Symptom Check List-90 Revisited (SCL-90R) to measure global psychological distress. Linear mixed model analyzes were used to examine the temporal relationship between the initial phase (0-20 and 0-40 sessions) and the later phase (40-60 sessions).Change in Early Maladaptive Schemas does not precede change in global psychological distress. Conversely, global psychological distress does not precede change in Early Maladaptive Schemas; the improvement in both indicators is concurrent.In this study, we could not confirm that the decrease of Early Maladaptive Schemas precedes decrease of global psychological distress. We found a concurrent relationship.

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Sequential pattern mining (SPM) is a data mining technique used for identifying common association rules in multiple sequential datasets and patterns in ordered events. In this study, we aimed to identify the relationships between commonly occurring internal medicine diseases in canine patients. We obtained medical records of dogs referred to the Konkuk University Veterinary Medicine Teaching Hospital. The data used for SPM included comorbidities and intervals between the diagnoses of internal medicine diseases. Additionally, we estimated the 3-year risk of developing an additional disease after the initial diagnosis of a commonly occurring veterinary internal medicine disease using logistic regression. We identified 547 canine patients diagnosed with ≥ 1 internal medicine disease. The SPM-based analysis assessed comorbidities and intervals for each of the five most common internal medical diseases, including hyperadrenocorticism, myxomatous mitral valve disease, canine atopic dermatitis, chronic kidney disease, and chronic pancreatitis. The highest values of the association rule were 3.01%, 6.02%, 3.9%, 4.1%, and 4.84%, and the shortest intervals were 1.64, 13.14, 5.37, 17.02, and 1.7 days, respectively. This study proposes that SPM is an effective technique for identifying common associations and temporal relationships between internal medicine diseases, and can be used to assess the probability of additional admission due to the development of the subsequent disease that may be diagnosed in canine patients. The results of this study will help veterinarians suggest appropriate preventive measures or other medical treatments for canine patients with medical conditions that have not yet been diagnosed, but are likely to develop in the short term.

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BACKGROUND: Concurrent insulin resistance and elevated blood pressure are commonly observed in cardiovascular disease (CVD) and have long been proposed to contribute to CVD. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident CVD remains unclear. METHODS: Longitudinal analysis of data on 57,192 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between Triglyceride-Glucose Index (TyG, calculated as ln [TG (mg/dL) × FBG (mg/dL)/2]) and blood pressure (BP) assessed by cross-lagged analyses in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 879 participants with known diabetes, 56,313 nonCVD participants were included for further analysis of the CVD outcome. Cox regression models were used to examine the hazard ratios (HRs) upon the cumulative TyG (CumTyG) and BP(CumBP) in the exposure period. RESULTS: The standard regression coefficient from baseline TyG to follow-up systolic BP was 0.0142 (95% CI 0.0059-0.0226), which was greater than the standard regression coefficient from baseline systolic BP to follow-up TyG (- 0.0390; 95% CI - 0.0469 to - 0.0311). The same results were observed in the cross-lag between TyG and diastolic blood pressure [0.0271 (0.0185 to 0.0356) vs. - 0.0372 (- 0.0451 to - 0.0293)]. During a median follow-up of 9.98 years, 3981 CVD cases occurred. Significant interactions were observed between the median CumTyG (8.61) and CumSBP thresholds (130, 140 mmHg) (P = 0.0149), the median CumTyG (8.61) and CumDBP thresholds (80, 90 mmHg) (P = 0.0441). Compared to CumTyG < 8.61 and CumSBP < 130 mmHg, after adjusting for potential confounding factors, the HR gradually increased in the high co-exposure groups. The hazard ratios (HRs) and 95% confidence intervals (CIs) for Q2-Q6 were 1.39 (1.24, 1.57), 1.94 (1.69, 2.22), 2.40 (2.12, 2.71), 2.74 (2.43, 3.10), and 3.07 (2.74, 3.45). Additionally, the CVD risks in the co-exposure were more prominent in younger participants. CONCLUSIONS: These findings suggest that elevated TyG has a greater impact on future blood pressure changes than vice versa. Dual assessment and management of insulin resistance and blood pressure contribute to the prevention of CVD, especially in younger individuals.

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This case probes the potential temporal relationship between pancreatic neuroendocrine tumor (PNET) and depression. This patient has chronic symptoms of depression with no formal diagnosis until within a year of doctors suspecting her diagnosis of pancreatic cancer. An excisional biopsy confirmed a grade 1 neuroendocrine tumor (NET) in the pancreas, and postoperative psychiatric consultation confirmed continued elevated depression. This report presents an illustrative example of the ongoing research questions surrounding the relationship between the timing of a depression diagnosis and a PNET diagnosis. The depression-before-diagnosis relationship in pancreatic cancer patients is an observation that warrants further studies as depression could be a valuable early warning sign of pancreatic cancer.

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OBJECTIVE: Stroke is a leading cause of mortality and disability. This study aimed to investigate the temporal and directional relationships between post-stroke depressive symptoms and cognitive impairment using a cross-lagged panel design. Depressive symptoms and cognitive impairment are two common post-stroke complications. However, the precise underlying mechanism remains unclear despite their close relationship. Therefore, elucidating the causal relationship between these two issues is of great clinical significance for improving the poor prognosis of stroke. METHODS: This study employed a hospital-based multicenter prospective cohort design. A total of 610 patients with ischemic stroke were eligible. Depressive symptoms (measured using the seventeen-item Hamilton Rating Scale for Depression) and cognitive function (measured using the Montreal Cognitive Assessment) were assessed at baseline and the 12-month follow-up. Spearman's correlation was used to examine the correlation between cognitive function and depressive symptoms. Additionally, a cross-lagged panel analysis was employed to elucidate the causal relationship between these factors after adjusting for potential covariates. RESULTS: The results of a four-iteration cross-lagged panel analysis substantiated a bidirectional relationship between post-stroke depressive symptoms and cognitive function over time. Specifically, higher scores for early depressive symptoms were associated with lower scores for later cognitive function; additionally, higher baseline cognitive function scores were associated with lower depressive symptom scores at a later point. CONCLUSION: This study establishes a reciprocally causal long-term relationship between depressive symptoms and cognitive function after an ischemic stroke. Therefore, interventions aimed at improving cognitive function and ameliorating depressive symptoms may positively affect both cognition and mood. TRIAL REGISTRATION: ChiCTR-ROC-17013993.

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AIM: Clozapine is indicated as the last-line agent for the treatment of refractory schizophrenia due to its side effects. This study included an Asian schizophrenia population and investigated the effect of clozapine on the risks of all-cause, natural, and suicide mortality. METHODS: This study included a large-scale schizophrenia inpatient cohort derived from the National Health Insurance Research Database from January 1, 2001, to December 31, 2019 (n = 43,025). Of them, we selected those who received clozapine (clozapine cohort, n = 5800). From those who never used clozapine, we selected two individuals for each patient in the clozapine cohort by matching by age, sex, and the year of the index date (ratio: 1:2, control cohort, n = 11,583). The clozapine and nonclozapine control cohorts together were defined as the study cohort (n = 17,383). Multivariate Cox proportional-hazards regression with a time-dependent model was performed to investigate the effect of individual antipsychotic agents on mortality. RESULTS: All individual first-generation antipsychotics were not associated with mortality risk. However, most individual second-generation antipsychotics exerted protective effects against all-cause and natural mortality. Furthermore, only clozapine and risperidone were significantly associated with a low risk of suicide mortality. Only clozapine exhibited a dose-dependent relationship with all-cause, natural, and suicide mortality. CONCLUSIONS: This study provides robust evidence supporting the strong protective effect of clozapine on all-cause, suicide, and natural mortality risks in an Asian population. Under close monitoring, clozapine use can be advantageous in patients with schizophrenia who are at a high risk of suicide.

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Objectives: Less information is available about the temporal relationship between depression in the elderly and cognitive decline. In the current study, we (1) evaluated the temporal association between depression and cognitive decline in older adults over a 4-year period; (2) indicated which cognitive domains have a strong temporal relationship with depression.Methods: Using data from China Family Panel Studies, we examined the relationship between depression and cognition among adults aged 65 and older with a cross-lagged design.Results: The results showed that initial depression affected subsequent cognitive function, especially immediate and delayed recall, but that cognition decline did not predict depression over time.Conclusion: The findings suggest that depression precedes cognitive decline in older adults, which is of great significance for the future research of mild cognitive impairment and dementia in the elderly.

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Chylothorax and chylous ascites occur when lymphatic fluid accumulates in the pleural space or peritoneum, respectively. They are classified as either traumatic or non-traumatic, and lymphomas are the most common non-traumatic cause. Lymphomas can obstruct the lymphatic architecture causing lipid-rich chyle to leak out below the level of the obstructing mass. Bilateral chylothoraces presenting in the presence of chylous ascites, secondary to Non-Hodgkin Lymphoma, are rare. We describe a case of a 55-year-old man with recurring large-volume chylous ascites secondary to Non-Hodgkin lymphoma who developed bilateral chylothoraces. Initially, he presented with dyspnea and hypoxia and was found to have bilateral pleural effusions, requiring bilateral thoracentesis for diagnostic and therapeutic management. The fluid removed from the pleural space was found to be lymphatic fluid, and the patient was eventually discharged home with instructions to follow up with oncology for further management. The case reveals a temporal relationship where a huge volume of chylous ascites develops into a chylothorax.

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Studies of the ecosystem services (ES) and human wellbeing (HWB) relationship have proliferated in recent decades, but few have examined how ES affect HWB over time in a region (i.e., the temporal ES-HWB relationship) and how this relationship varies between regions. Thus, this study was intended to address these questions using data from Inner Mongolia. We first quantified multiple indicators of ES and objective HWB from 1978 to 2019, and then quantified their temporal relationship with correlation analysis over the entire duration and during four development periods, respectively. Our results showed that, depending on the time periods of analysis, geographic locations, and indicators, the temporal ES-HWB relationship varied substantially in both correlation strength and directionality (r values ranged from -0.93 to +1). Specifically, food-related provisioning services and cultural services often showed significant positive relationships with income, consumption, and basic living needs (r values ranged from +0.43 to +1), but erratic relationships with equity, employment, and social relationships (r values ranged from -0.93 to +0.96). Also, the positive correlations between food-related provisioning services and HWB were generally weaker in the urbanized regions. Cultural services and HWB were more strongly correlated in later development periods, whereas the relationship between regulating services and HWB was quite variable in space and time. The variations in the relationship over different development periods may be attributable to changing environmental and socioeconomic conditions, while the variations between regions were likely due to spatial heterogeneity of influencing factors. Our findings have an important policy implication for Inner Mongolia and beyond: sustainable management based on the ES and HWB relationship must be temporally adaptive and spatially tailored.

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PURPOSE: Insulin resistance (IR) is closely associated with lipid accumulation. Here, we investigated the temporal relationship between the two conditions after bariatric surgery. MATERIALS AND METHODS: In total, 409 participants were enrolled from three bariatric centers in China from 2009 to 2018. We evaluated whether baseline IR (proxied by homeostasis model assessment of insulin resistance (HOMA-IR)) and lipid accumulation (proxied by visceral adiposity index (VAI) and lipid accumulation product (LAP)) were associated with follow-up IR and lipid accumulation (3 months postoperatively) using linear regression models. We then conducted a cross-lagged panel analysis model to simultaneously examine the bidirectional relationship between IR and lipid accumulation. RESULTS: Multivariable linear regression analyses showed that baseline HOMA-IR was associated with follow-up VAI (ß = 0.430, 95% CI: 0.082-0.778, p = 0.016) and LAP (ß = 0.070, 95% CI: 0.010-0.130, p = 0.022). There was no relationship between baseline lipid accumulation and follow-up IR. Further cross-lagged panel analyses indicated that the path coefficient from baseline HOMA-IR to follow-up VAI (ß2 = 0.145, p = 0.003) was significantly greater than the coefficient from baseline VAI to follow-up HOMA-IR (ß1 = - 0.013, p = 0.777). Similarly, the path coefficient from baseline HOMA-IR to follow-up LAP (ß2 = 0.141, p = 0.003) was significantly greater than the coefficient from baseline LAP to follow-up HOMA-IR (ß1 = 0.041, p = 0.391). CONCLUSION: Our study demonstrated a unidirectional relationship from HOMA-IR to VAI and LAP, suggesting that the change in IR may precede lipid accumulation after surgery.

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Background The temporal relationship between type 2 diabetes (T2DM) and left ventricular hypertrophy (LVH) is not well established. This study aims to examine the temporal sequence between T2DM and LVH/cardiac geometry patterns in middle-aged adults. Methods and Results The longitudinal cohort consisted of 1000 adults (682 White individuals and 318 Black individuals; 41.1% men; mean age, 36.2 years at baseline) who had data on fasting glucose/T2DM, left ventricular mass index (LVMI), and relative wall thickness collected twice at baseline and follow-up over 9.4 years on average. The cross-lagged path analysis model in 905 adults who did not take antidiabetic medications and the longitudinal prediction model in 1000 adults were used to examine the temporal relationships of glucose/T2DM with LVMI, LVH, relative wall thickness, and remodeling patterns. After adjustment for age, race, sex, smoking, alcohol drinking, body mass index, heart rate, hypertension, and follow-up years, the path coefficient from baseline LVMI to follow-up glucose was 0.088 (P=0.005); the path from baseline glucose to follow-up LVMI was -0.009 (P=0.758). The 2 paths between glucose and relative wall thickness were not significant. The path analysis parameters did not differ significantly between race, sex, and follow-up duration subgroups. Incidence of T2DM was higher in the baseline LVH group than in the normal LVMI group (24.8% versus 8.8%; P=0.017 for difference). Incidence of LVH and concentric LVH was higher in the baseline T2DM group than in the group without T2DM (50.0% versus 18.2% for LVH [P=0.005 for difference]; 41.7% versus 12.6% for concentric LVH [P=0.004 for difference]), with adjustment for covariates. Conclusions This study suggests that the temporal relationship between T2DM and LVH is likely bidirectional. The path from LVMI/LVH to glucose/T2DM is stronger than the path from glucose/T2DM to LVMI/LVH.

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BACKGROUND: No studies have assessed the association between sleep duration and obesity in Chinese ethnic minorities. Whether the relationship between sleep duration and obesity is different between Chinese Han people and Chinese ethnic minorities remains unclear. The study aimed to explore the relationship between sleep duration and obesity among Chinese Han people and Chinese ethnic minorities. METHODS: We applied data from the Guizhou Population Health Cohort Study (GPHCS), which 9,280 participants were recruited in the baseline survey from 2010 to 2012, and 8,163 completed the follow-up survey from 2016 to 2020. A total of 5,096 participants (3,188 Han Chinese and 1,908 ethnic minorities) were included in the ultimate analysis. Information on sleep duration (total 24-hour sleep time), body mass index (BMI), and waist circumference (WC) was collected at the baseline and follow-up survey, respectively. Cross-lagged panel analyses were conducted to explore the temporal relationship between sleep duration and obesity for Han people and ethnic minorities. RESULTS: For Han people, the results from cross-lagged panel analyses indicated that baseline sleep duration was significantly associated with follow-up BMI (ßBMI = -0.041, 95% CIBMI: -0.072 ~ -0.009) and follow-up WC (ßWC = -0.070, 95%CIWC: -0.103 ~ -0.038), but baseline BMI (ßBMI = -0.016, 95% CIBMI: -0.050 ~ 0.018) and baseline WC (ßWC = -0.019, 95% CIWC: -0.053 ~ 0.016) were not associated with follow-up sleep duration. In addition, the relationship between baseline sleep duration and follow-up BMI was gender-specific and significant only in the Han people female (ßBMI = -0.047, 95% CIBMI: -0.090 ~ -0.003) but not in the Han people male (ßBMI = -0.029, 95% CIBMI: -0.075 ~ 0.016). For ethnic minorities, the results indicated that there was no relationship between sleep duration and obesity at all, either from sleep duration to obesity (ßBMI = 0.028, 95%CIBMI: -0.012 ~ 0.068; ßWC = 0.020, 95%CIWC: -0.022 ~ 0.062), or from obesity to sleep duration (ßBMI = -0.022, 95%CIBMI: -0.067 ~ 0.022; ßWC = -0.042, 95%CIWC: -0.087 ~ 0.003). CONCLUSION: The relationship pattern between sleep duration and obesity across Han people and ethnic minorities is different. Future sleep-aimed overweight and obesity intervention should be conducted according to population characteristics.

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BACKGROUND: Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. METHODS: Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceride/high-density lipoprotein) in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 8824 participants with known diabetes, 43,360 nondiabetic participants were included for further analysis of the T2D outcome. Cox regression models were used to examine the adjusted hazard ratios (aHRs) upon the cumulative hsCRP (CumCRP) and AIP (CumAIP) in the exposure period. RESULTS: In temporal analysis, the adjusted standardized correlation coefficient (ß1) of hsCRP_2006/2007 and AIP_2010/2011 was 0.0740 (95% CI, 0.0659 to 0.0820; P < 0.001), whereas the standardized correlation coefficient (ß2) of AIP_2006/2007 and hsCRP_2010/2011 was - 0.0293 (95% CI, - 0.0385 to - 0.0201; P < 0.001), which was significantly less than ß1 (P < 0.001). During a median follow-up of 7.9 years, 5,118 T2D cases occurred. Isolated exposure to CumAIP or CumCRP was dose-dependently associated with T2D risks, independent of traditional risk factors. Significant interactions were observed between the median CumAIP (- 0.0701) and CumCRP thresholds (1, 3 mg/L) (P = 0.0308). Compared to CumAIP < - 0.0701 and CumCRP < 1 mg/L, those in the same CumAIP stratum but with increasing CumCRP levels had an approximately 1.5-fold higher T2D risk; those in higher CumAIP stratum had significantly higher aHRs (95% CIs): 1.64 (1.45-1.86), 1.87 (1.68-2.09), and 2.04 (1.81-2.30), respectively, in the CumCRP < 1, 1 ≤ CumCRP < 3, CumCRP ≥ 3 mg/L strata. Additionally, the T2D risks in the co-exposure were more prominent in nonhypertensive, nondyslipidemic, nonprediabetic, or female participants. CONCLUSIONS: These findings suggest a stronger association between elevated hsCRP and future AIP changes than vice versa and highlight the urgent need for combined assessment and management of chronic inflammation and atherogenic dyslipidemia in primary prevention, particularly for those with subclinical risks of T2D.

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BACKGROUND AND AIMS: This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults. METHODS AND RESULTS: The cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later. After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%). CONCLUSIONS: The bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM.

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BACKGROUND AND PURPOSE: Research into the temporal relationship between atrial tachyarrhythmias (atrial tachycardia [AT] and atrial fibrillation [AF]) and stroke has produced conflicting findings. Systematic categorization of stroke subtypes may help clarify the discussion. OBJECTIVES: The objective of the study was to examine the presence and timing of AT/AF in relation to ischemic stroke subtypes, categorized as either cardioembolic (CE) or non-CE. METHODS: Consecutive patients presenting to the Austin Hospital with acute stroke from 2012 to 2019 and a cardiac implantable electronic device (CIED) were identified. Using a case-control design, the temporal proximity of AT/AF episodes in the 90 days prior to stroke was compared in the CE and non-CE stroke groups. RESULTS: 5,591 patients presented to the Austin Hospital with acute stroke from 2012 to 2019, of whom 31 patients with an ischemic stroke and a CIED with ≥90 days of monitoring were identified. Twelve strokes were adjudicated as CE and 19 as non-CE by a stroke neurologist. Six of the 12 CE stroke patients (50%) experienced AT/AF within 30 days preceding their stroke, while none of the 19 non-CE stroke patients recorded any AT/AF in the same period (p = 0.001). Four CE stroke patients (33%) had no AT/AF preceding their strokes at any time. The odds ratio for CE stroke was highest (39; 95% confidence interval [CI]: 1.92-791.5) when AT/AF occurred in the 30 days prior, declining to 20.65 (95% CI: 1.00-427.66) and 6.07 (95% CI: 0.94-39.04) in the subsequent 31-60- and 61-90-day windows, respectively. CONCLUSIONS: CE strokes were associated with a significantly higher proportion of preceding AT/AF compared with non-CE strokes. These findings support a potential temporal relationship between AT/AF and CE stroke and demonstrate that stroke subtyping can better characterize the relationship between AF and ischemic stroke. However, this study's findings are limited by its sample size and small number of informative cases.

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AIMS AND OBJECTIVES: This study examined the sequential relationships of food intake and the moderating role of the characteristics of intake and resident conditions. BACKGROUND: Nursing home residents commonly experience insufficient food intake. While multilevel factors influence intake, evidence on sequential relationships is lacking. DESIGN: The study was an observational study using secondary, behavioural analyses following the STROBE Statement. METHODS: Videotaped observations (N = 160) collected from a dementia communication trial during 2011-2014 were coded using the refined Cue Utilisation and Engagement in Dementia Mealtime Video-coding Scheme during 2018-2019. The 160 videos involved 27 residents living with dementia and 36 staff in 9 nursing homes. Independent variables were the state (solid intake, liquid intake, no intake) of an intake episode occurring during mealtime (current episode), eating technique (resident-initiated, staff-facilitated) used in the next episode occurring after the current episode (subsequent episode), interval between adjacent episodes, and resident comorbidities and dementia stage. The dependent variable was the state of subsequent episode. RESULTS: Successful liquid and solid intake increased odds of subsequent liquid and solid intake. Comorbidities were associated with decreased odds of subsequent liquid and solid intake for staff-facilitated episodes. When liquid intake occurred, staff-facilitation decreased odds of subsequent liquid intake; longer intervals between adjacent episodes increased odds of subsequent solid intake. CONCLUSION: Food intake was strongly and sequentially associated, and such temporal relationships were dependent on characteristics of the intake process and resident conditions. RELEVANCE TO CLINICAL PRACTICE: The study findings supported that initiating successful intake facilitates continuity of successful intake during mealtime. Behavioural interventions tailored by comorbidities that modify characteristics of the food intake process may improve food intake.

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