Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

The L-shaped association of mid-upper arm circumference with all-cause and cause-specific mortality in US adults: a population-based prospective cohort study.

BACKGROUND: The arm circumference is a feasible and reliable indicator in evaluating the nutritional status of children. However, its application in general adults has yet to be thoroughly investigated. OBJECTIVE: This study aimed to evaluate the association between mid-upper arm circumferences (MUACs) and mortality in general adults. METHODS: The nationally representative cohort from the National Health and Nutrition Examination Survey (1999-2018) was analyzed with mortality information obtained through linkage to the National Death Index. The baseline MUACs were collected as exposure. Survey-weighted Cox proportional hazard regressions were performed to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) of mortality risk for individuals with different MUACs. Restricted cubic spline analyses were performed to examine the nonlinear association of MUAC with all-cause and cause-specific mortality. RESULTS: A total of 52,159 participants were included in this study. During a median follow-up time of 117 months, 7157 deaths were documented, with leading causes of cardiovascular disease (CVD), cancer, and respiratory disease. Individuals in the first quartile (Q1) of MUAC tended to have higher all-cause mortality risk than the rest after full adjustment. Similarly, CVD mortality risk in Q1 was higher than that in the second quartile (Q2) and the third quartile (Q3); respiratory mortality risk in Q1 was higher than in Q2. MUAC was non-linearly associated with all-cause mortality and CVD mortality. Individuals in Q1 MUAC (≤ 29.3) tended to have higher all-cause mortality risk, with HRs (95% CIs) estimated to be 0.76 (0.67-0.87) for Q2 (29.4, 32.5), 0.69 (0.59-0.81) for Q3 (32.6, 36.0), and 0.59 (0.46-0.75) for Q4 (≥ 36.1) after adjustment of demographic, lifestyle, and comorbidity covariates. Similarly, compared with Q1, HRs (95% CIs) for CVD mortality were estimated to be 0.73 (0.58-0.93) for Q2 and 0.57 (0.43-0.47) for Q3; HRs (95% CIs) for respiratory mortality was estimated to be 0.57 (95% CI, 0.37-0.87) for Q2 with other differences not significant. CONCLUSION: The MUAC was inversely associated with long-term mortality in general adults in the United States and may serve as a valuable measurement in adult health evaluations.

Association between the Number of Days/Week of Different Levels of Physical Activity and Chronic Pain in People of Different Races: A Mendelian Randomization Study.

OBJECTIVE: Regular physical activity is beneficial for health, but the effect of the number of days/week of physical activity on chronic pain (CP) remains unclear, so we used a two-sample Mendelian randomization (MR) analysis to explore the relationship between the number of days/weeks of different levels of physical activity and chronic pain in people of different races. METHODS: We obtained summary data from genome-wide association studies (GWASs) on the number of days/week of physical activity and multisite chronic pain in European, South Asian, East Asian, Middle Eastern, and African American populations. The single-nucleotide polymorphisms (SNPs) of the exposed data were visualized with a Manhattan plot via the R program. MR analysis was performed by the MR-Base platform. RESULTS: The results indicated that a higher number of days/week with ≥10 min of walking protects against CP in African American and Afro-Caribbean populations (inverse-variance weighting, IVW p < 0.05) but has little effect on people of different races (IVW p > 0.05). A higher number of days/week with ≥10 min of moderate physical activity increased the risk of CP in European and South Asia (IVW p < 0.05) but had little effect on people of different races (IVW p > 0.05). The number of days/week of ≥10 min of vigorous physical activity increased the risk of CP in Europeans (IVW p < 0.05) and protected against CP in African Americans and Afro-Caribbeans (IVW p < 0.05). CONCLUSIONS: A higher number of days/week of moderate and vigorous physical activity increased the risk of CP in Europeans; however, a higher number of days/week of walking and vigorous physical activity may protect against CP in African American and Afro-Caribbean individuals.

Association of Nap Frequency With Hypertension or Ischemic Stroke Supported by Prospective Cohort Data and Mendelian Randomization in Predominantly Middle-Aged European Subjects.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). METHODS: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. RESULTS: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08-1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10-1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06-1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28-1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04-1.62]). CONCLUSIONS: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

Identification of Potential Diagnostic Biomarkers From Circulating Cells During the Course of Sleep Deprivation-Related Myocardial Infarction Based on Bioinformatics Analyses.

Background: Myocardial infarction (MI) is the leading cause of death from non-infectious diseases worldwide and results in rapid deterioration due to the sudden rupture of plaques associated with atherosclerosis, a chronic inflammatory disease. Sleep is a key factor that regulates immune homeostasis of the body. The imbalance in circulating immune cells caused by sleep deprivation (SD) may represent a risk factor leading to the rapid deterioration of plaques and MI. Therefore, it is of profound significance to identify diagnostic biomarkers for preventing SD-related MI. Methods: In the present study, we identified coexpressed differentially expressed genes (co-DEGs) between peripheral blood mononuclear cells from MI and SD samples (compared to controls) from a public database. LASSO regression analysis was applied to identify significant diagnostic biomarkers from co-DEGs. Moreover, receiver operating characteristic (ROC) curve analysis was performed to test biomarker accuracy and diagnostic ability. We further analyzed immune cell enrichment in MI and SD samples using the CIBERSORT algorithm, and the correlation between biomarkers and immune cell composition was assessed. We also investigated whether diagnostic biomarkers are involved in immune cell signaling pathways in SD-related MI processes. Results: A total of 10 downregulated co-DEGs from the sets of MI-DEGs and SD-DEGs were overlapped. After applying LASSO regression analysis, SYTL2, KLRD1, and C12orf75 were selected and validated as diagnostic biomarkers using ROC analysis. Next, we found that resting NK cells were downregulated in both the MI samples and SD samples, which is similar to the changes noted for SYTL2. Importantly, SYTL2 was strongly positively correlated not only with resting NK cells but also with most genes related to NK cell markers in the MI and SD datasets. Moreover, SYTL2 was highly associated with genes in NK cell signaling pathways, including the MAPK signaling pathway, cytotoxic granule movement and exocytosis, and NK cell activation. Furthermore, GSEA and KEGG analyses provided evidence that the DEGs identified from MI samples with low vs. high SYTL2 expression exhibited a strong association with the regulation of the immune response and NK cell-mediated cytotoxicity. Conclusion: In conclusion, SYTL2, KLRD1, and C12orf75 represent potential diagnostic biomarkers of MI. The association between SYTL2 and resting NK cells may be critically involved in SD-related MI development and occurrence.

Association of both prenatal and early childhood multiple metals exposure with neurodevelopment in infant: A prospective cohort study.

BACKGROUND: Impaired neurodevelopment of children has become a growing public concern; however, the associations between metals exposure and neurocognitive function have remained largely unknown. OBJECTIVES: We systematically evaluated the associations of multiple metals exposure during pregnancy and childhood on the neurodevelopment of children aged 2-3 years. METHODS: We measured 22 metals in the serum and urine among703 mother-child pairs from the Guangxi Birth Cohort Study. The neurocognitive development of children was assessed by the Gesell Development Diagnosis Scale (GDDS; Chinese version). Multiple linear regression models were used to evaluate the relationship between the metals (selected by elastic net regression) and the outcomes. The Bayesian kernel machine regression (BKMR) was used to evaluate the possible joint effect between the multiple metal mixture and the outcomes. RESULTS: Prenatal aluminum (Al) exposure was negatively associated with the fine motor developmental quotient (DQ) (ß = -1.545, 95%CI: 2.231, -0.859), adaption DQ (ß = -1.182, 95%CI: 1.632, -0.732), language DQ (ß = -1.284, 95% CI: 1.758, -0.809), and social DQ (ß = -1.729, 95% CI: 2.406, -1.052) in the multi-metal model. Prenatal cadmium (Cd) exposure was negatively associated with gross motor DQ (ß = -2.524, 95% CI: 4.060, -0.988), while postpartum Cd exposure was negatively associated with language DQ (ß = -1.678, 95% CI: 3.227, -0.129). In stratified analyses, infants of different sexes had different sensitivities to metal exposure, and neurobehavioral development was more significantly affected by metal exposure in the first and second trimester. BKMR analysis revealed a negative joint effect of the Al, Cd, and selenium (Se) on the language DQ score; postpartum Cd exposure played a major role in this relationship. CONCLUSION: Prenatal exposure to Al, Ba, Cd, molybdenum (Mo), lead (Pb), antimony (Sb), and strontium (Sr), and postpartum exposure to cobalt (Co), Cd, stannum (Sn), iron (Fe), nickel (Ni), and Se are associated with neurological development of infants. The first and second trimester might be the most sensitive period when metal exposure affects neurodevelopment.

Nontrivial amplification below the threshold for excitable cell signaling.

In many asymptotically stable fluid systems, arbitrarily small fluctuations can grow by orders of magnitude before eventually decaying, dramatically enhancing the fluctuation variance beyond the minimum predicted by linear stability theory. Here using influential quantitative models drawn from the mathematical biology literature, we establish that dramatic amplification of arbitrarily small fluctuations is found in excitable cell signaling systems as well. Our analysis highlights how positive and negative feedback, proximity to bifurcations, and strong separation of timescales can generate nontrivial fluctuations without nudging these systems across their excitation thresholds. These insights, in turn, are relevant for a broader range of related oscillatory, bistable, and pattern-forming systems that share these features. The common thread connecting all of these systems with fluid dynamical examples of noise amplification is non-normality.