Prediction of Intradialytic Blood Pressure Variation Based on Big Data.

INTRODUCTION: Cardiovascular (CV) events are the major cause of morbidity and mortality associated with blood pressure (BP) in hemodialysis (HD) patients. BP varies significantly during HD treatment, and the dramatic variation in BP is a well-recognized risk factor for increased mortality. The development of an intelligent system capable of predicting BP profiles for real-time monitoring is important. Our aim was to build a web-based system to predict changes in systolic BP (SBP) during HD. METHODS: In this study, dialysis equipment connected to the Vital Info Portal gateway collected HD parameters that were linked to demographic data stored in the hospital information system. There were 3 types of patients: training, test, and new. A multiple linear regression model was built using the training group with SBP change as the dependent variable and dialysis parameters as the independent variables. We tested the model's performance on test and new patient groups using coverage rates with different thresholds. The model's performance was visualized using a web-based interactive system. RESULTS: A total of 542,424 BP records were used for model building. The accuracy was greater than 80% in the prediction error range of 15%, and 20 mm Hg of true SBP in the test and new patient groups for the model of SBP changes suggested the good performance of our prediction model. In the analysis of absolute SBP values (5, 10, 15, 20, and 25 mm Hg), the accuracy of the SBP prediction increased as the threshold value increased. DISCUSSION: This databae supported our prediction model in reducing the frequency of intradialytic SBP variability, which may help in clinical decision-making when a new patient receives HD treatment. Further investigations are needed to determine whether the introduction of the intelligent SBP prediction system decreases the incidence of CV events in HD patients.

Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

Psychometric Properties of the Big Three Perfectionism Scale: Rasch Analysis.

The Big Three Perfectionism Scale (BTPS) is one of commonly used measures for assessing individuals' perfectionism. The main purpose of this current study was to assess the psychometric properties of the Big Three Perfectionism Scale (BTPS) within the framework of the Rasch model. The sample consisted of 502 adolescents (53% males and 47% females). This study revealed were several important findings. First, adolescents interpreted the categories of the rating scales of the BTPS as intended and items demonstrated good targeting with the operating ranges from - 4.79 to 4.47 logits for rigid perfectionism, from - 3.84 to 3.76 logits for self-critical perfectionism and from - 4.04 to 3.92 logits for narcissistic perfectionism. Second, rigid perfectionism, self-critical perfectionism and narcissistic perfectionism exhibited unidimensionally, providing justification for the use of summed scores for each scale. Third, the average item difficulty of facets was different within each scale, with the facets of self-worth contingencies, socially prescribed perfectionism and other-oriented perfectionism being more difficult to endorse in their belonging scale. Fourth, there were no DIF items across sex, suggesting that items in three scales functioned equally across boys and girls. Fifth, rigid perfectionism (r = 0.15) and self-critical perfectionism (r = 0.55) were positively associated with neuroticism, but self-critical perfectionism (r = - 0.24) and narcissistic perfectionism (r = - 0.29) were negatively related with agreeableness. Finally, sex moderated the associations between rigid perfectionism and neuroticism. In sum, the findings in this study enhance psychometric properties of the BTPS.

Associations Between Personality and Depressive Symptoms in an Adolescent Clinical Population: Consideration of Personality Stability.

The study used trait-state-occasion TSO models to explore longitudinal personality stability in young adolescents with the onset of depressive symptoms and to quantify time-invariant and time-varying personality components in predicting the course of depressive symptoms. A total of 326 young clinical adolescents were recruited from high schools, and only 290 adolescents (112 boys; 178 girls) were followed up for 4 time points. Personality measures were implemented twice each year with an interval of 6 months, providing four assessment waves (T1 to T4); depression measures were administered at the initial stage (T1) and the third wave (T3), respectively. The results showed that five domains of personality in adolescents with depressive symptoms were largely characterized by the stable trait factor (65%-81%). The average autoregressive effects across the four waves were significant for all Big Five personality domains except openness. Moreover, excluding time-varying variance, conscientiousness, extraversion and agreeableness were negatively associated with T1 depressive symptoms; however, only the latter two domains retained significant relationships in the second year of intervention. An elevated level of neuroticism was consistently associated with higher levels of depressive symptoms over interventions. Trait factors of extraversion, agreeableness and neuroticism were associated with depressive symptoms in early adolsecnets, providing some implications for clinical practitioners.

Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

A Novel Sensor for Undrained Shear Strength Measurement in Very Soft to Soft Marine Sediments Based on Optical Frequency Domain Reflectometry Technology.

Due to the short supply of conventional fill materials, such as sand, land reclamation using dredged marine deposits has recently been proposed, in which marine deposits with high water content are blow-filled into reclaiming areas. The strength development of the filled marine soils is of great importance during the sedimentation and consolidation to guide the filling process and construction of reclamation. In this study, a novel sensor based on optical frequency domain reflectometry (OFDR) technology with a simple design was developed for undrained shear strength measurement. The novel sensor consists of an optical fiber and a series of polyoxymethylene coins. Owing to the merits of OFDR technology on high resolution, fully distributed sensing, and immunity to electromagnetic interference, the novel sensor can be used to determine undrained shear strength profiles of very soft to soft marine sediments/soils with good accuracy. The sensor was calibrated in remolded marine deposits with different water contents. The good feasibility and performance of the novel sensor for undrained shear strength measurement were well validated in two physical model tests on marine deposits treated by horizontal drains with vacuum preloading.

Is personality stable in adolescence? Disentangling time-invariant and time-varying factors of personality in a trait-state-occasion model.

This study applied trait-state-occasion (TSO) modelling to investigate the extent to which inter-individual differences in personality were accounted for by time-invariant and time-varying factors during adolescence. The participants were 753 high school students, and only 661 students were followed for 4 years. The mean age in the first year was 15.23 years and 52.8% were females. The results showed that the full TSO model had the best representation of adolescent personality, and the means of the proportions of variance explained by trait factors for the Big Five ranged between 56% and 83%, suggesting that inter-individual differences in personality are mainly accounted for by stable trait variance over the course of adolescence. Furthermore, the five dimensions of personality differed not only in the amounts of trait variance but also in the stability of time-varying factors. These findings have significant implications for personality research.

Preradiation tooth extraction and jaw osteoradionecrosis: Nationwide population-based retrospective study in Taiwan.

OBJECTIVE: Radiotherapy (RT) for head and neck cancer (HNC) within 7 days of tooth extraction is contraindicated because it may increase the risk of osteoradionecrosis of the jaw (ORNJ). However, delayed RT could compromise survival in patients with HNC. By using a national healthcare database, we reviewed the contraindications and analysed other risk factors for ORNJ. DESIGN: A retrospective cohort study. SETTING: By using Taiwan's National Health Insurance Research Database, 5,062 HNC patients with at least one tooth extraction 1-21 days before the first RT day (index day) and without any extractions during or after RT from 2000 to 2013 were included. The patients were divided into two groups according to the time of tooth extraction before the index day: 1-7 days and 8-21 days. PARTICIPANTS: Taiwanese patients with head and neck cancer. MAIN OUTCOMES MEASURE: Univariate and multivariate Cox proportional hazard regression models were used to evaluate the risk factors of ORNJ. RESULTS: The overall incidence of ORNJ in the included patients was 1.03% (mean follow-up duration, 4.07 ± 3.01 years; range, 1.00-13.99 years). Tooth extraction within 7 days before RT was not associated with increased ORNJ risk (hazard ratio [HR] =0.734; P = .312). Significant risk factors for ORNJ included oral cancer (adjusted HR = 3.961), tumour excision surgery within 3 months before RT (adjusted HR = 3.488) and mandibulectomy within 3 months before RT (adjusted HR = 5.985; all P < .001). CONCLUSION: In a mean follow-up of 4 years, tooth extraction within 7 days before RT for HNC treatment did not increase the ORNJ risk compared with tooth extraction 7-21 days before RT.

Myopia Prevention and Outdoor Light Intensity in a School-Based Cluster Randomized Trial.

PURPOSE: To investigate the effectiveness of a school-based program promoting outdoor activities in Taiwan for myopia prevention and to identify protective light intensities. DESIGN: Multi-area, cluster-randomized intervention controlled trial. PARTICIPANTS: A total 693 grade 1 schoolchildren in 16 schools participated. Two hundred sixty-seven schoolchildren were in the intervention group and 426 were in the control group. METHODS: Initially, 24 schools were randomized into the intervention and control groups, but 5 and 3 schools in the intervention and control groups, respectively, withdrew before enrollment. A school-based Recess Outside Classroom Trial was implemented in the intervention group, in which schoolchildren were encouraged to go outdoors for up to 11 hours weekly. Data collection included eye examinations, cycloplegic refraction, noncontact axial length measurements, light meter recorders, diary logs, and questionnaires. MAIN OUTCOME MEASURES: Change in spherical equivalent and axial length after 1 year and the intensity and duration of outdoor light exposures. RESULTS: The intervention group showed significantly less myopic shift and axial elongation compared with the control group (0.35 diopter [D] vs. 0.47 D; 0.28 vs. 0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia progression (odds ratio, 0.46; 95% confidence interval [CI], 0.28-0.77; P = 0.003). The myopic protective effects were significant in both nonmyopic and myopic children compared with controls. Regarding spending outdoor time of at least 11 hours weekly with exposure to 1000 lux or more of light, the intervention group had significantly more participants compared with the control group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in school (≥200 minutes) showed significantly less myopic shift (measured by light meters; ≥1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; ≥3000 lux: 0.16 D; 95% CI, 0.002-0.32; P = 0.048). CONCLUSIONS: The school-based outdoor promotion program effectively reduced the myopia change in both nonmyopic and myopic children. Outdoor activities with strong sunlight exposure may not be necessary for myopia prevention. Relatively lower outdoor light intensity activity with longer time outdoors, such as in hallways or under trees, also can be considered.

Intelligent system to predict intradialytic hypotension in chronic hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication and a major risk factor of increased mortality during hemodialysis (HD). However, predicting the occurrence of intradialytic blood pressure (BP) fluctuations clinically is difficult. This study aimed to develop an intelligent system with capability of predicting IDH. METHODS: In developing and training the prediction models in the intelligent system, we used a database of 653 HD outpatients who underwent 55,516 HD treatment sessions, resulting in 285,705 valid BP records. We built models to predict IDH at the next BP check by applying time-dependent logistic regression analyses. RESULTS: Our results showed the sensitivity of 86% and specificity of 81% for both nadir systolic BP (SBP) of <90 mmHg and <100 mmHg, suggesting good performance of our prediction models. We obtained similar results in validating via test data and data of newly enrolled patients (new-patient data), which is important for simulating prospective situations wherein dialysis staff are unfamiliar with new patients. This compensates for the retrospective nature of the BP records used in our study. CONCLUSION: The use of this validated intelligent system can identify patients who are at risk of IDH in advance, which may facilitate well-timed personalized management and intervention.

Prenatal Diagnosis of Persistent Left Superior Vena Cava is Associated with Coarctation of the Aorta - A Case Report.

A singleton pregnant woman was found to have persistent left superior vena cava (PLSVC) of the fetus at 22 weeks by ultrasound. Follow-up scans revealed PLSVC, dilated coronary sinus, dominant right heart, some pericardial effusion, and hypertrophy of the right ventricular wall. The woman had an abdominal delivery at 34 weeks due to rupture of membranes. The baby was found to have coarctation of the aorta postnatally and had aortic reconstruction at 31 days of age. A prenatal ultrasound finding of PLSVC might be associated with coarctation of the aorta and it warrants specialist follow-ups and complete workup of echocardiography prenatally and postnatally.

Trophic cascade effects of avian predation on a willow in an urban wetland.

Trophic cascades play a crucial role in ecosystem functioning. In this study, we tested the effects of avian predation on willows (Salix warburgii) and associated arthropods in an urban wetland. We excluded birds by netting around willow branches for 20 months from September-November 2010 to June 2012. We compared the leaf count, leaf area, leaf biomass, bud count, catkin (flower) count and herbivory from pairs of bird-exclusion and no-exclusion branches on 11 trees. Simultaneously, we compared herbivorous and predatory arthropod abundances associated with bird-exclusion and no-exclusion branches. Another nine trees were used as reference branches to assess whether the bird exclusion impacted other branches of the same trees (i.e., no-exclusion branches). Bird exclusion resulted in increased herbivory 1 year after the treatment, followed by a reduced leaf count, leaf area, leaf biomass, bud count and catkin count in the second year. The bird-exclusion branches exhibited greater spider abundance than the no-exclusion branches. However, herbivorous arthropod abundances were similar between the branch types. The reference branches had similar values in all plant traits and for all arthropod abundances to those of the no-exclusion branches. This study demonstrated the branch-level effects of trophic cascades on willows via the exclusion of birds and a resulting reduction in herbivory. However, whether and how the arthropods mediate such effects require further investigation. This study adds to the limited empirical data demonstrating the effects of trophic cascades on plant reproduction. Our findings highlight the importance of bird conservation in urban wetlands.

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. METHODS: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. RESULTS: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. CONCLUSIONS: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

Nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study: Design and methods.

AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Response Shifts in Depression Intervention for Early Adolescents.

OBJECTIVE: Patient-reported outcome measures are increasingly required as metrics for determining the efficacy of depression interventions. However, the scores obtained from self-reports over the course of treatment may be biased because respondents restructured the factors of the depression symptoms (reconceptualization), changed their values of the symptoms in reflecting depression (reprioritization), or adjusted their standards of assessing the levels of symptoms (recalibration). The aim of present study is to assess response shifts on the depression measure. METHOD: This study uses the procedures for assessing longitudinal measurement invariance to evaluate response shift effects on the Beck Depression Inventory II (BDI-II) with 320 early adolescents suffering from depression (43.8% boys and 56.2% girls) over the course of their treatment in the school settings. RESULTS: The findings reveal clear signs of response shifts (recalibration) in the BDI-II for depressed students. Compared with the factor scores before treatment, the factor scores after treatment were underestimated, especially on the negative attitude and performance difficulty factors. CONCLUSIONS: Estimates of treatment efficacy based on observed test scores appear to be confounded by response shifts.

Long-term remote organ consequences following acute kidney injury.

Acute kidney injury (AKI) has been a global health epidemic problem with soaring incidence, increased long-term risks for multiple comorbidities and mortality, as well as elevated medical costs. Despite the improvement of patient outcomes following the advancements in preventive and therapeutic strategies, the mortality rates among critically ill patients with AKI remain as high as 40-60 %. The distant organ injury, a direct consequence of deleterious systemic effects, following AKI is an important explanation for this phenomenon. To date, most evidence of remote organ injury in AKI is obtained from animal models. Whereas the observations in humans are from a limited number of participants in a relatively short follow-up period, or just focusing on the cytokine levels rather than clinical solid outcomes. The remote organ injury is caused with four underlying mechanisms: (1) "classical" pattern of acute uremic state; (2) inflammatory nature of the injured kidneys; (3) modulating effect of AKI of the underlying disease process; and (4) healthcare dilemma. While cytokines/chemokines, leukocyte extravasation, oxidative stress, and certain channel dysregulation are the pathways involving in the remote organ damage. In the current review, we summarized the data from experimental studies to clinical outcome studies in the field of organ crosstalk following AKI. Further, the long-term consequences of distant organ-system, including liver, heart, brain, lung, gut, bone, immune system, and malignancy following AKI with temporary dialysis were reviewed and discussed.

HBP1 promoter methylation augments the oncogenic ß-catenin to correlate with prognosis in NSCLC.

ß-catenin nuclear accumulation is frequently identified in human non-small cell lung cancer (NSCLC). The HMG-box transcription factor 1 (HBP1) is a known repressor of ß-catenin transactivation. However, the role of HBP1 in relation to ß-catenin nuclear accumulation has not been addressed in human cancer patients. In addition, the mechanism of HBP1 gene alteration in NSCLC remains unclear, although HBP1 mutation and gene deletion of HBP1 are reported in breast and colon cancers. Here, we demonstrate that HBP1 acts as a tumour suppressor and serves as a prognostic biomarker in NSCLC clinical and cell models. The immunohistochemistry data indicated that 30.5% (25/82) of tumours from NSCLC patients showed absence or low expression of HBP1 protein. A significant inverse correlation between mRNA/protein expression and promoter hypermethylation suggested that promoter hypermethylation is responsible for low expression of HBP1 in NSCLC patients. Reactivation of HBP1 expression by demethylation reagent or ectopic expression of HBP1 suppressed ß-catenin transactivation. Conversely, HBP1 knockdown increased ß-catenin transactivation. Importantly, preserved expression of HBP1 had a significantly protective effect on prognosis in patients with ß-catenin nuclear accumulation, suggesting that low expression of HBP1 in NSCLC patients with ß-catenin nuclear accumulation was one of the major determinants of prognosis. Our data from cellular and clinical models suggest that HBP1 is a suppressor of cancer progression, making it a potential prognostic predictor and therapeutic target to attenuate lung cancer progression.

Hirami lemon (Citrus reticulata var. depressa) modulates the gut-brain axis in a chronic mild stress-induced depression mouse model.

Citrus reticulata var. depressa, commonly known as Hirami lemon, is a native citrus species found in Taiwan and Okinawa islands of Japan. While several Citrus species are known to possess antidepressant activity by modulating the gut microbiota, the antidepressant effect of Hirami lemon and its underlying mechanisms have not been thoroughly investigated. In this study, we explored the potential antidepressant efficacy of the fruit extract (CD) and the essential oil (CDE) from Hirami lemon peel using a chronic mild stress (CMS)-induced mouse model and analyzed the association of gut microbiome changes. Our findings revealed that mice subjected to CMS exhibited anxiety- and depression-like behaviors as assessed by elevated plus-maze and forced swimming tests, respectively. Significantly, oral administration of CDE and CD notably reversed CMS-induced depression- and anxiety-like behaviors in CMS-induced mice. Moreover, compared to the non-stressed group, CMS significantly altered the gut microbiome, characterized by highly diverse bacterial communities, reduced Bacteroidetes, and increased Firmicutes. However, oral administration of CDE and CD restored gut microbiota dysbiosis. We also performed a qualitative analysis of CD and CDE using UPLC-MS and GC-MS, respectively. The CD contained 25 compounds, of which 3 were polymethoxy flavones and flavanones. Three major compounds, nobiletin, tangeretin and hesperidin, accounted for 56.88% of the total relative peak area. In contrast, the CDE contained 11 terpenoids, of which 8 were identified as major compounds, with D-limonene (45.71%) being the most abundant, followed by γ-terpinene (34.65%), linalool (6.46%), p-cymene (2.57%), α-terpineol (2.04%), α-pinene (1.89%), α-terpinolene (1.46%), and ß-pinene (1.16%), accounting for 95.94% of the total oil. In conclusion, our study demonstrated the potential of Hirami lemon as a source of natural antidepressant agents for the prevention and treatment of major depressive disorders.

Plasma selenium and zinc alter associations between nephrotoxic metals and chronic kidney disease: Results from NHANES database 2011-2018.

Introduction: Chronic kidney disease (CKD) is a condition defined as a persistent change in kidney structure or function, or both, that compromises human health. Environmental exposure to heavy metals (e.g. cadmium, lead, arsenic and mercury) is common, and high exposure levels are known to cause nephrotoxicity. Micronutrients such as selenium and zinc are positively associated with better kidney function and renal outcomes. This study determined the associations between CKD and heavy metal exposures measured in blood or urine within a community-dwelling population, and assessed whether and how selenium and zinc modified the associations. Method: Data were extracted from 4 cycles of the US National Health and Nutrition Examination Survey (NHANES) database (2011-2012, 2013-2014, 2015-2016 and 2017-2018). Results: Univariate analysis showed that higher quartiles of plasma lead and cadmium concentration were more likely associated with CKD than the lowest quartile, and along with folate, were linked to greater odds of CKD. Conversely, as plasma selenium and serum zinc increased, the odds of CKD decreased. Multivariate analysis had similar results after adjusting for relevant confounders. Higher plasma cadmium quartiles were associated with higher odds of CKD. Associations between higher quartiles of plasma selenium and serum zinc were significantly associated with lower odds of CKD. Conclusion: Elevated blood levels of heavy metals increase CKD, whereas elevated concentrations of plasma selenium and serum zinc decrease CKD. A high serum zinc concentration appears to interact with low-toxicity heavy metals to reduce CKD risk. This study suggests that increased selenium and zinc in the body along with avoidance of heavy metal exposures could protect against CKD.