Relation of early-stage renal insufficiency and cardiac structure and function in a large population of asymptomatic Asians: a cross-sectional cohort analysis.

Background: Few studies have addressed early-stage kidney disease and preclinical cardiac structural and functional abnormalities from a large-scale Asian population. Further, the extent to which measures of myocardial function and whether these associations may vary by testing various formulas of renal insufficiency remains largely unexplored. Objective: To explore the associations among renal function, proteinuria, and left ventricular (LV) structural and diastolic functional alterations. Design: A cross-sectional, retrospective cohort study. Setting: Registered data from a cardiovascular health screening program at MacKay Memorial Hospital from June 2009 to December 2012. Participants: Asymptomatic individuals. Measurements: Renal function was evaluated in terms of estimated glomerular filtration rate (eGFR) by both MDRD and CKD-EPI formulas and severity of proteinuria, which were further related to cardiac structure, diastolic function (including LV e' by tissue Doppler), and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Results: Among 4942 participants (65.8% men, mean age 49.4 ± 11.2 years), the mean CKD-EPI/MDRD eGFR was 90.6 ± 15.7 and 88.5 ± 16.9 ml/min/1.73m2, respectively. Lower eGFR, estimated either by the MDRD or CKD-EPI method, and higher proteinuria were significantly associated with lower LV e' and higher NT-proBNP (all p<0.05) even after adjusting for clinical covariates. In general, lower eGFR estimated by CKD-EPI and MDRD displayed similar impacts on worsening e' and NT-proBNP, rather than E/e', in multivariate models. Finally, lower LV e' or higher composite diastolic score, rather than E/e', demonstrated remarkable interaction with eGFR level estimated by either CKD-EPI or MDRD on circulating NT-proBNP level (p interaction <0.05). Limitations: Proteinuria was estimated using a urine dipstick rather than more accurately by the urine protein-to-creatinine ratio. Also, pertaining drug history and clinical hard outcomes were lacking. Conclusion: Both clinical estimate of renal insufficiency by eGFR or proteinuria, even in a relatively early clinical stage, were tightly linked to impaired cardiac diastolic relaxation and circulating NT-proBNP level. Elevation of NT-proBNP with worsening renal function may be influenced by impaired myocardial relaxation.

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.

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.

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.

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.

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.

Perennial biomass cropping and use: Shaping the policy ecosystem in European countries.

Demand for sustainably produced biomass is expected to increase with the need to provide renewable commodities, improve resource security and reduce greenhouse gas emissions in line with COP26 commitments. Studies have demonstrated additional environmental benefits of using perennial biomass crops (PBCs), when produced appropriately, as a feedstock for the growing bioeconomy, including utilisation for bioenergy (with or without carbon capture and storage). PBCs can potentially contribute to Common Agricultural Policy (CAP) (2023-27) objectives provided they are carefully integrated into farming systems and landscapes. Despite significant research and development (R&D) investment over decades in herbaceous and coppiced woody PBCs, deployment has largely stagnated due to social, economic and policy uncertainties. This paper identifies the challenges in creating policies that are acceptable to all actors. Development will need to be informed by measurement, reporting and verification (MRV) of greenhouse gas emissions reductions and other environmental, economic and social metrics. It discusses interlinked issues that must be considered in the expansion of PBC production: (i) available land; (ii) yield potential; (iii) integration into farming systems; (iv) R&D requirements; (v) utilisation options; and (vi) market systems and the socio-economic environment. It makes policy recommendations that would enable greater PBC deployment: (1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; (2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low-carbon bioenergy and bioproducts; (3) support innovation in biomass utilisation value chains; and (4) continue long-term, strategic R&D and education for positive environmental, economic and social sustainability impacts.

Anti-Inflammatory Activities of Constituents from Cinnamomum insularimontanum Hayata Leaves and Their Mechanisms.

Cinnamomum insularimontanum is an endemic species of Taiwan. Although most Cinnamomum plants have significant biological activity, the bioactivity investment of C. insularimontanum is rare. Since inflammation plays an important role in many diseases, anti-inflammatory compounds can be developed into healthcare products. Therefore, we first conducted a study on the anti-inflammatory activity of C. insularimontanum leaves. First, we examined the antiinflammation activity of essential oil from C. insularimontanum leaves, and it revealed potent anti-inflammatory activity. A total of 23 volatile compounds were identified in C. insularimontanum leaves' essential oil by using GC/MS analysis. Among them were 1,8-cineole (35.94%), α-eudesmol (6.17%), pinene (7.55%), sabinene (5.06%), and isobornyl acetate (4.81%). According to previous studies, 1,8-cineole might be an anti-inflammation principal compound of C. insularimontanum leaves. Next, the ethanolic extracts of C. insularimontanum leaves also exhibited good anti-inflammatory activity. Two bioactive compounds, isoburmanol (F1) and burmanol (F2), were isolated from the ethyl acetate soluble fraction by using the bioactivity-guided separation protocol and spectroscopic analysis. F1 was obtained from C. insularimontanum for the first time, and F2 was isolated for the first time from natural resources. Both F1 and F2 could inhibit the production of nitric oxide (NO), and the IC50 values were 14.0 µM and 43.8 µM, RAW 264.7 cells after induction of lipopolysaccharide. Furthermore, F1 and F2 also revealed significant inhabitation effects on iNOS and COX-2 protein expression. The anti-inflammation activity of F1 and F2 was different from the common pathway of inhibiting NF-κB. Both of them could inhibit the production of NO and PGE2 by directly inhibiting the AP-1 (c-Jun) protein and then inhibiting the downstream iNOS and COX-2. Although both F1 and F2 possessed significant anti-inflammatory activity, the activity of F1 was better than F2. Through molecular docking simulation analysis, the results show that F1 and F2 interact with AP-1, inhibit the binding of AP-1 to DNA, and cause AP-1 to fail to transcribe the related factors of inflammation. The binding ability of AP-1 and F1 was stronger than F2, and that is the reason why F1 exhibited better activities in both downstream proteins and inflammatory cytokines. Based on the results obtained in this study, the essential oil and F1 and F2 isolated from C. insularimontanum leaves have good anti-inflammatory activities, and it is expected to be used as a reference for the development of medical care products in the future.

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.

Change of Optical Coherence Tomography Morphology and Associated Structural Outcome in Diabetic Macular Edema after Ranibizumab Treatment.

(1) Background: To investigate the correlation between therapeutic outcome and morphologic changes for diabetic macular edema (DME) after intravitreal injection of ranibizumab (IVIR). (2) Methods: This retrospective study included 228 eyes received IVIR for DME. Each participant was traced for two years after the initial IVIR, while the data of ophthalmic examination, optical coherence tomography (OCT) image, and systemic diseases were collected. The study population was categorized into different subgroups according to the existence of OCT morphologic change and the initial OCT morphologic pattern, including diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). The primary outcomes were the baseline best-corrected visual acuity (BCVA) and central macular thickness (CMT) during a two-year study period. The distribution of OCT morphologic change and its relation to primary outcome were analyzed. (3) Results: Comparing the 42 eyes (18.4%) with OCT morphological changes to another 186 eyes (81.6%) without such alteration, the former showed a poorer baseline BCVA (0.84 ± 0.39 vs. 0.71 ± 0.36, p = 0.035), worse final BCVA (0.99 ± 0.44 vs. 0.67 ± 0.30, p = 0.001), and thicker final CMT (354.21 ± 89.02 vs. 305.33 ± 83.05, p = 0.001). Moreover, the VMIA developed in 14.9% of all DME patients presenting the most common morphologic change among DRT, CME, and SRD. Besides, the presence of stroke was independently correlated to the morphologic change (adjusted odds ratio [aOR]: 6.381, 95% confidence interval (CI): 1.112-36.623, p = 0.038). (4) Conclusions: The change of OCT morphology in DME patients receiving IVIR was correlated to worse structural and visual outcome while the formation of VMIA most commonly occurred after initial treatment.

Examination of Gender-Related Differential Item Functioning Through Poly-BW Indices.

The existing differential item functioning (DIF) detection approaches relying on item difficulty or item discrimination are limited for understanding the associates of DIF items, and consequently, DIF items were conventionally either deleted or ignored. Given the importance of minimizing DIF items in test construction, teachers or testing practitioners need more information regarding possible associates of DIF items. Using an example of a teacher-made mathematics achievement test, this study aimed to examine how the Poly-BW indices (power, defenselessness, disturbance, and hint) contributed to the properties of gender-related DIF items. Data from a 34-item mathematics achievement test that involved 1,439 seventh-grade students from Taiwan (51.01% boys and 48.99% girls) showed that the differences of the defenselessness (mp) and power (cp) indices between men and women served as salient predictors of the DIF measures estimated by the Poly Simultaneous Item Bias Test (Poly-SIBTEST) procedure and with satisfactory accuracy of hit rates. Items with relatively large defenselessness for men were likely to present male-favoring DIFs, whereas items with relatively large power for men were likely to present female-favoring DIFs. The Poly-BW indices yielded directions for modifying items for teachers in practice.

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.

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.

Optical Coherence Tomographic Patterns as Predictors of Structural Outcome After Intravitreal Ranibizumab in Diabetic Macula Edema.

BACKGROUND/OBJECTIVES: The purpose of this study was to present an association between the treatment response of diabetic macular edema (DME) to intravitreal ranibizumab (IVR) injections and different morphology patterns using spectral domain optical coherence tomography (SD-OCT). SUBJECTS/METHODS: This retrospective study included 216 eyes of 142 subjects who received IVR for DME and were observed for at least 2 years. Medical charts and SD-OCT images of consecutive patients were reviewed at baseline, 1, 3, 6, 12, and 24 months after first IVR treatment. The OCT patterns were characterized as diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). All patients were classified into four groups based on the OCT findings. RESULTS: For a total of 216 eyes, 36 eyes were classified into the DRT group, 76 in the CME group, 42 in the SRD group, and 62 in the VMIA group. There were significant central macula thickness (CMT) improvements in all groups at the 1st month and the 2nd year, except for the DRT group at the 2nd year. Patients with OCT findings of hyperreflective dots (HRDs), metabolic parameters of hyperlipidemia, and coronary artery disease (CAD) had significantly less improvements in CMT at 2-year follow-up (P=0.029, 0.007, <0.001, respectively). CONCLUSION: A trend toward decreased effectiveness after long-term IVR treatment was observed in the DRT group. Consistent IVR treatment could still achieve favorable improvement in the reduction of CMT in 2-year follow-up in the VMIA group. Different OCT patterns in DME may affect the therapeutic role of anti-VEGF agents and predict the structure outcome.

Essential Oils of Alpinia nantoensis Retard Forskolin-Induced Melanogenesis via ERK1/2-Mediated Proteasomal Degradation of MITF.

The anti-melanogenic activity of essential oils of Alpinia nantoensis and their bioactive ingredients were investigated in vitro. Treatment with leaf (LEO) and rhizome (REO) essential oils of A. nantoensis, significantly reduced forskolin-induced melanin production followed by down-regulation of tyrosinase (TYR) and tyrosinase related protein-1 (TRP-1) expression at both transcriptional and translational levels. Further studies revealed that down-regulation TYR and TRP-1 were caused by LEO/REO-mediated suppression of Microphthalmia-associated transcription factor (MITF), as evidenced by reduced nuclear translocation of MITF. Also, we found that LEO/REO induce the sustained activation of ERK1/2, which facilitate subsequent proteasomal degradation of MITF, as confirmed by that LEO/REO failed to inhibits MITF activity in ERK1/2 inhibitor treated cells. In addition, a significant increase of ubiquitinated MITF was observed after treatment with LEO and REO. Furthermore, the chemical composition of LEO and REO were characterized by gas chromatography-mass spectrometry (GC-MS) resulted that camphor, camphene, α-pinene, ß-pinene, isoborneol and D-limonene were the major compounds in both LEO and REO. Further studies revealed that α-pinene and D-limonene were the active components responsible for the anti-melanogenic properties of LEO and REO. Based on the results, this study provided a strong evidence that LEO and REO could be promising natural sources for the development of novel skin-whitening agents for the cosmetic purposes.

Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFß signaling through TGFBR1 stabilization.

Pulmonary fibrosis (PF) is a major public health problem with limited therapeutic options. There is a clear need to identify novel mediators of PF to develop effective therapeutics. Here we show that an ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), is highly upregulated in the lung tissues from both patients with idiopathic pulmonary fibrosis and a mouse model of bleomycin (BLM)-induced PF. Global deletion of Txndc5 markedly reduces the extent of PF and preserves lung function in mice following BLM treatment. Mechanistic investigations demonstrate that TXNDC5 promotes fibrogenesis by enhancing TGFß1 signaling through direct binding with and stabilization of TGFBR1 in lung fibroblasts. Moreover, TGFß1 stimulation is shown to upregulate TXNDC5 via ER stress/ATF6-dependent transcriptional control in lung fibroblasts. Inducing fibroblast-specific deletion of Txndc5 mitigates the progression of BLM-induced PF and lung function deterioration. Targeting TXNDC5, therefore, could be a novel therapeutic approach against PF.

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.

Effects of continuity of care on the postradiotherapy survival of working-age patients with oral cavity cancer: A nationwide population-based cohort study in Taiwan.

OBJECTIVES: Cancer of the oral cavity, a well-known global health concern, remains one of most common causes of cancer mortality. Continuity of care (COC), a measurement of the extent to which an individual patient receives care from a given provider over a specified period of time, can help cancer survivors process their experiences of dealing with the illness and recuperation; however, limited research has focused on the survival rate of working-age patients with oral cancer. METHODS: A total of 14,240 working-age patients (20 0.38) and non-high COC (COCI ≤ 0.38) groups. After propensity-score matching, the mortality risk in the low and intermediate COC groups was also found to be significantly higher than that in the high COC group (aHR = 1.178, 95% CI = 1.074-1.292, p < 0.001 and aHR = 1.189, 95% CI = 1.107-1.277, p = 0.001, respectively). CONCLUSIONS: In Taiwan, COC and prior dental treatment before RT significantly affected the survival rate of working-age patients with oral cancer. This result merits policymakers' attention.