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G-protein-coupled receptor 39 (GPR39) plays a role in cellular and physiological processes, including insulin secretion, cell death inhibition, wound healing, and obesity. Increasing evidence suggests that GPR39 is potently stimulated by zinc ions (Zn2+) and is therefore considered a putative Zn2+ receptor. Given the importance of Zn2+ in the reproductive system, we proposed that GPR39 might have a functional role in the reproductive system. However, the localization of GPR39 in the reproductive system remains unknown. Here, we used mice expressing a Gpr39 promoter-driven LacZ reporter system to detect Gpr39 expression in the reproductive system at different phases of the estrous cycle and found an interesting region-specific distribution of Gpr39 in the mouse oviduct epithelium, with strong expression at the ampulla and weak expression at the isthmus, which was consistent with the results using reverse transcription polymerase chain reaction and immunofluorescence. Moreover, using ZnSeAMG staining, we found that Zn2+, the putative ligand of GPR39, also found a distribution similar to GPR39 expression, suggesting that their potential interaction mediates fertilization and embryo transportation.

Previous data showed that poor metabolic control existed in Guangdong type 1 diabetes mellitus(T1DM) patients. Thus, scheduled follow-ups were initiated in our diabetic clinic. This study aimed to assess the effect of scheduled management and explore related factors. From June 2011 to November 2018, 342 patients with T1DM registered in our diabetic clinic. Clinical data was obtained, HbA1c and plasma lipids were measured at enrollment and then once a year. Patients who had been followed-up for three years were included. A total of 201 patients (59.7% female) were analyzed, with median age of 26.9(18.1,35.5) years and diabetic duration of 5.6(0.4,8.8) years. HbA1c levels fell from 8.0±2.0% at enrollment to 7.3±1.2% in the third year progressively (P Disclosure Y. Zhou: None. J. Yan: None. D. Yang: None. S. Luo: None. X. Zheng: None. P. Ling: None. Z. Wu: None. Q. Huang: None. Y. Xian: None. C. Wang: None. Q. Lin: None. H. Liu: None. B. Yao: None. J. Weng: None. Funding Natural Science Foundation of Guangdong Province (2018A030313251); Science and Technology Planning Project of Guangzhou (201709010037)

Objective: To develop and evaluate a smartphone-based short food frequency questionnaire. Methods: We developed a digitalized short food frequency questionnaire adapted to the diet habit of the Chinese people. Seventy participants were recruited by quota sampling. Participants completed an FFQ face to face (1st FFQ) and a 3-day dietary record (DR) at the baseline for validation. A second FFQ (2nd FFQ) was completed 3 weeks later for reproducibility study, either face to face or on the phone. Results: Sixty-seven participants completed the study per protocol and rendered eligible FFQs and 3-day DR. Twenty-one people were interviewed on the phone for 2nd FFQ and correlation coefficients of energy and nutrient intakes with 1st FFQ were 0.848∼0.959(all P Conclusion: Our FFQ had satisfying reproducibility and validity in general and diabetic population and was ready to apply to remote surveys. Disclosure D. Yang: None. C. Wang: None. S. Luo: None. X. Zheng: None. Q. Lin: None. X. Wei: None. J. Yan: None. J. Weng: None.

Objective: Data are limited on insulin resistance (IR) status in patients with type 1 diabetes (T1D). This study aimed to assess the IR status and the effect of onset age on IR in patients with T1D. Methods: Through the Guangdong T1D registry study, we identified adult patients (aged≥18 years) with a diabetes duration≥1 year. Clinical data were collected. A previously established model based on euglycemic-hyperinsulinemic clamp were used to calculate the estimated glucose disposal rate (eGDR) via clinical parameters. Participants were categorized into groups based on age of onset: childhood-onset group (cT1D, age of onset Results: This analysis included 872 adults with T1D (58.3% female). The mean (SD) eGDR was 8.98 (3.34) mg/kg/min. There was a negative correlation between the level of IR status and the onset age (r=-0.093, p=0.003). The IR status assessed by eGDR decreased alongside an increase in age of onset (p=0.018). Compared with participants with older age of onset, patients in cT1D group had a higher level of A1c, lower proportion of participants with A1c less than 7%, higher daily insulin dose and higher frequency of hypoglycemic events (all p Conclusions: Age of onset was significantly and negatively correlated with IR status. Childhood-onset patients with T1D are more likely to benefit from treatment of IR condition. Disclosure D. Yang: None. C. Wang: None. X. Zheng: None. S. Luo: None. Q. Lin: None. J. Yan: None. J. Weng: None.

Development of the next-generation, high-energy-density, low-cost batteries will likely be fueled by sodium (Na) metal batteries because of their high capacity and the abundance of Na. However, their practical application is significantly plagued by the hyper-reactivity of Na metal, unstable solid electrolyte interphase (SEI), and dendritic Na growth, leading to continuous electrolyte decomposition, low Coulombic efficiency, large impedance, and safety concerns. Herein, we add a small amount of SnCl2 additive in a common carbonate electrolyte so that the spontaneous reaction between SnCl2 and Na metal enables in situ formation of a Na–Sn alloy layer and a compact NaCl-rich SEI. Benefitting from this design, rapid interfacial ion transfer is realized and direct exposure of Na metal to the electrolyte is prohibited, which jointly achieve a nondendritic deposition morphology and a markedly reduced voltage hysteresis in a Na/Na symmetric cell for over 500 h. The Na/SnCl2-added electrolyte/Na3V2(PO4)3 full cel...

Fault trend prediction can indicate future fault process changing trend and help operators to remove serious process fault in advance. The existing process fault prediction methods are often based on the empirical linear model, which is inappropriate for the nonlinear catalyst deactivation fault. In order to forecast the process deterioration trend accurately, a fault trend prediction method based on a combined fault model is proposed. Firstly, an improved process fault model is developed by combining the empirical model and catalyst deactivation fault mechanism. Then, Kalman filter is used to estimate fault model parameters. Future process changing trend is forecasted by performing the fuzzy adaptive unscented Kalman predictor. Simulations on a continuous stirred reactor show that the proposed method can predict process changing trend under the catalyst deactivation condition more accurately.

Room-temperature sodium metal batteries with metallic Na anodes and flammable organic solvent-based electrolytes are breeding severe safety concerns. Herein, by introducing non-flammable, highly-fluorinated ethers as bridge solvents, we enable superior miscibility of an all-fluoride fire extinguishant into fluorinated carbonate electrolytes. Besides the intrinsic non-flammability of the designed electrolyte, the embedded PFMP extinguishant further enhances the battery safety by its efficacy to in situ dissipate the internal heat at an elevated temperature (ΔH = +88.1 J g−1). Moreover, the cyclability is greatly improved by using such an electrolyte. The Na/Na symmetrical cells can cycle for 1100 h at 1.0 mA h cm−2 and more than 800 h at 5.0 mA h cm−2. Paired with a high voltage Na3V2(PO4)2O2F cathode, the full cell exhibits a high initial coulombic efficiency of 94.7% and a capacity retention of 87.1% after 1000 cycles at 0.5C, which is mainly ascribed to the thin F-rich interphases established on both the Na metal anode and the cathode.

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused over 9.2 million confirmed cases and 478,000 deaths (as of June 24th, 2020). The high intensive care unit (ICU) admission rate and mortality of COVID-19 is continuously posing a serious strain on the global health-care system. While most patients present with mild to moderate symptoms, some patients may develop life-threatening sepsis, respiratory failure, acute respiratory distress syndrome (ARDS) and multiple organ failure. However, current antiviral and supportive therapies are not sufficient to prevent or treat the above complications especially in severely ill COVID-19 patients [1]. Thus, it is urgent to find the underlying mechanism dominating such life-threatening complications. It is well recognized that lung damage and multi-organ failure in this subgroup of patients arise due to overwhelming systemic hyper-inflammation. Therefore, promising anti-inflammatory candidate agents targeting diverse mechanisms related to cytokine storm will be therapeutically relevant (Fig. 1 ). Open in a separate window Fig. 1 Potential therapies of COVID-19 by targeting inflammation and cytokine storm. SARS-CoV-2 enters and infects cells by binding to TMPRSS2 and ACE2, subsequently releases virus RNA, one of the PAMPs, and recruits dendritic cells, macrophages and neutrophils. The released type I interferon and pro-inflammatory cytokines and chemokines induce the innate immune response while adaptive immune response is ignited by activating T and B lymphocytes to defend against the virus. Meanwhile, intact viruses or the components can directly activate the NLRP3 inflammasome, leading to IL-1β secretion. In most infections, moderate immune response and antiviral response are capable to combat the infection. Nevertheless, in individuals with immunological dysfunction, persistent hyper-inflammation triggers a cytokine storm, leading to the lung injury and ARDS or eventually swept through the whole body, causing MODS. During the pathological progression, the inhibition of NRLP3, JAK1/2, IL-6, BRD4 and the infusion of IVIG may be beneficial in suppressing the overwhelming inflammation and arrest or reverse the COVID-19 disease. Abbreviations: ACE2, angiotensin converting enzyme 2; ARDS, acute respiratory distress syndrome; IVIG, intravenous immunoglobulin; MODS, multiple organ dysfunction syndrome; NLRP3, Nod-like receptor protein 3; PAMP, pathogen-associated molecular pattern; TMPRSS2, transmembrane serine protease 2.

Silicon-based lithium ion battery is reckoned as an ideal choice owing to its ultrahigh theoretical capacity and rich natural resources. However, its practical application is largely hampered by the low Coulombic efficiency (CE) and fast capacity decay arising from the substantial volumetric variations and the unstable solid-electrolyte interphase (SEI). Herein, we propose a binder-based optimization, where a three-dimensional (3D) binder network is devised with organic polyvinyl alcohol (PVA) backbones cross-linked by a functional boric acid (BA). Apart from the improved mechanics, B–OH bond is able to set a chemical bridge between the binder and Si surface by dehydration with Si–OH group, which enables the coherent link with Si surface. More importantly, the electron deficient B element readily accepts electrons during the cell formation and thus facilitates the buildup of an effective SEI film. The obtained lithium borate species significantly reduce the interfacial side reactions and improve the initial Coulombic efficiency (ICE). After optimization of the key parameters, a high ICE (92.76%) with excellent rate capability (~2920.73 mAh g−1 at 10 C) is obtained. After 500 cycles, the Si anode retained a capacity of ~1883.7 mAh g−1, massively outperforming the pure PVA-based Si counterpart (~317.9 mAh g−1).

The high theoretical capacity and earth-abundancy of metallic sodium (Na) endow it with high potential as the ultimate anode for batteries based on Na-ion chemistry. Nevertheless, dendritic Na, the unstable solid electrolyte interphase (SEI) and an infinite volume change of Na metal, drive rapid cell deterioration and potential safety hazards. In tackling these challenges, we take advantage of the spontaneous reaction between molten Na and SnO2 that triggers the formation of a percolated Na–Sn alloy/Na2O framework throughout Na metal, effectively anchoring the “hostless” Na into a dual ion/electron-conductive matrix and simultaneously improving the electrode surface chemistry. By density functional theory (DFT) calculations, we validate the high “sodiophilicity” and low Na+ diffusion barrier enabled by the Na–Sn alloy/Na2O framework. As such, stable Na plating/striping is realized in symmetric cells using both carbonate and ether-based electrolytes without any additive. The full cell paired with Na3V2(PO4)3 cathode further demonstrates superior capacity retention of 83% over 300 cycles (1C), along with a promising rate performance at 10C.

Aims: Our aim was to investigate the impact of glycemic variability (GV) on the relationship between glucose management indicator (GMI) and laboratory glycated hemoglobin A1c (HbA1c). Methods: Adult patients with type 1 diabetes mellitus (T1D) were enrolled from five hospitals in China. All subjects wore the iPro™2 system for 14 days before HbA1c was measured at baseline, 3 months and 6 months. Data derived from iPro™2 sensor was used to calculate GMI and GV parameters [standard deviation (SD), glucose coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE)]. Differences between GMI and laboratory HbA1c were assessed by the absolute value of the hemoglobin glycation index (HGI). Results: A total of 91 sensor data and corresponding laboratory HbA1c, as well as demographic and clinical characteristics were analyzed. GMI and HbA1c were 7.20 ± 0.67% and 7.52 ± 0.73%, respectively. The percentage of subjects with absolute HGI 0 to lower than 0.1% was 21%. GMI was significantly associated with laboratory HbA1c after basic adjustment (standardized β = 0.83, p Conclusions: This study validated the GMI formula using the iPro™2 sensor in adult patients with T1D. GV influenced the relationship between GMI and laboratory HbA1c.

Background: Previous studies show that the use of do-it-yourself artificial pancreas system (DIYAPS) may be associated with better glycemic control characterized by improved estimated hemoglobin A1c (eHbA1c) and time in range among adults with type 1 diabetes (T1D). However, few studies have demonstrated the changes in laboratory-measured HbA1c, which is a more accepted index for glycemic control, after using a DIYAPS. Methods: This is a retrospective before-after study approaching patients who reported self-use of AndroidAPS. The main inclusion criteria included: T1D; aged ⩾18 years; having complete record of ⩾3 months of continuous AndroidAPS use; with laboratory-measured HbA1c and quality of life scale data before and after 3 months of AndroidAPS use; and not pregnant. The primary outcome was the change in HbA1c between baseline and 3 months after initiation of AndroidAPS use. Results: Overall, 15 patients (10 females) were included; the median age was 32.2 years (range: 19.2–69.4), median diabetes duration was 9.7 years (range: 1.8–23.7) and median baseline HbA1c was 7.3% (range: 6.4–10.1). The 3 months of AndroidAPS use was associated with substantial reductions in HbA1c [6.79% (SD: 1.29) versus 7.63% (SD: 1.06), p = 0.002] and glycemic variability when compared with sensor-augmented pump therapy. A lower level of fear of hypoglycemia [22.13 points (SD: 6.87) versus 26.27 points (SD: 5.82), p = 0.010] was also observed after using AndroidAPS. Conclusions: The 3 months of AndroidAPS use was associated with significant improvements in glucose management and quality of life among adults with T1D.

Germanium is considered as a potential anode material for sodium-ion batteries due to its fascinating theoretical specific capacity. However, its poor cyclability resulted from the sluggish kinetics and large volume change during repeated charge/discharge poses major threats for its further development. One solution is using its ternary compound as an alternative to improve the cycling stability. Here, high-purity CuGeO3 nanowires were prepared via a facile hydrothermal method, and their sodium storage performances were firstly explored. The as-obtained CuGeO3 delivered an initial charge capacity of 306.7 mAh g−1 along with favorable cycling performance, displaying great promise as a potential anode material for sodium ion batteries.

Objective: To assess the effectiveness of mobile health application TangTangQuan (TTQ) in management of type 1 diabetes (T1D) in China. Methods: TTQ is designed to provide diabetes self-management education (DSME) for patients with T1D.The innovation of TTQ is to break the isolation of individual T1D patients by socializing their self-management data, and let them find the “patients like me.” TTQ included four major modules: personal diabetes diary, games for DSME, peer support communities and online education courses. Patients recorded and uploaded their diabetes diary via TTQ, and peer patients or family members were able to make comments, or share their own experiences, or interact with the up loaders under the posts. Free download and registration of TTQ was available in major APP stores for mobiles in China since September 2015. The self-report demographic and clinical data were collected through TQQ. Results: During September 2015 and December 2017, a total of 7641 patients (M/F, 3716/3925) aged 21.28±14.43 years, with duration of T1D 2.50 (1.00,6.90) years, have signed up and joined the management of TTQ, from 21 provinces in China. Fifty two percent were 18 to 45 years old and 41% were less than 18 years old. Twenty four percent of them were active in peer support communities including sharing their experiences in management of T1D. Among 2903 patients with duration of diabetes ≥1 year who have used TTQ for ≥1 year,435 have continuous record for 1 year of self-meter blood glucose (SMBG) at least 4 times per day in TTQ. Among these patients, SMBG frequency was 2.43/week(1.40,13.13) and 2.88/week(0.63,11.92) (P=0.967), HbA1c was 6.59±1.40% and 6.40±1.39%(P=0.002), the frequency of hypoglycemia was 6.75/week (4.00,11.50) and 6.25/week (2.75,9.67) (P=0.005) before and after one year use of TTQ, respectively. Conclusions: TTQ has the potential to be a novel intervention for engaging T1D patients and their families in positive communication to support DSME. Disclosure P. Ling: None. S. Luo: None. J. Yan: None. X. Zheng: None. D. Yang: None. X. Zeng: None. J. Weng: None.

BEYOND II was a multicenter, single-arm, observational study in which physicians received education based on T2DM treatment guidelines and effective patient education, reinforced by self-audit and peer-to-peer review over a 6-month period. The primary outcome measure was the proportion of study centers meeting individual improvement goals set by the Study Committee, based on HbA1c TableVariableBaseline cohort (N=6386)Post-education cohort (N=6353)P-valueProportion of centers meeting individual improvement targets, n/n (%; 95% CI)--35/71 (49.3%; 37.2 to 61.4%)--Mean HbA1c, % (SD)8.10 (1.732)7.72 (1.579) Disclosure J. Weng: None. J. Zhao: None. Z. Zhou: None. X. Guo: None. X. Zheng: None. S. Luo: None.

Background: Preconception care (PCC) can improve pregnancy outcomes in women with type 1 diabetes (T1D). Little was known on current status of PCC in China. We aimed to investigate the current practice and attitude about PCC from the perspective of the patients’ family members. Method: We conducted in-depth interviews with family members of T1D women. By purposive sampling we included their husbands, parents and parents-in-law. Transcripts of the interviews were coded into themes by 3 researchers via thematic framework method and analyzed in NVIVO 11. The recruitment ended when no new themes emerged. Results: We interviewed 16 family members of 14 T1D women (10 husbands, 4 mothers, 1 father and 1 mother-in-law) and rendered 9 themes. 1. Knowledge of T1D and PCC: most demonstrated little knowledge of both due to lack of education. 2. Content of PCC: dietary guidance and glycaemic control were most required. 3. Timing of starting PCC: adulthood was most recommended while the rest adolescence. 4. Approach of PCC: internet and on-site consultation were well recognized while tutorials and materials as supplements. 5. Multi-disciplinary cooperation: most suggested that endocrinology professionals take the main responsibility of PCC with other professionals. 6. Attitude on pregnancy: most thought women had the obligation of childbearing while the rest showed respect to the women’s own decision. 7. Concern: worries on complications during pregnancy, inheritance of T1D, social discrimination and economic cost. 8. Doctor-patient communication: most considered the information and consultation time provided by doctors were inadequate. 9. Peer support: peer communication was mainly supported in order to convey experience and confidence while the minority opposed it fearing the spread of negative information. Conclusions: Family members of T1D women scarcely owned knowledge of PCC and suffered various concerns. Their participation in PCC should be encouraged and mental support should be enhanced. Disclosure C. Wang: None. S. Luo: None. X. Zheng: None. X. Hu: None. J. Yan: None. Y. Guo: None. S. Xiong: None. D. Yang: None. L. Qiu: None. B. Yao: None. J. Weng: None.

Objectives: To assess the awareness of preconception counseling in childbearing age women with T1DM (type 1 diabetes mellitus) in China. Methods: Women with T1DM in childbearing age were enrolled from 11 hospitals in Beijing, Jinan, Nanjing, Shanghai, Chengdu, Changsha and Guangzhou from May 2015 to August 2017. Demographic data, clinical characteristics and information on preconception counseling were collected. Redcap was used to establish the database and SPSS 20.0 was adopted to analyze data. Results: A total of 178 T1DM women with age 30.43±4.34 years and duration of T1DM 20.52±7.62 years were enrolled. Patients were pregnant (≤13 weeks, n=89; 13-28 weeks, n=30; ≥28 weeks, n=12) or planning pregnancy (n=47). There were 85.9% of patients realizing pregnancy was permitted when HbA1c< 7.0% while 2.2% worrying T1DM women cannot be pregnant due to genetic susceptibility or potential injury. Most patients had the awareness to perform thyroid function test (92.0%), blood/urine ketone test (94.2%), diabetic retinopathy (90.8%) and nephropathy screening (95.4%) before pregnancy. Patients considered it was necessary to tighten glycemic control(100.0%) and postprandial glucose monitoring should be included (90.1%). Most patients(93.6%) admitted intake of multivitamin and folic acid was essential and 96.0% of them knew weight control and exercise for at least 30 mins per day,while only 78.5% thought preparing for a delivery in advance of the third trimester was necessary. Among 131 pregnant women, 65.6% received preconception counseling; patients with preconception counseling had better glycemic control before pregnancy compared with those without counseling (HbA1c 6.73±0.93% vs. 7.55±1.38%, P=0.028; severe hypoglycemic 25.6% vs. 61.9%, P Conclusion: The awareness of preconception counseling had been improved but was still not sufficient. Effective preconception counseling was associated with better glycemic control before pregnancy in pregnant women with T1DM. Disclosure Y. Zhou: None. J. Yan: None. S. Luo: None. X. Zheng: None. P. Ling: None. Z. Wu: None. J. Lv: None. L. Qiu: None. D. Yang: None. J. Weng: None.

Accumulating evidence suggests that air pollution is a risk factor for adverse respiratory and cardiovascular health outcomes. However, the different impacts of exposure to air pollutants on influenza virus activity and influenza-like illness (ILI) have not been well documented in epidemiological studies. We examined the association between air pollutants of particular matters

Background Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM. Methods This cross-sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year. Participants with HbA1c levels

Probability of missing nodal disease (false negative, %) for selected values of the number of nodes examined. Table S2. Nodal staging score for selected values of the number of nodes examined. (DOCX 54 kb)

Motivated by the analysis of quality of life data from a clinical trial on early breast cancer, we propose in this paper a generalized partially linear mean-covariance regression model for longitudinal proportional data, which are bounded in a closed interval. Cholesky decomposition of the covariance matrix for within-subject responses and generalized estimation equations are used to estimate unknown parameters and the nonlinear function in the model. Simulation studies are performed to evaluate the performance of the proposed estimation procedures. Our new model is also applied to analyze the data from the cancer clinical trial that motivated this research. In comparison with available models in the literature, the proposed model does not require specific parametric assumptions on the density function of the longitudinal responses and the probability function of the boundary values and can capture dynamic changes of time or other interested variables on both mean and covariance of the correlated proportional responses. Copyright © 2017 John Wiley & Sons, Ltd.

Sodium (Na) metal anodes stand out with their remarkable capacity and natural abundance. However, the dendritic Na growth, infinite dimensional changes, and low Coulombic efficiency (CE) present key bottlenecks plaguing practical applications. Here, heteroatom-doped (nitrogen, sulfur) hollow carbon fibers (D-HCF) are rationally synthesized as a nucleation-assisting host to enable a highly reversible Na metal. The "sodiophilic" functional groups introduced by the heteroatom-doping and large surface area (≈1052 m2 g-1 ) synchronously contribute to a homogenous plating morphology with dissipated local current density. High "sodiophilicity" of the D-HCF is confirmed by first-principle calculations and experimental results, where strong adsorption energy of -3.52 eV with low Na+ nucleation overpotential of 3.2 mV at 0.2 mA cm-2 is realized. As such, highly reversible plating/stripping is achieved at 1.0 mA cm-2 with average CE approximating 99.52% over 600 cycles. The as-assembled Na@D-HCF symmetric cells exhibit a prolonged lifetime for 1000 h. A full-cell paired with Na3 V2 (PO4 )3 cathode further demonstrates stable electrochemical behavior for 200 cycles at 1 C along with excellent rate performance (102 mAh g-1 at 5 C). The results clearly show the effectiveness of the D-HCF in manipulating Na+ deposition and thus the significance of nucleation control in realizing dendrite-free metal anodes.

OBJECTIVES: Meningioma is the most common extra-axial tumour, however, little is known about the effect of the disease and its treatment on the brain, and patients functional and cognitive outcomes. We hypothesised that peri-operative factors can effect patients cognitive outcome. DESIGN: We aimed to identify clinical and radiological features associated with cognitive outcome in patients who had undergone resections of a supratentorial meningioma. Subjects: 28 active participants with both complete cognitive and radiological outcomes were identified in our database of focal brain injuries. The cognitive tests performed were the National Adult Reading Test (NART) and Cattell Culture Fair Test (CCFT). METHODS: NART and CCFT scores were converted into intelligence quotient (IQ) scores, for use as markers of cognitive outcome. Independent t-tests and ANOVA statistics were utilised to identify features associated with lower IQ scores. RESULTS: There was a negative correlation between age and CCFT IQ scores (r=-0.632, P=0.007). Factors predisposing patients to poorer cognitive outcomes included: recurrent tumour (P

In this paper, we develop robust estimation for the mean and covariance jointly for the regression model of longitudinal data within the framework of general- ized estimating equations (GEE). The proposed approach integrates the robust method and joint mean-covariance regression modeling. Robust generalized estimating equa- tions using bounded scores and leverage-based weights are employed for the mean and covariance to achieve robustness against outliers. The resulting estimators are shown to be consistent and asymptotically normally distributed. Simulation studies are conducted to investigate the effectiveness of the proposed method. As expected, the robust method outperforms its non-robust version under contaminations. Finally, we illustrate by analyzing a hormone data set. By downweighing the potential out- liers, the proposed method not only shifts the estimation in the mean model, but also shrinks the range of the innovation variance, leading to a more reliable estimation in the covariance matrix.

Motivated by the analysis of quality of life data from a clinical trial on early breast cancer, we propose in this paper a generalized partially linear mean-covariance regression model for longitudinal proportional data, which are bounded in a closed interval. Cholesky decomposition of the covariance matrix for within-subject responses and generalized estimation equations are used to estimate unknown parameters and the nonlinear function in the model. Simulation studies are performed to evaluate the performance of the proposed estimation procedures. Our new model is also applied to analyze the data from the cancer clinical trial that motivated this research. In comparison with available models in the literature, the proposed model does not require specific parametric assumptions on the density function of the longitudinal responses and the probability function of the boundary values and can capture dynamic changes of time or other interested variables on both mean and covariance of the correlated proportional responses. Copyright © 2017 John WileySons, Ltd.

Dysregulated antigen receptor-mediated NF-kappaB activation can contribute to development of autoimmunity, chronic inflammation, and malignancy. A chemical biology screening strategy has identified a substituted benzimidazole that selectively inhibits antigen receptor-mediated NF-kappaB activation without blocking other NF-kappaB activation pathways. A library of analogs was synthesized and the structure-activity relationship and metabolic stability for the series is presented.

Both G and V type nerve agents possess a center of chirality about phosphorus. The S(p) enantiomers are generally more potent inhibitors than their R(p) counterparts toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To develop model compounds with defined centers of chirality that mimic the target nerve agent structures, we synthesized both the S(p) and the R(p) stereoisomers of two series of G type nerve agent model compounds in enantiomerically enriched form. The two series of model compounds contained identical substituents on the phosphorus as the G type agents, except that thiomethyl (CH(3)-S-) and thiocholine [(CH(3))(3)NCH(2)CH(2)-S-] groups were used to replace the traditional nerve agent leaving groups (i.e., fluoro for GB, GF, and GD and cyano for GA). Inhibition kinetic studies of the thiomethyl- and thiocholine-substituted series of nerve agent model compounds revealed that the S(p) enantiomers of both series of compounds showed greater inhibition potency toward AChE and BChE. The level of stereoselectivity, as indicated by the ratio of the bimolecular inhibition rate constants between S(p) and R(p) enantiomers, was greatest for the GF model compounds in both series. The thiocholine analogues were much more potent than the corresponding thiomethyl analogues. With the exception of the GA model compounds, both series showed greater potency against AChE than BChE. The stereoselectivity (i.e., S(p) > R(p)), enzyme selectivity, and dynamic range of inhibition potency contributed from these two series of compounds suggest that the combined application of these model compounds will provide useful research tools for understanding interactions of nerve agents with cholinesterase and other enzymes involved in nerve agent and organophosphate pharmacology. The potential of and limitations for using these model compounds in the development of biological therapeutics against nerve agent toxicity are also discussed.

The disorder trimethylaminuria (TMAu) often manifests itself in a body odor for individuals affected. TMAu is due to decreased metabolism of dietary-derived trimethylamine (TMA). In a healthy individual, 95% or more of TMA is converted by the flavin-containing monooxygenase 3 (FMO3, EC 1.14.13.8) to non-odorous trimethylamine N-oxide (TMA N-oxide). Several single nucleotide polymorphisms (SNPs) of the FMO3 gene have been described and result in an enzyme with decreased or abolished functional activity for TMA N-oxygenation thus leading to TMAu. Herein, we report two novel mutations observed from phenotyping and genotyping two self-reporting individuals. Sequence analysis of the exon regions of the FMO3 gene of a young woman with severe TMAu revealed heterozygous mutations at positions 187 (V187A), 158 (E158K), 308 (E308G), and 305 (E305X). Familial genetic analysis showed that the E158K/V187A/E308G derived from the same allele from the mother, and the E305X was derived from the father. FMO3 variants V187A and V187A/E158K were characterized for oxygenation of several common FMO3 substrates (i.e., 5- and 8-DPT, mercaptoimidazole (MMI), TMA, and sulindac sulfide) and for its thermal stability. Our findings show that with the combination of V187A/E158K mutations in FMO3, the enzyme activity is severely affected and possibly contributes to the TMAu observed. In another study, genotyping analysis of a 17 year old female revealed a mutation that caused a frame shift after K415 and resulted in a protein variant with only 486 amino acid residues that was associated with severe TMAu.

To explore the factors associated with glycemic control in adults with type 1 diabetes mellitus (T1D) on an insulin pump.A total of 108 patients aged over 18 years and on an insulin pump therapy for6 months were selected from 16 centers of Guangdong Type 1 diabetes Translational Medicine Study. They were classified into two groups according to the (American Diabetes Association) ADA Hemoglobin A1c target (7.0%). Those reaching the target (n = 59) were compared with those failed (n = 49) using ANOVA and Logistic regression.There were 75 females and 33 males with a median age of 32.0 (25.9-40.9) years and a median disease duration of 7.9(4.2-12.3) years. Logistic regression analysis revealed an odds ratio of 4.48(95%CI 1.53-13.15, P = 0.00) for total daily basal insulin dose within 0.2-0.3 units per kilogram, an OR of 1.31 (95%CI 1.05-1.63, P = 0.01) for self-monitoring of blood glucose (SMBG) and an OR of 3.43 (95%CI 1.18-10.01, P = 0.02) for males.Higher frequencies of SMBG and appropriate basal insulin dose are essential for adult patients with T1D on an insulin pump.

Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM.This cross-sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year. Participants with HbA1c levels7% were compared against those with HbA1c levels ≥ 7%. A multivariate logistic regression model was used to examine factors associated with glycaemic control.Among the 827 participants, the mean age was 34.2 ± 12.1 years and the median (interquartile range) duration of diabetes was 6.1 (3.4, 10.4) years. The median HbA1c level was 8.5% (7.5%, 10.2%). Only one-fifth of participants had HbA1c levels7%. Insufficient glycaemic control (HbA1c ≥ 7%) was strongly associated with infrequent self-monitoring of blood glucose (OR = 1.21, 95% CI 1.14 ~ 1.29, p = 0.000), high insulin dose (OR = 1.27, 95% CI 1.07 ~ 1.52, p = 0.006), smoking (OR = 3.11, 95% CI 1.44 ~ 6.72, p = 0.004), low-frequency clinical visits (OR = 2.74, 95% CI 1.47 ~ 5.10, p = 0.001), the presence of diabetic autoantibodies (OR = 1.63, 95% CI 1.07 ~ 2.48, p = 0.022) and low fasting C-peptide (FCP) levels (OR = 1.21, 95% CI 1.01 ~ 1.46, p = 0.049) after adjustment for age at disease onset, education level, household income and diet control.Most adult patients with T1DM did not achieve the HbA1c target. Identifying determinants for glycaemic control provides us valuable information to improve glycaemic control in these patients. Copyright © 2015 John WileySons, Ltd.

G-protein-coupled receptor 39 (GPR39) plays a role in cellular and physiological processes, including insulin secretion, cell death inhibition, wound healing, and obesity. Increasing evidence suggests that GPR39 is potently stimulated by zinc ions (Zn

The pollution characteristics of current atmospheric particulates was summarized in the present investigation. The composition and proportion of the pollution sources used for dirt pickup resistance and stain removal test were adjusted, and the pollution sources used for new type dirt pickup resistance and stain removal test produced. In addition, a new dirt pickup method was adopted, and a set of new type laboratory dirt pickup resistance and stain removal tests developed by taking comprehensive consideration of the existing state and dirt pickup mode of actual atmospheric particulates. It verifies the rationality, feasibility and effectiveness of new test methods for dirt pickup resistance and stain removal based on the contrast test over the new and old test methods.

Aims/hypothesis Insulin resistance (IR) is a risk factor to assess the development of micro- and macro-vascular complications in type 1 diabetes (T1D). However, diabetes management in adults with T1D is limited by the difficulty of lacking simple and reliable methods to estimate insulin resistance. The aim of this study was to develop a new model to estimate IR via clinical parameters in adults with T1D. Methods A total of 36 adults with adulthood onset T1D (n = 20) or childhood onset T1D (n = 16) were recruited by quota sampling. After an overnight insulin infusion to stabilize the blood glucose at 5.6 to 7.8 mmol/L, they underwent a 180-minute euglycemic-hyperinsulinemic clamp. Glucose disposal rate (GDR, mg kg-1 min-1) was calculated by data collected from the last 30 minutes during the test. Demographic factors (age, sex, and diabetes duration) and metabolic parameters (blood pressure, glycated hemoglobin A1c [HbA1c], waist to hip ratio [WHR], and lipids) were collected to evaluate insulin resistance. Then, age at diabetes onset and clinical parameters were used to develop a model to estimate lnGDR by stepwise linear regression. Results From the stepwise process, a best model to estimate insulin resistance was generated, including HbA1c, diastolic blood pressure, and WHR. Age at diabetes onset did not enter any of the models. We proposed the following new model to estimate IR as in GDR for adults with T1D: lnGDR = 4.964 − 0.121 × HbA1c (%) − 0.012 × diastolic blood pressure (mmHg) − 1.409 × WHR, (adjusted R2 = 0.616, P

In longitudinal data analysis, a correct specification of the within-subject covariance matrix cultivates an efficient estimation for mean regression coefficients. In this article, we consider robust variable selection method in a joint mean and covariance model. We propose a set of penalized robust generalized estimating equations to simultaneously estimate the mean regression coefficients, the general- ized autoregressive coefficients, and innovation variances introduced by the modified Cholesky decomposition. The set of estimating equations select important covari- ate variables in both mean and covariance models together with the estimating procedure. Under some regularity conditions, we develop the oracle property of the proposed robust variable selection method. Finally, a simulation study and a detailed data analysis are carried out to assess and illustrate the small sample per- formance; they show that the proposed method performs favorably by combining the robustifying and penalized estimating techniques together in the joint mean and covariance model.

Background Pregnancy-related care can reduce the risk of adverse pregnancy outcomes in women with type 1 diabetes. But little is known about the special health-care needs related to pregnancy of these women, or about the gap between these needs and health-care provision in China. We aimed to identify the perceived needs in women with type 1 diabetes and health-care providers for pregnancy-related care. The goal is for the findings to assist in the establishment of optimised management of this population in China. Methods We did in-depth interviews, a method widely used in social science to investigate people's attitudes and behaviours. The intended interviewees included women with type 1 diabetes (aged ≥18 years) and health-care providers of both diabetes-related and pregnancy-related disciplines living in Guangdong, China. Written informed consent was obtained from all participants. Selective sampling was used to ensure that the recruited women with type 1 diabetes covering different areas of Guangdong, and were of diverse age, disease duration, marital and child-bearing status, income, and education level; and to ensure that the included health-care providers were from different types of health-care facilities. Transcripts of the interviews were coded into themes by three investigators (SX, SL, and CW) via a thematic framework method and NVIVO (version 10) qualitative software. The recruitment ended when no new themes emerged. Rendered themes of women with type 1 diabetes and health-care providers were compared by thorough discussion within the study team. Findings The recruitment started in April, 2015, and ended in June, 2016. 30 women with type 1 diabetes (mean age 26·9, SD 5·7 years) and 35 health-care providers (17 physicians and 18 nurses; 24 from general hospitals and 11 from community health facilities) were included in the study. Pregnant women and health-care providers agreed that pregnancy-related health-care resources were scarce and knowledge of pregnancy-related health care needs of both patients and health-care providers was limited. Both groups agreed that pregnancy-related health care in various forms should be started at the age of maturity (18 years old) and done by well-trained multidisciplinary health-care providers. Both groups acknowledged the importance of peer support in pregnancy-related health care. And both groups agreed on the need for guidelines for planned pregnancy and management of blood glucose and diabetic complications during pregnancy. However, health-care providers reported that bodyweight management, fetal development monitoring, type 1 diabetes-specific screening tests, and postnatal lifestyle should also be emphasised. Health-care providers had a generally positive attitude to outcomes of pregnancy if glycaemic control was satisfactory, whereas patients tended to have a pessimistic perspective. Finally, women with type 1 diabetes expressed great unmet needs: thorough and timely communication with health-care providers, psychological consultation, and type 1 diabetes knowledge in non-diabetician health-care providers. Most health-care providers did not show awareness of these needs, although they were aware of insufficient pregnancy-related knowledge and expressed their intent for further training. Interpretation Women with type 1 diabetes had various unmet needs for pregnancy-related health care, but the health-care resources were scarce in Guangdong. Both patients and health-care providers had gaps in knowledge of the need for pregnancy-related health care, indicating that further education should be given to patients, and the role of professional and psychosocial support should be enhanced. These findings identify gaps between the needs of women with type 1 diabetes and current health care provision, and would be helpful to guide the establishment of a patient-centered pregnancy-related health care system in Guangdong. Funding National Health and Family Planning Commission Foundation for public welfare industry research project (201502011), World Diabetes Foundation (WDF14-921), and Sun Yat-Sen University clinical research 5010 program (2007030).

Background Sparse data on pregnancy outcomes for women with type 1 diabetes exist in Chinese women. We aimed to investigate maternal, perinatal, and fetal and neonatal outcomes in women with type 1 diabetes in China. Method We did a retrospective study in 11 hospitals in Beijing, Jinan, Nanjing, Shanghai, Chengdu, Changsha, Guangzhou. We compiled data on pregnancy outcomes of women with type 1 diabetes from anonymised medical records of maternal and infant birth between Jan 1, 2004, to Dec 31, 2014. We analysed perinatal maternal mortality, perinatal neonatal mortality, and perinatal birth defect rate. These outcomes in the general population were estimated from the annual report of national health statistic and the report of birth defects in China. We used χ 2 or Fisher's exact test for statistical analyses of categorical data. Ethics approval was granted by all the participating hospitals. Findings We included 289 women with type 1 diabetes with a singleton pregnancy, of whom 26 (9%) had a history of adverse pregnancy outcomes at the start of the study period. At start of pregnancy, mean age was 27·6 years (SD 4·2) and mean diabetes duration was 5·26 years (SD 5·49). Nine women were excluded because of elective terminations and 15 were excluded because no data on pregnancy outcomes were available; thus, 265 women were included in the analysis. In patients with HbA 1c records available, 41 (57%) of 72 achieved the preconception HbA 1c target (≤7·0%; ie, 53·00 mmol/mol), and 49 (38%) of 130 achieved the third trimester HbA 1c target (≤6·0 %; ie, 42 mmol/mol). Nine (3%) pregnancy losses were recorded in the first trimester, 20 (8%, including ten stillbirths) in the second trimester, and six (2%) in the third trimester. Main adverse maternal outcomes were procession of diabetic complications (30 [11%] women), pre-eclampsia or eclampsia (47 [18%]), and total pregnancy losses (35 [13%]). Of 230 livebirths, 44 (19%) preterm births, 12 (5%) cardiac congenital malformations, and 18 (8%) early neonatal deaths were recorded. Of 236 infants (230 livebirths and 6 stillbirths in the third trimester), main adverse neonatal outcomes were large for gestational age (68 [29%]) and small for gestational age (12 [5%]); 96 (41%) had to admitted to the neonatal department. Overall, perinatal maternal mortality was 423·73 (95% CI 397·18–451·12) per 100 000 person-years, perinatal neonatal mortality was 55·08% (54·14–56·04), and the incidence of birth defects was 847·45 (835·92–859·05) per 100 000 person-years. Birth defects were the leading cause of neonatal perinatal deaths (10 [29%] of 34). Compared with the general population in China, women with type 1 diabetes did not have increased perinatal maternal mortality (risk ratio 11·76, 95% CI 1·65–83·78; p=0·082), but their infants had significantly higher risks of perinatal mortality (risk ratio 7·58, 95% CI 4·33–13·26; p Interpretation Adverse pregnancy outcomes are more frequent in women with type 1 diabetes than in the general population. Management of type 1 diabetes in pregnant women needs to be improved. Funding Chinese National Health and Family Planning Commission Foundation for Public Welfare Industry Research Project (201502011), Sun Yat-Sen University Clinical Research 5010 Program (2007030), and World Diabetes Foundation (WDF14-921).

Nerve agents are highly toxic organophosphorus compounds (OPs) that are used as chemical warfare agents. Developing a catalytic bioscavenger to efficiently detoxify nerve agents in the bloodstream of affected individuals has been recognized as an attractive approach to prevent nerve agent toxicity. However, the search for nerve agent catalysts has been hindered by the lack of efficient direct assays for nerve agent hydrolysis. In addition, authentic nerve agents are restricted and access to use for experiments by the general research community is prohibited. Herein we report development of a method that combines use of novel nerve agent model compounds possessing a thiocholine leaving group that reacts with the fluorescent thio-detection probe, BES-Thio, to afford detection of sub-micromolar amounts of nerve agent model compounds hydrolysis products. The detection sensitivity of BES-Thio assay was approximately 10 times better than the Ellman assay. This developed method is useful as a direct, sensitive screening method for evaluating OP hydrolysis efficiency from catalytic cholinesterases. When the assay was assembled in the presence of oxime, OP-inhibited cholinesterases that were able to be reactivated by specific oxime showed oxime-assisted enzyme-mediated OP hydrolysis. Therefore, this method is also useful to screen oxime analogs to identify novel agents that can reactivate OP-inhibited cholinesterases or to screen various enzymes to identify pseudo-catalytic bioscavengers that can be readily reactivated by clinically approved oximes.

Patients with Alzheimer's disease (AD) suffer from brain amyloidosis related to defective clearance of amyloid-beta (Abeta) by the innate immune system. To improve the innate immune system of AD patients, we studied immune stimulation of macrophages by 1alpha,25(OH)2-vitamin D3(1,25D3) in combination with curcuminoids. AD patients' macrophages segregate into Type I (positively stimulated by curcuminoids regarding MGAT-III transcription) and Type II (not stimulated). In both Type I and Type II macrophages, 1,25D3 strongly stimulated Abeta phagocytosis and clearance while protecting against apoptosis. Certain synthetic curcuminoids in combination with 1,25D3 had additive effects on phagocytosis in Type I but not Type II macrophages. In addition, we investigated the mechanisms of 1,25D3 and curcuminoids in macrophages. The 1,25D3 genomic antagonist analog MK inhibited 1,25D3 but not curcuminoid effects, suggesting that 1,25D3 acts through the genomic pathway. In silico, 1,25D3 showed preferential binding to the genomic pocket of the vitamin D receptor, whereas bisdemethoxycurcumin showed preference for the non-genomic pocket. 1,25D3 is a promising hormone for AD immunoprophylaxis because in Type I macrophages combined treatment with 1,25D3 and curcuminoids has additive effects, and in Type II macrophages 1,25D3 treatment is effective alone. Human macrophages are a new paradigm for testing immune therapies for AD.