Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study

OBJECTIVETo investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure.RESEARCH DESIGN AND METHODSA comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities.RESULTSThe rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]).CONCLUSIONSThe substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.     

Enhancing Social Initiations Using Naturalistic Behavioral Intervention: Outcomes from a Randomized Controlled Trial for Children with Autism

Deficits in social skills are common in children with Autism Spectrum Disorder (ASD), and there is an urgent need for effective social skills interventions, especially for improving interactions with typically developing peers. This study examined the effects of a naturalistic behavioral social skills intervention in improving social initiations to peers through a randomized controlled trial. Analyses of multimethod, multi-informant measures indicated that children in the active group (SIMI) demonstrated greater improvement in the types of initiations which were systematically prompted and reinforced during treatment (i.e., behavior regulation). Generalization to joint attention and social interaction initiation types, as well as collateral gains in broader social functioning on clinician- and parent-rated standardized measures were also observed.

     

Texture Analysis of Three-Dimensional MRI Images May Differentiate Borderline and Malignant Epithelial Ovarian Tumors

ObjectiveTo explore the value of magnetic resonance imaging (MRI)-based whole tumor texture analysis in differentiating borderline epithelial ovarian tumors (BEOTs) from FIGO stage I/II malignant epithelial ovarian tumors (MEOTs).Materials and MethodsA total of 88 patients with histopathologically confirmed ovarian epithelial tumors after surgical resection, including 30 BEOT and 58 MEOT patients, were divided into a training group (n = 62) and a test group (n = 26). The clinical and conventional MRI features were retrospectively reviewed. The texture features of tumors, based on T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging, were extracted using MaZda software and the three top weighted texture features were selected by using the Random Forest algorithm. A non-texture logistic regression model in the training group was built to include those clinical and conventional MRI variables with p value < 0.10. Subsequently, a combined model integrating non-texture information and texture features was built for the training group. The model, evaluated using patients in the training group, was then applied to patients in the test group. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the models.ResultsThe combined model showed superior performance in categorizing BEOTs and MEOTs (sensitivity, 92.5%; specificity, 86.4%; accuracy, 90.3%; area under the ROC curve [AUC], 0.962) than the non-texture model (sensitivity, 78.3%; specificity, 84.6%; accuracy, 82.3%; AUC, 0.818). The AUCs were statistically different (p value = 0.038). In the test group, the AUCs, sensitivity, specificity, and accuracy were 0.840, 73.3%, 90.1%, and 80.8% when the non-texture model was used and 0.896, 75.0%, 94.0%, and 88.5% when the combined model was used.ConclusionMRI-based texture features combined with clinical and conventional MRI features may assist in differentitating between BEOT and FIGO stage I/II MEOT patients.     

Molecular evidence for a clonal relationship between synchronous uterine endometrioid carcinoma and ovarian clear cell carcinoma: a new example of “precursor escape”?

Journal of Molecular Medicine - Synchronous endometrial and ovarian carcinomas (SEOCs) that share the same endometrioid histology are generally considered as the result of metastatic spread from...     

Altered gray matter structural covariance networks at both acute and chronic stages of mild traumatic brain injury

Cognitive and emotional impairments observed in mild traumatic brain injury (mTBI) patients may reflect variances of brain connectivity within specific networks. Although previous studies found altered functional connectivity (FC) in mTBI patients, the alterations of brain structural properties remain unclear. In the present study, we analyzed structural covariance (SC) for the acute stages of mTBI (amTBI) patients, the chronic stages of mTBI (cmTBI) patients, and healthy controls. We first extracted the mean gray matter volume (GMV) of seed regions that are located in the default-mode network (DMN), executive control network (ECN), salience network (SN), sensorimotor network (SMN), and the visual network (VN). Then we determined and compared the SC for each seed region among the amTBI, the cmTBI and the healthy controls. Compared with healthy controls, the amTBI patients showed lower SC for the ECN, and the cmTBI patients showed higher SC for the both DMN and SN but lower SC for the SMN. The results revealed disrupted ECN in the amTBI patients and disrupted DMN, SN and SMN in the cmTBI patients. These alterations suggest that early disruptions in SC between bilateral insula and the bilateral prefrontal cortices may appear in amTBI and persist into cmTBI, which might be potentially related to the cognitive and emotional impairments.

     

A simple fluorescence assay for trypsin through a protamine-induced carbon quantum dot-quenching aggregation platform

The development of a simple detection strategy for trypsin (Try) is urgent, and is ascribed to the diagnostic value of Try in several diseases. Herein, a facile but effective fluorescence strategy for Try was developed based on the protamine (Pro)-induced aggregation of carbon quantum dots (CQDs). The fluorescence of negatively charged CQDs was quenched with Pro due to the assembly of CQDs and Pro (CQDs/Pro) through electrostatic interaction. However, the highly positively charged Pro, which is rich in basic arginine residues, was preferred to be hydrolyzed by Try. Try can induce the deaggregation of CQDs/Pro, thereby enabling the release of CQDs to restore the fluorescence intensity. Thus, the use of CQDs/Pro as a testing platform will be employed as a “turn-on” method for Try. In addition, the fluorescence-resuming response was proportional to Try, ranging from 25 ng mL⁻¹ to 500 ng mL⁻¹ with a limit of detection (LOD) of 8.08 ng mL⁻¹. This “turn-on” fluorescence assay for Try was label-free, convenient, and relatively free of interference from coexisting substances. Actual applications for Try monitoring and trypsin inhibitor screening also illustrated the considerable prospect of CQDs in the clinical field, combined with the superiority of the simple mixing operation.

In this work, a simple melting method was developed for carbon quantum dot fabrication to integrate with protamine as an effective signal-on fluorescence strategy for trypsin detection.

With increasing attention being paid to human health for disease diagnosis and treatment, increasing efforts have been spent on the development of new analytical methods toward biological macromolecule detection.^1,2 Trypsin (Try) is one of the most vital digestive proteases produced in pancreatic acinar cells, and can catalyze the hydrolysis of peptides mainly found at the C-terminus of lysine and arginine residues.^3–5 Abnormal Try activity will be reflected in pancreatic function and the corresponding pathological changes of the human body. In general, Try is a biomarker for several diseases, such as acute pancreatitis, cystic fibrosis, and pancreatic cancer.^5–7 Therefore, accurate monitoring for Try levels through simple and economical assays has attracted increasing interest in disease diagnosis and treatment.At present, considerable efforts have been devoted to developing efficient and reliable methods for Try detection based on various strategies, including colorimetry,⁸ electrochemistry,⁹ and fluorescence methods.¹⁰ Fluorescent approaches have been widely used due to their characteristics of simplicity, rapidity, sensitivity, and realizing real-time detection.^11,12 Fluorescent methods for Try have mainly been developed based on the hydrolytic effect of Try using peptide chains or specific proteins as substrates,^7,10,13,14 and using fluorescent dots, like CdTe QDs.¹⁴ Although current fluorescent methods are accurate and reliable, a simple and easy sensing system that detects Try with a controllable response integration modulated by Try through a biocompatible probe is still lacking. Given its special structural properties, protamine (Pro) is a highly cationic peptide under physiological conditions that possesses unique physiological function and substrates for enzymatic catalysis.⁸ The arginine-rich structure of protamine can also be catalyzed by Try as an ideal substrate for Try monitoring.^8,15,16 Hence, the interaction system containing Pro and a fluorescence probe, such as AIEgen, can be applied for the analytical assembly of Try.¹⁷ With regard to the relatively complicated preparation of AIE, other fluorescent probes for Try detection are desirable and urgently needed.Among the current fluorescent nanomaterials, fluorescent carbon quantum dots (CQDs) have been used to construct biosensors due to their safety, unique optical properties, and ease of modification.^18–20 Changing the structure or the surface properties of CQDs can result in a difference in the interaction and function between CQDs and external substances.^21,22 Thus, various fluorescent sensors based on CQDs have been established to detect specific targets varying from ions, nucleic acids, and drugs.^22–25 Positively and negatively charged carbon dots with controlled N-doping play opposite adsorption interaction with ssDNA in different applications.^21–23 Hence, a series of different application systems can be proposed to establish by utilizing the different surface properties of CQDs.Herein, negatively charged CQDs, fabricated from a simple melting operation, were applied as the sensing probe for Try detection without any complex surface functionalization or conjugation and compared with other reported quantum dots,²⁶ as shown in Scheme 1. Using Pro as the selective enzymatic substrate for Try, the integration of the prepared CQDs and Pro induce them to assemble and form an aggregation-caused quenching system of CQDs and Pro (CQDs/Pro) via electrostatic interaction. Under the strong and specific hydrolysis of Try to Pro, Pro loses its function with CQDs, and then the CQDs/Pro disaggregates to recover the fluorescence intensity. This facile system using Pro as the medium for inducing CQD aggregation provided novel insights into the design of some quantum dots with the appropriate surface property for the fabrication of simple, selective, and effective fluorescence assays for bioanalysis without a complicated surface functionalization.Open in a separate windowScheme 1The fabrication of CQDs and its electrostatic interaction with protamine as a simple quenching platform for trypsin detection.     

FGF23 Is Endogenously Phosphorylated in Bone Cells

Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi‐site O‐glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S‐X‐D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG‐SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14‐kDa carboxy‐terminal—but not the 17‐kDa N‐terminal—fragment. Sequential serine‐to‐alanine site‐directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy‐terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography‐coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23^R179Q, confirming labeling results. A phosphopeptide‐specific antibody was raised against phospho‐Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine‐phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone. © 2014 American Society for Bone and Mineral Research.