Facets of impulsivity and reward in relation to binge-eating disorder course of illness among children: findings from the Adolescent Brain Cognitive Development study.

BACKGROUND: The present study examined facets of impulsivity and reward sensitivity [as measured by the UPPS-P Impulsive Behavior Scale and Behavioral Activation and Behavioral Inhibition Scales (BIS/BAS)] as multivariable predictors of subsequent binge-eating disorder (BED) course of illness in middle childhood. METHODS: The current sample included children aged 9-10 years (N = 9,438) who took part in the baseline and 1-year follow-up assessments of the Adolescent Brain Cognitive Development (ABCD) study. BED course was operationalized as those who never developed BED or subthreshold BED (SBED) ('control'), were diagnosed with BED/SBED at year 1 but not baseline ('developers'), were diagnosed with BED/SBED at baseline but not year 1 ('remitters'), or were diagnosed with BED/SBED at both times ('maintainers'). RESULTS: Higher baseline BIS/BAS reward responsivity scores were related to the greater likelihood of belonging to the maintainer group relative to the control and remitter groups (ORs1.12-1.19). Regarding covariates, higher baseline body mass index percentile and internalizing symptoms were related to the greater likelihood of BED development, remittance, and maintenance compared to the control group (ORs = 1.04-1.14); no variables were uniquely related to BED development. Exploratory analyses showed that the likelihood of belonging to the maintainer group compared to the control group was greatest at higher levels of negative urgency in combination with high reward responsivity. CONCLUSIONS: Heightened reward responsivity may convey risk for poorer BED course in children, while emotional disorder symptomatology may act as a more general risk and maintenance factor for BED.

Day-level associations of physical activity and sedentary time in mother-child dyads across three years: a multi-wave longitudinal study using accelerometers.

Understanding associations between mothers' and children's physical activity and sedentary behavior on more fine-grained timescales can provide insights into real-time intervention opportunities. This study examined the extent to which mothers' and their children's device-measured moderate-to-vigorous physical activity (MVPA) and sedentary time (SDT) were associated at the day level during non-school time. Mother-child dyads (N = 193; baseline Mean ages = 40.69 ± 6.11 [mother] and 9.57 ± 0.89 [child] years) provided 3,135 paired days of accelerometry data from six bi-annual waves across three years. Controlling for covariates, multilevel models revealed that mothers' and their children's MVPA and SDT were positively associated at the day level during non-school time, both on weekdays and weekends. During weekdays, the day-level association for SDT was stronger for older than younger children, and the day-level association for MVPA was stronger for boys than girls. Designing family-based interventions targeting school-age children and their mothers during non-school time across the week may be useful for promoting active lifestyles.

How acute affect dynamics impact longitudinal changes in physical activity among children.

Research examined how acute affect dynamics, including stability and context-dependency, contribute to changes in children's physical activity levels as they transition from late-childhood to early-adolescence. Children (N = 151) (ages 8-12 years at baseline) participated in an ecological momentary assessment and accelerometry study with six semi-annual bursts (7 days each) across three years. A two-stage mixed-effects multiple location-scale model tested random intercept, variance, and slope estimates for positive affect as predictors of moderate-to-vigorous physical activity (MVPA). Multi-year declines in MVPA were greater for children who had greater subject-level variance in positive affect. Children who experienced more positive affect when alone did not experience steeper declines in physical activity. Interventions aiming for long-term modifications in children's physical activity may focus on buffering the effects of within-day fluctuations in affect or tailoring programs to fit the needs of "acute dynamic process phenotypes."

Dynamic associations between anxiety, stress, physical activity, and eating regulation over the course of a behavioral weight loss intervention.

Negative emotional experiences are associated with dysregulated eating behaviors that impede weight management. While weight loss interventions promote physical activity and self-regulation of eating, no studies have examined how physical activity may directly influence eating by attenuating associations between negative emotions and eating. OBJECTIVE: The current study examined how momentary negative emotions (stress and anxiety), moderate-to-vigorous intensity physical activity (MVPA), and their interactions predict eating dysregulation (i.e., intensity of eating temptations, inability to resist eating tempting foods, overeating), as well as how these associations change during a weight loss intervention. METHODS: Women with overweight/obesity (N = 55) completed 14-day ecological momentary assessment (EMA) protocols with objective measurement of physical activity (i.e., bout-related MVPA time) before and after a three-month internet-based weight loss program. RESULTS: Three-way interactions emerged predicting overeating and eating tempting foods. When women experienced higher than usual levels of momentary anxiety or stress at end-of-treatment, they were less likely to subsequently overeat or eat tempting foods when they had recently engaged in more MVPA (relative to their usual level). No significant associations were found for ratings of temptation intensity. CONCLUSIONS: Findings suggest MVPA may exert direct effects on eating regulation. Specifically, MVPA appears to increasingly buffer the effect of negative emotional states on dysregulated eating behavior over the course of a weight loss intervention. Future work is needed to develop ways of communicating to patients how activity can have both indirect and direct effects on body weight, and examine whether such knowledge improves outcomes.

Simulation of a Temperature-Compensated Voltage Sensor Based on Photonic Crystal Fiber Infiltrated with Liquid Crystal and Ethanol.

A simulated design for a temperature-compensated voltage sensor based on photonic crystal fiber (PCF) infiltrated with liquid crystal and ethanol is presented in this paper. The holes distributed across the transverse section of the PCF provide two channels for mode coupling between the liquid crystal or ethanol and the fiber core. The couplings are both calculated accurately and explored theoretically using the finite element method (FEM). The influence of voltage on the alignment of the liquid crystal molecules and confinement loss of the fiber mode are studied. Liquid crystal molecules rotate which changes its properties as the voltage changes. As the characteristics of the liquid crystal will be affected by temperature, therefore, we further fill using ethanol, which is merely sensitive to temperature, into one hole of the PCF to realize temperature compensation. The simulated results show that the sensitivity is up to 1.29977 nm/V with the temperature of 25 °C when the voltage ranges from 365 to 565 V. The standard deviation of the wavelength difference is less than 2 nm within the temperature adjustment from 25 to 50 °C for temperature compensation. The impacts of the construction parameters of the PCF on sensing performances of this voltage sensor are also analyzed in this paper.

Expression of Small Noncoding RNAs in Urinary Exosomes Classifies Prostate Cancer into Indolent and Aggressive Disease.

PURPOSE: This is the first report of the development and performance of a platform that interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes. The Sentinel™ PCa Test classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel CS Test stratifies patients with prostate cancer between those with low risk prostate cancer (Grade Group 1) from those with intermediate and high risk disease (Grade Group 2-5), and the miR Sentinel HG Test stratifies patients with prostate cancer between those with low and favorable intermediate risk prostate cancer (Grade Group 1 or 2) and those with high risk (Grade Group 3-5) disease. MATERIALS AND METHODS: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.0 microarrays. Using proprietary selection and classification algorithms, informative sncRNAs were selected to customize an interrogation OpenArray™ platform that forms the basis of the tests. The tests were validated using a case-control sample of 1,436 subjects. RESULTS: The performance of the miR Sentinel PCa Test demonstrated a sensitivity of 94% and specificity of 92%. The Sentinel CS Test demonstrated a sensitivity of 93% and specificity of 90% for prediction of the presence of Grade Group 2 or greater cancer, and the Sentinel HG Test demonstrated a sensitivity of 94% and specificity of 96% for the prediction of the presence of Grade Group 3 or greater cancer. CONCLUSIONS: The Sentinel PCa, CS and HG Tests demonstrated high levels of sensitivity and specificity, highlighting the utility of interrogation of urinary exosomal sncRNAs for noninvasively diagnosing and classifying prostate cancer with high precision.

Clinicopathological Characteristics and Survival Outcomes of Primary Hepatic Neuroendocrine Tumor: A Surveillance, Epidemiology, and End Results (SEER) Population-Based Study.

BACKGROUND Primary hepatic neuroendocrine tumor (PHNET) is a rare primary liver tumor that remains poorly understood. Here, we explored the clinicopathological characteristics and survival outcomes of PHNET patients. MATERIAL AND METHODS PHNET patients diagnosed between 1988 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in the cohort. Kaplan-Meier analysis was used to determine the survival outcomes. Multivariable Cox regression models were used to identify the risk factors for overall survival (OS) and disease-specific survival (DSS). RESULTS A total of 291 PHNET patients from the SEER database met the inclusion criteria for analysis. The majority of the patients were female (53.6%), white (77.7%), and married (49.5%). The 1-, 3-, and 5-year OS were 57.1%, 39.4%, and 30.2%, and the 1-, 3-, and 5-year DSS rates were 61.3%, 44.3%, and 36.7%, respectively. Multivariate Cox regression models showed that older age, unmarried status, poor differentiated grade, and no tumor-directed surgery were independent risk factors for poor OS and DSS. CONCLUSIONS Older age, unmarried status, poor differentiated grade, and no tumor-directed surgery were associated with poorer prognosis of PHNET. Surgical resection is an effective and reliable treatment method for patients with PHNET.

Gender differences in the acquisition of suturing skills with the da Vinci surgical system.

BACKGROUND: The percentage of female medical students has been significant elevating worldwide. The demographic shift is expected to influence the proportion of male versus female surgeons soon. The objective of this study was to evaluate the gender differences in the acquisition of robotic suturing skills. METHODS: We compared the robotic suturing performance between 39 male and 19 female medical students. We separated the training into two parts: phase I, involving virtual reality (VR) robotic simulation, and phase II, involving robotic dry-laboratory simulation training. Participants first conducted step-by-step exercises on the VR robotic simulator and then the robotic skin-suturing pad using the da Vinci robot. RESULTS: The metric analysis of the VR task "suture sponge" showed that female students required less time (difference: -170.7 seconds, 95% CI: -247.4 to -94.0) and had fewer errors (error difference: -50, 95% CI: -74.2 to -25.8) to complete the suture sponge exercise compared to male students. Moreover, female students completed more stitches than male students (differences in mean stitch achieved: .35; 95% CI: .06 to .65). However, there was no difference in the quality scores of stitches by gender (p = 0.85). CONCLUSION: Female medical students performed better in the VR task of suture spongy and achieved more stitches than male students with the da Vinci system despite no difference in robotic suture quality by gender. Because this is the first study comparing gender performance on a robotic platform, further studies are required to investigate if different training approaches will affect the performance by gender.

LINC01121 Inhibits Cell Apoptosis While Facilitating Proliferation, Migration, and Invasion Though Negative Regulation of the Camp/PKA Signaling Pathway via GLP1R.

BACKGROUND/AIMS: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. METHODS: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. RESULTS: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. CONCLUSION: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

Efficient directional coupling from multilayer-graphene-based long-range SPP waveguide to metal-based hybrid SPP waveguide in mid-infrared range.

Graphene-based and metal-based surface plasmon polariton (SPP) waveguides have attracted intense research interest because they can be used as basic components to propagate electromagnetic (EM) waves in future optical integrated systems. We propose a directional coupler, which can couple EM energy from a multilayer-graphene-based cylindrical long-range SPP waveguide to a metal-based cylindrical hybrid SPP waveguide in the mid-infrared range. This coupler exhibits relatively low coupling length, high coupling efficiency, low insertion loss, and high extinction ratio after adjustment of the wave vector mismatch of the two waveguides. Moreover, this coupler is tolerant to practical fabrication errors like misalignment of graphene layres, and can effectively work in the range of Fermi energy Ef > 0.6 eV when the mobility of graphene varies from 10000 to 800 cm2/Vs. Hence, the coupler offers potential applications in signal routing and information exchange between graphene-based and metal-based SPP waveguides in photonic integrated circuits.

The Black-White Disparity in Sexually Transmitted Diseases During Pregnancy: How Do Racial Segregation and Income Inequality Matter?

BACKGROUND: We investigate the roles of residential racial segregation and income inequality for the black-white disparity in acquiring sexually transmitted diseases (STD) during pregnancy in a multilevel framework. METHODS: The analytic sample consisted of non-Hispanic white (n = 79,271) and non-Hispanic black (n = 17,669) mothers from 2012 population birth data from Pennsylvania. We used the 2009 to 2013 American Community Survey for neighborhood characteristics of mothers; we used multilevel models. RESULTS: First, neighborhood-level factors are important for understanding this disparity because racial segregation and income inequality are significantly associated with acquiring STD during pregnancy, regardless of race. Second, racial segregation moderates the relationships between race/ethnicity and the acquisition of STD during pregnancy. White mothers are more vulnerable to neighborhood segregation than black mothers, and black mothers are less likely to acquire STD during pregnancy than white mothers if they reside with co-ethnics. Third, mothers residing in the most socioeconomically disadvantaged neighborhoods-as indicated by both absolute and relative measures of income inequality-have the highest odds of acquiring STD during pregnancy, regardless of race. CONCLUSIONS: Neighborhood-level segregation and income inequality are important for understanding the acquisition of STDs during pregnancy. Our findings have important implications for future research and for place-specific prevention and intervention to reduce the racial disparity in STD during pregnancy.

Efficacy and safety profile of drug-eluting beads transarterial chemoembolization by CalliSpheres® beads in Chinese hepatocellular carcinoma patients.

BACKGROUND: This study aimed to investigate the efficacy and safety of drug eluting beads transarterial chemoembolization (DEB-TACE) treatment by CalliSpheres® in Chinese patients with hepatocellular carcinoma (HCC) as well as the predicting factors for response. METHODS: 99 patients with HCC were consecutively enrolled in this study. All participants were treated by CalliSpheres® DEB-TACE. Clinical response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Common Terminology Criteria for Adverse Events (CTCAE) was used to assess the adverse events and liver dysfunction during and after the operation. RESULTS: Post treatment, 16 patients (16.2%) achieved CR and 59 (59.6%) achieved PR, the ORR was 75.8%. Subgroup analysis showed that patients with higher BCLC stage were of worse CR and ORR rates, and the CR as well as ORR between patients with cTACE history and patients without cTACE history were similar. Univariate logistic regression analysis displayed that number of nodules > 3, higher BCLC stage and previous cTACE might be correlated with worse ORR but with no statistical significance. As to liver function, CTCAE grades of laboratory indexes for liver function were increased at 1 week compared to baseline and recovered to the baseline grades at 1-3 months post operation. Besides, most of the common adverse events were light and moderate in our study. CONCLUSIONS: In conclusion, DEB-TACE by CalliSpheres® was efficient and well tolerated in Chinese HCC patients, and BCLC stage, number of nodules and cTACE history were possibly correlated with treatment response.

Preclinical Efficacy of Anti-RON Antibody-Drug Conjugate Zt/g4-MMAE for Targeted Therapy of Pancreatic Cancer Overexpressing RON Receptor Tyrosine Kinase.

Aberrant expression of the RON receptor tyrosine kinase, a cell surface protein, is a pathogenic feature in pancreatic cancer, which renders it a drug target for targeted therapy. Nevertheless, development of therapeutics targeting RON for pancreatic cancer therapy is hampered due to the lack of full addiction by pancreatic cancer cells to RON signaling for growth and survival. Here we describe a novel strategy using anti-RON antibody-directed drug delivery in the form of an antibody-drug conjugate for inhibition and/or eradication of pancreatic cancers. Monoclonal antibody Zt/g4 specific to the RON Sema domain was selected as the drug carrier based on its ability to induce robust RON internalization. Conjugation of Zt/g4 with monomethyl auristatin E, designated as Zt/g4-MMAE, was achieved through a protease-sensitive dipeptide linker to reach a drug to antibody ratio of 3.29:1. Zt/g4-MMAE was stable in human plasma with a dissociation rate less than 4% within a 10 day period. In vitro, Zt/g4-MMAE rapidly induced RON internalization, resulting in cell cycle arrest followed by massive cell death. The maximal effect was seen in pancreatic cancer cells with more than 10 000 receptor molecules per cell. Zt/g4-MMAE also synergized in vitro with chemotherapeutics including gemcitabine, 5-fluorouracil, and oxaliplatin to further reduce PDAC cell viability. In vivo, Zt/g4-MMAE exerts a long-lasting activity, which not only inhibited but also eradicated pancreatic xenograft tumors. These finding indicate that Zt/g4-directed drug delivery is highly effective for eradicating pancreatic tumors. Thus, Zt/g4-MMAE is a novel biotherapeutic with potential for therapy of RON-expressing pancreatic malignancies.

Unfolded-protein response-associated stabilization of p27(Cdkn1b) interferes with lens fiber cell denucleation, leading to cataract.

Failure of lens fiber cell denucleation (LFCD) is associated with congenital cataracts, but the pathobiology awaits elucidation. Recent work has suggested that mechanisms that direct the unidirectional process of LFCD are analogous to the cyclic processes associated with mitosis. We found that lens-specific mutations that elicit an unfolded-protein response (UPR) in vivo accumulate p27(Cdkn1b), show cyclin-dependent kinase (Cdk)-1 inhibition, retain their LFC nuclei, and are cataractous. Although a UPR was not detected in lenses expressing K6W-Ub, they also accumulated p27 and showed failed LFCD. Induction of a UPR in human lens epithelial cells (HLECs) also induced accumulation of p27 associated with decreased levels of S-phase kinase-associated protein (Skp)-2, a ubiquitin ligase that regulates mitosis. These cells also showed decreased lamin A/C phosphorylation and metaphase arrest. The suppression of lamin A/C phosphorylation and metaphase transition induced by the UPR was rescued by knockdown of p27. Taken together, these data indicate that accumulation of p27, whether related to the UPR or not, prevents the phosphorylation of lamin A/C and LFCD in maturing LFCs in vivo, as well as in dividing HLECs. The former leads to cataract and the latter to metaphase arrest. These results suggest that accumulation of p27 is a common mechanism underlying retention of LFC nuclei.

The expression analysis of Bmpr1a and Bmp2 during hindgut development in rat embryos with anorectal malformations.

The aim of this study was to determine Bmpr1a and Bmp2 expression patterns during anorectal development in normal and anorectal malformation (ARM) embryos with a view to establishing the possible role of Bmpr1a and Bmp2 in ARM pathogenesis. ARM was induced with ethylenethiourea on the 10th gestational day (GD10) in rat embryos. The embryos were harvested by Cesarean deliveries. The expression of Bmpr1a and Bmp2 was evaluated in normal rat embryos (n=213) and ARM embryos (n=236) from GD14 to GD16. Immunohistochemical staining revealed, in normal embryos, that Bmpr1a and Bmp2 was mainly expressed on the epithelium of the urorectal septum (URS) and the cloacal membrane (CM) on GD14 and GD15. When the rectum separated from the urogenital sinus (UGS) on GD16, Bmpr1a- and Bmp2-immunolabeled cells were observed on the anorectal epithelium. In ARM embryos, the epithelium of the hindgut and URS demonstrated faint immunostaining for Bmpr1a and Bmp2. Analyses by Western blot and Real-time PCR revealed that Bmpr1a and Bmp2 protein and mRNA expression were significantly decreased in the ARM hindgut compared with normal hindgut on GD14 and GD15 (P<0.05). In ARM embryos, an imbalance in the spatiotemporal expression of Bmpr1a and Bmp2 was noted during anorectal morphogenesis from GD14 to GD16. Therefore, downregulation of Bmpr1a and Bmp2 at the time of cloacal separation into the primitive rectum and UGS might be related to the development of ARM.

Application of LA-ICP-AES to Distinguish the Different Turquoise Mines.

Currently, the technological development of non-destructive analysis and micro-damage analysis of turquoise is fast. LA-ICP-AES, an almost non-destructive analysis, has multiple advantages. This paper attempts to use this analysis method to examine sample turquoise from five places of origin on Mount East Qinling, including ancient turquoise ore in Laziya, in order to attain its major element and microelement data. Then the paper uses PCA to analyze and study its chemical elements in a comparative way. Three main elements are gained through analysis, and their cumulative variance contribution rate has reached 84.96%. The former two main elements' variance contribution rate is 72.289%. Therefore, the corresponding elements, including V2O5, NiO, B2O3, SrO, BaO, CaO, ZrO, MnO2, are the featured chemical elements of turquoise from different places of origin. Through comparative analysis and research on corresponding chemical elements, turquoise samples produced by different ores vary in terms of the content of some chemical element and chemical components. Two analysis methods combined together will basically realize the appreciation of turquoise in various places of origin. In addition, the research indicates that some chemical contents have positive or negative correlations. Such correlations can be regarded as features of producing area, and can also provide clues as to the cause of formation of turquoise ore. This study preliminarily indicates that LA-ICP-AES combined with PCA and comparative analysis of chemical composition and content has the function of distinguishing turquoise produced in different places of origin to a certain extent.

Risk factors of metabolic syndrome after liver transplantation.

BACKGROUND: Liver transplantation is a treatment of choice for both acute and chronic liver failure. Accompanied with the increase of long-term survival rates of recipients, metabolic syndrome and its individual components, including obesity, hyperglycemia, hypertension and hyperlipidemia, have become more frequent post liver transplantation. Here we reviewed the literature concerning the risk factors for the development of metabolic complications in liver recipients. DATA SOURCES: PubMed was searched for English-language articles published from January 2000 to June 2015. The search criteria focused on risk factors for metabolic syndrome after liver transplantation. RESULT: The risk factors of metabolic syndrome in liver recipients include older age, obesity, pre-transplantation diabetes mellitus, hepatitis C virus infection, certain genetic polymorphisms and the use of immunosuppressive drugs. CONCLUSION: Active intervention of the risk factors will reduce the occurrence rate of metabolic syndrome after liver transplantation and improve the recipients' quality of life.