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Data collected longitudinally as part of usual health care is becoming increasingly available for research, and is often available across several centres. Because the frequency of follow-up is typically determined by the patient’s health, the timing of measurements may be related to the outcome of interest. Failure to account for the informative nature of the observation process can result in biased inferences. While methods for accounting for the association between observation frequency and outcome are available, they do not currently account for clustering within centres. We formulate a semi-parametric joint model to include random effects for centres as well as subjects. We also show how inverse-intensity weighted GEEs can be adapted to account for clustering, comparing stratification, frailty models, and covariate adjustment to account for clustering in the observation process. The finite-sample performance of the proposed methods is evaluated through simulation and the methods illustrated using a study of the relationship between outdoor play and air quality in children aged 2-9 living in the Greater Toronto Area.Vip3Aa is an insecticidal protein that can effectively control certain lepidopteran pests and has been used widely in biological control. However, the mechanism of action of Vip3Aa is unclear. In the present study, we showed that Vip3Aa could cause autophagy in Sf9 cells, which was confirmed by the increased numbers of GFP-Atg8 puncta, the appearance of autophagic vacuoles, and an elevated Atg8-II protein level. Moreover, we found that the AMPK-mTOR-ULK1 pathway is involved in Vip3Aa-induced autophagy, which might be associated with the destruction of ATP homeostasis in Vip3Aa-treated cells. Both the elevated p62 level and the increased numbers of GFP-RFP-Atg8 yellow fluorescent spots demonstrated that autophagy in Sf9 cells was inhibited at 24 h after Vip3Aa treatment. With the prolongation of Vip3Aa treatment time, this inhibition became more serious and led to autophagosome accumulation. Genetic knockdown of ATG5 or the use of the autophagy inhibitor 3-MA further increased the sensitivity of Sf9 cells to Vip3Aa. Overexpression of ATG5 reduced the cell mortality of Vip3Aa-treated cells. In summary, the results revealed that autophagy induced by Vip3Aa has a pro-survival role, which might be related to the development of insect resistance.Insulin resistance (IR) is a complex pathological condition resulting from the dysregulation of cellular response to insulin hormone in insulin-dependent cells and is recognized as a pathogenic hallmark and strong risk factor for metabolic syndrome. The present study aims to elucidate the molecular mechanism of the pathogenesis of IR. Here, we used human umbilical vein endothelial cells (HUVECs) to establish the IR cell model induced by 1 × 10-6 mmol/L insulin. After 48 h, reactive oxygen species (ROS) and glucose consumption were measured by DCFH-DA and GOD-POD methods, respectively. The results of Microarray analysis demonstrated that there were 10 differentially expressed miRNAs (DEMs) selected based on Fold change (FC) and P value in the IR cell model compared with HUVECs. The enriched gene ontology (GO) terms analysis showed that the target genes of these 10 DEMs were significantly enriched in biological process, cellular component and molecular function, and the significantly enriched Kyoto Encyclopedia of Genes or Genomes (KEGG) pathways mainly include AMPK signaling pathway and PI3K signaling pathway. Amongst all, the expression level of miR-3138 was highest in the IR cell model evaluated by qRT-PCR. Through Targetscan, KSR2 mRNA was predicted as a target of miR-3138. And mRNA and protein expression levels of miR-3138, KSR2, GLUT4, AMPK, PI3K, Akt were examined using qRT-PCR and Western blotting, respectively. The interaction between miR-3138 and KSR2 was evaluated by dual-luciferase reporter assay. Our results showed that miR-3138 significantly deteriorated the IR of HUVECs via KSR2/AMPK/GLUT4 signaling pathway.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare phenomenon that leads to concomitant thrombosis and hemorrhage in children with SLE. LAHPS in pediatric SLE (pSLE) has a protracted course requiring long-term immunosuppressive therapy. Due to the rarity of this syndrome and paucity of reported cases, there is lack of standardized management. selleck chemicals We herewith report 5 children with pSLE with LAHPS.

We retrospectively reviewed clinical features, laboratory features, treatment and outcome for 5 children with lupus anticoagulant hypoprothrombinemia syndrome with SLE and a review of literature of similar cases published.

Mean age of presentation was 10.2 ± 2.38 years (mean ± SD) and female to male ratio was 41. All children presented with mild to severe bleeding manifestations like gum bleed, epistaxis, hematuria, menorrhagia and subarachnoid bleed. Coagulation profile revealed prolonged PT and aPTT, with low prothrombin levels and positive Lupus anticoagulant in all children. Mixing studies were characteristic in these children. On comparing laboratory parameters majority had low C3, C4 levels, ANA and anti-DsDNA antibody positivity and three children had anticardiolipin positivity. One child had lupus nephritis along with LAHPS at presentation. All responded well to steroids and supportive measures.

High index of suspicion is needed when child with lupus presents with bleeding manifestations for early diagnosis and treatment.

High index of suspicion is needed when child with lupus presents with bleeding manifestations for early diagnosis and treatment.The treatment homicide co-victims receive from the criminal justice system often leaves them aggrieved and feeling alienated. A neglected but important area of investigation is the courtroom workgroup’s handling of murder cases. This exploratory study examines the nature and extent to which varying secondary victimization experiences are common among co-victims as the murder cases are processed through the court system. The sample consists of 27 co-victims connected to 24 separate cases where the murders occurred in a major metropolitan area in the southeastern United States. Drawing upon focus group data, Nvivo 10 was employed to identify themes that illustrate common secondary victimization experiences among co-victims along with positive and mixed reactions to court processes and personnel. The findings indicate that court requirements to provide notifications are infrequently met and attorney’s practice to supply information about case progress and counseling to family members regarding plea-bargaining and sentencing decisions are greatly restrictive.