Adapting the multilevel model for estimation of the reliable change index (RCI) with multiple timepoints and multiple sources of error

ObjectiveOne of the primary tools in the assessment of individual‐level patient outcomes is Jacobson and Truax, (1991’s) Reliable Change Index (RCI). Recent efforts to optimize the RCI have revolved around three issues: (a) extending the RCI beyond two timepoints, (b) estimating the RCI using scale scores from item response theory or factor analysis and (c) estimation of person‐ and time‐specific standard errors of measurement.MethodWe present an adaptation of a two‐stage procedure, a measurement error‐corrected multilevel model, as a tool for RCI estimation (with accompanying Statistical Analysis System syntax). Using DASS‐21 data from a community‐based mental health center (N = 379), we illustrate the potential for the model as unifying framework for simultaneously addressing all three limitations in modeling individual‐level RCI estimates.ResultsCompared to the optimal‐fitting RCI model (moderated nonlinear factor analysis scoring with measurement error correction), an RCI model that uses DASS‐21 total scores produced errors in RCI inferences in 50.8% of patients; this was largely driven by overestimation of the proportion of patients with statistically significant improvement.ConclusionEstimation of the RCI can now be enhanced by the use of latent variables, person‐ and time‐specific measurement errors, and multiple timepoints.     

Hepatitis B Virus-Associated Hepatocellular Carcinoma

Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.     

Identification of RAD51–BRCA2 Inhibitors Using N-Acylhydrazone-Based Dynamic Combinatorial Chemistry

RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further ¹⁹F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors.     

Effects of quercetin on the gastrointestinal tract in rats and mice

Intraperitoneal administration of quercetin (6.25–50 mg/kg) significantly (p<0.5-0.01) reduced intestinal transit in mice and this effect was antagonized by yohimbine and phentolamine but not by atropine or naloxone. Quercetin (12.5–50 mg/kg) reduced also (p<0.05-0.01) intraluminal accumulation of fluid and diarrhoea induced by castor oil and these effects were antagonized by yohimbine. Finally quercetin (12.5–50 mg/kg) reduced the area of gastric ulcer but not the number. It is suggested that α2-adrenergic receptors mediate the effect of quercetin on intestinal motility and secretion.     

Intrapartum translabial ultrasound with pushing used to predict the difficulty in vacuum-assisted delivery of fetuses in non-occiput posterior position

Objective: Our aim is to evaluate the capacity of intrapartum translabial ultrasound (ITU) with pushing in the prediction of difficulty of fetal extraction in vacuum assisted deliveries. Prospective, observational study performed (2/2015–8/2015) on 75 nulliparous women, ≥37 weeks with singleton pregnancies at full dilatation who had ITU-with-pushing performed, previous to vacuum-placement for fetal extraction. Working on the translabial sagittal-plane, we assessed: Angle-Progression (AoP), Progression-Distance (PD) and Head-Direction (HD); in the axial plane we evaluated: Midline-Angle (MLA) and Head-Perineum-Distance (HPD). Vacuum extractions were classified as easy-difficulty (ED) (≤3 vacuum-pulls), difficult-unsuccessful (DD) (>3 vacuum-pulls). We did not assess occipito-posterior-presentations.

Results: Seventy nulliparous were studied (44-ED,26-DD). We observed no differences in obstetric, neonatal or intrapartum characteristics between the two study groups, with the following exceptions: newborn weight (3272?±?438?g versus 3540?±?372?g; p?=?0.011) and number of vacuum-pulls (1.4-ED-vs-4.4-DD; p?<?0.0005). AoP-pushing was 143.9°?±?14.6° in ED and 115.1°±?12.9° in DD (p?<?0.0005); Head-Up was 79.5% versus 38.4% (p?<?0.0005); PD-Pushing was 42.7?±?11.3?mm versus 30.4?±?9.8?mm (p?<?0.0005); MLA-Pushing was 27.6°±?26.6° versus 57.5°±26.5°(p=0.025); HPD-Pushing was 40.8?±?10.0?mm versus 47.4?±?10.9?mm (p?=?0.039).

Conclusion: We identified that the presence of an AoP-Pushing?>?128° predicts an Easy-Vacuum-Delivery (≤3 Vacuum-Pulls) in >85% of cases (Sen 80%–FPR 9.3%).