Maternal attachment influences mother–infant styles of regulation and play with objects at nine months

We examined the association between the quality of maternal representations of attachment evaluated by the Adult Attachment Interview (AAI) and mother styles of regulating attention and emotion during free play with objects in 41 mother dyads when infants were nine months old. The secure mother dyads showed a greater duration of engagement matches, with more positive matches, and a greater capacity to move from non-matched to matched states. Secure mother dyads demonstrated greater involvement in play with objects than insecure mother dyads. Insecure mother dyads showed a greater duration of mismatches and spent more time in negative matches. Correlations between maternal AAI scores and the variables studied also showed that the maternal Passivity and Unresolved scales were associated with less adequate dyadic attention and emotion regulation, while the maternal Coherence scale was associated with more adequate dyadic attention and emotion regulation.     

DRD4 7-repeat polymorphism moderates the association between maternal unresolved loss or trauma and infant disorganization

Abstract

Previous studies have related attachment disorganization in children to either dopamine D4 receptor polymorphisms or maternal unresolved loss or trauma and frightening or anomalous parenting. In this study it was examined whether the interaction between genetic (DRD4 7-repeat and -521 C/T) and environmental risk factors (maternal unresolved loss/trauma and maternal frightening behavior) was associated with infant disorganization. A moderating role of the DRD4 gene was found. Maternal unresolved loss or trauma was associated with infant disorganization, but only in the presence of the DRD4 7-repeat polymorphism. The increase in risk for disorganization in children with the 7-repeat allele exposed to maternal unresolved loss/trauma compared to children without these combined risks was 18.8 fold. Similar moderating effects were not found for maternal frightening behavior. Our findings indicate that children are differentially susceptible to unresolved loss or trauma dependent on the presence of the 7-repeat DRD4 allele.     

Improving knowledge of patient skills thanks to automatic analysis of online discussions

Objective

Automatically analyze the online discussions related to diabetes and extract information on patient skills for managing this disease.

Methods

Two collections of about 7000 and 23,000 messages from online discussion fora and 174 skills from an available taxonomy are processed with Natural Language Processing methods and semantically enriched. Skills are projected on the messages to detect those skills which are mentioned by patients. Quantitative and qualitative evaluation is performed.

Results

The method recognizes almost all the aimed skills in fora. The quality of the skills’ recognition varies with the method's parameters. Most of the selected messages are relevant to at least one of the associated skills. Manual analysis shows a substantial number of messages is dedicated to daily self-care and psychosocial skills.

Conclusion

Study of real exchanges between patients leads to a better understanding of their skills in daily self-management of diabetes.

Practice implications

Our experiments can be useful for a better understanding and better knowledge of self-management of diseases by patients. They can also refine existing patient education programs.     

BOOSTING T CELL COSTIMULATION IN CANCER: THE POSSIBILITIES SEEM ENDLESS

Effective immune strategies for eradication of human malignancies will require a thorough understanding of the interactions of cancer with the immune system. It will be crucial to understand how to optimize and sustain a T cell immune response. Recently, our understanding of the molecular interaction that occurs between an APC and a T cell during cognate interaction has increased dramatically. In this review, various costimulatory and inhibitory molecules of the B7 and TNF families will be discussed. The emphasis will be on how these costimulatory molecules impact T cell activation and on how they can be potentially used for the treatment of cancer. costimulation cancer T cell activation     

Robust infrarenal aortic aneurysm lumen centerline detection for rupture status classification

The objective of this work is to develop a robust method for human abdominal aortic aneurysm (AAA) centerline detection that can contribute to the accurate computation of features for the prediction of AAA rupture risk. A semiautomatic algorithm is proposed for detecting the lumen centerline in contrast-enhanced abdominal computed tomography images based on online adaboost classifiers, which does not require prior image segmentation. The algorithm was developed and applied to thirty ruptured and thirty unruptured AAA image data sets and the tortuosities of the detected centerline were measured to assess the correlation between AAA tortuosity and the binary ruptured and unruptured labels. The lumen of each data set was segmented manually by a trained radiologist and the resulting centerlines of each data set were defined as the gold standard to evaluate the accuracy of the algorithm and to compare it against two widely used segmentation techniques. The average mean relative accuracy of the offline adaboost classifier is 91.9% with a standard deviation of 1.6%; for the online adaboost classifier it is 93.6% with a standard deviation of 1.9% (p < 0.05). The online adaboost classifier outperforms the offline adaboost classifier while their computational costs are similar. Aneurysm tortuosity computed from an accurately derived lumen centerline using online adaboost is statistically higher for ruptured aneurysms compared to unruptured aneurysms, indicating that tortuosity can be used to assess rupture risk in the vascular clinic.     

Peptidoglycan recognition proteins in Drosophila immunity

Innate immunity is the front line of self-defense against infectious non-self in vertebrates and invertebrates. The innate immune system is mediated by germ-line encoding pattern recognition molecules (pathogen sensors) that recognize conserved molecular patterns present in the pathogens but absent in the host. Peptidoglycans (PGN) are essential cell wall components of almost all bacteria, except mycoplasma lacking a cell wall, which provides the host immune system an advantage for detecting invading bacteria. Several families of pattern recognition molecules that detect PGN and PGN-derived compounds have been indentified, and the role of PGRP family members in host defense is relatively well-characterized in Drosophila. This review focuses on the role of PGRP family members in the recognition of invading bacteria and the activation and modulation of immune responses in Drosophila.     

Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis,molecular docking and molecular dynamics simulation

In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC₅₀=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC₅₀=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (ΔE_ele+ΔG_GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.KEY WORDS: Genistein derivatives, Acetylcholinesterase (AChE), Kinetics analysis, Molecular docking, Molecular dynamics simulation, MM/GBSAAbbreviations: ACh, acetylcholine; AChEIs, acetylcholinesterase inhibitors; AChE, acetylcholinesterase; AD, Alzheimer׳s disease; BuChE, butyrylcholinesterase; BuSCh, S-butyrylthiocholine chloride; CAS, catalytic active site; DTNB, 5,5′-dithiobis-(2-nitrobenzoic acid); GAFF, generalized AMBER force field; G1, 3-(4-methoxyphenyl)-7-(2-(piperidin-1-yl)ethoxy)-4H-chromen-4-one; G2, (S)-3-(4-methoxyphenyl)-7-(2-(2-methylpiperidin-1-yl)ethoxy)-4H-chromen-4-one; iso-OMPA, tetraisopropyl pyrophosphoramide; MD, molecular dynamics; MM/GBSA, molecular mechanics/generalized born surface area; PAS, peripheral anionic site; PDB, protein data bank; PME, particle mesh Ewald; RMSD, root-mean-square deviation; S-ACh, acetylthiocholine iodide; ΔE_ele, electrostatic energy contribution; ΔE_MM, gas-phase interaction energy between receptor and ligand; ΔE_vdw, van der Waals energy contribution; SASA, solvent accessible surface area; ΔG_exp, experimental binding free energy; ΔG_GB, polar desolvation energy term; ΔG_pred, total binding free energy; ΔG_SA, nonpolar desolvation energy term; ΔS, conformational entropy contribution     

Fundamental aspects of solid dispersion technology for poorly soluble drugs

The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug–polymer two-component system, the drug–polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.KEY WORDS: Solid dispersion, Poorly soluble drug, Phase separation, Drug–polymer interaction     

A Re‐examination of the MDM2/p53 Interaction Leads to Revised Design Criteria for Novel Inhibitors

The general model of epitope‐type MDM2 inhibitor was developed based on the structural information on the complexes between MDM2 and various low molecular weight ligands found in the PDB database. Application of this model to our in‐house library has led us to a new scaffold capable of interrupting protein–protein interactions. A synthetic library based on this and related scaffolds resulted in new classes of compounds that possess biochemical and cellular activity and good pharmacokinetic properties. We assume that such general approach to PPI inhibitors design may be useful for the development of inhibitors of various PPI types, including Bcl/XL.