Parenting children with neurodevelopmental disorders and/or behaviour problems

Background Parenting behaviours influence child well‐being and development. However, much of the research on parenting behaviours and their correlates has focused on caregivers of healthy, typically developing children. Relatively less is known about the parenting behaviours of caregivers of children with chronic health conditions. Objective To examine and compare three parenting behaviours (positive interactions, consistency and ineffective parenting) among caregivers of children with neurodevelopmental disorders and/or externalizing behaviour problems, before and after accounting for child and family socio‐demographic characteristics. Methods Participants (n= 14 226) were drawn from the National Longitudinal Survey of Children and Youth, a long‐term study of Canadian children that follows their development and well‐being from birth to early adulthood. Children (and their caregivers) were divided into four groups according to the presence of a neurodevelopmental disorder (NDD; n= 815), the presence of an externalizing behaviour problem (EBP; n= 1322), the presence of both conditions (BOTH; n= 452) or neither of these conditions (NEITHER; n= 11 376). Results Caregivers of children in the NEITHER group reported significantly higher positive interaction scores and lower ineffective parenting behaviours than caregivers of children in any of the other three groups. Caregivers of children in the EBP and BOTH groups reported similar levels of consistency, but significantly lower levels than caregivers of NDD or NEITHER children. These associations largely remained after accounting for child and family socio‐demographic characteristics, with two exceptions: caregivers' reports of positive interactions were no longer significantly associated with child's NDD and BOTH conditions. Conclusions Parenting children with multiple health conditions can be associated with less positive, less consistent and more ineffective parenting behaviours. Understanding the factors that are associated with the challenges of caring for these children may require additional research attention.     

Comparative effectiveness of statins in secondary prevention among the older people aged 75 years and over

International Journal of Clinical Pharmacy - Background While there is clear evidence for the benefit of statins in the secondary prevention of cardiovascular and cerebrovascular events, there is a...     

Leukotriene B<Subscript>4</Subscript> receptors BLT1 and BLT2 are involved in interleukin-8 production in human neutrophils induced by <Emphasis Type="Italic">Trichomonas vaginalis</Emphasis>-derived secretory products

Objective and method  

Trichomonas vaginalis is a flagellated protozoan parasite that causes human trichomoniasis. Although T. vaginalis itself can secrete lipid mediator leukotriene (LT) B₄ leading to neutrophil activation, information regarding the signaling mechanism involved in neutrophil activation induced by T. vaginalis-secreted LTB₄ is limited. We investigated whether LTB₄ contained in the T. vaginalis-derived secretory products (TvSP) is closely involved in interleukin (IL)-8 production in human neutrophils via LTB₄ receptors BLT1 or BLT2.     

Trichomonas vaginalis-secreted cysteinyl leukotrienes promote migration,degranulation and MCP-1 production in mast cells

Trichomonas vaginalis, a flagellated extracellular protozoan parasite that infects the human genitourinary tract, is usually transmitted by sexual contact. Our previous study showed that the leukotriene B₄ (LTB₄), a T vaginalis-secreted lipid mediator, induces interleukin (IL)-8 production and promotes mast cell degranulation and migration via BLT1 in human. In this study, we investigated whether T vaginalis produces another leukotrienes and whether it causes increased MCP-1 production, mast cell migration and degranulation by activating mast cells. We found that cysteinyl leukotrienes (CysLTs) were contained in T vaginalis-derived secretory product (TvSP) by ELISA. The TvSP-stimulated human mast cell line (HMC-1) exhibited significantly increased monocyte chemoattractant protein-1 (MCP-1) secretion compared to the unstimulated cells. Inhibition of NOX2 activation of cells by treatment of NOX inhibitor or NOX2 siRNA reduced TvSP-stimulated MCP-1 production in HMC-1 cells. It was also confirmed that the receptor for CysLTs is expressed in mast cells. The CysLT receptor (CysLTR) antagonist inhibited TvSP-stimulated MCP-1 production of mast cells, as well as ROS production, migration and degranulation of mast cells, and reduced phospho-NF-kB expression. These results suggest that T vaginalis-secreted CysLTs promote migration, degranulation and MCP-1 production in human mast cells through CysLT receptor-mediated NOX2 activation.     

Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l‐plastin in atopic dermatitis

Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP‐inducible protein l ‐plastin and confirmed upregulation of l ‐plastin and p‐l ‐plastin in TSLP‐treated human eosinophilic leukaemic (EoL‐1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)‐3, IL‐4, IL‐5 or IL‐13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l ‐plastin and an increase in migration of TSLP and cytokine‐treated eosinophils. In addition, phosphorylation of l ‐plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP‐induced phosphorylation of l ‐plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p‐l ‐plastin as a potential drug target for eosinophil‐targeted allergy therapy.     

l‐Asparaginase‐mediated downregulation of c‐Myc promotes 1,25(OH)2D3‐induced myeloid differentiation in acute myeloid leukemia cells

Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long‐term remission. Although differentiation induction therapy utilizing 1,25(OH)₂D₃ (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l ‐asparaginase (ASNase)‐mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation. ASNase treatment enhanced VD3‐driven phenotypic and functional differentiation of three‐different AML cell lines into monocyte/macrophages, along with c‐Myc downregulation. Using gene silencing with shRNA and a chemical blocker, we found that reduced c‐Myc is a critical factor for improving VD3 efficacy. c‐Myc‐dependent inhibition of mTORC1 signaling and induction of autophagy were involved in the enhanced AML cell differentiation. In addition, in a postculture of AML cells after each treatment, ASNase supports the antileukemic effect of VD3 by inhibiting cell growth and inducing apoptosis. Finally, we confirmed that the administration of ASNase significantly improved VD3 efficacy in the prolongation of survival time in mice bearing tumor xenograft. Our results are the first to demonstrate the extended application of ASNase, which is currently used for acute lymphoid leukemia, in VD3‐mediated differentiation induction therapy for AML, and suggest that this drug combination may be a promising novel strategy for curing AML.     

Spread dynamics of invasive species

Species invasions are a principal component of global change, causing large losses in biodiversity as well as economic damage. Invasion theory attempts to understand and predict invasion success and patterns of spread. However, there is no consensus regarding which species or community attributes enhance invader success or explain spread dynamics. Experimental and theoretical studies suggest that regulation of spread dynamics is possible; however, the conditions for its existence have not yet been empirically demonstrated. If invasion spread is a regulated process, the structure that accounts for this regulation will be a main determinant of invasion dynamics. Here we explore the existence of regulation underlying changes in the rate of new site colonization. We employ concepts and analytical tools from the study of abundance dynamics and show that spread dynamics are, in fact, regulated processes and that the regulation structure is notably consistent among invasions occurring in widely different contexts. We base our conclusions on the analysis of the spread dynamics of 30 species invasions, including birds, amphibians, fish, invertebrates, plants, and a virus, all of which exhibited similar regulation structures. In contrast to current beliefs that species invasions are idiosyncratic phenomena, here we provide evidence that general patterns do indeed exist.     

A semi-automated volumetric software for segmentation and perfusion parameter quantification of brain tumors using 320-row multidetector computed tomography: a validation study

Purpose

We developed a semi-automated volumetric software, NPerfusion, to segment brain tumors and quantify perfusion parameters on whole-brain CT perfusion (WBCTP) images. The purpose of this study was to assess the feasibility of the software and to validate its performance compared with manual segmentation.

Methods

Twenty-nine patients with pathologically proven brain tumors who underwent preoperative WBCTP between August 2012 and February 2015 were included. Three perfusion parameters, arterial flow (AF), equivalent blood volume (EBV), and Patlak flow (PF, which is a measure of permeability of capillaries), of brain tumors were generated by a commercial software and then quantified volumetrically by NPerfusion, which also semi-automatically segmented tumor boundaries. The quantification was validated by comparison with that of manual segmentation in terms of the concordance correlation coefficient and Bland-Altman analysis.

Results

With NPerfusion, we successfully performed segmentation and quantified whole volumetric perfusion parameters of all 29 brain tumors that showed consistent perfusion trends with previous studies. The validation of the perfusion parameter quantification exhibited almost perfect agreement with manual segmentation, with Lin concordance correlation coefficients (ρ _c) for AF, EBV, and PF of 0.9988, 0.9994, and 0.9976, respectively. On Bland-Altman analysis, most differences between this software and manual segmentation on the commercial software were within the limit of agreement.

Conclusions

NPerfusion successfully performs segmentation of brain tumors and calculates perfusion parameters of brain tumors. We validated this semi-automated segmentation software by comparing it with manual segmentation. NPerfusion can be used to calculate volumetric perfusion parameters of brain tumors from WBCTP.