An investigation into the effect of oxLDL and cyclic nucleotides on platelet cytoskeletal function

Atherosclerosis is a major underlying cause in cardiovascular disease and a significant health concern in developed countries. Part of the mechanism by which platelets are linked to this process is via their activation by oxidised Low-Density Lipoproteins (oxLDL), which drives both atherogenesis and thrombosis. However, the mechanism by which oxLDL drives plateletactivation and thrombosis is unclear.The combinations of matrix protein within the vascular wall and within the thrombus, especially if oxLDL is present can affect the size and strength of the thrombus formed. We have previously shown that platelets bind effectively to fibrinogen, but that this can be reversed by prostacyclin (PGI2). We now demonstrate that the combination of fibrinogen and oxLDL as a matrix protein induced a significant increase in platelet adhesion and spreading in a dose-dependent manner. Furthermore, we identified that oxLDL partially blocked the reversal of spread platelets by PGI2, as the surface area of the platelet was unaffected in contrast to those platelets spread only on fibrinogen. This suggested that oxLDL modulated the reversal of platelet spreading by PGI2. However, oxLDL mediated inhibition of surface area reduction by PGI2 was independent of the secondary mediators ADP and TxA2.To understand how oxLDL might cause this change in PGI2 mediated reversal of platelet function, we first identified the cAMP production in spread cells. This indicated that cAMP production was inhibited by oxLDL but was still significantly higher than control spread platelets. This indicated that the reversal of stress fibres could be induced by limited increases in cAMP whilst higher increases then affected lamellipodia and reduced overall platelet surface area. These two pieces of data suggested that the RhoGTPases, Rac and RhoA might be differentially controlled within spread platelets. This was confirmed as platelets spread on oxLDL and fibrinogen in the presence of PGI2 showed elevated levels of Rac activity, whilst RhoA activity was significantly inhibited. Furthermore, we found that pMLC was elevated in platelets spread on fibrinogen, fibrinogen and nLDL as well as oxLDL, in line with stress fibre formation and increase in Rho activity in the absence of PGI2.To understand the effect of this reversal of stress fibres on thrombus formation, we post perfused cAMP elevating agents over platelet aggregates preformed on fibrinogen +/- oxLDL or nLDL. Our data suggest that at high shear PGI2 or the AC (adenylyl cyclase) activator, forskolin cannot induce reversal of stress fibres, whilst the phosphodiesterase 3 inhibitor, milrinone can. In contrast at low shear, PGI2 and forskolin can induce a complete reversal of stress fibres. This data indicates that shear stress can alter PGI2 effects on spread platelets, potentially due to changes in PDE3 activity, and therefore can help to provide a prothrombotic environment.In summary, our data shows that oxLDL and fibrinogen play an important role in promoting a prothrombotic and proinflammatory phenotype, contributing to atherogenicity and atherothrombosis. Investigating the contribution of oxLDL and fibrinogen and their involvement in atherothrombosis, in the context of these results will provide novel insights and identify new pathways of immunothrombosis

Reading-to-Writing Mediation Model of Higher-Order Literacy

INTRODUCTION: Writing difficulties frequently manifest comorbidly with reading challenges, and reading is implicated in particular acts of writing, such as reviewing and editing. Despite what is known, however, there remain significant barriers to understanding the nature of reading-writing relations, as few studies are comprehensive in the number and types of literacy skills evaluated. This study consists of a secondary data analysis of two studies employing structural equation modeling (SEM) to evaluate relations among reading and writing components skills independently, using the Direct and Inferential Mediation Model (DIME) of reading comprehension and Not-so-Simple View of Writing (NSVW) as theoretical frameworks. METHODS: We examine relations between reading and writing components from these models with a sample of upper elementary students with/at-risk for learning disabilities ( RESULTS: The findings suggest that higher order fluency and comprehension skills are differentially related to writing activities and products. DISCUSSION: The pattern of results helps elucidate the mechanisms of how various reading and writing skills transfer and relate. The results have implications for targeted and implicit instruction in multicomponent interventions and the use of screeners to identify areas of risk

The Reading Profiles of Late Elementary English Learners With and Without Risk for Dyslexia

Few studies have systematically investigated the reading skill profiles of English Learners (ELs) in late elementary school, a critical developmental period for language and literacy and the most common grades for initial identification with specific learning disabilities (O’Connor et al., 2013). We investigated the reading skill profiles of 331 ELs in 3rd and 4th grades, including ELs with and without risk for dyslexia due to significant deficits in word and pseudo-word reading accuracy and fluency. We utilized latent profile analysis and factor mixture modeling to investigate: (1) the nature and distribution of reading skill profiles; (2) whether these profiles were associated with differences in reading comprehension growth across one academic year; and (3) the stability of reading profiles across an academic year. We selected a two class solution (reading disabled and typically developing) based on model fit indices, theoretical considerations, pattern of results across profile-solutions and time-points, and parameterizations, making the approach stronger and more generalizable. These classes demonstrated clear, consistent differences in performance across reading component skills, with the RD class scoring consistently below the TD class across code-based and meaning-based domains of reading. Across the year, the TD class demonstrated significantly higher patterns of growth in reading comprehension (χ2 (1) = 206.21, p \u3c 0.001). Class membership was largely stable (97% of participants maintain class membership). These results suggest that ELs with risk for dyslexia demonstrate multiple component skill deficits that may require long-term, comprehensive, intensive interventions to remediate

The Impact of Human Resources Practices on Organizational Performance: Mediating Role of Supply Chain Operational Performance Among Pakistani SMEs

Purpose: The primary aim of this quantitative study was to test the impact of the cultural capabilities and training & Development on Organizational Performance of Pakistani SMEs. In order to achieve the goals of the study, literature review has been done; tools and seven hypotheses were developed.   Methodology: data have been collected through structured self-administered questionnaire adopted and adapted from the earlier similar studies.  Based on 62 itemized survey, data have been collected from 379 Pakistani SMEs situated in ten cities. A pilot study was conducted and data analysis techniques as; Descriptive, Pearson Correlation, Regression, Convergent Validity, Discriminate validity, Composite reliability, Partial Least Square through Structural Educational Modeling, are employed to check the reliability, validity of model fitness and testing the hypotheses.     Conclusion: Study methodologies can include structural equation modelling and enhanced monitoring of supply chain management as well facilitating to their success can be resulted from the continued research in this area, as well as application of the model to different enterprises and situations.   Implications: This study provided guidance and controlling panel for the Small and Medium Enterprises Authority (SMEs) of Pakistani government at first place as it advises either SMEDA should pay attention to modernize SMEs with the help of technology and influence performance of industry. Future study may employ other methodologies to evaluate and confirm the currently presented casual links

Structure Altering Effects of a Multicomponent Reading Intervention: An Application of the Direct and Inferential Mediation (DIME) Model of Reading Comprehension in Upper Elementary Grades

We evaluate the direct and inferential mediation (DIME) model for reading comprehension with a sample of struggling readers in Grades 3 to 5 (N = 364) in the context of a large-scale randomized controlled trial (RCT) investigating two theoretically distinct reading interventions (text processing + foundational skills [n = 117] or text processing only [n = 120]) and a control condition (n = 127). We investigate whether the intervention affects not just reading comprehension levels, but also how variables within the reading system interrelate. This approach allows the focus to shift from intervention as influencing a change in reading comprehension status to a complex set of processes. We fit structural equation models (SEMs) to evaluate the DIME model at baseline and a change model that included reading comprehension and word reading at posttest. There were no significant mean differences between groups in reading comprehension. However, significant differences emerged on the direct and indirect effects of background knowledge, vocabulary, word reading, strategies, and inferencing on comprehension across grade levels and treatment conditions. Related to treatment groups, background knowledge, vocabulary, and inferencing were significantly related to comprehension at posttest for students who received text processing and/or foundational skills interventions. The results have implications for the direct instruction of higher-order reading skills in the context of multicomponent interventions

The Not-So-Simple View of Writing in Struggling Readers/Writers

Research suggests that executive function, motivation, transcription, and composition processes are implicated in the writing quality and productivity of children with and without learning difficulties. However, numerous components embedded within these constructs create both conceptual and empirical challenges to the study of written expression. These challenges are reflected in the writing research by way of poor delineation of constructs and insufficient distinction among domain general resources (e.g. working memory) versus processes related to the academic domain of writing (e.g. pre-planning), as well as among lower- (e.g. handwriting) and higher-order (e.g. editing) writing-specific processes. The current study utilizes the Not-so-Simple View of Writing (NSVW) as an organizing framework for examining the relations among multiple components, correlates, and attributes of writing in a sample of struggling readers/writers (n = 402) in grades 3–5. Data were collected on measures of (a) handwriting, spelling, planning, revision, and editing, derived from the Test of Oral Written Language (TOWL-4), (b) executive function derived from the NIH Examiner, and (c) motivation/self-efficacy derived from the Student Contextual Learning Scale. Structural equation modeling was utilized to test direct and indirect relations in the NSVW model. Results showed generally moderate correlations among observed/latent variables and found support for relations among writing-specific processes. Domain-general resources (executive function and motivation/self-efficacy) were related to spelling directly and indirectly to writing. Domain-specific processes (handwriting, spelling, planning, editing, and revision) were related to writing. The results have implications for explicit instruction of writing processes and for future research on empirical models

The Impact of Oil Prices on Foreign Reserves and Exchange Rates in Iraq During The Period (2012-2022)

The aim of the study investigates the, impact of oil prices at the international level on exchange rates And foreign reserves in Iraq for the duration (2012-2022). Its importance lies in studying the issue of developments in international oil prices and their impact on exchange rates and foreign reserves, due to the importance of international oil prices to the Iraqi economy. The study focuses on the sharp fluctuations in crude oil prices, which caused major economic problems and challenges for the Iraqi economy during the period (2014-2020), as well as affecting the exchange rates and foreign reserves. This study aims to examine and analyze the impact of oil prices on foreign reserves and exchange rates in Iraq during the research period. It is based on the hypothesis that there is a positive relationship between oil prices and indicators of the exchange rate and foreign reserves in Iraq, as the higher the oil prices, the higher these indicators will be with positive values, and vice versa. It adopts The method is analytical and descriptive for analyzing statistical data and financial and economic indicators in order to obtain and analyze results. It reveals a significant decrease in oil prices during the year 2020 from (64) dollars per barrel in 2019 to (41) dollars per barrel in 2020, with a decrease rate of (-34%), as a result of termination procedures witnessed by the international markets due to the spread of Corona virus. The results also show that the exchange rates of the US dollar against the Iraqi dinar fluctuated between increase and decrease in the official and parallel prices result of the drop-in oil prices. has decided to raise the official exchange rate from (1182) in 2019 to (1460) in 2020. In addition, there was decrease in the volume of foreign reserves at the Central Bank of Iraq as a result of the drop. Hence, Iraq’s total foreign exchange reserves have decreased. Finally, the study shows an increase in Iraqi foreign reserves during the years 2021-2022, reaching (100) billion dollars at the end of 2022, , in addition to the policy of the Central Bank of Iraq to raise prices of exchange to confront currency trafficking and money laundering

Collective Dynamics of coupled Lorenz oscillators near the Hopf Boundary: Intermittency and Chimera states

We study collective dynamics of networks of mutually coupled identical Lorenz oscillators near subcritical Hopf bifurcation. This system shows induced multistable behavior with interesting spatio-temporal dynamics including synchronization, desynchronization and chimera states. We find this network may exhibit intermittent behavior due to the complex basin structures, where, temporal dynamics of the oscillators in the ensemble switches between different attractors. Consequently, different oscillators may show dynamics that is intermittently synchronized (or desynchronized), giving rise to {\it intermittent chimera states}. The behaviour of the intermittent laminar phases is characterized by the characteristic time spend in the synchronization manifold, which decays as power law. This intermittent dynamics is quite general and can be extended for large number of oscillators interacting with nonlocal, global and local coupling schemes

Prediction of cognitive and intellectual competence in kindergarten schools associated with general measures of health: a study on children with age ranges between 4 to 7 years

BACKGROUND Stunting refers to the low “height-for-age” measurement. Literature suggests that it is associated with delayed or diminished physical development, cognition and intellectual abilities. OBJECTIVES: This study aimed to estimate the physical growth measures among children under 4 to 7 years of age and to determine its relationship with cognitive deficits & intellectual performances