Unlocking Potential: Exploring the Impact of Selective Attention Training on Enhancing Communication in Children with Autism

This study investigates the concept of selective attention and its significance in fostering desired behavioral changes, both verbal and nonverbal, in autistic children. The research involved implementing a specialized behavioral program as part of the daily routine for a group of male children aged 3–6 years. The program was conducted over a period of 35 days, with one-hour sessions each day. For the outcome assessment, several tools were utilized, including diagnostic criteria for autism, a social adaptation scale tailored to the Jordanian environment, and the Schiller Behavior Assessment Scale. The CARS, adapted for the Saudi environment, was also employed. Prior to implementation, no statistically significant differences were observed in the average scores for verbal and nonverbal communication, responses to selective attention (specifically involving objects), and the development in interpersonal communication. However, after the implementation, significant differences were found in these areas. In addition to the aforementioned results, the study recommendations emphasized the importance of employing visual communication strategies and organized environments in autism programs. Furthermore, the inclusion of autistic children in training programs to enhance fundamental learning skills, image concept training with non-distracting backgrounds, and the establishment of support rooms within autism care centers to address communication weaknesses were also highlighted

Myogenic transcranial motor evoked potentials monitoring cannot always predict neurologic outcome after spinal cord ischemia in rats

AbstractObjectivesA day after undergoing an operation of the thoracic aorta, a patient showed signs of spastic paraplegia, but on myogenic transcranial motor evoked potential monitoring, the myogenic transcranial motor evoked potentials recorded from the left anterior tibial muscle appeared normal. We sought to confirm these observations by using a rat spinal ischemia model to define the possibility of false-negative results in myogenic transcranial motor evoked potential monitoring by motor function behavior and spinal histopathology.MethodsSpinal ischemia was induced for 6 minutes (group A, n = 6) or 10 minutes (group B, n = 6) with an intra-aortic balloon. After ischemia, motor function was assessed periodically by using the motor deficit index (0, complete recovery; 6, complete paraplegia). Myogenic transcranial motor evoked potentials were recorded from the right soleus muscle before ischemia, 2 and 6 minutes after the start of spinal ischemia, and at 30 minutes, 24 hours, and 72 hours of reperfusion.ResultsAll group A rats showed normal motor function at 72 hours of reperfusion, whereas all group B rats displayed complete spastic paraplegia (motor deficit index = 6) at 72 hours of reperfusion. However, transcranial motor evoked potential was preserved in both group B and group A. Histopathologic analysis in group B revealed the presence of extensive necrotic changes of the gray matter distributed between laminae V through VII in the L3 to L5 segments but normal appearance of α motor neurons.ConclusionAccording to our data, in using myogenic transcranial motor evoked potential monitoring during thoracic or thoracoabdominal aneurysm repair, we should be aware that transcranial motor evoked potentials cannot always be used to predict neurologic outcome after the operation

Endothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responses

A single extracellular stimulus can promote diverse behaviors among isogenic cells by differentially regulated signaling networks. We examined Ca2+ signaling in response to VEGF (vascular endothelial growth factor), a growth factor that can stimulate different behaviors in endothelial cells. We found that altering the amount of VEGF signaling in endothelial cells by stimulating them with different VEGF concentrations triggered distinct and mutually exclusive dynamic Ca2+ signaling responses that correlated with different cellular behaviors. These behaviors were cell proliferation involving the transcription factor NFAT (nuclear factor of activated T cells) and cell migration involving MLCK (myosin light chain kinase). Further analysis suggested that this signal decoding was robust to the noisy nature of the signal input. Using probabilistic modeling, we captured both the stochastic and deterministic aspects of Ca2+ signal decoding and accurately predicted cell responses in VEGF gradients, which we used to simulate different amounts of VEGF signaling. Ca2+ signaling patterns associated with proliferation and migration were detected during angiogenesis in developing zebrafish

A phased SNP-based classification of sickle cell anemia HBB haplotypes

Background: Sickle cell anemia causes severe complications and premature death. Five common beta-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful. The first method of haplotype classification used restriction fragment length polymorphisms (RFLPs) to detect single nucleotide polymorphisms (SNPs) in the beta-globin gene cluster. This is labor intensive, and error prone. Methods: We used genome-wide SNP data imputed to the 1000 Genomes reference panel to obtain phased data distinguishing parental alleles. Results: We successfully haplotyped 813 sickle cell anemia patients previously classified by RFLPs with a concordance >98%. Four SNPs (rs3834466, rs28440105, rs10128556, and rs968857) marking four different restriction enzyme sites unequivocally defined most haplotypes. We were able to assign a haplotype to 86% of samples that were either partially or misclassified using RFLPs. Conclusion: Phased data using only four SNPs allowed unequivocal assignment of a haplotype that was not always possible using a larger number of RFLPs. Given the availability of genome-wide SNP data, our method is rapid and does not require high computational resources.NIH Bethesda, MDBoston Univ, Sch Med, Dept Med, 72 E Concord St, Boston, MA 02118 USABoston Univ, Bioinformat Program, Boston, MA 02215 USAKing Saud Univ, Coll Med, Sickle Cell Dis Res Ctr, Riyadh, Saudi ArabiaKing Saud Univ, Coll Med, Dept Pediat, Riyadh, Saudi ArabiaKing Faisal Univ, Al Omran Sci Chair, Al Hasa, Saudi ArabiaImam Abdulrahman bin Faisal Univ, Inst Res & Med Consultat, Dammam, Saudi ArabiaEscola Paulista Med, Hematol & Blood Transfus Div, São Paulo, BrazilBoston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USAEscola Paulista Med, Hematol & Blood Transfus Div, São Paulo, BrazilNIH: R01 HL 068970NIH: RC2 HL 101212NIH: R01 87681NIH: T32 HL007501Web of Scienc

Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p

Module-based multiscale simulation of angiogenesis in skeletal muscle

<p>Abstract</p> <p>Background</p> <p>Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem.</p> <p>Results</p> <p>We present an object-oriented module-based computational integration strategy to build a multiscale model of angiogenesis that links currently available models. As an example case, we use this approach to integrate modules representing microvascular blood flow, oxygen transport, vascular endothelial growth factor transport and endothelial cell behavior (sensing, migration and proliferation). Modeling methodologies in these modules include algebraic equations, partial differential equations and agent-based models with complex logical rules. We apply this integrated model to simulate exercise-induced angiogenesis in skeletal muscle. The simulation results compare capillary growth patterns between different exercise conditions for a single bout of exercise. Results demonstrate how the computational infrastructure can effectively integrate multiple modules by coordinating their connectivity and data exchange. Model parameterization offers simulation flexibility and a platform for performing sensitivity analysis.</p> <p>Conclusions</p> <p>This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions.</p

Structural Analysis to Determine the Core of Hypoxia Response Network

The advent of sophisticated molecular biology techniques allows to deduce the structure of complex biological networks. However, networks tend to be huge and impose computational challenges on traditional mathematical analysis due to their high dimension and lack of reliable kinetic data. To overcome this problem, complex biological networks are decomposed into modules that are assumed to capture essential aspects of the full network's dynamics. The question that begs for an answer is how to identify the core that is representative of a network's dynamics, its function and robustness. One of the powerful methods to probe into the structure of a network is Petri net analysis. Petri nets support network visualization and execution. They are also equipped with sound mathematical and formal reasoning based on which a network can be decomposed into modules. The structural analysis provides insight into the robustness and facilitates the identification of fragile nodes. The application of these techniques to a previously proposed hypoxia control network reveals three functional modules responsible for degrading the hypoxia-inducible factor (HIF). Interestingly, the structural analysis identifies superfluous network parts and suggests that the reversibility of the reactions are not important for the essential functionality. The core network is determined to be the union of the three reduced individual modules. The structural analysis results are confirmed by numerical integration of the differential equations induced by the individual modules as well as their composition. The structural analysis leads also to a coarse network structure highlighting the structural principles inherent in the three functional modules. Importantly, our analysis identifies the fragile node in this robust network without which the switch-like behavior is shown to be completely absent

Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis

Vascular abnormalities contribute to many diseases such as cancer and diabetic retinopathy. In angiogenesis new blood vessels, headed by a migrating tip cell, sprout from pre-existing vessels in response to signals, e.g., vascular endothelial growth factor (VEGF). Tip cells meet and fuse (anastomosis) to form blood-flow supporting loops. Tip cell selection is achieved by Dll4-Notch mediated lateral inhibition resulting, under normal conditions, in an interleaved arrangement of tip and non-migrating stalk cells. Previously, we showed that the increased VEGF levels found in many diseases can cause the delayed negative feedback of lateral inhibition to produce abnormal oscillations of tip/stalk cell fates. Here we describe the development and implementation of a novel physics-based hierarchical agent model, tightly coupled to in vivo data, to explore the system dynamics as perpetual lateral inhibition combines with tip cell migration and fusion. We explore the tipping point between normal and abnormal sprouting as VEGF increases. A novel filopodia-adhesion driven migration mechanism is presented and validated against in vivo data. Due to the unique feature of ongoing lateral inhibition, ‘stabilised’ tip/stalk cell patterns show sensitivity to the formation of new cell-cell junctions during fusion: we predict cell fates can reverse. The fusing tip cells become inhibited and neighbouring stalk cells flip fate, recursively providing new tip cells. Junction size emerges as a key factor in establishing a stable tip/stalk pattern. Cell-cell junctions elongate as tip cells migrate, which is shown to provide positive feedback to lateral inhibition, causing it to be more susceptible to pathological oscillations. Importantly, down-regulation of the migratory pathway alone is shown to be sufficient to rescue the sprouting system from oscillation and restore stability. Thus we suggest the use of migration inhibitors as therapeutic agents for vascular normalisation in cancer

Systems Biology Modeling Reveals a Possible Mechanism of the Tumor Cell Death upon Oncogene Inactivation in EGFR Addicted Cancers

Despite many evidences supporting the concept of “oncogene addiction” and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers