Somali Family Priorities And Perspectives Regarding Middle School Engagement

The purpose of this research was to investigate Somali families’ priorities and perspectives regarding middle school engagement. A survey was used which asked parents to rate the importance of different school engagement efforts, both at home and at school. Parents were then asked to answer open-ended questions regarding school engagement. Findings suggest that Somali parents prioritize those events and activities that directly benefit the child’s academics, more so than events and activities related to school-wide information and involvement. Furthermore, parents asked for better communication, more resources, and more equitable practices from educators. They also saw the importance of the education that school offered and sought to reinforce that at home. Recommendations are then given based on these findings, so that educators and parents can build more meaningful partnerships, with the goal of enhancing students academic achievement

The Ising Model for Neural Data: Model Quality and Approximate Methods for Extracting Functional Connectivity

We study pairwise Ising models for describing the statistics of multi-neuron spike trains, using data from a simulated cortical network. We explore efficient ways of finding the optimal couplings in these models and examine their statistical properties. To do this, we extract the optimal couplings for subsets of size up to 200 neurons, essentially exactly, using Boltzmann learning. We then study the quality of several approximate methods for finding the couplings by comparing their results with those found from Boltzmann learning. Two of these methods- inversion of the TAP equations and an approximation proposed by Sessak and Monasson- are remarkably accurate. Using these approximations for larger subsets of neurons, we find that extracting couplings using data from a subset smaller than the full network tends systematically to overestimate their magnitude. This effect is described qualitatively by infinite-range spin glass theory for the normal phase. We also show that a globally-correlated input to the neurons in the network lead to a small increase in the average coupling. However, the pair-to-pair variation of the couplings is much larger than this and reflects intrinsic properties of the network. Finally, we study the quality of these models by comparing their entropies with that of the data. We find that they perform well for small subsets of the neurons in the network, but the fit quality starts to deteriorate as the subset size grows, signalling the need to include higher order correlations to describe the statistics of large networks.Comment: 12 pages, 10 figure

Use of Learning Media by Undergraduate Medical Students in Pharmacology: A Prospective Cohort Study

The ubiquity of the internet and computer-based technologies has an increasing impact on higher education and the way students access information for learning. Moreover, there is a paucity of information about the quantitative and qualitative use of learning media by the current student generation. In this study we systematically analyzed the use of digital and non-digital learning resources by undergraduate medical students. Daily online surveys and semi-structured interviews were conducted with a cohort of 338 third year medical students enrolled in a general pharmacology course. Our data demonstrate a predominant use of digital over non-digital learning resources (69 +/- 7% vs. 31 +/- 7%;p 300 pages) (10.6 +/- 3.3%),internet search (7.9 +/- 1.6%) and e-learning cases (7.6 +/- 3.0%). When comparing learning media use of teaching vs. pre-exam self-study periods, textbooks were used significantly less during self-study (-55%;p < 0.01), while exam questions (+334%;p < 0.01) and e-learning cases (+176%;p < 0.01) were utilized more. Taken together, our study revealed a high prevalence and acceptance of digital learning resources by undergraduate medical students, in particular mobile applications

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Modulation of FLT3-ITD Localization and Targeting of Distinct Downstream Signaling Pathways as Potential Strategies to Overcome FLT3-Inhibitor Resistance

OBJECTIVES: Internal tandem duplications (ITDs) of the Fms-like tyrosine kinase 3 (FLT3) represent the most frequent molecular aberrations in acute myeloid leukemia (AML) and are associated with an inferior prognosis. The pattern of downstream activation by this constitutively activated receptor tyrosine kinase is influenced by the localization of FLT3-ITD depending on its glycosylation status. Different pharmacological approaches can affect FLT3-ITD-driven oncogenic pathways by the modulation of FLT3-ITD localization. AIMS: The objective of this study was to investigate the effects of N-glycosylation inhibitors (tunicamycin or 2-deoxy-D-glucose) or the histone deacetylase inhibitor valproic acid (VPA) on FLT3-ITD localization and downstream activity. We sought to determine the potential differences between the distinct FLT3-ITD variants, particularly concerning their susceptibility towards combined treatment by addressing either N-glycosylation and the heat shock protein 90 (HSP90) by 17-AAG, or by targeting the PI3K/AKT/mTOR pathway by rapamycin after treatment with VPA. METHODS: Murine Ba/F3 leukemia cell lines were stably transfected with distinct FLT3-ITD variants resulting in IL3-independent growth. These Ba/F3 FLT3-ITD cell lines or FLT3-ITD-expressing human MOLM13 cells were exposed to tunicamycin, 2-deoxy-D-glucose or VPA, and 17-AAG or rapamycin, and characterized in terms of downstream signaling by immunoblotting. FLT3 surface expression, apoptosis, and metabolic activity were analyzed by flow cytometry or an MTS assay. Proteome analysis by liquid chromatography–tandem mass spectrometry was performed to assess differential protein expression. RESULTS: The susceptibility of FLT3-ITD-expressing cells to 17-AAG after pre-treatment with tunicamycin or 2-deoxy-D-glucose was demonstrated. Importantly, in Ba/F3 cells that were stably expressing distinct FLT3-ITD variants that were located either in the juxtamembrane domain (JMD) or in the tyrosine kinase 1 domain (TKD1), response to the sequential treatments with tunicamycin and 17-AAG varied between individual FLT3-ITD motifs without dependence on the localization of the ITD. In all of the FLT3-ITD cell lines that were investigated, incubation with tunicamycin was accompanied by intracellular retention of FLT3-ITD due to the inhibition of glycosylation. In contrast, treatment of Ba/F3-FLT3-ITD cells with VPA was associated with a significant increase of FLT3-ITD surface expression depending on FLT3 protein synthesis. The allocation of FLT3 to different cellular compartments that was induced by tunicamycin, 2-deoxy-D-glucose, or VPA resulted in the activation of distinct downstream signaling pathways. Whole proteome analyses of Ba/F3 FLT3-ITD cells revealed up-regulation of the relevant chaperone proteins (e.g., calreticulin, calnexin, HSP90beta1) that are directly involved in the stabilization of FLT3-ITD or in its retention in the ER compartment. CONCLUSION: The allocation of FLT3-ITD to different cellular compartments and targeting distinct downstream signaling pathways by combined treatment with N-glycosylation and HSP90 inhibitors or VPA and rapamycin might represent new therapeutic strategies to overcome resistance towards tyrosine kinase inhibitors in FLT3-ITD-positive AML. The treatment approaches addressing N-glycosylation of FLT3-ITD appear to depend on patient-specific FLT3-ITD sequences, potentially affecting the efficacy of such pharmacological strategies

The Impact of Paid Sick Days on Public Health in an Elementary School Population

Background: The societal impact of Paid Sick Days (PSDs) has not been fully addressed in Vermont. Evidence suggests that PSDs benefit the well being of the employee in addition to saving expenses for the employer and the state. PSDs prevent the spread of diseases such as influenza and allow the ailing individual to receive proper medical attention. Inadequate PSDs not only affect the individual who needs time away from work due to illness, but extend to their entire family. Studies have documented the adverse effects from lack of PSDs on the ability for parents to care for their child. The following facts are known: • 7 states require private sector employees to provide “flexible” PSDs for family members (Vermont does not). • 66% of employers in Vermont do not provide PSDs for their employees. • Parents with PSDs or vacation are 5.2 times more likely to take time off from work to care for their sick child. We hypothesize that elementary aged children of working parents, who have an insufficient amount of PSDs, are more likely to attend school with an acute illness and are more likely to receive inadequate health care (i.e., miss well child check ups).https://scholarworks.uvm.edu/comphp_gallery/1015/thumbnail.jp

A kinetic model of the transformation of a micropatterned amorphous precursor into a porous single crystal

Biogenic single crystals with complex shapes are believed to be generated by the crystallisation of an amorphous precursor. Recent biomimetic experiments on the crystallisation of calcite via amorphous-to-crystalline transition point to the fact that the transformation kinetics may be controlled by the micropattern and the macroscopic shape of the amorphous precursor phase. Here we analyse a simple kinetic model, based on thermodynamic considerations, showing that the presence of cavities in the micropatterned precursor phase might interfere with the transformation process and control its kinetics. The size of the cavities couples to the total surface energy and, hence, to crystal nucleation and growth, while the spacing of the cavities, as compared to the typical diffusion path, controls the possible nucleation of competing crystals.Chemistry and Chemical Biolog

Nivolumab for relapsed/refractory classical Hodgkin lymphoma after brentuximab vedotin failure – Polish Lymphoma Research Group real-life experience

AimPolish centers analyzed retrospectively the real-life experience with nivolumab in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) patients, after brentuximab vedotin (BV ) failure. BackgroundDespite the effective frontline treatment, for cHL patients relapsing after autologous stem cell transplantation, the only effective strategy remains the novel agents. Nivolumab, a checkpoint inhibitor, demonstrates the clinical benefit with an acceptable safety profile. Materials and methodsRetrospective analysis included 16 adult patients with R/R cHL after BV failure. All patients received single-agent nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. ResultsAfter six cycles of nivolumab the overall response rate was 81% (complete remission rate of 56%, partial remission rate of 25%). The median PFS was not reached after a median follow-up of 19 months. Adverse events (AEs) of any grade occurred in 12 patients (75%), including grade 3 AEs observed in 5 patients (31%). There were no AEs of grade 4 or 5. After a median of 25 nivolumab doses, 62% of responding patients proceeded to allogeneic stem cell transplantation. ConclusionNivolumab monotherapy demonstrated a high efficacy and safety in R/R cHL patients after BV failure. More patients and longer follow-up may further establish the potential benefit