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AbstractBullying is an omnipresent problem with high prevalence in children and adolescents. There are many antibullying state laws and practices in place however its real level impact is ambiguous at best. We studied the prevalence of bullying in the United States, examine the practices, laws, and interventions in place to prevent bullying and its real-life impact. Various studies have reported that the ground-level change brought about by these policies and programs varies and is not quite significant. The effectiveness of existing policies and legislations remains unclear and measurable objective change or impact is not yet observed. Therefore, a rethink of the strategies is needed. The focus must be on community-level programs and interventions with inclusive approaches involving all the stakeholders are critical for addressing this menace.

There is an ongoing diagnostic and treatment challenge for migrant youth with PTSD that many clinicians face. Somatic symptoms and dissociative symptoms are often misinterpreted due to cultural and language barriers for migrant youth. Current studies have helped clinicians to develop a better understanding of the migrant youth’s journey including potentially traumatic and adverse events they encounter. This includes determining if pre-migration, migration, and post-migration stressors have had an impact on the individual. This has also helped clinicians, educators, and legal advocates to utilize a collaborative approach to address the migrant youth’s needs for managing the severity of PTSD symptoms.

Absorption of riboflavin (RF) across membrane barriers is essential to cellular oxidation reduction processes. Riboflavin carrier protein (RCP), a 37-kDa secretory protein, is proposed to play an important role in RF absorption, although information on the mammalian ortholog remains unclear. This study alludes to the existence of a mammalian RF carrier protein and further characterizes its carrier role and fate using avian RCP in human placental trophoblast (BeWo), another mammalian cell line, monkey kidney (COS-1), and the avian control, chicken hepatic (LMH/2A) cells. The presence of RCP and its involvement in RF internalization was analyzed by immunofluorescence and immunobinding assays using chicken RCP (cRCP) antibodies. In the presence of anti-cRCP, cellular RF uptake is significantly decreased (5% of control) in BeWo cells. Kinetic analyses of intracellular accumulation of (125)I-cRCP revealed a J(max) and K(m) of 28.56 +/- 2.70 pmol/mg protein/min and 142.43 +/- 82.16 nM, respectively, in BeWo cells and 75.14 +/- 7.6 pmol/mg protein/min and 104.37 +/- 23.96 nM in the species-specific control, LMH/2A cells. Subcellular fractionation studies revealed colocalization of both radiolabeled RF and cRCP within endosomal and lysosomal fractions, further elucidating RCP's role in trafficking RF through the cell. Following intracellular release of RF from the carrier complex, the protein is either subject to lysosomal breakdown or is conserved via recycling mechanisms for continued RF sequestration and uptake. In summary, mammalian placental trophoblasts exhibit specific carrier protein dependence that sequesters and essentially mediates RF internalization via the proposed receptor-mediated endocytic pathway.

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The objective of this study was to determine the effect of different cell culture media glucose concentrations on the functional activity of PepT-1 in Caco-2 cells. Uptake kinetics of Gly-Sar into Caco-2 cells that were maintained in iso-osmotic media containing 25 or 5.5 mM glucose were determined in the presence and absence of amino acid-selective chemical modifiers and dithiothreitol. Inhibition of Gly-Sar uptake into Caco-2 cells was measured in the presence of dipeptides and xenobiotics exhibiting various binding affinities for the PepT-1. The effect of extracellular glucose on PepT-1 gene expression was assessed using comparative RT-PCR. Long-term exposure of Caco-2 cells to 25 mM glucose reduced maximum transport capacity for Gly-Sar uptake without altering PepT-1 gene expression. In contrast, binding affinity of Gly-Sar and other dipeptides or xenobiotics was not significantly changed. Chemical modification of Lys and Tyr residues decreased Vmax, while Cys modification increased the maximum transport capacity of the carrier. Preincubation of Caco-2 cells with dithiothreitol restored PepT-1 activity in cells maintained at 25 mM glucose. In conclusion, cell culture media containing 25 mM glucose decreases maximum transport capacity of PepT-1 in Caco-2 cells without affecting substrate recognition, at least in part, mediated via an oxidative pathway. © 2003 Wiley-Liss Inc. and the American Pharmaeceutical Association J Pharm Sci 92:594–603, 2003

The objective of this study was to determine the effect of different cell culture media glucose concentrations on the functional activity of PepT‐1 in Caco‐2 cells. Uptake kinetics of Gly‐Sar into Caco‐2 cells that were maintained in iso‐osmotic media containing 25 or 5.5mM glucose were determined in the presence and absence of amino acid‐selective chemical modifiers and dithiothreitol. Inhibition of Gly‐Sar uptake into Caco‐2 cells was measured in the presence of dipeptides and xenobiotics exhibiting various binding affinities for the PepT‐1. The effect of extracellular glucose on PepT‐1gene expression was assessed using comparative RT‐PCR. Long‐term exposure of Caco‐2 cells to 25mM glucose reduced maximum transport capacity for Gly‐Sar uptake without altering PepT‐1gene expression. In contrast, binding affinity of Gly‐Sar and other dipeptides or xenobiotics was not significantly changed. Chemical modification of Lys and Tyr residues decreased Vmax, while Cys modification increased the maximum transport capacity of the carrier. Preincubation of Caco‐2 cells with dithiothreitol restored PepT‐1 activity in cells maintained at 25mM glucose. In conclusion, cell culture media containing 25mM glucose decreases maximum transport capacity of PepT‐1 in Caco‐2 cells without affecting substrate recognition, at least in part, mediated via an oxidative pathway.

The article looks at the legislative changes in the U.S. Leahyâ€'Smith America Invents Act (AIA) a U.S. patent law, both in practice and procedure, effective from March 16, 2013 and the change was the conversion from a first-inventor patent system to a firstâ€'inventorâ€'toâ€'file patent system.

Arnold: Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; UCB: Consultancy; Amgen: Consultancy, Research Funding.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by autoantibodies against platelet glycoproteins (GP). These autoantibodies are detected in only 40-60% of ITP patients even when sensitive techniques are used. Our understanding of the mechanisms of ITP is limited by the variability in clinical presentation, varied differences in treatment responses and the lack of reliable biomarkers. Several studies have exploited the possibilities of other immune-mediated mechanisms to account for low platelet counts in the absence of detectable antibodies. Thus, we hypothesized that other autoantibodies that target antigens involved in the platelet lifecycle can be important in ITP, such as thrombopoietin (TPO) and the thrombopoietin receptor (cMpl). The objective of this study was to evaluate the frequency and clinical significance of autoantibodies against TPO and cMpl in patients with ITP compared to patients with other thrombocytopenic disorders and healthy controls.