A Scoping Review of School-Based Efforts to Support Students Who Have Experienced Trauma

School Mental Health - The current review sought to describe the published literature relative to addressing trauma in schools. Through a systematic review of peer-reviewed publications as well as...     

Cellular Pharmacokinetic Model-Based Analysis of Genistein,Glyceollin, and MK-571 Effects on 5 (and 6)-Carboxy-2′,7′-Dichloroflourescein Disposition in Caco-2 Cells

Pharmacokinetic modeling was used to describe 5 (and 6)-carboxy-2′,7′-dichloroflourescein (CDF) disposition in Caco-2 cells following CDF or CDFDA (CDF diacetate) dosing. CDF transcellular flux was modeled by simple passive diffusion. CDFDA dosing models were based on simultaneous fitting of CDF levels in apical, basolateral, and intracellular compartments. Predicted CDF efflux was 50% higher across the apical versus the basolateral membrane. This difference was similar following apical and basolateral CDFDA dosing, despite intracellular levels being 3-fold higher following basolateral dosing, thus supporting nonsaturable CDF efflux kinetics. A 3-compartment catenary model with intracellular CDFDA hydrolysis described CDF disposition. This model predicted that apical CDF efflux was not altered in the presence of MK-571, and that basolateral membrane clearance was enhanced to account for reduced intracellular CDF in the presence of this multidrug resistance-associated protein (MRP) inhibitor. Similar effects were predicted for glyceollin, while genistein exposure had no predicted effects on CDF efflux. These modulator effects are discussed in the context of model predicted intracellular CDF concentrations relative to reports of CDF affinity (measured by K_m) for MRP2 and MRP3. This model-based analysis confirms the complexity of efflux kinetics and suggests that other transporters may have contributed to CDF efflux.     

Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775)

Lysergic acid diethylamide (LSD) is perhaps one of the best‐known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as ‘research chemicals’ or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM‐775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM‐775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM‐775. A powdered sample of LSM‐775 was characterized by X‐ray crystallography, nuclear magnetic resonance spectroscopy (NMR), gas chromatography mass spectrometry (GC–MS), high mass accuracy electrospray MS/MS, high performance liquid chromatography (HPLC) diode array detection, HPLC quadrupole MS, and GC solid‐state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM‐775 acts as a nonselective agonist at 5‐HT_1A and 5‐HT_2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM‐775 activates 5‐HT_2A receptors and produces hallucinogen‐like effects in vivo. LSM‐775 did not induce the head twitch response unless 5‐HT_1A receptors were blocked by pretreatment with the antagonist WAY‐100,635 (1 mg/kg, subcutaneous). These findings suggest that 5‐HT_1A activation by LSM‐775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM‐775 is only capable of producing weak LSD‐like effects in humans.     

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Viral delivery of P450 reductase recapitulates the ability of constitutive overexpression of reductase enzymes to potentiate the activity of mitomycin C in human breast cancer xenografts

Indolequinones such as mitomycin C (MMC) require enzymatic bioreduction to yield cytotoxic moieties. An attractive approach to overcome the potential variability in reductive bioactivation between tumors is to exploit specific enzyme-bioreductive drug combinations in an enzyme-directed gene therapy (GDEPT) approach. To this end, human breast cancer cell lines (T47D, MDA468, and MDA231) that overexpress either DT-diaphorase (DTD) or NADPH:cytochrome P450 reductase (P450R) have been developed. Cytotoxicity of MMC was evaluated in the panel of cell lines following aerobic or anoxic exposure in vitro. DTD and/or P450R overexpression sensitized cells to MMC in air with no further increase in the cytotoxicity of MMC under anoxia. The most profound effect was seen in the MDA468 cells, where a 27-fold increase in potency was observed for MMC in the DTD-overexpressing cell line. The MMC sensitization achieved through DTD and P450R overexpression in MDA468 cells was maintained in vivo. Xenografts established from the clonal lines exhibited significant tumor control following MMC treatment (treated/control [T/C] 17% and 51% for DTD and P450R xenografts, respectively) that was not seen in wild-type tumors (T/C 102%). Delivery of a clinically relevant adenoviral vector encoding P450R to MDA468 wild-type tumors yielded comparable P450R activity to that seen in the P450R clonal xenografts and resulted in greater MMC sensitization (T/C 46%). The model systems developed will facilitate the identification of novel indolequinone agents that are targeted toward a specific enzyme for bioactivation and are consequently of potential use in a GDEPT approach.     

The Interaction Between Radiation and Complexes of Cis-Pt(II) and Rh(II): Studies at the Molecular and Cellular Level

Summary

A range of Rh(II) carboxylates and cis-Pt(II) complexes have been examined for their ability to increase the radiation sensitivity of aerobic and hypoxic V79 cells in vitro. The transition metal complexes sensitize in both air and nitrogen, with the greater effect generally occurring in nitrogen. The cis-Pt(II) complexes only show small levels of sensitization with dose modification factors (DMFs) of no more than 1·2. In contrast, the Rh(II) complexes can give DMFs of 2·0. Radiation chemical experiments show the transition metal complexes to have substantially lower redox potentials than metronidazole and, in addition, neither type of complex undergoes electron transfer reaction or adduct formation on interaction with radicals derived from DNA bases. Thus, the inorganic complexes do not operate by mechanisms similar to those occurring with electron affinic or stable free radical sensitizers. The increase in radiation sensitivity for cells treated with the Rh(II) carboxylates, but not the cis-Pt(II) complexes, is attributed to the ability of the Rh compounds to deplete intracellular thiols. Further, the efficiency of sensitization by the Rh(II) complexes and their ability to interact with cellular thiols depends upon the nature of the carboxylate ligand and follows the order butyrate > propionate > acetate > methoxyacetate. The differences between the carboxylates may be due to differences in drug uptake. A combination of the Rh(II) complexes with misonidazole given to hypoxic cells irradiated in vitro gives an additive response. However, it was not possible to demonstrate a similar effect in tumours in mice given the combination of Rh(II) methoxyacetate and the misonidazole analogue RSU 1070.     

Performance measures provide assessments of pain and function in people with advanced osteoarthritis of the hip or knee

BACKGROUND AND PURPOSE: Pain and physical function are core outcome measures for people with osteoarthritis, and self-report questionnaires have been the preferred assessment method. There is evidence suggesting that self-reports of physical function represent what people experience when performing activities rather than their ability to perform activities. The purpose of this study was to examine the factorial validity of performance-specific assessments of pain and function. SUBJECTS: The sample consisted of 177 participants who had osteoarthritis of the hip (n=81) or knee (n=96) and who were awaiting total joint arthroplasty. METHODS: Through a cross-sectional design, participants performed 4 performance activities (self-paced walk test, stair test, Timed "Up & Go" Test, and Six-Minute Walk Test). OUTCOMES: were time or distance (function) and pain ratings obtained immediately after each activity. The authors conceptualized 2 correlated factors, with pain items loading uniquely on 1 factor and functional items loading on the second factor, and uncorrelated error terms. Confirmatory factor analysis was applied. RESULTS: Initial analysis yielded results consistent with the conceptualized model in this study with the exception of a nonzero correlation between the stair pain and function error terms. Dropping the stair test provided results consistent with the conceptualized model. DISCUSSION AND CONCLUSION: Given the limitations of self-report alone as a method of obtaining reasonably distinct assessments of pain and function, the extent to which performance-specific assessments could accomplish this goal was examined in this study. It was found that collectively the walk test, Timed "Up & Go" Test, and Six-Minute Walk Test yielded 2 factors consistent with the health concepts of pain and function. The authors believe that the application of these tests may provide clinicians and clinical researchers with more distinct impressions of pain and function that complement information from self-report measures.     

Cross-cultural validation and psychometric evaluation of the Participation and Environment Measure for Children and Youth in Korea

Purpose: To develop the Korean version of the Participation and Environment Measure for Children and Youth (KPEM-CY) and examine its psychometric properties.

Method: The PEM-CY was cross-culturally translated into Korean using a specific guideline: pre-review of participation items, forward/backward translation, expert committee review, pre-test of the KPEM-CY and final review. To establish internal consistency, test–retest reliability and construct validity of the KPEM-CY, 80 parents of children with disabilities aged 5–13 years were recruited in South Korea.

Results: Across the home, school and community settings, 76% of participation items and 29% of environment items were revised to improve their fit with Korean culture. Internal consistency was moderate to excellent (0.67–0.92) for different summary scores. Test–retest reliability was excellent (>0.75) in the summary scores of participation frequency and extent of involvement across the three settings and moderate to excellent (0.53–0.95) in all summary scores at home. Child’s age, type of school and annual income were the factors that significantly influenced specific dimensions of participation and environment across all settings.

Conclusions: Results indicated that the KPEM-CY is equivalent to the original PEM-CY and has initial evidence of reliability and validity for use with Korean children with disabilities.

• Implications for rehabilitation

• Because ‘participation’ is a key outcome of the rehabilitation, measuring comprehensive participation of children with disabilities is necessary.

• The PEM-CY is a parent-report survey measure to assess comprehensive participation of children and youth and environment, which affect their participation, at home, school and in the community.

• A cross-cultural adaptation process is mandatory to adapt the measurement tool to a new culture or country.

• The Korean PEM-CY has both reliability and validity and can therefore generate useful clinical data for Korean children with disabilities.

     

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.