325 research outputs found

    Critical Temperatures in Plasma Membrane Vesicles are Dependent on the Cell Cycle

    Get PDF

    Deformation of Earth’s upper mantle: insights from naturally occurring fabric types

    Get PDF
    Flow of the Earth’s upper mantle is controlled by the rheology of olivine, therefore comprehending the factors affecting olivine fabric development is critical for understanding global tectonic processes. Microstructural, FTIR and isotope analysis of olivine in Higashi-akaishi and Lihir peridotites provides insight into the relationship between olivine deformation, geochemistry and water. These results have fundamental implications for interpreting seismic anisotropy and are applicable to a wide range of tectonic environments to better constrain mantle deformation

    Family Correlates of Daughter’s and Son’s Locus of Control Expectancies during Childhood

    Get PDF
    Children who expect they can bring about good outcomes and avoid bad outcomes tend to experience more personal successes. Little is known about factors that contribute to these ‘control expectancies’. The purpose of the present study was to determine whether children’s internal control expectancies occur in the context of parents’ internal control expectancies, low family strain, and high family cohesiveness and whether these factors are more strongly related to daughters’ than sons’ control expectancies. A community sample of 85 children aged 9 to 11 years old and their parents (85 mothers; 63 fathers) completed rating scales. Fathers’ more internal control expectancies and mothers’ reports of fewer family strains were associated with daughters’ but not sons’ greater internal control expectancies, and greater family cohesiveness was related to both daughters’ and sons’ internal control orientations. These findings suggest that family factors may contribute to children’s, particularly daughters’, development of internal control expectancies

    Mobile devices for the remote acquisition of physiological and behavioral biomarkers in psychiatric clinical research

    Get PDF
    Psychiatric disorders are linked to a variety of biological, psychological, and contextual causes and consequences. Laboratory studies have elucidated the importance of several key physiological and behavioral biomarkers in the study of psychiatric disorders, but much less is known about the role of these biomarkers in naturalistic settings. These gaps are largely driven by methodological barriers to assessing biomarker data rapidly, reliably, and frequently outside the clinic or laboratory. Mobile health (mHealth) tools offer new opportunities to study relevant biomarkers in concert with other types of data (e.g., self-reports, global positioning system data). This review provides an overview on the state of this emerging field and describes examples from the literature where mHealth tools have been used to measure a wide array of biomarkers in the context of psychiatric functioning (e.g., psychological stress, anxiety, autism, substance use). We also outline advantages and special considerations for incorporating mHealth tools for remote biomarker measurement into studies of psychiatric illness and treatment and identify several specific opportunities for expanding this promising methodology. Integrating mHealth tools into this area may dramatically improve psychiatric science and facilitate highly personalized clinical care of psychiatric disorders

    Exploring innovative strategies to improve perinatal mental health in Scotland:co-development of an action research agenda with women, families and practitioners

    Get PDF
    Perinatal mental health (PNMH) is an ongoing concern for women and families, as well as for health and social care services. It is estimated that 10-20% of women will experience mental health issues and up to 10% of fathers may also experience difficulties with their mental health. This issue was recently highlighted by national media.Our previous stakeholder consultation work identified service gaps for women in the mild-moderate category of PNMH. This project aimed to explore this identified gap further by bringing together a diverse group of partners, including women/families, practitioners and researchers to co-develop a collaborative action-research agenda. Project design and delivery was developed in collaboration with an expert with lived experience to ensure all elements were relevant and relatable.It is crucial to involve all stakeholders, including those with lived experience and practitioners, in discussions regarding successful interventions for perinatal mental health. This approach ensures that families receive better outcomes in a sustainable and scalable manner

    Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513.

    Get PDF
    BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing\u27s Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 10(6) BE (2)-c cells followed by immediate treatment with 50-100 mg/kg/day doses of OZ513 administered IP three times per week out to 23 days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N = 6), and OZ513 treated mice (N = 5). RESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth. CONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear

    Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513.

    Get PDF
    BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing\u27s Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 10(6) BE (2)-c cells followed by immediate treatment with 50-100 mg/kg/day doses of OZ513 administered IP three times per week out to 23 days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N = 6), and OZ513 treated mice (N = 5). RESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth. CONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear

    Traumatic abdominal wall hernias in children: A case for early exploration

    Get PDF
    Purpose Traumatic abdominal wall hernia (TAWH) is a rare consequence of blunt abdominal trauma (BAT). We examined a series of patients suffering TAWH to evaluate its frequency, rate of associated concurrent intraabdominal injuries (CAI) and correlation with CT, management and outcomes. Methods A Level 1 pediatric trauma center trauma registry was queried for children less than 18 years old suffering TAWH from BAT between 2009 and 2019. Results 9370 patients were admitted after BAT. TAWH was observed in 11 children, at incidence 0.1%. Eight children (73%) were male, at mean age 10 years, and mean ISS of 16. Six cases (55%) were because of MVC, three (27%) impaled by a handlebar or pole, and two (18%) dragged under large machinery. Seven (64%) had a CAI requiring operative or interventional management. Patients with CAI were similar to those without other injury, with 20% and 50% CT scan sensitivity and specificity for detection of associated injury, respectively. Five patients had immediate hernia repair with laparotomy for repair of intraabdominal injury, three had delayed repair, two have asymptomatic unrepaired TAWH, and one resolved spontaneously. Conclusions Children with TAWH have high rates of CAI requiring operative repair. CT scans have low sensitivity and specificity for detecting associated injuries. A high suspicion of injury and low threshold for exploration must be maintained in TAWH cases

    Comparing Adult Cannabis Treatment-Seekers Enrolled in a Clinical Trial with National Samples of Cannabis Users in the United States

    Get PDF
    Background—Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods—Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results—Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions—These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings
    • …
    corecore