Promising cytotoxic activity profile of fermented wheat germ extract (Avemar®) in human cancer cell lines

Fermented wheat germ extract (FWGE) is currently used as nutrition supplement for cancer patients. Limited recent data suggest antiproliferative, antimetastatic and immunological effects which were at least in part exerted by two quinones, 2-methoxy benzoquinone and 2,6-dimethoxybenzquinone as ingredients of FWGE. These activity data prompted us to further evaluate the in vitro antiproliferative activity of FWGE alone or in combination with the commonly used cytotoxic drugs 5-FU, oxaliplatin or irinotecan in a broad spectrum of human tumor cell lines. We used the sulforhodamine B assay to determine dose response relationships and IC50-values were calculated using the Hill equation. Drug interaction of simultaneous and sequential drug exposure was estimated using the model of Drewinko and potential clinical activity was assessed by the model of relative antitumor activity (RAA). Apoptosis was detected by DNA gel electrophoresis

Play completion predicts fewer child psychological difficulties: A longitudinal study of mentalizing processes

Play therapy is widely used with children, including children who experienced sexual abuse. This longitudinal study examined whether more pretend play completion (PPC) at Time 1 predicted fewer child difficulties when this was assessed 3 years later at Time 2. Participants were 91 children (aged 3–8 at Time 1), including 51 children who experienced sexual abuse (child sexual abuse [CSA]). Play was coded with the Children’s Play Therapy Instrument, and child psychological difficulties were assessed with the Child Behavior Checklist. More PPC at Time 1 predicted fewer child psychological difficulties 3 years later at Time 2. This was the case in children who had experienced CSA as well as the comparison group, showing that PPC is predicts better psychological adjustment in both abused and nonabused children. The study provides the first longitudinal evidence of the important role of pretend play narrative completion in predicting less internalizing and externalizing difficulties. The findings have important clinical implications for play therapists. It suggests that interventions that encourage children to elaborate and complete their play narratives could facilitate agency and psychological adjustment, as well as recovery after trauma. This is in line with the idea that through play children discover that they can “play with reality” and gain control over how they tell their stories. (PsycInfo Database Record (c) 2023 APA, all rights reserved

Force Oscillations Distort Avalanche Shapes

Contradictory scaling behavior in experiments testing the principle of universality may be due to external oscillations. Thus, the effect of damped oscillatory external forces on slip avalanches in slowly deformed solids is simulated using a mean-field model. Akin to a resonance effect, oscillatory driving forces change the dynamics of avalanches with durations close to the oscillation period. This problem can be avoided by tuning mechanical resonance frequencies away from the range of the inverse avalanche durations. The results provide critical guidance for experimental tests for universality and a quantitative understanding of avalanche dynamics under a wide range of driving conditions

Development and implementation of the ECHO model in a school setting to address youth electronic cigarette use in Kansas: A protocol

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Introduction: Schools remain at the frontlines of addressing issues, such as e-cigarette use, that impact students. Despite e-cigarette use remaining a significant public health concern in the U.S., schools have limited resources (e.g., staff, capacity, programming) to address it, especially in rural and frontier areas. This ECHO Pilot Project aimed to build capacity and equip schools and school staff in the state of Kansas to address high rates of youth e-cigarette use by providing prevention support and information on best practices for e-cigarette cessation. Methods and analysis: The pilot used the established Project ECHO model to disseminate evidence-based strategies for e-cigarette prevention and cessation among youth to schools across Kansas. The pilot selected 20 interdisciplinary school teams representing both rural and urban middle and high schools across the state to participate in seven ECHO sessions. ECHO sessions proceeded throughout Fall 2021, with the final session in Spring 2022. School participants completed pre-post surveys as well as component-specific surveys following each ECHO session. In addition, each school team created an individualized action plan to comprehensively address e-cigarette use at their school based on the information provided throughout the ECHO. Survey data, school tobacco/nicotine policies, and action plans will be analyzed to assess process and final outcomes. Discussion: If successful, this pilot will demonstrate that the ECHO model is an effective platform for building school staff knowledge and skills to implement evidence-based strategies in both urban and rural settings. It is anticipated that the pilot will build capacity and equip schools and school staff to address high rates of youth e-cigarette use by providing support for school-based prevention programs and referrals for e-cigarette cessation which will lessen the burden of nicotine-related problems in Kansas schools and communities. Finally, the pilot will provide evidence that the ECHO model can be successfully and equitably applied in a school setting and may be a viable method for addressing other public health-related issues faced by schools

Applied-force oscillations in avalanche dynamics

Until now most studies of discrete plasticity have focused on systems that are assumed to be driven by a monotonically increasing force; in many real systems, however, the driving force includes damped oscillations or oscillations induced by the propagation of discrete events or “slip avalanches.” In both cases, these oscillations may obscure the true dynamics. Here we effectively consider both cases by investigating the effects of damped oscillations in the external driving force on avalanche dynamics. We compare model simulations of slip avalanches under mean-field dynamics with observations in slip-avalanche experiments on slowly compressed micrometer-sized Au specimens using open-loop force control. The studies show very good agreement between simulations and experiments. We find that an oscillatory external driving force changes the average avalanche shapes only for avalanches with durations close to the period of oscillation of the external force. This effect on the avalanche shapes can be addressed in experiments by choosing suitable specimen dimensions so that the mechanical resonance does not interact with the avalanche dynamics. These results are important for the interpretation of avalanche experiments with built-in oscillators, and for the prediction and analysis of avalanche dynamics in systems with resonant vibrations

The prevalence of comorbidities in COPD patients, and their impact on health status and COPD symptoms in primary care patients: a protocol for an UNLOCK study from the IPCRG

[Abstract] Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality with high social and economic costs. The prevalence of COPD has been reported to vary between 6 and 26.1% worldwide.1 COPD has also been associated with a high prevalence of one or more comorbid conditions, which have an impact on health status and mortality.2–5 Although several diseases have been studied as COPD comorbidities6,7 few studies have looked at the issue of multimorbidity in COPD.8–10 COPD, like other chronic disorders, has been associated with comorbidities that increase in number and severity with age, and are more prevalent among deprived social groups.5,8 There is evidence that comorbidities increase the risk for exacerbations, reduce health status, and increase the risk of mortality.5,8 COPD guidelines (e.g., GOLD recommendations) still consider the diagnosis and management of comorbidities from an individual disease point of view.11 Consequently, health services focus on individual diseases rather than multimorbidity.10–13 A better knowledge of the prevalence and impact of multimorbidity facing COPD patients in primary care would help to evaluate whether a different approach (i.e., multimorbidity) should be taken. [...]The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study will include data from the Optimum Patient Care Research Database, and is undertaken in collaboration with Optimum Patient Care and the Respiratory Effectiveness Group, which will provide the data for this initiative without charge to the UNLOCK Group.info:eu-repo/semantics/publishedVersio

Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma

BackgroundIn patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication.MethodsWe assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events.ResultsThere were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20–50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT.ConclusionsThe intake of ASA until thrombocytopenia with a platelet count of 20–50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia

Respiratory function and respiratory complications in spinal cord injury: protocol for a prospective, multicentre cohort study in high-income countries

Introduction Pneumonia is one of the leading complications and causes of death after a spinal cord injury (SCI). After a cervical or thoracic lesion, impairment of the respiratory muscles decreases respiratory function, which increases the risk of respiratory complications. Pneumonia substantially reduces patient’s quality of life, may prolong inpatient rehabilitation time, increase healthcare costs or at worse, lead to early death. Respiratory function and coughing can be improved through various interventions after SCI, but the available evidence as to which as

Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein

Hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-gamma and TN Fu is present in serum. In animal models of the disease, IFN-gamma and INF-alpha have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-gamma, and INF-alpha have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL18 binding protein (IL18BP) resulting in an excess of free IL18 Here we studied whether IL-18B P could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18B P treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-gamma and TNF-alpha production by CD8+ T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18B P is beneficial in an animal model of HLH and in combination with anti infectious therapy may be a promising strategy to treat HLH patients

S1 is associated with chronic low back pain: a functional and structural MRI study

A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients