Oxidative Phosphorylation (OXPHOS) Modulation of Immune Response in Melanoma

https://openworks.mdanderson.org/sumexp21/1168/thumbnail.jp

Factors in patients’ experience of hospital care: Evidence from California, 2009–2011

The use of measures of patient-centered care to evaluate hospital care is mandated by The Patient Protection and Affordable Care Act of 2010. Using three years of data from 315 California acute-care hospitals and data collected from patients via the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, we seek to evaluate patients’ hospital-care experience by (1) analyzing patients’ experience-of-care scores in light of these hospitals’ patient profiles, structural characteristics, and outcomes in 2011, and (2) determining and analyzing the extent of changes in patients’ experience of care over the three-year period 2009–2011. For 2011, we find significant variation in patients’ experience-of-care scores associated with hospitals’ different patient profiles and structural characteristics. In spite of these single-year differences, virtually all aspects of patients’ experience of care showed improvement over the 2009-2011 period

Phosphate concentration and arbuscular mycorrhizal colonisation influence the growth, yield and expression of twelve PHT1 family phosphate transporters in foxtail millet (Setaria italica)

Phosphorus (P) is an essential element which plays several key roles in all living organisms. Setaria italica (foxtail millet) is a model species for panacoid grasses including several millet species widely grown in arid regions of Asia and Africa, and for the bioenergy crop switchgrass. The growth responses of S. italica to different levels of inorganic phosphate (Pi) and to colonisation with the arbuscular mycorrhizal fungus Funneliformis mosseae (syn. Glomus mosseae) were studied. Phosphate is taken up from the environment by the PHT1 family of plant phosphate transporters, which have been well characterized in several plant species. Bioinformatic analysis identified 12 members of the PHT1 gene family (SiPHT1;1-1;12) in S. italica, and RT and qPCR analysis showed that most of these transporters displayed specific expression patterns with respect to tissue, phosphate status and arbuscular mycorrhizal colonisation. SiPHT1;2 was found to be expressed in all tissues and in all growth conditions tested. In contrast, expression of SiPHT1;4 was induced in roots after 15 days growth in hydroponic medium of low Pi concentration. Expression of SiPHT1;8 and SiPHT1;9 in roots was selectively induced by colonisation with F. mosseae. SiPHT1;3 and SiPHT1;4 were found to be predominantly expressed in leaf and root tissues respectively. Several other transporters were expressed in shoots and leaves during growth in low Pi concentrations. This study will form the basis for the further characterization of these transporters, with the long term goal of improving the phosphate use efficiency of foxtail millet

The effects of concurrent oral paliperidone or risperidone use with paliperidone long-acting injection

Introduction: Dosing recommendations for paliperidone long-acting injectable antipsychotic (LAIA) do not include oral antipsychotic (OAP) overlap; however, OAPs are often given concurrently despite limited evidence describing both the risks and benefits of this practice. Methods: A retrospective chart review was conducted in patients initiated on paliperidone palmitate (PP) during a psychiatric hospitalization to compare patients who received OAP overlap versus those who did not. The primary outcome is the proportion of patients who receive prescription claims for benztropine, a medication commonly prescribed for extrapyramidal symptoms, at the time of LAIA discontinuation and 6 months postdischarge. Secondary outcomes include prescription claims for beta blockers and diphenhydramine, number of psychiatric emergency visits and hospitalizations, length of stay of the index hospitalization, frequency of LAIA discontinuation and the time to LAIA discontinuation. Results: There is a significant difference in the proportion of benztropine prescription claims in the OAP overlap group versus the no-overlap group at the time of LAIA discontinuation (30% vs 0%, P =.046) but not at 6 months postdischarge. There are also significant differences in the number of psychiatric emergency visits (0.7 vs 0.1, P =.02) and psychiatric hospitalizations (0.6 vs 0.1, P =.029) at the time of LAIA discontinuation. No other differences are observed in defined secondary outcomes. Discussion: Patients who receive OAP overlap while receiving PP receive more benztropine and have more psychiatric emergency visits and hospitalizations than those treated without OAP. Larger studies with better control for confounding variables are needed to confirm these results

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ABSTRACT. Objective. To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-a (TNF-a) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA. Methods. Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA. Results. The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10 -4 ) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-a inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01). Conclusion. DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that primarily attacks synovial joints, leading to articular destruction and functional disability. It typically presents as symmetric peripheral polyarthritis and most commonly involves the small joints of the hands and feet 1,2 . One of the hallmarks of RA is progressive bone erosion. Research on the mechanisms by which RA induces osteolysis has focused on the osteoclast's roles in shifting the normal balance between bone formation and resorption. This imbalance is generated by key molecules that regulate osteoclast differentiation, such as cross-talk between receptor activators of nuclear factor-kB ligand (RANKL) and Wingless (Wnt) signaling pathway, which is important for the growth and differentiation of osteoblasts 3,4 . Dickkopf-1 (DKK-1) is an endogenous, secreted inhibitory factor in the canonical Wnt signaling by binding the Wnt coreceptor LRP5/6 5 . Studies have demonstrated that activation of the Wnt signaling pathway in mature osteoblasts upregulates osteoprotegerin (OPG), which blocks RANKL-induced osteoclastogenesis and results in the inhibition of bone resorption Cytokines play a pivotal role in RA pathogenesis. Tumor necrosis factor-a (TNF-a) contributes substantially to the pathology of RA. Interestingly, studies have shown that upregulation of DKK-1 could activate TNF receptor-1 (TNFR1) in cultivated articular mesenchymal cells 11 . TNF-a inhibitor could downregulate DKK-1 in ankylosing spondylitis (AS) 12 . Moreover, interleukin 1 (IL-1) can modulate the RANKL/OPG pathway, and may also affect the ability of the osteoblast to repair bone at sites of articular erosio

Digital twins, synthetic patient data, and in-silico trials: can they empower paediatric clinical trials?

Summary: Randomised controlled trials are the gold standard to assess the effectiveness and safety of clinical interventions; however, many paediatric trials are discontinued early due to challenges in patient enrolment. Hence, most paediatric clinical trials suffer from lack of adequate power. Additionally, trials are expensive and might expose patients to unproven therapies. Alternatives to overcome these issues using virtual patient data—namely, digital twins, synthetic patient data, and in-silico trials—are now possible due to rapid advances in digital health-care tools and interventions. However, such digital innovations have been rarely used in paediatric trials. In this Viewpoint, we propose using virtual patient data to empower paediatric trials. The use of virtual patient data has the advantages of decreased exposure of children to potentially ineffective or risky interventions, shorter trial durations leading to more rapid ascertainment of safety and effectiveness of interventions, and faster drug approvals. Use of virtual patient data could lead to more personalised treatment options with low costs and could result in faster clinical implementation of interventions in children. However, ethical and regulatory concerns, including replacing humans with digital data, data privacy, and security should be addressed and the safety and sustainability of digital data innovation ensured before virtual patient data are adopted widely

A Prospective Study of Inflammatory Cytokines and Diabetes Mellitus in a Multiethnic Cohort of Postmenopausal Women

Background: Inflammatory cytokines, including tumor necrosis factor ␣, IL-6 (interleukin 6), and highsensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations

Weak Magnetic Fields Enhance the Efficacy of Radiation Therapy

Purpose: The clinical efficacy of radiation therapy is mechanistically linked to ionization-induced free radicals that cause cell and tissue injury through direct and indirect mechanisms. Free radical reaction dynamics are influenced by many factors and can be manipulated by static weak magnetic fields (WMF) that perturb singlet-triplet state interconversion. Our study exploits this phenomenon to directly increase ionizing radiation (IR) dose absorption in tumors by combining WMF with radiation therapy as a new and effective method to improve treatment. Methods and Materials: Coils were custom made to produce both homogeneous and gradient magnetic fields. The gradient coil enabled simultaneous in vitro assessment of free radical/reactive oxygen species reactivity across multiple field strengths from 6 to 66 G. First, increases in IR-induced free radical concentrations using oxidant-sensitive fluorescent dyes in a cell-free system were measured and verified. Next, human and murine cancer cell lines were evaluated in in vitro and in vivo models after exposure to clinically relevant doses of IR in combination with WMF. Results: Cellular responses to IR and WMF were field strength and cell line dependent. WMF was able to enhance IR effects on reactive oxygen species formation, DNA double-strand break formation, cell death, and tumor growth. Conclusions: We demonstrate that the external presence of a magnetic field enhances radiation-induced cancer cell injury and death in vitro and in vivo. The effect extends beyond the timeframe when free radicals are induced in the presence of radiation into the window when endogenous free radicals are produced and therefore extends the applicability of this novel adjunct to cancer therapy in the context of radiation treatment