Equitable Access to Mental Health and Substance Use Care: An Urgent Need

Due to the deepening mental health and substance use crisis in the U.S., there's an urgent need for equitable access to care that is timely, clinically effective, and adequately reimbursed by insurers. This need encompasses psychiatrists, psychologists, social workers, other counselors, and treatment facilities as well as mental health and substance use care delivered by primary care providers.Multiple studies, including analyses of insurance claims and surveys of employers and providers, have demonstrated that in-network health insurance coverage for treatment of mental health and substance use conditions remains inadequate and not "on par" with access to in-network health insurance coverage for physical health treatment.This patient-experience survey conducted by NORC (Survey) explored key topics such as: 1) how often mental health or substance use care is needed but not received; 2) how difficult it is to find in-network providers accepting new patients; 3) how often and why patients use out-ofnetwork providers for mental health or substance use care versus physical health care; 4) how often patients feel that mental health or substance use care from PCPs and other physical health providers is insufficient; 5) how often services are denied; and more

Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury

The article reviews agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury

Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Gliomas are the most common and aggressive primary brain tumors for which unfortunately no effective treatment modalities exist despite advances in molecular biology as the knowledge base to unravel the extremely complex molecular mechanisms of tumorigenesis is limited. In this study an attempt has been made to understand the molecular pathological basis of tumorigenesis which led to an identification of an oncogene, CDC2, and an epigenetic strategy has been evaluated to control the tumorigensis by downregulating this oncogene.</p> <p>Methods</p> <p>Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. Real-Time PCR was used to determine the level of CDC2 mRNA. Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated.</p> <p>Results</p> <p>Human glioma tissue microarrays indicated the positive expression rates of CDC2/CyclinB1 with a positive correlation with pathologic grades (r = 0.982, r = 0.959, respectively). Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. And the viral particles containing small interfering RNA for CDC2 were subsequently injected into subcutaneous and intracranial xenogeneic graft tuomrs of nude mice. For subcutaneous tumors, injection of CDC2-shRNA retroviruses significantly decreased tumor weight and volume compared with control. Immunohistochemistry indicated that CDC2 are negative and TUNEL are positive in tumors treated with recombinant retrovirus. For mice implanted with intracranial gliomas, treatment of CDC2-shRNA retroviruses increased survival times compared with control.</p> <p>Conclusion</p> <p>CDC2 gene plays an important role in the proliferation of human gliomas. Downregulation of CDC2 could potentialy inhibit human gliomas cells growth ex vivo and in vivo. From these results, it was suggested that CDC2 might be a potential target on gene therapy of human gliomas.</p

Conformal and continuous deposition of bifunctional cobalt phosphide layers on p-silicon nanowire arrays for improved solar hydrogen evolution

Vertically aligned p-silicon nanowire (SiNW) arrays have been extensively investigated in recent years as promising photocathodes for solar-driven hydrogen evolution. However, the fabrication of SiNW photocathodes with both high photoelectrocatalytic activity and long-term operational stability using a simple and affordable approach is a challenging task. Herein, we report conformal and continuous deposition of a di-cobalt phosphide (Co2P) layer on lithography-patterned highly ordered SiNW arrays via a cost-effective drop-casting method followed by a low-temperature phosphorization treatment. The as-deposited Co2P layer consists of crystalline nanoparticles and has an intimate contact with SiNWs, forming a well-defined SiNW@Co2P core/shell nanostructure. The conformal and continuous Co2P layer functions as a highly efficient catalyst capable of substantially improving the photoelectrocatalytic activity for the hydrogen evolution reaction (HER) and effectively passivates the SiNWs to protect them from photo-oxidation, thus prolonging the lifetime of the electrode. As a consequence, the SiNW@Co2P photocathode with an optimized Co2P layer thickness exhibits a high photocurrent density of -21.9 mA.cm(-2) at 0 V versus reversible hydrogen electrode and excellent operational stability up to 20 h for solar-driven hydrogen evolution, outperforming many nanostructured silicon photocathodes reported in the literature. The combination of passivation and catalytic functions in a single continuous layer represents a promising strategy for designing high-performance semiconductor photoelectrodes for use in solar-driven water splitting, which may simplify fabrication procedures and potentially reduce production costsThis work was funded by ERDF funds through the Portuguese Operational Programme for Competitiveness and Internationalization COMPETE 2020, and national funds through FCT – The Portuguese Foundation for Science and Technology, under the project “PTDC/CTM-ENE/2349/2014” (Grant Agreement No. 016660). The work is also partially funded by the Portugal-China Bilateral Collaborative Programme (FCT/21102/28/12/2016/S). L. F. Liu acknowledges the financial support of the FCT Investigator Grant (IF/01595/2014) and Exploratory Grant (IF/01595/2014/CP1247/CT0001). L. Qiao acknowledges the financial support of the Ministry of Science and Technology of China (Grant Agreement No. 2016YFE0132400).info:eu-repo/semantics/publishedVersio

Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The steroid and xenobiotic receptor, SXR, is an orphan nuclear receptor that regulates metabolism of diverse dietary, endobiotic, and xenobiotic compounds. SXR is expressed at high levels in the liver and intestine, and at lower levels in breast and other tissues where its function was unknown. Since many breast cancer preventive and therapeutic compounds are SXR activators, we hypothesized that some beneficial effects of these compounds are mediated through SXR.</p> <p>Methods</p> <p>To test this hypothesis, we measured proliferation of breast cancer cells in response to SXR activators and evaluated consequent changes in the expression of genes critical for proliferation and cell-cycle control using quantitative RT-PCR and western blotting. Results were confirmed using siRNA-mediated gene knockdown. Statistical analysis was by t-test or ANOVA and a P value ≤ 0.05 was considered to be significant.</p> <p>Results</p> <p>Many structurally and functionally distinct SXR activators inhibited the proliferation of MCF-7 and ZR-75-1 breast cancer cells by inducing cell cycle arrest at the G1/S phase followed by apoptosis. Decreased growth in response to SXR activation was associated with stabilization of p53 and up-regulation of cell cycle regulatory and pro-apoptotic genes such as p21, PUMA and BAX. These gene expression changes were preceded by an increase in inducible nitric oxide synthase and nitric oxide in these cells. Inhibition of iNOS blocked the induction of p53. p53 knockdown inhibited up-regulation of p21 and BAX. We infer that NO is required for p53 induction and that p53 is required for up-regulation of cell cycle regulatory and apoptotic genes in this system. SXR activator-induced increases in iNOS levels were inhibited by siRNA-mediated knockdown of SXR, indicating that SXR activation is necessary for subsequent regulation of iNOS expression.</p> <p>Conclusion</p> <p>We conclude that activation of SXR is anti-proliferative in p53 wild type breast cancer cells and that this effect is mechanistically dependent upon the local production of NO and NO-dependent up-regulation of p53. These findings reveal a novel biological function for SXR and suggest that a subset of SXR activators may function as effective therapeutic and chemo-preventative agents for certain types of breast cancers.</p

New trends in the economic systems management in the context of modern global challenges

New trends in the economic systems management in the context of modern global challenges: collective monograph / scientific edited by M. Bezpartochnyi, in 2 Vol. // VUZF University of Finance, Business and Entrepreneurship. – Sofia: VUZF Publishing House “St. Grigorii Bogoslov”, 2020. – Vol. 1. – 309 p