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This study examined the association between enrollment in Maryland's behavioral health home (BHH) program and use of outpatient mental health services among people with serious mental illness. The study sample, drawn from Maryland Medicaid administrative claims data from 2012 through 2017, included 12,232 individuals ages 21-64 with a serious mental illness who were enrolled in a BHH (N=3,319) or never enrolled (N=8,913). A marginal structural modeling approach with inverse probability of treatment weighting was used to examine the association between BHH enrollment and outpatient mental health utilization, measured as the number of visits per 3-month period. BHH enrollment was associated with 0.8 additional outpatient mental health visits per 3-month period, or approximately three additional visits annually. A specialty mental health system-based health home model with a primary goal of improving access to general medical care was associated with increased use of outpatient mental health services. A specialty mental health system-based health home model with a primary goal of improving access to general medical care was associated with increased use of outpatient mental health services.The etiology of lumbocrural pain is closely related to intervertebral disc degeneration (IDD). Long noncoding RNAs (lncRNAs) serve crucial roles in IDD progression. This study investigated the effect of lncRNA H19 on autophagy and apoptosis of nucleus pulposus cells (NPCs) in IDD. The rat model of IDD was established. Normal NPCs and degenerative NPCs (DNPCs) were cultured in vitro. H19 expression in IDD rat was detected. DNPCs were treated with si-H19 to evaluate autophagy and apoptosis of DNPCs. The binding relationships between H19 and miR-139-3p, and miR-139-3p and CXCR4 were verified. DNPCs were co-transfected si-H19 and miR-139-3p inhibitor. The phosphorylation of NF-κB pathway-related p65 in DNPCs was detected. LncRNA H19 was upregulated in IDD rats. Downregulation of H19 inhibited autophagy and apoptosis of DNPCs. LncRNA H19 sponged miR-139-3p to inhibit CXCR4 expression. si-H19 and miR-139-3p inhibitor co-treatment induced autophagy and apoptosis, and enhanced CXCR4 expression. si-H19 decreased p-p65 phosphorylation, while si-H19 and miR-139-3p inhibitor co-treatment partially elevated p-p65 phosphorylation. In conclusion, lncRNA H19 facilitated the autophagy and apoptosis of DNPCs by the miR-139-3p/CXCR4/NF-κB axis, thereby aggravating IDD. This study may offer new insights for the management of IDD.Gene therapy is one of the promising approaches for regenerative medicine. Local and long-term expression of essential growth factors allows to achieve the desired therapeutic effect. However, some aspects of prolonged usage of genetic constructs encoding growth factors, such as toxicity, mutagenicity, genotoxicity, and ability to disseminate from the injection site and mediate ectopic expression of therapeutic proteins, are poorly investigated. These aspects of gene therapy drugs' usage became the subject of this study. To study plasmid biodistribution, toxicity, mutagenicity, and genotoxicity, we used previously described bicistronic genetic construct encoding human brain-derived neurotrophic factor (hBDNF) and human urokinase plasminogen activator (huPA) for nerve repair. Biodistribution studies were conducted in mice a course of intramuscular plasmid injections was followed by the study of the content of the plasmid (real-time polymerase chain reaction) and recombinant proteins (enzyme-linked immunosorben genetic constructs strongly depend on their sequence and delivery approach, which requires conducting of their safety studies in each specific case. Impact statement Gene therapy is one of the promising approaches for regenerative medicine. Local and long-term expression of essential growth factors allows to achieve the desired therapeutic effect. However, some aspects of prolonged usage of genetic constructs encoding growth factors, such as toxicity, mutagenicity, genotoxicity, and ability to disseminate from the injection site and mediate ectopic expression of therapeutic proteins, are poorly investigated. https://www.selleckchem.com/products/msa-2.html These aspects of gene therapy became the subject of this study. To our knowledge, this is a unique study that provides a thorough safety investigation of a bicistronic plasmid after its readministration. Functional connectivity quantifies the statistical dependencies between the activity of brain regions, measured using neuroimaging data such as functional MRI BOLD time series. The network representation of functional connectivity, called a Functional Connectome (FC), has been shown to contain an individual fingerprint allowing participants identification across consecutive testing sessions. Recently, researchers have focused on the extraction of these fingerprints, with potential applications in personalized medicine. Here, we show that a mathematical operation denominated degree-normalization can improve the extraction of FC fingerprints. Degree-normalization has the effect of reducing the excessive influence of strongly connected brain areas in the whole-brain network. We adopt the differential identifiability framework and apply it to both original and degree-normalized FCs of 409 individuals from the Human Connectome Project, in resting-state and 7 fMRI tasks. Our results indicate that degree-normalization systematically improves three fingerprinting metrics, namely differential identifiability, identification rate and matching rate. Moreover, the results related to the matching rate metric suggest that individual fingerprints are embedded in a low-dimensional space. The results suggest that low-dimensional functional fingerprints lie in part in weakly connected subnetworks of the brain, and that degree-normalization helps uncovering them. This work introduces a simple mathematical operation that could lead to significant improvements in future FCs fingerprinting studies. The results suggest that low-dimensional functional fingerprints lie in part in weakly connected subnetworks of the brain, and that degree-normalization helps uncovering them. This work introduces a simple mathematical operation that could lead to significant improvements in future FCs fingerprinting studies.
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