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arker trajectories and clinical outcomes in the era of near-universal adoption of electronic health records.BACKGROUND Prescription opioid overprescribing is a focal point for legislators, but little is known about opioid prescribing patterns of primary care nurse practitioners (NPs) and physician assistants (PAs). OBJECTIVE To identify prescription opioid overprescribers by comparing prescribing patterns of primary care physicians (MDs), nurse practitioners (NPs), and physician assistants (PAs). DESIGN Retrospective, cross-sectional analysis of Medicare Part D enrollee prescription data. PARTICIPANTS Twenty percent national sample of 2015 Medicare Part D enrollees. MAIN MEASURES We identified potential opioid overprescribing as providers who met at least one of the following (1) prescribed any opioid to > 50% of patients, (2) prescribed ≥ 100 morphine milligram equivalents (MME)/day to > 10% of patients, or (3) prescribed an opioid > 90 days to > 20% of patients. KEY RESULTS Among 222,689 primary care providers, 3.8% of MDs, 8.0% of NPs, and 9.8% of PAs met at least one definition of overprescribing. 1.3% of MDs, 6.3% of NPs, and 8.8% of PAs prescribed an opioid to at least 50% of patients. NPs/PAs practicing in states with independent prescription authority were > 20 times more likely to overprescribe opioids than NPs/PAs in prescription-restricted states. CONCLUSIONS Most NPs/PAs prescribed opioids in a pattern similar to MDs, but NPs/PAs had more outliers who prescribed high-frequency, high-dose opioids than did MDs. Efforts to reduce opioid overprescribing should include targeted provider education, risk stratification, and state legislation.INTRODUCTION N6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown. MATERIALS AND METHODS We investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. RESULTS m6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC. CONCLUSIONS Our study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC.Cytochrome p450-mediated metabolism of GRS (indolinone antiaggregant) and its effects on activities of cytochrome p450 isoenzymes were studied. Inhibition of 6 isomers of cytochrome p450 in human liver microsomes was studied with the use of specific substrates. It was found that human liver cytochrome p450 enzymes could not induce degradation of GRS and that GRS was not an inductor or inhibitor of cytochrome p450 family members 1A2, 2C9, 2C19, 2D6, 2C8, and 3A4. Hence, clinical use of the prospective antiaggregant would not involve the risk of uncontrolled fluctuations in GRS concentrations in the organism because of interactions between the drugs.The specific features of interactions between megakaryocytic and granulocytic hematopoiesis lineages and myelofibrosis were studied in patients with active phase (before treatment) of chronic myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. In patients with chronic myeloid leukemia, a direct correlation was found between the severity of both early and advanced myelofibrosis and the number of megakaryocytes in the bone marrow irrespectively of the type of the bone marrow tumor. The parameters of granulocytic hematopoiesis lineage were higher in myelofibrosis. In patients with chronic lymphocytic leukemia and multiple myeloma, negative correlations between the severity of early and advanced myelofibrosis and the number of megakaryocytes in the bone marrow and platelets in the peripheral blood were found. In chronic lymphocytic leukemia, negative correlations between the severity of early and advanced myelofibrosis and the number of neutrophils in the bone marrow and peripheral blood were detected. In patients with multiple myeloma, negative correlations between the severity of advanced myelofibrosis and number of neutrophils in the bone marrow and peripheral blood were detected.We investigate biodistribution of gallium-labeled hydroxyethylidenediphosphonic acid (68Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (68Ga-DTPMP) in intact Wistar rats. It was shown that 68Ga-DTPMP accumulated mainly in the bone tissue providing high femur/blood and femur/muscle ratios and had high stability in vivo. In contrast, 68Ga-HEDP was characterized by low stability and high uptake of radioactivity in blood throughout the study. So 68Ga-DTPMP can be considered as a new prospective radiotracer in oncology for imaging bone tissue metastasis by positron emission tomography.We studied the possibility of developing an autism model based on chronic prenatal psychological stress caused by variable frequency ultrasound 20-45 kHz. The offspring of female rats stressed during pregnancy demonstrated reduced time of social contacts in the social interaction test, increased anxiety in the open-field test, and memory impairment in the Morris water maze test in comparison with the control (intact) rat offspring. We also found a reducing trend in the BDNF gene expression in the amygdala in males of the experimental group. The results showed the possibility of developing the animal autism model based on prenatal stress.Previously, we established a 1H NMR metabolomics method using reversed-phase solid-phase extraction column (RP-SPEC), and succeeded in distinguishing wild from cultivated samples of Saposhnikoviae radix (SR), and between SR and its substitute, Peucedanum ledebourielloides root (PR). Herein, we performed LC-HR/MS metabolomics using fractions obtained via RP-SPEC to identify characteristic components of SR and PR. One and three characteristic components were respectively found for SR and PR; these components were isolated with their m/z values and retention times as a guide. The characteristic component of SR was identified as 4'-O-β-D-glucosyl-5-O-methylvisamminol (1), an indicator component used to identify SR in the Japanese Pharmacopoeia. In contrast, the characteristic components of PR were identified as xanthalin (2), 4'-O-β-D-apiosyl (1 → 6)-β-D-glucosyl-5-O-methylvisamminol (3), and 3'-O-β-D-apiosyl (1 → 6)-β-D-glucosylhamaudol (4) based on spectroscopic data such as 1D- and 2D-NMR, MS, and specific optical rotation. Among them, 4 is a novel compound. For the correlation between the NMR metabolomics results in the present and our previous report, only 1 and 2 were found to correlate with the chemical shifts, and the other compounds had no correlation. As the chemical shifts for compounds 1, 3, and 4 were similar to each other, especially for the aglycone moiety, they could not be distinguished because of the sensitivity and resolution of 1H NMR. Accordingly, combining NMR and LC/MS metabolomics with their different advantages is considered useful for metabolomics of natural products. The series of methods used in our reports could aid in quality evaluations of natural products and surveying of marker components.Fragile X-related protein 1 (FXR1) is a member of the fragile X family of RNA-binding proteins, which regulates a number of neurological and neuropsychiatric disorders such as fragile X syndrome, and is expected as a novel therapeutic target for some psychiatric diseases. However, it is unknown how FXR1 changes and functions in post-traumatic stress disorder (PTSD), a common mental disorder related to trauma and stressor. In this study, we characterized the expression pattern of FXR1 in the pathophysiological process of PTSD and further investigated the possible mechanism underlying these changes by finding an upstream regulator, namely miRNA-132 (miR-132). this website Furthermore, we verified whether miR-132 silence had an effect on the PTSD-like behaviors of single prolonged stress (SPS) rats through open field test, forced swimming test, and water maze test. At last, we examined the expression levels of PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We showed that the levels of FXR1 and fragile X mental retardation protein (FMRP), an autosomal homolog of FXR1, were decreased in the hippocampus of PTSD rats, but the levels of PSD95 and synapsin I were increased, which could be reversed by downregulation of miR-132. The results revealed that miR-132 could modulate PTSD-like behaviors in rats following SPS through regulating FXR1 and FMRP.The goal of the current study was to test associations between various ASD-related behavior problems and negative peer experiences in adolescents with ASD. Data were obtained from the Bullying and School Experiences of Children with ASD Survey completed by parents in the Interactive Autism Network (IAN). The current study focused on data from 279 parents of 7th-11th graders with ASD who spent at least half of the school day in a general education setting. Logistic regression analyses found that frequent meltdowns, poor hygiene, rigid rule-keeping, and self-injury were associated with negative peer experiences. Surprisingly, repetitive behaviors and verbal tics were associated with a lower likelihood of experiencing verbal victimization.Animal-Assisted Therapy (AAT) is an intervention for children with Autism Spectrum Disorder (ASD). This study explores parent perspectives of the impact of five AAT sessions involving trained dogs with their children with ASD. A phenomenological qualitative approach was used to explore first-hand perspectives of parents. In-depth, semi-structured interviews were conducted. Data were analyzed using thematic analysis. Seventeen parents reported that the presence of the dogs facilitated their children's engagement, enjoyment, and motivation. Parents also reported that this contributed to gains in the child's communication with others and the dog (n = 11, 64.7%), behavioral regulation (n = 12, 70.6%), and community participation (n = 14, 82.3%). These findings indicate that parents supported the use of AAT and that dogs facilitated therapeutic gains.