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1.
Transplantation ; 108(2): 483-490, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38259180

ABSTRACT

BACKGROUND: Improper opioid prescription after surgery is a well-documented iatrogenic contributor to the current opioid epidemic in North America. In fact, opioids are known to be overprescribed to liver transplant patients, and liver transplant patients with high doses or prolonged postsurgical opioid use have higher risks of graft failure and death. METHODS: This is a retrospective cohort study of 552 opioid-naive patients undergoing liver transplant at an academic center between 2012 and 2019. The primary outcome was the discrepancy between the prescribed discharge opioid daily dose and each patient's own inpatient opioid consumption 24 h before discharge. Variables were analyzed with Wilcoxon and chi-square tests and logistic regression. RESULTS: Opioids were overprescribed in 65.9% of patients, and 54.3% of patients who required no opioids the day before discharge were discharged with opioid prescriptions. In contrast, opioids were underprescribed in 13.4% of patients, among whom 27.0% consumed inpatient opioids but received no discharge opioid prescription. The median prescribed opioid daily dose was 333.3% and 56.3% of the median inpatient opioid daily dose in opioid overprescribed and underprescribed patients, respectively. Importantly, opioid underprescribed patients had higher rates of opioid refill 1 to 30 and 31 to 90 d after discharge, and the rate of opioid underprescription more than doubled from 2016 to 2019. CONCLUSIONS: Opioids are both over- and underprescribed to liver transplant patients, and opioid underprescribed patients had higher rates of opioid refill. Therefore, we proposed to prescribe discharge opioid prescriptions based on liver transplant patients' inpatient opioid consumption to provide patient-centered opioid prescriptions.


Subject(s)
Liver Transplantation , Transplants , Humans , Liver Transplantation/adverse effects , Analgesics, Opioid/adverse effects , Retrospective Studies , Prescriptions
2.
PLoS Genet ; 17(6): e1009626, 2021 06.
Article in English | MEDLINE | ID: mdl-34181637

ABSTRACT

How organisms control when to transition between different stages of development is a key question in biology. In plants, epigenetic silencing by Polycomb repressive complex 1 (PRC1) and PRC2 plays a crucial role in promoting developmental transitions, including from juvenile-to-adult phases of vegetative growth. PRC1/2 are known to repress the master regulator of vegetative phase change, miR156, leading to the transition to adult growth, but how this process is regulated temporally is unknown. Here we investigate whether transcription factors in the VIVIPAROUS/ABI3-LIKE (VAL) gene family provide the temporal signal for the epigenetic repression of miR156. Exploiting a novel val1 allele, we found that VAL1 and VAL2 redundantly regulate vegetative phase change by controlling the overall level, rather than temporal dynamics, of miR156 expression. Furthermore, we discovered that VAL1 and VAL2 also act independently of miR156 to control this important developmental transition. In combination, our results highlight the complexity of temporal regulation in plants.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Gene Expression Regulation, Developmental , MicroRNAs/genetics , Polycomb Repressive Complex 1/genetics , Polycomb Repressive Complex 2/genetics , Repressor Proteins/genetics , Alleles , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Epigenesis, Genetic , Gene Expression Regulation, Plant , MicroRNAs/metabolism , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/metabolism , Plant Shoots/genetics , Plant Shoots/growth & development , Plant Shoots/metabolism , Plants, Genetically Modified , Polycomb Repressive Complex 1/metabolism , Polycomb Repressive Complex 2/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Repressor Proteins/metabolism , Time Factors
3.
Development ; 147(8)2020 04 27.
Article in English | MEDLINE | ID: mdl-32198155

ABSTRACT

In Arabidopsis, loss of the carboxypeptidase ALTERED MERISTEM PROGRAM1 (AMP1) produces an increase in the rate of leaf initiation, an enlarged shoot apical meristem and an increase in the number of juvenile leaves. This phenotype is also observed in plants with reduced levels of miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, suggesting that AMP1 might promote SPL activity. However, we found that the amp1 mutant phenotype is only partially corrected by elevated SPL gene expression, and that amp1 has no significant effect on SPL transcript levels, or on the level or the activity of miR156. Although AMP1 has been reported to promote miRNA-mediated translational repression, amp1 did not prevent the translational repression of the miR156 target SPL9 or the miR159 target MYB33. These results suggest that AMP1 regulates vegetative phase change downstream of, or in parallel to, the miR156/SPL pathway, and that it is not universally required for miRNA-mediated translational repression.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/embryology , Arabidopsis/genetics , Carboxypeptidases/metabolism , MicroRNAs/metabolism , Plant Leaves/embryology , Plant Leaves/genetics , Protein Biosynthesis , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant , Genes, Plant , MicroRNAs/genetics , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Phenotype , Repressor Proteins/genetics , Repressor Proteins/metabolism , Time Factors , Transcription Factors/genetics , Transcription Factors/metabolism
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