The top 14 treatment uncertainties around the treatment of eczema provide guidance for researchers and funding bodies to ensure that future research answers questions that are important to both clinicians and patients.
During development, an organism undergoes many rounds of pattern formation, generating ever-greater complexity with each ensuing round of cell division and specification. The instructions for executing this process are encoded in the cis-regulatory modules that direct the expression of developmental transcription factors and signaling molecules. Each transcription factor binding site within a cis-regulatory module contributes information about when, where, or how much a gene is turned on, and by dissecting the modules driving a given gene, all the inputs governing expression of the gene can be accurately identified. Furthermore, by mapping the output of each gene to the inputs of other genes, it is possible to reverse engineer developmental circuits and even whole networks. At this higher level of organization, common bilaterian strategies for specifying progenitor fields, locking down regulatory states, and driving development forward emerge.
An essential node in the gene regulatory network (GRN) for endomesoderm specification in the sea urchin embryo lies within the regulatory system of the otx gene. According to the predictions of the GRN, based on perturbation analysis and expression data, the beta1/2 transcription unit of this gene is engaged during specification in interactions with two other regulatory genes, krox and gatae. It is predicted to be driven into activity by the krox gene, to form a positively reinforcing functional loop with the gatae gene, and to respond to its own output as well. Here we isolate the relevant otx cis-regulatory element, and examine the specific input predictions of the GRN at the level of its genomic DNA sequence. This beta1/2-otx regulatory module performs the necessary functions, as shown by use of expression constructs. It requires gatae, otx, and krox inputs, as predicted, and it operates as an "AND" logic processor in that removal of any one of these inputs essentially destroys activity. The necessary target sites were identified in the module sequence, and mutation of these sites was demonstrated to produce the same respective effects on construct expression as does blocking its regulatory inputs by treatment with morpholino antisense oligonucleotides. For spatial expression in the endoderm, one particular pair of Gata sites is essential and these function synergistically with an adjacent Otx site. We thus demonstrate directly the structure/function relationships of the genomic regulatory code, at this key node of the endomesoderm GRN.
A total of 38 patients met inclusion criteria, and mirtazapine was most commonly used (42%). There was no significant difference between groups of appetite-stimulating medications with regard to mean change in meal intake, weight, albumin, or documented improvement in diet. Within groups, each agent showed numerical improvement in percentage meal intake, with a mean change from initiation to discontinuation of 17.12%. Almost half (48%) of the patients experienced improvement in diet after the start of medications. No serious adverse effects were observed. Conclusion and Relevance: In inpatients, there was no difference in change in meal intake or weight between dronabinol, megestrol, or mirtazapine, but they may show numerical improvements in meal intake. To our knowledge, this is the first study to evaluate the use of dronabinol, megestrol, and mirtazapine initiated in the inpatient setting.
BackgroundPrescription opioids have been linked to over half of the 28,000 opioid overdose deaths in 2014. High rates of prescription opioid non-medical use have continued despite nearly all states implementing large-scale prescription drug monitoring programs (PDMP), which points to the need to examine the impact of state PDMP’s on curbing inappropriate opioid prescribing. In the short-term, PDMPs have been associated with short-term prescribing declines. Yet little is known about how such policies differentially impact patient subgroups or are interpreted by prescribing providers. Our objective was to compare volumes of prescribed opioids before and after Indiana implemented opioid prescribing emergency rules and stratify the changes in opioid prescribing by patient and provider subgroups.MethodsAn interrupted time series analysis was conducted using data obtained from the Indiana PDMP. Prescription level data was merged with census data to characterize patient socioeconomic status. Analyses were stratified by patients’ gender, age, opioid dosage, and payer. The primary outcome indicator was the total morphine equivalent dose (MED) of dispensed opioids per day in the state of Indiana. Also considered were number of unique patients, unique providers, and prescriptions; MED per transaction and per day; and number of days supplied.ResultsAfter controlling for time trends, we found that total MED for opioids decreased after implementing the new emergency rules, differing by patient gender, age, and payer. The effect was larger for males than females and almost 10 times larger for 0–20 year olds as compared to the 60+ age range. Medicare and Medicaid patients experienced more decline in prescribing than patients with private insurance. Patients with prescriptions paid for by workers’ comp experienced the most significant decline. The emergency rules were associated with decline in both the number of prescribers and the number of day supply.ConclusionsAlthough the Indiana opioid prescribing emergency rules impacted statewide prescribing behavior across all individual patient and provider characteristics, the emergency rules’ effect was not consistent across patient characteristics. Further studies are needed to assess how individual patient characteristics influence the interpretation and application of state policies on opioid prescribing.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.