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Trends in Biotechnology Nov 2023If biomanufacturing can become a sustainable route for producing chemicals, it will provide a critical step in reducing greenhouse gas emissions to fight climate change.... (Review)
Review
If biomanufacturing can become a sustainable route for producing chemicals, it will provide a critical step in reducing greenhouse gas emissions to fight climate change. However, efforts to industrialize microbial synthesis of chemicals have met with varied success, due, in part, to challenges in translating laboratory successes to industrial scale. With a particular focus on Escherichia coli, this review examines the lessons learned when studying microbial physiology and metabolism under conditions that simulate large-scale bioreactors and methods to minimize cellular waste through reduction of maintenance energy, optimizing the stress response and minimizing culture heterogeneity. With general strategies to overcome these challenges, biomanufacturing process scale-up could be de-risked and the time and cost of bringing promising syntheses to market could be reduced.
Topics: Bioreactors; Industrial Microbiology
PubMed: 37271589
DOI: 10.1016/j.tibtech.2023.05.002 -
Molecules (Basel, Switzerland) Apr 2022A diastereoselective synthesis of the β-anomer of glycinamide ribonucleotide (β-GAR) has been developed. The synthesis was accomplished in nine steps from D-ribose and...
A diastereoselective synthesis of the β-anomer of glycinamide ribonucleotide (β-GAR) has been developed. The synthesis was accomplished in nine steps from D-ribose and occurred in 5% overall yield. The route provided material on the multi-milligram scale. The synthetic β-GAR formed was remarkably resistant to anomerization both in solution and as a solid.
Topics: Glycine; Hydroxymethyl and Formyl Transferases; Phosphoribosylglycinamide Formyltransferase; Ribonucleotides
PubMed: 35458726
DOI: 10.3390/molecules27082528 -
Chemical Science May 2022The synthesis of secondary and tertiary amines through the reductive amination of carbonyl compounds is one of the most significant reactions in synthetic chemistry.... (Review)
Review
The synthesis of secondary and tertiary amines through the reductive amination of carbonyl compounds is one of the most significant reactions in synthetic chemistry. Asymmetric reductive amination for the formation of chiral amines, which are required for the synthesis of pharmaceuticals and other bioactive molecules, is often achieved through transition metal catalysis, but biocatalytic methods of chiral amine production have also been a focus of interest owing to their selectivity and sustainability. The discovery of asymmetric reductive amination by imine reductase (IRED) and reductive aminase (RedAm) enzymes has served as the starting point for a new industrial approach to the production of chiral amines, leading from laboratory-scale milligram transformations to ton-scale reactions that are now described in the public domain. In this perspective we trace the development of the IRED-catalyzed reductive amination reaction from its discovery to its industrial application on kg to ton scale. In addition to surveying examples of the synthetic chemistry that has been achieved with the enzymes, the contribution of structure and protein engineering to the understanding of IRED-catalyzed reductive amination is described, and the consequent benefits for activity, selectivity and stability in the design of process suitable catalysts.
PubMed: 35655886
DOI: 10.1039/d2sc00124a -
Saudi Journal of Biological Sciences Jan 2021Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of... (Review)
Review
Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of polarity. They are classified into two main groups: bioemulsifier and biosurfactant, depending on their molecular weight. Microbial surfactants occur in various categories according to their chemical nature and producing organisms. These biomolecules are produced by diverse groups of microorganisms including fungi, bacteria, and yeasts. Their production is significantly influenced by substrate type, fermentation technology and microbial strains. Owing to inherent multifunctional properties and assorted synthetic aptitude of the microbes, microbial surfactants are mostly preferred than their chemical counterparts for various industrial and biomedical applications including bioremediation, oil recovery; as supplements in laundry formulations and as emulsion-stabilizers in food and cosmetic industries as well as therapeutic agents in medicine. The present review discusses on production of microbial surfactants as promising and alternative broad-functional biomolecules for various biotechnological applications.
PubMed: 33424354
DOI: 10.1016/j.sjbs.2020.10.058 -
American Journal of Preventive Medicine Sep 2022Nonopioid analgesics are more effective for most oral pain, but data suggest that dental prescribing of opioids is excessive. This study evaluates the extent to which...
INTRODUCTION
Nonopioid analgesics are more effective for most oral pain, but data suggest that dental prescribing of opioids is excessive. This study evaluates the extent to which opioids exceed recommendations and the characteristics associated with opioid overprescribing by Veterans Health Administration dentists.
METHODS
This was a national cross-sectional study of Veterans' dental visits from 2015 to 2018. Overprescribing was defined per national guidelines as >120 morphine milligram equivalents (primary outcome). The association of dental visit and patient demographic and medical characteristics was modeled with overprescribing (defined as >120 morphine milligram equivalents) using Poisson regression with clustering by facility and patient. A secondary analysis assessed opioid prescriptions >3 days' supply. The dates of analysis were January 2020‒May 2021.
RESULTS
Of the 196,595 visits, 28.7% exceeded 120 morphine milligram equivalents. Friday visits and people with chronic oral pain or substance misuse were associated with a higher prevalence of overprescribing. Women, older Veterans, and Black and Latinx Veterans were less likely to be overprescribed than men, younger Veterans, and White Veterans, respectively. Routine dental visits had a higher prevalence of opioid overprescribing than invasive visits. Opioid overprescribing decreased over time. White Veterans were more likely to receive oxycodone and hydrocodone, whereas people of Black race and Latinx ethnicity were more likely to receive codeine and tramadol. In the secondary analysis, 68.5% of opioid prescriptions exceeded a 3-day supply.
CONCLUSIONS
Nearly 1 in 3 opioids prescribed by Veterans Health Administration dentists exceed guidelines. Prescribing higher potency and quantities of opioids, especially on Fridays and to certain demographic groups, should be addressed as part of dental opioid stewardship programs.
Topics: Analgesics, Opioid; Chronic Pain; Cross-Sectional Studies; Dentists; Female; Humans; Male; Morphine Derivatives; Practice Patterns, Physicians'; Veterans Health
PubMed: 35341616
DOI: 10.1016/j.amepre.2022.01.023 -
Journal of Pediatric Rehabilitation... 2022Pregnant women with spinal cord injuries are often advised to continue oral baclofen during pregnancy to manage spasticity, though the potential for adverse events in...
BACKGROUND
Pregnant women with spinal cord injuries are often advised to continue oral baclofen during pregnancy to manage spasticity, though the potential for adverse events in neonates is not well understood.
OBJECTIVE
Here, a case is described in which a male neonate with intrauterine baclofen exposure, born at 34 3/7 weeks via Cesarean section, demonstrated a two-minute episode of extensor posturing at fifteen minutes of life possibly concerning for baclofen withdrawal. His mother had taken baclofen 30 milligrams orally four times per day throughout pregnancy for management of spasticity associated with a remote cervical spinal cord injury. Due to concern for possible withdrawal, the neonate was started on a baclofen taper beginning within hours of birth while evaluation for alterative etiologies was underway. Symptoms were monitored using the Finnegan Neonatal Abstinence Scale. The neonate tolerated the baclofen taper well and was successfully tapered off by the fourteenth day of life with full resolution of symptoms and no apparent neurologic deficits.
CONCLUSION
Further research is needed to assess the incidence of neonatal baclofen withdrawal with regard to maternal dosage and route of administration, and to determine the most appropriate monitoring and management protocols for the neonate.
Topics: Baclofen; Cesarean Section; Female; Humans; Infant, Newborn; Injections, Spinal; Male; Muscle Relaxants, Central; Muscle Spasticity; Pregnancy; Spinal Cord Injuries
PubMed: 35094999
DOI: 10.3233/PRM-210023 -
International Journal of Medical... Mar 2022The national increase in opioid use and misuse has become a public health crisis in the U.S. To tackle this crisis, the systematic evaluation and monitoring of opioid...
BACKGROUND
The national increase in opioid use and misuse has become a public health crisis in the U.S. To tackle this crisis, the systematic evaluation and monitoring of opioid prescribing patterns is necessary. Thus, opioid prescriptions from electronic health records (EHRs) must be standardized to morphine milligram equivalent (MME) to facilitate monitoring and surveillance. While most studies report MMEs to describe opioid prescribing patterns, there is a lack of transparency regarding their data pre-processing and conversion processes for replication or comparison purposes.
METHODS
In this work, we developed Opioid2MME, a SQL-based open-source framework, to convert opioid prescriptions to MMEs using EHR prescription data. The MME conversions were validated internally using F-measures through manual chart review; were compared with two existing tools, as MedEx and MedXN; and the framework was tested in an external academic EHR system.
RESULTS
We identified 232,913 prescriptions for 49,060 unique patients in the EHRs, 2008-2019. We manually annotated a sample of prescriptions to assess the performance of the framework. The internal evaluation for medication information extraction achieved F-measures from 0.98 to 1.00 for each piece of the extracted information, outperforming MedEx and MedXN (F-Scores 0.98 and 0.94, respectively). MME values in the internal EHR system obtained a F-measure of 0.97 and identified 3% of the data as outliers and 7% missing values. The MME conversion in the external EHR system obtained 78.3% agreement between the MME values obtained with the development site.
CONCLUSIONS
The results demonstrated that the framework is replicable and capable of converting opioid prescriptions to MMEs across different medical institutions. In summary, this work sets the groundwork for the systematic evaluation and monitoring of opioid prescribing patterns across healthcare systems.
PubMed: 35325663
DOI: 10.1016/j.ijmedinf.2022.104739 -
The Annals of Otology, Rhinology, and... Oct 2022Little data is available on opioid usage in the adult population for benign oropharyngeal surgery. The objective here is to evaluate opioid prescribing patterns, opioid... (Observational Study)
Observational Study
OBJECTIVES
Little data is available on opioid usage in the adult population for benign oropharyngeal surgery. The objective here is to evaluate opioid prescribing patterns, opioid consumption, and patient pain patterns following benign oropharyngeal surgery, specifically tonsillectomy and adenoidectomy, tonsillectomy alone, and expansion sphincter pharyngoplasty.
METHODS
Patients aged ≥18 years old and received a tonsillectomy, tonsillectomy and adenoidectomy, or expansion sphincter pharyngoplasty between November 2019 and August 2020 were included. Patients were provided a survey which included a visual analog scale for recording their pain postoperatively and the amount of opioid they had remaining.
RESULTS
About 103 patients completed the post-operative questionnaire. Patients were prescribed 38 837 morphine milligram equivalents and used 28 644: approximately 26% went unused, which is the equivalent of 1346 5 mg oxycodone pills. Opioid consumption correlated with the initial dosage: patients consumed 12% more narcotic on average as the initial prescription went upwards by 50 morphine milligram equivalents. Obstructive sleep apnea, history of smoking, and being female predicted increased opioid usage in this cohort. Pain was reported the highest on postoperative day 1. A prescription of approximately 225 morphine milligram equivalents (150 mg oxycodone) was associated with decreased opioid use in this cohort. Larger initial prescriptions did not result in fewer requests for refills.
CONCLUSION
A significant amount of opioid medication went unused in this study. A prescription of 225 morphine milligram equivalents (or 150 mg oxycodone) provided appropriate analgesia for the majority of patients. Larger prescriptions may result in increased opioid consumption and may not reduce the amount of refills. More study is needed to confirm these findings.
Topics: Adolescent; Adult; Analgesics, Opioid; Female; Humans; Male; Oxycodone; Pain, Postoperative; Practice Patterns, Physicians'; Prospective Studies
PubMed: 34694150
DOI: 10.1177/00034894211053290 -
Pain Medicine (Malden, Mass.) May 2021To provide clinical data for the conversion of Schedule II opioids to buprenorphine buccal film and to demonstrate sustained analgesia and a reduction in morphine...
OBJECTIVE
To provide clinical data for the conversion of Schedule II opioids to buprenorphine buccal film and to demonstrate sustained analgesia and a reduction in morphine milligram equivalents after conversion.
DESIGN
Retrospective review of electronic medical records.
SETTING
Group clinical practice providing outpatient chronic pain management care in Winston-Salem, North Carolina.
SUBJECTS
Patients who received opioids for chronic pain between January 1, 2016, and June 30, 2019, were selected for chart review if they were converted to buprenorphine buccal film from a Schedule II opioid.
METHODS
Patients who met inclusion criteria were stratified into subgroups on the basis of preconversion morphine milligram equivalents, whether they remained on opioids for breakthrough pain postconversion, and pre- and postconversion numerical rating scale pain scores. Outcomes of interest included the differences between pre- and postconversion numerical rating scale pain scores and daily morphine milligram equivalents for each subgroup.
RESULTS
Of 157 patients reviewed, 87.9% were successfully converted to buprenorphine buccal film. Overall, numerical rating scale pain scores were stable after conversion. Statistically significant reductions were demonstrated in the <90 daily morphine milligram equivalent subgroup. Postconversion daily morphine milligram equivalents decreased by 85.4% from baseline. Change in daily morphine milligram equivalents is representative of patients who remained on breakthrough pain medication.
CONCLUSIONS
Results demonstrate continued analgesia after conversion to buprenorphine buccal film despite reductions in daily morphine milligram equivalents. Most patients were able to convert directly from their long-acting opioid to buprenorphine buccal film and stabilized without the use of concomitant opioids for breakthrough pain. Aggressive titration strategies were associated with greater success.
Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Pain Management; Retrospective Studies
PubMed: 32914182
DOI: 10.1093/pm/pnaa226 -
CNS Spectrums Jun 2022Aripiprazole lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three... (Review)
Review
Aripiprazole lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three different injection intervals using four different dosage strengths. The relationship between dosage strength (milligram injected), injection interval (time between injection visits), and expected steady-state plasma aripiprazole concentrations may not be readily apparent. This article illustrates the relationship by providing visual scenarios of steady-state plasma aripiprazole concentrations for the five AL regimens. The efficacy of AL was originally demonstrated in a pivotal study of two AL regimens (approved as 441 mg monthly and 882 mg monthly). The three additional regimens (662 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months) were approved based on pharmacokinetic bridging studies and population pharmacokinetic models. For this paper, expected steady-state concentrations for each AL regimen were derived from the published population pharmacokinetic models and compared using median values and ranges. The five labeled AL regimens differ in dosage strength and injection interval; however, model-simulated concentrations illustrate that each regimen produces steady-state plasma aripiprazole concentrations within the upper and lower bounds associated with known efficacy for AL 441 mg and 882 mg administered monthly. This visual presentation of the relationship between dosage strength of the AL injection, the interval between successive injections, and steady-state aripiprazole plasma concentrations may demonstrate for clinicians how dosage strength and injection interval can be considered in selecting the AL regimen option that best fits the clinical circumstances of the individual patient.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Delayed-Action Preparations; Humans; Injections, Intramuscular
PubMed: 33267924
DOI: 10.1017/S1092852920002072