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British Journal of Anaesthesia Jul 2021Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and...
BACKGROUND
Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied.
METHODS
Surgical patients (N=740) with pathological stage I-III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database.
RESULTS
On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24-0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02-1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways.
CONCLUSIONS
Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.
Topics: Adenocarcinoma of Lung; Aged; Analgesics, Opioid; Female; Genomics; Humans; Intraoperative Care; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Pain, Postoperative; Prospective Studies; Retrospective Studies; Survival Rate
PubMed: 34147159
DOI: 10.1016/j.bja.2021.03.030 -
Cardiology Research Apr 2013Fenofibrate is a third-generation fibric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol,... (Review)
Review
Fenofibrate is a third-generation fibric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; to increase high-density lipoprotein cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia; and to reduce triglycerides in patients with severe hypertriglyceridemia. In this review, the key characteristics of available fenofibrate formulations are examined. A literature search was conducted, focusing on comparative studies examining bioavailability, food effects, absorption, and lipid efficacy. Fenofibrate is highly lipophilic, virtually insoluble in water, and poorly absorbed. Coadministration with meals was necessary to maximize bioavailability of early formulations. Micronized and nanoparticle formulations of fenofibrate with reduced particle sizes were developed, resulting in greater solubility, improved bioavailability, and in some cases, the ability to be given irrespective of food. A recently introduced hydrophilic choline salt of fenofibric acid also can be taken without regard to meals, is absorbed throughout the gastrointestinal tract, has the highest bioavailability among marketed formulations, and is approved for coadministration with a statin. Differences in bioavailability of fenofibrate formulations have resulted in low-dose (40 - 67) mg and standard-dose (120 - 200 mg) formulations. Different formulations are not equivalent on a milligram-to-milligram basis. In order to prevent medication errors, resulting in underdosing or overdosing with attendant consequences, it is important for healthcare providers to recognize that the formulations of fenofibrate and fenofibric acid that are currently available vary substantially in relation to food effect, equivalency on a milligram-to-milligram basis, and indication to be coadministered with a statin.
PubMed: 28352420
DOI: 10.4021/cr270w -
The Cochrane Database of Systematic... Jul 2007Respiratory distress syndrome is a serious complication of prematurity causing significant immediate and long-term mortality and morbidity. (Review)
Review
BACKGROUND
Respiratory distress syndrome is a serious complication of prematurity causing significant immediate and long-term mortality and morbidity.
OBJECTIVES
The objective of this review was to assess the effects of corticosteroids administered to pregnant women to accelerate fetal lung maturity prior to preterm delivery.
SEARCH STRATEGY
The Cochrane Pregnancy and Childbirth Group trials register was searched.
SELECTION CRITERIA
Randomised and quasi-randomised trials of corticosteroid drugs capable of crossing the placenta compared with placebo or no treatment in women expected to deliver preterm as a result of either spontaneous preterm labour, prelabour rupture of the membranes preterm, or elective preterm delivery.
DATA COLLECTION AND ANALYSIS
Eligibility and trial quality were assessed by one reviewer.
MAIN RESULTS
Eighteen trials including data on over 3700 babies were included. Antenatal administration of 24 milligrams of betamethasone, of 24 milligrams of dexamethasone, or two grams of hydrocortisone to women expected to give birth preterm was associated with a significant reduction in mortality (odds ratio 0.60, 95% confidence interval 0.48 to 0.75), respiratory distress syndrome (odds ratio 0.53, 95% confidence interval 0.44 to 0.63) and intraventricular haemorrhage in preterm infants. These benefits extended to a broad range of gestational ages and were not limited by gender or race. No adverse consequences of prophylactic corticosteroids for preterm birth have been identified.
AUTHORS' CONCLUSIONS
Corticosteroids given prior to preterm birth (as a result of either preterm labour or elective preterm delivery) are effective in preventing respiratory distress syndrome and neonatal mortality. However there is not enough evidence to evaluate the use of repeated doses of corticosteroids in women who remain undelivered, but who are at continued risk of preterm birth.(This abstract has been prepared centrally.).
Topics: Female; Glucocorticoids; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Respiratory Distress Syndrome, Newborn
PubMed: 17636582
DOI: 10.1002/14651858.CD000065.pub2 -
Journal of Blood Medicine 2021The prevalence of chewing and the use of ascorbic acid is increasing from time to time. Their subchronic effects on hematological indices are not well examined. The...
BACKGROUND
The prevalence of chewing and the use of ascorbic acid is increasing from time to time. Their subchronic effects on hematological indices are not well examined. The present study was aimed to investigate their subchronic effects on hematological indices in rats.
MATERIALS AND METHODS
A total of 36 adult (7-8 weeks) wild-type rats weighing between 213 and 229g were used in this study. They received extract (Ce) (100 milligrams/kilogram, 200 milligram/kilogram and 300 milligram/kilogram b.w), juice (2.5 mL/kg), ascorbic acid (AA 200 milligram/kilogram), and 2% tween 80 in distilled water (T80W- v/v) for twelve weeks. Hematological indices were measured with Sysmex KX-21. Data were analyzed by SPSS version 21.0 and Microsoft Excel.
RESULTS
Neutrocytes (p < 0.01), lymphocytes (p < 0.05), plateletcrit (p < 0.05), average size of platelets (p < 0.05), platelet size variability (p < 0.01), platelet-large cell ratio (p < 0.05) and neutrocytes/lymphocytes ratio (p < 0.001) were significantly greater, while hemoglobin concentration per red blood cell (p < 0.05) and hemoglobin concentration per volume of red blood cells were significantly reduced (p < 0.05) in rats received khat. The red cell distribution width (p < 0.05), platelet size variability (p < 0.05) and platelet-large cell ratio (p < 0.01) were significantly greater in rats received ascorbic acid.
CONCLUSION
Crude extract and juice changed some hematological indices and increased platelet activities. The platelet activity was also increased by ascorbic acid. The mechanisms for these changes need to be investigated.
PubMed: 34602828
DOI: 10.2147/JBM.S328703 -
Journal of Natural Products Jul 2021Monosaccharides play important roles in living organisms. They are present in essential glycoproteins, nucleic acids, and glycolipids as well as cell walls and bioactive...
Monosaccharides play important roles in living organisms. They are present in essential glycoproteins, nucleic acids, and glycolipids as well as cell walls and bioactive natural product glycosides and polysaccharides. Monosaccharides are optically active, and as a routine, scientists make sure that their absolute configurations are determined when new natural glycosides are isolated. Many determination methods for the absolute configuration of monosaccharides have been reported, and thus far, taking advantage of their optical rotation differences is the most used and efficient method to distinguish enantiomers. This method, however, is not very convenient, because it requires a milligram amount of each pure sample and the availability of a polarimeter. Identification methods dealing with comparison of the retention times of the d- and l-diastereomeric monosaccharide derivatives by GC, TLC values, HPLC, or UPLC have been also reported. Although effective, these methods still require sample preparation and a few milligrams of the test compounds. A new method with simple sample preparation to distinguish enantiomers of monosaccharides by analyzing the H NMR spectra of their diastereomeric derivatives has been developed. The monosaccharide components of a commercially available saponin-rich and monoglycosides have been successfully identified using this procedure.
Topics: Biological Products; Magnetic Resonance Spectroscopy; Molecular Structure; Monosaccharides; Panax; Stereoisomerism
PubMed: 34191514
DOI: 10.1021/acs.jnatprod.0c01120 -
JTCVS Open Dec 2022Enhanced Recovery After Surgery protocols are relatively new in cardiac surgery. Enhanced Recovery After Surgery addresses perioperative analgesia by implementing...
OBJECTIVE
Enhanced Recovery After Surgery protocols are relatively new in cardiac surgery. Enhanced Recovery After Surgery addresses perioperative analgesia by implementing multimodal pain control regimens that include both opioid and nonopioid components. We investigated the effects of an Enhanced Recovery After Surgery protocol at our institution on postoperative outcomes with particular focus on analgesia.
METHODS
Single-center retrospective study comparing perioperative opioid use before and after implementation of an Enhanced Recovery After Surgery protocol at our institution. Subjects were divided into 2 cohorts: Enhanced Recovery After Surgery (study group from year 2020) and pre-Enhanced Recovery After Surgery (control group from year 2018). Baseline and perioperative variables including total opioid use from the day of surgery to postoperative day 5 were collected. Opioid use was calculated as morphine milligram equivalents and compared between the 2 cohorts.
RESULTS
A total of 466 patients were included: 250 in the Enhanced Recovery After Surgery group and 216 in the pre-Enhanced Recovery After Surgery group. Both groups had similar baseline characteristics, but the Enhanced Recovery After Surgery group had significantly more subjects with intravenous drug use history ( < .0001), endocarditis ( < .0001), and liver disease ( = .007) compared with the pre-Enhanced Recovery After Surgery group. Every day from the day of surgery to postoperative day 5, the Enhanced Recovery After Surgery group had significant reduction (57%) in opioid use compared with the pre-Enhanced Recovery After Surgery group. Total opioid use for the entire length of stay was 259 morphine milligram equivalents in the Enhanced Recovery After Surgery group versus 452 morphine milligram equivalents in the pre-Enhanced Recovery After Surgery group ( < .0001). Subgroup analysis of subjects with intravenous drug use history did not demonstrate a significant reduction in opioid use.
CONCLUSIONS
Enhanced Recovery After Surgery protocols with an emphasis on multimodal pain management throughout perioperative care are associated with a significant reduction in the postoperative use of opioid analgesics.
PubMed: 36590721
DOI: 10.1016/j.xjon.2022.08.008 -
Experimental Physiology Mar 1997The question of whether there are causative or compensatory changes in placental transport physiology affecting fetal growth is considered. Reductions in uterine and... (Review)
Review
The question of whether there are causative or compensatory changes in placental transport physiology affecting fetal growth is considered. Reductions in uterine and umbilical blood flow in growth retardation will reduce maternofetal exchange of lipophilic solutes, such as O2 and CO2, but will not have a major effect on the transfer of hydrophilic solutes. These solutes are transferred across the placenta by paracellular diffusion, transporter protein-mediated transport and endocytosis-exocytosis. Neither paracellular diffusion nor endocytosis-exocytosis has been investigated in relation to fetal growth. The weight of evidence is that there is no change in the activity and expression of the syncytiotrophoblast GI UTI glucose transporter in fetal growth retardation. However, there is strong evidence that the activity of the system A amino acid transporter, per milligram of placental membrane protein, is altered in relation to fetal growth, but in a complex manner. There is also some weaker evidence that the activity of the Na(+)-H+ exchanger, per milligram of placental membrane protein, is directly related to birth-weight. There are no data for other solute transporters; a considerable amount of work still remains to be done in order to understand the relationship between placental function and fetal growth rate.
Topics: Animals; Embryonic and Fetal Development; Female; Humans; Placenta; Pregnancy; Regional Blood Flow
PubMed: 9129953
DOI: 10.1113/expphysiol.1997.sp004034 -
Biophysical Reviews Feb 2023Here I will review the development of gene expression systems for production of bovine rhodopsin in the Khorana laboratory with particular focus on stable mammalian cell... (Review)
Review
Here I will review the development of gene expression systems for production of bovine rhodopsin in the Khorana laboratory with particular focus on stable mammalian cell lines made using human embryonic kidney cells (HEK293S). The synthesis of a gene encoding bovine rhodopsin was completed in 1986. This gene was expertly designed with the built-in capacity for DNA duplex cassette replacement mutagenesis which made site-directed mutagenesis relatively straightforward. Intense effort was expended over several years in order to identify a gene expression system capable of producing rhodopsin in milligram amounts as required for biophysical studies. Mammalian expression systems, both transient and stable, were found to be the most favourable based on several criteria including receptor expression levels, correct folding and post translational processing, and capacity for purification of fully functional receptor. Transient expression using COS-1 cells was preferred for routine small-scale production of rhodopsin mutants, while HEK293S stable cell lines were used when milligram amounts of rhodopsin mutants were needed; for example, when conducting NMR studies.
PubMed: 36909956
DOI: 10.1007/s12551-022-01037-2 -
MAbs 2021Advances in antibody discovery technologies, especially with the availability of humanized mice and phage/yeast library approaches, enable the generation of a large...
Advances in antibody discovery technologies, especially with the availability of humanized mice and phage/yeast library approaches, enable the generation of a large diversity of antibodies against nearly any target of interest. As a result, there is an increasing demand for the production of larger numbers of purified antibodies at quantities (10s-100s of milligrams) sufficient for functional screening assays, drug-ability/develop-ability studies and immunogenicity assessments. To accommodate this need, new methods are required that bridge miniature high throughput/plate-based purification and conventional, one at a time, two-step purification at much larger scales. Thus, we developed a semi-automated, mid-scale (i.e., 1-75 mg) purification process that uses a combination of parallel affinity capture and automated sequential polishing to provide substantially improved throughput while delivering high purity. We optimized the affinity capture step to perform 24 monoclonal antibody purifications in parallel using a Protein Maker for 20-200 mL culture media. The eluant is transferred directly to an AKTA pure system equipped with an autosampler for sequential preparative size exclusion chromatography to remove aggregates and undesirable impurities, as well as exchange the antibody into a buffer suitable for most uses, including cell-based assays. This two-step purification procedure, together with plate-based protein analytical methods, can purify 24-48 monoclonal antibodies in <20 hours and generate up to 80 mg per sample. A stringent clean-in-place protocol for both systems and column maintenance was designed and established to minimize endotoxin contamination. This process has proven to be very reliable and robust, enabling the production of thousands of antibodies of sufficient quality and quantity that are suitable for cell-based assays, biochemical/biophysical characterization, and in vivo animal models.
Topics: Animals; Antibodies, Monoclonal; Chromatography, Affinity; Chromatography, Gel; Mice; Staphylococcal Protein A
PubMed: 34781834
DOI: 10.1080/19420862.2021.2000348 -
American Journal of Public Health Dec 2017To evaluate a community-level sodium-reduction intervention in Boston, Massachusetts. Reducing sodium in the food offerings of community settings may help reduce...
OBJECTIVES
To evaluate a community-level sodium-reduction intervention in Boston, Massachusetts. Reducing sodium in the food offerings of community settings may help reduce hypertension disparities.
METHODS
We examined changes in the proportion of prepackaged foods with greater than 200 milligrams of sodium in 7 hospitals, 8 YMCAs, 4 community health centers, and 2 organizations serving homeless populations. Research assistants documented prepackaged items in cafeterias, kiosks, and vending machines before and after the intervention (2013-2015). We assessed intervention change via linear mixed models accounting for repeated observations.
RESULTS
There were 161 access points at baseline (4347 facings) and 171 (4996 facings) at follow-up. The percentage of prepackaged products with greater than 200 milligrams of sodium decreased from 29.0% at baseline to 21.5% at follow-up (P = .003). Changes were driven by improvements in hospital cafeterias and kiosks (P = .003). The percentage of products with greater than 200 milligrams of sodium in YMCA vending decreased 58% (from 27.2% to 11.5%; P = .017); other organizations had nonsignificant declines.
CONCLUSIONS
We found modest reductions in the percentage of higher-sodium prepackaged products across community institutions. Community-level interventions may increase availability of lower-sodium products in the food supply.
Topics: Boston; Community Health Centers; Food; Food Dispensers, Automatic; Food Service, Hospital; Health Promotion; Hospitals; Humans; Hypertension; Snacks; Sodium, Dietary
PubMed: 29048959
DOI: 10.2105/AJPH.2017.304070