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Methods in Molecular Biology (Clifton,... 2024Root metaproteome analysis can reveal the functions that govern plant-microbe and microbe-microbe interactions under specific environmental conditions. Efficient protein...
Root metaproteome analysis can reveal the functions that govern plant-microbe and microbe-microbe interactions under specific environmental conditions. Efficient protein extraction method from microbes associated with plant roots is crucial for the comprehensive analysis of the metaproteome. In this chapter, a straightforward protein extraction method for roots of Arabidopsis inoculated with a microbial community that uses only milligrams of tissue is outlined. In addition, the plant inoculation using a synthetic community (SynCom) and the methods for a nanoflow liquid chromatography coupled to a high-resolution/high-accuracy mass spectrometer (LC-MS/MS) are described.
Topics: Arabidopsis; Plant Roots; Proteomics; Tandem Mass Spectrometry; Chromatography, Liquid; Workflow; Bacteria; Proteome
PubMed: 38941015
DOI: 10.1007/978-1-0716-3910-8_7 -
Journal of Pediatric Orthopedics Jun 2024Posterior spinal fusion (PSF) and hip reconstruction are commonly indicated surgeries in children with cerebral palsy (CP), particularly those functioning at GMFCS...
BACKGROUND
Posterior spinal fusion (PSF) and hip reconstruction are commonly indicated surgeries in children with cerebral palsy (CP), particularly those functioning at GMFCS levels IV and V. These are large and often painful procedures, and previous literature suggests that hip surgery is more painful than spine surgery in this patient population. The purpose of this study is to investigate pain scores and opioid use following hip and spine surgery in a large cohort of children with CP, including many patients who have undergone both types of surgery.
METHODS
A retrospective chart review was performed to identify children with CP who underwent hip reconstruction and/or PSF at a tertiary children's hospital between 2004 and 2022. Charts were reviewed for demographic data, pain scores, pain medication usage, duration of hospital stay, and complications.
RESULTS
Data were collected for 200 patients (101 male, 99 female) who met inclusion criteria. Eighty-seven patients underwent hip reconstruction, 62 spinal fusion, and 51 both hip and spine surgery asynchronously. Median (interquartile range) age at the time of surgery was significantly older for spinal fusion compared with hip surgery [13.1 (4.9) vs. 8.1 (5.7) y, P<0.0001]. Length of stay was significantly longer after PSF, with a median of 6 (4) days compared with 2 (1) days after hip surgery (P<0.0001). Both maximum and average daily pain scores were similar following hip and spine surgery, with the exception that average pain scores for hip surgery were slightly higher on postoperative day 1, hip=1.73 vs. spine=1.0 (P<0.0001). The amount of opioids used, expressed as morphine milligram equivalents (MME)/kg were similar in the hip and spine surgery groups; however, it was significantly lower in the hip surgery group on postoperative day 0, hip=0.06 versus spine=0.17 (P<0.0001). For the 51 patients who underwent both hip and spine surgery, the amount of opioids used mirrored that for the entire group (similar MME/kg, though only statistically significantly less on POD 0 and 3), and pain scores were not significantly different between the 2 groups except in 2 circumstances. The 2 exceptions in these 51 patients both demonstrated lower pain scores in patients after hip surgery, including lower maximum pain scores on POD 1 (P=0.041), and lower average pain scores on POD3 (P=0.043).
CONCLUSIONS
This is the largest series to date comparing postoperative pain in children with CP after hip and spine surgery, including 51 of 200 patients who underwent both types of surgery. The results of this study demonstrate that hip surgery is not more painful than spine surgery in children with CP, and conflict with the traditional belief that hip surgery is more painful. This is important information for health care providers when counseling patients and families regarding these surgeries in children with CP.
LEVEL OF EVIDENCE
Level 3.
PubMed: 38934603
DOI: 10.1097/BPO.0000000000002762 -
Cureus May 2024The opioid-abuse epidemic is a problem that continues to persist world-wide. As such, appropriately evaluating and treating such patients is crucial, especially when...
The opioid-abuse epidemic is a problem that continues to persist world-wide. As such, appropriately evaluating and treating such patients is crucial, especially when considering the various complications that may arise. In rare cases, opioid overdoses can be complicated by compartment syndrome, rhabdomyolysis, and acute renal failure. All three of these complications can result in life threatening emergencies. We present a case of a 38-year-old male who was brought to the emergency department after reportedly being found lying on the ground for an unknown period of time from suspected heroin overdose. He was initially treated with 2 milligrams (mg) of intramuscular naloxone en route via emergency medical services with appropriate response. Shortly after arrival to the emergency department, the patient complained of severe right lower extremity pain, paresthesia and paralysis. Patient developed acute lower extremity compartment syndrome that was further complicated by rhabdomyolysis and acute renal failure. While emergency medicine physicians are familiar with the common complications of heroin overdose including mental status changes, respiratory depression and gastrointestinal symptoms, they must also be familiar with the less common ones. Notably, acute compartment syndrome. Compartment syndrome is ultimately a clinical diagnosis and warrants emergent surgical consultation. Every patient presenting to the emergency department warrants a complete, thorough physical examination to evaluate for any and all life-threatening conditions, regardless of the presenting complaint.
PubMed: 38933622
DOI: 10.7759/cureus.61144 -
Journal of Diabetes and Metabolic... Jun 2024Prior research has yielded mixed results regarding the impact of acarbose intake on glycemic markers. To provide a more comprehensive analysis, a systematic review and... (Review)
Review
PURPOSE
Prior research has yielded mixed results regarding the impact of acarbose intake on glycemic markers. To provide a more comprehensive analysis, a systematic review and meta-analysis was performed to compile data from various randomized controlled trials (RCTs) examining the effects of acarbose intake on fasting blood sugar (FBS), insulin, hemoglobin A1C (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) in adults.
METHODS
To identify relevant literature up to April 2023, a comprehensive search was conducted on various scholarly databases, including PubMed, Web of Science, and Scopus databases. The effect size of the studies was evaluated using a random-effects model to calculate the weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity between studies was assessed using Cochran's Q test and I.
RESULTS
This systematic review and meta-analysis included a total of 101 RCTs with a total of 107 effect sizes. The effect sizes for FBS in milligrams per deciliter (mg/dl), insulin in picomoles per liter (pmol/l), hemoglobin A1C (HbA1c) in percentage (%), and homeostasis model assessment of insulin resistance (HOMA-IR) were 92, 46, 80, and 22, respectively. The pooled analysis indicated that acarbose intake resulted in significant decreases in FBS ( = 0.018), insulin ( < 0.001), HbA1c ( < 0.001), and HOMA-IR ( < 0.001).
CONCLUSION
The findings of this systematic review and meta-analysis suggest that acarbose intake can potentially lead to significant improvements in glycemic parameters by decreasing the levels of FBS, HbA1c, and insulin. However, larger and more rigorously designed studies are still needed to further evaluate and strengthen this association.
PubMed: 38932875
DOI: 10.1007/s40200-023-01336-9 -
Pharmaceuticals (Basel, Switzerland) May 2024Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of...
Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of in vivo and in vitro studies have demonstrated that also has anticancer activity in multiple types of cancers. After oral administration, the phenylketone moiety of is rapidly reduced to the hydroxyl group to form the chiral hydroxy metabolite (). To the best of our knowledge, there is no information in the literature on the stereochemical course of transformation and the anthelmintic and antitumor activity of individual enantiomers of . In the present study, we describe in detail the direct HPLC resolution of on a 100 mm × 4.6 mm Chirapak IG-3 column packed with 3 μm silica particles containing amylose (3-chloro-5-methylphenylcarbamate) as a selector. At 25 °C and using pure methanol as the mobile phase, the enantioseparation and resolution factors were 2.38 and 6.13, respectively. These conditions were scaled up at a semi-preparative scale using a 250 mm × 10 mm Chiralpak IG column to isolate multi-milligram amounts of both enantiomeric forms of the chiral metabolite. The chiroptical properties of the collected enantiomers were determined and, through a theoretical study, were related to the more stable conformations of MBZ-OH. The first and second eluted enantiomers were dextrorotatory and levorotatory, respectively, in dimethylformamide solution. Finally, by recording the retention factors of the enantiomers as the water content in the water-acetonitrile mobile phases was progressively varied, U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography retention mechanism on the Chirapak IG-3 chiral stationary phase.
PubMed: 38931363
DOI: 10.3390/ph17060696 -
Methods in Molecular Biology (Clifton,... 2024The continuous improvement of expression platforms is necessary to respond to the increasing demand for recombinant proteins that are required to carry out structural or...
The continuous improvement of expression platforms is necessary to respond to the increasing demand for recombinant proteins that are required to carry out structural or functional studies as well as for their characterization as biotherapeutics. While transient gene expression (TGE) in mammalian cells constitutes a rapid and well-established approach, non-clonal stably transfected cells, or "pools," represent another option, which is especially attractive when recurring productions of the same protein are required. From a culture volume of just a few liters, stable pools can provide hundreds of milligrams to gram quantities of high-quality secreted recombinant proteins.In this chapter, we describe a highly efficient and cost-effective procedure for the generation of Chinese Hamster Ovary cell stable pools expressing secreted recombinant proteins using commercially available serum-free media and polyethylenimine (PEI) as the transfection reagent. As a specific example of how this protocol can be applied, the production and downstream purification of recombinant His-tagged trimeric SARS-CoV-2 spike protein ectodomain (SmT1) are described.
Topics: CHO Cells; Cricetulus; Animals; Recombinant Proteins; Transfection; Polyethyleneimine; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Cricetinae; Culture Media, Serum-Free
PubMed: 38926275
DOI: 10.1007/978-1-0716-3878-1_7 -
British Journal of Clinical Pharmacology Jun 2024The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However,...
Low-dose pegylated recombinant human granulocyte-colony stimulating factor as hematopoietic support for adjuvant chemotherapy in Chinese patients with breast cancer: An open-label, randomized, non-inferiority trial.
AIMS
The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However, for Eastern Asians, the optimal dose remains unknown.
METHODS
This open-label, randomized, non-inferiority trial (NCT05283616) enrolled Chinese female breast cancer patients receiving adjuvant chemotherapy. Participants were randomized to receive either 3 or 6 mg of PEG-rhG-CSF per cycle, stratified by body weight (BW; ≤60 kg vs. >60 kg). The primary endpoint was timely absolute neutrophil count (ANC) recovery before the second cycle of chemotherapy.
RESULTS
A total of 122 patients were randomized and 116 were included for efficacy analyses. The timely ANC recovery rate in the 3 mg arm was 89.8%, compared to 93.0% in the 6 mg arm (one-sided 95% confidence interval [CI] lower limit for difference: -11.7%), meeting the prespecified non-inferiority margin of 15%. The rate was 93.3% with PEG-rhG-CSF 3 mg and 96.6% with 6 mg in patients with BW ≤ 60 kg, and 86.2% and 89.3%, respectively, in those with BW > 60 kg. Although the incidence of severe neutropenia was similar across arms, the occurrence of excessively high ANC and white blood cell counts was higher in the 6 mg arm. No grade ≥3 adverse events related to PEG-rhG-CSF occurred.
CONCLUSION
Three milligrams of PEG-rhG-CSF per cycle provided non-inferior neutrophil protection and attenuated neutrophil overshoot compared to 6 mg doses. This low-dose regimen could be a new supportive care option for Chinese breast cancer patients receiving anthracycline-based adjuvant chemotherapy.
PubMed: 38925586
DOI: 10.1111/bcp.16151 -
JAMA Network Open Jun 2024Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing,...
IMPORTANCE
Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing, data are needed to define the procedures and populations for which most opioid prescribing occurs.
OBJECTIVE
To identify the surgical procedures accounting for the highest proportion of opioids dispensed to adults after surgery in the United States.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional analysis of the 2020-2021 Merative MarketScan Commercial and Multi-State Databases, which capture medical and pharmacy claims for 23 million and 14 million annual privately insured patients and Medicaid beneficiaries, respectively, included surgical procedures for individuals aged 18 to 64 years with a discharge date between December 1, 2020, and November 30, 2021. Procedures were identified using a novel crosswalk between 3664 Current Procedural Terminology codes and 1082 procedure types. Data analysis was conducted from November to December 2023.
MAIN OUTCOMES AND MEASURES
The total amount of opioids dispensed within 3 days of discharge from surgery across all procedures in the sample, as measured in morphine milligram equivalents (MMEs), was calculated. The primary outcome was the proportion of total MMEs attributable to each procedure type, calculated separately among procedures for individuals aged 18 to 44 years and those aged 45 to 64 years.
RESULTS
Among 1 040 934 surgical procedures performed (mean [SD] age of patients, 45.5 [13.3] years; 663 609 [63.7%] female patients), 457 016 (43.9%) occurred among individuals aged 18 to 44 years and 583 918 (56.1%) among individuals aged 45 to 64 years. Opioid prescriptions were dispensed for 503 058 procedures (48.3%). Among individuals aged 18 to 44 years, cesarean delivery accounted for the highest proportion of total MMEs dispensed after surgery (19.4% [11 418 658 of 58 825 364 MMEs]). Among individuals aged 45 to 64 years, 4 of the top 5 procedures were common orthopedic procedures (eg, arthroplasty of knee, 9.7% of total MMEs [5 885 305 of 60 591 564 MMEs]; arthroscopy of knee, 6.5% [3 912 616 MMEs]).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of the distribution of postoperative opioid prescribing in the United States, a small number of common procedures accounted for a large proportion of MMEs dispensed after surgery. These findings suggest that the optimal design and targeting of surgical opioid stewardship initiatives in adults undergoing surgery should focus on the procedures that account for the most opioid dispensed following surgery over the life span, such as childbirth and orthopedic procedures. Going forward, systems that provide periodic surveillance of opioid prescribing and associated harms can direct quality improvement initiatives to reduce opioid-related morbidity and mortality.
Topics: Humans; Analgesics, Opioid; Adult; Female; Middle Aged; Male; Cross-Sectional Studies; Pain, Postoperative; Practice Patterns, Physicians'; Patient Discharge; United States; Adolescent; Young Adult; Drug Prescriptions; Surgical Procedures, Operative
PubMed: 38922619
DOI: 10.1001/jamanetworkopen.2024.17651 -
Pediatrics Jun 2024Surgery is one of the most common indications for opioid prescribing to pediatric patients. We identified which procedures account for the most pediatric surgical opioid...
BACKGROUND AND OBJECTIVES
Surgery is one of the most common indications for opioid prescribing to pediatric patients. We identified which procedures account for the most pediatric surgical opioid prescribing.
METHODS
We conducted a cross-sectional analysis of commercial and Medicaid claims in the Merative MarketScan Commercial and Multi-State Medicaid Databases. Analyses included surgical procedures for patients aged 0 to 21 years from December 1, 2020, to November 30, 2021. Procedures were identified using a novel crosswalk between 3664 procedure codes and 1082 procedure types. For each procedure type in the crosswalk, we calculated the total amount of opioids in prescriptions dispensed within 3 days of discharge from surgery, as measured in morphine milligram equivalents (MMEs). We then calculated the share of all MMEs accounted for by each procedure type. We conducted analyses separately among patients aged 0 to 11 and 12 to 21 years.
RESULTS
Among 107 597 procedures for patients aged 0 to 11 years, the top 3 procedures accounted for 59.1% of MMEs in opioid prescriptions dispensed after surgery: Tonsillectomy and/or adenoidectomy (50.3%), open treatment of upper extremity fracture (5.3%), and removal of deep implants (3.5%). Among 111 406 procedures for patients aged 12 to 21 years, the top 3 procedures accounted for 33.1% of MMEs: Tonsillectomy and/or adenoidectomy (12.7%), knee arthroscopy (12.6%), and cesarean delivery (7.8%).
CONCLUSIONS
Pediatric surgical opioid prescribing is concentrated among a small number of procedures. Targeting these procedures in opioid stewardship initiatives could help minimize the risks of opioid prescribing while maintaining effective postoperative pain control.
PubMed: 38919985
DOI: 10.1542/peds.2024-065814 -
Hospital Pharmacy Aug 2024Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg. To describe the dose, clinical...
Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg. To describe the dose, clinical course, and outcomes for inadvertent metformin ingestions in children 5 years old and younger reported to our statewide poison center network. We searched the poison center database 2011 to 2021 for metformin ingestions in patients 5 years and younger. Variables included age, sex, weight, dose, symptoms, outcome, and more. We used descriptive statistics with medians and interquartile ranges (IQR) for continuous variables. Of 669 cases, exposures by age were 208 (31.1%) 1 to 2 years, and 275 (41.1%) 2 years. Weight was recorded in 342 (51.1%) (median 13.5 kg; IQR: 3.7 kg), and dose in 149 (22.3%) (median 500 mg; IQR: 500 mg). Milligram/kilogram values were available for 103 (15.4%) with median 42.4 mg/kg, IQR: 39 mg/kg. Most (647, 98.5%) exposures were unintentional. Most (445/669, 66.5%) were managed at a non-healthcare facility, while 204 (30.7%) were already at or referred to a healthcare facility. Of these 204 patients, 169 (82.8%) were evaluated and treated at the emergency department and discharged. Four (2%) were admitted to critical care, and 7 (3.4%) to the ward. Medical outcomes by effect were 5 (0.7%) minor, 2 (0.3%) moderate, 253 (37.8%) none, 292 (43.6%) not followed (minimal effects possible), and no major effects or deaths. Of 20 clinical occurrences reported, vomiting was most common (8, 1.2%). Despite little recorded dosage information, pediatric metformin ingestions under 85 mg/kg had predominantly uneventful medical outcomes.
PubMed: 38919762
DOI: 10.1177/00185787241230628