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β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo

Sci Rep. 2022 Nov 10;12(1):19199. doi: 10.1038/s41598-022-23842-1.

ABSTRACT

Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP-DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.

PMID:36357780 | DOI:10.1038/s41598-022-23842-1

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Hydroxychloroquine dose: balancing toxicity and SLE flare risk

Nat Rev Rheumatol. 2022 Nov 10. doi: 10.1038/s41584-022-00868-3. Online ahead of print.

NO ABSTRACT

PMID:36357774 | DOI:10.1038/s41584-022-00868-3

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Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis

Bone Marrow Transplant. 2022 Nov 10. doi: 10.1038/s41409-022-01865-6. Online ahead of print.

ABSTRACT

The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.

PMID:36357773 | DOI:10.1038/s41409-022-01865-6

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Exploring the Health and Economic Burden Among Truck Drivers in Australia: A Health Economic Modelling Study

J Occup Rehabil. 2022 Nov 10. doi: 10.1007/s10926-022-10081-4. Online ahead of print.

ABSTRACT

Background The transport and logistics industry contributes to a significant proportion of the Australian economy. However, few studies have explored the economic and clinical burden attributed to poor truck driver health. We therefore estimated the work-related mortality burden among truck drivers over a 10-year period. Methods Dynamic life table modelling was used to simulate the follow-up of the Australian male working-age population (aged 15-65 years) over a 10-year period of follow-up (2021-2030). The model estimated the number of deaths occurring among the Australian working population, as well as deaths occurring for male truck drivers. Data from the Driving Health study and other published sources were used to inform work-related mortality and associated productivity loss, hospitalisations and medication costs, patient utilities and the value of statistical life year (VoSLY). All outcomes were discounted by 5% per annum. Results Over 10 years, poor truck driver health was associated with a loss of 21,173 years of life lived (discounted), or 18,294 QALYs (discounted). Healthcare costs amounted to AU$485 million (discounted) over this period. From a broader, societal perspective, a total cost of AU$2.6 billion (discounted) in lost productivity and AU$4.7 billion in lost years of life was estimated over a 10-year period. Scenario analyses supported the robustness of our findings. Conclusions The health and economic consequences of poor driver health are significant, and highlight the need for interventions to reduce the burden of work-related injury or disease for truck drivers and other transport workers.

PMID:36357754 | DOI:10.1007/s10926-022-10081-4

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Radiologists Help Each Other to Improve Efficiency by Decreasing the Time to Look Up a Patient’s Relevant Clinical History in the Electronic Medical Record

J Digit Imaging. 2022 Nov 10. doi: 10.1007/s10278-022-00726-4. Online ahead of print.

ABSTRACT

The study aims to prove that it takes less time to look up relevant clinical history from an electronic medical record (EMR) if the information is already provided in a specific space in the EMR by a fellow radiologist. Patients with complex oncological and surgical histories need frequent imaging, and every time a radiologist may spend a significant amount of time looking up the same clinical information as their peers. In collaboration with ACMIO and Radiant Epic team, a space labeled “Specialty Comments” was added to the SNAPSHOT of patient’s chart in EMR. For our research purpose, the specialty comment was labeled as boxed history as a variable for data analysis. If the history was not provided in that particular space, it was labeled as without boxed history. Inclusion criteria included outpatients with complex oncological histories undergoing CT chest, abdomen, and pelvis with IV contrast. The time to look up history (LUT) was documented in minutes and seconds. Two assistant professors from Abdominal Imaging provided LUT. A total of 85 cases were included in the study, 39 with boxed history and 46 without boxed history. Comparing averages of the individual reader means for history, mean LUT differed by 2.03 min (without boxed history) versus 0.57 min (with boxed history), p < 0.0001. The t-test and the nonparametric Wilcoxon tests for a difference in the population means were highly significant (p < 0.0001). A history directed to radiologist’s needs resulted in a statistically significant decrease in time spent by interpreting radiologists to look through the electronic medical records for patients with complex oncological histories. Availability of history pertinent to radiology has wide-ranging advantages, including quality reporting, decrease in turnaround time, reduction in interpretation errors, and radiologists’ continued learning. The space for documenting clinical history may be reproduced, or some similar area may be developed by optimizing the electronic medical records.

PMID:36357753 | DOI:10.1007/s10278-022-00726-4

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The pattern of failure after Stereotactic Radiation Therapy (SRT) for oligo-metastases: predictive factors for poly-progression

J Cancer Res Clin Oncol. 2022 Nov 10. doi: 10.1007/s00432-022-04461-9. Online ahead of print.

ABSTRACT

PURPOSE: Patients with oligo-metastatic disease (OMD) can be safely treated with Stereotactic Radiation Therapy (SRT). Further disease progression is common in these patients. In most cases, patients relapse again with oligo-metastases, however some can experience a poly-progression after a local ablative treatment (LAT). The purpose of this study was to retrospectively identify factors associated with poly-progression in patients receiving SRT for OMD.

METHODS: Data from a monocentric database were retrospectively analyzed. Patients treated with SRT for OMD and who developed progression after LAT were selected. Patients were categorized as oligo- or poly-progressive according to the number of new/progressing metastases (≤ or > 5). Herein, we analyzed data about patients’ characteristics, oligo-metastatic presentation and radiation treatment characteristics to evaluate their relationship with progression type.

RESULTS: From 2013 to 2021, data on 700 patients progressing after LAT were analyzed. Among them, 227 patients (32.4%) experienced a poly-progression; the median time to poly-progression was 7.72 months (range 1-79.6). Five variables associated with poly-progression were found to be statistically significant in the univariate analysis: performance status (p < 0.001), site of the primary tumor (p = 0.016), ablative dose (p = 0.002), treated site (p = 0.002), single or double organ (p = 0.03). Of those, all but the number of involved organs retained their significant predictive value on the multivariate analysis.

CONCLUSION: Our study identified four independent factors associated with poly-progression in patients with OMD receiving SRT. Our data may support comprehensive characterization of OMD, better understanding of factors associated with progression.

PMID:36357737 | DOI:10.1007/s00432-022-04461-9

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Colonic bowel prep and body mass index: does one size fit all? A multi-centre review

Int J Colorectal Dis. 2022 Nov 11. doi: 10.1007/s00384-022-04274-9. Online ahead of print.

ABSTRACT

PURPOSE: To investigate whether body mass index (BMI) is a risk factor for inadequate bowel preparation in elective colonoscopy. The null hypothesis being BMI does not affect bowel preparation adequacy.

METHODS: A retrospective cohort study of all participants with complete medical records who had an elective colonoscopy was conducted across three tertiary teaching hospitals in Perth, Western Australia, from January 2016 to July 2019. Participants were separated into BMI subgroups of healthy weight, overweight and obese (≥ 30 kg/m2). Data were extracted from medical records, colonoscopy and histopathology reports and were analysed using SPSS v.27.

RESULTS: Of the 1082 cases analysed, 52.7% (n = 570) were male. The median age was 61 (range 18-85 years). The median BMI was 27.8 (range 20-52). The median procedure time is 28 (range 2-69 min). Routine follow-up was the clinical indication for 65% of colonoscopy procedures undertaken during the study period. Multivariate logistic regression, controlled for statistically insignificant confounders of age, type of bowel preparation agent, grade of the endoscopist, the indication for procedure and year of procedure, showed that being obese was significantly and independently associated with inadequate bowel preparation (OR 2.0, 95% CI (1.4-2.9) p < 0.001). Another significant factor was male (OR 1.6, 95% CI (1.2-2.1) p = 0.002).

CONCLUSION: This study shows that obese patients are more likely to have inadequate bowel preparation at colonoscopy. Given the increased complication rates and health care costs associated with repeating colonoscopies and the increased risk of colorectal cancer in obese patients, it may be worth tailoring a more extensive bowel preparation regimen to ensure adequate visualisation of the colonic mucosa on the first attempt.

PMID:36357734 | DOI:10.1007/s00384-022-04274-9

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Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial

Nat Microbiol. 2022 Nov 10. doi: 10.1038/s41564-022-01262-1. Online ahead of print.

ABSTRACT

Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, double-blind placebo-controlled phase of ENSEMBLE, an international randomized efficacy trial of a single dose of Ad26.COV2.S. We also evaluated correlates of protection in the trial cohort. Of the three antibody immune markers we measured, we found most support for 50% inhibitory dilution (ID50) neutralizing antibody titre as a correlate of risk and of protection. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; P = 0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID50 (<2.7 IU50 ml-1) and increased to 89% (78%, 96%) at ID50 = 96.3 IU50 ml-1. Comparison of the vaccine efficacy by ID50 titre curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine and the COV002-UK trial of the AZD1222 vaccine supported the ID50 titre as a correlate of protection across trials and vaccine types.

PMID:36357712 | DOI:10.1038/s41564-022-01262-1

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Left-sided Hepatectomy Leads to Less Postoperative Liver Failure and Comparable Overall Survival to Right-sided Hepatectomy in Type II or IV Perihilar Cholangiocarcinoma

Ann Surg Oncol. 2022 Nov 10. doi: 10.1245/s10434-022-12756-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Right-side hepatectomy (RH) is used in oncological resection for perihilar cholangiocarcinoma (PHC); however, the decision between performing left-side hepatectomy (LH) or RH is still controversial. We compared surgical and oncologic outcomes of LH and RH in PHC type II or IV where either hepatectomy was expected to have a negative margin.

METHODS: From 2001 to 2020, 99 patients underwent major liver resection for type II or IV PHC. Patients with unilateral vascular invasion, unilateral tumor growth, and atrophy of unilateral liver were excluded. Preoperative characteristics, perioperative, and long-term outcomes were compared between the remaining RH and LH patients.

RESULTS: After excluding 47 cases with side predominance, the RH group (n = 29) and LH group (n = 23) were compared. Clinical characteristics and disease severity did not differ between the groups. Portal vein embolization (RH: 48.3% vs. LH: 0.0%, p < 0.001) and days from diagnosis to operation (RH: 31.0 ± 16.2 vs. LH: 18.8 ± 13.4, p = 0.006) were significantly higher in the RH group. The RH group had statistically higher rate of postoperative hepatic failure (RH: 55.2% vs. LH: 21.7%, p = 0.015) and a higher mortality rate that was not significant (RH: 13.8% vs. LH: 0%, p = 0.120). The R0 resection rate (RH: 72.4% vs. LH: 78.3%, p = 0.629), median disease-free (p = 0.620), and overall (p = 0.487) survival did not differ between groups. R1 resection and lymph node metastasis were significant risk factors for disease-free survival in multivariate analysis.

CONCLUSIONS: In type II or type IV PHC where either LH or RH was feasible, LH provided a shorter period of preoperative preparation, lower postoperative hepatic failure rate, similar R0 rate, and comparable long-term outcomes. LH should be considered a reasonable option in type II or IV PHC.

PMID:36357701 | DOI:10.1245/s10434-022-12756-x

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Detection of m6A from direct RNA sequencing using a multiple instance learning framework

Nat Methods. 2022 Nov 10. doi: 10.1038/s41592-022-01666-1. Online ahead of print.

ABSTRACT

RNA modifications such as m6A methylation form an additional layer of complexity in the transcriptome. Nanopore direct RNA sequencing can capture this information in the raw current signal for each RNA molecule, enabling the detection of RNA modifications using supervised machine learning. However, experimental approaches provide only site-level training data, whereas the modification status for each single RNA molecule is missing. Here we present m6Anet, a neural-network-based method that leverages the multiple instance learning framework to specifically handle missing read-level modification labels in site-level training data. m6Anet outperforms existing computational methods, shows similar accuracy as experimental approaches, and generalizes with high accuracy to different cell lines and species without retraining model parameters. In addition, we demonstrate that m6Anet captures the underlying read-level stoichiometry, which can be used to approximate differences in modification rates. Overall, m6Anet offers a tool to capture the transcriptome-wide identification and quantification of m6A from a single run of direct RNA sequencing.

PMID:36357692 | DOI:10.1038/s41592-022-01666-1