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Scientific Reports Jul 2024The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its...
The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.
Topics: Isoflurane; Animals; Fear; Mice; Memory Disorders; Zona Incerta; Male; Anesthetics, Inhalation; Neurons; Mice, Inbred C57BL; Dexmedetomidine; Female; Proto-Oncogene Proteins c-fos; Memory
PubMed: 38956153
DOI: 10.1038/s41598-024-66106-w -
Scientific Reports Jul 2024Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of...
Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of real-time and video-recorded pain assessment, and their agreement, in young, adult bulls undergoing surgical castration. Ten Nelore and nine Angus bulls underwent general anesthesia and surgical castration. Three-minute real-time observations and simultaneous videos were recorded at - 48 h (M0), before sedation, under fasting (M1), after surgery, 3 h after sternal recumbency (M2), after rescue analgesia (M3) and at 24 h (M4). Animals received morphine (after M2), dipyrone (after M3), and flunixin meglumine after surgical castration (M4). Two trained evaluators assessed real-time (n = 95) and video-recorded time-points (n = 95) using the Unesp-Botucatu Cattle Pain Scale (UCAPS). Both assessment methods inferred 'very good' reliability (≥ 0.81) with minimal bias, however, video-recorded assessment (4.33 ± 2.84) demonstrated slightly higher scores compared to real-time (3.08 ± 2.84). The results from this study suggest that UCAPS can be used in real-time or video-recorded to assess pain and guide analgesic therapy in cattle.
Topics: Animals; Male; Cattle; Pain Measurement; Video Recording; Orchiectomy; Reproducibility of Results; Clonixin; Pain; Morphine; Dipyrone; Pain, Postoperative
PubMed: 38956118
DOI: 10.1038/s41598-024-65890-9 -
The Journal of Pharmacology and... Jul 2024People with sickle cell disease (SCD) often experience chronic pain as well as unpredictable episodes of acute pain, which significantly affect their quality of life and...
People with sickle cell disease (SCD) often experience chronic pain as well as unpredictable episodes of acute pain, which significantly affect their quality of life and life expectancy. Current treatment strategies for SCD-associated pain primarily rely on opioid analgesics, which have limited efficacy and cause serious adverse effects. Cannabis has emerged as a potential alternative, yet its efficacy remains uncertain. In this study, we investigated the antinociceptive effects of Δ-tetrahydrocannabinol (THC), cannabis' intoxicating constituent, in male HbSS mice, which express >99% human sickle hemoglobin, and male HbAA mice, which express normal human hemoglobin A, as a control. Acute THC administration (0.1-3 mg-kg, intraperitoneal, i.p.) dose-dependently reduced mechanical and cold hypersensitivity in HbSS, but not HbAA mice. In the tail-flick assay, THC (1 and 3 mg-kg, i.p.) produced substantial antinociceptive effects in HbSS mice. By contrast, THC (1 mg-kg, i.p.) did not alter anxiety-like behavior (elevated plus maze) or long-term memory (24-h novel object recognition). Subchronic THC treatment (1 and 3 mg-kg, i.p.) provided sustained relief of mechanical hypersensitivity but led to tolerance in cold hypersensitivity in HbSS mice. Together, the findings identify THC as a possible therapeutic option for the management of chronic pain in SCD. Further research is warranted to elucidate its mechanism of action and possible interaction with other cannabis constituents. The study explores THC's efficacy in alleviating pain in sickle cell disease (SCD) using a humanized mouse model. Findings indicate that acute THC administration reduces mechanical and cold hypersensitivity in SCD mice without impacting emotional and cognitive dysfunction. Subchronic THC treatment offers sustained relief of mechanical hypersensitivity but leads to cold hypersensitivity tolerance. These results offer insights into THC's potential as an alternative pain management option in SCD, highlighting both its benefits and limitations.
PubMed: 38955494
DOI: 10.1124/jpet.124.002285 -
The Journal of Pharmacology and... Jul 2024Secondary spinal cord injury (SCI) is characterized by increased cytokines and chemokines at the site of injury that have been associated with the development of...
Secondary spinal cord injury (SCI) is characterized by increased cytokines and chemokines at the site of injury that have been associated with the development of neuropathic pain. Nearly 80% of SCI patients report suffering from chronic pain, which is poorly managed with available analgesics. While treatment with the FDA-approved β-adrenergic receptor agonist, formoterol, improves various aspects of recovery post-SCI , its effects on cytokines, chemokines and neuropathic pain remain unknown. Female mice were subjected to moderate (60 kdyn) or severe (80 kdyn) SCI followed by daily treatment with vehicle or formoterol (0.3 mg/kg, i.p.) beginning 8h after injury. The expression of pro-inflammatory cytokines/chemokines, such as IP-10, MIP-1a, MCP-1, BCA-1 and NF-κB, was increased in the injury site of vehicle-treated mice 24h post-SCI, which was ameliorated with formoterol treatment, regardless of injury severity. Thermal hyperalgesia and mechanical allodynia, as measured by Hargreaves infrared apparatus and von Frey filaments, respectively, were assessed prior to SCI and then weekly beginning 21 days post injury (DPI). While all injured mice exhibited decreased withdrawal latency following thermal stimulation compared to baseline, formoterol treatment reduced this response ~15% by 35 DPI. Vehicle-treated mice displayed significant mechanical allodynia, as evidenced by a 55% decrease in withdrawal threshold from baseline. In contrast, mice treated with formoterol maintained a consistent withdrawal time at all times tested. These data indicate that formoterol reduces inflammation post-SCI, likely contributing to mitigation of neuropathic pain, and further supporting the therapeutic potential of this treatment strategy. Chronic pain is a detrimental consequence of spinal cord injury (SCI). We show that treatment with the FDA-approved drug formoterol after SCI decreases injury site pro-inflammatory chemo/cytokines and alters markers of glial cell activation and infiltration. Additionally, formoterol treatment improves locomotor function and body composition, and decreases lesion volume. Finally, formoterol treatment decreased mechanical allodynia and thermal hyperalgesia post-SCI. These data are suggestive of the mechanism of formoterol-induced recovery, and further indicate its potential as a therapeutic strategy for SCI.
PubMed: 38955493
DOI: 10.1124/jpet.124.002171 -
Saudi Medical Journal Jul 2024To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB...
OBJECTIVES
To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT).
METHODS
A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35).
RESULTS
Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, <0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, =0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity).
CONCLUSION
A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.
Topics: Humans; Tuberculosis, Pulmonary; Male; Female; Cytokines; Adult; Middle Aged; Retrospective Studies; Interferon-gamma Release Tests; Interleukin-2; Interleukin-8; ROC Curve; Interleukin-6; Interleukin-10
PubMed: 38955446
DOI: 10.15537/smj.2024.45.7.20240310 -
Saudi Medical Journal Jul 2024To estimate the incidence of post tonsillectomy bleeding and to identify its predisposing factors among the pediatric population.
OBJECTIVES
To estimate the incidence of post tonsillectomy bleeding and to identify its predisposing factors among the pediatric population.
METHODS
A retrospective cohort study included 1280 pediatric patients (18 years or younger) who underwent tonsillectomy at King Abdullah Specialized Children Hospital, Riyadh, Saudi Arabia between 2019 and 2020. The study sample was divided into 2 groups based on the development of postoperative bleeding and were compared using Chi-square test and independent t-test. Significant variables (-value ≤0.05) were included in the logistic regression model to determine the predictors of bleeding following tonsillectomy.
RESULTS
The bleeding rate following tonsillectomy was 3.4% in 43 (95% confidence interval [CI] 2.4-4.5) patients. In the multivariable logistic regression model, the significant predictors of post tonsillectomy bleeding were age ≥12 years (odds ratio [OR]: 2.685, =0.027), decreased postoperative oral intake (OR: 4.244, =0.042), and single use of postoperative analgesia (OR: 53.124, <0.001). Out of the 43 patients, 39 (90.7%) patients experienced secondary bleeding, and more than half of the patients who developed bleeding required surgical intervention 27 (62.8%).
CONCLUSION
Tonsillectomy is a safe and common surgical procedure but carries risks for postoperative bleeding. Age ≥12 years, poor postoperative oral intake, and the use of a single postoperative analgesic increase the risk of bleeding. We encourage healthcare providers to ascertain early resumption of oral intake and ensure effective pain management. We recommend a dual alternating analgesic regimen with weight-based dosing for optimal pain control. Furthermore, educating caregivers about the importance of adequate oral intake following tonsillectomy may improve patient outcomes.
Topics: Humans; Tonsillectomy; Retrospective Studies; Postoperative Hemorrhage; Child; Incidence; Male; Female; Adolescent; Saudi Arabia; Child, Preschool; Risk Factors; Age Factors; Cohort Studies; Pain, Postoperative; Logistic Models; Infant
PubMed: 38955443
DOI: 10.15537/smj.2024.45.7.20240253 -
PloS One 2024Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological...
Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram.
BACKGROUND
Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings.
METHODS
Multichannel EEG datasets from two different sources were used in this study: (1) sedation dataset consisting of 102 healthy volunteers receiving propofol (N = 36), sevoflurane (N = 36), or dexmedetomidine (N = 30), and (2) publicly available sleep EEG dataset (N = 994). Forty-four quantitative time, frequency and entropy features were extracted from EEG recordings and were used to train the machine learning algorithms on sleep dataset to predict sleep stages in the sedation dataset. The predicted sleep states were then compared with the Modified Observer's Assessment of Alertness/ Sedation (MOAA/S) scores.
RESULTS
The performance of the model was poor (AUC = 0.55-0.58) in differentiating sleep stages during propofol and sevoflurane sedation. In the case of dexmedetomidine, the AUC of the model increased in a sedation-dependent manner with NREM stages 2 and 3 highly correlating with deep sedation state reaching an AUC of 0.80.
CONCLUSIONS
We addressed an important clinical question to identify biological sleep promoting sedatives using EEG signals. We demonstrate that propofol and sevoflurane do not promote EEG patterns resembling natural sleep while dexmedetomidine promotes states resembling NREM stages 2 and 3 sleep, based on current sleep staging standards.
Topics: Humans; Electroencephalography; Machine Learning; Hypnotics and Sedatives; Male; Adult; Female; Sleep; Propofol; Sevoflurane; Dexmedetomidine; Sleep Stages; Young Adult
PubMed: 38954679
DOI: 10.1371/journal.pone.0304413 -
Science Signaling Jul 2024Opioids trigger myelin insulation of reward circuit axons in a feedforward loop of addiction.
Opioids trigger myelin insulation of reward circuit axons in a feedforward loop of addiction.
Topics: Humans; Analgesics, Opioid; Animals; Axons; Myelin Sheath; Reward; Opioid-Related Disorders
PubMed: 38954639
DOI: 10.1126/scisignal.adr3505 -
Natural Product Research Jul 2024The ocean's vast and diverse ecosystem offers a rich reservoir of bioactive compounds with immense clinical potential. Marine organisms produce structurally unique and...
The ocean's vast and diverse ecosystem offers a rich reservoir of bioactive compounds with immense clinical potential. Marine organisms produce structurally unique and biologically active compounds, leading to breakthroughs in therapeutic development. Notable examples include anticancer agents like trabectedin and cytarabine, and the analgesic ziconotide. Marine compounds also exhibit potent antimicrobial and antiviral properties, addressing critical challenges like antibiotic resistance and emerging viral infections. Despite the promise, challenges such as sustainable harvesting and complex extraction processes persist. Advances in synthetic biology and metabolic engineering provide solutions for sustainable production, ensuring a stable supply of these valuable compounds. The integration of marine bioactives into modern medicine could revolutionize treatments for cancer, chronic pain, and infectious diseases, underscoring the need for continued investment in marine bioprospecting and biotechnological innovation.
PubMed: 38954510
DOI: 10.1080/14786419.2024.2373965 -
International Orthopaedics Jul 2024Trigger finger (TF) is a common hand condition that can be treated with surgery. We conducted a systematic review and meta-analysis to assess whether ultrasound-guided...
PURPOSE
Trigger finger (TF) is a common hand condition that can be treated with surgery. We conducted a systematic review and meta-analysis to assess whether ultrasound-guided (US-guided) percutaneous surgery is superior to other conventional surgical methods.
METHODS
We conducted a comprehensive search in Medline, Embase, and the Cochrane Library to identify relevant studies. We included randomized clinical trials (RCTs) and observational studies comparing US-guided TF release with blind percutaneous or open approaches. We combined Risk Ratios (RR) and Mean Differences (MD) with 95% Confidence Intervals (CI) across studies. Data processing and analysis were conducted using R software, version 4.3.1.
RESULTS
Our analysis included eight RCTs and two observational studies with 555 patients. US-guided surgery significantly reduced postoperative DASH scores (MD -3.75 points; 95% CI = -7.48, -0.02; p < 0.01), shortened time to resume activities (MD -11.52 days; 95% CI = -16.13, -6.91; p < 0.01), hastened discontinuation of oral analgesics (MD -4.44 days; 95% CI = -8.01, -0.87; p < 0.01), and improved patient satisfaction scores (RR 1.13; 95% CI = 1.04, 1.23; p = 0.75). There were no significant differences in VAS scores, time to movement recovery, or surgical success rate.
CONCLUSION
Ultrasound-guided percutaneous release is a safe, effective, and superior alternative for treating TF compared to other methods, leading to improved DASH scores, quicker recovery, faster cessation of oral analgesics, and enhanced patient satisfaction.
PubMed: 38953949
DOI: 10.1007/s00264-024-06243-z