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Medicine Jun 2024Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients.
METHODS
In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements.
RESULTS
The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05).
CONCLUSION
Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.
Topics: Humans; Ropivacaine; Female; Hydromorphone; Middle Aged; Nerve Block; Pain, Postoperative; Prospective Studies; Anesthetics, Local; Breast Neoplasms; Mastectomy, Modified Radical; Analgesics, Opioid; Adult; Interleukin-6; Paraspinal Muscles; Ultrasonography, Interventional; Drug Therapy, Combination; Pain Measurement
PubMed: 38941366
DOI: 10.1097/MD.0000000000038758 -
PloS One 2024Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial...
Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial neural crest cells (CNCs) that form facial bones and cartilage. We previously reported that PAE rapidly represses expression of >70 ribosomal proteins (padj = 10-E47). Ribosome dysbiogenesis causes nucleolar stress and activates p53-MDM2-mediated apoptosis. Using primary avian CNCs and the murine CNC line O9-1, we tested whether nucleolar stress and p53-MDM2 signaling mediates this apoptosis. We further tested whether haploinsufficiency in genes that govern ribosome biogenesis, using a blocking morpholino approach, synergizes with alcohol to worsen craniofacial outcomes in a zebrafish model. In both avian and murine CNCs, pharmacologically relevant alcohol exposure (20mM, 2hr) causes the dissolution of nucleolar structures and the loss of rRNA synthesis; this nucleolar stress persisted for 18-24hr. This was followed by reduced proliferation, stabilization of nuclear p53, and apoptosis that was prevented by overexpression of MDM2 or dominant-negative p53. In zebrafish embryos, low-dose alcohol or morpholinos directed against ribosomal proteins Rpl5a, Rpl11, and Rps3a, the Tcof homolog Nolc1, or mdm2 separately caused modest craniofacial malformations, whereas these blocking morpholinos synergized with low-dose alcohol to reduce and even eliminate facial elements. Similar results were obtained using a small molecule inhibitor of RNA Polymerase 1, CX5461, whereas p53-blocking morpholinos normalized craniofacial outcomes under high-dose alcohol. Transcriptome analysis affirmed that alcohol suppressed the expression of >150 genes essential for ribosome biogenesis. We conclude that alcohol causes the apoptosis of CNCs, at least in part, by suppressing ribosome biogenesis and invoking a nucleolar stress that initiates their p53-MDM2 mediated apoptosis. We further note that the facial deficits that typify PAE and some ribosomopathies share features including reduced philtrum, upper lip, and epicanthal distance, suggesting the facial deficits of PAE represent, in part, a ribosomopathy.
Topics: Animals; Neural Crest; Zebrafish; Ribosomes; Ethanol; Tumor Suppressor Protein p53; Apoptosis; Mice; Proto-Oncogene Proteins c-mdm2; Cell Nucleolus; Ribosomal Proteins; Skull; Zebrafish Proteins
PubMed: 38941348
DOI: 10.1371/journal.pone.0304557 -
ELife Jun 2024Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought...
Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here, we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPA receptor (AMPAR) or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling.
Topics: Receptors, AMPA; Animals; Action Potentials; Synapses; Neuronal Plasticity; GABAergic Neurons; Synaptic Transmission; Cells, Cultured; gamma-Aminobutyric Acid; Homeostasis
PubMed: 38941139
DOI: 10.7554/eLife.87753 -
JAMA Network Open Jun 2024Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations....
IMPORTANCE
Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations. Consequently, professional bodies advise against the use of varenicline and bupropion and recommend caution with nicotine replacement therapy (NRT). Contemporary estimates of the use of smoking cessation pharmacotherapies during pregnancy are lacking.
OBJECTIVE
To quantify the proportion of individuals using prescribed smoking cessation pharmacotherapies during pregnancy and during the first trimester specifically, in 4 countries.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study used linked birth records, hospital admission records, and dispensing records of prescribed medications from all pregnancies resulting in birth between 2015 and 2020 in New South Wales, Australia; New Zealand; Norway; and Sweden. Data analyses were conducted in October and November 2023.
EXPOSURE
Prescribed smoking cessation pharmacotherapy use (varenicline, NRT, and bupropion) during pregnancy was defined as days' supply overlapping the period from date of conception to childbirth.
MAIN OUTCOMES AND MEASURES
Prevalence of use among all pregnancies and pregnancies with maternal smoking were calculated. Among women who used a pharmacotherapy, the proportion of women with use during the first trimester of pregnancy was also calculated.
RESULTS
Among 1 700 638 pregnancies in 4 countries, 138 033 (8.1%) had maternal smoking and 729 498 (42.9%) were younger than 30 years. The prevalences ranged from 0.02% to 0.14% for varenicline, less than 0.01% to 1.86% for prescribed NRT, and less than 0.01% to 0.07% for bupropion. Among pregnant individuals who smoked, use of pharmacotherapies was up to 10 times higher, with maximum prevalences of 1.25% for varenicline in New South Wales, 11.39% for NRT in New Zealand, and 0.39% for bupropion in New Zealand. Use in the first trimester occurred among more than 90% of individuals using varenicline, approximately 60% among those using NRT, and 80% to 90% among those using bupropion.
CONCLUSIONS AND RELEVANCE
In this cohort study of pregnant individuals in 4 high-income countries, the low prevalence of varenicline and bupropion use during pregnancy and higher prevalence of NRT use aligned with current clinical guidelines. As most use occurred in the first trimester, there is a need for evidence on the risk of congenital malformations for these medications.
Topics: Humans; Female; Pregnancy; Smoking Cessation; Adult; Retrospective Studies; Smoking Cessation Agents; Varenicline; Bupropion; New Zealand; Tobacco Use Cessation Devices; Pregnancy Complications; Sweden; New South Wales; Norway; Young Adult; Smoking; Pregnancy Trimester, First
PubMed: 38941092
DOI: 10.1001/jamanetworkopen.2024.19245 -
Translational Vision Science &... Jun 2024To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PURPOSE
To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated low-level red light (RLRL) and 0.01% atropine exposure in premyopic schoolchildren.
METHODS
Prospective randomized trial. Sixty-nine schoolchildren with cycloplegic refraction >-0.75 D and ≤0.50 D were randomly assigned to RLRL and 0.01% atropine groups. SRVD, DRVD, and RT were measured using swept-source optical coherence tomography at baseline and six months. The macular zone was divided into three concentric rings (fovea, parafovea, and perifovea) using the Early Treatment Diabetic Retinopathy Study.
RESULTS
After six months, the whole, parafoveal, and perifoveal SRVD significantly increased in the two groups (all P < 0.05). Multivariate regression analyses showed that none of these changes varied significantly between the two groups (all P > 0.05), whereas foveal SRVD remained stable in both groups (all P > 0.05). In the RLRL group, the whole and perifoveal DRVD increased significantly (all P < 0.05), whereas no statistical difference was observed in the foveal and parafoveal DRVD. DRVD remained stable in the 0.01% atropine group (all P > 0.05). No significant differences were observed in RT changes between the two groups (all P > 0.05). In comparison, there were no significant changes in SRVD, DRVD, or RT after six months in the placebo group in our previous study.
CONCLUSIONS
SRVD increased similarly in the RLRL and 0.01% atropine groups, whereas DRVD increased only in the former group. There were no significant RT changes in either group after six months of treatment in premyopic schoolchildren.
TRANSLATIONAL RELEVANCE
This research observed the effects of low-level red light and 0.01% atropine on retinal vasculature, offering valuable insights into myopia progression prevention.
Topics: Humans; Atropine; Male; Female; Child; Prospective Studies; Retinal Vessels; Mydriatics; Tomography, Optical Coherence; Myopia; Ophthalmic Solutions; Phototherapy; Microvascular Density; Red Light
PubMed: 38940757
DOI: 10.1167/tvst.13.6.23 -
ELife Jun 2024Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these...
Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline (NA) reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both NA and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
Topics: Animals; Dopaminergic Neurons; Serotonergic Neurons; Dorsal Raphe Nucleus; Mice; Disease Models, Animal; Oxidopamine; Parkinsonian Disorders; Male; Mice, Inbred C57BL; Desipramine; Norepinephrine
PubMed: 38940422
DOI: 10.7554/eLife.90278 -
Annals of Agricultural and... Jun 2024We read with interest the article by Kulesza et al. about a narrative review on the question of whether cannabidiol is really effective in treating lower back pain [1]....
We read with interest the article by Kulesza et al. about a narrative review on the question of whether cannabidiol is really effective in treating lower back pain [1]. After a literature search using suitable search terms and application of inclusion and exclusion criteria, the authors included 10 studies in the analysis [1]. One of the articles included was an editorial and four papers were reviews [1]. Cannabidiol has been found to be ineffective in treating lower back pain and further studies are needed to answer the question of interest. The review is impressive, but several points require discussion.
Topics: Cannabidiol; Humans; Low Back Pain
PubMed: 38940097
DOI: 10.26444/aaem/186635 -
Journal of Integrative Neuroscience Jun 2024root, cataloged as "" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations...
BACKGROUND
root, cataloged as "" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration.
METHODS
The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms.
RESULTS
The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (), glial fibrillary acidic protein (), and in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of components in neurodegeneration ( = 4.35 × 10-5) and TNF signaling pathway ( = 9.94 × 10-5).
CONCLUSIONS
The and analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, root is a promising herbal treatment option for antiepileptic and neuroprotective applications.
Topics: Animals; Neuroprotective Agents; Trimethyltin Compounds; Plant Extracts; Rheum; Plant Roots; Male; Anticonvulsants; Epilepsy; Hippocampus; Disease Models, Animal; Neurodegenerative Diseases; Computer Simulation; Network Pharmacology; Protein Interaction Maps; Rats
PubMed: 38940090
DOI: 10.31083/j.jin2306122 -
Journal of Integrative Neuroscience Jun 2024Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules...
BACKGROUND
Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus.
METHODS
Mice were provided access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis.
RESULTS
Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice.
CONCLUSIONS
Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.
Topics: Animals; Hippocampus; Microtubules; Actin Cytoskeleton; Male; Ethanol; Mice; Mice, Inbred C57BL; Central Nervous System Depressants; Disease Models, Animal; Behavior, Animal
PubMed: 38940085
DOI: 10.31083/j.jin2306118 -
Frontiers in Bioscience (Landmark... Jun 2024
Review
Topics: Humans; Cocaine-Related Disorders; Gastrointestinal Microbiome; Cocaine; Animals; Yin-Yang
PubMed: 38940056
DOI: 10.31083/j.fbl2906215