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The perioperative period of any surgery is accompanied by immune suppression. The level of Toll-like receptor 4 (TLR4) is known to increase in inflammation and after nerve injury and contributes to the development of neuropathic pain. The interaction of TLRs in response to the effect of opioids results in paradoxical hyperalgesia. Regional anesthesia techniques are the standard of care for perioperative pain management in children.
Learn More >Repetitive neuromuscular magnetic stimulation (rNMS) of the trapezius muscles showed beneficial effects in preventing episodic migraine. However, clinical characteristics that predict a favorable response to rNMS are unknown. The objective of this analysis is to identify such predictors.
Learn More >Low-intensity shockwave therapy (LiST) has been applied in the clinical treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but few studies have focused on the prediction of its therapeutic effect before treatment.
Learn More >Machine learning (ML) has been largely applied for predicting migraine classification. However, the prediction of efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine is still in the early stages. This study aims to evaluate whether the combination of machine learning and amygdala-related functional features could help predict the efficacy of NSAIDs in patients with migraine without aura (MwoA). A total of 70 MwoA patients were enrolled for the study, including patients with an effective response to NSAIDs (M-eNSAIDs, = 35) and MwoA patients with ineffective response to NSAIDs (M-ieNSAIDs, = 35). Furthermore, 33 healthy controls (HCs) were matched for age, sex, and education level. The study participants were subjected to resting-state functional magnetic resonance imaging (fMRI) scanning. Disrupted functional connectivity (FC) patterns from amygdala-based FC analysis and clinical characteristics were considered features that could promote classification through multivariable logistic regression (MLR) and support vector machine (SVM) for predicting the efficacy of NSAIDs. Further, receiver operating characteristic (ROC) curves were drawn to evaluate the predictive ability of the models. The M-eNSAIDs group exhibited enhanced FC with ipsilateral calcarine sulcus (CAL), superior parietal gyrus (SPG), paracentral lobule (PCL), and contralateral superior frontal gyrus (SFG) in the left amygdala. However, the M-eNSAIDs group showed decreased FC with ipsilateral caudate nucleus (CAU), compared to the M-ieNSAIDs group. Moreover, the M-eNSAIDs group showed higher FC with left pre-central gyrus (PreCG) and post-central gyrus (PoCG) compared to HCs. In contrast, the M-ieNSAIDs group showed lower FC with the left anterior cingulate cortex (ACC) and right SFG. Furthermore, the MwoA patients showed increased FC with the left middle frontal gyrus (MFG) in the right amygdala compared to HCs. The disrupted left amygdala-related FC patterns exhibited significant correlations with migraine characteristics in the M-ieNSAIDs group. The MLR and SVM models discriminated clinical efficacy of NSAIDs with an area under the curve (AUC) of 0.891 and 0.896, sensitivity of 0.971 and 0.833, and specificity of 0.629 and 0.875, respectively. These findings suggest that the efficacy of NSAIDs in migraine could be predicted using ML algorithm. Furthermore, this study highlights the role of amygdala-related neural function in revealing underlying migraine-related neuroimaging mechanisms.
Learn More >Gut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively.
Learn More >Pediatric primary chronic pain disorders come with diagnostic uncertainty, which may obscure diagnostic expectations for referring providers and the decision to accept or re-direct patients into interdisciplinary pediatric chronic pain programs based on diagnostic completeness. We aimed to attain expert consensus on diagnostic expectations for patients who are referred to interdisciplinary pediatric chronic pain programs with six common primary chronic pain diagnoses.
Learn More >Neuropathic pain (NP) caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition that has a major impact on quality of life. However, NP pathogenesis remains unclear. The purpose of this study was to identify differentially expressed genes (DEGs) and specific and meaningful gene targets for the diagnosis and treatment of NP.
Learn More >There is a growing public health concern regarding inappropriate prescribing practices of discharge analgesia. A tertiary Australian hospital first developed its after an initial audit in 2015. Adherence to the guidelines were evaluated in 2016 and 2017 which show reduced compliance from 93.5% in 2016 to 83.4% in 2017.
Learn More >Cutaneous immune-related adverse events (irAEs) are the most common irAEs caused by immune-checkpoint inhibitors (ICI). Psoriasiform eruptions, both and flares, may occur. Evidence is lacking on inverse psoriasis subtype.
Learn More >Cartilage and other skeletal soft tissues heal poorly after injury, in part due to their lack of vascularity and low metabolic rate. No pharmacologic approaches have proven effective in preventing chronic degenerative disease after joint injury. Mesenchymal stromal cells (MSCs) have been investigated for their ability to treat pain associated with osteoarthritis (OA) and preserve articular cartilage. Limitations of MSCs include variability in cell phenotype, low engraftment and retention rates, and inconsistent clinical outcomes. Therefore, acellular biologic therapies such as extracellular vesicles (EVs) are currently being investigated. MSC-derived EVs have been found to replicate many of the therapeutic effects of their cells of origin, but the mechanisms driving this remain unclear. Recent evidence in non-orthopedic tissues suggests MSCs can rescue injured cells by donating mitochondria, restoring mitochondrial function in recipient cells, preserving cell viability, and promoting tissue repair. Our group hypothesized that MSCs package mitochondria for export into EVs, and that these so-called "mitoEVs" could provide a delivery strategy for cell-free mitochondria-targeted therapy. Therefore, the goals of this study were to: 1) characterize the vesicle fractions of the MSCs secretome with respect to mitochondrial cargoes, 2) determine if MSC-EVs contain functional mitochondria, and 3) determine if chondrocytes can take up MSC-derived mitoEVs. We isolated exosome, microvesicle, and vesicle-free fractions from MSC-conditioned media. Using a combination of dynamic light scattering and nanoparticle tracking, we determined that MSC-EV populations fall within the three size categories typically used to classify EVs (exosomes, microvesicles, apoptotic bodies). Fluorescent nanoparticle tracking, immunoblotting, and flow cytometry revealed that mitochondrial cargoes are abundant across all EV size populations, and mitoEVs are nearly ubiquitous among the largest EVs. Polarization staining indicated a subset of mitoEVs contain functional mitochondria. Finally, flow cytometry and fluorescent imaging confirmed uptake of mitoEVs by chondrocytes undergoing rotenone/antimycin-induced mitochondrial dysfunction. These data indicate that MSCs package intact, functional mitochondria into EVs, which can be transferred to chondrocytes in the absence of direct cell-cell interactions. This work suggests intercellular transfer of healthy MT to chondrocytes could represent a new, acellular approach to augment mitochondrial content and function in poorly-healing avascular skeletal soft tissues.
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