Effects of chronic daily headache with subclinical depression on brain volume: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The relationship between chronic daily headache (CDH), depression symptoms, and brain volume remains unclear. METHODS: To investigate the effects of CDH on brain volume and the impact of depressive symptoms (DSs) as well as the effects of demography and medication overuse, PubMed, Embase, and Web of Science databases were systematically searched using appropriate keyword strings to retrieve observational studies from inception to May 2023. RESULTS: Two distinct comparisons were made in CDH patients: (1) those with DSs versus their pain-free counterparts and (2) those without DSs versus pain-free controls. The first comprised nine studies enrolling 225 CDH patients with DSs and 234 controls. Beck depression inventory, Hamilton depression scale, and Hospital anxiety/depression scale were used to assess DSs, revealing significantly more DSs in CDH patients with DSs compared to their controls (all p < 0.05). Besides, the second analysed four studies involving 117 CDH patients without DSs and 155 comparators. Compared to CDH patients without DSs, those with DSs had a smaller brain volume than controls (p = 0.03). Furthermore, CDH patients with DSs who did not overuse medications showed a smaller right cerebral cortical volume than overusers (p = 0.003). A significant inverse correlation between female prevalence and brain volume (p = 0.02) was revealed using regression analysis. CONCLUSIONS: Pain-induced persistent depressive symptoms not only incur structural alterations but also encompass affective-motivational changes, involving medication use and gender-specific health concerns. SIGNIFICANCE: This study highlighted the importance of an integrated CDH treatment, emphasizing psychological interventions for the affective-motivational component alongside pain management.

CDDO regulates central and peripheral sensitization to attenuate post-herpetic neuralgia by targeting TRPV1/PKC-δ/p-Akt signals.

Postherpetic neuralgia (PHN) is a notorious neuropathic pain featuring persistent profound mechanical hyperalgesia with significant negative impact on patients' life quality. CDDO can regulate inflammatory response and programmed cell death. Its derivative also protects neurons from damages by modulating microglia activities. As a consequence of central and peripheral sensitization, applying neural blocks may benefit to minimize the risk of PHN. This study aimed to explore whether CDDO could generate analgesic action in a PHN-rats' model. The behavioural test was determined by calibrated forceps testing. The number of apoptotic neurons and degree of glial cell reaction were assessed by immunofluorescence assay. Activation of PKC-δ and the phosphorylation of Akt were measured by western blots. CDDO improved PHN by decreasing TRPV1-positive nociceptive neurons, the apoptotic neurons, and reversed glial cell reaction in adult rats. It also suppressed the enhanced PKC-δ and p-Akt signalling in the sciatic nerve, dorsal root ganglia (DRG) and spinal dorsal horn. Our research is the promising report demonstrating the analgesic and neuroprotective action of CDDO in a PHN-rat's model by regulating central and peripheral sensitization targeting TRPV1, PKC-δ and p-Akt. It also is the first study to elucidate the role of oligodendrocyte in PHN.

Linalool, a Fragrance Compound in Plants, Protects Dopaminergic Neurons and Improves Motor Function and Skeletal Muscle Strength in Experimental Models of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.

Preclinical Animal Study and Pilot Clinical Trial of Using Enriched Peripheral Blood-Derived Mononuclear Cells for Intervertebral Disc Degeneration.

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.

Accurate Intervertebral Disc Segmentation Approach Based on Deep Learning.

Automatically segmenting specific tissues or structures from medical images is a straightforward task for deep learning models. However, identifying a few specific objects from a group of similar targets can be a challenging task. This study focuses on the segmentation of certain specific intervertebral discs from lateral spine images acquired from an MRI scanner. In this research, an approach is proposed that utilizes MultiResUNet models and employs saliency maps for target intervertebral disc segmentation. First, a sub-image cropping method is used to separate the target discs. This method uses MultiResUNet to predict the saliency maps of target discs and crop sub-images for easier segmentation. Then, MultiResUNet is used to segment the target discs in these sub-images. The distance maps of the segmented discs are then calculated and combined with their original image for data augmentation to predict the remaining target discs. The training set and test set use 2674 and 308 MRI images, respectively. Experimental results demonstrate that the proposed method significantly enhances segmentation accuracy to about 98%. The performance of this approach highlights its effectiveness in segmenting specific intervertebral discs from closely similar discs.

Clinical Outcomes and Cost-Effectiveness of Osteoporosis Screening With Dual-Energy X-ray Absorptiometry.

OBJECTIVE: This study aimed to evaluate the clinical outcomes and cost-effectiveness of dual-energy X-ray absorptiometry (DXA) for osteoporosis screening. MATERIALS AND METHODS: Eligible patients who had and had not undergone DXA screening were identified from among those aged 50 years or older at Kaohsiung Veterans General Hospital, Taiwan. Age, sex, screening year (index year), and Charlson comorbidity index of the DXA and non-DXA groups were matched using inverse probability of treatment weighting (IPTW) for propensity score analysis. For cost-effectiveness analysis, a societal perspective, 1-year cycle length, 20-year time horizon, and discount rate of 2% per year for both effectiveness and costs were adopted in the incremental cost-effectiveness (ICER) model. RESULTS: The outcome analysis included 10337 patients (female:male, 63.8%:36.2%) who were screened for osteoporosis in southern Taiwan between January 1, 2012, and December 31, 2021. The DXA group had significantly better outcomes than the non-DXA group in terms of fragility fractures (7.6% vs. 12.5%, P < 0.001) and mortality (0.6% vs. 4.3%, P < 0.001). The DXA screening strategy gained an ICER of US$ -2794 per quality-adjusted life year (QALY) relative to the non-DXA at the willingness-to-pay threshold of US$ 33004 (Taiwan's per capita gross domestic product). The ICER after stratifying by ages of 50-59, 60-69, 70-79, and ≥ 80 years were US$ -17815, US$ -26862, US$ -28981, and US$ -34816 per QALY, respectively. CONCLUSION: Using DXA to screen adults aged 50 years or older for osteoporosis resulted in a reduced incidence of fragility fractures, lower mortality rate, and reduced total costs. Screening for osteoporosis is a cost-saving strategy and its effectiveness increases with age. However, caution is needed when generalizing these cost-effectiveness results to all older populations because the study population consisted mainly of women.

AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways.

This study aimed to investigate the regulatory role of Aldo-keto reductase family 1 member B1 (AKR1B1) in glioma cell proliferation through p38 MAPK activation to control Bcl-2/BAX/caspase-3 apoptosis signaling. AKR1B1 expression was quantified in normal human astrocytes, glioblastoma multiforme (GBM) cell lines, and normal tissues by using quantitative real-time polymerase chain reaction. The effects of AKR1B1 overexpression or knockdown and those of AKR1B1-induced p38 MAPK phosphorylation and a p38 MAPK inhibitor (SB203580) on glioma cell proliferation were determined using an MTT assay and Western blot, respectively. Furthermore, the AKR1B1 effect on BAX and Bcl-2 expression was examined in real-time by Western blot. A luminescence detection reagent was also utilized to identify the effect of AKR1B1 on caspase-3/7 activity. The early and late stages of AKR1B1-induced apoptosis were assessed by performing Annexin V-FITC/PI double-staining assays. AKR1B1 expression was significantly downregulated in glioma tissues and GBM cell lines (T98G and 8401). Glioma cell proliferation was inhibited by AKR1B1 overexpression but was slightly increased by AKR1B1 knockdown. Additionally, AKR1B1-induced p38 MAPK phosphorylation and SB203580 reversed AKR1B1's inhibitory effect on glioma cell proliferation. AKR1B1 overexpression also inhibited Bcl-2 expression but increased BAX expression, whereas treatment with SB203580 reversed this phenomenon. Furthermore, AKR1B1 induced caspase-3/7 activity. The induction of early and late apoptosis by AKR1B1 was confirmed using an Annexin V-FITC/PI double-staining assay. In conclusion, AKR1B1 regulated glioma cell proliferation through the involvement of p38 MAPK-induced BAX/Bcl-2/caspase-3 apoptosis signaling. Therefore, AKR1B1 may serve as a new therapeutic target for glioma therapy development.

Guilu Erxian Jiao enhances protein synthesis, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers in the skeletal muscle.

Guilu Erxian Jiao (GEJ) is a commonly used nutritional supplement due to its rich content of amino acids. It is also a traditional herbal medicine for improving degenerative joint. This study aimed to investigate the effect and mechanism of GEJ water extract (GEJ-WE) on skeletal muscle in C2C12 myotubes and C57BL/6J mice. Analysis of GEJ-WE were performed by high-performance liquid chromatography fingerprinting with chemical standards. Protein expression, mRNA level, glycogen content, mitochondria activity and ATP level were evaluated by western blots, real-time PCR, PAS staining, MTT and ATP bioluminescence assay, respectively. Skeletal muscle strength was evaluated by grip strength. Skeletal muscle volume, mass and fiber types were evaluated by micro computed tomography, histological analysis and immunofluorescence staining, respectively. Motor function was evaluated by rotarod performance and locomotor activity. In C2C12 myotubes, GEJ-WE significantly enhanced myogenic differentiation and myotube growth, protein synthesis signaling IGF-1/IGF-1R/IRS-1/Akt, Glut4 translocation, glycogen content, mitochondrial biogenesis signaling PGC-1α/NRF1/TFAM, mitochondrial activity and ATP production. However, IGF-1R antagonist AG1024 and PI3K inhibitor wortmannin reduced GEJ-WE-induced protein expression of MyHC, p-Akt, p-mTOR and p-GSK-3ß, Glut4 translocation and glycogen content. In C57BL/6J mice, GEJ-WE not only upregulated protein synthesis and mitochondrial biogenesis signaling, but it also increased muscle volume, relative muscle weight, cross-sectional area of myofibers, glycogen content and transition of fast-to-slow type fibers of skeletal muscles. Moreover, GEJ-WE enhanced grip strength and motor activity of mice. In conclusion, the upregulation of protein synthesis, myogenic differentiation, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers contributes to the mechanisms of GEJ-WE on the enhancement of skeletal muscle mass and motor function.

Development and Validation of the Osteoporosis Knowledge, Attitude, and Behaviors Questionnaire for Female Osteoporosis Patients in Taiwan: A Mediation Model.

This research develops the Osteoporosis Knowledge, Attitude and Behaviors Questionnaire (OKABQ) with the intent to evaluate the levels of osteoporosis knowledge, attitude and behavior change by developing and validating the OKABQ while establishing a mediation model of the research. A quantitative, descriptive and instrumental study was conducted in two phases: Phase I-development of the scale through Delphi Method by osteoporosis experts; and Phase II-evaluation of the validity and reliability of the scale and construction of a mediation model using SmartPLS. In Phase I, the content validity index (CVI) of the questionnaire was higher than 0.96 and the inter-rater reliability (IRR) kappa was 1.00. In Phase II, exploratory factor analysis showed that two predominating factors of attitude as a mediation were addressed by the 26-item OKABQ. The indirect effect results from the estimated model indicate that attitude mediates the relationship between knowledge and behaviors (ß = 0.114, t = 2.627, p < 0.001), which is positive and statistically significant. We concluded that the OKABQ is a valid measure of osteoporosis knowledge, attitudes and behaviors for women with osteoporosis. These assessment results could assist healthcare providers in mitigating insufficiency in health education and help patients better adapt to a more active bone-healthy lifestyle.

Enriched Peripheral Blood-Derived Mononuclear Cells for Treating Knee Osteoarthritis.

Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren-Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages in vitro. The in vivo anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund's adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients' knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.

Outcome predictors and clinical presentation of syringomyelia.

BACKGROUND: The prognosis of syringomyelia is not yet established. Syringomyelia derived from different etiologies contributes to similar symptoms. OBJECTIVE: Assess the syringomyelia in our medical institutes and describe the etiologies and clinical appearance of the disorder. And identify the predictors of a good outcome and to find the most suitable timing of surgical intervention according to our results. METHODS: This retrospective cohort study used databases in our hospitals to analyze 70 cases of syringomyelia between 1997 and 2014. All available information was obtained from medical records and radiological reports. We used American Spinal Injuries Association disability scores (ASIA scores), the modified Nurick classification system, and recorded the number of days the patient was hospitalized, for neurological and functional assessment. Univariate and multivariate analyses were used to evaluate the relationship between clinical factors and outcomes. RESULTS: Non-communicating syringomyelia was the most common type of syringomyelia. In univariate analysis, autonomic dysfunction and motor impairment were strong predictors of poor neurological and functional outcomes. In addition to the above factors, syrinxes at the cervical level predicted better functional outcomes than at any spinal level in multivariate analysis. CONCLUSIONS: Motor impairment, which is commonly seen in patients with syringomyelia in Taiwan, is a strong predictor to poor neurological and functional outcomes. Our study indicates that patients without autonomic dysfunction or motor impairment should receive timely surgical intervention to prevent symptomatic deterioration. We also found that cervical syringomyelia in particular has the potential for good functional recovery after adequate intervention.

Size Reduction of the Right Amygdala in Chronic Pain Patients with Emotional Stress: A Systematic Review and Meta-Analysis.

The structural impact of chronic pain on amygdala in chronic pain (CP) patients remains unclear, although major depression and anxiety are known to be associated with its increase and decrease in size, respectively. This study aimed at examining the relationship between emotional stress and amygdala size in CP patients. The effects of mediating and moderating variables were also examined. The PubMed, Embase, and Web of Science databases were searched for English clinical trials from inception to February 2022 using the appropriate keyword strings. We compared the differences in amygdala size assessed with magnetic resonance imaging between CP patients with emotional stress and healthy counterparts. Of the 49 full-text articles identified, 13 studies enrolling 1,551 participants including 738 CP patients with emotional stress and 813 controls were analyzed. Emotional stress evaluated with questionnaires based on Beck depression inventory, Hamilton depression/anxiety scale, state-trait anxiety inventory, and hospital anxiety and depression scale revealed significant differences between CP patients with emotional stress and controls, indicating a subclinical but significant level of emotional stress in CP patients. The results demonstrated an amygdala shrinkage among CP patients with emotional stress compared to the controls, especially the right side (P = .02). Besides, pain from a single body region was more likely to impact the amygdala size compared to diffuse pain (P = .02). Regression analysis revealed no significant association between continuous variables (age, gender, pain duration/intensity) and amygdala size. Our findings demonstrated that emotional stress was associated with a reduced right amygdala size in CP patients.

In vitro evaluation of electrospun polyvinylidene fluoride hybrid nanoparticles as direct piezoelectric membranes for guided bone regeneration.

A polyvinylidene fluoride (PVDF) piezoelectric membrane containing carbon nanotubes (CNTs) and graphene oxide (GO) additives was prepared, with special emphasis on the piezoelectric activity of the aligned fibers. Fibroblast viability on membranes was measured to study cytotoxicity. Osteoprogenitor D1 cells were cultured, and mineralization of piezoelectric composite membranes was assessed by ultrasound stimulation. Results showed that the electrospun microstructures were anisotropically aligned fibers. As the GO content increased to 1.0 wt% (0.2 wt% interval), the ß phase in PVDF slightly increased but showed the opposite trend with the increase in CNT. Excessive addition of GO and CNT hindered the growth of the ß phase in PVDF. The direct piezoelectric activity and mechanical properties showed the same trend as the ß phase in PVDF. Moreover, GO/PVDF with the same nanoparticle content showed better performance than CNT/PVDF composites. In this study, a comparison of the generated piezoelectric specific voltage (unit: 10-3 Vg-1 cm-2, linear stretch, g33) with control PVDF only (0.55 ± 0.16) revealed that the two composites containing 0.8 wt% GO- and 0.2 wt% CNT- with 15 wt% PVDF exhibited excellent piezoelectric voltages, which were 3.37 ± 1.05 and 1.45 ± 0.07 (10-3 Vg-1 cm-2), respectively. In vitro cultures of these two groups in contact with D1 cells showed significantly higher alkaline phosphatase secretion than the PVDF only group within 1-10 days of cell culture. Further application of ultrasound stimulation showed that the piezoelectric membrane differentiated D1 cells earlier than without ultrasound and induced higher proliferation and mineralization. This developing piezoelectric effect is expected to generate voltage through activities to enhance microcurrent stimulation in vivo.

Middle Cerebral Artery Compromise Associated With Post-traumatic Hydrocephalus: A Case Report.

Post-traumatic hydrocephalus (PTH) is a commonly encountered complication following decompressive craniectomy, and is usually characterized by symptoms including headache, nausea, vomiting, and papilledema. Extracranial herniation accompanied by hemiplegia is a rare complication in patients with PTH who underwent craniectomy after subdural hematoma removal. We report a case of PTH that presented with extracranial herniation within one month of decompressive craniectomy. Following ventriculoperitoneal shunt implantation, left hemiplegia improved dramatically with restoration of the left middle cerebral artery blood flow, which was evident on serial imaging. Vascular compromise is often overshadowed by increased intracranial pressure when clinicians are dealing with traumatic brain injury patients. Delicate neurological and radiological examinations and prompt early interventions could lead to optimal outcomes in patients receiving decompressive craniectomy.

Graphene Nanoplatelet/Multiwalled Carbon Nanotube/Polypyrrole Hybrid Fillers in Polyurethane Nanohybrids with 3D Conductive Networks for EMI Shielding.

This work reports the preparation of graphene nanoplatelet (GNP)/multiwalled carbon nanotube (MWCNT)/polypyrrole (PPy) hybrid fillers via in situ chemical oxidative polymerization with the addition of a cationic surfactant, hexadecyltrimethylammonium bromide. These hybrid fillers were incorporated into polyurethane (PU) to prepare GNP/MWCNT/PPy/PU nanohybrids. The electrical conductivity of the nanohybrids was synergistically enhanced by the high conductivity of the hybrid fillers. Furthermore, the electromagnetic interference (EMI) shielding effectiveness (SE) was greatly increased by interfacial polarization between the GNPs, MWCNTs, PPy, and PU. The optimal formulation for the preparation of GNP/MWCNT/PPy three-dimensional (3D) nanostructures was determined by optimization experiments. Using this formulation, we successfully prepared GNP/PPy nanolayers (two-dimensional) that are extensively covered by MWCNT/PPy nanowires (one-dimensional), which interconnect to form GNP/MWCNT/PPy 3D nanostructures. When incorporated into a PU matrix to form a nanohybrid, these 3D nanostructures form a continuous network of conductive GNP-PPy-CNT-PPy-GNP paths. The EMI SE of the nanohybrid is 35-40 dB at 30-1800 MHz, which is sufficient to shield over 99.9% of electromagnetic waves. Therefore, this EMI shielding material has excellent prospects for commercial use. In summary, a nanohybrid with excellent EMI SE performance was prepared using a facile and scalable method and was shown to have great commercial potential.

Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells.

The human type II collagen (Col II), specifically expressed in chondrocytes, is a crucial component of the adult hyaline cartilage. We examine the potential of artificial induction of Col II in human peripheral blood mononuclear cells (PBMNCs) as a novel Col II provider. Human PBMNCs were purified and were treated with high doses of macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), or granulocyte-colony stimulating factor (G-CSF) and examined the Col II expression at indicated days. Quantitative Col II expression was validated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and flow cytometry. We demonstrate that monocytes in PBMNCs can be artificially induced to express both Col II proteins and M2 macrophage markers by the high concentration of colony-stimulating factors, especially M-CSF and GM-CSF. The Col II proteins were detected on the cell membrane and in the cytoplasm by flow cytometry and immunocytostaining. Combination with IL-4 provided a synergistic effect with M-CSF/GM-CSF to trigger Col II expression in M2 macrophages. These CD206 and Col II double-expressing cells, named modified macrophages, share M2 macrophages' anti-inflammatory potency. We demonstrated that the modified macrophages could significantly attenuate the inflammatory progress of Complete Freund's adjuvant (CFA)-induced arthritis and collagen-induced arthritis in rodents. Here, we provide the first evidence that a modified macrophage population could ectopically express Col II and control the progress of arthritis in animals.

Protective Effects of the Chalcone-Based Derivative AN07 on Inflammation-Associated Myotube Atrophy Induced by Lipopolysaccharide.

Inflammation is a major cause of skeletal muscle atrophy in various diseases. 2-Hydroxy-4'-methoxychalcone (AN07) is a chalcone-based peroxisome-proliferator-activated receptor gamma (PPARγ) agonist with various effects, such as antiatherosclerosis, anti-inflammation, antioxidative stress, and neuroprotection. In this study, we examined the effects of AN07 on protein homeostasis pathway and mitochondrial function in inflammation-associated myotube atrophy induced by lipopolysaccharides (LPS). We found that AN07 significantly attenuated NF-κB activation, inflammatory factors (TNF-α, IL-1ß, COX-2, and PGE2), Nox4 expression, and reactive oxygen species levels in LPS-treated C2C12 myotubes. Moreover, AN07 increased SOD2 expression and improved mitochondrial function, including mitochondrial membrane potential and mitochondrial oxygen consumption rate. We also demonstrated that AN07 attenuated LPS-induced reduction of myotube diameter, MyHC expression, and IGF-1/IGF-1R/p-Akt-mediated protein synthesis signaling. Additionally, AN07 downregulated LPS-induced autophagy-lysosomal protein degradation molecules (LC3-II/LC3-I and degraded p62) and ubiquitin-proteasome protein degradation molecules (n-FoxO1a/MuRF1/atrogin-1). However, the regulatory effects of AN07 on protein synthesis and degradation signaling were inhibited by the IGF-1R inhibitor AG1024 and the PI3K inhibitor wortmannin. In addition, the PPARγ antagonist GW9662 attenuated the effects of AN07 against LPS-induced inflammation, oxidation, and protein catabolism. In conclusion, our findings suggest that AN07 possesses protective effects on inflammation-induced myotube atrophy and mitochondrial dysfunction.

Potential Roles of Teamwork and Unmet Needs on Surgical Learning Curves of Spinal Robotic Screw Placement.

Background: The aim of this study was to investigate the learning curve of robotic spine surgery quantitatively with the well-described power law of practice. Methods: Kaohsiung Medical University Hospital set up a robotic spine surgery team by the neurosurgery department in 2013 and the orthopedic department joined the well-established team in 2014. A total of consecutive 150 cases received robotic assisted spinal surgery. The 150 cases, with 841 transpedicular screws were enrolled into 3 groups: the first 50 cases performed by neurosurgeons, the first 50 cases by orthopedic surgeons, and 50 cases by neurosurgeons after the orthopedic surgeons joined the team. The time per screw and accuracy by each group and individual surgeon were analyzed. Results: The time per screw for each group was 9.56 ± 4.19, 7.29 ± 3.64, and 8.74 ± 5.77 minutes, respectively, with p-value 0.0017. The accuracy was 99.6% (253/254), 99.5% (361/363), and 99.1% (222/224), respectively, with p-value 0.77. Though the first group took time significantly more on per screw placement but without significance on the nonlinear parallelism F-test. Analysis of 5 surgeons and their first 10 cases of short segment surgery showed the time per screw by each surgeon was 12.28 ± 5.21, 6.38 ± 1.54, 8.68 ± 3.10, 6.33 ± 1.90, and 6.73 ± 1.81 minutes. The first surgeon who initiated the robotic spine surgery took significantly more time per screw, and the nonlinear parallelism test also revealed only the first surgeon had a steeper learning curve. Conclusion: This is the first study to demonstrate that differences of learning curves between individual surgeons and teams. The roles of teamwork and the unmet needs due to lack of active perception are discussed.