Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury.

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity, damaging the neurons. However, how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear. Herein, we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury. We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice. Lipid droplet accumulation could be induced by myelin debris in HT22 cells. Myelin debris degradation by phospholipase led to massive free fatty acid production, which increased lipid droplet synthesis, ß-oxidation, and oxidative phosphorylation. Excessive oxidative phosphorylation increased reactive oxygen species generation, which led to increased lipid peroxidation and HT22 cell apoptosis. Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway, thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells. Motor function, lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury. The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

Focal vibration of the plantarflexor and dorsiflexor muscles improves poststroke spasticity: a randomized single-blind controlled trial.

BACKGROUND: Post-stroke spasticity is a cause of gait dysfunction and disability. Focal vibration (FV) of agonist-antagonist upper limb muscle pairs reduces flexor spasticity; however, its effects on ankle plantarflexor spasticity are uncertain. OBJECTIVE: To assess the effects of focal vibration administered by a trained operator to the ankle plantarflexor and dorsiflexor muscles on post-stroke lower limb spasticity. METHODS: A randomized, single-blind controlled trial of 64 participants with stroke and plantarflexor spasticity assigned to 3 groups by centralized, computer-generated randomization (1:1:1): 1) physiotherapy alone (CON), 2) physiotherapy+gastrocnemius vibration (FV_GM) and 3) physiotherapy+tibialis anterior vibration (FV_TA). Physiotherapists and assessors were blinded to group assignment. The experimental groups underwent 15, 20-min vibration sessions at 40 Hz. We performed evaluations at baseline and after the final treatment: Modified Ashworth Scale (MAS), Clonus scale, Functional Ambulation Categories (FAC), Fugl-Meyer Assessment - Lower Extremity (FMA_LE), Modified Barthel Index (MBI), and electromyography and ultrasound elastography. Primary outcome was remission rate (number and proportion of participants) of the MAS. RESULTS: MAS remission rate was higher in FV_GM and FV_TA than CON groups (CON vs. FV_GM: p=0.009, odds ratio 0.15 [95% confidence interval 0.03-0.67]; CON vs. FV_TA: p=0.002, 0.12 [0.03-0.51]). Remission rate was higher in the experimental than CON groups for the Clonus scale (CON vs. FV_GM: p<0.001, OR 0.07 [95% CI 0.01-0.31]; CON vs. FV_TA: p=0.006, 0.14 [95% CI 0.03-0.61]). FAC remission rate was higher in the FV_TA than the CON (p=0.009, 0.18 [0.05-0.68]) and FV_GM (p=0.014, 0.27 [0.07-0.99]) groups. Ultrasound variables of the paretic medial gastrocnemius decreased more in FV_GM than CON and FV_TA groups (shear modulus: p=0.006; shear wave velocity: p=0.008). CONCLUSIONS: Focal vibration reduced post-stroke spasticity of the plantarflexor muscles. Vibration of the tibialis anterior improved ambulation more than vibration of the gastrocnemius or physiotherapy alone. Gastrocnemius vibration may reduce spasticity by changing muscle stiffness.

Effectiveness of contralaterally controlled functional electrical stimulation vs. neuromuscular electrical stimulation for recovery of lower extremity function in patients with subacute stroke: A randomized controlled trial.

Objective: This study aimed to compare the efficacy of contralaterally controlled functional electrical stimulation (CCFES) vs. neuromuscular electrical stimulation (NMES) for motor recovery of the lower extremity in patients with subacute stroke. Materials and methods: Seventy patients within 6 months post-stroke were randomly assigned to the CCFES group (n = 35) and the NMES group (n = 35). Both groups underwent routine rehabilitation plus 20-min electrical stimulation (CCFES or NMES) on ankle dorsiflexion muscles per day, 5 days a week, for 3 weeks. Ankle AROM (dorsiflexion), Fugl-Meyer assessment-lower extremity (FMA-LE), Barthel Index (BI), Functional Ambulation Category scale (FAC), 10-meter walking test, and surface electromyography (sEMG) were assessed at the baseline and at the end of the intervention. Result: Ten patients did not complete the study (five in CCFES and five in NMES), so only 60 patients were analyzed in the end. After the 3-week intervention, FMA-LE, BI, Ankle AROM (dorsiflexion), and FAC increased in both groups (p < 0.05). Patients in the CCFES group showed significantly greater improvements only in the measurement of Fugl-Meyer assessment-lower extremity compared with the NMES group after treatment (p < 0.05). The improvement in sEMG response of tibialis anterior by CCFES was greater than NMES (p < 0.05). Conclusion: Contralateral controlled functional electrical stimulation can effectively improve the motor function of the lower limbs better than conventional neuromuscular electrical stimulation in subacute patients after stroke, but the effect on improving the ability to walk, such as walking speed, was not good. Clinical trial registration: http://www.chictr.org.cn/, identifier: ChiCTR2100045423.

Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair.

Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration.

Management of Eisenmenger syndrome by cardiac defect closure combined bilateral lung transplantation with intraoperative venoarterial ECMO support.

BACKGROUND: Optimal surgical treatment for Eisenmenger syndrome in adult congenital heart disease remains in debate. CASE REPORT: We report a case of a 22-year-old female with Eisenmenger syndrome secondary to ventricular septum defect (VSD), who underwent cardiac defect closure combined with bilateral lung transplantation in our center. The patient had an uncorrected peri-membranous VSD and subsequently developed severe pulmonary hypertension. We patched the defect under cardiopulmonary bypass. Then a sequential bilateral lung transplantation was performed with venoarterial extracorporeal membrane oxygenation support. The patient had a good postoperative recovery and remained well at follow-up at 1 year. To conclude, cardiac defect repair combined bilateral lung transplantation may be a feasible option for selected patients with Eisenmenger Syndrome.

Effectiveness of Contralaterally Controlled Functional Electrical Stimulation versus Neuromuscular Electrical Stimulation on Upper Limb Motor Functional Recovery in Subacute Stroke Patients: A Randomized Controlled Trial.

Purpose: To compare the effectiveness of contralaterally controlled functional electrical stimulation (CCFES) versus neuromuscular electrical stimulation (NMES) on motor recovery of the upper limb in subacute stroke patients. Materials and Methods: Fifty patients within six months poststroke were randomly assigned to the CCFES group (n = 25) and the NMES group (n = 25). Both groups underwent routine rehabilitation plus 20-minute stimulation on wrist extensors per day, five days a week, for 3 weeks. Fugl-Meyer Assessment of upper extremity (FMA-UE), action research arm test (ARAT), Barthel Index (BI), and surface electromyography (sEMG) were assessed at baseline and end of intervention. Results: After a 3-week intervention, FMA-UE and BI increased in both groups (p < 0.05). ARAT increased significantly only in the CCFES group (p < 0.05). The changes of FMA-UE, ARAT, and BI in the CCFES group were not greater than those in the NMES group. The improvement in sEMG response of extensor carpi radialis by CCFES was greater than that by NMES (p = 0.026). The cocontraction ratio (CCR) of flexor carpi radialis did not decrease in both groups. Conclusions: CCFES improved upper limb motor function, but did not show better treatment effect than NMES. CCFES significantly enhanced the sEMG response of paretic extensor carpi radialis compared with NMES, but did not decrease the cocontraction of antagonist.

Ex vivo lung perfusion with perfusate purification for human donor lungs following prolonged cold storage.

BACKGROUND: Ex vivo lung perfusion (EVLP) has developed as the most effective technique for estimating marginal donor lungs. This study attempted to extend the EVLP running time to 12 hours with a dialyzer rather than periodically replacing the perfusate. METHODS: Human donor lungs rejected by the clinical lung transplantation (LTx) team were obtained. After cold storage lasting 18-24 hours, lungs were randomly assigned to 2 groups: a control group and a perfusate purification (PP) group. The control group underwent EVLP in the traditional way, while a dialyzer was added into the circuit as a bypass in the PP group. The effects on lung function, microenvironment, inflammatory response, and cell death were evaluated. RESULTS: A total of 8 rejected donor lungs were obtained and each group was assigned to 4 cases of EVLP. Three cases were prematurely terminated because of serious lung edema and decreased lung function. There were no significant differences in airway pressure, pulmonary artery pressure, and oxygen concentration between the two groups in the first 8 hours. The pH in the control group was significantly lower than that in the PP group, and the levels of potassium and lactate were significantly higher than those in the PP group. Inflammatory markers increased in both groups, while IL-6 and IL-10 were higher in the PP group in the first 6 hours. Hematoxylin and eosin (HE) staining revealed lung injuries in both groups, but no significant difference was noted in the HE-stained slides. There were significantly more TUNEL-positive cells in the control group (69.5%±4.0%) than in the PP group (47.5%±3.9%) (P=0.000). CONCLUSIONS: Using the modified method of EVLP reduces the high cost caused by exchanging perfusion fluid per hour and could prolong the normothermic preservation time of donor lungs.

Can the preoperative nutritional risk score be a predictor of the outcomes in critically ill patients of lung transplantation: a retrospective study.

BACKGROUND: Nutritional Risk Screening 2002 (NRS2002) and prognostic nutrition index (PNI) are nutritional risk screening instruments that are also used to predict the complications and morbidity after surgery. Our study aims to evaluate whether preoperative nutrition status at admission or postoperative nutrition treatment during admission for lung transplantation (LTX) was linked to clinical outcomes. METHODS: This study is a retrospective observational cohort study of 42 patients undergoing LTX. Using PNI and NRS-2002 screening instruments, patients were tested for dietary danger upon admission. Univariate and multivariate analyzes were performed to investigate the independent nutritional risk predictive value for post-operative complications, hospital length or intensive care unit (ICU) stay, and mortality. RESULTS: Age, the average calorie intake, parenteral nutrition within 7 days, furosemide, the time of postoperative mechanical ventilation (MV), postoperative extracorporeal membrane oxygenation (ECMO) between survivor and non-survivor had a significant difference. Univariate analyses of death in LTX, age [HR 1.06 (1.00-1.13), P=0.04], the average calorie intake first 3 days [HR 0.99 (0.99-1.00), P=0.02], parenteral nutrition within 7 days [HR 0.20 (0.05-0.77), P=0.02], furosemide [HR 0.08 (0.01-0.76), P=0.02] and postoperative ECMO [HR 6.40 (1.65-24.77), P=0.00] were independent predictors for increased mortality. And multivariate analyses found that only postoperative ECMO [HR 9.59 (1.07-86.13), P=0.04] was independent predictors for increased mortality, whereas PNI and NRS2002 were not. CONCLUSIONS: PNI and NRS2002 was not an independent predictor for post-operative mortality, and postoperative ECMO was only independent predictors for increased mortality in this study.

Effects of mirror training on motor performance in healthy individuals: a systematic review and meta-analysis.

OBJECTIVE: Mirror training (MTr) is a rehabilitation technique for patients with neurological diseases. There is no consensus on its effects on motor function in healthy individuals. This systematic review and meta-analysis considers the effects of MTr on motor function in healthy individuals. DESIGN: This is a systematic review and meta-analysis. DATA SOURCES: We searched six databases for studies assessing the effects of MTr on motor function in healthy individuals, published between January 1995 and December 2018. The Cochrane risk of bias was used to assess the quality of the studies. A meta-analysis was conducted with narrative synthesis. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: English-language randomised controlled trials reporting the behavioural results in healthy individuals were included. RESULTS: Fourteen randomised controlled trials involving 538 healthy individuals were eligible. Two short-term studies showed MTr was inferior to passive vision pattern (standardised mean difference 0.57 (95% CI 0.06 to 1.08), I2=0%, p=0.03). The methods varied and there is limited evidence supporting the effectiveness of MTr compared with three alternative training patterns, with insufficient evidence to support analyses of age, skill level or hand dominance. CONCLUSION: The limited evidence that MTr affects motor performance in healthy individuals is weak and inconsistent among studies. It is unclear whether the effects of MTr on motor performance are more pronounced than the direct vision pattern, passive vision pattern or action observation. Further studies are needed to explore the short-term and long-term benefits of MTr and its effects on motor learning in healthy individuals. PROSPERO REGISTRATION NUMBER: CRD42019128881.

Hydrogen Sulfide Modulates the S-Nitrosoproteome and the Mitochondrial Morphology in Endothelial Cells.

BACKGROUND: Hydrogen sulfide (H2S) is one of the endogenous gaseous molecules promoting the production of nitric oxide (NO) which has cardioprotective functions. However, the role of the H2S-mediated protein S-nitrosoproteome and its subsequent physiological response remains unclear. METHODS: Endothelial cells EAhy 926 were treated with 50 µM of H2S for 2 hours. The NO bound S-nitrosoproteins were purified by a biotin-switch and then digested by trypsin. Resulting peptides from control and H2S treatment were separately labeled by isobaric tag for relative and absolute quantitation 114/115, quantified by liquid chromatography tandem-mass spectrometry and analyzed by ingenuity pathway analysis (IPA) software. The microP software was applied to analyze the morphological changes of mitochondria. RESULTS: With the treatment of H2S, 416 S-nitrosylated proteins were identified. IPA analysis showed that these proteins were involved in five signaling pathways. The NO-bound cysteine residues and the S-nitrosylation levels (115/114) were shown for ten S-nitrosoproteins. Western blot further verified the S-nitrosylation of thioredoxin-dependant peroxide reductase, cytochrome c oxidase and cytochrome b-c1 complex that are involved in the mitochondrial signaling pathway. H2O2-induced mitochondrial swelling can be reduced by the pretreatment of H2S. CONCLUSIONS: The H2S-mediated endothelial S-nitrosoproteome has been confirmed. In the present study, we have proposed the cardioprotective role of H2S via maintaining mitochondrial homeostasis.

An Efficient VLSI Architecture for Multi-Channel Spike Sorting Using a Generalized Hebbian Algorithm.

A novel VLSI architecture for multi-channel online spike sorting is presented in this paper. In the architecture, the spike detection is based on nonlinear energy operator (NEO), and the feature extraction is carried out by the generalized Hebbian algorithm (GHA). To lower the power consumption and area costs of the circuits, all of the channels share the same core for spike detection and feature extraction operations. Each channel has dedicated buffers for storing the detected spikes and the principal components of that channel. The proposed circuit also contains a clock gating system supplying the clock to only the buffers of channels currently using the computation core to further reduce the power consumption. The architecture has been implemented by an application-specific integrated circuit (ASIC) with 90-nm technology. Comparisons to the existing works show that the proposed architecture has lower power consumption and hardware area costs for real-time multi-channel spike detection and feature extraction.

Arsenic modulates posttranslational S-nitrosylation and translational proteome in keratinocytes.

Arsenic is a class I human carcinogen (such as inducing skin cancer) by its prominent chemical interaction with protein thio (-SH) group. Therefore, arsenic may compromise protein S-nitrosylation by competing the -SH binding activity. In the present study, we aimed to understand the influence of arsenic on protein S-nitrosylation and the following proteomic changes. By using primary human skin keratinocyte, we found that arsenic treatment decreased the level of protein S-nitrosylation. This was coincident to the decent expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). By using LC-MS/MS, around twenty S-nitrosoproteins were detected in the biotin-switched eluent. With the interest that arsenic not only regulates posttranslational S-nitrosylation but also separately affects protein's translation expression, we performed two-dimensional gel electrophoresis and found that 8 proteins were significantly decreased during arsenic treatment. Whether these decreased proteins are the consequence of protein S-nitrosylation will be further investigated. Taken together, these results provide a finding that arsenic can deplete the binding activity of NO and therefore reduce protein S-nitrosylation.

Agreement of cardiac output measurement between pulse contour analysis and thermodilution in various body positions: a porcine study.

BACKGROUND: We elucidated the effects of various body positions on the agreement of cardiac output (CO) measurement between pulse contour analysis with the PiCCO monitor and thermodilution with pulmonary artery catheterization. METHODS: Fifteen anesthetized and mechanically ventilated pigs (40 ± 2 kg) were sequentially placed in various positions to facilitate simultaneous CO measurement. Between-methods agreement was assessed using the Bland-Altman method. Trending ability was assessed using Pearson product-moment correlation coefficient analysis. RESULTS: In supine, reverse Trendelenburg, Trendelenburg, and left lateral decubitus (lateral) positions, CO measured by these two methods was comparable (4.9 ± 1.5 versus 4.6 ± 1.6 L/min, 4.6 ± 2.2 versus 4.8 ± 1.8 L/min, 5.1 ± 2.1 versus 4.9 ± 2.1 L/min, and 5.4 ± 1.8 versus 5.0 ± 1.6 L/min; all P > 0.05). Mean bias between methods and limits of agreement (percentage error) were 0.3 ± 2.9 L/min (61%), -0.3 ± 3.3 L/min (71%), 0.1 ± 4.1 L/min (77%), and 0.5 ± 3.7 L/min (71%). Directional changes of paired CO revealed 66% (reverse Trendelenburg), 57% (Trendelenburg), and 66% (lateral) concordance. The correlation coefficient (r(2)) was 0.199, 0.127, and 0.108. For paired CO ≤6 L/min, mean bias between methods and limits of agreement (percentage error) were 0.2 ± 1.0 L/min (25%), -0.1 ± 1.0 L/min (28%), 0.2 ± 1.1 L/min (29%), and 0.5 ± 0.9 L/min (23%). Directional changes of paired CO revealed 84% (reverse Trendelenburg), 76% (Trendelenburg), and 65% (lateral) concordance. The correlation coefficient (r2) was 0.583, 0.626, and 0.213. CONCLUSIONS: The mean CO measured by pulse contour analysis and thermodilution did not agree well in various body positions. Moreover, the measurements tended to trend differently in response to positional changes. For paired CO ≤6 L/min, however, the between-methods agreement and the trending ability improved significantly.

Airway management of patients with craniofacial abnormalities: 10-year experience at a teaching hospital in Taiwan.

BACKGROUND: Airway management for patients with craniofacial abnormalities poses many challenges. It potentially has a high rate of morbidity and even mortality. METHODS: We reviewed our experience in administering anesthesia to patients with a diagnosis of mucopolysaccharidosis or Pierre Robin sequence in the past 10 years (July 1998 to October 2008). The anesthetic procedures, methods of airway management, and events of morbidity and mortality were evaluated. RESULTS: Thirty patients with mucopolysaccharidosis and 53 patients with Pierre Robin sequence were placed under general anesthesia. Although the anesthesiologists always encountered difficulties in managing the airway, most of the anesthetic procedures were performed safely except for 1 case that resulted in mortality. CONCLUSION: Managing the airway of patients with craniofacial abnormalities can potentially be difficult. It should be carried out by experienced anesthesiologists, with assistance from an otolaryngologist when necessary. A variety of different airway devices should be available if needed.

Intermittent small doses of propofol for sedation of pediatric patients undergoing magnetic resonance imaging.

BACKGROUND: Sedation of children is always necessary for magnetic resonance imaging (MRI). General anesthesia may be recommended for infants and small children to protect the airway or in children who have previously failed sedation. Our practice has been to use intermittent administration of small doses of propofol. METHODS: We retrospectively reviewed the anesthesia records of all children who underwent sedation for MRI between March 2004 and March 2007. RESULTS: A total of 120 children underwent sedation for MRI. Few adverse events (respiratory 3%, movement 8%) and no complications occurred during sedation. Almost all of the procedures (99%) were completed successfully. CONCLUSIONS: Our experience demonstrates that intermittent administration of small doses of propofol by experienced personnel for MRI can be used safely and effectively in pediatric patients.

Delayed tension pneumothorax during surgery.

Tension pneumothorax is a life-threatening emergency that rapidly results in cardiopulmonary arrest. It requires prompt diagnosis and treatment. We present 2 cases from our practice, 1 caused by blunt chest trauma and the other resulting from laparoscopic surgery. Both were successfully treated by insertion of a chest tube. The diagnosis and treatment of intraoperative pneumothorax is discussed together with a review of the literature.