Rocuronium, a monoquaternary steroid analogue of vecuronium, is designed to provide a rapid onset of action. Experimentally, it has been shown that two non-depolarizing neuromuscular relaxants ...administered together can produce either a neuromuscular block of a size expected to be the sum of the individual doses (additive effect) or a larger neuromuscular block (synergistic effect). Experimental observations have suggested that during onset rocuronium acts synergistically with other nondepolarizing agents, but that at a steady state the combined action is additive.
To investigate whether rocuronium can speed up the onset of atracurium for intubation, 120 patients who consented to receive elective surgery requiring tracheal intubation were randomly assigned to 3 equally divided groups to receive one of the following three different combinations of muscle relaxants: twice ED95 of rocuronium (0.6 mg/kg group 1), an equipotent mixture of ED95 of rocuronium and atracurium (0.3 mg/kg and 0.25 mg/kg respectively, group 2), and rocuronium 0.1 mg/kg to prime atracurium 0.42 mg/kg at 1 min interval. Intubation conditions were assessed 1 minute after intravenous muscle relaxant injection, and scored as good, acceptable and poor based on four clinical evaluators: the ease of laryngoscopy (score of 1-3), the relaxation of vocal cord (1-3), the degree of coughing (1-3), and movement of extremity (1-3). Adding up together, intubation condition that scored 4-5 was considered to be good, 6-7 acceptable, and 8-12 poor.
The conditions produced in the rocuronium and the mixture groups were similar and both were moderately better than those of the priming group. Good intubation conditions were achieved in 58% patients of the rocuronium group, 63% of the mixture group and 43% of the priming group. By Pearson Chi-square test, the comparisons did not show statistical significance between groups.
Statistically, rocuronium alone, mixture of equipotent atracurium and rocuronium, and using rocuronium to prime atracurium all provided similar onset for satisfactory intubation.
Tumor microenvironments (TMEs) activate various axes/pathways, predominantly inflammatory and hypoxic responses, impact tumorigenesis, metastasis and therapeutic resistance significantly. Although ...molecular pathways of individual TME are extensively studied, evidence showing interaction and crosstalk between hypoxia and inflammation remain unclear. Thus, we examined whether interferon (IFN) could modulate both inflammatory and hypoxic responses under normoxia and its relation with cancer development.
IFN was used to induce inflammation response and HIF-1α expression in various cancer cell lines. Corresponding signaling pathways were then analyzed by a combination of pharmacological inhibitors, immunoblotting, GST-Raf pull-down assays, dominant-negative and short-hairpin RNA-mediated knockdown approaches. Specifically, roles of functional HIF-1α in the IFN-induced epithelial-mesenchymal transition (EMT) and other tumorigenic propensities were examined by knockdown, pharmacological inhibition, luciferase reporter, clonogenic, anchorage-independent growth, wound-healing, vasculogenic mimicry, invasion and sphere-formation assays as well as cellular morphology observation.
We showed for the first time that IFN induced functional HIF-1α expression in a time- and dose- dependent manner in various cancer cell lines under both hypoxic and normoxic conditions, and then leading to an activated HIF-1α pathway in an IFN-mediated pro-inflammatory TME. IFN regulates anti-apoptosis activity, cellular metastasis, EMT and vasculogenic mimicry by a novel mechanism through mainly the activation of PI3K/AKT/mTOR axis. Subsequently, pharmacological and genetic modulations of HIF-1α, JAK, PI3K/AKT/mTOR or p38 pathways efficiently abrogate above IFN-induced tumorigenic propensities. Moreover, HIF-1α is required for the IFN-induced invasiveness, tumorigenesis and vasculogenic mimicry. Further supports for the HIF-1α-dependent tumorigenesis were obtained from results of xenograft mouse model and sphere-formation assay.
Our mechanistic study showed an induction of HIF-1α and EMT ability in an IFN-mediated inflammatory TME and thus demonstrating a novel interaction between inflammatory and hypoxic TMEs. Moreover, targeting HIF-1α may be a potential target for inhibiting tumor tumorigenesis and EMT by decreasing cancer cells wound healing and anchorage-independent colony growth. Our results also lead to rationale guidance for developing new therapeutic strategies to prevent relapse via targeting TME-providing IFN signaling and HIF-1α programming.
Retrospective cohort study. To validate computed tomography (CT) radiodensity in Hounsfield units (HU) as a prognostic marker for pedicle screw loosening or cage subsidence in minimally invasive ...transforaminal lumbar interbody fusion (MI-TLIF). The retrospective study involved 198 patients treated with MI-TLIF. Screw loosening (SL), cage subsidence (CS), and fusion status were assessed by plain radiographs. The risk factors of SL and CS were identified using logistic regression. A total of 258 levels and 930 screws were analyzed. During a 2-year follow-up, 16.2% and 24.7% of patients had CS and SL respectively. The cut-off value of L1 HU for predicting SL or CS was 117. The L1 HU < 117 and BMI ≥ 25 were two independent risk factors. The risk of SL or CS was 4.1 fold in patients L1 HU < 117 and 2.6 fold in patients with BMI ≥ 25. For patients concurrently having BMI ≥ 25 and pre-op L1 HU < 117, the risk was 4.3 fold. Fusion rate and clinical outcome were comparable in patients with SL or CS. L1 HU < 117 and BMI > 25 were two independent risk factors that can be screened preoperatively for preventing SL or CS and lead to better management of patients undergoing MI-TLIF.
Kagome-nets, appearing in electronic, photonic and cold-atom systems, host frustrated fermionic and bosonic excitations. However, it is rare to find a system to study their fermion-boson many-body ...interplay. Here we use state-of-the-art scanning tunneling microscopy/spectroscopy to discover unusual electronic coupling to flat-band phonons in a layered kagome paramagnet, CoSn. We image the kagome structure with unprecedented atomic resolution and observe the striking bosonic mode interacting with dispersive kagome electrons near the Fermi surface. At this mode energy, the fermionic quasi-particle dispersion exhibits a pronounced renormalization, signaling a giant coupling to bosons. Through the self-energy analysis, first-principles calculation, and a lattice vibration model, we present evidence that this mode arises from the geometrically frustrated phonon flat-band, which is the lattice bosonic analog of the kagome electron flat-band. Our findings provide the first example of kagome bosonic mode (flat-band phonon) in electronic excitations and its strong interaction with fermionic degrees of freedom in kagome-net materials.
•Butanol production from microalgae biodiesel residues via ABE fermentation.•More than twofold of butanol yield increase with additional butyrate of 18–20g/L.•The highest butanol production of ...3.86g/L was achieved with residues of 300g/L.•The highest butanol yield of 0.13g/g-carbohydrate was with residues of 100g/L.•One third of carbohydrate from residues cannot be utilized by C. acetobutylicum.
This study conducted batch experiments to evaluate the potential of butanol production from microalgae biodiesel residues by Clostridium acetobutylicum. The results indicated that with 90g/L of glucose as the sole substrate the highest butanol yield of 0.2g/g-glucose was found, but the addition of butyrate significantly enhanced the butanol yield. The highest butanol yield of 0.4g/g-glucose was found with 60g/L of glucose and 18g/L of butyrate. Using microalgae biodiesel residues as substrate, C. acetobutylicum produced 3.86g/L of butanol and achieved butanol yield of 0.13g/g-carbohydrate via ABE fermentation, but the results indicated that approximately one third of carbohydrate was not utilized by C. acetobutylicum. Biological butanol production from microalgae biodiesel residues can be possible, but further research on fermentation strategies are required to improve production yield.
Abstract
Background
Early versions of spinal muscular atrophy (SMA) scoliosis correction surgery often involved sublaminar devices. Recently, the utilization of pedicle screws has gained much ...popularity. Pedicle screws are generally believed to provide additional deformity correction, but pedicle size and rotational deformity limit their application in the thoracic spine, resulting in a hybrid construct involving pedicle screws and sublaminar wire. Studies of the efficacy of hybrid instrumentation in SMA scoliosis are often limited by the scarcity of the disease itself. In this study, we aimed to compare the surgical outcomes between hybrid constructs involving pedicle screws and sublaminar wire and sublaminar wire alone in patients with SMA scoliosis.
Methods
We retrospectively reviewed the clinical records and radiographic assessments of patients with SMA scoliosis who underwent corrective surgery between 1993 and 2017. The radiographic assessments included deformity correction and progressive changes in the major curve angle, pelvic tilt (PT) and coronal balance (CB). The correction of deformities was observed postoperatively and at the patient’s 2-year follow-up to test the efficacy of each type of construct.
Results
Thirty-three patients were included in this study. There were 14 and 19 patients in the wiring and hybrid construct groups, respectively. The hybrid construct group demonstrated a higher major curve angle correction (50.5° ± 11.2° vs. 36.4° ± 8.4°,
p
< 0.001), a higher apical vertebral rotation correction (10.6° ± 3.9° vs. 4.8° ± 2.6°,
p
< 0.001), and a reduced progression of the major curve angle at the 2-year follow-up (5.1° ± 2.9° vs. 8.7° ± 4.8°,
p
< 0.001). A moderate correlation was observed between the magnitude of correction of the apical vertebral rotation angle and the major curve (r = 0.528,
p
= 0.002).
Conclusion
This study demonstrated that hybrid instrumentation can provide a greater magnitude of correction in major curve and apical rotation as well as less major curve progression than sublaminar wire instrumentation alone in patients with SMA scoliosis. Level of evidence III
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low back pain is a common clinical problem that causes disability and impaired quality of life. While the reason behind low back pain was largely considered to be of musculoskeletal origin, the ...contribution of inflammatory cytokines and oxidative stress could never be overlooked. Exercise has been proven to be an effective approach to treat low back pain. However, the mechanism of the exercise effect on the inflammatory cytokines and oxidative stress is still largely unknown. In this study, we revealed that exercise intervention reduces Toll-like receptor 4 (TLR-4) pathway and enhances Sirtuin 1 (SIRT1) expression in low back pain patients. We also confirmed that exercise up-regulates the expression of peroxisome proliferator-activated receptor-gamma, PPAR-γ coactivator-1 and FoxOs family proteins and also increases the activity of catalase and superoxide dismutase in patients with low back pain. Furthermore, we found that exercise intervention attenuates the oxidative stress, pro-inflammatory cytokine concentrations and p53 expression in patients with low back pain. This study demonstrates that exercise intervention improves low back pain symptoms through regulation of the SIRT1 axis with repression of oxidative stress and TLR-4 inhibition.
Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical ...applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium- hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.
► Metal foams are used to replace conventional flow channels as the flow distributor. ► Cell with metal foam out-performs the conventional cell with flow channel plate. ► Mass transport limitation ...phenomenon is not as obvious as in conventional unit cell. ► This is due to metal foam’s high porosity plus convective flow through the foam. ► Even operated at 40°C, the current density reaches 1870mAcm−2 at 0.6V.
In this work, we report our experimental results of the PEM fuel cell with metal foam as flow distributor. These experimental results show the characteristics of the PEM fuel cell with the metal foam as flow distributor and extend our understanding of the relation between cell performance and mass transport properties into a region of parameters that the conventional PEM unit cell cannot provide. The comparison in polarization curve is made between the PEM unit cell with different metal-foam properties and the PEM unit cell with graphite flow channel plate as flow distributor. The experimental results show that the PEM fuel cell with metal foam as flow distributor possesses some unique characteristics compared with the conventional PEM unit cell with flow channel plate as flow distributor. The unique characteristics are listed in this paper with our preliminary analysis. Due to the high porosity of metal-foam (as high as 95%) plus convective flow through the metal-foam, mass transport limitation phenomenon is not as pronounced as in the case of conventional PEM unit cell with flow channel plate as flow distributor. Another interesting phenomenon is that electrical conductivity of metal-foam plays a significant role in performance, which is seldom the case in the conventional PEM unit cell with flow channel plate as flow distributor. Although there are several technical challenges to be overcome for the current form of metal-foam to replace flow channel plates, the unique mass-transport properties of metal foam plus its light weight are very attractive.
Patients with diabetes mellitus can experience hyperglycemia, which affects brain function and produces cognitive impairment or neurodegeneration. Neuroinflammation is an important cause of cognitive ...dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antihyperglycemic agents that reportedly possess anti-inflammatory properties and may produce beneficial cognitive effects. We hypothesized that SGLT2 inhibitors alleviate hyperglycemia-related inflammation in brain immune cells. Cultured BV-2 microglia were exposed to high glucose (HG) in the absence or presence of SGLT2 inhibitors including canagliflozin (Cana), dapagliflozin (Dapa), empagliflozin (Empa), and ertugliflozin (Ertu). Afterward, we evaluated the cytotoxic and inflammatory responses by specific biochemical assays. Treatments with non-toxic Cana or Dapa, but not Empa or Ertu, inhibited proliferation without cell death. Only Cana rescued BV-2 microglia from HG-induced cytotoxicity, including apoptosis or autophagic degradation. None of SGLT2 inhibitors affected the HG-stimulated induction of stress proteins HO-1 and HSP70. Also, compared to the other three SGLT2 inhibitors, Cana was better at inhibiting HG-induced oxidative/inflammatory stress, as evidenced by its ability to repress proinflammatory factors (e.g., oxygen free radicals, iNOS, NLRP3, IL-1β, and TNF-α) other than COX-2. Cana's action to alleviate HG insults was mediated not by altering SGLT2 protein expression, but by reducing HG-stimulated signaling activities of NFκB, JNK, p38, and PI3K/Akt pathways. Particularly, Cana imitated the effects of NFκB inhibitor on HG-induced iNOS and COX-2. Of the four SGLT2 inhibitors, Cana provided BV-2 microglia with the best protection against HG-induced inflammatory toxicity. Thus, Cana may help to reduce innate neuroimmune damage caused by hyperglycemia.