Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma.

Background Image-guided tumor ablation is the first-line therapy for early-stage hepatocellular carcinoma (HCC), with ongoing investigations into its combination with immunotherapies. Matrix metalloproteinase (MMP) inhibition demonstrates immunomodulatory potential and reduces HCC tumor growth when combined with ablative treatment. Purpose To evaluate the effect of incomplete cryoablation with or without MMP inhibition on the local immune response in residual tumors in a murine HCC model. Materials and Methods Sixty 8- to 10-week-old female BALB/c mice underwent HCC induction with use of orthotopic implantation of syngeneic Tib-75 cells. After 7 days, mice with a single lesion were randomized into treatment groups: (a) no treatment, (b) MMP inhibitor, (c) incomplete cryoablation, and (d) incomplete cryoablation and MMP inhibitor. Macrophage and T-cell subsets were assessed in tissue samples with use of immunohistochemistry and immunofluorescence (cell averages calculated using five 1-µm2 fields of view [FOVs]). C-X-C motif chemokine receptor type 3 (CXCR3)- and interferon γ (IFNγ)-positive T cells were assessed using flow cytometry. Groups were compared using unpaired Student t tests, one-way analysis of variance with Tukey correction, and the Kruskal-Wallis test with Dunn correction. Results Mice treated with incomplete cryoablation (n = 6) showed greater infiltration of CD206+ tumor-associated macrophages (mean, 1.52 cells per FOV vs 0.64 cells per FOV; P = .03) and MMP9-expressing cells (mean, 0.89 cells per FOV vs 0.11 cells per FOV; P = .03) compared with untreated controls (n = 6). Incomplete cryoablation with MMP inhibition (n = 6) versus without (n = 6) led to greater CD8+ T-cell (mean, 15.8% vs 8.29%; P = .04), CXCR3+CD8+ T-cell (mean, 11.64% vs 8.47%; P = .004), and IFNγ+CD8+ T-cell infiltration (mean, 11.58% vs 5.18%; P = .02). Conclusion In a mouse model of HCC, incomplete cryoablation and systemic MMP inhibition showed increased cytotoxic CD8+ T-cell infiltration into the residual tumor compared with either treatment alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Gemmete in this issue.

Bioenergetics of Axon Integrity and Its Regulation by Oligodendrocytes and Schwann Cells.

Axons are long slender portions of neurons that transmit electrical impulses to maintain proper physiological functioning. Axons in the central nervous system (CNS) and peripheral nervous system (PNS) do not exist in isolation but are found to form a complex association with their surrounding glial cells, oligodendrocytes and Schwann cells. These cells not only myelinate them for faster nerve impulse conduction but are also known to provide metabolic support. Due to their incredible length, continuous growth, and distance from the cell body (where major energy synthesis takes place), axons are in high energetic demand. The stability and integrity of axons have long been associated with axonal energy levels. The current mini-review is thus focused on how axons accomplish their high energetic requirement in a cell-autonomous manner and how the surrounding glial cells help them in maintaining their integrity by fulfilling their energy demands (non-cell autonomous trophic support). The concept that adjacent glial cells (oligodendrocytes and Schwann cells) provide trophic support to axons and assist them in maintaining their integrity comes from the conditional knockout research and the studies in which the metabolic pathways controlling metabolism in these glial cells are modulated and its effect on axonal integrity is evaluated. In the later part of the mini-review, the current knowledge of axon-glial metabolic coupling during various neurodegenerative conditions was discussed, along with the potential lacunae in our current understanding of axon-glial metabolic coupling.

Spatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb.

Carbon dioxide (CO2) is traditionally considered as metabolic waste, yet its regulation is critical for brain function. It is well accepted that hypercapnia initiates vasodilation, but its effect on neuronal activity is less clear. Distinguishing how stimulus- and CO2-induced vasodilatory responses are (dis)associated with neuronal activity has profound clinical and experimental relevance. We used an optical method in mice to simultaneously image fluorescent calcium (Ca2+) transients from neurons and reflectometric hemodynamic signals during brief sensory stimuli (i.e., hindpaw, odor) and CO2 exposure (i.e., 5%). Stimuli-induced neuronal and hemodynamic responses swiftly increased within locally activated regions exhibiting robust neurovascular coupling. However, hypercapnia produced slower global vasodilation which was temporally uncoupled to neuronal deactivation. With trends consistent across cerebral cortex and olfactory bulb as well as data from GCaMP6f/jRGECO1a mice (i.e., green/red Ca2+ fluorescence), these results unequivocally reveal that stimuli and CO2 generate comparable vasodilatory responses but contrasting neuronal responses. In summary, observations of stimuli-induced regional neurovascular coupling and CO2-induced global neurovascular uncoupling call for careful appraisal when using CO2 in gas mixtures to affect vascular tone and/or neuronal excitability, because CO2 is both a potent vasomodulator and a neuromodulator.

Fluorescently-tagged magnetic protein nanoparticles for high-resolution optical and ultra-high field magnetic resonance dual-modal cerebral angiography.

Extremely small paramagnetic iron oxide nanoparticles (FeMNPs) (<5 nm) can enhance positive magnetic resonance imaging (MRI) contrast by shortening the longitudinal relaxation time of water (T1), but these nanoparticles experience rapid renal clearance. Here, magnetic protein nanoparticles (MPNPs) are synthesized from protein-conjugated citric acid coated FeMNPs (c-FeMNPs) without loss of the T1 MRI properties and tagged with fluorescent dye (f-MPNPs) for optical cerebrovascular imaging. The c-FeMNPs shows average size 3.8 ± 0.7 nm with T1 relaxivity (r1) of 1.86 mM-1 s-1 and transverse/longitudinal relaxivity ratio (r2/r1) of 2.53 at 11.7 T. The f-MPNPs show a higher r1 value of 2.18 mM-1 s-1 and r2/r1 ratio of 2.88 at 11.7 T, which generates excellent positive MRI contrast. In vivo cerebral angiography with f-MPNPs enables detailed microvascular contrast enhancement for differentiation of major blood vessels of murine brain, which corresponds well with whole brain three-dimensional time-of-flight MRI angiograms (17 min imaging time with 60 ms repetition time and 40 µm isotropic voxels). The real-time fluorescence angiography enables unambiguous detection of brain capillaries with diameter < 40 µm. Biodistribution examination revealed that f-MPNPs were safely cleared by the organs like the liver, spleen, and kidneys within a day after injection. Blood biochemical assays demonstrated no risk of iron overload in both rats and mice. With hybrid neuroimaging technologies (e.g., MRI-optical) on the rise, f-MPNPs built on this platform can generate exciting neuroscience applications.

BAY 11-7082 inhibits the secretion of interleukin-6 by senescent human microglia.

The accumulation of senescent cells in aged tissues has been implicated in a variety of age-related diseases, including cancer and neurodegenerative disorders. Recent studies have demonstrated a link between age-associated increase of senescent glial cells in the brain and the pathogenesis of Alzheimer's disease (AD). However, there is a lack of in vitro cellular models of senescent human microglia, which significantly limits our approaches to study AD pathogenesis. Here, we show for the first time that ionizing radiation (IR) dose-dependently induces premature senescence in HMC3 human microglial cells. Senescence-associated ß-galactosidase activity, a well-characterized marker of cellular senescence, was substantially increased in irradiated HMC3 cells compared with control cells. Furthermore, we found that phosphorylated p53 levels and p21 expression levels were markedly higher in IR-induced senescent microglia than in control cells. Senescent human microglia exhibited the senescence-associated secretory phenotype (SASP), as evidenced by the increased secretion of pro-inflammatory cytokine interleukin-6 (IL-6). Treatment with an NF-κB inhibitor, BAY 11-7082, inhibits the secretion of IL-6 by senescent HMC3 cells. Collectively, our studies have established an in vitro cellular model of human microglial senescence and suggest that the NF-κB pathway may play a critical role in regulating the SASP of senescent HMC3 cells.

High-resolution pH imaging using ratiometric chemical exchange saturation transfer combined with biosensor imaging of redundant deviation in shifts featuring paramagnetic DOTA-tetraglycinate agents.

Chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS) methods differ respectively by detecting exchangeable and nonexchangeable proton signals by magnetic resonance. Because CEST contrast depends on both temperature and pH, simultaneous CEST and BIRDS imaging can be employed to separate these contributions. Here, we test if high-resolution pH imaging in vivo is possible with ratiometric CEST calibrated for temperature variations measured by BIRDS. Thulium- and europium-based DOTA-tetraglycinate agents, TmDOTA-(gly)4- and EuDOTA-(gly)4- , were used for high-resolution pH mapping in vitro and in vivo, using BIRDS for temperature adjustments needed for a more accurate ratiometric CEST approach. Although neither agent showed pH dependence with BIRDS in vitro in the pH range 6 to 8, each one's temperature sensitivity was enhanced when mixed because of increased redundancy. By contrast, the CEST signal of each agent was affected by the presence of the other agent in vitro. However, pH could be measured more accurately when temperature from BIRDS was detected. These in vitro calibrations with TmDOTA-(gly)4- and EuDOTA-(gly)4- enabled high-resolution pH imaging of glioblastoma in rat brains. It was concluded that temperature mapping with BIRDS can calibrate the ratiometric CEST signal from a cocktail of TmDOTA-(gly)4- and EuDOTA-(gly)4- agents to provide temperature-independent absolute pH imaging in vivo.

Methylated tetra-amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST.

Paramagnetic agents that utilize two mechanisms to provide physiological information by magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) are described. MRI with chemical exchange saturation transfer (CEST) takes advantage of the agent's exchangeable protons (e.g., -OH or -NHx , where 2 ≥ x ≥ 1) to create pH contrast. The agent's incorporation of non-exchangeable protons (e.g., -CHy , where 3 ≥ y ≥ 1) makes it possible to map tissue temperature and/or pH using an MRSI method called biosensor imaging of redundant deviation in shifts (BIRDS). Hybrid probes based upon 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelate (DOTA4- ) and its methylated analog (1,4,7,10-tetraazacyclododecane-α, α', α″, α‴-tetramethyl-1,4,7,10-tetraacetate, DOTMA4- ) were synthesized, and modified to create new tetra-amide chelates. Addition of several methyl groups per pendent arm of the symmetrical chelates, positioned proximally and distally to thulium ions (Tm3+ ), gave rise to favorable BIRDS properties (i.e., high signal-to-noise ratio (SNR) from non-exchangeable methyl proton peaks) and CEST responsiveness (i.e., from amide exchangeable protons). Structures of the Tm3+ probes elucidate the influence of methyl group placement on sensor performance. An eight-coordinate geometry with high symmetry was observed for the complexes: Tm-L1 was based on DOTA4- , whereas Tm-L2 and Tm-L3 were based on DOTMA4- , where the latter contained an additional carboxylate at the distal end of each arm. The distance of Tm3+ from terminal methyl carbons is a key determinant for sustaining BIRDS temperature sensitivity without compromising CEST pH contrast; however, water solubility was influenced by introduction of hydrophobic methyl groups and hydrophilic carboxylate. Combined BIRDS and CEST detection of Tm-L2, which features two high-SNR methyl peaks and a strong amide CEST peak, should enable simultaneous temperature and pH measurements for high-resolution molecular imaging in vivo.

Imaging Hallmarks of the Tumor Microenvironment in Glioblastoma Progression.

Glioblastoma progression involves multifaceted changes in vascularity, cellularity, and metabolism. Capturing such complexities of the tumor niche, from the tumor core to the periphery, by magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) methods has translational impact. In human-derived glioblastoma models (U87, U251) we made simultaneous and longitudinal measurements of tumor perfusion (Fp), permeability (Ktrans), and volume fractions of extracellular (ve) and blood (vp) spaces from dynamic contrast enhanced (DCE) MRI, cellularity from apparent diffusion coefficient (ADC) MRI, and extracellular pH (pHe) from an MRSI method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). Spatiotemporal patterns of these parameters during tumorigenesis were unique for each tumor. While U87 tumors grew faster, Fp, Ktrans, and vp increased with tumor growth in both tumors but these trends were more pronounced for U251 tumors. Perfused regions between tumor periphery and core with U87 tumors exhibited higher Fp, but Ktrans of U251 tumors remained lowest at the tumor margin, suggesting primitive vascularization. Tumor growth was uncorrelated with ve, ADC, and pHe. U87 tumors showed correlated regions of reduced ve and lower ADC (higher cellularity), suggesting ongoing proliferation. U251 tumors revealed that the tumor core had higher ve and elevated ADC (lower cellularity), suggesting necrosis development. The entire tumor was uniformly acidic (pHe 6.1-6.8) early and throughout progression, but U251 tumors were more acidic, suggesting lower aerobic glycolysis in U87 tumors. Characterizing these cancer hallmarks with DCE-MRI, ADC-MRI, and BIRDS-MRSI will be useful for exploring tumorigenesis as well as timely therapies targeted to specific vascular and metabolic aspects of the tumor microenvironment.

Effect of combinations of dexamethasone-ondansetron and dexamethasone-ondansetron-aprepitant versus aprepitant alone for early postoperative nausea and vomiting after day care gynaecological laparoscopy: A randomised clinical trial.

BACKGROUND AND AIMS: This study was designed to compare the effectiveness of the combination of dexamethasone-ondansetron with oral aprepitant alone and triple combination therapy with all three agents (dexamethasone-ondansetron and oral aprepitant) in the prevention of postoperative nausea and vomiting (PONV) in day care gynaecologic laparoscopy. METHODS: This was a randomised clinical trial conducted at a university teaching hospital. A total of 105 female patients were randomised into the aprepitant (A), dexamethasone-ondansetron (DO) and aprepitant-dexamethasone-ondansetron (ADO) groups. The patients in the A group received only 80 mg oral aprepitant 1 h before surgery. The patients in the DO group, received dexamethasone 8 mg at induction with ondansetron 4 mg before extubation. Patients in the ADO group received 80 mg oral aprepitant 1 h before surgery, dexamethasone 8 mg at induction and ondansetron 4 mg before extubation. Incidence of nausea and vomiting was compared between groups using the Chi-square test/Fisher's test. Bellville score for severity of PONV was analysed using the Kruskall-Wallis test. P value < 0.05 was regarded as significant. RESULTS: The incidence of PONV did not show a statistically significant difference between the three groups, with a P value of 0.13 (12.5%, 30.3% and 32.3% in groups ADO, DO and A, respectively). The severity of PONV measured using Bellville score was also not significantly different among the groups [median values (IQR) of 0 (0-0), 0 (0-1), and 0 (0-1)]. CONCLUSION: The combination of aprepitant, dexamethasone and ondansetron failed to demonstrate a statistically significant superiority over the other two antiemetic regimens.

Imaging the transmembrane and transendothelial sodium gradients in gliomas.

Under normal conditions, high sodium (Na+) in extracellular (Na+e) and blood (Na+b) compartments and low Na+ in intracellular milieu (Na+i) produce strong transmembrane (ΔNa+mem) and weak transendothelial (ΔNa+end) gradients respectively, and these manifest the cell membrane potential (Vm) as well as blood-brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa+mem and ΔNa+end. In vitro 23Na-MRSI established that the 23Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23Na-MRSI showed Na+i remained unshifted and Na+b was more shifted than Na+e, and these together revealed weakened ΔNa+mem and enhanced ΔNa+end in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa+mem (i.e., depolarized Vm) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na+end suggesting altered BBB integrity. We anticipate that 23Na-MRSI will allow biomedical explorations of perturbed Na+ homeostasis in vivo.

Memantine and Ibuprofen pretreatment exerts anti-inflammatory effect against streptozotocin-induced astroglial inflammation via modulation of NMDA receptor-associated downstream calcium ion signaling.

We had previously reported that neuroinflammation and memory impairment associated with intracerebroventricular streptozotocin (ICV STZ) injection in rats was due to glial activation and modulation of the N-methyl-D-aspartate (NMDA) receptor function. However, the exact role of the NMDA receptor and the molecules associated with downstream calcium ion signaling in STZ-induced astroglial activation is not known. Thus, in the present study, Memantine (an NMDA receptor antagonist) and Ibuprofen (an anti-inflammatory drug) were used as the pharmacological tool to investigate the molecular mechanisms involved in STZ-induced astroglial inflammation. We have studied the effect of STZ (100 µM) treatment for 24 h on NMDA receptor subunits (NR1, NR2A, and NR2B) expression and its associated calcium ion regulated molecules calcium/calmodulin-dependent protein kinase II subunit α (CaMKIIα), cyclic AMP-response element-binding (CREB) protein, Calpain, and Caspase 3. We have found a significant increase in the expression of NR1, NR2B, Calpain, and Caspase 3 expression, whereas a decrease in the level of NR2A, CaMKIIα, and CREB protein expression after 24 h of STZ treatment. These results indicate that STZ altered the NMDA receptor subunit expression and its downstream calcium (Ca2+) ion signaling molecules. We have also found that both Memantine (5 µM) and Ibuprofen (200 µM) significantly prevented the STZ-induced change in CaMKIIα, CREB, Calpain, and Caspase 3 expressions in C6 astrocytoma cells. Interestingly, only Memantine (and not Ibuprofen) was able to prevent the changes in NMDA receptor subunit expression in STZ-treated astrocytoma cells. STZ treatment also increased the level of glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and decreased the level of interleukin-10 (IL-10), indicating inflammatory condition, which was restored by both Memantine and Ibuprofen. These results suggest that both Memantine and Ibuprofen exert anti-inflammatory effect against STZ-induced astroglial activation and neuroinflammation via modulation of NMDA receptor-associated downstream calcium signaling cascade. However, only Memantine (not Ibuprofen) was able to revert STZ-induced changes in NMDA receptor subunit expression.

Memantine treatment exerts an antidepressant-like effect by preventing hippocampal mitochondrial dysfunction and memory impairment via upregulation of CREB/BDNF signaling in the rat model of chronic unpredictable stress-induced depression.

Mitochondrial and cognitive dysfunctions have long been associated with major depressive disorders (MDDs). Studies have shown that Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, possesses an antidepressant-like effect. Hence, the NMDA receptor can be a better therapeutic target for MDD. Therefore, the present study was designed to study the impact of Memantine on mitochondrial functional status and depression-like symptoms in the chronic unpredictable stress (CUS) model of depression. CUS for 28 days resulted in depression-like symptoms (as indicated by increased immobility time in the forced swim test) and a decline in the spatial learning and retention memory in the Morris water maze (MWM) test, which was prevented by Memantine (10 mg/kg/day) treatment. We observed elevated plasma corticosterone (CORT) levels, microdialysates glutamate concentration, and synaptosomal calcium (Ca2+) ion levels after 28 days of CUS. Memantine treatment prevented only increased plasma CORT and synaptosomal Ca2+ ion levels. Memantine treatment also restored CUS induced increase in oxidative stress parameters [increased neuronal nitric oxide synthase (nNOS) expression, nitric oxide (NO) levels, lipid peroxidation (LPO) and superoxide dismutase (SOD) activity], decrease in mitochondrial electron transport chain (ETC) enzymes activity and mitochondrial membrane potential (MMP). CUS also reduced the expression of cell survival genes, cyclic-AMP response element-binding protein (CREB), and brain-derived nerve growth factor (BDNF), which was reversed by treatment with Memantine. CUS, however, caused a non-significant decrease in the hippocampal adenosine triphosphate (ATP) levels and a non-significant increase in the expression of pro-apoptotic genes, Caspase 3, and the number of TUNEL positive cells, indicating that hippocampal mitochondrial dysfunction caused due to CUS was not severe enough to affect overall energy production, mitochondrial integrity, and cellular apoptosis status. Thus, Memantine treatment exerts an antidepressant-like effect by preventing CUS induced excitotoxicity, oxidative stress, and enhancing CUS induced decrease in mitochondrial functioning and expression of cell survival genes via upregulation of stress-responsive CREB/BDNF signaling.

Intranasal Insulin Enhances Intracerebroventricular Streptozotocin-Induced Decrease in Olfactory Discriminative Learning via Upregulation of Subventricular Zone-Olfactory Bulb Neurogenesis in the Rat Model.

Olfactory perception and learning play a vital role in the animal's entire life for habituation and survival. Insulin and insulin receptor signaling is well known to modulate the olfactory function and is also involved in the regulation of neurogenesis. A very high density of insulin receptors is present in the olfactory bulb (OB), the brain area involved in the olfactory function, where active adult neurogenesis also takes place. Hence, our study was aimed to explore the effect of intranasal insulin treatment and the involvement of the subventricular zone-olfactory bulb (SVZ-OB) neurogenesis on olfactory discriminative learning and memory in intracerebroventricular streptozotocin (ICV STZ) rat model. Our findings revealed that intranasal insulin treatment significantly increased ICV STZ-induced decrease in the olfactory discriminative learning. No significant change was observed in the post-treatment olfactory memory upon ICV STZ and intranasal insulin treatment. ICV STZ also caused a substantial decline in the SVZ-OB neurogenesis, as indicated by the reduction in the number of 5-bromo-2'-deoxyuridine (BrdU+) cells, BrdU+ Nestin+ cells, and Doublecortin (DCX+) cells, which was reversed by intranasal insulin treatment. Intranasal insulin treatment also increased the number of immature neurons reaching the olfactory bulb (OB) as indicated by an increase in the DCX expression in the OB as compared to the ICV STZ administered group. ICV STZ administration also resulted in the modulation of the expression of the genes regulating postnatal SVZ-OB neurogenesis like Mammalian achaete scute homolog 1 (Mash 1), Neurogenin 2 (Ngn 2), Neuronal differentiation 1 (Neuro D1), and T box brain protein 2 (Tbr 2). Intranasal insulin treatment reverted these changes in gene expression, which might be responsible for the observed increase in the SVZ-OB neurogenesis and hence the olfactory discriminative learning.

Standards of care for procedural sedation: Focus on differing perceptions among societies.

Adherence to established standards of care is important for anaesthesiologists to avoid undesirable legal consequences of their actions. The judiciary lays stress on the need to perpetuate healthy doctor-patient correspondence, good documentation, and to bestow a justifiable standard of care. But what defines standard of care and who delineates such standards is something that lacks clarity. The American Society for Gastrointestinal Endoscopy (ASGE) has recently released updated guidelines on the use of sedation and anaesthesia for gastrointestinal endoscopic procedures. Almost simultaneously, the American Society of Anesthesiologists (ASA) has brought out practice guidelines for moderate sedation and analgesia. In contrast to the ASA recommendations, ASGE does not view capnography as an essential monitoring modality for endoscopic procedures with moderate sedation because it has apparently not been shown to improve patient safety. However, they do agree that evidence supports its deployment during deep sedation. These differences in views between guidelines published by societies of substantial academic and clinical standing can confuse the agreement over what constitutes standard of care for the particular speciality. It is the expectation that guidelines and consensus statements in anaesthesiology be preferably issued by national or international organizations of the same speciality.

Comparision of Ambu AuraGain™ and LMA® ProSeal in children under controlled ventilation.

BACKGROUND AND AIMS: The LMA ProSeal® is considered a prototype among the second-generation supraglottic airway devices (SAD). The Ambu AuraGain™ is a relatively new, single use, second-generation SAD with a preformed shape. We conducted this study with the aim of comparing the difference in clinical performance between Ambu AuraGain™ and LMA ProSeal® in children receiving controlled ventilation. METHODS: Ninety-four children, aged between 6 months to 12 years, weighing 5 to 30 kg, belonging to American Society of Anesthesiologists Physical Status I and II, undergoing elective surgical procedures, were randomized into two groups. The primary end-point was oropharyngeal seal pressure, and the secondary parameters were the number of attempts, time of insertion, ease of placement of the device and gastric tube, and fiberoptic visualization of the laryngeal aperture. RESULTS: The mean oropharyngeal seal pressure with Ambu AuraGain™ was significantly higher than LMA ProSeal® (23.3 ± 4.6 cmH2O vs 20.6 ± 4.8 cmH2O, P = 0.007, respectively). The ease and success rate for device placement, fiberoptic visualization of the larynx, and complications were comparable. However, the time for insertion in Ambu AuraGain™ group was shorter when compared to LMA ProSeal® group, median (IQR [range]); 12 (10-15) s vs 20 (18-23) s (P < 0.001), respectively. The gastric drain was significantly easier to insert in Ambu AuraGain™ compared to LMA® ProSeal (P = 0.01). CONCLUSION: Our study suggests that Ambu AuraGain™ could be a useful disposable alternative to LMA ProSeal® for securing airway in children.

A Bimetallic Silver-Neodymium Theranostic Nanoparticle with Multimodal NIR/MRI/CT Imaging and Combined Chemo-photothermal Therapy.

An engineered metallic nanostructure is an excellent candidate for "theranosis" of cancer, having intrinsic properties of multimodal imaging and therapy. Toward this target, the development of silver-neodymium bimetallic nanoparticles (Ag-Nd BNPs) via microwave-assisted polyol synthesis is presented. The resultant Ag-Nd BNPs exhibit good monodispersity with average size of 10 nm, fluorescence in the near-infrared (NIR) region, and magnetic properties. The Ag-Nd BNPs also validate MRI, CT, and NIR trimodal imaging ability and enunciate valuable temperature response upon irradiation under a NIR laser. Aided by chitosan functionalization on the surface, the Ag-Nd BNPs deliver good biocompatibility and also promote the loading of paclitaxel, an anticancer drug. Isothermal titration calorimetry affirms the combination of strong binding affinity of drug and high loading efficiency of 7 drug molecules per nanoparticle. Moreover, Ag-Nd BNPs also illustrate a highly efficient photothermal effect in PBS. Therefore, the synergistic effects of paclitaxel and the photothermal effect make BNPs excellent "combined therapeutic agents", and also give them the important ability to destroy cancer cells in vitro at very low dose in comparison to single therapy. Thus, the Ag-Nd BNPs unveil a combination of MRI/CT/NIR imaging and chemo-photothermal therapy that ensures accurate diagnosis at an early stage and comprehensive eradication of tumor cells without affecting healthy cells.

Comparison of intubation success and glottic visualization using King Vision and C-MAC videolaryngoscopes in patients with cervical spine injuries with cervical immobilization: A randomized clinical trial.

BACKGROUND: Glottic visualization can be difficult with cervical immobilization in patients with cervical spine injury. Indirect laryngoscopes may provide better glottic visualization in these groups of patients. Hence, we compared King Vision videolaryngoscope, C-MAC videolaryngoscope for endotracheal intubation in patients with proven/suspected cervical spine injury. METHODS: After standard induction of anesthesia, 135 patients were randomized into three groups: group C (conventional C-MAC videolaryngoscope), group K (King Vision videolaryngoscope), and group D (D blade C-MAC videolaryngoscope). Cervical immobilization was maintained with Manual in line stabilization with anterior part of cervical collar removed. First pass intubation success, time for intubation, and glottic visualization (Cormack - Lehane grade and percentage of glottic opening) were noted. Intubation difficulty score (IDS) was used for grading difficulty of intubation. Five-point Likert scale was used for ease of insertion of laryngoscope. RESULTS: First attempt success rate were 100% (45/45), 93.3% (42/45), and 95.6% (43/45) in patients using conventional C-MAC, King Vision, and D blade C-MAC videolaryngoscopes, respectively. Time for intubation in seconds was significantly faster with conventional C-MAC videolaryngoscope (23.3 ± 4.7) compared to D blade C-MAC videolaryngoscope (26.7 ± 7.1), whereas conventional C-MAC and King Vision were comparable (24.9 ± 7.2). Good grade glottic visualization was obtained with all the three videolaryngoscopes. CONCLUSION: All the videolaryngoscopes provided good glottic visualization and first attempt success rate. Conventional C-MAC insertion was significantly easier. We conclude that all the three videolaryngoscopes can be used effectively in patients with cervical spine injury.

Doxorubicin-Conjugated Bimetallic Silver-Gadolinium Nanoalloy for Multimodal MRI-CT-Optical Imaging and pH-Responsive Drug Release.

Monodispersed chitosan-capped bimetallic nanoparticles (BNPs) of AgGd have been synthesized for "cancer theranosis" through environmentally benign microwave-assisted polyol synthesis. In the present article, we report the one-pot synthesis of AgGd BNPs with varied Ag:Gd molar ratios via coreduction of Ag+ and Gd3+ ions. Studies reveal a well-dispersed AgGd BNPs of average size 12 nm and also the presence of face-centered cubic (FCC) Ag and cubic Gd components within the individual crystal. Chitosan (CS) a biopolymer, as a capping agent facilitates the bioconjugation of doxorubicin (Dox), a potential anticancer drug on the surface of BNPs. The Dox was covalently conjugated onto the BNPs through pH-sensitive hydrazone linkage with CS. In vitro study reveals negligible drug release at physiological pH while release rate accelerates in acidic medium. The mutual properties of the host metals in AgGd BNPs at the nanoscale offer concurrent magnetic resonance imaging (MRI) and computed tomography (CT) contrast performances. Moreover, the paramagnetic behavior inherited by Gd in BNPs demonstrates both T1 and T2 contrast ability. BNPs ensures biocompatibility and also express sturdy therapeutic effects in HeLa cells when conjugated with Dox.

Copper incorporated microporous chitosan-polyethylene glycol hydrogels loaded with naproxen for effective drug release and anti-infection wound dressing.

Copper ion (Cu2+) incorporated microporous chitosan-polyethylene glycol films were developed as a multipotent wound dressing material. The mechanical properties, swelling behavior and moisture permeability of hydrogel films with varying Cu2+ concentration and the release of Cu2+ from films were evaluated. The results revealed the enhanced mechanical stability of films with increasing Cu2+ concentration without compromising moisture permeability and absorption capability of wound exudates. Microporous surface and swollen micropores in hydrated conditions were confirmed from morphological analysis. Degradation studies in lysozyme and H2O2 demonstrated increasing stability of films with increasing Cu2+ concentration up to 30days. Antibacterial tests revealed superiority in inhibiting biofilm formation in comparison to chitosan films. In vitro drug release, MTT assays and cell adhesion tests demonstrated the efficiency of Cu2+ incorporated hydrogels in sustained drug release and antibacterial activity with excellent keratinocyte cell response.