Exosomes from Human iPSC-Derived Retinal Organoids Enhance Corneal Epithelial Wound Healing.

This study investigated the therapeutic effects of exosomes derived from human-induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) on corneal epithelial wound healing. Exosomes were isolated from the culture medium of the hiPSC-derived ROs (Exo-ROs) using ultracentrifugation, and then they were characterized by a nanoparticle tracking analysis and transmission electron microscopy. In a murine model of corneal epithelial wounds, these exosomes were topically applied to evaluate their healing efficacy. The results demonstrated that the exosome-treated eyes showed significantly enhanced wound closures compared with the controls at 24 h post-injury. The 5-ethyl-2'-deoxyuridine assay and quantitative reverse transcription polymerase chain reaction revealed a substantial increase in cell proliferation and a decrease in inflammatory marker contents in the exosome-treated group. The RNA sequencing and exosomal microRNA analysis revealed that the Exo-RO treatment targeted various pathways related to inflammation and cell proliferation, including the PI3K-Akt, TNF, MAPK, and IL-17 signaling pathways. Moreover, the upregulation of genes related to retinoic acid and eicosanoid metabolism may have enhanced corneal epithelial healing in the eyes treated with the Exo-ROs. These findings suggest that hiPSC-derived RO exosomes could be novel therapeutic agents for promoting corneal epithelial wound healing.

Biomass- and Carbon Dioxide-Derived Polyurethane Networks for Thermal Interface Material Applications.

Recent environmental concerns have increased demand for renewable polymers and sustainable green resource usage, such as biomass-derived components and carbon dioxide (CO2). Herein, we present crosslinked polyurethanes (CPUs) fabricated from CO2- and biomass-derived monomers via a facile solvent-free ball milling process. Furan-containing bis(cyclic carbonate)s were synthesized through CO2 fixation and further transformed to tetraols, denoted FCTs, by aminolysis and utilized in CPU synthesis. Highly dispersed polyurethane-based hybrid composites (CPU-Ag) were also manufactured using a similar ball milling process. Due to the malleability of the CPU matrix, enabled by transcarbamoylation (dynamic covalent chemistry), CPU-based composites are expected to present very low interfacial thermal resistance between the heat sink and heat source. The characteristics of the dynamic covalent bond (i.e., urethane exchange reaction) were confirmed by the results of dynamic mechanical thermal analysis and stress relaxation analysis. Importantly, the high thermal conductivity of the CPU-based hybrid material was confirmed using laser flash analysis (up to 51.1 W/m·K). Our mechanochemical approach enables the facile preparation of sustainable polymers and hybrid composites for functional application.

Effect of fentanyl nasal packing treatment on patients with acute postoperative pain after closed reduction of nasal bone fracture: a randomized double-blind controlled trial.

PURPOSE: Nasal bone fracture reduction surgery is normally followed by nasal packing to control bleeding. Yet, patients suffer from pain and require further analgesic treatments following nasal packing and removal. This study aimed to evaluate the effect of fentanyl-soaked packing as a method of controlling pain after nasal surgeries in a prospective, randomized, double-blind controlled trial. METHODS: Sixty-five patients that have undergone closed nasal bone fracture reduction surgery were included in this study. Thirty-two patients were treated postoperatively with 50 mcg fentanyl-soaked Merocel®, a biodegradable synthetic polyurethane foams packing, and the other 33 patients were treated with saline-soaked packings. To analyze the relative nasal pain control effect of fentanyl, Numeric Rating Scale, patient satisfaction and Ramsay Sedation Scale were used. Patients were closely monitored to record relevant cardiopulmonary indicators and degree of adverse symptoms such as headache or sore throat. RESULTS: Fentanyl group had a significantly lower Numeric Rating Scale and higher patient satisfaction for most of the time periods after operation (p < .05). Symptoms of headache and sore throat were also significantly reduced. Ramsay Sedation Scale scores improved compared to the control group (p < .05). No significant differences in cardiopulmonary relevant indicators between the two experimental groups were observed (p > .05). CONCLUSION: Fentanyl-soaked packing significantly decreased postoperative pain with no observable adverse effects. Our results demonstrate that topical fentanyl application to nasal packing is an effective method of postoperative pain control after closed nasal bone fracture reduction surgery.

Comparison between cerebral state index and bispectral index during desflurane anesthesia.

BACKGROUND: Cerebral state index (CSI) is an anesthesia depth monitor alternative to bispectral index (BIS). Published comparative studies have used propofol or sevoflurane. However, studies using desflurane have not been reported yet. Different volatile anesthetics have different electroencephalography signatures. The performance of CSI may be different in desflurane anesthesia. Therefore, the objective of this study was to compare CSI and BIS during desflurane anesthesia. METHODS: Thirty-three patients were recruited. Desflurane and remifentanil were used to maintain general anesthesia. BIS and CSI were recorded simultaneously every minute. End-tidal concentration of desflurane was maintained at 4% from the beginning of surgery for 5 minutes. Pairwise data of CSI and BIS were obtained five times at one-minute intervals. This process was repeated in the order of 6%, 8%, and 10%. RESULTS: BIS and CSI were negatively correlated with the end-tidal concentration of desflurane with a similar degree of correlation (correlation coefficient BIS: -0.847, CSI: -0.844). The relationship between CSI and BIS had a good linearity with a slope close to 1 (R2 = 0.905, slope = 1.01). For the relationship between CSI and BIS at each end-tidal concentration of desflurane, CSI and BIS showed good linearity in 4% and 10% (R2 = 0.559, 0.540). However, the linearity and slope were decreased in 6% and 8% (R2 = 0.163, 0.014). CONCLUSIONS: CSI showed an equivalent degree of overall performance compared to BIS in desflurane anesthesia. Accounting for previous literature, CSI can be used as a good substitute for BIS regardless of the kind of anesthetics used.

Effect of the Spray Distance on the Properties of High Velocity Oxygen-Fuel (HVOF) Sprayed WC-12Co Coatings.

In this study influence of spray distance on the properties of WC-12Co coatings deposited by HVOF was investigated. WC-12Co coating was sprayed at spray distance of 300, 385 and 450 mm. From microstructure observation, it is confirmed that the porosity of coatings increases with increasing the spray distance. The X-ray diffraction patterns indicate that the coatings consist of pure WC, W, and Co as well as W2C and Co6W6C phases. The increase of the spray distance accelerated the decarburization of coatings. From micro hardness tests, it was found that the hardness and the fracture toughness decreased with increasing spray distance. These mechanical properties would be related with not only porosity but also the degree of decarburization.

Preparation and Properties of WC-Based Alloy Coatings with Controlled Co and Cr via High Velocity Oxy-Fuel Spray Technique.

WC based alloy coatings included different mass percent of Co and Cr have been synthesized on high carbon steel by using a facile high velocity oxy-fuel spray method. The mechanical nature of the coating films has been investigated by micro vickers hardness and fracture toughness. X-ray diffraction (XRD) and EDX analyses indicate that the three different samples (WC-10Co-4Cr, WC-17Co, and WC-12Co) consist of pure WC, W, Cr, and Co constituents as well as W2C and Co6W6C phases. The SEM and image analysis results show that WC-10Co-4Cr condition has higher porosity than those of WC-17Co, and WC-12Co coatings. WC-17Co coating showed the highest value in the hardness and fracture toughness test among three different samples. The obtained results revealed that the mechanical properties of WC based alloy coatings synthesized by a facile high velocity oxy-fuel spray method is very sensitive to Co content.

A Prospective, Comparative Study of the Pain of Local Anesthesia Using 2% Lidocaine, 2% Lidocaine With Epinephrine, and 2% Lidocaine With Epinephrine-Bupivicaine Mixture for Eyelid Surgery.

PURPOSE: A mixture of 2% lidocaine with epinephrine and bupivacaine was developed to achieve the fast-onset anesthetic effect of lidocaine and the long-lasting effect of bupivacaine. The authors compared pain scores between 2% lidocaine, 2% lidocaine with epinephrine, and 2% lidocaine with epinephrine-bupivicaine mixture during local anesthesia for eyelid surgeries. METHODS: This was a double-blind, randomized, prospective, comparative study. In total, 120 consecutive patients (43 males, 77 females, mean age = 47.2 ± 21.2) who underwent bilateral eyelid surgery under subcutaneous anesthesia were asked to report pain scores for each eye during the first injection of anesthesia. Each patient was randomly assigned to receive 1 of the 3 anesthetic agents in 1 eyelid, and 1 of the remaining 2 agents in the other. RESULTS: The pH values of the 2% lidocaine, 2% lidocaine with epinephrine, and 2% lidocaine with epinephrine-bupivicaine mixture were 6.23 ± 0.21, 4.21 ± 0.37, and 3.87 ± 0.19, respectively. The pain scores of each were 4.3 ± 1.8, 5.1 ± 1.8, and 5.7 ± 1.9, respectively. The 2% lidocaine with epinephrine produced a statistically significantly higher pain score than 2% lidocaine (p = 0.044, generalized estimating equation method). The mixture also showed a significantly higher pain score than 2% lidocaine (p = 0.003, generalized estimating equation method). CONCLUSIONS: Epinephrine seemed to increase subjective pain scores. Compared with 2% lidocaine with epinephrine, 2% lidocaine with epinephrine-bupivicaine mixture was not significantly different in terms of subjective symptoms or pH.

Corrigendum to "Local Relationship between Global-Flash Multifocal Electroretinogram Optic Nerve Head Components and Visual Field Defects in Patients with Glaucoma".

[This corrects the article DOI: 10.1155/2015/397495.].

Local Relationship between Global-Flash Multifocal Electroretinogram Optic Nerve Head Components and Visual Field Defects in Patients with Glaucoma.

Purpose. To investigate the local relationship between quantified global-flash multifocal electroretinogram (mfERG) optic nerve head component (ONHC) and visual field defects in patients with glaucoma. Methods. Thirty-nine patients with glaucoma and 30 normal controls were enrolled. The ONHC amplitude was measured from the baseline to the peak of the second positive deflection of the induced component. The ONHC amplitude was normalized by dividing ONHC amplitude by the average of seven largest ONHC amplitudes. The ONHC amplitude ratio map and ONHC deficiency map were constructed. The local relationship between the ONHC measurements and visual field defects was evaluated by calculating the overlap between the ONHC deficiency maps and visual field defect plots. Results. The mean ONHC amplitude measurements of patients with glaucoma (6.01 ± 1.91 nV/deg(2)) were significantly lower than those of the normal controls (10.29 ± 0.94 nV/deg(2)) (P < 0.001). The average overlap between the ONHC deficiency map and visual field defect plot was 71.4%. The highest overlap (75.0%) was between the ONHC ratios less than 0.5 and the total deviations less than 5%. Conclusions. The ONHC amplitude was reduced in patients with glaucoma compared to that in normal controls. Loss of the ONHC amplitude from the global-flash mfERG showed a high local agreement with visual field defects in patients with glaucoma.

Hepatitis B viral load predicts survival in hepatocellular carcinoma patients treated with sorafenib.

BACKGROUND AND AIM: Sorafenib is now considered as a standard treatment for advanced hepatocellular carcinoma (HCC). We evaluated the effect of hepatitis B virus (HBV) DNA titers on prognosis in HCC patients treated with sorafenib. METHODS: From 2008 to 2012, 78 HBV-related HCC patients who received sorafenib treatment at Severance Hospital were included in our analysis. The effect of pretreatment HBV-DNA levels on clinical outcomes for use in predicting prognosis after treatment with sorafenib was examined by univariate and multivariate analysis. RESULTS: Median overall survival and median progression-free survival were 5.2 months (95% confidence interval: 4.0-6.4) and 3.5 months (95% confidence interval: 2.3-4.7), respectively. Multivariate analysis revealed high levels of HBV-DNA (> 2000 IU/mL) to be an independent risk factor for worse overall survival (P=0.005; hazard ratio, 2.85) and disease progression among patients who did not receive concomitant prophylactic antiviral therapy during sorafenib treatment (P=0.008; hazard ratio, 87.4). Moreover, viral reactivation occurred more frequently in patients who did not receive concomitant prophylactic antiviral therapy than in those who did (4/38 vs 0/40; P=0.025). CONCLUSION: Higher HBV-DNA levels prior to sorafenib treatment were associated with poorer prognosis and increased viral reactivation thereafter. These results suggest the potential usefulness of prophylactic antiviral therapy when treating HBV-related HCC patients with sorafenib.

Prolonged clinical benefit from the maintenance hormone therapy in patients with metastatic breast cancer.

OBJECTIVE: We investigated the efficacy of maintenance hormone therapy (MHT), which was given to hormone positive metastatic breast cancer (MBC) patients in non-progression status to the previous chemotherapy. METHODS: This study retrospectively analyzed 76 MBC patients who had been treated with MHT from 2006 to 2010 at a single institute. RESULTS: For the 76 patients reviewed, the median progression free survival (PFS) to MHT was 14.4 months (95% CI, 11.6-17.3). Prolonged PFS was associated with less previous palliative chemotherapy, fewer metastatic sites, and the absence of visceral metastasis in univariate analysis. Multivariate analysis showed that only the number of previous palliative chemotherapy (HR 1.73, 95% CI, 1.00-2.98; P = 0.04) remained as a significant variable. MHT was generally well tolerated. CONCLUSIONS: MHT showed considerable efficacy and tolerability in this study. Further randomized prospective study is warranted.

Two cases of humoral hypercalcemia of malignancy in metastatic cholangiocarcinoma.

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.