Evidence for the Existence of Secretory Granule (Dense-Core Vesicle)-Based Inositol 1,4,5-Trisphosphate-Dependent Ca2+ Signaling System in Astrocytes

BACKGROUND: The gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain. The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored. PRINCIPAL FINDINGS: We have therefore studied the potential existence of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes using human brain tissue samples in contrast to cultured astrocytes that had primarily been used in the past. It was thus found that secretory granule marker proteins chromogranins and secretogranin II localize in the large dense core vesicles of astrocytes, thereby confirming the large dense core vesicles as bona fide secretory granules. Moreover, consistent with the major IP3-dependent intracellular Ca2+ store role of secretory granules in secretory cells, secretory granules of astrocytes also contained all three (types 1, 2, and 3) IP3R isoforms. SIGNIFICANCE: Given that the secretory granule marker proteins chromogranins and secretogranin II are high-capacity, low-affinity Ca2+ storage proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+ channels, i.e., increase both the mean open time and the open probability of the channels, these results imply that secretory granules of astrocytes function as the IP3-sensitive intracellular Ca2+ store

Structurally tuned lead magnesium titanate perovskite as a photoelectrode material for enhanced photoelectrochemical water splitting

This is the first demonstration of four distinct types of Lead Magnesium Titanate (PMT) perovskites including spheres, flakes, hierarchical flower and thin microbelt shapes that were finely tuned via facile solution method to develop cost effective and high performance photoanode materials for water splitting. The influence of solvent effects during structural tuning, purity, morphology, optical absorption, structural phase transition and stoichiometric formation of the prepared Lead Magnesium Titanate perovskites has been discussed in detail. A remarkable observation is that the thin microbelts structured PMT perovskite (PMTT) exhibited an excellent water splitting performance and it is more sensitive to the illuminated visible light. Owing to the unique structural features, the photoconversion efficiency value of PMTT perovskite is ∼3.9, 3.54, 2.85 and 1.52 times higher than those of other prepared PMT perovskites including pristine PbTiO3. The excellent water splitting performance of PMTT (thin microbelts) may be ascribed to the remarkable structural features that include a large surface area, high optical absorbance, more active sites and high interface area of the microbelts, which provide large contact areas between the electrolyte and highly active materials for electrolyte diffusion and a rapid route for charge transfer with minimal diffusion resistance. In addition, each thin microbelt is directly in contact with the Ni foam substrate, which can also shorten the diffusion path for the electrons. The demonstrated approach paves the way for low-cost and high-throughput production of next generation, high performance and highly active water splitting perovskite photocatalysts.</p

Structurally tuned lead magnesium titanate perovskite as a photoelectrode material for enhanced photoelectrochemical water splitting

This is the first demonstration of four distinct types of Lead Magnesium Titanate (PMT) perovskites including spheres, flakes, hierarchical flower and thin microbelt shapes that were finely tuned via facile solution method to develop cost effective and high performance photoanode materials for water splitting. The influence of solvent effects during structural tuning, purity, morphology, optical absorption, structural phase transition and stoichiometric formation of the prepared Lead Magnesium Titanate perovskites has been discussed in detail. A remarkable observation is that the thin microbelts structured PMT perovskite (PMTT) exhibited an excellent water splitting performance and it is more sensitive to the illuminated visible light. Owing to the unique structural features, the photoconversion efficiency value of PMTT perovskite is ∼3.9, 3.54, 2.85 and 1.52 times higher than those of other prepared PMT perovskites including pristine PbTiO3. The excellent water splitting performance of PMTT (thin microbelts) may be ascribed to the remarkable structural features that include a large surface area, high optical absorbance, more active sites and high interface area of the microbelts, which provide large contact areas between the electrolyte and highly active materials for electrolyte diffusion and a rapid route for charge transfer with minimal diffusion resistance. In addition, each thin microbelt is directly in contact with the Ni foam substrate, which can also shorten the diffusion path for the electrons. The demonstrated approach paves the way for low-cost and high-throughput production of next generation, high performance and highly active water splitting perovskite photocatalysts.</p

Clinical application of functional near-infrared spectroscopy for burn assessment

Significance: Early assessment of local tissue oxygen saturation is essential for clinicians to determine the burn wound severity.Background: We assessed the burn extent and depth in the skin of the extremities using a custom-built 36-channel functional near-infrared spectroscopy system in patients with burns.Methods: A total of nine patients with burns were analyzed in this study. All second-degree burns were categorized as superficial, intermediate, and deep burns; non-burned skin on the burned side; and healthy skin on the contralateral non-burned side. Hemodynamic tissue signals from functional near-infrared spectroscopy attached to the burn site were measured during fNIRS using a blood pressure cuff. A nerve conduction study was conducted to check for nerve damage.Results: All second-degree burns were categorized into superficial, intermediate, and deep burns; non-burned skin on the burned side and healthy skin on the contralateral non-burned side showed a significant difference distinguishable using functional near-infrared spectroscopy. Hemodynamic measurements using functional near-infrared spectroscopy were more consistent with the diagnosis of burns 1 week later than that of the degree of burns diagnosed visually at the time of admission.Conclusion: Functional near-infrared spectroscopy may help with the early judgment of burn extent and depth by reflecting differences in the oxygen saturation levels in the skin

A Prediction Rule to Identify Severe Cases among Adult Patients Hospitalized with Pandemic Influenza A (H1N1) 2009

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO2/FiO2 ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study

Background To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). Methods This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. Results A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). Conclusions Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. Trial registration ClinicalTrials.gov, NCT02715908. Registered 22 March 2016.This extension study was funded by LG Chem, Ltd. (formerly, LG Life Sciences, Ltd), Mochida Pharmaceutical Co., Ltd. and Korea Health Industry Development Institute