A Hierarchical Hydrogel Impregnation Strategy Enables Brittle-Failure-Free 3D-Printed Bioceramic Scaffolds.

3D-printed bioceramic scaffolds offer great potential for bone tissue engineering (BTE) but their inherent brittleness and reduced mechanical properties at high porosities can easily result in catastrophic fractures. Herein, this study presents a hierarchical hydrogel impregnation strategy, incorporating poly(vinyl alcohol) (PVA) hydrogel into the macro- and micropores of bioceramic scaffolds and synergistically reinforcing it via freeze-casting assisted solution substitution (FASS) in a tannic acid (TA)-glycerol solution. By effectively mitigating catastrophic brittle failures, the hydrogel-impregnated scaffolds showcase three- and 100-fold enhancement in mechanical energy absorption under compression (5.05 MJ m-3) and three-point bending (3.82 MJ m-3), respectively. The reinforcement mechanisms are further investigated by experimental and simulation analyses, revealing a multi-scale synergy of fracture and fragmentation resistance through macro and micro-scale fiber bridging, and nano and molecular-scale hydrogel reinforcement. Also, the scaffolds acquire additional antibacterial and drug-loading capabilities from the hydrogel phase while maintaining favorable cell biocompatibility. Therefore, this study demonstrates a facile yet effective approach for preparing brittle-failure-free bioceramic scaffolds with enhanced biological functionalities, showcasing immense potential for BTE applications.

Controllable and Reversible Assembly of Nanofiber from Natural Macromolecules via Protonation and Deprotonation.

Nanofiber is the critical building block for many biological systems to perform various functions. Artificial assembly of molecules into nanofibers in a controllable and reversible manner will create "smart" functions to mimic those of their natural analogues and fabricate new functional materials, but remains an open challenge especially for nature macromolecules. Herein, the controllable and reversible assembly of nanofiber (CSNF) from natural macromolecules with oppositely charged groups are successfully realized by protonation and deprotonation of charged groups. By controlling the electrostatic interaction via protonation and deprotonation, the size and morphology of the assembled nanostructures can be precisely controlled. A strong electrostatic interaction contributes to large nanofiber with high strength, while poor electrostatic interaction produces finer nanofiber or nanoparticle. And especially, the assembly, disassembly, and reassembly of the nanofiber occurs reversibly through protonation and deprotonation, thereby paving a new way for precisely controlling the assembly process and structure of nanofiber. The reversible assembly allows the nanostructure to dynamically reorganize in response to subtle perturbation of environment. The as-prepared CSNF is mechanical strong and can be used as a nano building block to fabricate high-strength film, wire, and straw. This study offers many opportunities for the biomimetic synthesis of new functional materials.

Portably and Visually Sensing Cytisine through Smartphone Scanning Based on a Post-Modified Luminescence Center Strategy in Zinc-Organic Frameworks.

Cytisine (CTS) is a useful medicine for treating nervous disorders and smoking addiction, and exploring a convenient method to detect CTS is of great significance for long-term/home medication to avoid the risk of poisoning, but it is full of challenges. Here, a modified metal-organic framework sensor Tb@Zn-TDA-80 with dual emission centers was prepared using a post-modified luminescence center strategy. The obtained Tb@Zn-TDA-80 can serve as a CTS sensor with high sensitivity and selectivity. To achieve portable detection, Tb@Zn-TDA-80 was further fabricated as a membrane sensor, M-Tb@Zn-TDA-80, which displayed an obvious CTS-responsive color change by simply dropping a CTS solution onto its surface. Benefiting from this unique functionality, M-Tb@Zn-TDA-80 successfully realized the visual detection and quantitative monitoring of CTS in the range of 5.26-52.6 mM by simply scanning the color with a smartphone. The results of nuclear magnetic resonance spectroscopy and theoretical computation illustrated that the high sensing efficiency of Tb@Zn-TDA-80 for CTS was attributed to the N-H⋅⋅⋅π and π⋅⋅⋅π interactions between the ligand and CTS. And luminescence quenching may result from the intramolecular charge transfer. This study provides a convenient method for ensuring long-term medication safety at home.

Correlation between initial tumor enlargement and magnetic resonance imaging characteristics following linear accelerator-based stereotactic radiosurgery for acoustic neuromas.

BACKGROUND: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. MATERIALS AND METHODS: In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. RESULTS: Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5 cm3 had a lower incidence of initial enlargement (p = 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8 ± 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (p = 0.045). No correlation was noted between initial enlargement and tumor control. CONCLUSION: Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5 cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.

Luminescent Sensor with High Sensitivity and Selectivity for Amikacin Detection in a Serum using a Unique Gallium-Organic Framework.

Amikacin is a widely used antibiotic in the treatment of Gram-negative bacteria, but high concentrations of amikacin can cause cochlear nerve damage. Therefore, accurate and quick detection of the concentration of amikacin is desired and important. In this work, we have synthesized a new gallium-organic framework {[(CH3)2(NH2)Ga(PPTA)]·0.5DMF}n (1) (H4PPTA = 4,4',4″,4″'-(1-4-phenlene-bis(pyridine-4,2,6-triyl)) with good solvent and pH stabilities. A structure analysis reveals that 1 is a twofold interpenetrated framework exhibiting a large 1D square aperture with a size of 10.8 Å × 14 Å. The experimental results show that 1 can be used as a stable, fast, and recyclable luminescent probe for the detection of amikacin in aqueous solution and serum. The limit of detection is 2.9 × 10-7 mol/L, which is lower than the harmful concentration of amikacin in human serum. This is the first example of a metal-organic framework used for luminescence sensing of amikacin.

Long-term follow-up and comparison of programmable and non-programmable ventricular cerebrospinal fluid shunts among adult patients with different hydrocephalus etiologies: a retrospective cohort study.

BACKGROUND: Programmable valve (PV) has been shown as a solution to the high revision rate in pediatric hydrocephalus patients, but it remains controversial among adults. This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients with different hydrocephalus etiologies. METHOD: We reviewed the chart of all patients with hydrocephalus receiving index ventricular cerebrospinal fluid (CSF) shunt operations conducted at a single institution from January 2017 to December 2017. Patients included in the study were followed up for at least 5 years. Statistical tests including independent t-test, chi-square test, and Fisher's exact test were used for comparative analysis, and Kaplan-Meier curve using log-rank test was performed to compare the revision-free survival between the PV and NPV groups. RESULTS: A total of 325 patients were included in the study, of which 181 patients were receiving PVs and 144 patients receiving NPV. There were 23 patients (12.8%) with PV and 22 patients (15.3%) with NPV receiving initial revision. No significant statistical difference in the initial revision rate was observed between the two groups (p = 0.52). No survival difference was found between the PV and NPV groups. However, better revision-free survival was noted in the PV group among idiopathic normal pressure hydrocephalus (iNPH) (p = 0.0274) and post-traumatic hydrocephalus (p = 0.017). CONCLUSIONS: The combination of the different etiologies of hydrocephalus and the features of PV and NPV results in different outcomes-revision rate and revision-free survival. PV use might be superior to NPV in iNPH and post-traumatic hydrocephalus patients. Further studies are needed to clarify the indications of PV use in adult hydrocephalus patients.

The antibacterial activity of a novel NK-lysin homolog and its molecular characterization and expression in the striped catfish, Pangasianodon hypophthalmus.

Aeromonas hydrophila was a common bacterial pathogen in aquaculture resulting in considerable losses to the striped catfish aquaculture industry. As an emergent antimicrobial peptide (AMP), NK-lysin (NKL) had activity against various microorganisms. However, the antibacterial activity of NKL from striped catfish (Pangasianodon hypophthalmus) both in vitro and vivo remains unclear. In this study, the cDNA sequence of P. hypophthalmus NK-lysin gene (PhNK-lysin) was cloned and characterized. The amino acid sequence of PhNK-lysin contains a signal peptide sequence of 17 amino acid (aa) residues and a mature peptide composed of 130 aa. The saposin B domain of mature peptide comprised six conserved cysteines forming three putative disulfide bonds. Phylogenetic analysis revealed that the PhNK-lysin was most closely related to that of the channel catfish (Ictalurus punctatus) NK-lysin. The transcriptional levels of the PhNK-lysin were significantly upregulated in response to A. hydrophila infection in various tissues including heart, liver, spleen, head kidney, trunk kidney and gill. The synthetic PhNK-lysin-derived peptide consisting of 38aa showed antibacterial activity against Vibrio harveii, Aeromonas hydrophila and Escherichia coli. The MIC for V. harveii, A. hydrophila and E. coli were 15.625 µM, 250 µM and 31.25 µM respectively. Besides, the synthetic PhNK-lysin decreased the bacterial load of liver and trunk kidney in vivo as well as increased the survival rate of A. hydrophila infected striped catfish. Hence, these data suggest that PhNK-lysin had antimicrobial effect and protects the host from pathogenic infection.

Spinal cord injury and spinal fracture in patients with ankylosing spondylitis.

BACKGROUND: Spinal cord injury (SCI) and spinal fracture are major complications in patients with ankylosing spondylitis (AS) who sustain spinal trauma. The purpose of this study was to investigate the incidence, predictors, and sequelae of spinal trauma in patients with AS. METHODS: This retrospective study included patients with AS who were admitted for spinal trauma between January 1, 2006, and June 30, 2016. The study compared clinical outcomes of patients between group 1: SCI alone, group 2: spinal fracture alone (no SCI), and group 3: both SCI and spinal fracture. RESULTS: Of the 6285 patients with AS admitted during the retrospective study period, only 105 suffered from spinal trauma and were enrolled in the study. Case number in group 1, 2, and 3 was 11(10.48%), 45(42.85%), and 49(46.67%), respectively. Among the patients with spinal fractures, 52.1% had SCI. Bamboo spine was significantly more prevalent in the fracture group than in the nonfracture group (78.7% vs. 36.4%; P = 0.006). Patients with SCI had more instances of subluxation or dislocation (48.3% vs. 8.9%; P < 0.001) and more cases of spinal epidural hematoma (SEH; 21.7% vs. 2.2%; P = 0.003) than patients without SCI. The rate of delayed diagnosis for spinal fracture was 31.4%, with one-third of patients developing delayed SCI. Among the patients with incomplete SCI, 58.3% achieved neurological improvement after treatment (P = 0.004). CONCLUSIONS: Patients with AS and bamboo spine at radiograph had a higher rate of spinal fracture, which may be an important factor in SCI in patients with AS. Spinal fractures involving the C3-C7 region, subluxation or dislocation, severe spinal fracture, and SEH were found to be predictive of SCI, and SCI in patients with AS resulted in higher mortality and complication rates.

Photo-Crosslinked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Dural Substitute to Prevent Post-Surgical Adhesion.

A dural substitute is frequently used to repair dura mater during neurosurgical procedures. Although autologous or commercially available dural substitutes matched most of the requirements; difficulties during dural repair, including insufficient space for suturing, insufficient mechanical strength, easy tear and cerebrospinal fluid leakage, represent major challenges. To meet this need, a photo-crosslinked hydrogel was developed as a dural substitute/anti-adhesion barrier in this study, which can show sol-to-gel phase transition in situ upon short-time exposure to visible light. For this purpose, hyaluronic acid (HA) and carboxymethyl cellulose (CMC), materials used in abdominal surgery for anti-adhesion purposes, were reacted separately with glycidyl methacrylate to form hyaluronic acid methacrylate (HAMA) and carboxymethyl cellulose methacrylate (CMCMA). The HA/CMC (HC) hydrogels with different HA compositions could be prepared by photo-crosslinking HAMA and CMCMA with a 400 nm light source using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photo-initiator. From studies of physico-chemical and biological properties of HC composite hydrogels, they are bio-compatible, bio-degradable and mechanically robust, to be suitable as a dural substitute. By drastically reducing attachment and penetration of adhesion-forming fibroblasts in vitro, the HC hydrogel can also act as an anti-adhesion barrier to prevent adhesion formation after dural repair. From in vivo study in rabbits, the HC hydrogel can repair dural defects as well as protect the dura from post-operative adhesion, endorsing the possible application of this hydrogel as a novel dural substitute.

Selectively Regulating Lewis Acid-Base Sites in Metal-Organic Frameworks for Achieving Turn-On/Off of the Catalytic Activity in Different CO2 Reactions.

Regulating Lewis acid-base sites in catalysts to investigate their influence in the chemical fixation of CO2 is significant but challenging. A metal-organic framework (MOF) with open metal Co sites, {(NH2 Me2 )[Co3 (µ3 -OH)(BTB)2 (H2 O)]⋅9 H2 O⋅5 DMF}n (1), was obtained and the results of the catalytic investigation show that 1 can catalyze cycloaddition of CO2 and aziridines to give 99 % yield. The efficiency of the cyclization of CO2 with propargyl amines is only 32 %. To improve the catalytic ability of 1, ligand XN with Lewis base sites was introduced into 1 and coordinated with the open Co sites, resulting in a decrease of the Lewis acid sites and an increase in the Lewis base sites in a related MOF 2 ({(NH2 Me2 )[Co3 (µ3 -OH)(NHMe2 )(BTB)2 (XN)]⋅8 H2 O⋅4 DMF}n ). Selective regulation of the type of active centers causes the yield of oxazolidinones to be enhanced by about 2.4 times, suggesting that this strategy can turn on/off the catalytic activity for different reactions. The catalytic results from 2 treated with acid solution support this conclusion. This work illuminates a MOF-construction strategy that produces efficient catalysts for CO2 conversion.

A Facile Strategy to Obtain Low-Cost and High-Performance Gold-Based Catalysts from Artificial Electronic Waste by [Zr48 Ni6 ] Nano-Cages in MOFs for CO2 Electroreduction to CO.

Expensive gold-based catalysts are frequently used for electrochemical CO2 reduction into CO. A feasible approach to obtain low-cost Au-based catalysts is needed. Herein, a novel framework 1 assembled from [Zr48 Ni6 ] nano-cages is prepared. It exhibits a high BET surface area of 1569 m2 g-1 and high solvents/pH stability. 1 can not only selectively extract AuCl4 - from artificial electronic waste, but can then be transformed into low-cost catalyst Au nanoparticle@1-x (Au NPs@1-x, x=1, 2, 3, 4) with tuneable Au NPs sizes. The CO2 RR investigations revealed that the Au NPs@1-3 displayed an excellent FECO of 95.2 % with a current density of 102.9 mA cm-2 at -1.1 V, and such high catalytic activity can be maintained for at least 15 h without obvious decrease because the confinement effect of [Zr48 Ni6 ] nano-cages prevents Au NPs agglomeration. This work offers a facile strategy to obtain low-cost and high-performance Au-based catalysts for various reactions activated by Au.

Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury.

Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.

Recyclable Luminescence Sensor for Dinotefuran in Water by Stable Cadmium-Organic Framework.

Due to the widespread use of dinotefuran around the world, its impact on food and environmental safety has aroused great concern, and the establishment of a rapid and convenient approach for dinotefuran detection is necessary but challenging. Herein, we synthesized a unique three-dimensional framework {[(CH3)2NH2]2[Cd3(BCP)2]·10H2O·3.5DMF}n (1). Single-crystal X-ray analysis indicates that 1 possesses a 4,8-connected anion framework that corresponds to alb topology, with a one-dimensional rectangular channel along the c-axis with the size of 4 Å × 10 Å. Compound 1 displays satisfactory solvent and thermal stability. Luminescent investigations reveal that 1 can selectively detect dinotefuran by fluorescence quenching among other pesticides, displaying excellent anti-interference performance with common ions in water. Importantly, the limit of detection is as low as 2.09 ppm, which is far below the residual concentration of the U.S. food standard. A fluorescence quenching mechanism study shows that there exists competitive energy absorption and static quenching processes. To our knowledge, 1 is the first MOF-based fluorescence probe for dinotefuran detection.

Prevalence of drug resistance mutations in HIV-infected individuals with low-level viraemia under combination antiretroviral therapy: an observational study in a tertiary hospital in Northern Taiwan, 2017-19.

BACKGROUND: Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics. OBJECTIVES: To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV. METHODS: A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV. RESULTS: Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P < 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P < 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV. CONCLUSIONS: HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.

Stepwise Increase of NdIII -Based Phosphorescence by AIE-Active Sensitizer: Broadening the AIPE Family from Transition Metals to Discrete Near-Infrared Lanthanide Complexes*.

We designed two near-infrared (NIR) lanthanide complexes [(L)2 -Nd(NO3 )3 ] (L=TPE2 -BPY for 1, TPE-BPY for 2) by employing aggregation-induced emission (AIE)-active tetraphenylethylene (TPE) derivatives as sensitizers, which possessed matched energy to NdIII , prevented competitive deactivation under aggregation, even shifted the excitation window toward 600 nm by twisted intramolecular charge transfer. Furthermore, benefiting from the 4 f electron shielding effect and antenna effect, the enhanced excitation energies of the AIE-active sensitizers by structural rigidification transferred into the inert NdIII excited state through 3 LMCT, affording the first aggregation-induced phosphorescence enhancement (AIPE)-active discrete NIR-emitting lanthanide complexes. As 1 equipped with more AIE-active TPE than 2, L→Nd energy transfer efficiency in the former was higher than that in the latter under the same conditions. Consequently, the crystal of 1 exhibited one of the longest lifetimes (9.69 µs) among NdIII -based complexes containing C-H bonds.

Photonic instantaneous frequency measurement using a dense wavelength-division multiplexer.

A photonic instantaneous frequency measurement receiver based on frequency to optical power mapping is proposed and experimentally demonstrated. One channel of a dense wavelength-division multiplexer (DWDM) is used as an optical filter to establish a power ratio function related to the frequency of the microwave signal. Different from most optical filters, the DWDM filter features smooth and quasilinear roll-off over a wide bandwidth. With the help of a laser of good wavelength stability and a bias controller, large measurement range and high accuracy are simultaneously achieved without multi-step operation. The instanstaneous frequency measurement receiver can measure the frequency with an accuracy of 0.2% of the signal frequency in the range of 1-40 GHz over 1.5 h in the experiment.

Demographic differences in people living with HIV according to recruitment sources: comparison between health-care systems and social media networks.

With the improvement of internet technology in health applications, the utilization of internet and social media as new survey methodologies and recruitment source for research participants have been encouraged, yet evidence of the feasibility in people living with HIV (PLHIV) study is still lacking. We conducted a cross-sectional survey to determine whether there are differences among PLHIV recruited from social media networks and health-care systems using an HIV stigma and discrimination questionnaire. The result revealed that PLHIV recruited from social media networks were younger, more sexually active, and had higher educational status and awareness of the country's HIV rights protection laws than those recruited from hospitals. By contrast, participants recruited from hospitals were more diverse regarding key population compositions, had lived with HIV for a longer duration, had a higher prevalence of concomitant physical disabilities than those recruited from social media networks, and fit Taiwan PLHIV characteristics described by 2016 census from Taiwan Centres for Disease Control. We conclude that sampling bias exists when utilizing social media networks for PLHIV studies.

Highly Sensitive and Selective Luminescence Sensor Based on Two-Fold Interpenetrated MOFs for Detecting Glutamate in Serum.

Glutamate is a biomarker for many nervous system diseases, and sensitively detecting glutamate is meaningful in the clinic. Therefore, a unique 3D framework of Cd-MOF (1) is synthesized and characterized. A single-crystal X-ray study reveals that it is a two-fold interpenetration (4,4)-connected framework with a PtS topology, where a large 1D rhombic channel with a size of 8 × 14 Å exists and the total potential void volume can reach 62%. Luminescence results demonstrate that 1 has good luminescence stability and can sensitively detect glutamate in water with a detection limit of 1.15 × 10-7 mol/L, which makes it the most sensitive MOF-based luminescence sensor of glutamate to date. More importantly, it also can serve as a luminescence sensor to detect glutamate in serum, and the quenching concentration needs to be only 43.1 µmol/L, which is much lower than the harmful level of glutamate (400 µmol/L) in glioma patients' blood. Compound 1 can be used at least five cycles. These results show that 1 has a potential application in monitoring glutamate in clinical scenarios.

Association of ocular diseases with schizophrenia, bipolar disorder, and major depressive disorder: a retrospective case-control, population-based study.

BACKGROUND: Psychiatric disorders and ocular neurovascular diseases may share a similar pathophysiological route of vascular structures or neurological changes. The aim of this study is to investigate the association between ocular neurovascular diseases and the risk of major psychiatric disorders. METHODS: This was a retrospective case-control, population-based study including patients aged ≥20 and were diagnosed between 1997 and 2013. Ocular neurovascular diseases diagnosed between 1997 and 2006 and newly diagnosed psychiatric disorders including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia between 2007 and 2013 were registered. Patients were propensity-score matched with control groups without psychiatric disorders in each cohort based on selected covariates. RESULTS: A total of one million sampled patients in the database were categorized based on their diagnoses; 2243 (37.4% men) were categorized into the BD group, 10,110 (35.2% men) into the MDD group, and 1623 (43.1% men) into the schizophrenia group. In the BD group, all glaucoma (OR 1.49, [1.18-1.89]), open-angle glaucoma (OR 2.08, [1.34-3.24]), and closed-angle glaucoma (OR 2.12, [1.36-3.33]) showed statistical significance of risk. In the MDD group, age-related macular degeneration (OR 1.33, [1.13-1.57]), all glaucoma (OR 1.24, [1.11-1.37]), open-angle glaucoma (OR 1.47, [1.21-1.80]), and dry eye syndrome (OR 1.22, [1.13-1.31]) were associated with a significantly higher risk. In the schizophrenia group, only all glaucoma (OR 1.47, [1.02-2.11]), glaucoma suspect (OR 1.88, [1.01-3.49]), and open-angle glaucoma (OR 2.19, [1.13-4.26]) showed statistical significance. CONCLUSIONS: In this population-based study, ocular neurovascular diseases, especially glaucoma, were associated with increased risks of BD, MDD, and schizophrenia.

Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study.

Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 µM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.