Visualization of distribution in the vitreous cavity via eye drops using ultra-heavily T2-weighted sequences in MRI: a preliminary study with enucleated pig eyes.

We investigated whether magnetic resonance imaging can visualize the distribution in the vitreous cavity via eye drops of ophthalmic solutions, gadolinium-based contrast agent, and 17O-water, and to clarify the usefulness of ultra-heavily T2-weighted sequences in the research of intraocular distribution. Five different solutions (V-ROHTO, TRAVATANZ, gadobutrol, H217O, and saline) were administered to excised pig eye specimens. The samples were scanned using T1 mapping, T2 mapping, 3D T2-weighted (echo times (TE): 500, 3200, and 4500 ms), a half-Fourier single-shot turbo-spin echo sequence (HASTE; TE: 440 and 3000 ms), and 3D-real inversion-recovery before eye drops administration. Subsequently, we used a plastic dropper to drop a 0.5 mL solution each, and images were obtained up to 26 h later. Temporal changes in the T1 and T2 values of the anterior chamber and vitreous cavity were compared. The other sequences were evaluated by determining temporal signal changes as signal intensity ratio (SIR) compared to "No drop." The T1 and T2 values of samples treated with gadobutrol and H217O decreased over time. The SIR of samples treated with gadobutrol and H217O showed remarkable changes in the 3D T2-weighted images, whereas no remarkable temporal changes were observed in the other solutions. Longer TEs resulted in remarkable changes. We demonstrated that visualization of distribution in the vitreous cavity via eye drops could be achieved with excised pig eyes using gadobutrol and H217O, but not with ophthalmic solutions. Ultra-heavily T2-weighted sequences may be promising for the early and highly sensitive visualization of the intraocular distribution of eye drops.

Multivariate sharp-wave ripples in schizophrenia during awake state.

AIMS: Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ. METHODS: We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed "ripple-gedMEG" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ. RESULTS: We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ. CONCLUSION: We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.

Intraocular pressure changes during intravitreal aflibercept injection based on treat-and-extend regimen in Japanese patients with neovascular age-related macular degeneration and glaucoma.

PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded. RESULTS: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery. CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.

Achaete-scute family bHLH transcription factor 2 activation promotes hepatoblastoma progression.

Achaete-scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet-On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, migration, invasion, and sphere-formation assays. Quantitative reverse-transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial-mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal-epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non-induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway-, EMT-, and stemness-related genes. ASCL2 activation may therefore be involved in the progression of HB.

Complement activation products in tears of dry eye and meibomian gland dysfunction.

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.

Stereotactic radiotherapy for ventricular tachycardia: A study protocol.

Background: Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired. Methods: This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients. Conclusion: Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation. Trial registration: The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030).