In this study, we show that the formation of polyploidy following sustained mitotic checkpoint activation appears to be preceded by the ubiquitin-dependent proteolysis of hBubR1. In addition, the level of hBubR1 is significantly reduced not only in polyploid cells created by sustained mitotic spindle damage, but also in 21 (31.3%) of 67 human colon adenocarcinomas tested. Importantly, the introduction of hBubR1 triggers the apoptosis of polyploid cells formed by aberrant exit from mitosis and inhibits the growth of tumors established with these cells in athymic nude mice. These results suggest that hBubR1-mediated apoptosis prevents the propagation of cells that breach the mitotic checkpoint and that the control of hBubR1 protein level is an important factor in the acquisition of preneoplastic polyploidy.

IS/OS and ELM are useful hallmarks for use in evaluation of foveal photoreceptor layer integrity, and are closely associated with final VA in DME. Pretreatment VA and photoreceptor status can predict potential restoration of photoreceptor integrity and subsequent visual recovery in DME.

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Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.

ABSTRACT.Purpose: To investigate the correlation between integrity of foveal photoreceptor layer and initial as well as final visual acuity (VA) after successful resolution of macular oedema (ME) associated with retinal vein occlusion (RVO). Methods: We retrospectively studied 31 eyes of 31 patients with resolved ME secondary to RVO. The integrity of foveal photoreceptor layer was studied using the junction between photoreceptor inner and outer segment (IS ⁄ OS) on spectral domain optical coherence tomography (SD OCT). The study eyes were categorized into three groups at final visit; V group with completely visible IS ⁄ OS, P group with partially detected IS ⁄ OS and I group with invisible IS ⁄ OS. Disrupted length of IS ⁄ OS and external limiting membrane (ELM) were measured. Results: Final VA (logMAR) was closely associated with the IS ⁄ OS integrity at final visit; final VA in V group (0.03 ± 0.05) was better than that in P group (0.21 ± 0.23) (p = 0.027) and final VA in P group was better than that in I group (0.70 ± 0.36) (p = 0.004). Better initial VA (logMAR) and shorter length of disrupted IS ⁄ OS at initial visit were closely associated with better final VA (logMAR). In addition, final VA (logMAR) was closely associated with the length of disrupted IS ⁄ OS and ELM at final visit. Conclusions: After resolution of ME associated with RVO, the final VA is associated with the integrity of foveal photoreceptor layer. Better VA and the smaller length of disrupted IS ⁄ OS on SD OCT at initial visit are indicators of better visual outcome in patients with RVO.

To examine the association of diabetes mellitus and early age-related macular degeneration (AMD) in Korean adults 50 years and older. Methods: This study included 3008 participants aged 50 to 87 years. Early AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Diabetes mellitus was defined as a fasting glucose level of 126 mg/dL or greater or the use of antidiabetic medications. Logistic regression was used to examine the association between diabetes mellitus and early AMD. Results: There were 88 subjects with early AMD and 315 subjects with diabetes mellitus. After adjusting for age, sex, current smoking, obesity, and hypertension, significant association was found between diabetes mellitus and early AMD. Subjects with diabetes mellitus were more likely to have early AMD (odds ratio, 1.87; 95% confidence interval, 1.07-3.28) than were those without diabetes mellitus. Conclusion: There is a relationship between diabetes mellitus and early AMD in Korean adults 50 years and older. The underlying biological processes remain to be determined.

Multiple intravitreal injections of anti-VEGF did not lead to significant change in RNFL thickness in wet AMD, DMR, and RVO patients. Furthermore, IOP fluctuations and number of injections did not appear to adversely affect RNFL thickness. Decreased RNFL thickness associated with severity of retinal ischemia in the DMR and RVO patients suggests that inner retinal ischemia itself could be a cause of RNFL loss rather than anti-VEGF effect.