© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Abatacept is a biological agent that modulates T-cell costimulation by blocking CD28 signalling. This cytotoxic T-lymphocyte-associated antigen-4-Ig fusion protein was approved for treatment of rheumatoid arthritis (RA). However, a few case reports have revealed respiratory failure after abatacept treatment. In this report, we present a patient with RA who developed severe acute respiratory distress syndrome (ARDS) and who passed away 2 months after starting abatacept. Danicopan A comprehensive analysis including radiology, blood examinations, infectious panel and flow cytometry lymphocyte analysis was done to determine the cause of respiratory failure. Since no infection was detected in this patient, an association between ARDS and abatacept is a strong possibility due to significant adverse reactions to the biological agent. Considering the rapid progression of respiratory failure after abatacept treatment in this report, we suggest that pulmonary function testing and lung structure evaluation be regarded throughout the early stage of treatment of patients with RA. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE To report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19). PARTICIPANT AND METHODS A 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated. RESULTS Slit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2. CONCLUSION SARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND/AIM To assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) treatment intensity in diabetic macular oedema (DMO). METHODS Retrospective analysis was performed in treatment-naïve patients with DMO from 2013 to 2018 using a database of aggregated de-identified electronic medical records (Vestrum Health). RESULTS At 1 year, 28 658 patient eyes underwent a mean of 6.4 anti-VEGF injections, gaining a mean of +4.2 letters (95% confidence interval for mean gain +4.0 to +4.5 letters, p less then 0.001). When stratified by anti-VEGF medication and by years 2013-2018, no clinically meaningful differences in injection frequency or 1-year VA change resulted. At 1 year, 50% of eyes received ≤6 injections, while less then 20% received 10-13 injections, representing monthly treatment. Mean letters gained at 1 year generally showed a linear relationship with mean number of anti-VEGF injections, beyond two injections. Eyes with good baseline VA (≥20/40) generally were at risk of VA loss at 1 year; those with moderately severe baseline impairment (20/70 to 20/200) who received ≥10 injections improved by a mean of +10.3 letters. CONCLUSION In clinical practice, patients with DMO undergo fewer anti-VEGF injections and exhibit worse visual gains compared with patients in randomised clinical trials. Visual outcomes correlate with treatment intensity at 1 year, with ceiling effects related to baseline VA. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND To identify and analyse the character and relationship between flat irregular pigment epithelial detachment feature (FIPED), choroidal thickness and choroidal neovascularisation (CNV) network seen on optical coherence tomography angiography (OCTA) in eyes with central serous chorioretinopathy (CSCR) in Chinese patients. METHOD In the present study, 152 eyes of 144 Chinese patients, who were previously diagnosed with CSCR, were retrospectively studied. Patients’ baseline characteristics, the course of CSCR, best-corrected visual acuity, the pattern of CNV on OCTA, FIPED and choroidal thickness detected by enhanced depth imaging-OCT (EDI-OCT) were analysed. RESULTS It was disclosed that 7.23% of CSCR patients had CNV. Age and the course of CSCR were found to be correlated with the occurrence of CNV. Among the eyes with CNV network (11 eyes), 100% of them had FIPED, whereas, among the eyes without CNV (141 eyes), 18.04% had FIPED. The maximum width and en-face area of PED were greater in the CNV group compared with that in the non-CNV group (p less then 0.001). It also was revealed that female gender and a poor vision were risk factors for CNV in eyes with CSCR. The choroidal thickness detected by EDI-OCT was also statistically significant between eyes with CNV and eyes without CNV. The patients who have CNV complicated with FIPED are susceptible to have low vision. CONCLUSION The present research demonstrated that the majority of CNV cases were linked to FIPED, and the thinner thickness of choroid. The greater width and en-face area of PED may point towards the presence of an underlying CNV network. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.The teleost fish, medaka (Oryzias latipes), employs the XX/XY genetic sex determination system. We show here that the phenotypic sex of medaka is affected by changes in lipid metabolism. Medaka larvae subjected to 5 days of starvation underwent female-to-male sex reversal. Metabolomic and RT-qPCR analyses indicated that pantothenate metabolism was suppressed by starvation. Consistently, inhibiting the pantothenate metabolic pathway caused sex reversal. The final metabolite in this pathway is coenzyme A, an essential factor for lipogenesis. Inhibiting fatty acid synthesis, the first step of lipogenesis, also caused sex reversal. The expression of dmrt1, a critical gene for male development, was suppressed by starvation, and a dmrt1 (Δ13) mutant did not show sex reversal under starvation. Collectively, these results indicate that fatty acid synthesis is involved in female-to-male sex reversal through ectopic expression of male gene dmrt1 under starvation. © 2020. Published by The Company of Biologists Ltd.Endocannabinoids (eCB) modulate growth cone dynamics and axonal pathfinding through the stimulation of cannabinoid type-1 receptors (CB1R), the function of which depends on their delivery and precise presentation at the growth cone surface. However, the mechanism involved in the axonal transport of CB1R and its transport role in eCB signaling remains elusive. As mutations in the kinesin-1 molecular motor have been identified in patients with abnormal cortical development and impaired white matter integrity, we studied the defects in axonal pathfinding and fasciculation in mice lacking the kinesin light chain 1 (Klc1 -/-) subunit of kinesin-1. Reduced levels of CB1R were found in corticofugal projections and axonal growth cones in Klc1 -/- mice. By live-cell imaging of CB1R-eGFP we characterized the axonal transport of CB1R vesicles and described the defects in transport that arise after KLC1 deletion. Cofilin activation, which is necessary for actin dynamics during growth cone remodeling, is impaired in the Klc1 -/- cerebral cortex. In addition, Klc1 -/- neurons showed expanded growth cones that were unresponsive to CB1R-induced axonal elongation. Together, our data reveal the relevance of kinesin-1 in CB1R axonal transport and in eCB signaling during brain wiring. © 2020. Published by The Company of Biologists Ltd.Flexible functional interactions among brain regions mediate critical cognitive functions. Such interactions can be measured using functional magnetic resonance imaging (fMRI) data either with instantaneous (zero-lag) or lag-based (time-lagged) functional connectivity. Because the fMRI hemodynamic response is slow, and sampled at a timescale (seconds) several orders of magnitude slower than the underlying neural dynamics (milliseconds), simulation studies have shown that lag-based fMRI functional connectivity, measured with approaches like Granger-Geweke causality (GC), provides spurious and unreliable estimates of underlying neural interactions. Experimental verification of this claim is challenging because neural ground truth connectivity is, often, unavailable concurrently with fMRI recordings. Here we demonstrate that, despite these widely-held caveats, GC networks estimated from fMRI recordings contain useful information for classifying task specific cognitive states. We estimated instantaneous and lag-bnvasive technique for mapping functionally connected networks in the human brain. The fMRI hemodynamic response is slow, noisy and sampled far more slowly (seconds) than the timescale of neuronal spikes (milliseconds). fMRI data is, therefore, considered unsuitable for mapping directed, time-lagged functional connectivity among brain regions. Here, we apply machine learning to fMRI data from 1000 human participants and show that directed connectivity, estimated with Granger-Geweke Causality from fMRI data, accurately predicts task-specific cognitive states, and individual subjects’ behavioral scores. Moreover, directed connectivity robustly identifies network configurations that may be challenging to identify with conventional, correlation-based approaches. Directed functional connectivity, as measured with fMRI, may be relevant for a complete understanding of brain function. Copyright © 2020 Ajmera et al.BACKGROUND The aim of this study was to compare the clinical characteristics, causes of death and factors impacting on the prognosis of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung disease (FILD) with a history of acute exacerbation (AE) of IPF or FILD. METHODS Retrospective data of hospital treatment periods caused by AE-IPF and AE-FILD were collected from medical records. Clinical features and survival data of IPF and non-IPF cases were evaluated and compared. The underlying and immediate causes of death were gathered from death certificates. RESULTS A total of 128 patients fulfilled the criteria for inclusion. IPF (n=79/62%), rheumatoid arthritis-associated interstitial lung disease (RA-ILD; n=17/14%) and asbestosis (n=11/8.6%) were the most common FILD subgroups in the study. The median survival after hospitalisation in AE-IPF was 2.6 months compared with 21 months in other AE-FILDs (p less then 0.001). The survival difference was not explained by age, gender or pulmonary function test results at the time of hospitalisation.