CENTRAL RETINAL VEIN OCCLUSION IN YOUNG INDIVIDUALS: A Comparison of Risk Factors and Clinical Outcomes.

PURPOSE: To compare the presentation and outcomes of patients younger than 50 years versus patients aged 50 years and older with central retinal vein occlusion (CRVO). METHODS: This single-center retrospective study included patients with CRVO presenting between January 2009 and July 2016. Charts were reviewed and data were abstracted. Presenting and final clinical parameters, treatment burden, and predisposing factors for CRVO were compared between the two groups. RESULTS: Thirty-six patients younger than 50 years and 233 patients aged 50 years and older at the time of CRVO onset were included. At presentation, younger patients had better visual acuity than older patients (20/80 vs. 20/224, P = 0.001) and a lower incidence of cystoid macular edema (54 vs. 79%, P = 0.001). Twenty-one of 36 (58%) younger patients had at least one identifiable nontraditional risk factor for CRVO. At final follow-up, younger patients received fewer total intravitreal injections (3.8 ± 5.8 at 34.2 months) compared with older patients (6.5 ± 8.8, at 37.6 months, P = 0.03) and had better final acuity (20/85 vs. 20/289, P = 0.004, respectively). CONCLUSION: Younger patients had better baseline and final acuities, a lower incidence of cystoid macular edema at presentation, and received fewer intravitreal injections than older patients. Workup for etiology of CRVO in younger patients may reveal nontraditional risk factors for CRVO.

Predictive signature of murine and human host response to typical and atypical pneumonia.

BACKGROUND: Pneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection. METHODS: We used murine models of typical bacterial, atypical bacterial and viral pneumonia to develop diagnostic signatures and understand the host's response to these types of infections. Mice were intranasally inoculated with Streptococcus pneumoniae, Mycoplasma pneumoniae, influenza or saline as a control. Peripheral blood gene expression analysis was performed at multiple time points. Differentially expressed genes were used to perform gene set enrichment analysis and generate diagnostic signatures. These murine-derived signatures were externally validated in silico using human gene expression data. The response to S. pneumoniae was the most rapid and robust. RESULTS: Mice infected with M. pneumoniae had a delayed response more similar to influenza-infected animals. Diagnostic signatures for the three types of infection had 0.94-1.00 area under the receiver operator curve (auROC). Validation in five human gene expression datasets revealed auROC of 0.82-0.96. DISCUSSION: This study identified discrete host responses to typical bacterial, atypical bacterial and viral aetiologies of pneumonia in mice. These signatures validated well in humans, highlighting the conserved nature of the host response to these pathogen classes.

Impact and Implication of Fovea-Involving Intraretinal Hemorrhage after Acute Branch Retinal Vein Occlusion.

PURPOSE: To compare clinical outcomes in patients with branch retinal vein occlusion (BRVO) with (group A) or without (group B) fovea-involving intraretinal hemorrhage (IRH). DESIGN: Retrospective cohort study. PARTICIPANTS: All patients diagnosed with acute, treatment-naive BRVO seen by the Duke Eye Center Retina Service from January 1, 2009, through June 30, 2017 who had treatment-naive BRVO with disease onset <3 months before presentation, macular involvement, spectral-domain OCT and color fundus photographs at presentation, and >12 months offollow-up. METHODS: Retrospective study using a database of patients diagnosed with BRVO over an 8-year period. The presence of fovea-involving IRH was determined from baseline fundus photographs by human graders and confirmed with multimodal imaging. Presenting features, treatment patterns, and clinical outcomes were compared. MAIN OUTCOME MEASURES: Visual acuity (VA), cystoid macular edema (CME), central subfield thickness (CST), and number of anti-vascular endothelial growth factor (VEGF) injections. RESULTS: Of 172 patients with BRVO, 33 (19.2%) presented with fovea-involving IRH. At presentation, group A had worse VA (0.54±0.06 logMAR [Snellen equivalent, 20/69] vs. 0.34±0.03 logMAR [Snellen equivalent, 20/44]; P = 0.001), greater CST (523.8±32 µm vs. 345.9±11.8 µm; P < 0.001), were more likely to have CME (93.9% vs. 48.2%; P < 0.001), and received more anti-VEGF injections in the first year (4.50±3.43 vs. 1.89±3.26; P < 0.001) than group B. Final VA was worse in group A (0.57±0.12 logMAR [Snellen equivalent, 20/74] vs. 0.35±0.05 logMAR [Snellen equivalent, 20/45]; P = 0.05). More patients in group A had loss of >2 lines of VA (36.4% vs. 18.7%; P = 0.04) or >3 lines (27.3% vs. 10.8%; P = 0.05) at final follow-up. Group A was more likely to have CME (63.6% vs. 27.3%; P < 0.001) at final follow-up with greater treatment burden, yet experienced a greater decrease in CST (-197.8±45.3 µm vs. -51.7±14.7 µm; P = 0.005). CONCLUSIONS: Acute BRVO presenting with fovea-involving IRH is associated with worse presenting features, greater treatment burden, and worse clinical outcomes despite current therapeutic interventions.

Investigating the mechanism of ADP-forming acetyl-CoA synthetase from the protozoan parasite Entamoeba histolytica.

ADP-forming acetyl-CoA synthetase (ACD) catalyzes the interconversion of acetyl-CoA and acetate. The related succinyl-CoA synthetase follows a three-step mechanism involving a single phosphoenzyme, but a novel four-step mechanism with two phosphoenzyme intermediates was proposed for Pyrococcus ACD. Characterization of enzyme variants of Entamoeba ACD in which the two proposed phosphorylated His residues were individually altered revealed that only His252 is essential for enzymatic activity. Analysis of variants altered at two residues proposed to interact with the phosphohistidine loop that swings between distinct parts of the active site are consistent with a mechanism involving a single phosphoenzyme intermediate. Our results suggest ACDs with different subunit structures may employ slightly different mechanisms to bridge the span between active sites I and II.