The enteropathogenic Escherichia coli (EPEC) multicargo chaperone CesT interacts with at least 10 effector proteins and is central to pathogenesis. CesT has been implicated in coordinating effector hierarchy, although the mechanisms behind this regulation are poorly understood. To address this question, we set out to functionally characterize CesT with respect to roles in (i) effector binding, (ii) effector recruitment to the type III secretion system (T3SS), and (iii) effector translocation into host cells. A CesT variant expression library was screened in EPEC using a newly developed semi-high-throughput secretion assay. Among many deficient CesT variants, a predominant number were localized to a novel CesT C-terminal region. These CesT C-terminal variants exhibited normal effector binding yet reduced effector secretion levels. Structural correlation and thermal spectroscopy analyses of purified CesT variants implicated multiple surface-exposed residues, a terminal helix region, and a flexible C-terminal triple-serine stretch in effector secretion. Site-directed mutagenesis of the flexible CesT C-terminal triple-serine sequence produced differential effector secretion, implicating this region in secretion events. Infection assays further indicated that the C-terminal region of CesT was important for NleA translocation into host cells but was dispensable for Tir translocation. The findings implicate the CesT C terminus in effector secretion and contribute to a model for multiple-cargo chaperone function and effector translocation into host cells during infection.

Background: Large-angle strabismus often demands a series of surgeries to achieve satisfactory alignment. This often necessitates bilateral surgery, which patients may be reluctant to undergo. Methods: Three patients with large-angle esotropia, not amenable to standard recession and resection procedures, underwent primary true muscle transplantation wherein a fragment of resected extraocular muscle was used to elongate the medial rectus muscle. Results: Postoperative deviation was within ± 10 PD of orthophoria and was maintained at follow-up of 6 to 12 months. There was mild underaction of the weakened muscle. Conclusion: True muscle transplantation is a good option because it permits correction of large-angle strabismus with two-muscle surgery, provides a satisfactory cosmetic alignment, and appears safe and predictable. J Pediatr Ophthalmol Strabismus 2005;42:211–215.

AimsTo analyse the prevalence of visual impairment (VI), compare it to certification of visual impairment (CVI) and analyse VI associations in patients with diabetic retinopathy (DR).MethodsRetrospective cohort study, which included 8007 patients with DR referred from the English diabetic eye screening programme to a tertiary referral eye hospital. Main outcome measure was VI, defined as vision in the best eye of <6/24. We conducted a multivariable logistic regression for VI as primary outcome of interest, controlling for age, sex, type of diabetes, baseline DR grade, ethnicity and index of multiple deprivation (IMD).ResultsMean age was 64.5 (SD 13.6) years; 61% of patients were men; and 31% of South Asian ethnicity. There were 68 patients with CVI during the study period, and 84% (272/325) of patients with VI did not have CVI after a mean follow-up of 1.87 (SD ±0.86) years. Older age showed a positive association with VI (OR per decade rise 1.88, 95% CI 1.70 to 2.08; p=1.8×10–34). Men had a lower risk of VI (OR 0.62, 95% CI 0.50 to 0.79, p=6.0×10–5), and less deprivation had a graded inverse association with VI (OR per IMD category increase 0.83, 95% CI 0.74 to 0.93, p value for linear trend 0.002).ConclusionThe majority of people with vision impairment are not registered at the point of care, which could translate to underestimation of diabetes-related VI and all-cause VI at a national level if replicated at other centres. Further work is needed to explore rates of VI and uptake of registration.

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