Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain.

Although immune tolerance evolved to reduce reactivity with self, it creates a gap in the adaptive immune response against microbes that decorate themselves in self-like antigens. This is particularly apparent with carbohydrate-based blood group antigens, wherein microbes can envelope themselves in blood group structures similar to human cells. In this study, we demonstrate that the innate immune lectin, galectin-4 (Gal-4), exhibits strain-specific binding and killing behavior towards microbes that display blood group-like antigens. Examination of binding preferences using a combination of microarrays populated with ABO(H) glycans and a variety of microbial strains, including those that express blood group-like antigens, demonstrated that Gal-4 binds mammalian and microbial antigens that have features of blood group and mammalian-like structures. Although Gal-4 was thought to exist as a monomer that achieves functional bivalency through its two linked carbohydrate recognition domains, our data demonstrate that Gal-4 forms dimers and that differences in the intrinsic ability of each domain to dimerize likely influences binding affinity. While each Gal-4 domain exhibited blood group-binding activity, the C-terminal domain (Gal-4C) exhibited dimeric properties, while the N-terminal domain (Gal-4N) failed to similarly display dimeric activity. Gal-4C not only exhibited the ability to dimerize but also possessed higher affinity toward ABO(H) blood group antigens and microbes expressing glycans with blood group-like features. Furthermore, when compared to Gal-4N, Gal-4C exhibited more potent antimicrobial activity. Even in the context of the full-length protein, where Gal-4N is functionally bivalent by virtue of Gal-4C dimerization, Gal-4C continued to display higher antimicrobial activity. These results demonstrate that Gal-4 exists as a dimer and exhibits its antimicrobial activity primarily through its C-terminal domain. In doing so, these data provide important insight into key features of Gal-4 responsible for its innate immune activity against molecular mimicry.

Evaluation of the impact of short term manual small incision cataract surgery (MSICS) training program on trainees with varying prior surgical experience using international council of ophthalmology-ophthalmology surgical competency assessment rubrics (ICO-OSCAR).

PURPOSE: To assess the learning curve of MSICS in three different groups of trainees with varying prior MSICS experience. To evaluate the effectiveness of ICO OSCAR for objective assessment of surgical skill transfer. METHODS: Ninety-five MSICS trainees were divided into three groups as 1st year resident, fellow and external trainee. Each group were evaluated for their surgical skill acquisition during one month MSICS training program using ICO-OSCAR. Each trainee performed an average of 19 surgeries. The progress in the learning curve of the three groups of trainees was analyzed by evaluating the mean scores in sets of five consecutive cases. Complications during the training period were also noted. RESULTS: The study evaluated a total of 1842 cases. The fellows and external trainees, with prior MSICS experience, had an initial mean score of 57.57 ± 16.16 and 56.86 ± 17.82 respectively, whereas the 1st year resident group had a relatively low initial mean score of 45.91(p = 0.009). The difference in mean scores between the 1st year resident group and other groups significantly reduced towards the end of training. The most common complications made by 1st year residents were in sclero-corneal tunnel construction. The external trainee group had statistically significant higher rates of zonular dialysis in the study. CONCLUSIONS: ICO-OSCAR is an effective tool for assessing MSICS training program. Structured short term MSICS surgical training program is effective in surgical skill transfer, especially in novice surgeons.

Kelly's VV-plasty for catheterising channels; first reported case series.

Anastomosis of catheterising channels (Mitrofanoff and ACE) to the skin can be a challenge. The Kelly VV plasty is a straightforward solution but has been described only as a point of technique. We used the previously described method with minor modification. The technique has been used in 14 patients, including 9 children and 5 adults for Mitrofanoff,ACE and Monti channels. At a median follow-up of 25 months all patients continue to catheterise; none have required revision surgery. The Kelly VV plasty is a potentially robust solution to the problem of skin anastomosis; technique merits wider adoption and evaluation.

Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis.

The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.