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In natural photosynthesis, the light-driven splitting of water into electrons, protons and molecular oxygen forms the first step of the solar-to-chemical energy conversion process. The reaction takes place in photosystem II, where the Mn4CaO5 cluster first stores four oxidizing equivalents, the S0 to S4 intermediate states in the Kok cycle, sequentially generated by photochemical charge separations in the reaction center and then catalyzes the O–O bond formation chemistry1–3. Here, we report room temperature snapshots by serial femtosecond X-ray crystallography to provide structural insights into the final reaction step of Kok’s photosynthetic water oxidation cycle, the S3→[S4]→S0 transition where O2 is formed and Kok’s water oxidation clock is reset. Our data reveal a complex sequence of events, which occur over micro- to milliseconds, comprising changes at the Mn4CaO5 cluster, its ligands and water pathways as well as controlled proton release through the hydrogen-bonding network of the Cl1 channel. Importantly, the extra O atom Ox, which was introduced as a bridging ligand between Ca and Mn1 during the S2→S3 transition4–6, disappears or relocates in parallel with Yz reduction starting at approximately 700 μs after the third flash. The onset of O2 evolution, as indicated by the shortening of the Mn1–Mn4 distance, occurs at around 1,200 μs, signifying the presence of a reduced intermediate, possibly a bound peroxide.

The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU).This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform.Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU.The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide.

Purpose To describe the surgical management of presumed trematode-induced granulomatous intermediate uveitis (PTIGIU) not responding to medical treatment in controlling the inflammation. Methods A prospective, interventional, single-center study in which patients with a history of fresh canal water contact and PTIGIU were enrolled. All patients underwent lensectomy–pars plana vitrectomy (PPV) and post-operative control of inflammation, functional and anatomical outcomes were assessed. Results Fifteen eyes of 12 patients were included in the study with median age of 11.6 ± 4 yrs. Six months following lensectomy-PPV, inflammation was well controlled in all patients. The eyes were divided into two groups: Group A: 10 patients with an attached retina while Group B: 5 patients who were in the cicatricial stage with tractional retinal detachment. All patients in group A had CDVA of 20/40 or better, unlike patients in group B who failed to achieve a CDVA better than 20/70 throughout their follow-up. In group B, final anatomical success was achieved in only 40% with hypotony occurring in 20%. Conclusion PTIGIU is associated with the presence of ciliary body granuloma which, if left untreated, can lead to drastic outcomes. Early lensectomy-PPV represents a viable management option in cases resistant to medical treatment, with a favorable outcome.

To evaluate the retinal vasculature in psoriasis patients and detect if metabolic syndrome is an additional risk factor. This cross-sectional analytic study was carried out on 80 eyes of 80 subjects; 28 eyes with psoriasis only (PS group), 12 eyes with additional metabolic syndrome to psoriasis (PMS group) and 40 eyes healthy controls (HS). The retinal capillary plexuses were evaluated by OCTA. The disease activity was evaluated by the Psoriasis Area and Severity Index (PASI) score and extent. The superficial capillary plexus (SCP) vascular density was significantly lower in PS group than HS while in PMS it was significantly lower only in whole image and superior and temporal perifoveal areas (p-value = 0.020, 0.030, 0.001 respectively). The changes correlated with the disease duration. The vascular density of the deep capillary plexus (DCP) was significantly lower in both PS and PMS groups (p-value

X-ray crystallography at X-ray free-electron laser sources is a powerful method for studying macromolecules at biologically relevant temperatures. Moreover, when combined with complementary techniq ...