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Histological analysis of the wall of the excretory ducts was performed in order to identify common and distinctive features of the structural and spatial organization of the excretory ducts of the human lacrimal gland. In the system of excretory ducts of the human lacrimal gland revealed changes in diameter, which are visualized in sections in the form of local narrowings and pear-shaped extensions (the phenomenon of siphonization). In addition to the siphon-like structure of some excretory ducts, the phenomenon of its spiraling is noted. At the same time the tendency to existence of the greatest throughput for secretion in interparticle and general output channels is noted.The obtained morphological data will help to elucidate the mechanism of secretion outflow from the bifurcated system of the excretory ducts of the human lacrimal gland., Проведено гістологічний аналіз стінки вивідних проток, з метою виявлення спільних і відмінних рис структурно-просторової організації системи екскреторних проток сльозової залози людини. В системі вивідних проток сльозової залози людини виявлені зміни діаметра, які візуалізовані на зрізах у вигляді локальних звужень і грушоподібних розширень (феномен сифонізації). Крім сифоноподібної будови деяких вивідних проток відзначений феномен його спіралізації. При цьому відмічена тенденцію до наявності найбільшої пропускної здатності для секреції у міжчасточкових і загальних вивідних протоках.Отримані морфологічні дані будуть сприяти з'ясуванню механізму відтоку секрету з роздвоєною системою вивідних проток сльозової залози людини.

The adult human body consists of trillions of cells. These cells are the building blocks for every organ and tissue in the body. During our lifetime, cells are constantly lost at different speeds due to natural turnover or damage. Extreme examples include the intestinal epithelium and the cardiomyocytes of the heart, with respective cellular turnover times of several days to nearly a lifetime. Adult stem cells are cells that have the capacity to replace lost cells through cell division. The research conducted in my PhD thesis is focussed on modeling adult stem cells and their progeny. Studying adult stem cell identity and function is important to understand how organs function on a cellular level and what goes wrong during disease. Every organ and every animal has its own strategy to exploit adult stem cells and to replace lost tissue. We have used in vivo lineage tracing and in vitro organoid technology to study a variety of organs in different vertebrates. We generated an unbiased map of proliferating cells and their progeny in neonatal, adult, and post damage murine hearts. Elucidating the proliferative populations of the heart important to survive a cardiac infarct. Using organoid technology, we established in vitro models of the human lacrimal gland and the snake venom gland. While both organs display unique biological properties, we uncover surprising similar adult stem cell behaviour. In short, my research describes new experimental models to study vertebrate adult stem cells and uncover their potential.

Background:Several large randomised controlled trials (RCTs) in primary Sjögren’s syndrome (pSS) failed to demonstrate drug efficacy.1-4 Many of these trials used ESSDAI as primary endpoint, showing large but similar response rates in active treatment and placebo groups.1,3,4 Given the heterogeneous nature of pSS, there is need for a composite endpoint including multiple clinically relevant parameters.Objectives:To develop and validate the Composite of Relevant Endpoints in Sjögren’s Syndrome (CRESS).Methods:A multidisciplinary team of pSS experts selected clinically relevant items and measurements to include in the CRESS. Definition of response of CRESS items was based on clinical relevance, previously defined minimal clinically important improvement (MCII) and data of the single-centre ASAP-III (abatacept) trial.1 CRESS was validated in three independent RCTs: TRACTISS (rituximab) trial2, multi-centre abatacept trial3 and ETAP (tocilizumab) trial4. CRESS response rates were assessed at the primary endpoint visit of all four trials.Results:Five complementary items were selected to form CRESS: systemic disease activity, patient-reported symptoms, tear gland, salivary gland and serological item. Definition of response per item is presented in Table 1. Total CRESS response was defined as response on ≥3 of 5 items. Since not all trials have ocular staining score or salivary gland ultrasonography (SGUS) available, the concise CRESS (cCRESS) was developed simultaneously, leaving Schirmer’s test and unstimulated whole saliva flow for the tear and salivary gland items, respectively. In the ASAP-III trial, CRESS response rates were 24/40 (60%) for abatacept vs. 7/39 (18%) for placebo at week 24 (pTable 1.CRESS items and definition of responseItemsMeasurementsDefinition of responseSystemic disease activityClinESSDAIScorePatient-reported symptomsESSPRIDecrease of ≥1 point or ≥15%Tear gland*Schirmer/OSS**-If abnormal Schirmer (≤5 mm) at baseline: increase of ≥5 mm in Schirmer-Or if abnormal OSS (≥3 points) at baseline: decrease ≥2 points in OSS-Or if both Schirmer/OSS normal scores at baseline: no change to abnormal in bothSalivary gland*UWS/SGUSIncrease of ≥25% in UWS (or if score is 0 at baseline, any increase)Or decrease of ≥25% in total Hocevar score (SGUS)SerologicalRF/IgGDecrease of ≥25% in RFOr decrease of ≥10% in IgGCRESS responderResponder on ≥3 of 5 itemsOcular Staining Score (OSS), Unstimulated whole salivary flow (UWS), Salivary gland ultrasonography (SGUS), Rheumatoid factor (RF), Immunoglobuline G (IgG)*Concise CRESS (cCRESS): CRESS without OSS and SGUS, leaving Schirmer and UWS for tear and salivary gland items, respectively**Mean of both eyesIn the external validation trials, cCRESS response rates for TRACTISS were: 33/67 (49%) rituximab vs. 20/66 (30%) placebo at week 48 (p=0.026). CRESS response rates (without SGUS) for the multi-centre abatacept trial were: 41/92 (45%) abatacept vs. 30/95 (32%) placebo at week 24 (p=0.067). cCRESS response rates (without rheumatoid factor) for ETAP were: 10/55 (18%) tocilizumab vs. 13/55 (24%) placebo at week 24 (p=0.482) (Figure 1A-D). Compared to ESSDAI MCII of ≥3 points decrease, CRESS was able to approximately halve placebo response rates in RCTs with high baseline ESSDAI scores (>5) (Figures 1E-H).Conclusion:CRESS shows lower placebo response rates compared to ESSDAI MCII, which is crucial for demonstrating treatment efficacy. With the CRESS, higher response rates in abatacept and rituximab treated patients compared to placebo were found in RCTs which previously showed negative primary endpoint results. CRESS confirmed that no differences were found for almost all outcome measures between tocilizumab and placebo,4 with low response rates. The CRESS is a well-balanced, feasible, composite endpoint for use in clinical trials in pSS patients.References:[1]Van Nimwegen 2020;9913(19):1–11[2]Bowman 2017;69(7):1440–50[3]Baer (doi:218599)[4]Felten (doi:21846)Acknowledgements:The authors would like to acknowledge all contributors of the included trials.Disclosure of Interests:Suzanne Arends: None declared, Liseth de Wolff: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Gwenny M. Verstappen: None declared, Jelle Vehof: None declared, Michele Bombardieri Consultant of: MedImmune, GlaxoSmithKline, Grant/research support from: MedImmune, Simon J. Bowman Consultant of: AstraZenecea/MedImmune, Bristol Myers Squibb, Celgene, Eli Lilly, Glenmark, GlaxoSmithKline, MTPharma, Novartis, Ono, Pfizer, Takeda, UCB, XTLBio, Elena Pontarini: None declared, Alan Baer Consultant of: Bristol Myers Squibb, Sanofi, VielaBio, Novartis, Marleen Nys Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Jacques-Eric Gottenberg Grant/research support from: Bristol Myers Squibb, Pfizer, Renaud FELTEN: None declared, Neelanjana Ray Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Arjan Vissink: None declared, Frans G.M. Kroese Speakers bureau: Bristol Myers Squibb, Roche and Janssen-Cilag, Consultant of: Bristol Myers Squibb, Grant/research support from: Unrestricted grants from Bristol Myers Squibb, Hendrika Bootsma Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Bristol Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol Myers Squibb and Roche

Ocular fluid is an extracellular fluid excreted from the tear gland. Several important markers from ocular fluid have been identified as having significant clinical diagnostic value for various diseases. The contact lens is disposable, relatively cheap and serves as a platform to obtain direct intimate contact with ocular fluid and is therefore an attractive and a promising platform for point-of-care diagnostic tests. Here, we present an entirely new concept of a wearable theranostic device, in the form of a contact lens (theranostic lens) with a dual-function hybrid surface, to modulate and detect a pathogenic attack by herpes simplex virus type 1 (HSV-1). The theranostic lenses were constructed using a Layer-by-Layer (LbL) surface engineering technique to produce a functional hybrid surface containing both an anti-HSV-1 polysulfonate compound and specific antibodies for viral detection. The resulting theranostic lenses retained good optically transparency and surface wettability, and were non-toxic towards human corneal epithelial cells (HCECs). We showed that the theranostic lenses could capture and concentrate interleukin-1α (IL-1α), which is upregulated during HSV-1 infection, using an artificial cornea model integrated with a microfluidic system mimicking tear flow. The theranostics lenses exhibited effective anti-HSV-1 activity and good analytical performance for the detection of IL-1α, with a limit of detection of 1.43 pg mL -1 and a wide linear range covering the clinically relevant region. Our strategy also tackles the major problems in tear diagnostics that are associated with the small volumes from tear sampling and the low concentration of biomarkers in these samples. This work offers a new paradigm for wearable, non-invasive healthcare devices combining diagnosis and protection against disease. We believe that this approach holds promise as a next-generation, point-of-care and de-centralized diagnostic/theranostic platform for a range of biomarkers.