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Background: Epidemiologic data on the number of cleft lip and/or palate (orofacial cleft (OFC)) births in Switzerland are currently sparse. However, this knowledge is essential for better understanding the etiologies underlying the various cleft phenotypes and providing expectant parents with the best possible healthcare planning and counseling., Methods: This is the first descriptive study to report data on the prevalence of the various cleft types, their sex, and regional distributions in Switzerland. Data for the years 1998-2021 were obtained from the Swiss Federal Statistical Office. Due to the notable initial underreporting of cleft cases from 1998 to 2006, this period was omitted from the final analyses., Results: Between 2007 and 2021, the prevalence of all Swiss OFC cases per 10,000 live births was 12.5, with a stable trend. Cleft lip was the least common anomaly. Except for cleft palate, which was more common in females, males were generally more affected by OFC than females. There was no discernible regional trend for any of the malformations, even though the prevalence differed throughout the seven Swiss regions., Conclusions: This study presents the first descriptive epidemiologic profiles for OFCs in Switzerland and emphasizes the importance of nationwide OFC registries with an accurate and reliable reporting system for the benefit of current and future patients with clefts, their parents or caregivers, and society as a whole., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Fibronectin (FN) is an extracellular matrix glycoprotein that is abundantly expressed by fibroblasts in contracting wounds, where it mediates cell adhesion, migration and proliferation. FN also efficiently binds to collagen. Therefore, we and others hypothesized that FN and its cellular receptor integrin α 5 β 1 might be involved in collagen matrix contracture by acting as linkers. However, there are conflicting reports on this issue. Moreover, several publications suggest an important role of collagen-binding integrin receptors α 2 β 1 and α 11 β 1 in collagen matrix contracture. Therefore, the aim of the present study was to determine the contributions of FN-integrin α 5 β 1 interactions relative to those of collagen receptors α 2 β 1 and α 11 β 1 in this process. To assess the role of cellular FN directly, we employed FN-deficient mouse fibroblasts, subjected them to a collagen gel contracture assay in vitro , and compared them to their wildtype counterparts. Exogenous FN was removed from serum-containing medium. For dissecting the role of major collagen receptors, we used two FN-deficient mouse fibroblast lines that both possess integrin α 5 β 1 but differ in their collagen-binding integrins. Embryo-derived FN-null fibroblasts, which express α 11 - but no α 2 -integrin, barely spread and tended to cluster on collagen gels. Moreover, FN-null fibroblasts required exogenously added FN to assemble α 5 β 1 -integrin in fibrillar adhesion contacts, and to contract collagen matrices. In contrast, postnatal kidney fibroblasts were found to express α 2 - but barely α 11 -integrin. When FN expression was suppressed in these cells by shRNA transfection, they were able to spread on and partially contract collagen gels in the absence of exogenous FN. Also in this case, however, collagen contracture was stimulated by adding FN to the medium. Antibody to integrin α 5 β 1 or RGD peptide completely abolished collagen contracture by FN-deficient fibroblasts stimulated by FN addition. We conclude that although collagen-binding integrins (especially α 2 β 1 ) can mediate contracture of fibrillar collagen gels by murine fibroblasts to some extent, full activity is causally linked to the presence of pericellular FN and its receptor integrin α 5 β 1 .

Uromodulin, the most abundant protein in normal urine, is essentially produced by the cells lining the thick ascending limb. There it regulates the activity of the cotransporter NKCC2 and is involved in sodium chloride handling and blood pressure regulation. Conflicting reports suggested that uromodulin may also be expressed in the distal convoluted tubule (DCT) where its role remains unknown. Using microdissection studies combined with fluorescent in situ hybridization and co-immunostaining analyses, we found a significant expression of uromodulin in mouse and human DCT at approximately 10% of thick ascending limb expression levels, but restricted to the early part of the DCT (DCT1). Genetic deletion of Umod in mouse was reflected by a major shift in NCC activity from the DCT1 to the downstream DCT2 segment, paralleled by a compensatory expansion of DCT2. By increasing the distal sodium chloride and calcium ion load with chronic furosemide administration, an intrinsic compensatory defect in the DCT from Umod -/- compared to wild type mice was found manifested as sodium wasting and hypercalciuria. In line, co-expression studies in HEK cells suggested a facilitating role for uromodulin in NCC phosphorylation, possibly via SPAK-OSR1 modulation. These experiments demonstrate a significant expression of uromodulin in the early part of mouse and human DCT. Thus, biosynthesis of uromodulin in the DCT1 is critical for its function, structure and plasticity, suggesting novel links between uromodulin, blood pressure control and risk of kidney stones., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely "fast", "intermediate", and "slow". Most cleft lip/palate fibroblasts were distributed between the "fast" (5 strains) and the "intermediate" group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the "fast" group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the "intermediate" migratory group to the level of the "fast", but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of "fast" cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling.