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Oligohydramnios (decreased amniotic fluid volume for gestational age) is a severe condition associated with high morbidity and mortality mainly due to fetal pulmonary hypoplasia. Currently, there are limited treatment options to promote fetal lung development. Administration of stem cells and their derivates have shown promising regenerative properties for several fetal and neonatal diseases related to arrested lung development. Herein, we first characterized pulmonary hypoplasia secondary to oligohydramnios in a surgical rat model. Experimental induction of oligohydramnios led to impaired lung growth, branching morphogenesis (fewer airspaces with decreased Fgf10, Nrp1, Ctnnb1 expression), proximal/distal progenitor cell patterning (decreased Sox2 and Sox9 expression), and TGF-β signaling. We then tested antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs). In oligohydramnios lungs, AFSC-EV administration improved lung branching morphogenesis and airway progenitor cell patterning at least in part through the release of miR-93-5p. Our experiments suggest that AFSC-EV miR-93-5p blocked SMAD 7, resulting in upregulation of pSMAD2/3 and restoration of TGF-β signaling. Conversely, oligohydramnios lungs treated with antagomir 93-5p transfected AFSC-EVs had decreased branching morphogenesis and TGF-β signaling. This is the first study reporting that antenatal administration of stem cell derivatives could be a potential therapy to rescue lung development in fetuses with oligohydramnios., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Collaborate, Analyse, Research and Audit (CARA) project set out to provide an infrastructure to enable Irish general practitioners (GPs) to use their routinely collected patient management software (PMS) data to better understand their patient population, disease management and prescribing through data dashboards. This paper explains the design and development of the CARA infrastructure., Methods: The first exemplar dashboard was developed with GPs and focused on antibiotic prescribing to develop and showcase the proposed infrastructure. The data integration process involved extracting, loading and transforming de-identified patient data into data models which connect to the interactive dashboards for GPs to visualise, compare and audit their data., Results: The architecture of the CARA infrastructure includes two main sections: extract, load and transform process (ELT, de-identified patient data into data models) and a Representational State Transfer Application Programming Interface (REST API) (which provides the security barrier between the data models and their visualisation on the CARA dashboard). CARAconnect was created to facilitate the extraction and de-identification of patient data from the practice database., Discussion: The CARA infrastructure allows seamless connectivity with and compatibility with the main PMS in Irish general practice and provides a reproducible template to access and visualise patient data. CARA includes two dashboards, a practice overview and a topic-specific dashboard (example focused on antibiotic prescribing), which includes an audit tool, filters (within practice) and between-practice comparisons., Conclusion: CARA supports evidence-based decision-making by providing GPs with valuable insights through interactive data dashboards to optimise patient care, identify potential areas for improvement and benchmark their performance against other practices.Supplementary file 1. Graphical abstract., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to determine the suitability of HP-treated caprine milk for yoghurt production and to evaluate the effect of HP treatment on yoghurt properties. Reconstituted caprine milk was subjected to HP treatment (350 MPa/10 min/20 °C); a lactic acid starter culture (YC-X16, Chr. Hansen) was added. Milk was fermented at a temperature of 43 °C until pH 4.60. Bacterial counts, pH, color, rheological characteristics, texture, microstructure, and the sensory attributes of the yoghurt were determined after production and after seven days of storage at a temperature of 4 °C. HP treatment increased color saturation and whiteness index and induced a minor increase in milk pH. Minor differences in the acidification curve were noted. During storage, Streptococcus thermophilus counts were significantly higher in yoghurt from HP-treated than from untreated milk, whereas Lactobacillus delbruecki ssp. bulgaricus counts remained stable. A color analysis did not reveal differences between the experimental and control yoghurts. After storage, yoghurt made from HP-treated milk was characterized by thicker consistency and lower rheological stability than the control yoghurt. The micrographs of the yoghurts confirmed the differences in rheological parameters. Yoghurt produced from HP-treated caprine milk and stored for seven days received the highest scores in the sensory evaluation.