Monitoring the neurotransmitter release of human midbrain organoids using a redox cycling microsensor as a novel tool for personalized Parkinson's disease modelling and drug screening.

In this study, we have aimed at developing a novel electrochemical sensing approach capable of detecting dopamine, the main biomarker in Parkinson's disease, within the highly complex cell culture matrix of human midbrain organoids in a non-invasive and label-free manner. With its ability to generate organotypic structures in vitro, induced pluripotent stem cell technology has provided the basis for the development of advanced patient-derived disease models. These include models of the human midbrain, the affected region in the neurodegenerative disorder Parkinson's disease. Up to now, however, the analysis of so-called human midbrain organoids has relied on time-consuming and invasive strategies, incapable of monitoring organoid development. Using a redox-cycling approach in combination with a 3-mercaptopropionic acid self-assembled monolayer modification enabled the increase of sensor selectivity and sensitivity towards dopamine, while simultaneously reducing matrix-mediated interferences. In this work, we demonstrate the ability to detect and monitor even small differences in dopamine release between healthy and Parkinson`s disease-specific midbrain organoids over prolonged cultivation periods, which was additionally verified using liquid chromatography-multiple reaction monitoring mass spectrometry. Furthermore, the detection of a phenotypic rescue in midbrain organoids carrying a pathogenic mutation in leucine-rich repeat kinase 2, upon treatment with the leucine-rich repeat kinase 2 inhibitor II underlines the practical implementability of our sensing approach for drug screening applications as well as personalized disease modelling.

Comparison of single layer staple closure versus double layer hand-sewn closure for equine pelvic flexure enterotomy.

Our objective was to compare thoracoabdominal (TA Premium™ 90) stapled enterotomy closure to traditional hand-sewn closure, using time to perform the technique, luminal diameter, and bursting pressure in ex-vivo specimens. The pelvic flexures of 13 client-owned horses were harvested. Each pelvic flexure had 1 enterotomy performed; 6 were closed via staples, 7 closures were hand-sewn. Luminal diameter at the enterotomy site was assessed via contrast radiography performed pre-and post-enterotomy. Bursting pressure of the closure was assessed by continuous manometry during rapid infusion. Time to perform stapled closure was significantly shorter than hand-sewn closure (P < 0.0001). Percent reduction of luminal diameters was significantly decreased in stapled specimens (P = 0.034). There was no significant difference in bursting strength between closure techniques (P = 0.196). In conclusion, stapled enterotomy closure offers statistically significant reduction in closure time and better maintains pre-enterotomy luminal diameter without reducing biomechanical strength, compared to a double layer hand-sewn closure.

Tomorrow today: organ-on-a-chip advances towards clinically relevant pharmaceutical and medical in vitro models.

Organ-on-a-chip technology offers the potential to recapitulate human physiology by keeping human cells in a precisely controlled and artificial tissue-like microenvironment. The current and potential advantages of organs-on-chips over conventional cell cultures systems and animal models have captured the attention of scientists, clinicians and policymakers as well as advocacy groups in the past few years. Recent advances in tissue engineering and stem cell research are also aiding the development of clinically relevant chip-based organ and diseases models with organ level physiology for drug screening, biomedical research and personalized medicine. Here, the latest advances in organ-on-a-chip technology are reviewed and future clinical applications discussed.

Use of tube cystostomy in the surgical management of obstructive urolithiasis in a Bactrian camel.

CASE DESCRIPTION: A 6-year-old castrated male Bactrian camel was evaluated because of a 14hour history of oliguria and stranguria that progressed to anuria. CLINICAL FINDINGS: Perineal urethral pulsations and intermittent tail flagging with no accompanying urination were observed. Ultrasonography of the urethra revealed multiple hyperechoic foci with shadowing artifact indicative of calculi present in the penile urethra distal to the sigmoid flexure. Rectal palpation revealed a pulsating hard urethra and intact distended urinary bladder. Further clinical examination was not possible because of challenges associated with handling the camel. TREATMENT AND OUTCOME: Urethral catheterization through a perineal urethral incision failed to achieve urinary bladder decompression. Tube cystostomy was performed to prevent bladder rupture. Urethrocystography performed 3 days after surgery revealed a urethral rupture at the level of the prepuce. Five weeks after surgery, the camel could urinate a steady stream via the urethrotomy site. Seven weeks after surgery, the cystostomy tube was removed, and the urethrotomy site was modified to provide a permanent urethral opening via perineal urethrostomy. During 6 years of subsequent periodic follow-up by telephone, the owner reported that the camel continued to do well and urinate through the revised opening. CLINICAL RELEVANCE: To the authors' knowledge, this is the first detailed description of a tube cystostomy in an adult camel with obstructive urolithiasis that includes information on the patient's long-term outcome. This technique was a viable option in the surgical management of obstructive urolithiasis in this camel and may be useful for other large camelids as well.