Postpartum development of metabolic dysfunction-associated steatotic liver disease in a lean mouse model of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with increased postpartum risk for metabolic dysfunction-associated steatotic liver disease (MASLD). GDM-related MASLD predisposes to advanced liver disease, necessitating a better understanding of its development in GDM. This preclinical study evaluated the MASLD development in a lean GDM mouse model with impaired insulin secretion capacity. Lean GDM was induced by short-term 60% high-fat diet and low-dose streptozotocin injections (60 mg/kg for 3 days) before mating in C57BL/6N mice. The control dams received only high-fat diet or low-fat diet. Glucose homeostasis was assessed during pregnancy and postpartum, whereas MASLD was assessed on postpartum day 30 (PP30). GDM dams exhibited a transient hyperglycemic phenotype during pregnancy, with hyperglycaemia reappearing after lactation. Lower insulin levels and impaired glucose-induced insulin response were observed in GDM mice during pregnancy and postpartum. At PP30, GDM dams displayed higher hepatic triglyceride content compared controls, along with increased MAS (MASLD) activity scores, indicating lipid accumulation, inflammation, and cell turnover indices. Additionally, at PP30, GDM dams showed elevated plasma liver injury markers. Given the absence of obesity in this double-hit GDM model, the results clearly indicate that impaired insulin secretion driven pregnancy hyperglycaemia has a distinct contribution to the development of postpartum MASLD.

Nonlinear 3D projection printing of concave hydrogel microstructures for long-term multicellular spheroid and embryoid body culture.

Long-term culture and monitoring of individual multicellular spheroids and embryoid bodies (EBs) remains a challenge for in vitro cell propagation. Here, we used a continuous 3D projection printing approach - with an important modification of nonlinear exposure - to generate concave hydrogel microstructures that permit spheroid growth and long-term maintenance, without the need for spheroid transfer. Breast cancer spheroids grown to 10 d in the concave structures showed hypoxic cores and signs of necrosis using immunofluorescent and histochemical staining, key features of the tumor microenvironment in vivo. EBs consisting of induced pluripotent stem cells (iPSCs) grown on the hydrogels demonstrated narrow size distribution and undifferentiated markers at 3 d, followed by signs of differentiation by the presence of cavities and staining of the three germ layers at 10 d. These findings demonstrate a new method for long-term (e.g. beyond spheroid formation at day 2, and with media exchange) 3D cell culture that should be able to assist in cancer spheroid studies as well as embryogenesis and patient-derived disease modeling with iPSC EBs.

[Waardenburg syndrome. A heterogenic disorder with variable penetrance]. / Waardenburg-Syndrom. Eine heterogene Erkrankung mit variabler Penetranz.

BACKGROUND: Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. PATIENTS AND METHODS: Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. RESULTS AND CONCLUSION: In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.

Identification of aquaporin 5 (AQP5) within the cochlea: cDNA cloning and in situ localization.

Dysfunction of fluid and electrolyte homeostasis is considered to cause variety of inner ear disorders. One group of candidate proteins that may play a critical role in the inner ear fluid homeostasis is the aquaporins, a family of proteins whose members have well defined roles in fluid transport in variety of organs. This study reports the identification of AQP5, a member of the aquaporin family, within the rat inner ear and its in situ localization. AQP5 was initially identified within rat cochlear RNA via RT-PCR and sequence analysis of the amplified fragments. Immunoblot of cochlear homogenate yielded a predominant AQP5-immunoreactive band of M(r) 35 kDa. The anti-AQP5 immunoreactivity, indicating expression of the AQP5 polypeptide, was localized within the cochlea in situ to the cell types that form the lateral wall of the cochlear duct-the external sulcus (ES) cells and the cells of the spiral prominence. Expression of AQP5 was observed in the apical turn but not the basal turn of the cochlea; nor was it observed in the vestibular neuroepithelia or its supporting cells. The restricted expression of AQP5 to the apical turns of the cochlea suggests its potential role in low frequency hearing.

Supporting collaboration through a nursing informatics curriculum stage II.

Collaboration is at the center of the process used to design, implement and evaluate an integrated informatics curriculum in a baccalaureate nursing program. This paper describes the second stage of a process to design the informatics nursing courses. The challenges to foster faculty collaborative relationships as well as to enhance the course content of all nursing informatics curriculum. A number of strategies were used to develop the collaborative efforts between the faculty and nursing staff in the clinical agencies. Information technology was incorporated into the didactic and clinical portions of courses through the use of creative teaching strategies. Therefore, the faculty have ensured a blend of information, technology, and the clinical care process throughout the curriculum.