A novel rat model for subchondral microdamage in acute knee injury: a potential mechanism in post-traumatic osteoarthritis.

OBJECTIVE: Subchondral microdamage may play an important role in post-traumatic osteoarthritis (PTOA) development following anterior cruciate ligament (ACL) rupture. It remains unknown whether this injury mechanism causes subchondral microdamage, or whether its repair occurs by targeted osteoclast-mediated remodeling. If so these events may represent a mechanism by which subchondral bone is involved in PTOA. Our objective was to test the hypothesis that subchondral microdamage occurs, and is co-localized with remodeling, in a novel rat model of ACL rupture. DESIGN: We developed a novel non-invasive rat animal model for ACL rupture and subchondral microdamage generation. By inducing ACL rupture noninvasively rather than surgically, this more closely mimics the clinical injury. MicroCT, MRI and histological methods were used to measure microstructural changes, ligament damage, and cellular/matrix degeneration, respectively. RESULTS: We reproducibly generated ACL rupture without damage to other soft joint tissues. Immediately after injury, increased microdamage was found in the postero-medial aspect of the tibia. Microstructural parameters showed increased resorption at 2 weeks, which returned to baseline. Dynamic histomorphometry showed increased calcein label uptake in the same region at 4 and 8 weeks. Chondrocyte death and protease activity in cartilage was also noted, however whether this was directly linked to subchondral changes is not yet known. Similarly, cartilage scoring showed degradation at 4 and 8 weeks post-injury. CONCLUSIONS: This study shows that our novel model can be used to study subchondral microdamage after ACL-rupture, and its association with localized remodeling. Cartilage degeneration, on a similar time-scale to other models, is also a feature of this system.

Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.

Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.

Improving the detection of illicit substance use in preoperative anesthesiological assessment.

AIM: Illicit substance use (ISU) is a worldwide burden, and its prevalence in surgical patients has not been well investigated. Co-consumption of legal substances, such as alcohol and tobacco, complicates the perioperative management and is frequently underestimated during routine preoperative assessment. The aim of this study was to compare the anesthesiologists' detection rate of ISU during routine preoperative assessment with a computerized self-assessment questionnaire. METHODS: In total, 2,938 patients were included in this study. Prior to preoperative assessment, patients were asked to complete a computer-based questionnaire that addressed ISU, alcohol use disorder (AUDIT), nicotine use (Fagerström) and socio-economic variables (education, income, employment, partnership and size of household). Medical records were reviewed, and the anesthesiologists' detection of ISU was compared to the patients' self-reported ISU. RESULTS: Seven point five percent of patients reported ISU within the previous twelve months. ISU was highest in the age group between 18 and 30 years (26.4%; P<0.01). Patients reporting ISU were more often men than women (P<0.01), smokers (P<0.01) and tested positive for alcohol use disorder (P<0.01). Anesthesiologists detected ISU in one in 43 patients, whereas the computerized self-assessment reported it in one in 13 patients. The detection was best in the subgroup self-reporting frequent ISU (P<0.01). CONCLUSIONS: Anesthesiologists underestimate the prevalence of ISU. Computer-based self-assessment increases the detection of ISU in preoperative assessment and may decrease perioperative risk. More strategies to improve the detection of ISU as well as brief interventions for ISU are required in preoperative assessment clinics.