Two-dimensional shear wave elastography of liver in healthy dogs: anaesthesia as a source of variability

Two-dimensional shear wave elastography (2D-SWE) is a non-invasive method to quantitatively evaluate the liver sti ness (LS), allowing the detection of hepatic pathological changes in both dogs and humans. In dogs, some factors such as patient movement and respiration can cause artefacts and potential errors of measurements. Therefore, anaesthesia has been suggested to reduce the e ect of the movement on 2D-SWE in dogs. This study was performed to evaluate the in uence of an anaesthetic protocol on 2D-SWE measurements for assessment of LS in healthy dogs. Forty- ve dogs were included and subjected to anaesthesia: in 11 dogs, the 2D- SWE was performed both before and under anaesthesia, in 19 dogs, the 2D-SWE was per- formed only when they were awake and in 15 dogs, the examination was carried out only under anaesthesia. The anaesthetic protocol was composed of intramuscular injection of a combination of dexmedetomidine, methadone and ketamine and intravenous administration of propofol for induction and iso urane for maintenance. The variability of 2D-SWE values according to anaesthesia was evaluated. Median 2D-SWE values were signi cantly higher in anesthetized dogs compared to awake dogs either by considering separately the dogs in which the examination was performed both awake and under anaesthesia and by considering all dogs included. According to our study, anaesthesia helped to avoid challenges related to patient movement and respiration; however, it was a source of variability on 2D-SWE values, and this factor should be considered before performing 2D-SWE under anaesthesia

Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis

Impaired proinsulin-to-insulin processing in pancreatic β-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. $^{1}$$^{,}$$^{2}$), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs. $^{3-8}$); nonetheless, the role of specific SL species in β-cell function and demise is unclear. Here we define the lipid signature of T2D-associated β-cell failure, including an imbalance of specific very-long-chain SLs and long-chain SLs. β-cell-specific ablation of CerS2, the enzyme necessary for generation of very-long-chain SLs, selectively reduces insulin content, impairs insulin secretion and disturbs systemic glucose tolerance in multiple complementary models. In contrast, ablation of long-chain-SL-synthesizing enzymes has no effect on insulin content. By quantitatively defining the SL-protein interactome, we reveal that CerS2 ablation affects SL binding to several endoplasmic reticulum-Golgi transport proteins, including Tmed2, which we define as an endogenous regulator of the essential proinsulin processing enzyme Pcsk1. Our study uncovers roles for specific SL subtypes and SL-binding proteins in β-cell function and T2D-associated β-cell failure

TWO-DIMENSIONAL SHEAR WAVE ELASTOGRAPHY OF LIVER IN HEALTHY DOGS: ANAESTHESIA AS A SOURCE OF VARIABILITY

Two-dimensional shear wave elastography (2D-SWE) is a non-invasive method to quantitatively evaluate the liver stiffness (LS), allowing the detection of hepatic pathological changes in both dogs and humans. In dogs, some factors such as patient movement and respiration can cause artefacts and potential errors of measurements. Therefore, anaesthesia has been suggested to reduce the effect of the movement on 2D-SWE in dogs. This study was performed to evaluate the influence of an anaesthetic protocol on 2D-SWE measurements for assessment of LS in healthy dogs. Forty-five dogs were included and subjected to anaesthesia: in 11 dogs, the 2D-SWE was performed both before and under anaesthesia, in 19 dogs, the 2D-SWE was performed only when they were awake and in 15 dogs, the examination was carried out only under anaesthesia. The anaesthetic protocol was composed of intramuscular injection of a combination of dexmedetomidine, methadone and ketamine and intravenous administration of propofol for induction and isoflurane for maintenance. The variability of 2D-SWE values according to anaesthesia was evaluated. Median 2D-SWE values were significantly higher in anesthetized dogs compared to awake dogs either by considering separately the dogs in which the examination was performed both awake and under anaesthesia and by considering all dogs included. According to our study, anaesthesia helped to avoid challenges related to patient movement and respiration; however, it was a source of variability on 2D-SWE values, and this factor should be considered before performing 2D-SWE under anaesthesia

L1CAM Expression in Microcystic, Elongated, and Fragmented (MELF) Glands Predicts Lymph Node Involvement in Endometrial Carcinoma

In endometrial carcinoma, both L1CAM overexpression and microcystic, elongated and fragmented (MELF) patterns of invasion have been related to epithelial-to-mesenchymal transition and metastatic spread. We aimed to assess the association between L1CAM expression, the MELF pattern, and lymph node status in endometrial carcinoma. Consecutive cases of endometrial carcinoma with MELF pattern were immunohistochemically assessed for L1CAM. Inclusion criteria were endometrioid-type, low-grade, stage T1, and known lymph node status. Uni- and multivariate logistic regression were used to assess the association of L1CAM expression with lymph node status. Fifty-eight cases were included. Most cases showed deep myometrial invasion (n = 42, 72.4%) and substantial lymphovascular space invasion (n = 34, 58.6%). All cases were p53-wild-type; 17 (29.3%) were mismatch repair-deficient. Twenty cases (34.5%) had positive nodes. No cases showed L1CAM positivity in ≥10% of the whole tumor. MELF glands expressed L1CAM at least focally in 38 cases (65.5%). L1CAM positivity in ≥10% of the MELF component was found in 24 cases (41.4%) and was the only significant predictor of lymph node involvement in both univariate (p < 0.001) and multivariate analysis (p < 0.001). In conclusion, L1CAM might be involved in the development of the MELF pattern. In uterine-confined, low-grade endometrioid carcinomas, L1CAM overexpression in MELF glands may predict lymph node involvement

Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis

Impaired proinsulin-to-insulin processing in pancreatic beta-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. (1)(,)(2)), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs. (3-8)); nonetheless, the role of specific SL species in beta-cell function and demise is unclear. Here we define the lipid signature of T2D-associated beta-cell failure, including an imbalance of specific very-long-chain SLs and long-chain SLs. beta-cell-specific ablation of CerS2, the enzyme necessary for generation of very-long-chain SLs, selectively reduces insulin content, impairs insulin secretion and disturbs systemic glucose tolerance in multiple complementary models. In contrast, ablation of long-chain-SL-synthesizing enzymes has no effect on insulin content. By quantitatively defining the SL-protein interactome, we reveal that CerS2 ablation affects SL binding to several endoplasmic reticulum-Golgi transport proteins, including Tmed2, which we define as an endogenous regulator of the essential proinsulin processing enzyme Pcsk1. Our study uncovers roles for specific SL subtypes and SL-binding proteins in beta-cell function and T2D-associated beta-cell failure