Adaptation strategies of the Icelandic horse with induced forelimb lameness at walk, trot and tölt.

BACKGROUND AND OBJECTIVE: Lameness assessment in the gaited Icelandic horse is complex. We aimed to describe their kinematic and temporal adaptation strategies in response to forelimb lameness at walk, trot and tölt. STUDY DESIGN: In vivo experiment. METHODS: Ten clinically non-lame Icelandic horses were measured before and after reversible forelimb lameness induction. Upper body and limb kinematics were measured using 11 inertial measurement units mounted on the poll, withers, pelvis (tubera sacrale) and all four limbs and hoofs (Equimoves®, 500 Hz). Horses were measured on a straight line at walk and trot in-hand and at walk, trot and tölt while ridden. Linear mixed models were used to compare baseline and lame conditions (random factor = 'horse'), and results are presented as the difference in estimated marginal means or percentage of change. RESULTS: Lameness induction significantly (p < 0.05) increased head vertical movement asymmetry at walk (HDmin/HDmaxHAND: 18.8/5.7 mm, HDmin/HDmaxRIDDEN: 9.8/0.3 mm) and trot (HDmin/HDmaxHAND: 18.1/7.8 mm, HDmin/HDmaxRIDDEN: 24.0/9.3 mm). At the tölt, however, HDmin did not change significantly (1.1 mm), but HDmax increased by 11.2 mm (p < 0.05). Furthermore, pelvis vertical movement asymmetry (PDmax) increased by 4.9 mm, sound side dissociation decreased (-8.3%), and sound diagonal dissociation increased (6.5%). Other temporal stride variables were also affected, such as increased stance duration of both forelimbs at walk, tölt and in-hand trot. MAIN LIMITATIONS: Only one degree of lameness (mild) was induced with an acute lameness model. CONCLUSIONS: Classical forelimb lameness metrics, such as vertical head and withers movement asymmetry, were less valuable at tölt compared to walk and trot, except for HDmax. Therefore, it is advised to primarily use the walk and trot to detect and quantify forelimb lameness in the Icelandic horse.

HER-3 surface expression increases in advanced colorectal cancer representing a potential therapeutic target.

HER-3 (also known as ErbB-3) is a human epidermal growth factor receptor tyrosine kinases family member, and its expression in CRC (colorectal cancer) tissues was previously associated with poor prognosis. In this study, HER-3 expression was analyzed by immunohistochemistry in two cohorts of early and advanced metastatic CRC patients. The first cohort included 180 patients diagnosed with CRC in absence of lymph nodes or distant metastases (Stage I and Stage II), while the second was obtained from 53 advanced metastatic CRC patients who developed synchronous (SM) and metachronous (MM) liver metastases. In the first early-stage CRC cohort, 86 out of 180 (47.8%) tumors showed membranous expression of HER-3, with a mean percentage of positive tumor cells of 25.7%; conversely, in advanced metastatic CRC primary tumors, HER-3 was detected in all specimens, with a mean percentage of positive tumor cells of 76.1%. Kaplan-Meier curves showed that in the advanced metastatic CRC group, patients with HER-3high tumors had a significantly lower Cancer-Specific Survival (CSS) rate compared to patients with HER-3low tumors (p = 0.021). Importantly, this worse CSS rate was observed only in the MM subgroup of patients with HER-3high tumors (p = 0.002). Multivariate analysis confirmed that high HER-3 expression represents a significant and strong risk factor for death in patients developing MM liver metastases (Hazard Ratio = 64.9; 95% Confidence Interval, 4.7-886.6; p = 0.002). In addition, using a specific anti-HER-3 antibody-drug conjugate, named EV20/MMAF, we showed that HER-3 + CRC cells can be efficiently targeted in vitro and in vivo. Overall, this study confirms that surface HER-3 is highly expressed in CRC and reveals that HER-3 expression increases in metastatic CRC patients compared to early stage. Importantly, the results suggest that HER-3 has a prognostic and therapeutic value in patients developing MM liver metastases.

Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis.

BACKGROUND: The TNM system is used to assess prognosis after colorectal cancer (CRC) diagnosis. Other prognostic factors reported include histopathological assessments of the tumour, tumour mutations and proteins in the blood. As some of these factors are strongly correlated, it is important to evaluate the independent effects they may have on survival. METHODS: Tumour samples from 2162 CRC patients were visually assessed for amount of tumour stroma, severity of lymphocytic infiltrate at the tumour margins and the presence of lymphoid follicles. Somatic mutations in the tumour were assessed for 2134 individuals. Pre-surgical levels of 4963 plasma proteins were measured in 128 individuals. The associations between these features and prognosis were inspected by a Cox Proportional Hazards Model (CPH). RESULTS: Levels of stroma, lymphocytic infiltration and presence of lymphoid follicles all associate with prognosis, along with high tumour mutation burden, high microsatellite instability and TP53 and BRAF mutations. The somatic mutations are correlated with the histopathology and none of the somatic mutations associate with survival in a multivariate analysis. Amount of stroma and lymphocytic infiltration associate with local invasion of tumours. Elevated levels of two plasma proteins, CA-125 and PPP1R1A, associate with a worse prognosis. CONCLUSIONS: Tumour stroma and lymphocytic infiltration variables are strongly associated with prognosis of CRC and capture the prognostic effects of tumour mutation status. CA-125 and PPP1R1A may be useful prognostic biomarkers in CRC.

Hospital-based study of dental pathology and faecal particle size distribution in horses with large colon impaction.

The aim of the study was to determine if horses with large colon impaction were more severely affected by oral pathology than control cases and to relate faecal particle size distribution to dental pathology in both study groups. A prospective study included 39 horses with large colon impaction and 72 control horses from a hospital-based population. An oral pathology score (OPscore) and periodontal disease index (PDI) were assigned to all horses and faecal samples were collected for estimating faecal particle size and analysis of particle size distribution. Horses with large colon impactions were not more severely affected by oral pathology than control horses for both OPscore (P = 0.2) and PDI (P = 0.3). Faecal particle size estimates were significantly higher in control animals (P <0.001). No significant association was found between faecal particle size estimates and OPscores in horses with large colon impaction or control horses. In horses with large colon impaction, faecal particle size estimates increased with increasing PDI (P = 0.05). No associations were found between dental pathology and faecal particle size estimates. Horses developing large colon impaction did not have worse dentition than control horses.