Effects of dietary camelina, flaxseed, and canola oil supplementation on transepidermal water loss, skin and coat health parameters, and plasma prostaglandin E2, glycosaminoglycan, and nitric oxide concentrations in healthy adult horses.

Camelina oil is derived from a low-input, high-yield crop and, in comparison to many other dietary fat sources currently used in equine diets, provides a greater amount of α-linolenic acid [ALA; (n-3)], than linoleic acid [LA; (n-6)]. However, no research exists assessing the effects of feeding camelina oil to horses in contrast to other commonly used oils. The objective of this study was to compare the effect of supplementing camelina oil to that of flaxseed and canola oil supplementation, on outcomes related to skin and coat health in horses. Thirty adult horses [23 mares, 7 geldings; 14.9 years ±â€…5.3 years; 544 ±â€…66 kg body weight (BW) (mean ±â€…SD)] underwent a 4-week wash-in period consuming hay and sunflower oil. Following the wash-in period, horses were blocked by location, age, and BW, and assigned to one of three treatment oils for 16 weeks (370 mg oil/kg BW): camelina (CAM), canola (OLA), or flaxseed (FLX) oil. Blood samples were collected and plasma prostaglandin E2 (PGE2; ELISA), nitric oxide (NO; Griess Reaction), and glycosaminoglycan (GAG; DMMB) concentrations were measured on weeks 0 (n = 30), 14 (n = 24), and 16 (n = 30). On weeks 0, 2, 4, 8, and 16, transepidermal water loss (TEWL) was measured pre- and post-acetone application using a VapoMeter (n = 26), and a 5-point-Likert scale was used to assess skin and coat characteristics on the side and rump of the horses (n = 30). All data were analyzed with repeated measures ANOVA using PROC GLIMMIX in SAS. Independent of treatment, coat color, and quality increased from baseline. There were no differences in the outcomes assessed between the horses supplemented camelina oil and those supplemented canola or flaxseed oil. These results suggest that independent of treatment, all oil supplements improved coat color and quality in horses. This provides indication that camelina oil is comparable to existing plant-based oil supplements in supporting skin and coat health and inflammation in horses.

Horses cannot produce omega-3 α-linolenic acid or omega-6 linoleic acid in the body, and as a result, these fatty acids are required in the diet. Camelina oil contains a lower ratio of omega-6 to omega-3 fatty acids (1:1.8) in comparison to alternative fat ingredients commonly included in many horse diets, such as soybean oil (1:0.12). Omega-3 fatty acids from flaxseed oil or marine-based oils can support skin and coat health and lower inflammation in horses; however, there is a lack of research investigating camelina oil supplementation and its benefits in horses. Thus, the objective of this study was to determine the effects of camelina oil on skin and coat health in horses. Horses were supplemented with sunflower oil for 4 weeks before being assigned to one of three treatment oils (camelina, canola, or flaxseed) for 16 weeks. Skin barrier function was assessed by measuring the transepidermal water loss of the chest, inner elbow, withers, and rump. Blood markers, including prostaglandin E2, nitric oxide, and glycosaminoglycan, were measured. Skin and coat parameters, including shine, softness, hair quality, color intensity, and moisture, were assessed using a 5-point scale on the rump and side of the horses. No differences in transepidermal water loss, blood markers, or skin and coat parameters were observed among treatments. Our results suggest that camelina oil is comparable to existing oil supplements in supporting skin and coat health and inflammation in horses.

Effects of dietary camelina, flaxseed, and canola oil supplementation on inflammatory and oxidative markers, transepidermal water loss, and coat quality in healthy adult dogs.

Introduction: Camelina oil contains a greater concentration of omega-3 (n-3) a-linolenic acid (C18:3n-3; ALA) than omega-6 (n-6) linoleic acid (C18:2n-6; LA), in comparison to alternative fat sources commonly used to formulate canine diets. Omega-3 FAs are frequently used to support canine skin and coat health claims and reduce inflammation and oxidative stress; however, there is a lack of research investigating camelina oil supplementation and its effects on these applications in dogs. The objective of this study was to evaluate the effects of camelina oil supplementation on coat quality, skin barrier function, and circulating inflammatory and oxidative marker concentrations. Methods: Thirty healthy [17 females; 13 males; 7.2 ± 3.1 years old; 27.4 ± 14.0 kg body weight (BW)] privately-owned dogs of various breeds were used. After a 4-week wash-in period consuming sunflower oil (n6:n3 = 1:0) and a commercial kibble, dogs were blocked by age, breed, and size, and randomly assigned to one of three treatment oils: camelina (n6:n3 = 1:1.18), canola (n6:n3 = 1:0.59), flaxseed (n6:n3 = 1:4.19) (inclusion level: 8.2 g oil/100 g of total food intake) in a randomized complete block design. Transepidermal water loss (TEWL) was measured using a VapoMeter on the pinna, paw pad, and inner leg. Fasted blood samples were collected to measure serum inflammatory and oxidative marker concentrations using enzyme-linked immunosorbent assay (ELISA) kits and spectrophotometric assays. A 5-point-Likert scale was used to assess coat characteristics. All data were collected on weeks 0, 2, 4, 10, and 16 and analyzed using PROC GLIMMIX in SAS. Results: No significant changes occurred in TEWL, or inflammatory and oxidative marker concentrations among treatments, across weeks, or for treatment by week interactions. Softness, shine, softness uniformity, color intensity, and follicle density of the coat increased from baseline in all treatment groups (P < 0.05). Discussion: Outcomes did not differ (P > 0.05) among treatment groups over 16-weeks, indicating that camelina oil is comparable to existing plant-based canine oil supplements, flaxseed, and canola, at supporting skin and coat health and inflammation in dogs. Future research employing an immune or exercise challenge is warranted, as the dogs in this study were not subjected to either.

The genetics of Autosomal Recessive Polycystic Kidney Disease (ARPKD).

ARPKD is a genetically inherited kidney disease that manifests by bilateral enlargement of cystic kidneys and liver fibrosis. It shows a range of severity, with 30% of individuals dying early on and the majority having good prognosis if they survive the first year of life. The reasons for this variability remain unclear. Two genes have been shown to cause ARPKD when mutated, PKHD1, mutations in which lead to most of ARPKD cases and DZIP1L, which is associated with moderate ARPKD. This mini review will explore the genetics of ARPKD and discuss potential genetic modifiers and phenocopies that could affect diagnosis.

Safety of Dietary Camelina Oil Supplementation in Healthy, Adult Dogs.

This study aimed to determine whether camelina oil is safe for use in canine diets, using canola oil and flax oil as controls, as they are similar and generally regarded as safe (GRAS) for canine diets. A total of thirty privately-owned adult dogs of various breeds (17 females; 13 males), with an average age of 7.2 ± 3.1 years (mean ± SD) and a body weight (BW) of 27.4 ± 14.0 kg were used. After a 4-week wash-in period using sunflower oil and kibble, the dogs were blocked by breed, age, and size and were randomly allocated to one of three treatment oils (camelina (CAM), flax (FLX), or canola (OLA)) at a level of 8.2 g oil/100 g total dietary intake. Body condition score (BCS), BW, food intake (FI), and hematological and select biochemical parameters were measured at various timepoints over a 16-week feeding period. All of the data were analyzed with ANOVA using the PROC GLIMMIX of SAS. No biologically significant differences were seen between the treatment groups in terms of BW, BCS, FI, and hematological and biochemical results. Statistically significant differences noted among some serum biochemical results were considered small and were due to normal biological variation. These results support the conclusion that camelina oil is safe for use in canine nutrition.

The cellular pathways and potential therapeutics of Polycystic Kidney Disease.

Polycystic Kidney Disease (PKD) refers to a group of disorders, driven by the formation of cysts in renal tubular cells and is currently one of the leading causes of end-stage renal disease. The range of symptoms observed in PKD is due to mutations in cilia-localising genes, resulting in changes in cellular signalling. As such, compounds that are currently in preclinical and clinical trials target some of these signalling pathways that are dysregulated in PKD. In this review, we highlight these pathways including cAMP, EGF and AMPK signalling and drugs that target them and may show promise in lessening the disease burden of PKD patients. At present, tolvaptan is the only approved therapy for ADPKD, however, it carries several adverse side effects whilst comparatively, no pharmacological drug is approved for ARPKD treatment. Aside from this, drugs that have been the subject of multiple clinical trials such as metformin, which targets AMPK signalling and somatostatins, which target cAMP signalling have shown great promise in reducing cyst formation and cellular proliferation. This review also discusses other potential and novel targets that can be used for future interventions, such as ß-catenin and TAZ, where research has shown that a reduction in the overexpression of these signalling components results in amelioration of disease phenotype. Thus, it becomes apparent that well-designed preclinical investigations and future clinical trials into these pathways and other potential signalling targets are crucial in bettering disease prognosis for PKD patients and could lead to personalised therapy approaches.

Minimum perceivable size difference: how well can radiologists visually detect a change in lung nodule size from CT images?

OBJECTIVE: The purpose of this study was to determine how well radiologists could visually detect a change in lung nodule size on the basis of visual image perception alone. SUBJECTS AND METHODS: Under IRB approval, 109 standard chest CT image series were anonymized and exported from PACS. Nine hundred forty virtual lung nodule pairs (six baseline diameters, six relative volume differences, two nodule types-solid and ground glass-and 14 repeats) were digitally inserted into the chest CT image series (same location, different sizes between the pair). These digitally altered CT image pairs were shown to nine radiologists who were tasked to visually determine which image contained the larger nodule using a two-alternative forced-choice perception experimental design. These data were statistically analyzed using a generalized linear mixed effects model to determine how accurately the radiologists were able to correctly identify the larger nodule. RESULTS: Nominal baseline nodule diameter, relative volume difference, and nodule type were found to be statistically significant factors (p < 0.001) in influencing the radiologists' accuracy. For solid (ground-glass) nodules, the baseline diameter needed to be at least 6.3 mm (13.2 mm) to be able to visually detect a 25% change in volume with 95 ± 1.4% accuracy. Accuracy was lowest for the nodules with the smallest baseline diameters and smallest relative volume differences. Additionally, accuracy was lower for ground-glass nodules compared to solid nodules. CONCLUSIONS: Factors that impacted visual size assessment were baseline nodule diameter, relative volume difference, and solid versus non-solid nodule type, with larger and more solid lesions offering a more precise assessment of change. KEY POINTS: • For solid nodules, radiologists could visually detect a 25% change in volume with 95% accuracy for nodules having greater than 6.3-mm baseline diameter. • For ground-glass nodules, radiologists could visually detect a 25% change in volume with 95% accuracy for nodules having greater than 13.2-mm baseline diameter. • Accuracy in detecting a change in nodule size began to stabilize around 90-100% for nodules with larger baseline diameters (> 8 mm for solid nodules, > 12 mm for ground-glass nodules) and larger relative volume differences (>15% for solid nodules, > 25% for ground-glass nodules).

A Simulation Paradigm for Evaluation of Subtle Liver Lesions at Pediatric CT: Performance and Confidence.

Purpose: To create and validate a systematic observer performance platform for evaluation of simulated liver lesions at pediatric CT and to test this paradigm to measure the effect of radiation dose reduction on detection performance and reader confidence. Materials and Methods: Thirty normal pediatric (from patients aged 0-10 years) contrast material-enhanced, de-identified abdominal CT scans obtained from July 1, 2012, through July 1, 2016, were retrospectively collected from the clinical database. The study was exempt from institutional review board approval. Zero to three simulated, low-contrast liver lesions (≤6 mm) were digitally inserted by using software, and noise was added to simulate reductions in volume CT dose index (representing radiation dose estimation) of 25% and 50%. Pediatric, abdominal, and resident radiologists (three of each) reviewed 90 data sets in three sessions using an online interface, marking each lesion location and rating confidence (scale, 0-100). Statistical analysis was performed by using software. Results: Mixed-effects models revealed a significant decrease in detection sensitivity as radiation dose decreased (P < .001). The mean confidence of the full-dose and 25% dose reduction examinations was significantly higher than that of the 50% dose reduction examinations (P = .011 and .012, respectively) but not different from one another (P = .866). Dose was not a significant predictor of time to complete each case, and subspecialty was not a significant predictor of sensitivity or false-positive results. Conclusion: Sensitivity for lesion detection significantly decreased as dose decreased; however, confidence did not change between the full-dose and 25% reduced-dose scans. This suggests that readers are unaware of this decrease in performance, which should be accounted for in clinical dose reduction efforts.Keywords: Abdomen/GI, CT, Liver, Observer Performance, Pediatrics, Perception Image© RSNA, 2019.

Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling.

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1, which encodes the large membrane protein, Fibrocystin, required for normal branching morphogenesis of the ureteric bud during embryonic renal development. The variation in ARPKD phenotype suggests that in addition to PKHD1 mutations, other genes may play a role, acting as modifiers of disease severity. One such pathway involves non-canonical Wnt/Planar Cell Polarity (PCP) signalling that has been associated with other cystic kidney diseases, but has not been investigated in ARPKD. Analysis of the AtminGpg6 mouse showed kidney, liver and lung abnormalities, suggesting it as a novel mouse tool for the study of ARPKD. Further, modulation of Atmin affected Pkhd1 mRNA levels, altered non-canonical Wnt/PCP signalling and impacted cellular proliferation and adhesion, although Atmin does not bind directly to the C-terminus of Fibrocystin. Differences in ATMIN and VANGL2 expression were observed between normal human paediatric kidneys and age-matched ARPKD kidneys. Significant increases in ATMIN, WNT5A, VANGL2 and SCRIBBLE were seen in human ARPKD versus normal kidneys; no substantial differences were seen in DAAM2 or NPHP2. A striking increase in E-cadherin was also detected in ARPKD kidneys. This work indicates a novel role for non-canonical Wnt/PCP signalling in ARPKD and suggests ATMIN as a modulator of PKHD1.

Clinically Significant Differences in Ki-67 Proliferation Index Between Primary and Metastases in Resected Pancreatic Neuroendocrine Tumors.

OBJECTIVE: Pancreatic neuroendocrine tumors (NETs) (pNETs) have a varied prognosis according to their grade. The European Neuroendocrine Tumor Society grading system uses assessment of the proliferation index via Ki-67 immunohistochemistry to aid prognosis. There is evidence that the proliferation index can vary significantly within a single tumor, but it is not fully understood to what extent heterogeneity occurs between the primary and metastatic sites and how this may affect the grade. The aim of this study is to determine whether the grade assigned to a pNET varies depending on which site is selected for Ki-67 immunolabeling. METHODS: Patients were selected from our institution's NET database. Patients were included if they had a confirmed pNETs, had multiple resection specimens, and had consented to research being performed on their specimens. Ki-67 immunohistochemistry was performed on all resected specimens meeting the inclusion criteria. RESULTS: Pancreatic neuroendocrine tumors specimens resected from 16 patients were analyzed. There was no trend to higher Ki-67 in metastatic than primary disease. Ki-67 was on average 3% higher in liver metastases than lymph node metastases (P < 0.001). CONCLUSIONS: The grade of pNETs varies according to the tumor selected for Ki-67 immunolabeling. Useful information can be gained by performing Ki-67 PI on liver metastases.

The assessment of Ki-67 as a prognostic marker in neuroendocrine tumours: a systematic review and meta-analysis.

INTRODUCTION: Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI). AIMS: To systematically review articles reporting the prognosis of patients by Ki-67 LI and thereby improve the ability of clinicians to prognosticate for their patients. METHOD: 265 abstracts were identified relating Ki-67 and survival. After exclusion criteria were applied, 22 articles remained. Articles were excluded if they described non-human specimens, were non-English language, published prior to 2000, reported non-GEP NETs, reported subgroups selected by treatment modality or included <20 cases. Random-effects meta-analysis was used to combine studies to estimate survival proportions. RESULTS: Authors used varied methods in which to present 5-year survival, with often limited survival information. This reduced the number of studies that could be included in the meta-analysis. 5-year survival for patients with grade 1 and 2 GEP NETs were estimated to be 89% (95% CI 85% to 92%, m=12 studies, n=977 participants) and 70% (95% CI 62% to 79%, m=9, n=726), respectively. Using an alternative grade 1/2 boundary of 5%, 5-year survival rates for Ki-67≤5% and 5-20% were estimated as 89% (95% CI 84% to 94%, m=7, n=654) and 51% (95% CI 44% to 59%, m=4, n=183), respectively. For Ki-67>20%, 5-year survival was estimated to be 25% (95% CI 12% to 38%, m=10, n=208). CONCLUSIONS: Standardisation of grade boundaries has allowed us to combine data from multiple studies and amass a body of evidence linking Ki-67 and survival.