Individualized everolimus treatment for tuberous sclerosis-related angiomyolipoma promotes treatment adherence and response.

Background: Everolimus is a potential alternative to embolization and nephrectomy for managing tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML). In 2016, National Health Service England approved its use through regional centres for renal AML ≥30 mm showing interval growth. Evidence of lesion stabilization or reduction after 6 months is mandated for continuation of long-term treatment. Methods: From November 2016 to June 2021, all potentially eligible adult TSC patients with AML across Yorkshire and Humber were referred for assessment and monitoring. Eligible patients underwent baseline renal magnetic resonance imaging (MRI) assessment and a follow-up MRI scan after 6 months on everolimus. Dose titration was guided by trough levels and lesion responsiveness using a new 3D MRI volumetric protocol. Results: Of 28 patients commencing treatment, 19 tolerated everolimus for >3 months. Overall, 11 patients (40%) discontinued treatment, mostly due to recurrent infections (42%) and allergic reactions (25%). Sixty-eight percent required dose adjustments from the initiating dose (10 mg) due to sub-optimal trough levels (38%), minimal AML response (15%) or adverse events (47%). 3D volumetric assessment confirmed a reduction in AML volume of a pre-selected index lesion in all treatment-naïve cases (n = 14), showing superiority over 2D measurements of lesion diameter. Conclusion: In this cohort, everolimus promoted AML regression in all patients who tolerated the drug for >6 months with stabilization observed over 3 years. Trough levels enabled individual dose titration to maximize responsiveness and minimize side effects. The use of 3D MRI assessment of lesion volume was superior to 2D measurements of lesion diameter in monitoring treatment response.

Research Note: The effect of selection for 16-week body weight on turkey serum metabolome.

The phenotype of modern commercial turkeys is substantially different than that of unselected, heritage turkey lines. These phenotypic changes have arisen from alterations in the genome/transcriptome, as well as the influence of many external factors on growth performance including nutrition, environment, and management. To investigate the phenotypic changes resulting from genetic selection for increased body weight, The Ohio State University maintains 2 unique genetic turkey lines: the randombred control (RBC2) line, which is comprised of genetics from 1960 era commercial turkeys and has been maintained without conscious selection for any trait; and the F line, which was originally selected from the RBC2 line and has been selected for increased 16 wk body weight for over 50 generations. This study used broad-spectrum mass-spectrometry profiling techniques to identify and quantify differences in the metabolome of the serum of F and RBC2 turkey lines. Serum samples from both F and RBC2 turkeys were subject to quantitative time of flight liquid chromatography tandem mass spectrometry analyses. Principle component analyses showed distinct populations of metabolites in the F vs. RBC2 serum, suggesting that increased body weight is associated with the accumulation of several metabolites. Comparing the spectral features to online databases resulted in the selection of 104 features with potentially identifiable chemical structures. Of these 104 features, 25 were found at higher levels in the serum of the RBC2 line turkeys, while 79 were found at a greater abundance in the F line turkeys. A more detailed analysis of these 104 features allowed for the putative identification of 49 compounds, which were clustered into 6 functional groups: 1) energy metabolism; 2) vitamins; 3) hormones and signaling molecules; 4) lipid derivatives, fatty acid metabolites, and membrane components; 5) amino acid/protein metabolism; and 6) microbial metabolites. Further validation and experimentation is needed to confirm the identity of these metabolites and understand their biological relevance and association with selection for increased body weight.

Effect of incubation temperature on neuropeptide Y and neuropeptide Y receptors in turkey and chicken satellite cells.

Neuropeptide Y (NPY) is an appetite stimulating peptide released from the central nervous system and impacts the function of many different cell types. A recent transcriptome study showed that NPY expression was altered when turkey breast muscle satellite cells were incubated at low or high temperatures, suggesting NPY may mediate temperature effects on satellite cells. However, to date minimal information exists describing the expression and function of NPY in satellite cells. The objective of this study was to determine how temperature impacts NPY and NPY receptor gene expression in satellite cells isolated from turkeys and chickens with differing genetic lineages. Two broiler and two turkey breast muscle satellite cell lines were incubated at 35, 38 or 41 °C during proliferation and differentiation. In both turkey lines, NPY, and receptors NPY2R and NPY5R expression increased at elevated temperatures after 72 h of proliferation. During differentiation NPY and NPY5R expression increased in both turkey lines with higher temperatures, whereas NPY2R was minimally affected by temperature. In contrast, in both chicken cell lines there were few significant differences for NPY and NPY receptor expression across temperature during proliferation. During differentiation, the temperature effect was different in the two chicken cell lines. In the BPM8 chicken line, there were few differences in NPY and NPY receptors across temperature; whereas elevated temperatures increased NPY, NPY2R, and NPY5R expression in the 708 line. The differences between turkey and chicken lines suggest NPY has species specific satellite cell functions in response to heat stress.