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Background: TXT2BFiT was one of the first few innovative mHealth programs designed for young adults (18-35 years) with demonstrated efficacy in weight management. However, research is lacking to understand intervention effectiveness, especially in complex, multi-component mHealth programs. This paper investigates participant perceptions of and engagement with the mHealth program components in the TXT2BFiT to understand program effects. Methods: Process evaluation data were collected continuously for the study duration. The TXT2BFiT program was a multi-component lifestyle program delivered intensively for 3-month followed by a 6-month maintenance phase. Program components included personalised coaching calls, text messages, emails, smartphone apps and website access. Process evaluation measures included frequency of use of components and frequency for number of components used (online survey data); dose delivered and engagement with program components (researcher logs and web platform reports); frequency, timing and difficulties experienced with program components (online survey data) and overall perceptions of program components (online survey data and semi-structured telephone interviews). Qualitative data analysis was performed using NVivo10. Results: Over 80 % of participants completed post-intervention (3-months, intervention, n = 110, control n = 104) and follow-up surveys (9-months, intervention, n = 96, control n = 104). Thirty intervention participants completed semi-structured telephone interviews. Participants reported high use of coaching calls, text messages and emails and no issues in content delivery from these components. These components were described as helping them to achieve their goals. Website and app use and engagement was low for the duration of the program. Participants would prefer incorporation of the self-monitoring apps and website resources into one smartphone application that can be individualised by entry of their personal data. Conclusions: Our process evaluation has allowed a comprehensive understanding of use and preference for different program components. The high value placed on the coaching calls is consistent with a desire for personalisation of the mHealth program and even further tailoring of text messages and emails. The findings of this study will be used to revise TXT2BFiT for future users. Trial registration: The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000924853). [ABSTRACT FROM AUTHOR]

DNA damage and alterations in DNA damage response (DDR) signaling could be one of the molecular mechanisms mediating focal kidney cyst formation in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that markers of DNA damage and DDR signaling are increased in human and experimental ADPKD. In the human ADPKD transcriptome, the number of up-regulated DDR-related genes was increased by 16.6-fold compared with that in normal kidney, and by 2.5-fold in cystic compared with that in minimally cystic tissue (P < 0.0001). In end-stage human ADPKD tissue, γ-H2A histone family member X (H2AX), phosphorylated ataxia telangiectasia and radiation-sensitive mutant 3 (Rad3)-related (pATR), and phosphorylated ataxia telangiectasia mutated (pATM) localized to cystic kidney epithelial cells. In vitro, pATR and pATM were also constitutively increased in human ADPKD tubular cells (WT 9-7 and 9-12) compared with control (HK-2). In addition, extrinsic oxidative DNA damage by hydrogen peroxide augmented γ-H2AX and cell survival in human ADPKD cells, and exacerbated cyst growth in the three-dimensional Madin-Darby canine kidney cyst model. In contrast, DDR-related gene expression was only transiently increased on postnatal day 0 in Pkd1 RC/RC mice, and not altered at later time points up to 12 months of age. In conclusion, DDR signaling is dysregulated in human ADPKD and during the early phases of murine ADPKD. The constitutive expression of the DDR pathway in ADPKD may promote survival of PKD1-mutated cells and contribute to kidney cyst growth., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

A hallmark of polycystic kidney diseases (PKDs) is aberrant proliferation, which leads to the formation and growth of renal cysts. Proliferation is mediated by cyclin-dependent kinases (Cdks), and the administration of roscovitine (a pan-Cdk inhibitor) attenuates renal cystic disease in juvenile cystic kidney (jck) mice. Cdk2 is a key regulator of cell proliferation, but its specific role in PKD remains unknown. The aim of this study was to test the hypothesis that Cdk2 deficiency reduces renal cyst growth in PKD. Three studies were undertaken: (i) a time course (days 28, 56, and 84) of cyclin and Cdk activity was examined in jck mice and compared with wild-type mice; (ii) the progression was compared in jck mice with or without Cdk2 ablation from birth; and (iii) the effect of sirolimus (an antiproliferative agent) on Cdk2 activity in jck mice was investigated. Renal disease in jck mice was characterized by diffuse tubular cyst growth, interstitial inflammation and fibrosis, and renal impairment, peaking on day 84. Renal cell proliferation peaked during earlier stages of disease (days 28-56), whereas the expression of Cdk2-cyclin partners (A and E) and Cdk1 and 2 activity, was maximal in the later stages of disease (days 56-84). Cdk2 ablation did not attenuate renal disease progression and was associated with persistent Cdk1 activity. In contrast, the postnatal treatment of jck mice with sirolimus reduced both Cdk2 and Cdk1 activity and reduced renal cyst growth. In conclusion, (i) the kinetics of Cdk2 and Cdk2-cyclin partners did not correlate with proliferation in jck mice; and (ii) the absence of Cdk2 did not alter renal cyst growth, most likely due to compensation by Cdk1. Taken together, these data suggest that Cdk2 is dispensable for the proliferation of cystic epithelial cells and progression of PKD.

Background/aim: The natural history of the renal microvasculature changes in PKD is not known. The aim of this study was to test the hypothesis that angiogenesis is coupled with kidney cyst expansion, and the loss of peritubular capillary networks precedes the onset of interstitial fibrosis., Methods: The renal microvasculature (RECA-1 and CD34) was evaluated in groups of Lewis polycystic kidney (LPK) rats and juvenile cystic kidney ( jck ) mice during the early, mid and late stage of disease. In addition, LPK rats and jck mice received sirolimus to determine if the reduction in renal cyst growth is in part mediated by the suppression of angiogenesis., Results: In LPK rats, the loss of peritubular capillaries occurred in early-stage disease and paralleled cyst formation whereas in jck mice it was delayed to the mid stage. In both models, vasa recta were displaced by growing cysts and regressed in LPK rats with disease progression but lengthened in jck mice. Cortical and medullary capillary neoangiogenesis occurred during the early stage in both models and persisted with progression. Treatment with sirolimus reduced cyst enlargement but did not alter the progression of renal microvasculature changes in either model., Conclusion: Regression of peritubular capillaries and disruption of vasa recta occur in parallel with angiogenesis and the progressive enlargement of kidney cysts. These data suggest that the regrowth of peritubular capillaries together with inhibition of angiogenesis are potential strategies to be considered in the treatment of PKD., Competing Interests: Gopala Rangan reports grants from Danone Nutricia Research and Otsuka Australia, outside the submitted work. The authors report no other conflicts of interest., (© 2020 O’Brien et al.)

Objective: To examine the association between liver fat content and very low-density lipoprotein (VLDL)-apolipoprotein (apo) B-100 kinetics and the corresponding responses to weight loss in obese subjects., Methods and Results: VLDL-apoB-100 kinetics were assessed using stable isotope tracers, and the fat content of the liver and abdomen was determined by magnetic resonance techniques in 25 obese subjects. In univariate analysis, liver fat content was significantly (P<0.05 in all) associated with body mass index (r=0.65), visceral fat area (r=0.45), triglycerides (r=0.40), homeostasis model assessment score (r=0.40), VLDL-apoB-100 concentrations (r=0.44), and secretion rate (r=0.45). However, liver fat content was not associated with plasma concentrations of retinol-binding protein 4, fetuin A, adiponectin, interleukin-6, and tumor necrosis factor-alpha. Of these 25 subjects, 9 diagnosed as having nonalcoholic fatty liver disease (which is highly prevalent in obese individuals and strongly associated with dyslipidemia) underwent a weight loss program. The low-fat diet achieved significant reduction in body weight, body mass index, liver fat, visceral and subcutaneous fat areas, homeostasis model assessment score, triglycerides, VLDL-apoB-100 concentrations, and VLDL-apoB-100 secretion rate. The percentage reduction of liver fat with weight loss was significantly associated with the corresponding decreases in VLDL-apoB-100 secretion (r=0.67) and visceral fat (r=0.84)., Conclusion: In patients with obesity, hepatic steatosis increases VLDL-apoB-100 secretion. Weight loss can help reduce this abnormality.