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Abstract Background Nephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

Objective: To describe levels of loneliness in cancer caregivers over a 6 month time period, and to examine factors that influence changes in loneliness in caregivers over time. Methods: Prospective, repeated measures design was utilized to examine levels of loneliness and factors that influence loneliness in 129 family caregivers of individuals undergoing cancer treatment at three time points over a 6 month period. Measures included: PROMIS global health and sleep disturbance; NIH Toolbox loneliness, self‐efficacy and perceived stress; Family Care Inventory mutuality scale; and Caregiver Reaction Assessment. Results: Approximately one third (30.2%, n = 39) of the caregivers had high levels of loneliness, and levels of loneliness did not change over the three time points (P =.985). For any given time point, caregivers who were not married (P =.008), not working (P =.027), with worse mental health (P =.015), more perceived‐stress (P <.0001), and more caregiver burden (P =.003) reported higher levels of loneliness. Conclusion: This study provides guidance for clinicians attempting to identify at‐risk caregivers by confirming the findings of previous research that caregivers with higher burden, stress and in poor mental health are at increased risk for loneliness. This study provides preliminary evidence that continuing to work during the caregiving trajectory may be beneficial to caregivers by reducing levels of loneliness. Future research is needed to confirm these findings and to examine novel interventions to reduce loneliness in cancer caregivers. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe cancer caregivers' participation in health-promoting behaviors and to identify factors influencing participation. SAMPLE & SETTING: 129 informal cancer caregivers at the National Institutes of Health Clinical Center. METHODS & VARIABLES: Cross-sectional survey methodology using Health-Promoting Lifestyle Profile-II (HPLP-II), PROMIS® Global Physical Health, NIH Toolbox Stress and Self-Efficacy, Caregiver Reaction Assessment, and Family Care Inventory Mutuality subscale. RESULTS: Caregivers reported the highest HPLP-II subscale scores for spirituality and interpersonal relationships and the lowest for physical activity. Caregivers who were older, with lower body mass indices, in better physical health, and with higher self-efficacy and mutuality participated in more health-promoting behaviors. Sixty percent of the caregivers reported that they exercised less since becoming a caregiver, and 47% reported that their diet was worse. IMPLICATIONS FOR NURSING: Future research is needed to examine novel interventions to increase health-promoting activities in cancer caregivers, and these interventions might be strengthened by including components that focus on increasing self-efficacy and/or improving the strength of the relationship between the caregiver and care recipient. [ABSTRACT FROM AUTHOR]