The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.We are grateful to F.B. Gertler (Massachusetts Institute of Technology) and S. Gupton (University of North Carolina) for the generous gift of the VAMP7-phlorin construct and the staffs of the Hartwell Center for Bioinformatics and Biotechnology, the Small Animal Imaging Center, the Animal Resources Center, the Cell and Tissue Imaging Center, and the Flow Cytometry and Cell Sorting Shared Resource at St. Jude Children's Research Hospital for technical assistance. This work was supported by grants from the US National Institutes of Health (R01CA129541, P01CA96832 and P30CA021765, R.J.G.), by the Collaborative Ependymoma Research Network (CERN) and by the American Lebanese Syrian Associated Charities (ALSAC)

CRISPR-Mediated Tagging of Endogenous Proteins with a Luminescent Peptide

Intracellular signaling pathways are mediated by changes in protein abundance and post-translational modifications. A common approach for investigating signaling mechanisms and the effects induced by synthetic compounds is through overexpression of recombinant reporter genes. Genome editing with CRISPR/Cas9 offers a means to better preserve native biology by appending reporters directly onto the endogenous genes. An optimal reporter for this purpose would be small to negligibly influence intracellular processes, be readily linked to the endogenous genes with minimal experimental effort, and be sensitive enough to detect low expressing proteins. HiBiT is a 1.3 kDa peptide (11 amino acids) capable of producing bright and quantitative luminescence through high affinity complementation (<i>K</i>_D = 700 pM) with an 18 kDa subunit derived from NanoLuc (LgBiT). Using CRISPR/Cas9, we demonstrate that HiBiT can be rapidly and efficiently integrated into the genome to serve as a reporter tag for endogenous proteins. Without requiring clonal isolation of the edited cells, we were able to quantify changes in abundance of the hypoxia inducible factor 1A (HIF1α) and several of its downstream transcriptional targets in response to various stimuli. In combination with fluorescent antibodies, we further used HiBiT to directly correlate HIF1α levels with the hydroxyproline modification that mediates its degradation. These results demonstrate the ability to efficiently tag endogenous proteins with a small luminescent peptide, allowing sensitive quantitation of the response dynamics in their regulated expression and covalent modifications

Cost-Related Immunosuppressive Medication Nonadherence Among Kidney Transplant Recipients

Background and objectives: Immunosuppressive medications are essential in preventing kidney transplant rejection. Continuous insurance coverage for outpatient immunosuppressive medications remains a major issue. The objective of this study was to establish the prevalence and consequences of cost-related immunosuppressive medication nonadherence

CRISPR-Mediated Tagging of Endogenous Proteins with a Luminescent Peptide

Intracellular signaling pathways are mediated by changes in protein abundance and post-translational modifications. A common approach for investigating signaling mechanisms and the effects induced by synthetic compounds is through overexpression of recombinant reporter genes. Genome editing with CRISPR/Cas9 offers a means to better preserve native biology by appending reporters directly onto the endogenous genes. An optimal reporter for this purpose would be small to negligibly influence intracellular processes, be readily linked to the endogenous genes with minimal experimental effort, and be sensitive enough to detect low expressing proteins. HiBiT is a 1.3 kDa peptide (11 amino acids) capable of producing bright and quantitative luminescence through high affinity complementation (<i>K</i>_D = 700 pM) with an 18 kDa subunit derived from NanoLuc (LgBiT). Using CRISPR/Cas9, we demonstrate that HiBiT can be rapidly and efficiently integrated into the genome to serve as a reporter tag for endogenous proteins. Without requiring clonal isolation of the edited cells, we were able to quantify changes in abundance of the hypoxia inducible factor 1A (HIF1α) and several of its downstream transcriptional targets in response to various stimuli. In combination with fluorescent antibodies, we further used HiBiT to directly correlate HIF1α levels with the hydroxyproline modification that mediates its degradation. These results demonstrate the ability to efficiently tag endogenous proteins with a small luminescent peptide, allowing sensitive quantitation of the response dynamics in their regulated expression and covalent modifications

Innovative strategies for managing swine welfare during the COVID-19 pandemic in Iowa

Coronavirus Disease 2019 (COVID-19) was declared a global pandemic on March 11, 2020 by the World Health Organization and its impact on animal agriculture in the United States was undeniable. By April, COVID-19 resulted in the simultaneous closure or reduced operations of many meat processing plants in the upper Midwest, leading to supply chain disruptions. In Iowa, the leading pork production and processing state, these disruptions caused producer uncertainty, confusion, and stress, including time-sensitive challenges for maintaining animal care. The Iowa Resource Coordination Center (IRCC) was quickly created and launched by the Iowa Department of Agriculture and Land Stewardship (IDALS). The IRCC included public representation from the Iowa Pork Producers Association (IPPA), Iowa Pork Industry Center (IPIC), and Iowa State University Extension and Outreach, and private partners including producers, veterinarians, and technical specialists. Supporting swine welfare, the IRCC provided information on management strategies, dietary alterations to slow pig growth, alternative markets, on-farm euthanasia, and mass depopulation under veterinary oversight. In a crisis, Iowa created a model that reacted to producers’ pragmatic, mental and emotional needs. This model could be quickly replicated with an introduction of foreign animal disease.This is the version of record for the article Johnson, A., C. Rademacher, J. Eggers, N. Gabler, L. Greiner, J. Kaisand, L. Karriker et al. "Innovative strategies for managing swine welfare during the COVID-19 pandemic in Iowa." Translational Animal Science 5, no. 4 (2021). Available online at DOI: 10.1093/tas/txab225. Copyright 2021 The Author(s). Attribution 4.0 International (CC BY 4.0). Posted with permission