Publications by authors named "C A Harris"

3,868 Publications

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C3 Glomerulopathy and Related Disorders in Children.

Clin J Am Soc Nephrol 2021 Sep 22. Epub 2021 Sep 22.

S Johnson, National Renal Complement Therapeutics Centre, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom of Great Britain and Northern Ireland.

: Membranoproliferative Glomerulonephritis (MPGN) and C3 Glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific aetiological data for paediatric MPGN/C3 glomerulopathy are lacking, and outcome data are based upon retrospective studies without aetiological data. : Eighty prevalent pediatric patients with MPGN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using COX proportional hazards model. Kidney and transplant graft survival was determined using Kaplan-Meier method. : Central histology review determined 39 C3 glomerulopathy, 31 immune-complex MPGN and 10 immune-complex glomerulonephritis (GN) cases. Patients were aged 2-15 (median 9 (IQR 7-11) years. Median complement C3 and C4 levels were 0.31g/L and 0.14g/L respectively; acquired (anti-complement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% patients respectively, across all groups including immune-complex GN. Median follow-up was 5.18 (IQR 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure with 9 transplants performed in 8 patients, 2 of which failed due to recurrent disease. Presence of >50% crescents on initial biopsy was the sole variable associated with kidney failure in multivariable analysis (Hazard Ratio 6.2, p = 0.045; 95% CI 1.05 to 36.6). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on initial biopsy. : Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric MPGN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.
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http://dx.doi.org/10.2215/CJN.00320121DOI Listing
September 2021

The circadian clock gene, Bmal1, regulates intestinal stem cell signaling and represses tumor initiation.

Cell Mol Gastroenterol Hepatol 2021 Sep 14. Epub 2021 Sep 14.

Department of Biomedical Sciences, University of Windsor, Windsor, N9B 3P4, Ontario. Electronic address:

Background: Circadian rhythms are daily physiological oscillations driven by the circadian clock: a 24-hour transcriptional timekeeper that regulates hormones, inflammation, and metabolism. Circadian rhythms are known to be important for health, but whether their loss contributes to colorectal cancer is not known.

Aims: We tested the non-redundant clock gene, Bmal1, in intestinal homeostasis and tumorigenesis, using the Apc model of colorectal cancer.

Methods: Bmal1 mutant, epithelium-conditional Bmal1 mutant, and photoperiod-disrupted mice bearing the Apc allele were assessed for tumorigenesis. Tumors and normal non-transformed tissue were characterized. Intestinal organoids were assessed for circadian transcription rhythms by RNA-sequencing, and in vivo and organoid assays were used to test Bmal1-dependent proliferation and self-renewal.

Results: Loss of Bmal1 or circadian photoperiod increases tumor initiation. In the intestinal epithelium the clock regulates transcripts involved in regeneration and intestinal stem cell signaling. Tumors have no self-autonomous clock function and only weak clock function in vivo. Apc clock-disrupted tumors exhibit high Yap (Hippo signaling) activity but exhibit low Wnt activity. Intestinal organoid assays reveal that loss of Bmal1 increases self-renewal in a Yap-dependent manner.

Conclusion: Bmal1 regulates intestinal stem cell pathways, including Hippo signaling, and the loss of circadian rhythms potentiates tumor initiation.
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http://dx.doi.org/10.1016/j.jcmgh.2021.08.001DOI Listing
September 2021

Alkali Metal- and Acid-Catalyzed Interconversion of Goniodomin A with Congeners B and C.

J Nat Prod 2021 Sep 14;84(9):2554-2567. Epub 2021 Sep 14.

Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.

Goniodomin A (GDA, ) is a phycotoxin produced by at least four species of dinoflagellates that are found globally in brackish estuaries and lagoons. It is a linear polyketide with six oxygen heterocyclic rings that is cyclized into a macrocyclic structure via lactone formation. Two of the oxygen heterocycles in comprise a spiro-bis-pyran, whereas goniodomin B (GDB) contains a 2,7-dioxabicyclo[3.3.1]nonane ring system fused to a pyran. When HO is present, undergoes facile conversion to isomer GDB and to an α,β-unsaturated ketone, goniodomin C (GDC, ). GDB and GDC can be formed from GDA by cleavage of the spiro-bis-pyran ring system. GDA, but not GDB or GDC, forms a crown ether-type complex with K. Equilibration of GDA with GDB and GDC is observed in the presence of H and of Na, but the equilibrated mixtures revert to GDA upon addition of K. Structural differences have been found between the K and Na complexes. The association of GDA with K is strong, while that with Na is weak. The K complex has a compact, well-defined structure, whereas Na complexes are an ill-defined mixture of species. Analyses of in vitro and cultures indicate that only GDA is present in the cells; GDB and GDC appear to be postharvest transformation products.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00586DOI Listing
September 2021

The provision of hospital at home care: results of a national survey of UK hospitals.

Int J Clin Pract 2021 Sep 12:e14814. Epub 2021 Sep 12.

University of Warwick, School of Medicine, Coventry, UK.

Background: Hospital at home (HaH) replicates elements of hospital-based care in the community, to facilitate the safe management of a broad spectrum of acute illness in the patient's usual environment. The extent to which this model of care has been adopted in the United Kingdom (UK) is unknown.

Methods: The Society for Acute Medicine Benchmarking Audit is a day of care survey undertaken annually within the UK. Participation is open to all hospital in the UK receiving acutely unwell medical patients. A questionnaire is used to collect hospital-level data on the structure and organisation of acute care delivery. The survey included questions designed to quantify the number of hospitals that offered HaH. When present, further questions were asked to clarify the characteristics of the HaH service in terms of workforce, range of diagnostic test and interventions. This information was used to build a picture of HaH service provision at a national scale.

Results: A total of 130 hospitals contributed organisational data to SAMBA19. The capability to refer to a hospital at home service was recognised by 46.9% (n = 61) of units. The majority of these services, 83.3% (n = 50) were nurse-led. The capability to provide a physician review at home was reported in 23.3% (n = 14). The majority of services could provide intravenous antibiotics at home, but access to other simple interventions, such as intravenous diuretics or acute supplemental oxygen, is limited.

Conclusion: At present, few Acute Medical Units in the UK have access to a hospital at home service capable of replicating essential elements of inpatient care. Significant changes to existing acute care organisations and investment in infrastructure are required to establish equal access to hospital-at-home care within the UK.
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http://dx.doi.org/10.1111/ijcp.14814DOI Listing
September 2021
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