Publications by authors named "Kenney G"

Article Synopsis
  • Several existing COA tools for assessing Sjögren's disease symptoms lack a comprehensive evaluation of health-related quality of life (HRQoL); this study aimed to create a new patient-reported outcome (PRO) instrument for better assessment in clinical settings and trials.
  • The development of the Sjögren's Related Quality of Life (SRQoL) included qualitative interviews with patients to capture their experiences and establish the content validity of the tool and associated severity assessment items (PGI-S and PGI-C).
  • After interviewing 20 participants, eight domains of HRQoL impact were identified, including emotional well-being, sleep, daily activities, cognition, physical functioning, social/family dynamics, work, and sexual functioning, signaling the SRQo
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Background And Objectives: Asthma is a common, potentially serious childhood chronic condition that disproportionately afflicts Black children. Hospitalizations and emergency department (ED) visits for asthma can often be prevented. Nearly half of children with asthma are covered by Medicaid, which should facilitate access to care to manage and treat symptoms.

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Bacteria protect themselves from the toxicity of antimicrobial metabolites they produce through several strategies. In one resistance mechanism, bacteria assemble a non-toxic precursor on an N-acyl-d-asparagine prodrug motif in the cytoplasm, then export it to the periplasm where a dedicated d-amino peptidase hydrolyzes the prodrug motif. These prodrug-activating peptidases contain an N-terminal periplasmic S12 hydrolase domain and C-terminal transmembrane domains (TMDs) of varying lengths: type I peptidases contain three transmembrane helices, and type II peptidases have an additional C-terminal ABC half-transporter.

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Objective: To examine geographic variation in preventable hospitalizations among Medicaid/CHIP-enrolled children and to test the association between preventable hospitalizations and a novel measure of racialized economic segregation, which captures residential segregation within ZIP codes based on race and income simultaneously.

Data Sources: We supplement claims and enrollment data from the Transformed Medicaid Statistical Information System (T-MSIS) representing over 12 million Medicaid/CHIP enrollees in 24 states with data from the Public Health Disparities Geocoding Project measuring racialized economic segregation.

Study Design: We measure preventable hospitalizations by ZIP code among children.

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Article Synopsis
  • Colibactin, a compound linked to colorectal cancer, is produced by gut bacteria and is activated from a non-toxic precursor when exported to the periplasm of the bacteria.
  • The activation process involves the enzyme ClbP, which has specific regions that play a role in both enzyme stability and substrate binding.
  • Structural studies suggest that ClbP dimerizes to effectively bind and activate the precursor colibactin, allowing for coordinated action on its harmful components.
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Triosephosphate isomerase (TPI) performs the 5th step in glycolysis, operates near the limit of diffusion, and is involved in "moonlighting" functions. Its dimer was found singly phosphorylated at Ser20 (pSer20) in human cells, with this post-translational modification (PTM) showing context-dependent stoichiometry and loss under oxidative stress. We generated synthetic pSer20 proteoforms using cell-free protein synthesis that showed enhanced TPI activity by 4-fold relative to unmodified TPI.

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We use the National Health Interview Survey from 2010 to 2017 and a difference-in-differences approach to assess the impact of the Affordable Care Cct (ACA) Medicaid expansion on coverage and access to care for a subset of low-income parents who were already eligible for Medicaid when the ACA was passed. Any gains in coverage would typically be expected to improve access to and affordability of care, but there were concerns that by increasing the total population with coverage and thereby straining provider capacity, that the ACA would reduce access to care for individuals who were already eligible for Medicaid prior to the passage of the law. We found that the expansion reduced uninsurance among previously eligible parents by 12.

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Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally characterized.

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Methanobactins are ribosomally synthesized and post-translationally modified peptidic (RiPP) natural products that are known for their ability to chelate copper ions. Crucial for their high copper affinity is a pair of bidentate ligands comprising a nitrogen-containing heterocycle and an adjacent thioamide or enethiol group. The previously uncharacterized proteins MbnB and MbnC were recently shown to synthesize these groups.

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Expansion of Medicaid and establishment of the Children's Health Insurance Program (CHIP) represent a significant success story in the national effort to guarantee health insurance for children. That success is reflected in the high rates of coverage and health care access achieved for children, including those in low-income families. But significant coverage gaps remain-gaps that have been increasing since 2016 and are likely to accelerate with the coronavirus disease 2019 (COVID-19) pandemic and the associated recession.

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The alkylating warhead of the pancreatic cancer drug streptozotocin (SZN) contains an -nitrosourea moiety constructed from -methyl-l-arginine (l-NMA) by the multi-domain metalloenzyme SznF. The enzyme's central heme-oxygenase-like (HO-like) domain sequentially hydroxylates N and N' of l-NMA. Its C-terminal cupin domain then rearranges the triply modified arginine to -hydroxy-methyl--nitroso-l-citrulline, the proposed donor of the functional pharmacophore.

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Despite the remarkable microbial diversity found within humans, our ability to link genes to phenotypes is based upon a handful of model microorganisms. We report a comparative genomics platform for Eggerthella lenta and other Coriobacteriia, a neglected taxon broadly relevant to human health and disease. We uncover extensive genetic and metabolic diversity and validate a tool for mapping phenotypes to genes and sequence variants.

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Background: Medicaid plays a critical role during the perinatal period, but pregnancy-related Medicaid eligibility only extends for 60 days post partum. In 2014, the Affordable Care Act's (ACA's) Medicaid expansions increased adult Medicaid eligibility to 138% of the federal poverty level in participating states, allowing eligible new mothers to remain covered after pregnancy-related coverage expires. We investigate the impact of ACA Medicaid expansions on insurance coverage among new mothers living in poverty.

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Objective: Assess management of neonatal abstinence syndrome (NAS) in California hospitals to identify potential opportunities to expand the use of best practices.

Study Design: We fielded an internet-based survey of 37 questions to medical directors or nurse managers at 145 birth hospitals in California.

Results: Seventy-five participants (52%) responded.

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Methanobactins (Mbns) are ribosomally-produced, post-translationally modified peptidic copper-binding natural products produced under conditions of copper limitation. Genes encoding Mbn biosynthetic and transport proteins have been identified in a wide variety of bacteria, indicating a broader role for Mbns in bacterial metal homeostasis. Many of the genes in the Mbn operons have been assigned functions, but two genes usually present, and , encode uncharacterized proteins predicted to reside in the periplasm.

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Aerobic methane oxidation is catalyzed by particulate methane monooxygenase (pMMO), a copper-dependent, membrane metalloenzyme composed of subunits PmoA, PmoB, and PmoC. Characterization of the copper active site has been limited by challenges in spectroscopic analysis stemming from the presence of multiple copper binding sites, effects of detergent solubilization on activity and crystal structures, and the lack of a heterologous expression system. Here we utilize nanodiscs coupled with native top-down mass spectrometry (nTDMS) to determine the copper stoichiometry in each pMMO subunit and to detect post-translational modifications (PTMs).

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Purpose: Little is known about the prevalence of opioid use disorder (OUD) among parents who are living with children and their receipt of treatment, which could reduce the harmful effects of OUD on families.

Methods: We used 2015-2017 cross-sectional national survey data to estimate prevalence and treatment of opioid use disorder and other substance use disorders (SUD) among parents living with children.

Results: An estimated 623,000 parents with opioid use disorder are living with children, and less than one-third of these parents received treatment for illicit drug or alcohol use at a specialty facility or doctor's office.

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Objective: To compare access at community health centers (CHCs) vs private offices (non-CHCs) under the Affordable Care Act.

Data Source: Ten state primary care audit conducted in 2012/2013 and 2016.

Study Design: CHCs and non-CHCs were called.

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Article Synopsis
  • Methane-oxidizing microbes use a copper-dependent enzyme called particulate methane monooxygenase (pMMO) to convert methane, a potent greenhouse gas, into less harmful substances.
  • While the isolated pMMO enzyme is less active than the whole microbial cells, indicating that other components may enhance its function, the study also highlights a homologous protein, PmoD, which is essential for copper-dependent growth on methane.
  • PmoD forms a specific copper center that is crucial for the function of pMMO and may provide insights into the roles of enzymes involved in the global carbon and nitrogen cycles.
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Children's participation in Medicaid and the Children's Health Insurance Program (CHIP) rose by 5 percentage points between 2013 and 2016. As a result, 1.7 million fewer Medicaid/CHIP-eligible children were uninsured in 2016.

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Methanobactins (Mbns) are ribosomally produced, post-translationally modified bacterial natural products with a high affinity for copper. MbnN, a pyridoxal 5'-phosphate-dependent aminotransferase, performs a transamination reaction that is the last step in the biosynthesis of Mbns produced by several Methylosinus species. Our bioinformatic analyses indicate that MbnNs likely derive from histidinol-phosphate aminotransferases (HisCs), which play a key role in histidine biosynthesis.

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Chalkophores.

Annu Rev Biochem

June 2018

Copper-binding metallophores, or chalkophores, play a role in microbial copper homeostasis that is analogous to that of siderophores in iron homeostasis. The best-studied chalkophores are members of the methanobactin (Mbn) family-ribosomally produced, posttranslationally modified natural products first identified as copper chelators responsible for copper uptake in methane-oxidizing bacteria. To date, Mbns have been characterized exclusively in those species, but there is genomic evidence for their production in a much wider range of bacteria.

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The US uninsurance rate has nearly been cut in half under the Affordable Care Act, and access to care has improved for the newly insured, but less is known about how the remaining uninsured have fared. In 2012-13 and again in 2016 we conducted an experiment in which trained auditors called primary care offices, including federally qualified health centers, in ten states. The auditors portrayed uninsured patients seeking appointments and information on the cost of care and payment arrangements.

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Metal homeostasis poses a major challenge to microbes, which must acquire scarce elements for core metabolic processes. Methanobactin, an extensively modified copper-chelating peptide, was one of the earliest natural products shown to enable microbial acquisition of a metal other than iron. We describe the core biosynthetic machinery responsible for the characteristic posttranslational modifications that grant methanobactin its specificity and affinity for copper.

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