Objective: Health literacy is the ability to find, understand, and use information and services to inform health-related decisions and actions. Inadequate health literacy is associated with health disparities, poor health outcomes, and increased emergency department (ED) visits and hospitalizations. Children with medical complexity (CMC) have high rates of acute health care utilization.
View Article and Find Full Text PDFGentisate and salicylate 1,2-dioxygenases (GDO and SDO) facilitate aerobic degradation of aromatic rings by inserting both atoms of dioxygen into their substrates, thereby participating in global carbon cycling. The role of acid-base catalysts in the reaction cycles of these enzymes is debatable. We present evidence of the participation of a proton shuffler during catalysis by GDO and SDO.
View Article and Find Full Text PDFEur J Prev Cardiol
November 2024
Aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway.
Methods And Results: A mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome.
Structure and functions of S100 proteins are regulated by two distinct calcium binding EF hand motifs. In this work, we used solution-state NMR spectroscopy to investigate the cooperativity between the two calcium binding sites and map the allosteric changes at the target binding site. To parse the contribution of the individual calcium binding events, variants of S100A12 were designed to selectively bind calcium to either the EF-I (N63A) or EF-II (E31A) loop, respectively.
View Article and Find Full Text PDFBackground And Objectives: Household economic hardship negatively impacts child health but may not be adequately captured by income. We sought to determine the prevalence of household material hardship (HMH), a measure of household economic hardship, and to examine the relationship between household poverty and material hardship in a population of children with medical complexity.
Methods: We conducted a cross-sectional survey study of parents of children with medical complexity receiving primary care at a tertiary children's hospital.
Cupin dioxygenases such as salicylate 1,2-dioxygense (SDO) perform aromatic C-C bond scission via a 3-His motif tethered iron cofactor. Here, transient kinetics measurements are used to monitor the catalytic cycle of SDO by using a nitro-substituted substrate analog, 3-nitrogentisate. Compared to the natural substrate, the nitro group reduces the enzymatic k by 500-fold, thereby facilitating the detection and kinetic characterization of reaction intermediates.
View Article and Find Full Text PDFObjective: Our objective was to determine the accuracy of a point-of-care instrument, the Hospitalizations-Office Visits-Medical Conditions-Extra Care-Social Concerns (HOMES) instrument, in identifying patients with complex chronic conditions (CCCs) compared to an algorithm used to identify patients with CCCs within large administrative data sets.
Methods: We compared the HOMES to Feudtner's CCCs classification system. Using administrative algorithms, we categorized primary care patients at a children's hospital into 3 categories: no chronic conditions, non-complex chronic conditions, and CCCs.
Calgranulin C performs antimicrobial activity in the human immune response by sequestering Zn(II). This biological function is afforded with the aid of two structurally distinct Ca(II)-binding EF hand motifs, wherein one of which bears an unusual amino acid sequence. Here, we utilize solution state NMR relaxation measurements to investigate the mechanism of Ca(II)-modulated enhancement of Zn(II) sequestration by calgranulin C.
View Article and Find Full Text PDFThe rare genetic disorder X-linked hypophosphatemia (XLH) is often exclusively considered to impact children, and, as such, adult patients with XLH may receive inadequate care because their symptoms are not associated with XLH. However, studies have shown that XLH has long-term adverse health consequences that continue throughout adulthood requiring comprehensive lifelong care. Indeed, XLH impacts patients' whole body, whole life, and whole family.
View Article and Find Full Text PDFFluorine Doped Tin Oxide (FTO) electrode was fabricated with reduced Graphene Oxide (rGO) for sensitive detection of Japanese encephalitis virus (JEV) non-structural 1 (NS1) protein. Beforehand, in-silico 3D structure, stability, and docking of recombinant JEV NS1 antigen (NS1-Ag) and antibody (Ab) was evaluated. The recombinant NS1 Ag of 42 kDa was produced in-house by successful cloning into pET-28a(+) plasmid and further expressed using BL21 Escherichia coli (E.
View Article and Find Full Text PDFGlycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications.
View Article and Find Full Text PDFParents’ own adverse childhood experiences (ACEs) impact their children’s physical and emotional health. Causal mechanisms are not fully understood but are likely multifactorial, affecting parent resiliency and attachment behaviors, with possible intergenerational transmission. Although universal screening for parental ACEs is controversial, they may be identified during pediatric care.
View Article and Find Full Text PDFChemical shift tensors obtained from solid-state NMR spectroscopy are very sensitive reporters of structure and dynamics in proteins. While accurate C and N chemical shift tensors are accessible by magic angle spinning (MAS) NMR, their quantum mechanical calculations remain challenging, particularly for N atoms. Here we compare experimentally determined backbone C and N chemical shift tensors by MAS NMR with hybrid quantum mechanics/molecular mechanics/molecular dynamics (MD-QM/MM) calculations for the carbohydrate-binding domain of galectin-3.
View Article and Find Full Text PDFWe report dynamic nuclear polarization (DNP)-enhanced magic-angle spinning (MAS) NMR spectroscopy in viral capsids from HIV-1 and bacteriophage AP205. Viruses regulate their life cycles and infectivity through modulation of their structures and dynamics. While static structures of capsids from several viruses are now accessible with near-atomic-level resolution, atomic-level understanding of functionally important motions in assembled capsids is lacking.
View Article and Find Full Text PDFS100A12 is a member of the Ca binding S100 family of proteins that functions within the human innate immune system. Zinc sequestration by S100A12 confers antimicrobial activity when the protein is secreted by neutrophils. Here, we demonstrate that Ca binding to S100A12's EF-hand motifs and Zn binding to its dimeric interface cooperate to induce reversible self-assembly of the protein.
View Article and Find Full Text PDFGentisate 1,2-dioxygenases (GDOs) are non-heme iron enzymes that catalyze the oxidation of dihydroxylated aromatic substrate, gentisate (2,5-dihydroxybenzoate). Salicylate 1,2-dioxygenase (SDO), a member of the GDO family, performs the ring scission of monohydroxylated substrates such as salicylate, thereby oxidizing a broader range of substrates compared to GDOs. Although the two types of enzymes share a high degree of sequence similarity, the origin of substrate specificity between SDO and GDOs is not understood.
View Article and Find Full Text PDFA homologous series of electronically tuned 2,2,2-nitrilotris(-arylacetamide) pre-ligands ( ) were prepared (R = NO, CN, CF, F, Cl, Br, Et, Me, H, OMe, NMe) and some of their corresponding Fe and Zn species synthesized. The iron complexes react rapidly with O, the final products of which are diferric mu-oxo bridged species. The crystal structure of the oxidized product obtained from DMA solutions contain a structural motif found in some diiron proteins.
View Article and Find Full Text PDFMagic angle spinning NMR spectroscopy is uniquely suited to probe the structure and dynamics of insoluble proteins and protein assemblies at atomic resolution, with NMR chemical shifts containing rich information about biomolecular structure. Access to this information, however, is problematic, since accurate quantum mechanical calculation of chemical shifts in proteins remains challenging, particularly for N. Here we report on isotropic chemical shift predictions for the carbohydrate recognition domain of microcrystalline galectin-3, obtained from using hybrid quantum mechanics/molecular mechanics (QM/MM) calculations, implemented using an automated fragmentation approach, and using very high resolution (0.
View Article and Find Full Text PDFSolid State Nucl Magn Reson
September 2018
The ability of various pulse types, which are commonly applied for distance measurements, to saturate or invert quadrupolar spin polarization has been compared by observing their effect on magnetization recovery curves under magic-angle spinning. A selective central transition inversion pulse yields a bi-exponential recovery for a diamagnetic sample with a spin-3/2, consistent with the existence of two processes: the fluctuations of the electric field gradients with identical single (W) and double (W) quantum quadrupolar-driven relaxation rates, and spin exchange between the central transition of one spin and satellite transitions of a dipolar-coupled similar spin. Using a phase modulated pulse, developed for distance measurements in quadrupolar spins (Nimerovsky et al.
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