Search Results (14)

Nutrition is fundamental to a child’s growth and development. However, nutritional health is often compromised by acute and chronic conditions and treatments that can commonly result in malnutrition. Malnutrition encompasses undernutrition and overnutrition and may be exacerbated by food insecurity. Recent health policy efforts in the United States (US) include those focused on quality measurement and social determinants of health (SDOH) to reduce risks for malnutrition and food insecurity. Nutrition-focused quality improvement programs (QIPs) have emerged as a successful model for benchmarking current nutrition care in adult patients and creating pathways for establishing best practices for timely malnutrition screening, intervention, and appropriate follow-up and care coordination. However, less is known about opportunities for nutrition-focused QIPs in hospital pediatric malnutrition care. This Perspective helps fill the gap by discussing the problem of pediatric malnutrition and current US quality frameworks and child nutrition programs related to malnutrition and food insecurity. In addition, this Perspective summarizes how nutrition-focused QIPs can impact malnutrition, including how QIPs can link hospital care with patient discharge planning and outpatient interventions. Finally, the Perspective outlines specific opportunities for the implementation of pediatric nutrition-focused QIPs to reduce office visits and/or inpatient readmissions through appropriate nutrition screening, assessment, and interventions. Full article

The recent approval of formulations of the endogenous neurosteroid allopregnanolone (brexanolone) and the synthetic neuroactive steroid SAGE-217 (zuranolone) to treat postpartum depression (PPD) has encouraged further research to elucidate why these potent enhancers of GABA_AR function are clinically effective in this condition. Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens are associated with reward/motivation and brain imaging studies report that individuals with PPD show reduced activity of this pathway in response to reward and infant engagement. However, the influence of neurosteroids on GABA-ergic transmission in the nucleus accumbens has received limited attention. Here, we investigate, in the medium spiny neurons (MSNs) of the mouse nucleus accumbens core, the effect of allopregnanolone, SAGE-217 and other endogenous and synthetic steroids of interest on fast phasic and tonic inhibition mediated by synaptic (α1/2βγ2) and extrasynaptic (α4βδ) GABA_ARs, respectively. We present evidence suggesting the resident tonic current results from the spontaneous opening of δ-GABA_ARs, where the steroid-enhanced tonic current is GABA-dependent. Furthermore, we demonstrate local neurosteroid synthesis in the accumbal slice preparation and reveal that GABA-ergic neurotransmission of MSNs is influenced by an endogenous neurosteroid tone. Given the dramatic fluctuations in allopregnanolone levels during pregnancy and postpartum, this neurosteroid-mediated local fine-tuning of GABAergic transmission in the MSNs will probably be perturbed. Full article

Lewy body dementia (LBD) is an often misdiagnosed and mistreated neurodegenerative disorder clinically characterized by the emergence of neuropsychiatric symptoms followed by motor impairment. LBD falls within an undefined range between Alzheimer’s disease (AD) and Parkinson’s disease (PD) due to the potential pathogenic synergistic effects of tau, beta-amyloid (Aβ), and alpha-synuclein (αsyn). A lack of reliable and relevant animal models hinders the elucidation of the molecular characteristics and phenotypic consequences of these interactions. Here, the goal was to evaluate whether the viral-mediated overexpression of αsyn in adult hTau and APP/PS1 mice or the overexpression of tau in Line 61 hThy1-αsyn mice resulted in pathology and behavior resembling LBD. The transgenes were injected intravenously via the tail vein using AAV-PHP.eB in 3-month-old hThy1-αsyn, hTau, or APP/PS1 mice that were then aged to 6-, 9-, and 12-months-old for subsequent phenotypic and histological characterization. Although we achieved the widespread expression of αsyn in hTau and tau in hThy1-αsyn mice, no αsyn pathology in hTau mice and only mild tau pathology in hThy1-αsyn mice was observed. Additionally, cognitive, motor, and limbic behavior phenotypes were not affected by overexpression of the transgenes. Furthermore, our APP/PS1 mice experienced premature deaths starting at 3 months post-injection (MPI), therefore precluding further analyses at later time points. An evaluation of the remaining 3-MPI indicated no αsyn pathology or cognitive and motor behavioral changes. Taken together, we conclude that the overexpression of αsyn in hTau and APP/PS1 mice and tau in hThy1-αsyn mice does not recapitulate the behavioral and neuropathological phenotypes observed in LBD. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Plasma biomarkers are critical for understanding disease mechanisms, treatment effects, and diagnosis. Mass spectrometry-based proteomics is a powerful tool for unbiased biomarker discovery. However, plasma proteomics is significantly hampered by signal interference from high-abundance proteins, low overall protein coverage, and high levels of missing data from data-dependent acquisition (DDA). To achieve quantitative proteomics analysis for plasma samples with a balance of throughput, performance, and cost, we developed a workflow incorporating plate-based high abundance protein depletion and sample preparation, comprehensive peptide spectral library building, and data-independent acquisition (DIA) SWATH mass spectrometry-based methodology. In this study, we analyzed plasma samples from both RA patients and healthy donors. The results showed that the new workflow performance exceeded that of the current state-of-the-art depletion-based plasma proteomic platforms in terms of both data quality and proteome coverage. Proteins from biological processes related to the activation of systemic inflammation, suppression of platelet function, and loss of muscle mass were enriched and differentially expressed in RA. Some plasma proteins, particularly acute-phase reactant proteins, showed great power to distinguish between RA patients and healthy donors. Moreover, protein isoforms in the plasma were also analyzed, providing even deeper proteome coverage. This workflow can serve as a basis for further application in discovering plasma biomarkers of other diseases. Full article

The rapid implementation of molecular HIV surveillance (MHS) has resulted in significant challenges for local health departments to develop real-time cluster detection and response (CDR) interventions for priority populations impacted by HIV. This study is among the first to explore professionals’ strategies to implement MHS and develop CDR interventions in real-world public health settings. Methods: Semi-structured qualitative interviews were completed by 21 public health stakeholders in the United States’ southern and midwestern regions throughout 2020–2022 to identify themes related to the implementation and development of MHS and CDR. Results for the thematic analysis revealed (1) strengths and limitations in utilizing HIV surveillance data for real-time CDR; (2) limitations of MHS data due to medical provider and staff concerns related to CDR; (3) divergent perspectives on the effectiveness of partner services; (4) optimism, but reluctance about the social network strategy; and (5) enhanced partnerships with community stakeholders to address MHS-related concerns. Conclusions: Enhancing MHS and CDR efforts requires a centralized system for staff to access public health data from multiple databases to develop CDR interventions; designating staff dedicated to CDR interventions; and establishing equitable meaningful partnerships with local community stakeholders to address MHS concerns and develop culturally informed CDR interventions. Full article

Pancreatic ductal adenocarcinoma remains a highly debilitating condition with no effective disease-modifying interventions. In our search for natural products with promising anticancer activity, we identified the aminolipopeptide trichoderin A as a potential candidate. While it was initially isolated as an antitubercular peptide, we provide evidence that it is also selectively toxic against BxPC-3 and PANC-1 human pancreatic ductal adenocarcinoma cells cultured under glucose deprivation. This has critical implications for the pancreatic ductal adenocarcinoma, which is characterized by nutrient deprivation due to its hypovascularized network. We have also successfully simplified the trichoderin A peptide backbone, allowing greater accessibility to the peptide for further biological testing. In addition, we also conducted a preliminary investigation into the role of peptide lipidation at the N-terminus. This showed that analogues with longer fatty acyl chains exhibited superior cytotoxicity than those with shorter acyl chains. Further structural optimization of trichoderin A is anticipated to improve its biological activity, whilst ongoing mechanistic studies to elucidate its intracellular mechanism of action are conducted in parallel. Full article

We investigated the effect of an antenatal lifestyle intervention of a low-glycaemic index (GI) diet and physical activity on energy-adjusted dietary inflammatory index (E-DII^TM) and explored its relationship with maternal and child health in women with overweight and obesity. This was a secondary analysis of 434 mother−child pairs from the Pregnancy Exercise and Nutrition Study (PEARS) trial in Dublin, Ireland. E-DII^TM scores were calculated for early (10–16 weeks) and late (28 weeks) pregnancy. Outcomes included lipids, inflammation markers, insulin resistance, mode of delivery, infant size, pre-eclampsia, and gestational diabetes. T-tests were used to assess changes in E-DII^TM. Chi-square, correlations, and multiple regression were employed to investigate relationships with outcomes. The mean (SD) age of participants was 32.45 (4.29) years with median (IQR) BMI 28.25 (26.70, 31.34) kg/m². There was no change in E-DII^TM in the controls (−0.14 (1.19) vs. −0.07 (1.09), p = 0.465) but E-DII^TM reduced by 10% after the intervention (0.01 (1.07) vs −0.75 (1.05), p < 0.001). No associations were found between early pregnancy E-DII^TM and maternal and child outcomes, except for increased odds of adverse cardiometabolic phenotype in women who delivered male (OR = 2.29, p = 0.010) but not female infants (OR = 0.99, p = 0.960). A low-GI antenatal intervention can reduce the inflammatory potential of diets. Sex differences should be explored further in future research. Full article

Anoplocephala perfoliata is a neglected gastro-intestinal tapeworm, commonly infecting horses worldwide. Molecular investigation of A. perfoliata is hampered by a lack of tools to better understand the host–parasite interface. This interface is likely influenced by parasite derived immune modulators released in the secretome as free proteins or components of extracellular vesicles (EVs). Therefore, adult RNA was sequenced and de novo assembled to generate the first A. perfoliata transcriptome. In addition, excretory secretory products (ESP) from adult A. perfoliata were collected and EVs isolated using size exclusion chromatography, prior to proteomic analysis of the EVs, the EV surface and EV depleted ESP. Transcriptome analysis revealed 454 sequences homologous to known helminth immune modulators including two novel Sigma class GSTs, five α-HSP90s, and three α-enolases with isoforms of all three observed within the proteomic analysis of the secretome. Furthermore, secretome proteomics identified common helminth proteins across each sample with known EV markers, such as annexins and tetraspanins, observed in EV fractions. Importantly, 49 of the 454 putative immune modulators were identified across the secretome proteomics contained within and on the surface of EVs in addition to those identified in free ESP. This work provides the molecular tools for A. perfoliata to reveal key players in the host–parasite interaction within the horse host. Full article

Oxidative stress plays a pivotal role in the pathogenesis of many diseases, but there is no accurate measurement of oxidative stress or antioxidants that has utility in the clinical setting. Cyclic Voltammetry is an electrochemical technique that has been widely used for analyzing redox status in industrial and research settings. It has also recently been applied to assess the antioxidant status of in vivo biological samples. This systematic review identified 38 studies that used cyclic voltammetry to determine the change in antioxidant status in humans and animals. It focusses on the methods for sample preparation, processing and storage, experimental setup and techniques used to identify the antioxidants responsible for the voltammetric peaks. The aim is to provide key information to those intending to use cyclic voltammetry to measure antioxidants in biological samples in a clinical setting. Full article

We conducted a prospective, paired-eye, investigator masked study in 30 children with myopia (−1.25 D to −4.00 D; age 10 to 14 years) to test the efficacy of a novel multifocal orthokeratology (MOK) lens compared to conventional orthokeratology (OK) in slowing axial eye growth. The MOK lens molded a center-distance, multifocal surface onto the anterior cornea, with a concentric treatment zone power of +2.50 D. Children wore an MOK lens in one eye and a conventional OK lens in the fellow eye nightly for 18 months. Eye growth was monitored with non-contact ocular biometry. Over 18 months, MOK-treated eyes showed significantly less axial expansion than OK-treated eyes (axial length change: MOK 0.173 mm less than OK; p < 0.01), and inner axial length (posterior cornea to anterior sclera change: MOK 0.156 mm less than OK, p < 0.01). The reduced elongation was constant across different baseline progression rates (range −0.50 D/year to −2.00 D/year). Visual acuity was less in MOK vs. OK-treated eyes (e.g., at six months, MOK: 0.09 ± 0.01 vs. OK: 0.02 ± 0.01 logMAR; p = 0.01). We conclude that MOK lenses significantly reduce eye growth compared to conventional OK lenses over 18 months. Full article

Syngas (mixture of CO, H₂ and CO₂) fermentation suffers from mass transfer limitation due to low solubility of CO and H₂ in the liquid medium. Therefore, it is critical to characterize the mass transfer in syngas fermentation reactors to guide in delivery of syngas to the microorganisms. The objective of this study is to measure and predict the overall volumetric mass transfer coefficient, k_La for O₂ at various operating conditions in a 7-L sparged and non-sparged continuous stirred-tank reactor (CSTR). Measurements indicated that the k_La for O₂ increased with an increase in air flow rate and agitation speed. However, k_La for O₂ decreased with the increase in the headspace pressure. The highest k_La for O₂ with air sparged in the CSTR was 116 h⁻¹ at 600 sccm, 900 rpm, 101 kPa, and 3 L working volume. Backmixing of the headspace N₂ in the sparged CSTR reduced the observed k_La. The mass transfer model predicted the k_La for O₂ within 10% of the experimental values. The model was extended to predict the k_La for syngas components CO, CO₂ and H₂, which will guide in selecting operating conditions that minimize power input to the bioreactor and maximize the syngas conversion efficiency. Full article

As part of an effort to characterize clusters and intermediate phases likely to be encountered along solution reaction pathways that produce iron and aluminum oxide-hydroxides from Fe and Al precursors, the complete structure of Al₁₀O₁₄(OH)₂ (akdalaite) was determined from a combination of single-crystal X-ray diffraction (SC-XRD) data collected at 100 K to define the Al and O positions, and solid-state nuclear magnetic resonance (NMR) and neutron powder diffraction (NPD) data collected at room temperature (~300 K) to precisely determine the nature of hydrogen in the structure. Two different synthesis routes produced different crystal morphologies. Using an aluminum oxyhydroxide floc made from mixing AlCl₃ and 0.48 M NaOH, the product had uniform needle morphology, while using nanocrystalline boehmite (Vista Chemical Company Catapal D alumina) as the starting material produced hexagonal plates. Akdalaite crystallizes in the space group P6₃mc with lattice parameters of a = 5.6244(3) Å and c = 8.8417(3) Å (SC-XRD) and a = 5.57610(2) Å and c = 8.77247(6) Å (NPD). The crystal structure features Al₁₃O₄₀ Keggin clusters. The structural chemistry of akdalaite is nonideal but broadly conforms to that of ferrihydrite, the nanomineral with which it is isostructural. Full article

Biomass and other carbonaceous materials can be gasified to produce syngas with high concentrations of CO and H₂. Feedstock materials include wood, dedicated energy crops, grain wastes, manufacturing or municipal wastes, natural gas, petroleum and chemical wastes, lignin, coal and tires. Syngas fermentation converts CO and H₂ to alcohols and organic acids and uses concepts applicable in fermentation of gas phase substrates. The growth of chemoautotrophic microbes produces a wide range of chemicals from the enzyme platform of native organisms. In this review paper, the Wood–Ljungdahl biochemical pathway used by chemoautotrophs is described including balanced reactions, reaction sites physically located within the cell and cell mechanisms for energy conservation that govern production. Important concepts discussed include gas solubility, mass transfer, thermodynamics of enzyme-catalyzed reactions, electrochemistry and cellular electron carriers and fermentation kinetics. Potential applications of these concepts include acid and alcohol production, hydrogen generation and conversion of methane to liquids or hydrogen. Full article