Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of oximes in KIKO mouse plasma.

Chemical warfare nerve agents (CWNAs) are potent and irreversible inhibitors of acetylcholinesterase (AChE). Oxime reactivators are an important part of the standard treatment for CWNA exposure as they can reactivate inhibited AChE. Evaluating the oxime candidates of interest in biological samples requires analytical detection methods and oxime reactivators as a class of compounds have historically been notoriously difficult to isolate, detect and analyze in an analytical laboratory, and there are currently no sensitive or robust analytical detection methods in the literature.

Enhancing HPV vaccination uptake through campus-based clinics and multi-channel health communication: A case study from Purdue University.

Objective: This study explores the effectiveness of health communication campaigns and campus-based interventions to promote vaccinations among college-aged students, focusing on human papillomavirus (HPV) immunization.

Participants: Leveraging previous initiatives, Purdue University implemented various campaign strategies and collaborated with the Indiana Immunization Coalition to administer vaccines ( = 1,827) across two clinics in late 2022.

Methods: Qualtrics surveys ( = 564) were administered to individuals post-vaccination(s).

Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer's Disease Using OrbiSIMS and LC-MS/MS.

Growing clinical evidence reveals that systematic molecular alterations in the brain occur 20 years before the onset of AD pathological features. Apolipoprotein E4 (ApoE4) is one of the most significant genetic risk factors for Alzheimer's disease (AD), which is not only associated with the AD pathological features such as amyloid-β deposition, phosphorylation of tau proteins, and neuroinflammation but is also involved in metabolism, neuron growth, and synaptic plasticity. Multiomics, such as metabolomics and proteomics, are applied widely in identifying key disease-related molecular alterations and disease-progression-related changes.

Evaluation of candidate International Standards for meningococcal capsular polysaccharide groups W and Y.

Two candidate International Standards for meningococcal capsular group W and Y (MenW and MenY, respectively) polysaccharides were assessed for their suitability as quantitative standards in various physicochemical assays. The study was designed to evaluate the intended purpose of these standards, namely, to standardize the quantification of the respective polysaccharide content in meningococcal polysaccharide and conjugate vaccines and their intermediate components. Twelve laboratories from eleven different countries participated in the collaborative study of candidate preparations for International Standards for MenW and MenY polysaccharide (coded 16/152 and 16/206, respectively).

Evidence for Multiple Binding Modes in the Initial Contact Between SARS-CoV-2 Spike S1 Protein and Cell Surface Glycans.

Infection of host cells by SARS-CoV-2 begins with recognition by the virus S (spike) protein of cell surface heparan sulfate (HS), tethering the virus to the extracellular matrix environment, and causing the subunit S1-RBD to undergo a conformational change into the 'open' conformation. These two events promote the binding of S1-RBD to the angiotensin converting enzyme 2 (ACE2) receptor, a preliminary step toward viral-cell membrane fusion. Combining ligand-based NMR spectroscopy with molecular dynamics, oligosaccharide analogues were used to explore the interactions between S1-RBD of SARS CoV-2 and HS, revealing several low-specificity binding modes and previously unidentified potential sites for the binding of extended HS polysaccharide chains.

NMR Reveals Functionally Relevant Thermally Induced Structural Changes within the Native Ensemble of G-CSF.

Structure-function relationships in proteins refer to a trade-off between stability and bioactivity, molded by evolution of the molecule. Identifying which protein amino acid residues jeopardize global or local stability for the benefit of bioactivity would reveal residues pivotal to this structure-function trade-off. Here, we use N-H heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy to probe the microenvironment and dynamics of residues in granulocyte colony-stimulating factor (G-CSF) through thermal perturbation.

Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways.

Phosphate and sulfate groups are integral to energy metabolism and introduce negative charges into biological macromolecules. One purpose of such modifications is to elicit precise binding/activation of protein partners. The physico-chemical properties of the two groups, while superficially similar, differ in one important respect-the valency of the central (phosphorus or sulfur) atom.

Using NMR to Dissect the Chemical Space and -Sulfation Effects within the - and -Glycoside Analogues of Heparan Sulfate.

Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped reservoir of potential therapeutic targets. The temporal and spatial variations in the HS structure underpin the concept of "heparanome" and a complex network of HS binding proteins. However, despite its widespread biological roles, the determination of direct structure-to-function correlations is impaired by HS chemical heterogeneity.

Development, preliminary validation and reliability of the colourful 'My Feelings Form' self-report for young children.

Background: Patient-reported outcome measures place the patient at the centre of his/her care. There are calls to introduce child-reported outcome measures to mental health services. We aimed to (a) develop an age-appropriate patient-reported outcome measure for children's mental health, and (b) validate this in a primary school and Child and Adolescent Mental Health Service (CAMHS).

Implementation of a pharmacist-led hormonal contraceptive prescribing service in a campus community pharmacy in Indiana, United States.

Objective(s): College-age people have the highest numbers of unintended pregnancies and pharmacies within college campuses are in a unique position to meet student needs. Our objective was to implement a pharmacist contraceptive prescribing service in a campus pharmacy and examine the service utilization.

Study Design: The Purdue University Pharmacy (Indiana, United States) implemented a pharmacist hormonal contraception prescribing service via a collaborative drug therapy management agreement with the campus student health center.

NMR spectroscopy and chemometric models to detect a specific non-porcine ruminant contaminant in pharmaceutical heparin.

Heparin has been used successfully as a clinical antithrombotic for almost one century. Its isolation from animal sources (mostly porcine intestinal mucosa) involves multistep purification processes starting from the slaughterhouse (as mucosa) to the pharmaceutical plant (as the API). This complex supply chain increases the risk of contamination and adulteration, mainly with non-porcine ruminant material.

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use.

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.

Review: systematic review of effectiveness of art psychotherapy in children with mental health disorders.

Art therapy and art psychotherapy are often offered in Child and Adolescent Mental Health services (CAMHS). We aimed to review the evidence regarding art therapy and art psychotherapy in children attending mental health services. We searched PubMed, Web of Science, and EBSCO (CINHAL®Complete) following PRISMA guidelines, using the search terms ("creative therapy" OR "art therapy") AND (child* OR adolescent OR teen*).

Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain.

SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on its surface. The protein primarily binds to the angiotensin-converting enzyme-2 (ACE2) receptor, using glycosaminoglycans (GAGs) as co-receptors.

MD simulation of the interaction between sialoglycans and the second sialic acid binding site of influenza A virus N1 neuraminidase.

The neuraminidases (NAs) of avian influenza viruses (IAVs) contain a second sialic acid-binding site (2SBS), historically known as the hemadsorption site, which is separated from the sialyl-hydrolase catalytic site and serves to facilitate NA catalytic activity towards multivalent sialyl-capped glycoconjugates. Transmission and adaptation of avian IAVs to humans decreases hemadsorption and catalytic activities of the NA. Here, we report the molecular recognition features of the NA 2SBS of two pandemic H1N1 IAVs, A/Brevig Mission /1/1918 (BM18) and A/California/04/2009 (CA09), differing by their 2SBS activity.

Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin.

The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1.

The interaction between oxytocin and heparin.

Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that patients taking a low molecular weight heparin, dalteparin (DAL), and then prescribed, OXT experienced a swifter labour compared to women given OXT alone. Herein are described the interactions between OXT and a number of heparin-based oligosaccharides; DAL; fondaparinux (FP), which is a synthetic heparin oligosaccharide that represents the predominant antithrombin binding-site, and a family of chemically-derived heparin hexasaccharides.

Multiomics Analyses of HNF4α Protein Domain Function during Human Pluripotent Stem Cell Differentiation.

During mammalian development, liver differentiation is driven by signals that converge on multiple transcription factor networks. The hepatocyte nuclear factor signaling network is known to be essential for hepatocyte specification and maintenance. In this study, we have generated deletion and point mutants of hepatocyte nuclear factor-4alpha (HNF4α) to precisely evaluate the function of protein domains during hepatocyte specification from human pluripotent stem cells.

O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes.

In this work, we explore the effects of O-acetylation on the physical and immunological characteristics of the WHO International Standards of Vi polysaccharide (Vi) from both Citrobacter freundii and Salmonella enterica serovar Typhi. We find that, although structurally identical according to NMR, the two Vi standards have differences with respect to susceptibility to de-O-acetylation and viscosity in water. Vi standards from both species have equivalent mass and O-acetylation-dependent binding to a mouse monoclonal antibody and to anti-Vi polyclonal antisera, including the WHO International Standard for human anti-typhoid capsular Vi PS IgG.

Multivariate analysis applied to complex biological medicines.

A biological medicine (or biologicals) is a term for a medicinal compound that is derived from a living organism. By their very nature, they are complex and often heterogeneous in structure, composition and biological activity. Some of the oldest pharmaceutical products are biologicals, for example insulin and heparin.