Reduction of Sleep Medications via a Combined Digital Insomnia and Pharmacist-Led Deprescribing Intervention: Protocol for a Feasibility Trial.

Background: Chronic insomnia is one of the most common health problems among veterans and negatively impacts their health, function, and quality of life. Although cognitive behavioral therapy for insomnia (CBT-I) is the first-line recommended treatment, sedative-hypnotic medications remain the most common. Sedative-hypnotics, however, have mixed effectiveness, are frequently prescribed longer than recommended, and are associated with numerous risks and adverse effects that negatively impact veteran function.

Chemokine binding to PSGL-1 is controlled by O-glycosylation and tyrosine sulfation.

Protein glycosylation influences cellular recognition and regulates protein interactions, but how glycosylation functions alongside other common posttranslational modifications (PTMs), like tyrosine sulfation (sTyr), is unclear. We produced a library of 53 chemoenzymatically synthesized glycosulfopeptides representing N-terminal domains of human and murine P-selectin glycoprotein ligand-1 (PSGL-1), varying in sTyr and O-glycosylation (structure and site). Using these, we identified key roles of PSGL-1 O-glycosylation and sTyr in controlling interactions with specific chemokines.

Long-Term Quality of Life in Congenital Heart Disease Surgical Survivors: Multicenter Retrospective Study of Surgical and ICU Explanatory Factors.

Objectives: Greater congenital heart disease (CHD) complexity is associated with lower health-related quality of life (HRQOL). There are no data on the association between surgical and ICU factors and HRQOL in CHD survivors. This study assess the association between surgical and ICU factors and HRQOL in child and adolescent CHD survivors.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Clinical pharmacist involvement in expanding naloxone distribution in a veteran population.

Purpose: To describe the process used in a clinical pharmacist specialist (CPS)-led Opioid Overdose Education and Naloxone Distribution (OEND) program initiative to increase naloxone distribution to veterans at high risk for overdose via provider education and identification of barriers to naloxone distribution.

Summary: Drug overdose is the leading cause of accidental death in the United States. One step toward counteracting the epidemic includes expanding access to and use of naloxone.

Corrigendum to "Q-slope and SSAM applied to excavated coal mine slopes" [MethodsX 8 (2021) 101191].

[This corrects the article DOI: 10.1016/j.mex.

Differential recognition of oligomannose isomers by glycan-binding proteins involved in innate and adaptive immunity.

The recognition of oligomannose-type glycans in innate and adaptive immunity is elusive due to multiple closely related isomeric glycan structures. To explore the functions of oligomannoses, we developed a multifaceted approach combining mass spectrometry assignments of oligomannose substructures and the development of a comprehensive oligomannose microarray. This defined microarray encompasses both linear and branched glycans, varying in linkages, branching patterns, and phosphorylation status.

Novel lamprey antibody recognizes terminal sulfated galactose epitopes on mammalian glycoproteins.

The terminal galactose residues of N- and O-glycans in animal glycoproteins are often sialylated and/or fucosylated, but sulfation, such as 3-O-sulfated galactose (3-O-SGal), represents an additional, but poorly understood modification. To this end, we have developed a novel sea lamprey variable lymphocyte receptor (VLR) termed O6 to explore 3-O-SGal expression. O6 was engineered as a recombinant murine IgG chimera and its specificity and affinity to the 3-O-SGal epitope was defined using a variety of approaches, including glycan and glycoprotein microarray analyses, isothermal calorimetry, ligand-bound crystal structure, FACS, and immunohistochemistry of human tissue macroarrays.

Q-slope and SSAM applied to excavated coal mine slopes.

The Q-slope classification system is used to assess the stability of excavated rock slopes and provide an indication of long-term stable, reinforcement-free slope angles. Q-slope is based on over 500 rock slope case studies from mines, road and rail cuttings hosted in igneous, sedimentary and metamorphic rocks around the world. Q-slope can be applied for slopes ranging from less than 5 m to more than 250 m in height in both civil and mining environments.

Pralatrexate in relapsed/refractory T-cell lymphoma: a retrospective multicenter study.

We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis.

Unique repertoire of anti-carbohydrate antibodies in individual human serum.

Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk. Recent studies indicate that many human protective antibodies are against carbohydrate antigens; however, little is known about repertoires and individual variation of anti-carbohydrate antibodies in healthy individuals. Here we analyzed anti-carbohydrate antibody repertoires (ACARs) of 105 healthy individual adult donors, aged 20-60 from different ethnic backgrounds to explore variations in antibodies, as defined by binding to glycan microarrays and by affinity purification.

Development of smart anti-glycan reagents using immunized lampreys.

Studies on the expression of cellular glycans are limited by a lack of sensitive tools that can discriminate specific structural features. Here we describe the development of a robust platform using immunized lampreys (Petromyzon marinus), which secrete variable lymphocyte receptors called VLRBs as antibodies, for generating libraries of anti-glycan reagents. We identified a wide variety of glycan-specific VLRBs detectable in lamprey plasma after immunization with whole fixed cells, tissue homogenates, and human milk.

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins.

Glycans and glycan binding proteins (GBPs or lectins) are essential components in almost every aspect of immunology. Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental immunological processes. In order to better study the glycan-GBP interactions, microscope glass slide-based glycan microarrays were conceived and proved to be an incredibly useful and successful tool.

Novel Reversible Fluorescent Glycan Linker for Functional Glycomics.

To aid in generating complex and diverse natural glycan libraries for functional glycomics, more efficient and reliable methods are needed to derivatize glycans. Here we present our development of a reversible, cleavable bifunctional linker 3-(methoxyamino)propylamine (MAPA). As the fluorenylmethyloxycarbonate (Fmoc) version (F-MAPA), it is highly fluorescent and efficiently derivatizes free reducing glycans to generate closed-ring derivatives that preserve the structural integrity of glycans.

Natural and Synthetic Sialylated Glycan Microarrays and Their Applications.

This focused chapter serves as a short survey of glycan microarrays that are available with sialylated glycans, including both defined and shotgun arrays, their generation, and their utility in studying differential binding interactions to sialylated compounds, highlighting N-glycolyl (Gc) modified sialylated compounds. A brief discussion of binding interactions by lectins, antibodies, and viruses, and their relevance that have been observed with sialylated glycan microarrays is presented, as well as a discussion of cross-comparisons of array platforms and efforts to centralize and standardize the glycan microarray data.

Adsorption of Carboxymethyl Cellulose onto Titania Particle Films Studied with in Situ IR Spectroscopic Analysis.

Adsorption of carboxymethyl cellulose (CMC) in aqueous solution onto a titania nanoparticle film has been studied using in situ attenuated total reflectance infrared spectroscopy (ATR-IR). CMC was adsorbed onto the positively charged titania surface in neutral, partially charged, and fully charged state. The response of the adsorbed polyelectrolyte layer was monitored upon changing the electrolyte pH and ionic strength.

"Immuno-flowFISH" for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia.

Imaging flow cytometry is emerging as a diagnostic tool for the assessment of leukemia. It has the functionality of standard flow cytometry and generates high-resolution digital images of each cell with quantifiable numerical data. We demonstrate the use of an automated high-throughput method for performing fluorescence in situ hybridization (FISH) on immunophenotyped whole cells in suspension and analyzed by imaging flow cytometry, a technique called "Immuno-flowFISH".

The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions.

Adsorption of a Polyethoxylated Surfactant from Aqueous Solution to Silica Nanoparticle Films Studied with In Situ Attenuated Total Reflection Infrared Spectroscopy and Colloid Probe Atomic Force Microscopy.

Polyethoxylated (PEO) surfactant adsorption to silica under aqueous conditions is an important physical process in a multitude of industries. Consequently, a considerable number of spectroscopic and other studies have been carried out to ascertain the molecular/structural details of the adsorbed surfactant and the kinetics of PEO surfactant adsorption. However, the use of infrared spectroscopy to probe surfactant adsorption at the silica/aqueous solution interface has been limited because of the instability of silica particle films under aqueous conditions and the opacity of silicon prisms below 1300 cm typically employed for these studies.

The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions.

Imaging of Early Response to Predict Prognosis in the First-Line Management of Follicular Non-Hodgkin Lymphoma with Iodine-131-Rituximab Radioimmunotherapy.

The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab (I-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV).

Nociceptin/orphanin FQ receptor expression in clinical pain disorders and functional effects in cultured neurons.

The nociceptin/orphanin FQ peptide receptor (NOP), activated by its endogenous peptide ligand nociceptin/orphanin FQ (N/OFQ), exerts several effects including modulation of pain signalling. We have examined, for the first time, the tissue distribution of the NOP receptor in clinical visceral and somatic pain disorders by immunohistochemistry and assessed functional effects of NOP and μ-opioid receptor activation in cultured human and rat dorsal root ganglion (DRG) neurons. Quantification of NOP-positive nerve fibres within the bladder suburothelium revealed a remarkable several-fold increase in detrusor overactivity (P < 0.