Standardized workflow for multiplexed charge detection mass spectrometry on orbitrap analyzers.

Individual ion mass spectrometry (IMS) is the Orbitrap-based extension of the niche mass spectrometry technique known as charge detection mass spectrometry (CDMS). While traditional CDMS analysis is performed on in-house-built instruments such as the electrostatic linear ion trap, IMS extends CDMS analysis to Orbitrap analyzers, allowing charge detection analysis to be available to the scientific community at large. IMS simultaneously measures the mass-to-charge ratios (m/z) and charges (z) of hundreds to thousands of individual ions within one acquisition event, creating a spectral output directly into the mass domain without the need for further spectral deconvolution.

End-To-End Automated Intact Protein Mass Spectrometry for High-Throughput Screening and Characterization of Bispecific and Multispecific Antibodies.

Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) represent a promising frontier in therapeutic antibody development, offering unique capabilities not achievable with traditional monoclonal antibodies. Despite their potential, significant challenges remain due to their increased molecular complexity. One prominent challenge is the correct assembly of light and heavy chains, as improper pairing leads to mispaired or incompletely assembled species that lack therapeutic efficacy and possess undesired properties, impairing the developability, manufacturability, and safety.

Machine learning approach to investigate pregnancy and childbirth risk factors of sleep problems in early adolescence: Evidence from two cohort studies.

Background: This study aimed to predict early adolescent sleep problems using pregnancy and childbirth risk factors through machine learning algorithms, and to evaluate model performance internally and externally.

Methods: Data from the China Jintan Child Cohort study (CJCC; n=848) for model development and the US Healthy Brain and Behavior Study (HBBS; n=454) for external validation were employed. Maternal pregnancy histories, obstetric data, and adolescent sleep problems were collected.

Automated Immunoprecipitation, Sample Preparation, and Individual Ion Mass Spectrometry Platform for Proteoforms.

Charge detection mass spectrometry (CDMS) is a well-established technique that provides direct mass spectral outputs regardless of analyte heterogeneity or molecular weight. Over the past few years, it has been demonstrated that CDMS can be multiplexed on Orbitrap analyzers utilizing an integrated approach termed individual ion mass spectrometry (IMS). To further increase adaptability, robustness, and throughput of this technique, here, we present a method that utilizes numerous integrated equipment components including a Kingfisher system, SampleStream platform, and Q Exactive mass spectrometer to provide a fully automated workflow for immunoprecipitation, sample preparation, injection, and subsequent IMS acquisition.

Assessing pain in persons with opioid use disorder: Approaches, techniques and special considerations.

Pain and opioid use disorder (OUD) are inextricably linked, as the former can be a risk factor for the development of the latter, and over a third of persons with OUD suffer concomitant chronic pain. Assessing pain among people with OUD is challenging, because ongoing opioid use brings changes in pain responses and most pain assessment tools have not been validated for this population. In this narrative review, we discuss the fundamentals of pain assessment for populations with OUD.

Opportunities to improve opioid use disorder care for hospitalised patients with endocarditis.

Background: Driven by increased injection opioid use, rates of hospitalisation for infective endocarditis, an infection associated with injection drug use, are increasing. In the USA, 1 in 10 hospitalised patients for opioid use disorder-associated infective endocarditis (OUD-IE) die in the hospital and 1 in 20 have a patient-directed discharge. Emerging models of care reveal opportunities for healthcare systems to meet the complex care needs of these patients.

The United States opioid crisis: Big pharma alone is not to blame.".

Objective: The opioid crisis in the United States continues essentially unabated, fueled by fentanyl contamination of the heroin supply and resulting in 79,770 reported opioid-involved overdose deaths in the calendar year 2022. To prevent another such crisis emerging, it is necessary to fully identify its root causes.

Methods: Despite the well-recognized role the pharmaceutical industry played in facilitating the crisis via the aggressive marketing of prescription opioids, several other less appreciated but perhaps more influential factors were also contributors, and the overall goal of this review is to ensure that these are not be lost to history in a concerted effort to blame opioid manufacturers and distributors.

High-Throughput Analyses of Therapeutic Antibodies Using High-Field Asymmetric Waveform Ion Mobility Spectrometry Combined with SampleStream and Intact Protein Mass Spectrometry.

Intact protein mass spectrometry (MS) coupled with liquid chromatography was applied to characterize the pharmacokinetics and stability profiles of therapeutic proteins. However, limitations from chromatography, including throughput and carryover, result in challenges with handling large sample numbers. Here, we combined intact protein MS with multiple front-end separations, including affinity capture, SampleStream, and high-field asymmetric waveform ion mobility spectrometry (FAIMS), to perform high-throughput and specific mass measurements of a multivalent antibody with one antigen-binding fragment (Fab) fused to an immunoglobulin G1 (IgG1) antibody.

Exploring the postoperative pain experiences of individuals with opioid use disorder and the nurses providing care in the USA: A qualitative descriptive study protocol.

Introduction: The goal of this study is to gain firsthand insights from individuals with a history of opioid use disorder (OUD) using medication for OUD on their experiences with postoperative pain care. This study also seeks to describe the experiences of nurses caring for individuals with OUD, and the challenges they may face managing complaints of pain in this population. Research suggests that hospitals can significantly enhance the quality of the care they deliver by investigating an individual's experience in the care setting.

Outcomes and experiences after child custody loss among mothers who use drugs: A mixed studies systematic review.

Background: Mothers who use drugs are more likely to experience child custody loss than mothers who do not use drugs. The negative impact of removal on children has been well characterized in current literature while less is known about the impact of custody loss on mothers. The purpose of this mixed studies systematic review is to describe the state of science on the maternal outcomes and experiences after child custody loss among mothers who use drugs.

Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study.

The opioid and cannabinoid receptor systems are inextricably linked-overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD).

Degradation of Dissolved RDX, NQ, and DNAN by Cathodic Processes in an Electrochemical Flow-Through Reactor.

Both legacy munitions compounds (e.g., RDX) and new insensitive high explosives (e.

Preparative Electrophoresis for HDL Particle Size Separation and Intact-Mass Apolipoprotein Proteoform Analysis.

The most abundant proteins on high-density lipoproteins (HDLs), apolipoproteins A-I (APOA1) and A-II (APOA2), are determinants of HDL function with 15 and 9 proteoforms (chemical-structure variants), respectively. The relative abundance of these proteoforms in human serum is associated with HDL cholesterol efflux capacity, and cholesterol content. However, the association between proteoform concentrations and HDL size is unknown.

Preoperative and Postoperative Hyperalgesia in Dental Patients on Chronic Opioid Therapy: A Pilot Study.

Objective: Opioid-induced hyperalgesia, a paradoxical increase in pain sensitivity associated with ongoing opioid use, may worsen the postoperative pain experience. This pilot study examined the effect of chronic opioid use on pain responses in patients undergoing a standardized dental surgery.

Methods: Experimental and subjective pain responses were compared prior to and immediately following planned multiple tooth extractions between patients with chronic pain on opioid therapy (≥30 mg morphine equivalents/d) and opioid-naïve patients without chronic pain matched on sex, race, age, and degree of surgical trauma.

"I Just Need Proper Treatment": Being Hospitalized for Endocarditis among Individuals Who Inject Drugs Being Hospitalized for Endocarditis.

Background: Rates of hospitalization for injection drug use-associated infective endocarditis (IDU-IE) are increasing. Much is known about the poor outcomes of patients with IDU-IE; less is known about the patient experience during hospitalization.

Objective: To explore the experience of being hospitalized for endocarditis among individuals who inject drugs, providing a foundation on which to develop strategies to improve care for these patients.

Electrochemical Synthesis of HO for -nitrophenol Degradation Utilizing a Flow-through Three-dimensional Activated Carbon Cathode with Regeneration Capabilities.

The growing ubiquity of recalcitrant organic contaminants in the aqueous environment poses risks to effective and efficient water treatment and reuse. A novel three-dimensional (3D) electrochemical flow-through reactor employing activated carbon (AC) encased in a stainless-steel (SS) mesh as a cathode is proposed for the removal and degradation of a model recalcitrant contaminant -nitrophenol (PNP), a toxic compound that is not easily biodegradable or naturally photolyzed, can accumulate and lead to adverse environmental health outcomes, and is one of the more frequently detected pollutants in the environment. As a stable 3D electrode, granular AC supported by a SS mesh frame as a cathode is hypothesized to 1) electrogenerate HO via a 2-electron oxygen reduction reaction on the AC surface, 2) initiate decomposition of this electrogenerated HO to form hydroxyl radicals on catalytic sites of the AC surface 3) remove PNP molecules from the waste stream via adsorption, and 4) co-locate the PNP contaminant on the carbon surface to allow for oxidation by formed hydroxyl radicals.

Pain Management and Substance Use Disorders: A Position Statement.

The American Society for Pain Management Nursing and the International Nurses Society on Addictions hold the position that persons with co-occurring pain and substance use disorder have the right to be treated with dignity and respect and receive evidence-based, high-quality assessment and management for both conditions using an integrated, holistic, multidimensional approach. Nonopioid and nonpharmacological approaches to pain management are recommended. Opioids should not be withheld from anyone if necessary to treat pain, and a team-based approach, including pain and addiction specialists, should be utilized when possible.

Safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with opioid use disorder.

Background: Patients with opioid use disorder (OUD) frequently leave the hospital as patient directed discharges (PDDs) because of untreated withdrawal and pain. Short-acting opioids can complement methadone, buprenorphine, and non-opioid adjuvants for withdrawal and pain, however little evidence exists for this approach. We described the safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with OUD at an academic hospital in Philadelphia, PA.

Delphi study to explore a new diagnosis for "ineffective" long-term opioid therapy for chronic pain.

A challenge in clinical, research, and policy spheres is determining whether and how to apply the Diagnostic and Statistical Manual-5 Opioid Use Disorder criteria to patients receiving long-term opioid therapy (LTOT) for the management of chronic pain. This study explored perspectives on the merits of creating a new diagnostic entity to characterize the problems that arise for certain patients prescribed LTOT and develop consensus on its definition and diagnostic criteria. We conducted 3 rounds of online surveys and held one discussion-based workshop to explore a new diagnostic entity and generate consensus with subject matter experts (n = 51) in pain and opioid use disorder, including a wide range of professional disciplines.

Automated Control of Injection Times for Unattended Acquisition of Multiplexed Individual Ion Mass Spectra.

Charge detection mass spectrometry (CDMS) provides mass domain spectra of large and highly heterogeneous analytes. Over the past few years, we have multiplexed CDMS on Orbitrap instruments, an approach termed Individual Ion Mass Spectrometry (IMS). Until now, IMS required manual adjustment of injection times to collect spectra in the individual ion regime.

Nursing Resources Linked to Postsurgical Outcomes for Patients With Opioid Use Disorder: An Observational Study.

Unlabelled: To determine whether better nursing resources (ie, nurse education, staffing, work environment) are each associated with improved postsurgical outcomes for patients with opioid use disorder (OUD).

Background: Hospitalized patients with OUD are at increased risk of adverse outcomes. Evidence suggests that adverse postsurgical outcomes may be mitigated in hospitals with better nursing resources, but this has not been evaluated among surgical patients with OUD.

Longitudinal association of early childhood lead exposure and adolescent heart rate variability: influence of parental education.

Lead exposure has been shown to dysregulate physiological stress responses. However, few studies have investigated the effect of lead exposure on later heart rate variability (HRV), an indicator of a stress response, in large samples of children. Furthermore, the interaction between social environmental factors and lead exposure in childhood, which commonly co-occur, remains understudied.