Predictive performance of population pharmacokinetic models of imatinib in chronic myeloid leukemia patients.

Background And Aim: Chronic myeloid leukemia is a myeloproliferative neoplasm associated with the specific chromosomal translocation known as the Philadelphia chromosome. Imatinib is a potent BCR-ABL tyrosine kinase inhibitor, which is approved as the first line therapy for CML patients. There are various population pharmacokinetic studies available in the literature for this population.

Case report: Pulse cyclophosphamide for treatment of multi-agent-refractory hepatic graft-versus-host disease.

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies.

Climate warming, environmental degradation and pollution as drivers of antibiotic resistance.

Antibiotic resistance is a major challenge to public health, but human-caused environmental changes have not been widely recognized as its drivers. Here, we provide a comprehensive overview of the relationships between environmental degradation and antibiotic resistance, demonstrating that the former can potentially fuel the latter with significant public health outcomes. We describe that (i) global warming favors horizontal gene transfer, bacterial infections, the spread of drug-resistant pathogens due to water scarcity, and the release of resistance genes with wastewater; (ii) pesticide and metal pollution act as co-selectors of antibiotic resistance mechanisms; (iii) microplastics create conditions promoting and spreading antibiotic resistance and resistant bacteria; (iv) changes in land use, deforestation, and environmental pollution reduce microbial diversity, a natural barrier to antibiotic resistance spread.

Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study.

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects.

Innate and adaptive immune cell interaction drives inflammasome activation and hepatocyte apoptosis in murine liver injury from immune checkpoint inhibitors.

Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies.

Large-scale integrative analysis of juvenile idiopathic arthritis for new insight into its pathogenesis.

Background: Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear.

Methods: To prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS).

Adverse childhood experiences among California student pharmacists.

Introduction: Adverse childhood experiences (ACEs) are associated with higher mental and physical illness and substance use disorders in adulthood. However, little is known about the prevalence of ACEs among student pharmacists and the factors associated with exposure. Our objective was to determine the prevalence of ACEs, resilience, and maladaptive coping strategies among student pharmacists in California.

A rigorous benchmarking of alignment-based HLA typing algorithms for RNA-seq data.

Accurate identification of human leukocyte antigen (HLA) alleles is essential for various clinical and research applications, such as transplant matching and drug sensitivities. Recent advances in RNA-seq technology have made it possible to impute HLA types from sequencing data, spurring the development of a large number of computational HLA typing tools. However, the relative performance of these tools is unknown, limiting the ability for clinical and biomedical research to make informed choices regarding which tools to use.

Steric stabilization of bioactive nanoparticles using elastin-like polypeptides.

Elastin-like polypeptides (ELP) are versatile, thermo-responsive polymers that can be conjugated to virtually any therapeutic cargo. Derived from short amino-acid sequences and abundant in humans, certain ELPs display low immunogenicity. Substrates for endogenous proteases, ELPs are biodegradable and thus, are candidate biomaterials.

Noncovalent Conjugation of OVA323 to ELP Micelles Increases Immune Response.

Subunit vaccines would benefit from a safe particle-based adjuvant. Elastin-like polypeptide (ELP)-based micelles are interesting candidate adjuvants due to their well-defined size and easy modification with protein-based cargo. Coiled coils can facilitate noncovalent modifications, while potentially enhancing antigen delivery through interaction with cell membranes.

Pharmacokinetic model of human exposure to ciprofloxacin through consumption of fish.

Fluoroquinolones are broad-spectrum antibiotics that accumulate in the environment. To assess human exposure through the food chain, we developed a pharmacokinetic model of fluoroquinolone accumulation in fish and a human pharmacokinetic model to predict gastrointestinal concentrations of ciprofloxacin, a common fluoroquinolone, following consumption of fish. At 70 ng/L ciprofloxacin, the average in North American surface waters, the fish steady-state concentration was calculated to be 7.

Inappropriate quetiapine use at a large academic medical center: frequency of misuse and associated costs of adverse effects.

Background: Quetiapine is an antipsychotic with dose-related receptor affinity, which is commonly prescribed by specialties outside of psychiatry. Quetiapine can have adverse effects including weight gain, hyperglycemia, and falls. Therefore, quetiapine is a good focus medication to assess the need for an antipsychotic stewardship protocol.

Whole blood transcriptomics identifies subclasses of pediatric septic shock.

Background: Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies.

The mitochondrial translocator protein (TSPO, 18 kDa): A key multifunctional molecule in liver diseases.

Translocator protein (TSPO, 18 kDa), previously known as peripheral-type benzodiazepine receptor, is an evolutionarily conserved and tryptophan-rich 169-amino-acid protein located on the outer mitochondrial membrane. TSPO plays a crucial role in various fundamental physiological functions and cellular processes. Its expression is altered in pathological conditions, thus rendering TSPO a potential tool for diagnostic imaging and an appealing therapeutic target.

Rational design of humanized antibody inhibitors for cathepsin S.

Cathepsin S (CTSS) is involved in pathogenesis of many human diseases. Inhibitors blocking its protease activity hold therapeutic potential. In comparison to small-molecule inhibitors, monoclonal antibodies capable of inhibiting CTSS enzymatic activity may possess advantageous pharmacological properties.

Synthesis and Preclinical Evaluation of 22-[F]Fluorodocosahexaenoic Acid as a Positron Emission Tomography Probe for Monitoring Brain Docosahexaenoic Acid Uptake Kinetics.

Docosahexaenoic acid [22:6(-3), DHA], a polyunsaturated fatty acid, has an important role in regulating neuronal functions and in normal brain development. Dysregulated brain DHA uptake and metabolism are found in individuals carrying the APOE4 allele, which increases the genetic risk for Alzheimer's disease (AD), and are implicated in the progression of several neurodegenerative disorders. However, there are limited tools to assess brain DHA kinetics that can be translated to humans.

A ribose-functionalized NAD with versatile activity for ADP-ribosylation.

An NAD featuring an adenosyl 4'-azido functions as a general substrate for poly-ADP-ribose polymerases. Its derived mono- and poly-ADP-ribosylated proteins can be adequately recognized by distinct ADP-ribosylation-specific readers. This molecule represents the first ribose-functionalized NAD with versatile activities across different ADP-ribosyltransferases and provides insight into developing new probes for ADP-ribosylation.

Chemical crosslinking and ligation methods for in vivo analysis of RNA structures and interactions.

RNA structures and interactions in living cells drive a variety of biological processes and play critical roles in physiology and disease states. However, studies of RNA structures and interactions have been challenging due to limitations in available technologies. Direct determination of structures in vitro has been only possible to a small number of RNAs with limited sizes and conformations.

Risk factors and outcome associated with coinfection with carbapenem-resistant and carbapenem-resistant or a descriptive analysis.

Background: Nearly 30% of patients infected with carbapenem-resistant (CRKP) were previously shown to be coinfected with carbapenem-resistant (CRPA) or (CRAB). Infections caused by multiple carbapenem-resistant pathogens present significant challenge to infection control and therapeutic management. The study objective was to identify risk factors for acquisition of multiple carbapenem-resistant pathogens and associated outcomes.

The full health, economic, and social benefits of prospective Strep A vaccination.

Recent research has documented a wide range of health, economic, and social benefits conferred by vaccination, beyond the direct reductions in morbidity, mortality, and future healthcare costs traditionally captured in economic evaluations. In this paper, we describe the societal benefits that would likely stem from widespread administration of safe and effective vaccines against Streptococcus pyogenes (Strep A), which was estimated to be the fifth-leading cause of infectious disease deaths globally prior to the COVID-19 pandemic. We then estimate the global societal gains from prospective Strep A vaccination through a value-per-statistical-life approach.

Risk of contralateral breast cancer among Asian/Pacific Islander women in the United States.

Purpose: While breast cancer studies often aggregate Asian/Pacific Islander (API) women, as a single group or exclude them, this population is heterogeneous in terms of genetic background, environmental exposures, and health-related behaviors, potentially resulting in different cancer outcomes. Our purpose was to evaluate risks of contralateral breast cancer (CBC) among subgroups of API women with breast cancer.

Methods: We conducted a retrospective cohort study of women ages 18 + years diagnosed with stage I-III breast cancer between 2000 and 2016 in the Surveillance, Epidemiology and End Results registries.

Causes and costs of global COVID-19 vaccine inequity.

Despite the rapid development of safe and effective COVID-19 vaccines and the widely recognized health and economic benefits of vaccination, there exist stark differences in vaccination rates across country income groups. While more than 70% of the population is fully vaccinated in high-income countries, vaccination rates in low-income countries are only around 30%. The paper reviews the factors behind global COVID-19 vaccine inequity and the health, social, and economic costs triggered by this inequity.

The macroeconomic burden of noncommunicable diseases and mental health conditions in South America.

Noncommunicable diseases and mental health conditions (referred to collectively as NMHs) are the greatest cause of preventable death, illness, and disability in South America and negatively affect countries' economic performance through their detrimental impacts on labor supply and capital investments. Sound, evidence-based policy-making requires a deep understanding of the macroeconomic costs of NMHs and of their distribution across countries and diseases. The paper estimates and projects the macroeconomic burden of NMHs over the period 2020-2050 in 10 South American countries.

Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.

The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling.