Association of Opioid and Concurrent Benzodiazepine, Skeletal Muscle Relaxant, and Gabapentinoid Usage on Healthcare Expenditure and Resource Utilization: A Serial Cross-Sectional Study, 2009 to 2019.

Background: Healthcare providers may be utilizing central nervous system (CNS) depressants to reduce opioid use due to recent changes in public policy. Combination use of these agents with opioids increases the risk of respiratory depression and death. Healthcare expenditures by individuals using these drug combinations have not been previously quantified.

Regulation of Oxidative Stress and Apoptosis in Streptozotocin-Induced Diabetic Rats by Egyptian Sidr Honey.

Diabetes mellitus is a global health issue characterized by hyperglycemia which leads over time to severe damage to numerous tissues. The present study aimed to estimate the effect of Egyptian Sidr honey against streptozotocin (STZ)-induced diabetes in rats. Diabetic rats were treated with Sidr honey daily for 4 consecutive weeks.

Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection.

Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution.

Harnessing exosomes as a platform for drug delivery in breast cancer: A systematic review for and studies.

Breast cancer remains a significant global health concern, emphasizing the critical need for effective treatment strategies, especially targeted therapies. This systematic review summarizes the findings from and studies regarding the therapeutic potential of exosomes as drug delivery platforms in the field of breast cancer treatment. A comprehensive search was conducted across bibliographic datasets, including Web of Science, PubMed, and Scopus, using relevant queries from several related published articles and the Medical Subject Headings Database.

AlphaFold2 Predictions of Conformational Ensembles and Atomistic Simulations of the SARS-CoV-2 Spike XBB Lineages Reveal Epistatic Couplings between Convergent Mutational Hotspots that Control ACE2 Affinity.

In this study, we combined AlphaFold-based atomistic structural modeling, microsecond molecular simulations, mutational profiling, and network analysis to characterize binding mechanisms of the SARS-CoV-2 spike protein with the host receptor ACE2 for a series of Omicron XBB variants including XBB.1.5, XBB.

Diabetic Kidney Disease Prevention Care Model Development.

More than one-third of people with diabetes develop diabetic kidney disease (DKD), which substantially increases risks of kidney failure, cardiovascular disease (CVD), hypoglycemia, death, and other adverse health outcomes. A multifaceted approach incorporating self-management education, lifestyle optimization, pharmacological intervention, CVD prevention, and psychosocial support is crucial to mitigate the onset and progression of DKD. The American Diabetes Association convened an expert panel to develop the DKD Prevention Model presented herein.

Why get involved? A cross-sectional survey of factors that influence student pharmacist membership in professional organizations.

Introduction: Understanding factors that motivate and deter student pharmacists from joining professional pharmacy organizations may assist schools and organizations in determining ways to recruit, engage, and support the next generation of pharmacy professionals. The objective is to identify motivating and hindering factors related to student pharmacist membership in professional pharmacy organizations.

Methods: A cross-sectional survey was sent to the American Association of Colleges of Pharmacy Student Services Personnel community members for distribution to student pharmacists at their respective schools.

Pharmacological potential of cyclic nucleotide signaling in immunity.

Cyclic nucleotides are important signaling molecules that play many critical physiological roles including controlling cell fate and development, regulation of metabolic processes, and responding to changes in the environment. Cyclic nucleotides are also pivotal regulators in immune signaling, orchestrating intricate processes that maintain homeostasis and defend against pathogenic threats. This review provides a comprehensive examination of the pharmacological potential of cyclic nucleotide signaling pathways within the realm of immunity.

Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape.

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with the host cell receptor ACE2 and a panel of diverse class one antibodies. The central objective of this investigation was to examine the molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing of ACE2 binding and antibody evasion for Omicron variants BA.1, BA2, BA.

Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.

Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM).

Regulatory roles of microRNAs in modulating mitochondrial dynamics, amyloid beta fibrillation, microglial activation, and cholinergic signaling: Implications for alzheimer's disease pathogenesis.

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aβ) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation.

Characterizing Antibiotic Regimen Modification Behavior, Patient Characteristics, and Outcomes for Patients with Gram-Negative Bacterial Infections, A Retrospective Single-Center Study.

Few studies describe the frequency of antibiotic regimen modification behaviors in the acute care setting. We sought to ascertain patient and treatment characteristics, details of regimen modification, and clinical outcomes with antibiotic modifications. This retrospective study included patients admitted to Hoag Memorial Hospital from 1 January 2019-31 March 2021 with a complicated infection caused by a Gram-negative organism resistant to extended-spectrum cephalosporins or with the potential for resistance (AmpC producers).

Accurate Characterization of Binding Kinetics and Allosteric Mechanisms for the HSP90 Chaperone Inhibitors Using AI-Augmented Integrative Biophysical Studies.

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs , leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking.

Broad-spectrum activity of membranolytic cationic macrocyclic peptides against multi-drug resistant bacteria and fungi.

The emergence of multidrug-resistant (MDR) strains causes severe problems in the treatment of microbial infections owing to limited treatment options. Antimicrobial peptides (AMPs) are drawing considerable attention as promising antibiotic alternative candidates to combat MDR bacterial and fungal infections. Herein, we present a series of small amphiphilic membrane-active cyclic peptides composed, in part, of various nongenetically encoded hydrophilic and hydrophobic amino acids.

Predicting FFAR4 agonists using structure-based machine learning approach based on molecular fingerprints.

Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4.

The characteristics of white dot syndromes following COVID-19 Vaccines: a systematic review.

Purpose: To review all studies reporting the onset of white dot syndromes following COVID-19 vaccines.

Methods: Our protocol was registered prospectively on PROSPERO [registration number: CRD42023426012]. We searched five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct up to May 2023.

Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1-deficient mice.

Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium.

Predisposing deleterious variants in the cancer-associated human kinases in the global populations.

Human kinases play essential and diverse roles in the cellular activities of maintaining homeostasis and growth. Genetic mutations in the genes encoding the kinases (or phosphotransferases) have been linked with various types of cancers. In this study, we cataloged mutations in 500 kinases genes in >65,000 individuals of global populations from the Human Genetic Diversity Project (HGDP) and ExAC databases, and assessed their potentially deleterious impact by using the in silico tools SIFT, Polyphen2, and CADD.

Improved survival outcomes with anakinra over etoposide-based therapies for the management of adults with hemophagocytic lymphohistiocytosis: a retrospective multicenter research network study.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening, hyperinflammatory syndrome for which etoposide-based regimens have historically been the standard of care. Recent reports have described positive outcomes with the utilization of ruxolitinib or anakinra although these studies are often limited to small samples.

Objectives: We aimed to compare the efficacy of ruxolitinib, anakinra, and etoposide-based therapies for the management of HLH in adult patients.

Role of protein kinase A and A kinase anchoring proteins in buffering and compartmentation of cAMP signalling in human airway smooth muscle cells.

Background And Purpose: In human airway smooth muscle (hASM) cells, not all receptors stimulating cAMP production elicit the same effects. This can only be explained if cAMP movement throughout the cell is restricted, yet the mechanisms involved are not fully understood. Phosphodiesterases (PDEs) contribute to compartmentation of many cAMP responses, but PDE activity alone is predicted to be insufficient if cAMP is otherwise freely diffusible.