PSMC2 promotes resistance against temozolomide in glioblastoma via suppressing JNK-mediated autophagic cell death.

Temozolomide is universally used to treat glioblastoma due to its unique ability to cross the blood-brain barrier and inhibit tumor growth through DNA alkylation. However, over time, the inevitable emergence of resistance to temozolomide impedes successful treatment of this cancer. As a result, there is an urgent need to identify new therapeutic targets to improve treatment outcomes for this malignancy.

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Unguarded liabilities: complex amino acid dependence exposes unique avenues of inhibition.

Recent reports from the Centers for Disease Control and Prevention approximate 500,000 cases of Lyme disease in the United States yearly, a significant economic burden on the healthcare system. The standard treatment for Lyme disease includes broad-spectrum antibiotics, which may be administered for extensive periods of time and result in significant impacts to the patient. Recently, we demonstrated that , the causative agent of Lyme disease, is uniquely dependent upon peptide acquisition via an oligopeptide transport (Opp) system.

Drug Property Optimization: Design, Synthesis, and Characterization of Novel Pharmaceutical Salts and Cocrystal-Salt of Lumefantrine.

Lumefantrine (LMF) is a low-solubility antimalarial drug that cures acute, uncomplicated malaria. It exerts its pharmacological effects against erythrocytic stages of spp. and prevents malaria pathogens from producing nucleic acid and protein, thereby eliminating the parasites.

Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board DNA Sequencing Data: Workflow and Estimated Costs.

Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants.

An interprofessional model to improve LGBTQ+ specific cultural competence in dental and pharmacy students.

Background: Disproportionate access to healthcare services among the Lesbian, Gay, Bisexual, Transgender, Queer or Questioning and others (LGBTQ+) population can be partially attributed to the lack of cultural competence among healthcare providers. The aim of this study was to evaluate the impact of an interprofessional model in improving cultural competence and clinical preparedness among dental and pharmacy students for providing LGBTQ+ specific care.

Methodology: This study is a retrospective observational study which used a novel interprofessional model of three different LGBTQ+ focused educational interventions within a group of dental and pharmacy students.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

Improvement of antioxidant capacity, aroma quality, and antifungal ability of cherry by phenyllactic acid treatment during low temperature storage.

Introduction: Sweet cherries ( L.) are highly valued for their taste and nutrients but are prone to decay due to their delicate skin and high respiration rate. Traditional chemical preservatives have drawbacks like residues and resistance, prompting the search for natural alternatives.

Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.

Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).

An updated overview on long-acting therapeutics for the prevention and treatment of human immunodeficiency virus (HIV) from a perspective of pharmaceutics.

Conventional drug formulations release active pharmaceutical ingredients (APIs) immediately after administration, while long-acting (LA) drug products are designed for prolonged therapeutic effects, thereby reducing administration frequency and improving patient compliance. The development of LA therapeutics for chronic disease treatment has significantly helped patients adhere to their regimens, reducing the need for daily doses and easing the burden on healthcare systems. Advances in treatment have transformed Human Immunodeficiency Virus (HIV) into a manageable chronic disease, and efforts are underway to eliminate HIV in the future.

K currents in ventricular cardiomyocytes of p.N98S-calmodulin mutant mice.

Missense mutations in calmodulin (CaM)-encoding genes are associated with life-threatening ventricular arrhythmia syndromes. Here, we investigated a role of cardiac K channel dysregulation in arrhythmogenic long QT syndrome (LQTS) using a knock-in mouse model heterozygous for a recurrent mutation (p.N98S) in the gene (Calm1).

Impact of HPMCAS Grade on the Release of Weakly Basic Drugs from Amorphous Solid Dispersions.

Oppositely charged species can form electrostatic interactions in aqueous solution, and these may lead to reduced solubility of the interacting components. Herein, insoluble complex formation between the lipophilic weakly basic drugs, cinnarizine or loratadine, and the enteric polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), was studied and used to better understand drug and polymer release from their corresponding amorphous solid dispersions (ASDs). Surface area normalized release experiments were performed at various pH conditions for three different grades of HPMCAS, LF, MF and HF, as well as their ASDs.

Recent advances in drying and development of solid formulations for stable mRNA and siRNA lipid nanoparticles.

Current RNA lipid nanoparticle (LNP) based products are typically liquid formulations that require ultra-cold storage temperatures for stability. To address this limitation, recent efforts have focused on enhancing stability and enabling room temperature storage by converting these formulations into solid forms through drying processes such as lyophilization, spray drying, and spray-freeze drying. Nevertheless, the drying process itself can influence the stability of RNA/LNP formulations.

Avian pathogenic Escherichia coli and ostriches: a deep dive into pathological and microbiological investigation.

Objective: A comprehensive research was conducted to investigate the incidence of avian pathogenic Escherichia coli (APEC) in ostrich farms in Egypt.

Methods: The study involved seven farms with bird ages ranging from 1 to 12 weeks and capacities of 2,000 to 5,000 birds per farm. 175 tissue specimens were collected from different organs (liver, spleen, heart, lung, kidney, intestine, and meat).

Population Pharmacokinetics of Meropenem Across the Adult Lifespan.

Background And Objective: We conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens.

Methods: A total of 99 patients were included. The population pharmacokinetic models used had two compartments: zero-order input and linear elimination.

Improving the storage quality of sweet cherry by natamycin nanoparticles/chitosan coating.

In this study, natamycin nanoparticles were prepared by anti-solvent method, and natamycin nanoparticles/chitosan coating was prepared and investigated for the preservation of sweet cherry. The results of particle size showed that the prepared natamycin nanoparticles were nano-sized, with a particle size of 209 ± 10 nm. The results of scanning electron microscope (SEM) showed that the apparent morphology was a uniform spherical structure.

COEPA ready: Innovative pedagogy for integrating social determinants of health in PharmD curricula.

Background: The American Association of Colleges of Pharmacy Curriculum Outcomes and Entrustable Professional Activities (COEPA) recognize the need for social determinants of health (SDH) education for pharmacy learners. However, there is a dearth of published strategies for incorporating comprehensive SDH education in Doctor of Pharmacy curricula. The objectives of this study were to: 1) highlight unpublished exemplars of SDH teaching models and 2) propose strategies for teaching SDH.

Prospective evaluation of a residency preparation checklist for PGY1 match success.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Effect of five lactic acid bacteria on the flavor quality of fermented sweet potato juice.

The purpose of this research was to assess the impact of 5 lactic acid bacteria (LAB), Lactiplantibacillus plantarum, Lacticaseibacillus casei, , Lacticaseibacillus rhamnosus and subsp. bulgaricus on the characteristic flavor of the fermented sweet potato juice. Following the fermentation process, significant variations were observed in the concentrations of sugars, organic acids, as well as the overall volatile aroma compounds.

Developing and applying potentially scalable recruitment strategies to accelerate ADRD research participation of Black adults.

More than 2 million older Americans from underrepresented racial and ethnic minority groups (URGs) have early-stage Alzheimer's disease and related dementias (ADRD). There are very few scalable recruitment strategies, particularly for Black older adults, to accelerate participation in ADRD research. The Indiana Alzheimer's Disease Research Center (IADRC) and its Community Advisory Board developed and implemented the innovative RAAISE-D Framework.

Applying the Andersen behavioral model to the medication therapy management program: an approach for improving medication safety in older adults.

Medication therapy problems (MTPs) are common among older adults and are associated with considerable morbidity, mortality, and healthcare costs. The Medicare Part D Medication Therapy Management (MTM) program, which includes Comprehensive Medication Reviews (CMRs), Targeted Medication Reviews (TMRs), and guidance on safe medication disposal, is designed to optimize therapeutic outcomes and reduce adverse events by addressing MTPs. Although this program has demonstrated success in reducing MTPs, its utilization remains low, with ongoing concerns about service access disparities, patient satisfaction, and long-term health outcomes.

Food insecurity is associated with greater difficulty accessing care among people living with HIV with or without comorbid non-communicable diseases in western Kenya.

Introduction: The relationship between food insecurity and access to healthcare in low-resource settings remains unclear. Some studies find that food insecurity is a barrier to accessing care, while others report that food insecurity is associated with a greater need for care, leading to more care utilisation. We use data from the Harambee study in western Kenya to assess the association between food insecurity and difficulty accessing care among people living with HIV (PLWH) with or without comorbid non-communicable diseases (NCDs).

Experiencing chronic cough symptoms for 3 years is associated with increased rates of healthcare resource use and higher healthcare costs in the United States compared to resolved chronic cough.

Objective: Chronic cough (CC) symptoms can persist as refractory or unexplained CC (RCC). We sought to characterize the clinical and economic burden of RCC.

Methods: In this retrospective US cohort study using data from Optum's de-identified CDM Database (01/2015-03/2022), CC was identified as ≥1 CC diagnosis or ≥3 cough events (with ≥8 weeks and ≤120 days between the first and third events and ≥3 weeks between any two events).