Perioperative Antibiotic Choice and Postoperative Infectious Complications in Pelvic Organ Prolapse Surgery.

Objective: The objective of this study was to determine how rates of postoperative infectious complications after pelvic organ prolapse surgery differ based on perioperative antibiotic administered. In particular, we sought to determine whether anaerobic coverage is associated with reduced rates of infectious complications.

Design: This was a retrospective cohort study.

Targeting SCD triggers lipotoxicity of cancer cells and enhances anti-tumor immunity in breast cancer brain metastasis mouse models.

Breast cancer brain metastases (BCBM) are a significant cause of mortality and are incurable. Thus, identifying BCBM targets that reduce morbidity and mortality is critical. BCBM upregulate Stearoyl-CoA Desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, suggesting a potential metabolic vulnerability of BCBM.

The metabolic cofactor Coenzyme A enhances alternative macrophage activation via MyD88-linked signaling.

Metabolites and metabolic co-factors can shape the innate immune response, though the pathways by which these molecules adjust inflammation remain incompletely understood. Here we show that the metabolic cofactor Coenzyme A (CoA) enhances IL-4 driven alternative macrophage activation [m(IL-4)] and . Unexpectedly, we found that perturbations in intracellular CoA metabolism did not influence m(IL-4) differentiation.

Relationship between patient safety indicator events and hospital location for inpatient hysterectomy.

Background: Previous studies suggest surgical quality outcomes are similar between rural and urban hospitals, but data about gynecology in rural hospitals is sparse.

Methods: This was a retrospective cohort study utilizing the National Inpatient Sample database from the Agency of Healthcare Research and Quality. Patients who underwent benign hysterectomy for non-prolapse indications between 2012-2016 were identified using ICD-9 and 10 codes.

Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways.

The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models.

Insights into the Structure-Capacity of Food Antioxidant Compounds Assessed Using Coulometry.

CDAC (coulometrically determined antioxidant capacity) involves the determination of the antioxidant capacity of individual compounds or their mixtures using constant-current coulometry, with electrogenerated Br as the titrant, and biamperometric detection of the endpoint via Br excess. CDAC is an accurate, sensitive, rapid, and cheap measurement of the mol electrons (mol e) transferred in a redox process. In this study, the CDAC of 48 individual antioxidants commonly found in foods has been determined.

A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions.

Glomerular disease due to podocyte malfunction is a major factor in the pathogenesis of chronic kidney disease. Identification of podocyte-specific signaling pathways is therefore a prerequisite to characterizing relevant disease pathways and developing novel treatment approaches. Here, we employed loss of function studies for () as a central podocyte gene to generate a cell type-specific disease model.

Neglect as an undefined and overlooked aspect of medical student mistreatment: A systematic review of the literature.

Purpose: Although the mistreatment of medical students is a well-researched topic, the scope of mistreatment often leaves out neglect, a subtype for which there is no accepted definition based in the published literature. This review sought to summarize the existing data on the prevalence and descriptors of neglect, identify strategies seen in the literature designed to improve it, and offer a synthesized definition of this phenomenon to guide future research.

Methods: Following PRISMA guidelines, a relevant systematic literature search from 2000 to April 2021 was performed to identify literature on neglect in clinical settings within American medical schools.

CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis.

Malignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of translatable vulnerabilities for metabolism-targeted therapy. How molecular alterations in tumors promote metabolic diversity and distinct targetable dependencies remains poorly defined. Here we create a resource consisting of lipidomic, transcriptomic, and genomic data from 156 molecularly diverse glioblastoma (GBM) tumors and derivative models.

Evaluation of Novel Rapid Analytical Methods to Categorize Extra Virgin Olive Oil Based on the Coulometrically Determined Antioxidant Capacity and on the Spectrophotometric Assessment of Phenolic Compounds.

The lack of a practical "fit for the purpose" analytical protocol is the main limitation that has hampered the exploitation of the EFSA analytical health claim on the extra virgin olive oil (EVOO) biophenols, more than ten years since its introduction. In this work, two analytical methods recently developed in our laboratories for categorizing EVOO have been evaluated on a set of 16 samples from Cilento (Campania Region, southern Italy) and compared to other commonly used quality indexes. The Coulometrically Determined Antioxidant Capacity (CDAC) is associated with the component responsible for the health-promoting properties and oxidative stability of EVOO.

Illuminating cellular and extracellular vesicle-mediated communication via a split-Nanoluc reporter and .

Tools to effectively demonstrate and quantify functional delivery in cellular communication have been lacking. This study reports the use of a fluorescently labeled split Nanoluc reporter system to demonstrate and quantify functional transfer between cells and in a subcutaneous tumor mouse model. Our construct allows monitoring of direct, indirect, and specifically extracellular vesicle-mediated functional communication.

Epithelial-to-Mesenchymal Transition and Phenotypic Marker Evaluation in Human, Canine, and Feline Mammary Gland Tumors.

Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties. EMT has been closely associated with cancer cell aggressiveness. The aim of this study was to evaluate the mRNA and protein expression of EMT-associated markers in mammary tumors of humans (HBC), dogs (CMT), and cats (FMT).

Targeting de novo lipid synthesis induces lipotoxicity and impairs DNA damage repair in glioblastoma mouse models.

Deregulated de novo lipid synthesis (DNLS) is a potential druggable vulnerability in glioblastoma (GBM), a highly lethal and incurable cancer. Yet the molecular mechanisms that determine susceptibility to DNLS-targeted therapies remain unknown, and the lack of brain-penetrant inhibitors of DNLS has prevented their clinical evaluation as GBM therapeutics. Here, we report that YTX-7739, a clinical-stage inhibitor of stearoyl CoA desaturase (SCD), triggers lipotoxicity in patient-derived GBM stem-like cells (GSCs) and inhibits fatty acid desaturation in GSCs orthotopically implanted in mice.

Role of Economic Evaluations on Pricing of Medicines Reimbursed by the Italian National Health Service.

Objective: The main objective of this study was to explore the extent to which the incremental cost-effectiveness ratio (ICER), alongside other factors, predicts the final outcome of medicine price negotiation in Italy. The second objective was to depict the mean ICER of medicines obtained after negotiation.

Methods: Data were extracted from company dossiers submitted to the Italian Medicines Agency (AIFA) from October 2016 to January 2021 and AIFA's internal database.

Extracellular Vesicles in Veterinary Medicine.

Extracellular vesicles (EVs) are cell-derived membrane-bound vesicles involved in many physiological and pathological processes not only in humans but also in all the organisms of the eukaryotic and prokaryotic kingdoms. EV shedding constitutes a fundamental universal mechanism of intra-kingdom and inter-kingdom intercellular communication. A tremendous increase of interest in EVs has therefore grown in the last decades, mainly in humans, but progressively also in animals, parasites, and bacteria.

Characterization and function of extracellular vesicles in a canine mammary tumour cell line: Ultracentrifugation versus size exclusion chromatography.

Extracellular vesicles (EVs) are cell-derived membrane-bound vesicles involved in many biological processes such as tumour progression. For years, ultracentrifugation (UC) has been considered the gold standard for EV isolation but limited purity and integrity allowed the diffusion of alternative techniques. In this study, EVs were isolated from a canine mammary tumour cell line using UC and size exclusion chromatography (SEC) and analysed for size and concentration by nanoparticle tracking analysis (NTA) and for protein expression by western blot (WB).

Orthotopic brain tumor models derived from glioblastoma stem-like cells.

There is an urgency for identifying effective therapies for glioblastoma (GBM), an incurable and lethal primary malignant brain tumor. Patient-derived xenograft mouse models, in which glioma stem cells, which retain the characteristics of the original tumor, are implanted into the brain of immunocompromised mice, represent a well-suited model for studying GBM. Such models are essential for studies involving the tumor microenvironment and for testing experimental therapeutics for brain tumors.

NUP133 Controls Nuclear Pore Assembly, Transcriptome Composition, and Cytoskeleton Regulation in Podocytes.

Steroid-resistant nephrotic syndrome (SRNS) frequently leads to end-stage renal disease, ultimately requiring kidney replacement therapies. SRNS is often caused by hereditary monogenic mutations, specifically affecting specialized epithelial cells (podocytes) of the glomerular filtration barrier. Mutations in several components of the nuclear pore complex, including NUP133 and NUP107, have been recently identified to cause hereditary SRNS.

α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier.

Background: The cell-matrix adhesion between podocytes and the glomerular basement membrane is essential for the integrity of the kidney's filtration barrier. Despite increasing knowledge about the complexity of integrin adhesion complexes, an understanding of the regulation of these protein complexes in glomerular disease remains elusive.

Methods: We mapped the composition of the podocyte integrin adhesome.

Geometric analysis of the urethral-vaginal interface curvature in women with and without stress urinary incontinence: A pilot magnetic resonance imaging study.

Aims: To evaluate differences in the curvature of the urethral-vaginal interface in women with and without stress urinary incontinence (SUI) using geometric morphometric analysis techniques.

Methods: We conducted a pilot case-control study using magnetic resonance imaging (MRI) scans of 18 women with and without SUI. The urethral-vaginal interface at the level of the mid-urethra was fitted with a second-order polynomial regression.

A Novel Model for Nephrotic Syndrome Reveals Associated Dysbiosis of the Gut Microbiome and Extramedullary Hematopoiesis.

Glomerular kidney disease causing nephrotic syndrome is a complex systemic disorder and is associated with significant morbidity in affected patient populations. Despite its clinical relevance, well-established models are largely missing to further elucidate the implications of uncontrolled urinary protein loss. To overcome this limitation, we generated a novel, inducible, podocyte-specific transgenic mouse model (), developing nephrotic syndrome in adult mice.

Evaluation of TFR-1 Expression in Feline Mammary Cancer and In Vitro Antitumor Efficacy Study of Doxorubicin-Loaded H-Ferritin Nanocages.

The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far.

EPB41L5 controls podocyte extracellular matrix assembly by adhesome-dependent force transmission.

The integrity of the kidney filtration barrier essentially relies on the balanced interplay of podocytes and the glomerular basement membrane (GBM). Here, we show by analysis of in vitro and in vivo models that a loss of the podocyte-specific FERM-domain protein EPB41L5 results in impaired extracellular matrix (ECM) assembly. By using quantitative proteomics analysis of the secretome and matrisome, we demonstrate a shift in ECM composition characterized by diminished deposition of core GBM components, such as LAMA5.