Development and characterization of nitazoxanide-loaded poly(ε-caprolactone) membrane for GTR/GBR applications.

Objective: Guided tissue/guided bone regeneration (GTR/GBR) membranes are widely used for periodontal bone regeneration, but their success depends on a bacteria-free environment. Systemic antibiotic treatment often proves inadequate, moreover, the increasing prevalence of antibiotic resistance in oral infections exacerbates this challenge. This study aimed to fabricate antibacterial membranes using a new class of antibiotics for local drug delivery, to eradicate infections and promote tissue regeneration.

Phage Therapy in Korea: A Prescribers' Survey of Attitudes Amongst Korean Infectious Diseases Specialists Towards Phage Therapy.

Background: Concerns about the rise in antimicrobial resistance have led to renewed interest in phage therapy worldwide, but perceptions among relevant medical professionals in Korea remain largely unknown.

Materials And Methods: We conducted a semi-quantitative online survey to evaluate the Korean infectious disease specialists' perception of phage therapy.

Results: We sent out the link to the questionnaire to 380 subjects and received 91 replies, with 90/91 respondents identifying as Korean infectious diseases specialists or trainees.

Cesarean scar ectopic pregnancy: nuances in diagnosis and treatment.

A cesarean scar ectopic pregnancy (CSEP) occurs when the embryo implants on the scar of a previous cesarean delivery. The number of births delivered by cesarean section has climbed by 50% over the last decade, from a nadir of 20.7% in 1996 to 32.

Placental Histopathologic Findings of a Large Cohort of Patients With SARS-CoV-2 Infection During Pregnancy.

Pregnant individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at a higher risk for adverse pregnancy outcomes. Previous small cohort studies have shown increased frequency of placental lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, and inflammation among patients with SARS-CoV-2, without controlling for cardiometabolic risk factors among many such patients. We aimed to evaluate whether SARS-CoV-2 infection during pregnancy is independently associated with placental abnormalities when controlling for risk factors that could affect placental histopathology.

Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial.

Introduction: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.

Methods And Analysis: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme.

Novel gene-intergenic fusion involving ubiquitin E3 ligase UBE3C causes distal hereditary motor neuropathy.

Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration of the lower motor neurons. There are currently 29 reported causative genes and four disease loci implicated in dHMN. Despite the high genetic heterogeneity, mutations in the known genes account for less than 20% of dHMN cases, with the mutations identified predominantly being point mutations or indels.

Data to Power Precision Phage Therapy: A Look at the Phage Directory-Phage Australia Partnership.

Phage Directory has recently partnered with Phage Australia to help optimize Australia's data-centric standardized approach to personalized phage therapy. Here is a behind-the-scenes look at the genesis of Phage Australia, how the Phage Directory-Phage Australia partnership started, and what it is working toward.

3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies.

Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics conditions and pathological conditions such as cancer. In comparison to biospecimens taken from tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options.

Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics.

The escalating issue of multidrug-resistant (MDR) bacteria indicates the urgent need for new and effective strategies to combat this global health challenge. Here, we describe a new combinatorial approach that can be put forward for experimental therapy application against MDR bacteria. Specifically, we have developed a tri-system that includes the coadministration of two different membrane-disrupting-type antimicrobial agents─a synthetic antimicrobial polymer and an antimicrobial peptide (AMP) colistin methanesulfonate ()─in conjunction with an antibiotic [doxycycline (), rifampicin (), or azithromycin ()].

Accuracy of Magnetic Resonance Imaging for Identifying Ovarian Cancer in a Community-Based Setting.

Many ovarian or adnexal masses have an indeterminate appearance on ultrasound that can raise concerns about cancer. Although magnetic resonance imaging (MRI) has been reported to reliably distinguish between benign and malignant masses, studies evaluating the accuracy of MRI in community-based practice settings are lacking. Women who underwent MRI to further evaluate an ultrasound-detected adnexal mass in 2016-2017 within a large community-based health system were identified.

Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child.

Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment.

Transcriptome analysis of islets from diabetes-resistant and diabetes-prone obese mice reveals novel gene regulatory networks involved in beta-cell compensation and failure.

The mechanisms underpinning beta-cell compensation for obesity-associated insulin resistance and beta-cell failure in type 2 diabetes remain poorly understood. We used a large-scale strategy to determine the time-dependent transcriptomic changes in islets of diabetes-prone db/db and diabetes-resistant ob/ob mice at 6 and 16 weeks of age. Differentially expressed genes were subjected to cluster, gene ontology, pathway and gene set enrichment analyses.

Topography of transcriptionally active chromatin in glioblastoma.

Molecular profiling of the most aggressive brain tumor glioblastoma (GBM) on the basis of gene expression, DNA methylation, and genomic variations advances both cancer research and clinical diagnosis. The enhancer architectures and regulatory circuitries governing tumor-intrinsic transcriptional diversity and subtype identity are still elusive. Here, by mapping H3K27ac deposition, we analyze the active regulatory landscapes across 95 GBM biopsies, 12 normal brain tissues, and 38 cell line counterparts.

A Phage Therapy Guide for Clinicians and Basic Scientists: Background and Highlighting Applications for Developing Countries.

Approximately 10% of global health research is devoted to 90% of global disease burden (the so-called "10/90 Gap") and it often neglects those diseases most prevalent in low-income countries. Antibiotic resistant bacterial infections are known to impact on healthcare, food security, and socio-economic fabric in the developing countries. With a global antibiotic resistance crisis currently reaching a critical level, the unmet needs in the developing countries are even more striking.

Phage Biobank: Present Challenges and Future Perspectives.

After a century of use in human infection, the preparation and administration of therapeutic bacteriophages (phages) still relies on ad hoc partnerships of researchers, biotech companies, clinicians and regulators. There is a clear need to improve the reproducibility, safety and speed of the provision of suitable phages. Here we discuss the specific characteristics and challenges of a sustainable phage biobank and, as we build a national consortium aimed at delivering phage therapeutics, suggest a roadmap toward national biobanking and phage therapy initiatives using the Australian context as a model.

MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma.

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E).

Skeletal glucocorticoid signalling determines leptin resistance and obesity in aging mice.

Objective: Aging and chronic glucocorticoid excess share a number of critical features, including the development of central obesity, insulin resistance and osteoporosis. Previous studies have shown that skeletal glucocorticoid signalling increases with aging and that osteoblasts mediate the detrimental skeletal and metabolic effects of chronic glucocorticoid excess. Here, we investigated whether endogenous glucocorticoid action in the skeleton contributes to metabolic dysfunction during normal aging.

Core transcriptional regulatory circuitries in cancer.

Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type-specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC).

TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines.

Background & Aims: We investigated the transcriptome of esophageal squamous cell carcinoma (ESCC) cells, activity of gene regulatory (enhancer and promoter regions), and the effects of blocking epigenetic regulatory proteins.

Methods: We performed chromatin immunoprecipitation sequencing with antibodies against H3K4me1, H3K4me3, and H3K27ac and an assay for transposase-accessible chromatin to map the enhancer regions and accessible chromatin in 8 ESCC cell lines. We used the CRC_Mapper algorithm to identify core regulatory circuitry transcription factors in ESCC cell lines, and determined genome occupancy profiles for 3 of these factors.

Vascular transcriptome landscape of Trail mice: Implications and therapeutic strategies for diabetic vascular disease.

Circulating plasma TRAIL levels are suppressed in patients with cardiovascular and diabetic diseases. To identify novel targets in vascular metabolic diseases, genome-wide transcriptome of aortic tissue from Trail versus Trail mice were interrogated. We found 861 genes differentially expressed with TRAIL deletion.

Publisher Correction: Safety of bacteriophage therapy in severe Staphylococcus aureus infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Safety of bacteriophage therapy in severe Staphylococcus aureus infection.

In this single-arm non-comparative trial, 13 patients in an Australian hospital with severe Staphylococcus aureus infections were intravenously administered a good manufacturing practice-quality preparation of three Myoviridae bacteriophages (AB-SA01) as adjunctive therapy. AB-SA01 was intravenously administered twice daily for 14 d and the clinical, haematological and blood biochemical parameters of the recipients were monitored for 90 d. The primary outcome was the assessment of safety and tolerability (that is, pain and redness at the infusion site and systemic adverse reactions, such as fever, tachycardia, hypotension, diarrhoea or abdominal pain and the development of renal or hepatic dysfunction).