Carriage of antimicrobial resistance genes in Escherichia coli of bovine origin.

The present study aimed to search for the presence of the plasmid-mediated antimicrobial resistance genes in 106 Escherichia coli (E. coli) isolates from a total of 240 fresh fecal samples collected from 12 private cattle farms in Bingol province of East Turkey from November 2021 to January 2022. In those colistin-resistant E.

Mixed method analysis of anthropogenic groundwater contamination of drinking water sources in Malawi.

Groundwater contamination poses significant challenges to public health and sustainable development in Malawi, where approximately 80 % of the population relies on groundwater sources for drinking water. This study investigates the presence and drivers of nitrate and E. coli contamination in groundwater used for drinking.

Spatial model of groundwater contamination risks from pit-latrines in a low-income country.

Pit-latrines are central to achieving UN Sustainable Development Goal 6 (SDG 6) of ensuring "clean water and sanitation for all". Unless safely managed, pit-latrines result in groundwater contamination, which increases morbidity and mortality. Despite this, there have been no long-term spatial projections of future pit-latrine contamination risks.

The Traumatic Inoculation Process Affects TSPO Radioligand Uptake in Experimental Orthotopic Glioblastoma.

Background: The translocator protein (TSPO) has been proven to have great potential as a target for the positron emission tomography (PET) imaging of glioblastoma. However, there is an ongoing debate about the potential various sources of the TSPO PET signal. This work investigates the impact of the inoculation-driven immune response on the PET signal in experimental orthotopic glioblastoma.

Interleukin-6-controlled, mesenchymal stem cell-based sodium/iodide symporter gene therapy improves survival of glioblastoma-bearing mice.

New treatment strategies are urgently needed for glioblastoma (GBM)-a tumor resistant to standard-of-care treatment with a high risk of recurrence and extremely poor prognosis. Based on their intrinsic tumor tropism, adoptively applied mesenchymal stem cells (MSCs) can be harnessed to deliver the theranostic sodium/iodide symporter () deep into the tumor microenvironment. Interleukin-6 (IL-6) is a multifunctional, highly expressed cytokine in the GBM microenvironment including recruited MSCs.

The Status of Sanitation in Malawi: Is SDG6.2 Achievable?

Ensuring access to adequate and equitable sanitation and ending open defecation by 2030 is the focus of Sustainable Development Goal 6.2 (SDG6.2).

Predicting delirium in older non-intensive care unit inpatients: development and validation of the DELIrium risK Tool (DELIKT).

Background: Effective delirium prevention could benefit from automatic risk stratification of older inpatients using routinely collected clinical data.

Aim: Primary aim was to develop and validate a delirium prediction model (DELIKT) suitable for implementation in hospitals. Secondary aim was to select an anticholinergic burden scale as a predictor.

Structure-Activity Relationship of Methyl 4-Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches.

A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S-transferase (GST) are two glutathione-related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4-aminobenzoate derivatives on GR and GST were examined in vitro.

Affinity-based and in a single step purification of recombinant horseradish peroxidase A2A isoenzyme produced by Pichia pastoris.

Horseradish peroxidase (HRP) is an oxidoreductase enzyme and oxidizes various inorganic and organic compounds. It has wide application areas such as immunological tests, probe-based test techniques, removal of phenolic pollutants from wastewater and organic synthesis. HRP is found in the root of the horseradish plant as a mixture of different isoenzymes, and it is very difficult to separate these enzymes from each other.

Mesenchymal Stem Cell-mediated Image-guided Sodium Iodide Symporter (NIS) Gene Therapy Improves Survival of Glioblastoma-bearing Mice.

Purpose: Mesenchymal stem cells (MSC) have emerged as cellular-based vehicles for the delivery of therapeutic genes in cancer therapy based on their inherent tumor-homing capability. As theranostic gene, the sodium iodide symporter (NIS) represents a successful target for noninvasive radionuclide-based imaging and therapy. In this study, we applied genetically engineered MSCs for tumor-targeted NIS gene transfer in experimental glioblastoma (GBM)-a tumor with an extremely poor prognosis.

Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma.

Sodium iodide symporter () gene transfer for active accumulation of iodide in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application of radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery barrier for nucleic acid nanoparticles. In the present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands for the transferrin receptor (TfR) and the epidermal growth factor receptor (EGFR), thus providing the potential for active transport across the BBB followed by targeting of tumor cells.

Screening of Chemical Libraries Using Embryos and Tadpoles for Phenotypic Drug Discovery.

Phenotypic drug discovery assesses the effect of small molecules on the phenotype of cells, tissues, or whole organisms without a priori knowledge of the target or pathway. Using vertebrate embryos instead of cell-based assays has the advantage that the screening of small molecules occurs in the context of the complex biology and physiology of the whole organism. Fish and amphibians are the only classes of vertebrates with free-living larvae amenable to high-throughput drug screening in multiwell dishes.

Inhibition Profiles and Molecular Docking Analysis of Benzohydrazide Derivatives on Red Blood Cell Carbonic Anhydrases Isozymes.

Background: Carbonic anhydrases (CAs, EC 4.2.1.

Evaluation of the association of anticholinergic burden and delirium in older hospitalised patients - A cohort study comparing 19 anticholinergic burden scales.

Aims: A recent review identified 19 anticholinergic burden scales (ABSs) but no study has yet compared the impact of all 19 ABSs on delirium. We evaluated whether a high anticholinergic burden as classified by each ABS is associated with incident delirium.

Method: We performed a retrospective cohort study in a Swiss tertiary teaching hospital using data from 2015-2018.

Deletion of endothelial α-parvin inhibits tumour angiogenesis, reduces tumour growth and induces tumour cell apoptosis.

Alpha-parvin (α-pv), an adaptor protein that mediates integrin-dependent cell-matrix interactions, is essential for endothelial cells migration and proliferation and is a key player in physiological angiogenesis. The role of α-pv in pathological angiogenesis is unknown. Here we demonstrate that endothelial α-pv is required for tumour angiogenesis.

Methyl benzoate derivatives as inhibitors of pentose phosphate pathway, which promotes cancer progression and drug resistance: An in silico study supported by in vitro results.

The pentose phosphate pathway (PPP), whose products are vital in biosynthetic events, is targeted in the treatment of many diseases such as cancer and malaria. The objective of this study was to identify new PPP inhibitors. The inhibition effects of methyl 4-amino benzoates on glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were analyzed through in vitro experiments and molecular docking studies were used to estimate inhibition mechanisms.

PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook.

Background: Prostate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model.

Selective sodium iodide symporter () genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes.

Lipo-oligomers, post-functionalized with ligands to enhance targeting, represent promising new vehicles for the tumor-specific delivery of therapeutic genes such as the sodium iodide symporter (). Due to its iodide trapping activity, NIS is a powerful theranostic tool for diagnostic imaging and the application of therapeutic radionuclides. I PET imaging allows non-invasive monitoring of the biodistribution of functional NIS expression, and application of I enables cytoreduction.

Acute health risks to community hand-pumped groundwater supplies following Cyclone Idai flooding.

This longitudinal flood-relief study assessed the impact of the March 2019 Cyclone Idai flood event on E. coli contamination of hand-pumped boreholes in Mulanje District, Malawi. It established the microbiological water-quality safety of 279 community supplies over three phases, each comprising water-quality survey, rehabilitation and treatment verification monitoring.

APLN/APLNR Signaling Controls Key Pathological Parameters of Glioblastoma.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM-expansion depends on a dense vascular network and, coherently, GBMs are highly angiogenic. However, new intratumoral blood vessels are often aberrant with consequences for blood-flow and vascular barrier function.

Comparing Tumor Cell Invasion and Myeloid Cell Composition in Compatible Primary and Relapsing Glioblastoma.

Glioblastoma (GBM) recurrence after treatment is almost inevitable but addressing this issue with adequate preclinical models has remained challenging. Here, we introduce a GBM mouse model allowing non-invasive and scalable de-bulking of a tumor mass located deeply in the brain, which can be combined with conventional therapeutic approaches. Strong reduction of the GBM volume is achieved after pharmacologically inducing a tumor-specific cell death mechanism.

Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties.

Background: The transcription factor NF-κB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma [GBM]). Precise therapeutic modulation of NF-κB activity can suppress central oncogenic signaling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive.

Methods: In a pharmacogenomics study with a panel of transgenic glioma cells, we observed that NF-κB can be converted into a tumor suppressor by the non-psychotropic cannabinoid cannabidiol (CBD).