Objective: The World Health Organization (WHO) has declared antimicrobial resistance (AMR) as one of the top threats to global public health. While AMR surveillance of human clinical isolates is well-established in many countries, the increasing threat of AMR has intensified efforts to detect antibiotic resistance genes (ARGs) accurately and sensitively in environmental samples, wastewater, animals, and food. Using five ARGs and the 16S rRNA gene, we compared quantitative PCR (qPCR) and metagenomic sequencing (MGS), two commonly used methods to uncover the wastewater resistome.
View Article and Find Full Text PDFExpert Opin Drug Metab Toxicol
November 2024
Background: Adverse drug-drug interactions (DDI) may occur when one drug accelerates or slows a second drug's metabolism by, respectively, inducing or inhibiting a cytochrome P450 (CYP) that metabolizes that second drug. We developed an method employing urinalysis to complement CYP induction and inhibition measurements widely used to predict DDIs.
Research Design And Methods: Focusing on Cyp3a enzymes, the major mammalian drug metabolizers, we applied luciferin-IPA, a selective Cyp3a probe substrate to mice after Cyp3a inducers and inhibitor treatments.
Background: It is a challenge for the ambulance service to identify which patients to convey to the emergency department (ED). Ideally this would be the patients with serious conditions requiring further care in the ED. However, patients presenting with non-specific chief complaints are difficult to prioritize and typically have normal or near normal vital signs despite up to one third having underlying serious conditions.
View Article and Find Full Text PDFBackground: Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment, primarily established for post-traumatic stress disorder (PTSD). While it is increasingly being applied to chronic pain, its efficacy in this area is not yet supported by the same level of evidence as that which exists for PTSD. Studies in this area often show heterogeneous results with small case numbers, and the potential side effects of EMDR in the treatment of chronic pain are not well understood.
View Article and Find Full Text PDFObjective: Despite the prevalence of emergency medical service assignments related to chest discomfort, limited research delves into nurses' experiences of caring for such patients. This study aimed to illuminate prehospital emergency nurses' (PENs') experiences of caring for patients with suspected acute myocardial infarction (AMI).
Design: A qualitative interview study.
Background: Sepsis is a frequent cause of global deaths with time critical diagnosis and treatment impacting outcomes. Prehospital emergency nurses are pivotal in assessment that influences timely diagnosis.
Aim: To gain a deep understanding of nurse's experiences when caring for those with suspected sepsis.
Background: The utilization of AI language models in education and academia is currently a subject of research, and applications in clinical settings are also being tested. Studies conducted by various research groups have demonstrated that language models can answer questions related to medical board examinations, and there are potential applications of these models in medical education as well.
Research Question: This study aims to investigate the extent to which current version language models prove effective for addressing medical inquiries, their potential utility in medical education, and the challenges that still exist in the functioning of AI language models.
Biosolids as by-products of wastewater treatment can contain a large spectrum of pathogens and antibiotic resistance genes (ARGs). Insect-based bioconversion using black soldier fly larvae (BSFL) is an emerging technology that has shown to reduce significant amounts of biosolids quickly and produce larvae biomass containing low heavy metal concentrations. However, to the best of our knowledge, this is the first study investigating the transfer of pathogens and ARGs from biosolids into the process' end-products, BSFL and frass.
View Article and Find Full Text PDFUnlabelled: Early identification of stroke symptoms is essential. The rate of stroke identification by call-takers at emergency medical communication centres (EMCCs) varies, and patients who are found in a lying down position are often not identified as having an ongoing stroke.
Objectives: this study aimed to explore signs and symptoms of stroke in patients who had fallen or were found in a lying position.
Partially automated driving functions (SAE Level 2) can control a vehicle's longitudinal and lateral movements. However, taking over the driving task involves automation risks that the driver must manage. In severe accidents, the driver's ability to avoid a collision must be assessed, considering their expected reaction behavior.
View Article and Find Full Text PDFUnderstanding allosteric regulation in biomolecules is of great interest to pharmaceutical research and computational methods emerged during the last decades to characterize allosteric coupling. However, the prediction of allosteric sites in a protein structure remains a challenging task. Here, we integrate local binding site information, coevolutionary information, and information on dynamic allostery into a structure-based three-parameter model to identify potentially hidden allosteric sites in ensembles of protein structures with orthosteric ligands.
View Article and Find Full Text PDFUbiquitin-specific proteases represent a family of enzymes that catalyze the cleavage of ubiquitin from specific substrate proteins to regulate their activity. USP48 is a rarely studied USP, which has recently been linked to inflammatory signaling via regulation of the transcription factor nuclear factor kappa B. Nonetheless, a crystal structure of USP48 has not yet been resolved and potent inhibitors are not known.
View Article and Find Full Text PDFUltraviolet (UV) light induces different classes of mutagenic photoproducts in DNA, namely cyclobutane pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and atypical thymine-adenine photoproducts (TA-PPs). CPD formation is modulated by nucleosomes and transcription factors (TFs), which has important ramifications for Ultraviolet (UV) mutagenesis. How chromatin affects the formation of 6-4PPs and TA-PPs is unclear.
View Article and Find Full Text PDFUltraviolet (UV) light is a pervasive threat to the DNA of terrestrial organisms. UV light induces helix-distorting DNA lesions, primarily cyclobutane pyrimidine dimers (CPDs) that form between neighboring pyrimidine bases. Unrepaired CPD lesions cause cytosine-to-thymine (C>T) substitutions in dipyrimidine sequences, which is the predominant mutation class in skin cancer genomes.
View Article and Find Full Text PDFPurpose: To describe the occurrence of corneal thinning in a patient following intrastromal injection of bevacizumab to treat lipid keratopathy.
Observations: A 36-year-old female presented with decreased vision in her right eye with central posterior corneal haze and underwent a treatment regimen including artificial tears, cyclosporine 0.05% drops, prednisolone 1% and oral Valacyclovir 1g with no improvement.
Background: Pre-hospital emergency nurse (PEN) specialists are faced with patients presenting with non-specific chief complaints (NSC) to the emergency medical service (EMS) on a daily basis. These patients are often elderly and one in three has a serious condition and their acuity is not recognized.
Objective: The aim of the current study was to explore PEN specialists' experiences in caring for patients presenting with non-specific chief complaints.
The relevance of scientific investigations, whether simulative or empirical, is strongly related to the environment used and the scenarios associated with it. Within the field of cooperative intelligent transport systems, use-cases are defined to describe the benefits of applications. This has already been conducted in the available safety-relevant Day 1 applications longitudinal and intersection collision risk warning through the respective technical specifications.
View Article and Find Full Text PDFImmune checkpoint blockade (ICB) therapy is a central pillar of melanoma treatment leading to durable response rates. Important mechanisms of action of ICB therapy include disinhibition of CD4 and CD8 T cells. Stimulated CD4 T helper 1 cells secrete the effector cytokines interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF), which induce senescence in tumor cells.
View Article and Find Full Text PDFObjectives: To explore the emergency medical dispatchers (EMDs) experiences of managing emergency medical calls.
Design: A qualitative interview study with an inductive approach. EMDs were interviewed individually using a semistructured interview guide.
The purpose of this clinical series was to evaluate the clinical and radiographic outcomes of 20 zirconia dental implants, with a minimum follow-up of two years. Patients with at least one zirconia dental implant were included, with a mean follow-up of 34.05 months.
View Article and Find Full Text PDFPurpose: The combination of glaucoma drainage device (GDI), pars plana vitrectomy (PPV), and corneal transplantation is well reported in adults. However, little is known about the outcomes of such combined procedures in pediatric patients. We present a retrospective, single-center study to evaluate the safety and outcomes of concurrent GDI and/or PPV with corneal transplantation in patients 18 years and younger.
View Article and Find Full Text PDFNIMA-related kinase 1 (Nek1) has lately garnered attention for its widespread function in ciliogenesis, apoptosis, and the DNA-damage response. Despite its involvement in various diseases and its potential as a cancer drug target, no directed medicinal chemistry efforts toward inhibitors against this dark kinase are published. Here, we report the structure-guided design of a potent small-molecule Nek1 inhibitor, starting from a scaffold identified by kinase cross-screening analysis.
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