The University of Kentucky's Drug Quality Task Force (DQTF) conducted a study to perform consumer-level quality assurance screening of vasopressin injections used in their healthcare pharmacies. The primary objective was to identify potential quality defects by examining intralot and interlot variability using Raman spectrometry and statistical analyses. Raman spectra were collected noninvasively and nondestructively from vasopressin vials (n=51) using a Thermo Scientific Smartraman DXR3 Analyzer.
View Article and Find Full Text PDFThe development of precise and efficient detection methods is essential for the real-time monitoring of antibiotics, especially in environmental and biological matrices. This study aims to address this challenge by introducing a novel electrochemical sensor for the targeted detection of moxifloxacin hydrochloride (MFN), a fourth-generation fluoroquinolone. The sensor is based on a holmium niobate (HNO) and functionalized carbon nanofiber (f-CNF) nanocomposite, synthesized via a hydrothermal approach and subsequently characterized for its structural and electrochemical properties.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
The establishment of reproductive barriers such as postzygotic ybrid ncompatibility (HI) remains the key to speciation. Gene duplication followed by differential functionalization has long been proposed as a major model underlying HI, but little supporting evidence exists. Here, we demonstrate that a newborn F-box gene, , of the nematode specifically inactivates an essential phosphoglucomutase encoded by in its sister species and their hybrids.
View Article and Find Full Text PDFTransposable elements (TEs) can alter host gene structure and expression, whereas host organisms develop mechanisms to repress TE activities. In the nematode , a small interfering RNA pathway dependent on the helicase ERI-6/7 primarily silences retrotransposons and recent genes of likely viral origin. By studying gene expression variation among wild strains, we found that structural variants and transposon remnants likely underlie expression variation in and the pathway targets.
View Article and Find Full Text PDFAfrican wild dogs (Lycaon pictus) are unique among canids in their specialized hunting strategies and social organization. Unlike other, more omnivorous canids, L. pictus is a hypercarnivore that consumes almost exclusively meat, particularly prey larger than its body size, which it hunts through cooperative, exhaustive predation tactics.
View Article and Find Full Text PDFJ Antimicrob Chemother
October 2024
Background: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates.
Objectives: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality.
Methods: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil.
A total of 55 food and clinical . Schwarzengrund isolates were assayed for plasmid content, among which an IncFIB-IncFIC(FII) fusion plasmid, conferring streptomycin resistance, was detected in 17 isolates. Among the 17 isolates, 9 were food isolates primarily collected from poultry meat, and 8 clinical isolates collected from stool, urine, and gallbladder.
View Article and Find Full Text PDFChlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide.
View Article and Find Full Text PDFThe African wild dog (Lycaon pictus) is a highly social canid that engages in sophisticated, coordinated group hunting tactics to procure large game. It is one of the most effective hunters of the African savannah, due to its highly developed communication methods. It also has large, mobile ears which enhance its auditory capabilities while hunting and assist with thermoregulation.
View Article and Find Full Text PDFanimals with a compromised pharynx accumulate bacteria in their intestinal lumen and activate a transcriptional response that includes anti-bacterial response genes. In this study, we demonstrate that animals with defective pharynxes are resistant to Orsay virus (OrV) infection. This resistance is observed for animals grown on OP50 and on BIGb0172, a bacterium naturally associated with .
View Article and Find Full Text PDFClin Ther
April 2024
Purpose: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC.
Methods: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals.
The model organism Caenorhabditis elegans is susceptible to infection by obligate intracellular pathogens, specifically microsporidia and viruses. These intracellular pathogens infect intestinal cells, or, for some microsporidia, epidermal cells. Strikingly, intestinal cell infections by viruses or microsporidia trigger a common transcriptional response, activated in part by the ZIP-1 transcription factor.
View Article and Find Full Text PDFMicrobes associated with an organism can significantly modulate its susceptibility to viral infections, but our understanding of the influence of individual microbes remains limited. The nematode Caenorhabditis elegans is a model organism that in nature inhabits environments rich in bacteria. Here, we examine the impact of 71 naturally associated bacteria on C.
View Article and Find Full Text PDFThis study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot.
View Article and Find Full Text PDFPurpose: The University of Kentucky Drug Quality Study team briefly reviews the growing concerns over pharmaceutical manufacturing quality in the globalized environment, reviews the historical approach by the US Food and Drug Administration (FDA) that prioritizes process over product in enforcing quality with manufacturers, reviews the science of process analytical technology (PAT) such as near-infrared (NIR) spectroscopy, illustrates the use of PAT methods for assessing uniformity and quality in injectable pharmaceuticals, and demonstrates the application of NIR spectroscopy in a health-system pharmacy setting while maintaining current good practice quality guidelines and regulations (cGxP).
Summary: Given that the current approach to monitoring quality in pharmaceutical manufacturing was developed in the late 1960s at a time when manufacturing was mostly domestic, the current approach prioritizes process over product, and the global footprint of manufacturing is straining federal resources to fulfill their task of monitoring quality, an approach to augment the quality monitoring process has been developed. PAT methodologies are supported by FDA for monitoring quality and offer a fast, low-cost, nondestructive solution.
In , the QR neuroblast and its progeny migrate from the posterior to the anterior part of the animal during the L1 stage. We previously showed that the final position of QR.pa daughters varies among wild isolates, with CB4932 displaying a particularly anterior QR.
View Article and Find Full Text PDFMany developmental processes depend on precise temporal control of gene expression. We have previously established a theoretical framework for regulatory strategies that can govern such high temporal precision, but experimental validation of these predictions was still lacking. Here, we use the time-dependent expression of a Wnt receptor that controls neuroblast migration in as a tractable system to study a robust, cell-intrinsic timing mechanism in vivo.
View Article and Find Full Text PDFSM03, an anti-CD22 recombinant IgG1 mAb, is currently in a phase III clinical trial for the treatment of rheumatoid arthritis (NCT04312815). SM03 showed good safety and efficacy in phase I systemic lupus erythematosus and phase II moderate to severe rheumatoid arthritis clinical trials. We propose the success of SM03 as a therapeutic to systemic autoimmune diseases is through the utilization of a novel mechanism of action unique to SM03.
View Article and Find Full Text PDFIntracellular pathogens are challenged with limited space and resources while replicating in a single host cell. Mechanisms for direct invasion of neighboring host cells have been discovered in cell culture, but we lack an understanding of how bacteria directly spread between host cells in vivo. Here, we describe the discovery of intracellular bacteria that use filamentation for spreading between the intestinal epithelial cells of a natural host, the rhabditid nematode Oscheius tipulae.
View Article and Find Full Text PDFFront Cell Infect Microbiol
November 2021
Oomycetes are a group of eukaryotic organisms that includes many important pathogens of animals and plants. Within this group, the genus is characterised by the presence of specialised gun cells carrying a harpoon-like infection apparatus. While several pathogens have been morphologically described, there are currently no host systems developed to study the infection process or host responses in the lab.
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