Compound heterozygous TMEM67 biallelic variants including a novel frameshift mutation in two Filipino adolescent siblings with Joubert syndrome.

Joubert Syndrome (JS) is a congenital cerebellar ataxia typically inherited in an autosomal recessive pattern, although rare X-linked inheritance can occur. It is characterized by hypotonia evolving into ataxia, global developmental delay, oculomotor apraxia, breathing dysregulation, and multiorgan involvement. To date, there are 40 causative genes implicated in JS, all of which encode proteins of the primary cilium.

Novel relatives of Mecsek Mountains mammarenavirus (family Arenaviridae) in hedgehogs living in different sampling areas in Hungary.

Mammarenaviruses (genus Mammarenavirus, family Arenaviridae) are rodent-borne zoonotic viruses consisting of 52 viral species, including ten that are pathogenic to humans. Currently, only two endemic mammarenavirus species are known in Europe: the human pathogenic Mammarenavirus choriomeningitidis (LCMV) and the recently discovered hedgehog-origin Mammarenavirus mecsekense (MEMV). In this study, 59 faecal specimens from Northern white-breasted hedgehogs (Erinaceus roumanicus) from different geographic regions in Hungary were investigated for mammarenavirus presence and complete genome characterization using newly designed screening primers by RT-semi-nested PCR and sequencing methods.

Insect frass fertilizer as soil amendment for improved forage and soil health in circular systems.

Insect farming is expected to increase in coming years, thus generating high quantities of frass (insect excreta). Frass valorization hinges on basic agronomic research prior to industry upscaling. Here, we investigated soil physiochemical properties, SMAF (Soil Management Assessment Framework) soil health, CO efflux, and bermudagrass [Cynodon dactylon (L.

Cushing syndrome.

Cushing syndrome (CS) is a constellation of signs and symptoms caused by excessive exposure to exogenous or endogenous glucocorticoid hormones. Endogenous CS is caused by increased cortisol production by one or both adrenal glands (adrenal CS) or by elevated adrenocorticotropic hormone (ACTH) secretion from a pituitary tumour (Cushing disease (CD)) or non-pituitary tumour (ectopic ACTH secretion), which stimulates excessive cortisol production. CS is associated with severe multisystem morbidity, including impaired cardiovascular and metabolic function, infections and neuropsychiatric disorders, which notably reduce quality of life.

Characterizing safety, toxicity, and breast cancer risk reduction using a long-term fulvestrant eluting implant.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure.

Erector spinae plane block for management of acute opioid withdrawal in the emergency department: A case report.

Background: Gastrointestinal symptoms of acute opioid withdrawal are distressing for patients and are often difficult to manage with conventional therapies. Insufficiently managed opioid withdrawal symptoms may lead patients to leave against medical advice, which can increase their risk of relapse and result in poor outcomes from untreated conditions. We assessed the impact of an erector spinae plane block on the acute gastrointestinal symptoms of opioid withdrawal.

Nanoplastics in focus: Exploring interdisciplinary approaches and future directions.

Nanoplastics (NPs) are gaining increasing attention due to their widespread distribution and potential environmental and biological impacts. Spanning a variety of ecosystems - from soils and rivers to oceans and polar ice - NPs interact with complex biological and geochemical processes, posing risks to organisms across multiple trophic levels. Despite their growing presence, understanding the behavior, transport, and toxicity of nanoplastics remains challenging due to their diverse physical and chemical properties as well as the heterogeneity of environmental matrices.

Development of a curcumin-piperine nanoparticle system using dissolving microneedles for transdermal drug delivery in malaria treatment: In vitro evaluation.

The combination of the active compounds curcumin and piperine (CP) is effective as an antimalarial; however, the solubility and bioavailability of CP are very low. This study aims to formulate CP in nanoparticles (NP), which are then fabricated into dissolving microneedles (DMN). The NPs were prepared with a concentration ratio of CP-Chitosan-So.

Robotic versus manual disinfection of global priority pathogens at COVID-19 dedicated hospitals.

Background: Twelve bacterial families were identified as global priority pathogens by the World Health Organization in 2017, recognizing the greatest threat they pose to human health and the declining antibiotic efficacy. Robotics has emerged as a swift and contactless tool for disinfecting bacterial surface contamination in healthcare facilities, however, head-to-head comparison of disinfection efficacy of robotic versus manual disinfections is limited. This study aimed at comparing how robotic disinfection performs over manual disinfection against the global priority pathogens in the healthcare setting.

The regulatory mechanism controlling nitrification inhibitors-induced mitigation of nitrification and NO-N leaching in alkaline purple soil.

Nitrification inhibitors (NIs) are critical to reduce nitrogen (N) leaching losses. However, the efficacy of different NIs can be highly variable across soils and crop types, and a deeper understanding of the mechanistic basis of this efficiency variation, especially in purple soil under vegetable production, is lacking. To enrich this knowledge gap, the impact of different NIs amendment (3,4-dimethylpyrazole phosphate, DMPP; dicyandiamide, DCD; nitrapyrin, NP) on nitrification and the microbial mechanistic basis of controlling nitrate (NO-N) leaching of vegetable purple soil was explored in southwest China.

Nanoplastic in aqueous environments: The role of chemo-electric properties for nanoplastic-mineral interaction.

Due to increasing plastic production, the continuous release of primary and secondary nanoplastic particles (NPs, <1 μm) has become an emerging contaminant in terrestrial environments. The fate and transport of NPs in subsurface environments remain poorly understood, largely due to the complex interplay of mineralogical, chemical, biological, and morphological heterogeneity. This study examines interactions between abundant subsurface minerals and NPs under controlled water chemistry (1 mM KCl, pH 5.

Heavy metal(loid)s and nutrients in sewage sludge in Portugal - Suitability for use in agricultural soils and assessment of potential risks.

The presence of heavy metal(loid)s in sewage sludge is a cause of concern and an obstacle to its agricultural valorisation. This study analysed the elemental composition of sewage sludge from 42 Portuguese wastewater treatment plants (WWTPs) during summer and winter, investigating heavy metal(loid) contamination, nutrient content, and potential risks related to sludge application to agricultural soils. Levels of 8 heavy metal(loid)s were investigated, ranging from not detected (Hg) to 5120 mg kg dw (Zn), decreasing in the order Zn > Cu > Cr > Ni > Pb > As>Cd > Hg.

An injectable nanocomposite hydrogel with deep penetration ability for enhanced photothermal and chemotherapy.

The excessive extracellular matrix (ECM) in solid tumors significantly inhibits the deep penetration and homogeneous distribution of nanodrugs, which greatly reduces the therapeutic efficacy. In the present work, an injectable polyelectrolyte hydrogel (CD@IPH) containing collagenase and doxorubicin-loaded polyacrylic acid@polyaniline nanoparticles (DOX@NP) were developed for improved photothermal and chemotherapy. The collagenase is released quickly from the polyelectrolyte hydrogel in the first 12 h, effectively degrading ECM and enhancing the deep penetration and evenly distribution of DOX@NP in tumor tissues.

Harmonizing excellence: Crafting the nexus of competencies, standards, and degree demands in nurse practitioner education.

Nurse practitioner (NP) programs have a long history of producing safe and competent NPs; however, bold, transformative leadership is needed to set a minimum standard for quality NP education to support a 21st-century healthcare system. This paper is a call to action for leaders in NP education to transition NP education to the DNP degree utilizing the 2022 National Task Force Standards for Quality NP Education and a competency-based approach as defined in the 2021 AACN Essentials. There is now an opportunity to redesign healthcare systems with quality and equity as a primary consideration and DNP-prepared NPs are positioned to lead this redesign.

Peripheral Evolution of Tanshinone IIA and Cryptotanshinone for Discovery of a Potent and Specific NLRP3 Inflammasome Inhibitor.

Natural products (NPs) continue to serve as an invaluable source in drug discovery, and peripheral evolution of NPs is a highly efficient evolution strategy. Herein, we describe a unified "methyl to amide" peripheral evolution of Tanshinone IIA and Cryptotanshinone for discovery of NLRP3 inflammasome inhibitors. There were 54 compounds designed and prepared, while the chemoinformatic analysis revealed that these evolved NP analogues occupy a unique chemical space.

Painful diabetic neuropathy is associated with accelerated epigenetic aging.

About one out of two diabetic patients develop diabetic neuropathy (DN), of these 20% experience neuropathic pain (NP) leading to individual, social, and health-economic burden. Risk factors for NP are largely unknown; however, premature aging was recently associated with several chronic pain disorders. DNA methylation-based biological age (DNAm) is associated with disease risk, morbidity, and mortality in different clinical settings.

Harnessing Anti-Inflammatory and Regenerative Potential: GelMA Hydrogel Loaded with IL-10 and Kartogenin for Intervertebral Disc Degeneration Therapy.

Intervertebral disc degeneration (IVDD) is a major contributor to chronic back pain and disability, with limited effective therapeutic options. Current treatment options, including conservative management and surgical interventions, often fail to effectively halt disease progression and come with notable side effects. IVDD is characterized by the breakdown of the extracellular matrix (ECM) and the infiltration of inflammatory cells, which exacerbate disc degeneration.

Outcomes of a PA/APRN grand rounds pilot: A novel model for increasing engagement.

This article describes a framework for the development, implementation, and effect of advanced practice provider (APP) grand rounds. A team of certified registered nurse anesthetists (CRNAs), NPs, and physician associates/assistants (PAs) developed and operationalized a grand rounds initiative in 2019. Since January 2020, 34 live monthly learning sessions have been held in person and virtually.

Nanoplastic-Induced Developmental Toxicity in Ascidians: Comparative Analysis of Chorionated and Dechorionated Embryos.

Nanoplastics pose a growing threat to marine ecosystems, particularly affecting the early developmental stages of marine organisms. This study investigates the effects of amino-modified polystyrene nanoparticles (PS-NH, 50 nm) on the embryonic development of , a model ascidian species. Both chorionated and dechorionated embryos were exposed to increasing concentrations of PS-NH so morphological alterations could be assessed with a high-content analysis of the phenotypes and genotoxicity.

Fundamental Understanding of Bio-Nano Interface of Lysozyme on Polyphenol Coated Silver Nanoparticles: Mechanistic Insights into the Effect of Protein Corona on the Antibacterial Efficacy.

Recent times have witnessed revolutionary progress in the design and development of functionalized nanomaterials as promising tools for biomedicinal applications. However, the gap in the fundamental understanding of the "biological responses" of the nanomaterials after the formation of "protein-corona" when it is exposed to the body system has drawn a thin line from its discoveries to real clinical trial. In this article we have synthesized two different silver NPs capped with the polyphenols of (guava) leaf extract and the other with one of its major polyphenolic groups, morin.

Structural Characterization of the Platinum Nanoparticle Hydrogen-Evolving Catalyst Assembled on Photosystem I by Light-Driven Chemistry.

Directed assembly of abiotic catalysts onto biological redox protein frameworks is of interest as an approach for the synthesis of biohybrid catalysts that combine features of both synthetic and biological materials. In this report, we provide a multiscale characterization of the platinum nanoparticle (NP) hydrogen-evolving catalysts that are assembled by light-driven reductive precipitation of platinum from an aqueous salt solution onto the photosystem I protein (PSI), isolated from cyanobacteria as trimeric PSI. The resulting PSI-NP assemblies were analyzed using a combination of X-ray energy-dispersive spectroscopy (XEDS), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), small-angle X-ray scattering (SAXS), and high-energy X-ray scattering with atomic pair distribution function (PDF) analyses.

Influence of pain, sequential movement or short-term rest performance on the evaluation results of neck muscle mechanical properties: a case-control study.

Introduction: Individuals with neck pain (NP) often experience altered muscle mechanical properties (MMPs), such as increased tone and stiffness. Myotonometry has become a reliable, noninvasive tool for measuring MMPs. However, the effect of movement and rest on MMPs in acute neck pain (ANP) individuals remains insufficiently explored.

Molecular mechanisms behind the anti corona virus activity of small metal oxide nanoparticles.

The recent COVID-19 pandemic has set a strong quest for advanced understanding of possible tracks in abating and eliminating viral infections. In the view that several families of "pristine" small oxide nanoparticles (NPs) have demonstrated viricidal activity against SARS-CoV-2, we studied the effect of two NPs, with presumably different reactivity, on two viruses aiming to evaluate two "primary suspect" routes of their antiviral activity, either specific blocking of surface proteins or causing membrane disruption. The chosen NPs were non-photoactive 3.

Random Survival Forest Machine Learning for the Prediction of Cardiovascular Events Among Patients With a Measured Lipoprotein(a) Level: A Model Development Study.

Background: Established risk models may not be applicable to patients at higher cardiovascular risk with a measured Lp(a) (lipoprotein[a]) level, a causal risk factor for atherosclerotic cardiovascular disease.

Methods: This was a model development study. The data source was the Nashville Biosciences Lp(a) data set, which includes clinical data from the Vanderbilt University Health System.