The effects of RT-qPCR standards on reproducibility and comparability in monitoring SARS-CoV-2 levels in wastewater.

Reverse transcription-quantitative PCR (RT-qPCR) is widely used for monitoring viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in wastewater. Various materials, including plasmid DNA, synthetic nucleic acids, PCR amplicons, genomic DNA, and cDNA, are currently used for SARS-CoV-2 quantification by generating standard curves. We assessed three common standards on quantifying SARS-CoV-2 RNA across nine wastewater treatment plants in Finland, as part of the national wastewater surveillance effort.

Simultaneous biomass concentration and subsequent quantitation of multiple infectious disease agents and antimicrobial resistance genes from community wastewater.

Wastewater-based surveillance (WBS) of infectious disease agents is increasingly seen as a reliable source of population health data. To date, wastewater-based surveillance efforts have largely focused on individual pathogens. However, given that wastewater contains a broad range of pathogens circulating in the population, a more comprehensive approach could enhance its usability.

Comparison of Different Reverse Transcriptase-Polymerase Chain Reaction-Based Methods for Wastewater Surveillance of SARS-CoV-2: Exploratory Study.

Background: Many countries have applied the wastewater surveillance of the COVID-19 pandemic to their national public health monitoring measures. The most used methods for detecting SARS-CoV-2 in wastewater are quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and reverse transcriptase-droplet digital polymerase chain reaction (RT-ddPCR). Previous comparison studies have produced conflicting results, thus more research on the subject is required.

Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

Background And Objectives: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH).

Methods: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records.

Wastewater-based surveillance is an efficient monitoring tool for tracking influenza A in the community.

Around the world, influenza A virus has caused severe pandemics, and the risk of future pandemics remains high. Currently, influenza A virus surveillance is based on the clinical diagnosis and reporting of disease cases. In this study, we apply wastewater-based surveillance to monitor the amount of the influenza A virus RNA at the population level.

Detection of SARS-COV-2 variants and their proportions in wastewater samples using next-generation sequencing in Finland.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants may have different characteristics, e.g., in transmission, mortality, and the effectiveness of vaccines, indicating the importance of variant detection at the population level.

Developing wastewater-based surveillance schemes for multiple pathogens: The WastPan project in Finland.

Wastewater comprises multiple pathogens and offers a potential for wastewater-based surveillance (WBS) to track the prevalence of communicable diseases. The Finnish WastPan project aimed to establish wastewater-based pandemic preparedness for multiple pathogens (viruses, bacteria, parasites, fungi), including antimicrobial resistance (AMR). This article outlines WastPan's experiences in this project, including the criteria for target selection, sampling locations, frequency, analysis methods, and results communication.

Clinically relevant sequence types of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae detected in Finnish wastewater in 2021-2022.

Background: Antimicrobial resistance (AMR) is a critical threat to human health. Escherichia coli and Klebsiella pneumoniae are clinically the most important species associated with AMR and are the most common carbapenemase-producing (CP) Enterobacterales detected in human specimens in Finland. Wastewater surveillance has emerged as a potential approach for population-level surveillance of AMR, as wastewater could offer a reflection from a larger population with one sample and minimal recognized ethical issues.

Genomic epidemiology of nosocomial carbapenemase-producing in sewerage systems in the Helsinki metropolitan area, Finland.

Multi-drug resistance is emerging in , which is the third most common carbapenemase-producing (CP) in humans in Finland due to recent outbreaks. The objective of this study was to determine if wastewater surveillance (WWS) could detect CP strains causing infections in humans. Selective culturing was used to isolate CP from the hospital environment, hospital wastewater, and untreated municipal wastewater in Helsinki, Finland, between 2019 and 2022.

Gene Expression Profile as a Predictor of Seizure Liability.

Analysis platforms to predict drug-induced seizure liability at an early phase of drug development would improve safety and reduce attrition and the high cost of drug development. We hypothesized that a drug-induced in vitro transcriptomics signature predicts its ictogenicity. We exposed rat cortical neuronal cultures to non-toxic concentrations of 34 compounds for 24 h; 11 were known to be ictogenic (tool compounds), 13 were associated with a high number of seizure-related adverse event reports in the clinical FDA Adverse Event Reporting System (FAERS) database and systematic literature search (FAERS-positive compounds), and 10 were known to be non-ictogenic (FAERS-negative compounds).

Wastewater surveillance of antibiotic-resistant bacterial pathogens: A systematic review.

Infectious diseases caused by antibiotic-resistant bacterial (ARB) pathogens are a serious threat to human and animal health. The active surveillance of ARB using an integrated one-health approach can help to reduce the emergence and spread of ARB, reduce the associated economic impact, and guide antimicrobial stewardship programs. Wastewater surveillance (WWS) of ARB provides composite samples for a total population, with easy access to the mixed community microbiome.

Detection and quantification of SARS-CoV-2 RNA in wastewater influent in relation to reported COVID-19 incidence in Finland.

Wastewater-based surveillance is a cost-effective concept for monitoring COVID-19 pandemics at a population level. Here, SARS-CoV-2 RNA was monitored from a total of 693 wastewater (WW) influent samples from 28 wastewater treatment plants (WWTP, N = 21-42 samples per WWTP) in Finland from August 2020 to May 2021, covering WW of ca. 3.

Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury.

We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug -acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% ( < 0.

Regulation of Parvalbumin Interactome in the Perilesional Cortex after Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) causes 10-20% of structural epilepsy, with seizures typically originating in the cortex. Alterations in the neuronal microcircuits in the cortical epileptogenic zone, however, are poorly understood. Here, we assessed TBI-induced changes in perisomatic gamma aminobutyric acid (GABA)-ergic innervation in the perilesional cortex.

Plau/Plaur double-deficiency did not worsen lesion severity or vascular integrity after traumatic brain injury.

Binding of urokinase-type plasminogen activator receptor (uPAR) to its ligand uPA or to its plasma membrane partner, platelet-derived growth factor receptor β (PDGFRβ), promotes neuroprotection, cell proliferation, and angiogenesis. Following injury, single deficiency in uPA or uPAR leads in increased tissue loss and compromised vascular remodeling. We hypothesized that double-deficiency of uPAR (Plaur) and uPA (Plau) would result in increased lesion area and poor vascular integrity after traumatic brain injury (TBI).

Dynamics of clusterin protein expression in the brain and plasma following experimental traumatic brain injury.

Progress in the preclinical and clinical development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI) necessitates the discovery of prognostic biomarkers for post-injury outcome. Our previous mRNA-seq data revealed a 1.8-2.

In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury-Lessons Learned.

We developed a pipeline for the discovery of transcriptomics-derived disease-modifying therapies and used it to validate treatments in vitro and in vivo that could be repurposed for TBI treatment. Desmethylclomipramine, ionomycin, sirolimus and trimipramine, identified by in silico LINCS analysis as candidate treatments modulating the TBI-induced transcriptomics networks, were tested in neuron-BV2 microglial co-cultures, using tumour necrosis factor α as a monitoring biomarker for neuroinflammation, nitrite for nitric oxide-mediated neurotoxicity and microtubule associated protein 2-based immunostaining for neuronal survival. Based on (a) therapeutic time window in silico, (b) blood-brain barrier penetration and water solubility, (c) anti-inflammatory and neuroprotective effects in vitro ( < 0.

Extracellular Vesicles as Diagnostics and Therapeutics for Structural Epilepsies.

Extracellular vesicles (EVs) are small vesicles involved in intercellular communication. Data is emerging that EVs and their cargo have potential as diagnostic biomarkers and treatments for brain diseases, including traumatic brain injury and epilepsy. Here, we summarize the current knowledge regarding changes in EV numbers and cargo in status epilepticus (SE) and traumatic brain injury (TBI), which are clinically significant etiologies for acquired epileptogenesis in animals and humans.

Deficiency of urokinase-type plasminogen activator and its receptor affects social behavior and increases seizure susceptibility.

Extracellular proteolysis initiated by the binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) regulates the development of inhibitory neuronal circuits in the cerebral cortex and tissue remodeling after epileptogenic brain injury. To study the function of different components of the uPA-uPAR system on behavior and epileptogenesis, and to complement our previous studies on naïve and injured mice deficient in the uPA-encoding gene Plau or the uPAR-encoding gene Plaur, we analyzed the behavioral phenotype, seizure susceptibility, and perineuronal nets surrounding parvalbumin-positive inhibitory interneurons in Plau and Plaur (double knockout dKO) mice. In a climbing test, dKO mice showed reduced interest towards the environment as compared with Wt mice (p < 0.

Precipitation-based extracellular vesicle isolation from rat plasma co-precipitate vesicle-free microRNAs.

The microRNA (miRNA) cargo contained in plasma extracellular vesicles (EVs) offers a relatively little explored source of biomarkers for brain diseases that can be obtained noninvasively. Methods to isolate EVs from plasma, however, are still being developed. For EV isolation, it is important to ensure the removal of vesicle-free miRNAs, which account for approximately two-thirds of plasma miRNAs.

Age- and quality-dependent DNA methylation correlate with melanin-based coloration in a wild bird.

Secondary sexual trait expression can be influenced by fixed individual factors (such as genetic quality) as well as by dynamic factors (such as age and environmentally induced gene expression) that may be associated with variation in condition or quality. In particular, melanin-based traits are known to relate to condition and there is a well-characterized genetic pathway underpinning their expression. However, the mechanisms linking variable trait expression to genetic quality remain unclear.

Effect of resource availability on evolution of virulence and competition in an environmentally transmitted pathogen.

Understanding ecological and epidemiological factors driving pathogen evolution in contemporary time scales is a major challenge in modern health management. Pathogens that replicate outside the hosts are subject to selection imposed by ambient environmental conditions. Increased nutrient levels could increase pathogen virulence by pre-adapting for efficient use of resources upon contact to a nutrient rich host or by favouring transmission of fast-growing virulent strains.

Transcription factors Tp73, Cebpd, Pax6, and Spi1 rather than DNA methylation regulate chronic transcriptomics changes after experimental traumatic brain injury.

Traumatic brain injury (TBI) induces a wide variety of cellular and molecular changes that can continue for days to weeks to months, leading to functional impairments. Currently, there are no pharmacotherapies in clinical use that favorably modify the post-TBI outcome, due in part to limited understanding of the mechanisms of TBI-induced pathologies. Our system biology analysis tested the hypothesis that chronic transcriptomics changes induced by TBI are controlled by altered DNA-methylation in gene promoter areas or by transcription factors.