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Objective: The objective of this study was to evaluate the association of nocturia and urinary urgency with reproductive factors, including parity, the postpartum period, the menopause, hormone replacement therapy, hysterectomy, and surgery for stress urinary incontinence (SUI). Study Design: In 2003-2004, questionnaires eliciting urinary symptoms, reproductive factors, SUI surgery, and potential confounders were mailed to 3000 randomly selected women aged 18-79 years, identified from the Finnish Population Register. Nocturia was defined as 2 or more voids/night. Sudden compelling desire to urinate often or always (scale of never, rarely, often, always) was regarded as urgency. Pregnant and puerperal (6 weeks after delivery) women and those reporting urinary tract infection were excluded. Results: Responses totaled 2002 (67%). Parity, postpartum (defined as six weeks to one year after delivery) and postmenopausal periods were associated with increased nocturia and SUI surgery with increased urgency (adjusted for age, comorbidity, medication, anthropometric, sociodemographic and lifestyle factors). Hormone therapy and hysterectomy were associated with neither symptom. Conclusion: Reproductive factors associated with nocturia differed from those related to urgency. [Copyright &y& Elsevier]

Background Although new therapeutic approaches for burn treatment have made progress, there is still need for better methods to enhance wound healing and recovery especially in severely burned patients. Nanofibrillar cellulose (NFC) has gained attention due to its renewable nature, good biocompatibility and excellent physical properties that are of importance for a range of applications in pharmaceutical and biomedical fields. In the present study, we investigated the potential of a wood based NFC wound dressing in a clinical trial on burn patients. Previously, we have investigated NFC as a topical functionalized wound dressing that contributes to improve wound healing in mice. Methods Wood based NFC wound dressing was tested in split-thickness skin graft donor site treatment for nine burn patients in clinical trials at Helsinki Burn Centre. NFC dressing was applied to split thickness skin graft donor sites. The dressing gradually dehydrated and attached to donor site during the first days. During the clinical trials, physical and mechanical properties of NFC wound dressing were optimized by changing its composition. From patient 5 forward, NFC dressing was compared to commercial lactocapromer dressing, Suprathel® (PMI Polymedics, Germany). Results Epithelialization of the NFC dressing-covered donor site was faster in comparison to Suprathel®. Healthy epithelialized skin was revealed under the detached NFC dressing. NFC dressing self-detached after 11–21 days for patients 1–9, while Suprathel® self-detached after 16–28 days for patients 5–9. In comparison studies with patients 5–9, NFC dressing self-detached on average 4 days earlier compared with Suprathel®. Lower NFC content in the material was evaluated to influence the enhanced pliability of the dressing and attachment to the wound bed. No allergic reaction or inflammatory response to NFC was observed. NFC dressing did not cause more pain for patients than the traditional methods to treat the skin graft donor sites. Conclusion Based on the preliminary clinical data, NFC dressing seems to be promising for skin graft donor site treatment since it is biocompatible, attaches easily to wound bed, and remains in place until donor site has renewed. It also detaches from the epithelialized skin by itself. [ABSTRACT FROM AUTHOR]

In this work, we describe an improved series of N-phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective against high-priority gram-positive bacteria. The most potent compounds show low nanomolar IC 50 values against Escherichia coli DNA gyrase, and in addition, compound 7c also inhibits E. coli topoisomerase IV in the nanomolar concentration range, making it a promising candidate for the development of potent dual inhibitors for these enzymes. All tested compounds show high selectivity towards the human isoform DNA topoisomerase IIα. Compounds 6a, 6d, 6e and 6f show MIC values between 0.031 and 0.0625 μg/mL against vancomycin-intermediate S. aureus (VISA) and Enterococcus faecalis strains. Compound 6g shows an inhibitory effect against the methicillin-resistant S. aureus strain (MRSA) with a MIC of 0.0625 μg/mL and against the E. faecalis strain with a MIC of 0.125 μg/mL. In a time-kill assay, compound 6d showed a dose-dependent bactericidal effect on the MRSA strain and achieved bactericidal activity at 8 × MIC after 8 h. The duration of the post-antibiotic effect (PAE) on the MRSA strain for compound 6d was 2 h, which corresponds to the PAE duration for ciprofloxacin. The compounds were not cytotoxic at effective concentrations, as determined in an MTS assay on the MCF-7 breast cancer cell line., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nace Zidar reports financial support was provided by Slovenian Research Agency. Cristina D. Cruz, Paivi Tammela reports financial support was provided by Research Council of Finland. Marton Simon Czikkely reports financial support was provided by Hungarian Ministry of Culture and Innovation. Nace Zidar has patent New N-phenylpyrrolamide inhibitors of DNA gyrase and topoisomerase IV with antibacterial activity pending to University of Ljubljana. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, the non-standardized design of these chips and perfusion control systems has been a barrier to quantitative high-throughput screening (HTS). Here we present a scalable OOC microfluidic platform for applied kinetic in vitro assays (AKITA) that is applicable for high, medium, and low throughput. Its standard 96-well plate and 384-well plate layouts ensure compatibility with existing laboratory workflows and high-throughput data collection and analysis tools. The AKITA plate is optimized for the modeling of vascularized biological barriers, primarily the blood-brain barrier, skin, and lung, with precise flow control on a custom rocker. The integration of trans-epithelial electrical resistance (TEER) sensors allows rapid and repeated monitoring of barrier integrity over long time periods. Together with automated liquid handling and compound permeability testing analyses, we demonstrate the flexibility of the AKITA platform for establishing human-relevant models for preclinical drug and precision medicine's efficacy, toxicity, and permeability under near-physiological conditions.

Cryptophytes are a promising source of bioactive compounds that have not been fully explored. This research investigated the antimicrobial activity of total phenolic compounds (TPC) and exopolysaccharides (EPS) extracted from several cryptophytes against a range of harmful foodborne bacteria and fungi. To measure the minimum inhibitory concentration (MIC) value, the broth microdilution method was used. In the antibacterial evaluation of TPC, the MIC ranged between 31.25 and 500 μg/mL, while for the antifungal activity test, it varied from 31.25 to 125 μg/mL. In the antibacterial activity test of EPS, the MIC values ranged from 125 to 1,000 μg/mL, whereas in the antifungal susceptibility test, it ranged between 62.5 and 1,000 μg/mL. The most resistant pathogen against TPC was Escherichia coli , while Campylobacter jejuni was the most susceptible. In the case of EPS, the most resistant pathogen was Salmonella Typhimurium, while Aspergillus versicolor exhibited the highest susceptibility. Overall, in terms of antimicrobial activity, TPC was more effective than EPS. Finally, the tolerance level (TL) for TPC and EPS was ≤4 in all tested samples, indicating their bactericidal/fungicidal mechanism of action. In conclusion, TPC and EPS isolated from cryptophytes demonstrated remarkable antimicrobial properties and ability to fully eradicate pathogens, and could be considered as natural preservatives in the food industry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abidizadegan, Peltomaa, Ilina, Tammela and Blomster.)

This study presents the discovery of a new series of N -phenylpyrrolamide inhibitors of bacterial DNA gyrase with improved antibacterial activity. The most potent inhibitors had low nanomolar IC 50 values against Escherichia coli DNA gyrase (IC 50 ; 2-20 nM) and E. coli topoisomerase IV (22i, IC 50 = 143 nM). Importantly, none of the compounds showed activity against human DNA topoisomerase IIα, indicating selectivity for bacterial targets. Among the tested compounds, 22e emerged as the most effective against Gram-positive bacteria with minimum inhibitory concentration (MIC) values of 0.25 μg mL -1 against Staphylococcus aureus ATCC 29213 and MRSA, and 0.125 μg mL -1 against Enterococcus faecalis ATCC 29212. For Gram-negative bacteria, compounds 23b and 23c showed the greatest efficacy with MIC values ranging from 4 to 32 μg mL -1 against E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ATCC 17978 and A. baumannii ATCC 19606. Notably, compound 23b showed promising activity against the clinically relevant Gram-negative pathogen Klebsiella pneumoniae ATCC 10031, with an MIC of 0.0625 μg mL -1 . Furthermore, compounds 23a and 23c exhibited significantly lower susceptibility to resistance development compared to novobiocin in S. aureus ATCC 29213 and K. pneumoniae ATCC 10031. Overall, the most promising compounds of this series showed excellent on-target potency, marking a significant improvement over previous N -phenylpyrrolamide inhibitors., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

A considerable number of antibacterial agents are derived from bacterial metabolites. Similarly, numerous known compounds that impede bacterial virulence stem from bacterial metabolites. Enteropathogenic Escherichia coli (EPEC) is a notable human pathogen causing intestinal infections, particularly affecting infant mortality in developing regions. These infections are characterized by microvilli effacement and intestinal epithelial lesions linked with aberrant actin polymerization. This study aimed to identify potential antivirulence compounds for EPEC infections among bacterial metabolites harvested from marine actinobacteria ( Kocuria sp. and Rhodococcus spp.) from the Arctic Sea by the application of virulence-based screening assays. Moreover, we demonstrate the suitability of these antivirulence assays to screen actinobacteria extract fractions for the bioassay-guided identification of metabolites. We discovered a compound in the fifth fraction of a Kocuria strain that interferes with EPEC-induced actin polymerization without affecting growth. Furthermore, a growth-inhibiting compound was identified in the fifth fraction of a Rhodococcus strain. Our findings include the bioassay-guided identification, HPLC-MS-based dereplication, and isolation of a large phospholipid and a likely antimicrobial peptide, demonstrating the usefulness of this approach in screening for compounds capable of inhibiting EPEC virulence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pylkkö, Schneider, Rämä, Andersen and Tammela.)

A wide array of carbon materials finds extensive utility across various industrial applications today. Nonetheless, the production processes for these materials continue to entail elevated temperatures, necessitate the use of inert atmospheres, and often involve the handling of aggressive and toxic chemicals. The prevalent method for large-scale carbon material production, namely the pyrolysis of waste biomass and polymers, typically unfolds within the temperature range of 500-700 °C under a nitrogen (N 2 ) atmosphere. Unfortunately, this approach suffers from significant energy inefficiency due to substantial heat loss over extended processing durations. In this work, we propose an interesting alternative: the carbonization of photothermal nanocellulose/polypyrrole composite films through CO 2 laser irradiation in the presence of air. This innovative technique offers a swift and energy-efficient means of preparing carbon materials. The unique interaction between nanocellulose and polypyrrole imparts the film with sufficient stability to retain its structural integrity post-carbonization. This breakthrough opens up new avenues for producing binder-free electrodes using a rapid and straightforward approach. Furthermore, the irradiated film demonstrates specific and areal capacitances of 159 F g -1 and 62 μF cm -2 , respectively, when immersed in a 2 M NaOH electrolyte. These values significantly surpass those achieved by current commercial activated carbons. Together, these attributes render CO 2 -laser carbonization an environmentally sustainable and ecologically friendly method for carbon material production., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

The coronavirus disease 2019 (COVID-19) pandemic has heavily challenged the global healthcare system. Despite the vaccination programs, the new virus variants are circulating. Further research is required for understanding of the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and for discovery of therapeutic agents against the virus. Here, we took advantage of drug repurposing to identify if existing drugs could inhibit SARS-CoV-2 infection. We established an open high throughput platform for in vitro screening of drugs against SARS-CoV-2 infection. We screened ∼1000 drugs for their ability to inhibit SARS-CoV-2-induced cell death in the African green monkey kidney cell line (Vero-E6), analyzed how the hit compounds affect the viral N (nucleocapsid) protein expression in human cell lines using high-content microscopic imaging and analysis, determined the hit drug targets in silico, and assessed their ability to cause phospholipidosis, which can interfere with the viral replication. Duvelisib was found by in silico interaction assay as a potential drug targeting virus-host protein interactions. The predicted interaction between PARP1 and S protein, affected by Duvelisib, was further validated by immunoprecipitation. Our results represent a rapidly applicable platform for drug repurposing and evaluation of the new emerging viruses' responses to the drugs. Further in silico studies help us to discover the druggable host pathways involved in the infectious cycle of SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Benzothiazole-based bacterial DNA gyrase and topoisomerase IV inhibitors are promising new antibacterial agents with potent activity against Gram-positive and Gram-negative bacterial strains. The aim of this study was to improve the uptake of these inhibitors into the cytoplasm of Gram-negative bacteria by conjugating them to the small siderophore mimics. The best conjugate 18b displayed potent Escherichia coli DNA gyrase and topoisomerase IV inhibition. The interaction analysis of molecular dynamics simulation trajectory showed the important contribution of the siderophore mimic moiety to binding affinity. By NMR spectroscopy, we demonstrated that the hydroxypyridinone moiety alone was responsible for the chelation of iron(iii). Moreover, 18b showed an enhancement of antibacterial activity against E. coli JW5503 in an iron-depleted medium, clearly indicating an increased uptake of 18b in this bacterial strain., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study aimed to identify inhibitors of the translocated intimin receptor (Tir) of enteropathogenic Escherichia coli (EPEC). EPEC is an intestinal pathogen that causes diarrhea and is a major health concern worldwide. Because Tir is a key virulence factor involved in EPEC pathogenesis, inhibiting its function is a potential strategy for controlling EPEC infections. Virtual screening was applied to chemical libraries to search for compounds that inhibit Tir-mediated bacterial adherence to host cells. Three sites were targeted using the cocrystal structure published earlier. A selection of compounds was then assessed in a cell-based infection model and fluorescence microscopy assay. The results of this study provide a basis for further optimization and testing of Tir inhibitors as potential therapeutic agents for EPEC infections., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)