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OBJECTIVES: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD. METHODS: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop. RESULTS: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating - sum of boxes, clinical dementia rating - global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from -US$66 897 to US$11 896. CONCLUSIONS: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models.
- MeSH
- Alzheimerova nemoc * ekonomika farmakoterapie MeSH
- analýza nákladů a výnosů * MeSH
- ekonomické modely MeSH
- kognitivní dysfunkce * ekonomika MeSH
- kvalitativně upravené roky života MeSH
- lidé MeSH
- metody pro podporu rozhodování MeSH
- progrese nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Treponema pallidum subspecies pertenue (TPE) is the causative agent of human and nonhuman primate (NHP) yaws infection. The discovery of yaws bacterium in wild populations of NHPs opened the question of transmission mechanisms within NHPs, and this work aims to take a closer look at the transmission of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Our study determined eleven whole TPE genomes from NHP isolates collected from three national parks in Tanzania: Lake Manyara National Park (NP), Serengeti NP, and Ruaha NP. The bacteria were isolated from four species of NHPs: Chlorocebus pygerythrus (vervet monkey), Cercopithecus mitis (blue monkey), Papio anubis (olive baboon), and Papio cynocephalus (yellow baboon). Combined with previously generated genomes of TPE originating from NHPs in Tanzania (n = 11), 22 whole-genome TPE sequences have now been analyzed. Out of 231 possible combinations of genome-to-genome comparisons, five revealed an unexpectedly high degree of genetic similarity in samples collected from different NHP species, consistent with inter-species transmission of TPE among NHPs. We estimated a substitution rate of TPE of NHP origin, ranging between 1.77 × 10-7 and 3.43 × 10-7 per genomic site per year. CONCLUSIONS/SIGNIFICANCE: The model estimations predicted that the inter-species transmission happened recently, within decades, roughly in an order of magnitude shorter time compared to time needed for the natural diversification of all tested TPE of Tanzanian NHP origin. Moreover, the geographical separation of the sampling sites (NPs) does not preclude TPE transmission between and within NHP species.
- MeSH
- Cercopithecus aethiops MeSH
- Cercopithecus mikrobiologie MeSH
- frambézie * mikrobiologie přenos MeSH
- fylogeneze * MeSH
- genom bakteriální MeSH
- lidé MeSH
- nemoci opic mikrobiologie přenos MeSH
- Papio anubis mikrobiologie MeSH
- Papio cynocephalus mikrobiologie genetika MeSH
- primáti mikrobiologie MeSH
- sekvenování celého genomu * MeSH
- Treponema pallidum genetika izolace a purifikace klasifikace MeSH
- Treponema MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Tanzanie MeSH
OBJECTIVE: The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators. METHODS: The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects. RESULTS: Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters. CONCLUSIONS: In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.
- MeSH
- anizotropie MeSH
- bílá hmota patologie diagnostické zobrazování MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek * patologie diagnostické zobrazování MeSH
- schizofrenie * patologie diagnostické zobrazování MeSH
- šedá hmota patologie diagnostické zobrazování MeSH
- zobrazování difuzních tenzorů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.
- MeSH
- fylogeneze MeSH
- molekulární evoluce * MeSH
- RNA * genetika metabolismus MeSH
- rostliny genetika MeSH
- telomerasa * genetika metabolismus MeSH
- telomery * metabolismus genetika MeSH
- Viridiplantae genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Evidence on the impact of complex neighborhood environment, including air pollution, greenness, and neighborhood socioeconomic deprivation (nSED) on cognitive health in older adults remains scarce. Both cognition and neighborhood environment are associated with physical activity, but little is known about the potential mediating role of physical activity in this association. METHODS: Cross-sectional data of the Czech arm of the HAPIEE cohort study examined 4,178 participants (55.6% women) aged 45-69 years. Global cognitive score was constructed from memory, verbal fluency, and concentration domains. The exposures, assigned to participant's addresses, include 4-year (2000-2003) average concentrations of PM2.5, greenness index calculated from tree crown canopy cover estimation (2000), and census-based nSED characteristics. Physical activity and other covariates were assessed by a questionnaire. Structural equation modelling was used to estimate standardized β coefficients for the relationships between neighborhood environment, physical activity and cognitive performance. RESULTS: After controlling for a range of covariates, global cognitive function was inversely associated with PM2.5 (β = -0.087; 95%CI: 0.122 to -0.052) and nSED (β = -0.147; 95%CI: 0.182 to -0.115), and positively associated with greenness (β = 0.036; 95%CI: 0.001 to 0.069). We identified a weak but statistically significant mediating role of physical activity in the associations of PM2.5 exposures and nSED on global cognitive score. Total mediation proportions ranged from 3.9% to 6.5% for nSED and PM2.5, respectively. CONCLUSIONS: The neighborhood environment was associated with cognitive health in older individuals; the associations were partially mediated by physical activity.
- MeSH
- charakteristiky bydlení * MeSH
- charakteristiky okolí bydliště MeSH
- cvičení * MeSH
- kognice * MeSH
- látky znečišťující vzduch analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- pevné částice analýza MeSH
- průřezové studie MeSH
- senioři MeSH
- znečištění ovzduší analýza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.
- MeSH
- Brucella * genetika izolace a purifikace MeSH
- brucelóza * diagnóza mikrobiologie MeSH
- DNA bakterií genetika MeSH
- lidé MeSH
- limita detekce MeSH
- mléko mikrobiologie MeSH
- rekombinasy * metabolismus genetika MeSH
- senzitivita a specificita MeSH
- skot MeSH
- techniky amplifikace nukleových kyselin * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Nanoparticles have drawn significant interest in a range of applications, ranging from biomedical to environmental sciences, due to their distinctive physicochemical characteristics. In this study, it was reported that simple biological production of Ag, Se, and bimetallic Ag2Se nanoparticles (NPs) with Pseudomonas aeruginosa is a promising, low-cost, and environmentally friendly method. For the first time in the scientific literature, Ag2Se nanoparticles have been generated via green bacterial biosynthesis. UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and EDX were used to characterize the produced NPs. Biosynthesized NPs were examined for antibacterial, antibiofilm, and photocatalytic properties, and it was determined that the effects of NPs were dose dependent. The biosynthesized AgNPs, SeNPs, and Ag2Se NPs showed anti-microbial activity against Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentrations (MICs) of E. coli and S. aureus were between 150 and 250 μg/mL. The NPs showed antibiofilm activity against E. coli and S. aureus at sub-MIC levels and reduced biofilm formation by at least 80% at a concentration of 200 μg/mL of each NPs. To photocatalyze the breakdown of Congo red, Ag, Se, and Ag2Se NPs were utilized, and their photocatalytic activity was tested at various concentrations and intervals. A minor decrease of photocatalytic degradation was detected throughout the NPs reuse operation (five cycles). Based on the encouraging findings, the synthesized NPs demonstrated antibacterial, antibiofilm, and photocatalytic properties, suggesting that they might be used in pharmaceutical, medical, environmental, and other applications.
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- biofilmy * účinky léků MeSH
- Escherichia coli * účinky léků MeSH
- katalýza MeSH
- kovové nanočástice * chemie MeSH
- mikrobiální testy citlivosti * MeSH
- Pseudomonas aeruginosa * účinky léků metabolismus MeSH
- selen chemie farmakologie MeSH
- sloučeniny stříbra chemie farmakologie MeSH
- Staphylococcus aureus * účinky léků MeSH
- stříbro * chemie farmakologie metabolismus MeSH
- technologie zelené chemie * MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Evidence-based nursing practice (EBNP) has been regarded core competencies in nursing practice and education. Defining evidence-based nursing practice and translating evidence into nursing practice by nursing students who are green to clinical practice in their education journey remain unclear. AIM: To explore how pre-registered nursing students define and characterize evidence-based nursing practice as they participate in their clinical practicum. DESIGN: This study used an interpretive phenomenological qualitative study design. SETTINGS AND PARTICIPANTS: Twenty nursing students were interviewed for their clinical practicum experience from four universities, one nursing college and one hospital-based nursing school in Hong Kong. METHODS: Data was generated through semi-structured in-depth interview and analyzed following interpretative phenomenological analysis guidelines, using a cyclical coding process. RESULTS: Four themes emerged regarding nursing students' definition of EBNP, highlighting that EBNP is 'identifying a reliable learning source', by which they can 'rationalize their nursing practice', and enabling them to 'establish care standard through critical thinking', and eventual 'fostering their professionalism' to improve health outcomes and reduce potential harms. CONCLUSION: Nursing students defined and characterized evidence-based nursing practice as core competencies in accompany their practicum that enables them to learn and grow professionally with a universal desire to be qualified, cope with doubt, and improve patient outcome. They recognized the challenges in identifying evidence and emphasized conservative approach to validate the evidence to avoid patient harm. Students expressed doubt towards their instructors EBNP when observing procedures untaught at school, which requires the curriculum model to foster students' skills in applying and appraising evidence and instructors' capacity to rationalize and role model EBNP.
- MeSH
- dospělí MeSH
- klinické kompetence * normy MeSH
- kvalitativní výzkum * MeSH
- lidé MeSH
- ošetřovatelství založené na důkazech * MeSH
- rozhovory jako téma metody MeSH
- studenti ošetřovatelství * psychologie MeSH
- studium ošetřovatelství bakalářské * normy metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Hongkong MeSH
BACKGROUND: Pancreaticoduodenectomy is associated with an incidence of postoperative complications of approximately 41%. One of the most severe complications is a postoperative pancreatic fistula. The exact cause of postoperative fistula development is still unknown, but it appears to be multifactorial. Proper perfusion of pancreatic remnant is essential for the healing of pancreaticojejunostomy. To date, there is no method to reliably evaluate the vascular supply of the remnant. One of the methods for the assessment of organ perfusion is the indocyanine green fluorescence. This study aims to determine if indocyanine green fluorescence is a reliable method to measure the perfusion of the post-resection pancreatic remnant. The secondary outcome is to determine if intraoperative evaluation of the vascular supply of the post-resection remnant may predict the increased risk of postoperative pancreatic fistula development. METHODS: This study is designed as a prospective, observational study. All consecutive patients undergoing open or robotic pancreaticoduodenectomies at our department during the 1st May 2024-31st December 2026 period will be enrolled. The exclusion criteria are an allergy to indocyanine green and refusal by the patient. The adequacy of the vascular supply of the post-resection pancreatic remnant will be intraoperatively evaluated using a fluorescence detector. Patients will be divided into two groups: Those with high risk of pancreatic fistula development and those with low risk. The incidence of pancreatic fistulas in both groups is to be compared. Postoperative data including morbidity, mortality, hospital stay, intensive care unit stay and postoperative fistula development will be collected. DISCUSSION: If an intraoperative assessment of the perfusion of post-resection pancreatic remnant using indocyanine green is proven to be a suitable method to estimate the increased risk of the pancreatic fistula, the list of the existing known risk factors could be expanded. In the most high-risk patients the modification of the surgical procedure could be considered. TRIAL REGISTRATION: Number: NCT06198400 ClinicalTrials.Gov. Date 08.01.2024.
- MeSH
- fluorescence MeSH
- indokyanová zeleň * MeSH
- lidé MeSH
- pankreas krevní zásobení chirurgie MeSH
- pankreatická píštěl * etiologie epidemiologie MeSH
- pankreatoduodenektomie * škodlivé účinky metody MeSH
- pooperační komplikace * etiologie diagnóza MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- protokol klinické studie MeSH
The pungency of chili peppers, the most popular hot spice used worldwide, is caused by capsaicinoids (CPDs), the content of which can vary greatly due to varietal differences and growing conditions. For the first time, a novel simple method for the fast determination of CPDs in chili peppers and chili products was developed based on adsorptive transfer cyclic square-wave voltammetry (AdTCSWV), using adsorption of lipophilic CPDs on an unmodified glassy carbon electrode surface from methanolic extracts of chili pepper samples. The CSWV is based on short oxidation of adsorbed CPDs to quinoid products, and their subsequent reduction and re-oxidation to provide specific analytical signals with a linear range from 0.05 to 1.00 mg L-1. This principle was also implemented in tandem coulometric and amperometric detection of CPDs after HPLC separation. The two-step electrochemical detection provides increased selectivity for CPDs in case of CPDs co-elution with other electrochemically oxidizable components that cannot be reversibly reduced.
