Relevant Levels Research Articles

New Horizons in Micro/Nanoplastic-Induced Oxidative Stress: Overlooked Free Radical Contributions and Microbial Metabolic Dysregulations in Anaerobic Digestion.

Excessive production of reactive oxygen species (ROS) induced by micro/nanoplastics (MPs/NPs) is highly toxic to microbes. However, the mechanisms underlying ROS generation and metabolic regulation within anaerobic guilds remain poorly understood. In this study, we investigated the effects of environmentally relevant levels of polypropylene (PP)-MPs/NPs on oxidative stress and microbial ecology during anaerobic digestion (AD). Electron paramagnetic resonance spectroscopy revealed that PP-MPs/NPs elevated the concentrations of environmentally persistent free radicals (EPFRs) and derived hydroxyl radicals (•OH). EPFRs were identified as the primary contributors to •OH generation, as evidenced by a high Spearman correlation coefficient (r = 0.884, p < 0.001) and free radical-quenching studies. The formation of •OH enhanced ROS production by 86.2-100.9%, resulting in decreased cellular viability and methane production (by 37.5-50.5%) at 100 mg/g TS PP-MPs/NPs. Genome-centric metagenomic and metatranscriptomic analyses suggested that PP-MPs/NPs induced the reassembly of community structures, re-evolution of functional traits, and remodeling of interspecies interactions. Specifically, PP-MPs/NPs induced a shift in methanogen consortia from hydrogenotrophic Methanofollis sp. to acetoclastic and hydrogenotrophic Methanothrix soehngenii, primarily because of the latter's diverse ingestion patterns, electron bifurcation complexes, and ROS-scavenging abilities. Downregulation of genes associated with antioxidative defense systems (i.e., sodN, katA, and osmC) and ROS-driven redox signal transduction pathways (c-di-AMP and phosphorylation signaling pathways) provided insights into the mechanisms underlying ROS-induced microbial metabolic dysregulation. Our findings enhance the understanding of microbial ecological and metabolic traits under MPs/NPs stressors, facilitating the control of MPs/NPs toxicity and the stabilization of AD processes.

Cost of integrated immunization campaigns in Nigeria and Sierra Leone: bottom-up costing studies

BackgroundTo improve the efficient use of scarce resources, low- and middle-income countries and development partners are increasingly encouraged to deliver multiple vaccines and other interventions in a single integrated campaign. However, little is known regarding the cost of delivering vaccines through integrated campaigns, and the extent to which efficiencies are achieved. To fill this evidence gap, we estimated the cost of integrated immunization campaigns in Nigeria and Sierra Leone, and the potential savings from integration.MethodsWe conducted a retrospective ingredients-based costing study from a payer perspective of a campaign held in 2019 in Sierra Leone with measles-rubella vaccine and oral polio vaccine, during which nutrition supplements were also offered in part of the country, and yellow fever campaigns held in three states in Nigeria in 2019 and 2020, where in one state (Anambra) meningococcal A vaccines were co-delivered. We collected data from 108 health facilities, all relevant administrative levels, and implementing partners. We estimated the full financial and economic cost of each campaign, the average unit cost of delivery, as well as the cost by activity and resource type. We also estimated the cost savings from integration in Anambra state by modelling out the cost of the alternative of two standalone campaigns.ResultsThe average financial delivery cost was $0.34 per dose in Sierra Leone, and the economic cost was $0.73 per dose. In Nigeria, the financial cost per dose was $0.29–$0.35 across the three states, and the economic cost per dose was $0.62–$0.85. Facilities and wards delivering more doses achieved a lower financial and economic unit cost of delivery, demonstrating evidence of economies of scale. We estimated that Anambra may have saved at least $1,204,133 in financial resources by integrating yellow fever and meningitis A vaccine delivery, amounting to $0.17 per dose delivered. When including opportunity costs, the economic cost saving was estimated at $0.34 per dose delivered.ConclusionsThe study offers evidence on what it costs to deliver integrated campaigns, and shows that integrated delivery is likely to result in significant cost savings. Where high delivery volumes can be achieved, integrated campaigns can benefit from economies of scale. The findings can be used to inform planning and budgeting for immunization campaigns in low- and middle-income countries.

Mitotic Arrest Deficient 2 Like 1 Contributes to Colorectal Cancer Cell Migration, Invasion, and Oxaliplatin Resistance Through the Wnt/β-Catenin Pathway.

Colorectal cancer (CRC) is a highly prevalent malignancy, requiring chemotherapy for advanced stages of the disease. Previously, we found that mitotic arrest deficient 2 like 1 (MAD2L1) was upregulated and facilitated malignant proliferation in CRC. However, the association between MAD2L1 expression and tumor progression, as well as chemotherapy resistance in CRC, remains unclear. The progression capacities of CRC cells were assessed using transwell and wound healing assays, and the resistance to cisplatin in oxaliplatin-resistant CRC cells was assessed using CCK-8 assay and flow cytometry. Relevant protein levels of epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin pathway were analyzed using western blotting. Revealing the impact of MAD2L1 on metastasis and drug resistance in CRC through inhibition of the Wnt/β-catenin pathway. Knockdown of MAD2L1 attenuated the malignant progression of CRC cells, inhibited EMT, and blocked the Wnt/β-catenin pathway. MAD2L1 was significantly upregulated in oxaliplatin-resistant CRC cells, accompanied by the activation of the Wnt/β-catenin pathway. Knockdown of MAD2L1 effectively reversed oxaliplatin resistance, leading to apoptosis and downregulation of the protein expression levels of β-catenin, P-glycoprotein (P-gp), and ABCG2. After the knockdown of MAD2L1, the inhibition of the Wnt/β-catenin pathway exhibited a synergistic effect, effectively suppressing malignant progression and reversing oxaliplatin resistance in CRC cells. So, knockdown of MAD2L1 suppressed cell malignant progression, equally sensitized resistant CRC cells to oxaliplatin, potentially by blocking the activation of the Wnt/β-catenin pathway.

Psychometric Measurements of the Adherence to Refills and Medication Scales Among Patients With HIV/AIDS in Indonesia

ObjectiveThis study aimed to conduct a psychometric evaluation of the Adherence to Refills and Medications Scale (ARMS) among patients with HIV/AIDS in Indonesia. MethodsPsychometric analysis was conducted at 2 hospitals and 7 public health centers at the voluntary counseling and testing clinic. Content validity was measured by assessing the relevance and clarity of each ARMS item. Construct validity was also assessed. Reliability was evaluated using internal consistency and test-retest reliability. ResultsThis study involved 11 experts in the assessment of the content validity and 240 participants in the estimation of the construct validity. All ARMS items were generally considered easy to understand and relevant, with scale-level content validity index based on the average method (S-CVI/Ave) of 0.9 (>0.78) and item-level content validity index (I-CVI) in the range from 0.5 to 1 for the relevance level and S-CVI/Ave of 0.95 (>0.78) and I-CVI in the range from 0.8 to 1 for the clarity level. Two items (numbers 2 and 3) were revised based on experts’ suggestions to enhance comprehension. Confirmatory factor analysis supported 2 subscales: adherence to taking medications and adherence to refilling prescriptions. Good reliability was supported by internal consistency (Cronbach’s α 0.793) and test-retest reliability (intraclass correlation coefficient 0.722) for the overall adherence score. ConclusionsThe Indonesian version of ARMS is a valid and reliable medication adherence scale when used in Indonesian patients with HIV/AIDS.

Rising temperature impacts the trace metal uptake and toxicity in aquatic plants - A case study of Ni and Co in Elodea canadensis Michx.

The global warming and environmental pollution are two crucial contemporary concerns. As both are strongly connected with urbanisation and anthropogenic impact on the environment, they often affect the ecosystem simultaneously. Aquatic habitats are particularly susceptible to thermal and chemical pollution. Temperature influences nearly all physical and chemical features of water bodies and trace metals are known for their toxicity to aquatic organisms. However, effects of multiple stressors, cumulative effects as well as response and possible adaptations of organisms are still open questions. Thus, the aim of this study was to characterize the combined effect of temperature and two trace metals (Co and Ni) on the metal bioaccumulation and viability of a model aquatic macrophyte Elodea canadensis Michx. We exposed shoots of E. canadensis to three temperatures and four metal concentrations (together and separately) applied at environmentally relevant levels. Shoot growth and metal concentration in plants were measured after 120 h. Moreover, after 24, 72 and 120 h the changes in leaf cell morphology and viability were analysed. The results showed that metal accumulation was dose-dependent and was not affected by temperature. The growth of plants was not affected by temperature nor metals. On the other hand, the exposure to Co and Ni and the elevated temperature negatively affected cell viability of E. canadensis leaves which manifested by increased permeability of plasma membranes and visible necroses. The greatest damaged leaf areas were determined after 120 h in the highest concentration of both metals and the highest temperature which indicates synergistic impact of trace metals and temperature on performance of macrohydrophytes. The observed phenomena suggest that global warming and/or thermal pollution may have implications for the performance of aquatic macrophytes in chemically polluted waters, their ability to spread and colonize polluted habitats and their suitability in phytoremediation.

Stakeholder involvement in the development of a serious game for and with healthcare professionals

Abstract Increasing pressure on the quality, accessibility and affordability of Dutch health services underlines the need for integrated approaches to healthcare that include lifestyle as preventive measure. Integrated healthcare requires coordinated collaboration between healthcare providers, which is facilitated by the concept of Positive Health as a unifying language. To support primary care providers (PCP) in developing knowledge and skills related to lifestyle as prevention, interdisciplinary collaboration and the concept of Positive Health, we are developing education in the form of a serious game: Game2Connect. Co-creation by active involvement of a consortium of educational institutes, healthcare organisations, a game developer, and PCP as end-users of Game2Connect plays a key role in its development. Data from interviews with PCP (on barriers and facilitators for health-promoting and collaborative behaviours), healthcare recipients (on input for case studies) and consortium meetings were incorporated into an initial version of Game2Connect, which is currently being piloted to assess and improve its utility and usability. Pilot sessions included an observed playthrough, followed by a usability questionnaire and a semi-structured group discussion. So far, 2 pilot sessions were held with consortium members (n = 16), and 3 sessions were held with PCP (n = 22). Learning indicators (e.g. PCP clarifying fellow players’ misconceptions) were observed in all sessions. Usability scores indicate high levels of challenge, content relevance, and positive affect, ranging between 3.3-3.6 on a 4-point scale. Qualitative feedback from group discussions resulted in the development of new case studies to appeal to a broader range of PCP, and the adjustment of a goal-setting exercise as a game component to encourage its use. These results suggest that serious gaming may be a viable and engaging method to educate PCP, especially when developed in active collaboration with stakeholders.

Patients with dementia: prevalence and type of drug–drug interactions

BackgroundPatients with Alzheimer’s disease (AD) and other dementias are more frequently exposed to polymedication, mainly due to the presence of comorbidities, are particularly vulnerable to drug-related problems, and present greater risk of adverse effects due to drug–drug interactions (DDIs).PurposeTo assess the prevalence of clinically relevant interactions in dementia patients using a routine database, we describe the most frequent interactions and risk factors associated with them to facilitate specific interventions and programs to prevent and minimize them.MethodsAn observational, descriptive, and cross-sectional study that included patients with AD and other types of dementia (n = 100, 64% female) was conducted to identify potential DDI in their treatment using the Lexi-Interact/Lexicomp® database.ResultsA total of 769 drugs were prescribed, involving 190 different active ingredients; 83% of the treatments included five or more drugs. DDI occurred in 87% of the patients, of which 63.2% were female. A total of 689 DDIs were found, grouped in 448 drug pairs, with a mean of 6.9 ± 7.1 (range, 0–31) DDIs per patient, and 680 DDIs were considered clinically relevant. It was observed that 89.8% of the DDIs had a moderate level of severity, 23.5% had a good level of relevance, and pharmacodynamic-based DDIs accounted for 89.5%. The drugs most frequently involved in DDIs were quetiapine (24.5%) and acetylsalicylic acid (10%). A total of 97 DDIs were detected between the acetylcholinesterase inhibitors (AChEIs), and the remaining drugs were administered concomitantly. One of the most frequent DDIs was between AChEIs and beta-blocking agents (n = 29, 4.3%). The most important factors that showed the strongest association with the presence of drug interactions were the use of AChEIs (p = 0.01) and the total number of drugs (p = 0.014) taken by the patient.ConclusionPatients with dementia present increased risk of DDIs. Among the most common drugs are psychotropic drugs, which are involved in pharmacodynamic interactions caused by the concomitant use of CNS-targeted drugs. The results highlight the difficulty to evaluate DDIs in clinical practice due to polymedication and variety of comorbidities. Therefore, it is important to review their treatment and consider metabolism inhibition or induction, and potentially P450 substrate overlapping.

Integration of a dose management system in the public hospitals of Cyprus: Key areas and initial outcomes.

Despite the growing use of dose management systems (DMSs), there is limited guidance on their optimal setup. This study aims to fill this gap by outlining the process followed to integrate "DOSE" (Qaelum NV, Belgium) DMS within the Cypriot public hospitals. DOSE was connected to the available central PACS, followed by a thorough data and functioning validation. A preliminary study was also conducted to assess the DOSE's ability to establish typical dose values in diagnostic radiography. Overall, over 70 x-ray units were configured. For some connections, it was necessary to first adjust the unit's DICOM attributes or to utilise the DICOM coercion technique. The DICOM image header was sometimes preferred over the DICOM RDSR, as the chosen data source. This study underscored the importance of understanding the equipment's technical capabilities for a successful DMS integration, while personnel with expertise in diagnostic radiology and the IT aspects of medical physics proved to have a vital role in the process. The pilot study showed that DOSE is an effective tool for establishing typical dose values and assessing compliance with relevant dose levels.

Prioritization of important plant areas for conservation of frailejones (Espeletiinae, Asteraceae) in the Northern Andes

AbstractThe tropical Andes region harbors areas that are highly significant for biodiversity at both global and local scales. However, despite the severe conservation threats that this region has to confront, conservation initiatives are limited, by funding and because of the need for more information to decide which areas are priorities for conservation. Identifying Important Plant Areas (IPAs) offers a valuable methodology for establishing conservation priorities, a particularly complex task in a mega-biodiverse region such as the northern Andean tropics. Due to its iconic recognition and conservation value, this study focused on the Espeletiinae subtribe (Asteraceae) as a model group; hence, the distribution data for 138 species was compiled from 5560 georeferenced records. Using the IPA methodology, we divided the study area, this is, the distribution area of the subtribe in the Andean tropics, into 220 Units of Analysis (UA) represented by 10 × 10 km plots. Refined species’ distribution areas, incorporating richness, threatened species, and ecosystem-based richness distributions, were analyzed using newly generated maps to evaluate the conservation value of each UA. Our analysis identified 176 UAs with some level of relevance using sub-criterion cA1 (with 59 species) and 51 UAs using sub-criterion cB (with 76 species). Integrating both criteria, we classified 11 UAs as high-priority, 62 as medium-priority, and 147 as low-priority, highlighting the IPAs that require focused conservation efforts. Two identified high-priority IPAs are located in Venezuela and nine in Colombia, predominantly associated with the Eastern Cordillera. These areas concentrate between 7 and 12 species. They are mainly linked to the páramo complexes of Colombia and the Sierra Nevada in Venezuela, primarily within Cool Temperate Moist Grassland ecosystems on mountains. Our results provide a spatial planning procedure and analytical tool for decision-makers to guide conservation management and actions across northern Andes.

Enhancing Employee Performance: The Impact of Engagement, Job Rotation, Compensation, and Motivation

This research aims to determine the influence of employee engagement, transfers, compensation and motivation on employee performance. Apart from that, you can see the review from an Islamic perspective. The population of this study were employees of the Jakarta Cakung Primary Tax Service Office with a sample size of 89 respondents. The sampling technique uses a non-probability sampling method, with a saturated sampling technique through distributing questionnaires. The data analysis method uses the Partial Least Square Structural Equation Modeling (PLS-SEM) method. The model in this research provides a strong influence with a strong level of relevance in predicting the influence between variables with a large level of suitability. employee engagement has a positive and significant effect on employee performance. Furthermore, mutations have a positive and significant effect on employee performance. Compensation has a positive and significant effect on employee performance. Motivation has a positive and significant effect on employee performance. Managerial Implications Organizations should prioritize enhancing employee engagement through effective communication and involvement in decision-making processes to boost performance. Additionally, strategic employee mutations or transfers can be leveraged to match skills with job roles more effectively. Fair and competitive compensation packages are essential to motivate employees and enhance their commitment.

Long-term exposure to environmentally relevant Bisphenol-A levels affects growth, swimming, condition factor, sex ratio and histology of juvenile zebrafish

Bisphenol A (BPA) is an environmental estrogen which perturbs hormone signaling pathways adversely affecting aquatic organisms. To evaluate the impact of developmental exposure to long term yet environmentally relevant low doses of BPA, wild-type juvenile zebrafish of 35 days post fertilization were treated with BPA (1 and 10 µg/L), treatment control (0.5% v/v methanol) and control for 60 days. Both BPA treatments led to significantly increased morality overtime. Length increment and specific growth rates became significantly high in BPA exposed zebrafish overtime. Obesogenic property of BPA was not evident with longexposure to low BPA doses. A significantly high and BPA dose-dependent female-biased sex ratios were observed following the juvenile exposure. Significantly low swimming speed was recorded in the fish of both BPA-treated tanks than that of control. Condition factor was significantly low in BPA exposed fish indicating the poor-wellness. There were numerous histopathological alterations of gonads, liver and kidney indicating impacts of juvenile exposure in zebrafish. Altered growth, swimming, mortality, feminization and histopathological changes in zebrafish induced by BPA indicate the risks associated with developmental exposures. The findings call for more comprehensive studies to comprehend the ecological risks imposed by low concentrations of environmental estrogens in urban aquatic ecosystems.

Beyond low lignin: Identifying the primary barrier to plant biomass conversion by fermentative bacteria.

Renewable alternatives for nonelectrifiable fossil-derived chemicals are needed and plant matter, the most abundant biomass on Earth, provide an ideal feedstock. However, the heterogeneous polymeric composition of lignocellulose makes conversion difficult. Lignin presents a formidable barrier to fermentation of nonpretreated biomass. Extensive chemical and enzymatic treatments can liberate fermentable carbohydrates from plant biomass, but microbial routes offer many advantages, including concomitant conversion to industrial chemicals. Here, testing of lignin content of nonpretreated biomass using the cellulolytic thermophilic bacterium, Anaerocellum bescii, revealed that the primary microbial degradation barrier relates to methoxy substitutions in lignin. This contrasts with optimal lignin composition for chemical pretreatment that favors high S/G ratio and low H lignin. Genetically modified poplar trees with diverse lignin compositions confirm these findings. In addition, poplar trees with low methoxy content achieve industrially relevant levels of microbial solubilization without any pretreatments and with no impact on tree fitness in greenhouse.

Research on Design Parameters for Fatigue Performance of Asphalt Mixtures.

The fatigue performance of the asphalt mixture was the main focus of this study, with five typical factors-phase angle, cumulative dissipated energy, failure strain, failure stiffness modulus, and strain rate-identified as potential design indexes. The effect of asphalt content on the parameters under different gradation and stress ratios was tested. It was observed that the selected parameters exhibited varying levels of sensitivity and relevance to the fatigue behavior of asphalt mixtures under cyclic loads. By comparison, the strain rate proved sensitive to the asphalt content and independent of the other parameters, namely aggregate gradations and stress ratio, thus establishing the strain rate as a critical design index based on fatigue performance. On this basis, a design method based on the fatigue performance for the asphalt mixtures is herein proposed. It was confirmed that the asphalt mixture formulated using the proposed method exhibited enhanced fatigue endurance compared to those designed using the conventional method.

Marx and the Big Mac: An Empirical Exploration of Marx’s Exploitation Theory for Introductory Economics Courses

Undergraduate economics courses have low relevance, belonging, and growth mindset levels. For instance, Bayer et al. found that less than 30 percent of the students in their sample strongly agreed with the statement “The class gave me a useful framework for thinking about important issues.” Integrating pluralist methodologies into introductory economics classes may be one solution for overcoming this issue. This article introduces an empirical activity designed to teach students about Marx’s theory of exploitation. The activity utilizes the 10-K annual report from a publicly traded company, in this case, McDonald’s, to analyze the rate of exploitation of workers. Through this exercise, students delve into the theory of exploitation, analyze data from the 10-K, calculate the rate of exploitation, and engage in discussions about its application to contemporary social and political issues. JEL Classification: A22, P16, B24

Modular Point-of-Need Tropane Alkaloid Detection at Regulatory Levels: Combining Solid-Liquid Extraction from Buckwheat with a Paper-Immobilized Liquid-Phase Microextraction and Immuno-Detection in Interconnectable 3D-Printed Devices.

Contamination with tropane alkaloids in cereals is expected to increase globally. However, current identification tools (e.g., liquid chromatography-mass spectrometry) for tropane alkaloids are time-consuming and expensive. Furthermore, their miniaturized alternatives lack sensitivity and robustness. Therefore, there is a pressing need for inexpensive and effective screening methods. Here, an on-site applicable modular workflow for tropane alkaloid detection in buckwheat is presented. The modular workflow combines paper microfluidics and interconnectable 3D-printed sample preparation tools and was evaluated for different tropane alkaloids, including atropine and scopolamine. Furthermore, integration with an indirect competitive lateral flow immunoassay (icLFIA) for atropine detection at relevant levels was demonstrated. In the modular workflow, to minimize matrix coextraction, tropane alkaloids were extracted from the milled buckwheat cereals by a mixture of alkaline aqueous and immiscible organic solvents (extraction recoveries: 66-79%). The tropane alkaloids were subsequently concentrated with a newly developed paper-immobilized liquid-phase microextraction (PI-LPME, extraction recoveries: 34-60%, concentration factor to immobilized solution in paper: 60-108×). After the PI-LPME, with an integrated 3D-printed setup, the tropane alkaloids were directly eluted (elution recoveries: 83-93%) and detected with the icLFIA. Digital read-out of the icLFIA, by employing a hand-held reader, enabled semiquantification of atropine (IC50 = 0.56 ng mL-1 in standard solutions). The modular workflow was validated by analyzing 24 blank and spiked buckwheat cereal samples with 5 and 10 μg kg-1 atropine. A cutoff value was established with an estimated false negative rate of 1% and estimated false positive rate of 0.68%. Therefore, the modular workflow can aid in fast, inexpensive, and on-site atropine detection by nonexperts, and when integrated with a scopolamine-specific icLFIA expanded toward scopolamine detection. Moreover, the developed sample extraction and concentration method (PI-LPME) is suitable for the analysis of many other compounds with pH-dependent polarity.

Effects of Inosine-5′-monophosphate Dehydrogenase (IMPDH/GuaB) Inhibitors on Borrelia burgdorferi Growth in Standard and Modified Culture Conditions

Borrelia burgdorferi’s inosine-5′-monophosphate dehydrogenase (IMPDH, GuaB encoded by the guaB gene) is a potential therapeutic target. GuaB is necessary for B. burgdorferi replication in mammalian hosts but not in standard laboratory culture conditions. Therefore, we cannot test novel GuaB inhibitors against B. burgdorferi without utilizing mammalian infection models. This study aimed to evaluate modifications to a standard growth medium that may mimic mammalian conditions and induce the requirement of GuaB usage for replication. The effects of two GuaB inhibitors (mycophenolic acid, 6-chloropurine riboside at 125 μM and 250 μM) were assessed against B. burgdorferi (guaB+) grown in standard Barbour–Stoenner–Kelly-II (BSK-II) medium (6% rabbit serum) and BSK-II modified to 60% concentration rabbit serum (BSK-II/60% serum). BSK-II directly supplemented with adenine, hypoxanthine, and nicotinamide (75 μM each, BSK-II/AHN) was also considered as a comparison group. In standard BSK-II, neither mycophenolic acid nor 6-chloropurine riboside affected B. burgdorferi growth. Based on an ANOVA, a dose-dependent increase in drug effects was observed in the modified growth conditions (F = 4.471, p = 0.001). Considering higher drug concentrations at exponential growth, mycophenolic acid at 250 μM reduced spirochete replication by 48% in BSK-II/60% serum and by 50% in BSK-II/AHN (p &lt; 0.001 each). 6-chloropurine riboside was more effective in both mediums than mycophenolic acid, reducing replication by 64% in BSK-II/60% serum and 65% in BSK-II/AHN (p &lt; 0.001 each). These results demonstrate that modifying BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces the effects of GuaB inhibitors. This represents the first use of GuaB inhibitors against Borrelia burgdorferi, building on tests against purified B. burgdorferi GuaB. The strong effects of 6-chloropurine riboside indicate that B. burgdorferi can salvage and phosphorylate these purine derivative analogs. Therefore, this type of molecule may be considered for future drug development. Optimization of this culture system will allow for better assessment of novel Borrelia-specific GuaB inhibitor molecules for Lyme disease interventions. The use of GuaB inhibitors as broadcast sprays or feed baits should also be evaluated to reduce spirochete load in competent reservoir hosts.

Implications of Lead (Pb)-Induced Transcriptomic and Phenotypic Alterations in the Aged Zebrafish (Danio rerio).

Lead (Pb) is a well-known neurotoxin with established adverse effects on the neurological functions of children and younger adults, including motor, learning, and memory abilities. However, its potential impact on older adults has received less attention. Using the zebrafish model, our study aims to characterize the dose-response relationship between environmentally relevant Pb exposure levels and their effects on changes in behavior and transcriptomics during the geriatric periods. We exposed two-year-old zebrafish to waterborne lead acetate (1, 10, 100, 1000, or 10,000 µg/L) or a vehicle (DMSO) for 5 days. While lower concentrations (1-100 µg/L) reflect environmentally relevant Pb levels, higher concentrations (1000-10,000 µg/L) were included to assess acute toxicity under extreme exposure scenarios. We conducted adult behavior assessment to evaluate the locomotor activity following exposure. The same individual fish were subsequently sacrificed for brain dissection after a day of recovery in the aquatic system. RNA extraction and sequencing were then performed to evaluate the Pb-induced transcriptomic changes. Higher (1000-10,000 ug/L) Pb levels induced hyperactive locomotor patterns in aged zebrafish, while lower (10-100 ug/L) Pb levels resulted in the lowest locomotor activity compared to the control group. Exposure to 100 µg/L led to the highest number of differentially expressed genes (DEGs), while 10,000 µg/L induced larger fold changes in both directions. The neurological pathways impacted by Pb exposure include functions related to neurotransmission, such as cytoskeletal regulation and synaptogenesis, and oxidative stress response, such as mitochondrial dysfunction and downregulation of heat shock protein genes. These findings emphasize a U-shape dose-response relationship with Pb concentrations in locomotor activity and transcriptomic changes in the aging brain.

Elites and ordinariness in cross-status encounters: Adding Goffman's ritual interaction order to sociological interpretations

Elites and higher-class people often downplay – even conceal – their status when interacting with people of lower class/status than themselves. This finding has been reported from several countries in the Global North. It is also shown in research from disparate academic fields and disciplines: the sociology of class, psychology, cognitive decision-making, and microsociology. This paper reviews and synthesises the literature on elites and high-status people who downplay social differences in cross-status social interaction. It makes two main contributions: First, I show that the phenomenon is more widespread transnationally than especially Nordic researchers have assumed. The second contribution comes from tracing the theoretical interpretations in the research. I notice tendencies of an individual – structure dualism in some strands of research, with the relevant analytical levels being the broader moral repertoires and predispositions. Other strands of research suffer from overly individualist interpretations. I argue that what is missing in most current research on cross-status interaction, is an adequate theoretical grasp of the social situation. I discuss how the study of cross-status interaction can be fertilised by the classical microsociological idea of situations’ existence in themselves, a social domain that cannot be reduced to dispositions or broader culture. I engage here especially Erving Goffman's ritual interaction order. From this vantage point, I also highlight situational variation, something attended to by few studies of cross-status interaction.

Absence of genotoxicity following pulmonary exposure to metal oxides of copper, tin, aluminum, zinc, and titanium in mice.

Inhalation of nanosized metal oxides may occur at the workplace. Thus, information on potential hazardous effects is needed for risk assessment. We report an investigation of the genotoxic potential of different metal oxide nanomaterials. Acellular and intracellular reactive oxygen species (ROS) production were determined for all the studied nanomaterials. Moreover, mice were exposed by intratracheal instillation to copper oxide (CuO) at 2, 6, and 12 μg/mouse, tin oxide (SnO2) at 54 and 162 μg/mouse, aluminum oxide (Al2O3) at 18 and 54 μg/mouse, zinc oxide (ZnO) at 0.7 and 2 μg/mouse, titanium dioxide (TiO2) and the benchmark carbon black at 162 μg/mouse. The doses were selected based on pilot studies. Post-exposure time points were 1 or 28 days. Genotoxicity, assessed as DNA strand breaks by the comet assay, was measured in lung and liver tissue. The acellular and intracellular ROS measurements were fairly consistent. The CuO and the carbon black bench mark particle were potent ROS generators in both assays, followed by TiO2. Al2O3, ZnO, and SnO2 generated low levels of ROS. We detected no increased genotoxicity in this study using occupationally relevant dose levels of metal oxide nanomaterials after pulmonary exposure in mice, except for a slight increase in DNA damage in liver tissue at the highest dose of CuO. The present data add to the body of evidence for risk assessment of these metal oxides.

"Urgency" and "emergency" in the system of law-making proccess: conceptual and categorical dimension

It is indicated that the course of events at the global and regional levels of social development during recent years is difficult to characterize unambiguously from the standpoint of purely positive or negative aspects. However, it can be unequivocally noted that modern socio-political processes at the global and regional levels have a particularly sensitive effect on legal phenomena and processes. In the article, the author focuses on the relevance of the study of the conceptual and categorical foundations of the categories «urgency» and «emergency» and the peculiarities of their manifestation within the framework of law­making process. According to the author of the article, the achievement of the above is due to the need to carry out a comprehensive and conceptual analysis through the prism of scientific views and approaches of scientists. Attention was drawn to the fact that in connection with numerous factors of a subjective and objective nature, in particular, the duration of the war on the territory of Ukraine, the spread of the SARS- CoV-2 virus, the development of technologies, especially in the information field, the issues of new mechanisms for the development and adoption of the system are being updated normative legal acts taking into account the existing requirements and realities of the modern state of development of society, law and the state. Analysis of doctrinal approaches to this issue will provide clarification of the conceptual and categorical aspects of the relevant legal categories. It is substantiated that in cognitive terms it is expedient to analyze these legal categories through the prism of scientific views and concepts, which will allow generalizing their properties and improving their definitions. The content of the work includes a doctrinal analysis of the concepts of «urgency» and «emergency» as special legal categories. It was concluded that the categories «emergency» and «urgency» within the framework of law-making have a high level of relevance; require thorough, comprehensive scientific research within the framework of legal theory; are characterized by the presence of a common purpose, essential differences.