Search Results (86)

Antibiotic resistance remains one of the most formidable challenges to modern medicine, threatening to outpace therapeutic innovation and undermine decades of clinical progress. While resistance was once viewed narrowly as a clinical phenomenon, it is now understood as the outcome of complex ecological and molecular interactions that span soil, water, agriculture, animals, and humans. Environmental reservoirs act as silent incubators of resistance genes, with horizontal gene transfer and stress-induced mutagenesis fueling their evolution and dissemination. At the molecular level, advances in genomics, structural biology, and systems microbiology have revealed intricate networks involving plasmid-mediated resistance, efflux pump regulation, integron dynamics, and CRISPR-Cas interactions, providing new insights into the adaptability of pathogens. Simultaneously, the environmental dimensions of resistance, from wastewater treatment plants and aquaculture to airborne dissemination, highlight the urgency of adopting a One Health framework. Yet, alongside this growing threat, novel therapeutic avenues are emerging. Innovative β-lactamase inhibitors, bacteriophage-based therapies, engineered lysins, antimicrobial peptides, and CRISPR-driven antimicrobials are redefining what constitutes an “antibiotic” in the twenty-first century. Furthermore, artificial intelligence and machine learning now accelerate drug discovery and resistance prediction, raising the possibility of precision-guided antimicrobial stewardship. This review synthesizes molecular insights, environmental drivers, and therapeutic innovations to present a comprehensive landscape of antibiotic resistance. By bridging ecological microbiology, molecular biology, and translational medicine, it outlines a roadmap for surveillance, prevention, and drug development while emphasizing the need for integrative policies to safeguard global health. Full article

Background: Acromioclavicular joint (ACJ) injuries frequently result from trauma to the shoulder girdle and are particularly common among young, physically active individuals. These injuries account for approximately 9% of all traumatic shoulder girdle injuries and often lead to functional impairment and pain. The TightRope^® system, LARS™ band, and Bosworth screw are among over 160 currently described surgical techniques for managing ACJ dislocations. However, there is no consensus regarding the optimal surgical approach, particularly for the management of moderate Rockwood Type III ACJ dislocations. Materials and Methods: In this retrospective study, data from 246 patients who underwent surgery for ACJ dislocation between 2010 and 2018 at the Department of Orthopedics and Trauma Surgery, Medical University of Vienna, were analyzed. Patients were divided into four cohorts based on the surgical technique used: Bosworth screw, LARS (acute), LARS (chronic), and TightRope. Clinical and radiological outcomes were assessed pre- and postoperatively using the Visual Analog Scale (VAS), Constant, Disability of the Arm, Shoulder and Hand Score (DASH), Simple Shoulder Test (SST), University of California—Los Angeles Shoulder Score (UCLA), Short Form Health Survey (SF-36), and American Shoulder and Elbow Surgeons score (ASES), as well as radiographic analysis. Radiological measurements of the acromioclavicular (AC) and coracoclavicular (CC) joint spaces were taken on both the injured and uninjured shoulders to analyze and compare the reduction in joint gaps. Results: All surgical methods resulted in significant reductions in AC and CC joint gaps. The TightRope and LARS acute groups showed the greatest reductions, with minimal complication rates. Complication analysis revealed significant differences in clavicular elevation (p < 0.001) and CC-ligament ossification (p = 0.006), which were most frequent in the Bosworth group and least common in TightRope^® patients, with LARS showing intermediate values. AC joint arthrosis was uncommon in all four groups and did not differ significantly (p = 0.13). Overall, TightRope^® was associated with the most favorable complication profile. The postoperative VAS score in the TightRope group was 1.52 ± 2.06, and the Constant score was 96.83 ± 5.41, reflecting high patient satisfaction. Conclusions: All systems led to satisfactory radiological and clinical outcomes, with the LARS™ band showing particular effectiveness in chronic ACJ dislocations. While all techniques provided good results, the TightRope^® system demonstrated the most favorable overall profile in our cohort and may therefore be considered a promising contemporary option. Further studies are needed to determine the optimal treatment for moderate ACJ dislocations and to assess the cost-effectiveness of these surgical techniques. Full article

Latvia faces one of the lowest nurse-to-population ratios in the EU, resulting in critical staff shortages in intensive care units (ICUs). Nurses frequently care for more patients than recommended, which not only compromises patient safety but also places heavy psycho-emotional burdens on staff. The aim of this study was to examine organizational-level relationships between objectively measured ICU nursing workload and subjectively reported psycho-emotional outcomes, including moral distress, burnout, and intention to leave one’s job. A secondary analysis combined data from two cross-sectional studies conducted in 2025. Workload was measured using 3420 Nursing Activities Score (NAS) protocols from three hospitals, while 155 ICU nurses from 16 units completed validated instruments assessing moral distress, burnout, and turnover intentions. The findings revealed persistent nurse shortages, with one ICU showing deficits exceeding 70% and mean NASs above 100 points per nurse per shift. Nurses reported moderate moral distress, particularly in situations of unsafe patient ratios and aggressive treatment, while burnout levels were moderate to high, especially in personal and work-related dimensions. About one-quarter of respondents were actively considering leaving their jobs. Moral distress significantly correlated with burnout (r = 0.357, p < 0.001), and organizational-level comparison indicated that higher workload was associated with greater emotional strain. These results not only highlight urgent national challenges but also resonate with international evidence on the link between unsafe staffing, moral distress, and workforce sustainability. Implementing systematic workload monitoring, safe staffing ratios, and structured support mechanisms is essential to safeguard ICU nurses’ well-being, reduce turnover, and protect patient safety in both Latvian and global contexts. Full article

Based on questionnaire data and in-depth interviews with newly arrived students (NAS) from mainland China, this study investigates the construction of their social networks and the mechanisms through which they access social support in the context of migration. Drawing on Berry’s acculturation theory, Bronfenbrenner’s ecological systems theory, and Bourdieu’s concept of social capital, this study provides a theoretically grounded analysis of how NAS balance cultural distance and social needs. The findings reveal that NAS do not form social connections uniformly; rather, they strategically allocate social resources according to the degree of homophily and the strength of social ties. Specifically, weak ties with mainland peers—characterized by high cultural homophily—primarily offer emotional support; strong ties with local Hong Kong peers—marked by low homophily but high interaction frequency—mainly serve instrumental needs such as academic assistance and daily companionship; while strong ties with Hong Kong peers of mainland background combine both emotional and instrumental support, functioning as a core relational bridge in the NAS’s adaptation process. These three types of relationships form a complementary structure within NAS’s social networks. Reliability and validity tests further confirmed that four items (social satisfaction, peer attitude, sense of belonging, integration/adaptation) provide a coherent measure of social integration. The study suggests that NAS’s social practices are not merely about “integration” or “alienation,” but rather represent a dynamic strategy of balancing relational costs, cultural distance, and practical needs in the operation of social capital and characterised by dynamic negotiation and contextual adjustment. Full article

Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies. Low-voltage activated (T-type) calcium channels (Ca_V3.2 isoform) could be a promising therapeutic target for the development of novel pain therapies. Indeed, our published findings suggest that novel neuroactive steroid (NAS) analogs that modulate the activity of Ca_V3.2 channels have unique anti-nociceptive properties. However, the concern with current NASs appears to be their hypnotic/sedative properties, thus potentially hindering the future development of NASs for novel pain therapies. Hence, we developed a new line of NASs that are effective blockers of neuronal Ca_V3.2 channels in pain pathways while having more favorable pharmacodynamic properties, i.e., lack of sedative/hypnotic side effects. We present two promising novel analogs of NASs—B372 ((3β,5α,17β)-3-Hydroxyandrostan-17-carbonitrile) and YX23 ((3β,5α,17β)-3-Methoxyestran-17-ol). Using an in vitro approach, we show that B372 and YX23 are effective in blocking Ca_V3.2 channels. Using an in vivo approach, we show that they are effective anti-nociceptives in wild-type but not Ca_V3.2 knock-out mice. Importantly, we show that they lack sedative/hypnotic effects. Full article

Flocking control in networked agent systems (NASs) has been extensively studied, yet many existing methods overlook two critical issues: the need for fast, predictable convergence, and resilience against false data injection (FDI) attacks. To tackle these challenges, this paper proposes a secure predefined-time quasi-flocking control scheme leveraging neural networks. First, a predefined-time control protocol is formulated via a time-varying scaling function, which ensures that all agents achieve quasi-flocking behavior within a prescribed time, independent of their initial conditions. This design guarantees rapid and predictable convergence. Second, radial basis function (RBF) neural networks are employed to estimate the unknown disturbances induced by FDI attacks. A novel adaptive update law is developed to dynamically compensate for these uncertainties in real-time. Lyapunov-based analysis rigorously proves that the proposed control strategy achieves predefined-time quasi-flocking while preserving robustness against adversarial attacks. Finally, extensive simulation results demonstrate that the proposed approach ensures rapid convergence and robust performance in flocking control. Full article

Accurate and spatially detailed soil moisture (SM) data are essential for hydrological research, precision agriculture, and ecosystem monitoring. The NASA’s Soil Moisture Active Passive (SMAP) product offers unprecedented information on global soil moisture. To provide more detailed information about the cropland SM data for the Contiguous United States (CONUS), a 1-km SMAP product has been produced using the THySM model in support of USDA NASS operations. However, the current 1-km product contains substantial data gaps, which poses challenges for applications that require continuous daily data. Data Interpolation Empirical Orthogonal Functions (DINEOF+) is an interpolation technique that uses singular value decomposition (SVD) to address missing data problems. Previous studies have applied DINEOF+ to reconstruct the 1-km daily SM dataset but without further analysis of the reconstruction errors. In this study, we perform a comprehensive validation of DINEOF+ reconstructed SM by using both the original SMAP data and in situ measurements across the CONUS. Our results show that the reconstructed SM closely aligns with the original SM with R² > 0.65 and bias ranging from 0.01 to 0.02 m³/m³. When compared to in situ SM, the mean absolute error (MAE) ranges between 0.01 and 0.04 m³/m³ and the time series correlation coefficient ranges from 0.6 to 0.8. Our findings suggest that DINEOF+ effectively recovers missing data and improves the temporal resolution of SM time series. However, we also note that the accuracy of the reconstructed SM is dependent on the quality of the original SMAP data, emphasizing the need for continued improvements in SM retrievals by satellite. Full article

Background/Objectives: It is increasingly recognized that traumatic life experiences render individuals more vulnerable to gastrointestinal (GI) symptoms and chronic bowel conditions like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). In this study, we examined whether this effect is mediated by negative affectivity. Methods: A total of 281 participants recruited in the Netherlands, including 94 with IBD, 95 with IBS and 92 controls, were assessed for lifetime trauma, trait anxiety, depression, and GI (IBD/IBS) disease activity. Results: The results confirmed that negative affectivity fully mediated the association between trauma and GI symptomatology, with trauma and depression explaining 38–40% (IBD|IBS) of the variance in disease activity and trauma and anxiety explaining 31–33% (IBD|IBS) of the variance in disease activity. Upon correction for condition (patient/controls), the predictive capacity increased even further, with trauma and depression now accounting for 43–44% (IBD|IBS) and trauma and anxiety for 40% (IBD and IBS) of the GI symptom heterogeneity. Conclusions: The results are in line with studies linking trauma to negative affectivity and negative affectivity to a more aggressive GI disease course. More generally, they show that the somatic and affective consequences of trauma should not be considered in isolation but must be treated as a covariant whole. Full article

In the evolving landscape of dairy farming, data ownership and privacy have become critical issues. This commentary paper delves into the complexities and implications of data management in the dairy industry, informed by insights from a multidisciplinary group of stakeholders. While the authors bring a U.S. perspective, the challenges discussed are globally relevant, given the dominant role of multinational corporations in shaping data practices across regions. The discussions, conducted through structured meetings and iterative online exchanges, emphasized the pressing legal and ethical concerns, the role of technology, and the necessity of developing comprehensive guidelines to safeguard data integrity and benefit all stakeholders. Key points include the global nature of data protection regulations, the potential of blockchain and IoT devices to enhance transparency, and the importance of equitable value distribution. By fostering an environment of transparency and fairness, the dairy industry can harness the power of data to drive innovation and sustainability while protecting the rights of those who generate it. This paper provides a pathway to address these challenges by raising awareness and proposing general actions for the industry’s future. Full article

Cutaneous melanoma (CM) is an aggressive and metastatic tumor, resulting in high mortality rates. Despite significant advances in therapeutics, the available treatments still require improvements. Thus, purinergic signaling emerged as a potential pathway to cancer therapy due to its involvement in cell communication, proliferation, differentiation, and apoptosis. In addition, due to safety and acceptable clinical tolerability, carotenoids from microalgae have been investigated as adjuvants in anti-melanoma therapy. Then, this work aimed to investigate the in vitro anti-melanogenic effect of carotenoid extract (CA) and total biomass (BM) of the Scenedesmus obliquus microalgae on two cutaneous melanoma cell lines (A375 and B16F10). Cells were cultivated under ideal conditions and treated with 10, 25, 50, and 100 μM of CA or BM for 24 h. The effects of the compounds on viability, oxidant status, and purinergic signaling were verified. The IC50 cell viability results showed that CA and BM decreased B16F10 viability at 24.29 μM and 74.85 μM, respectively and decreased A375 viability at 73.93 μM and 127.80 μM, respectively. Carotenoid treatment for 24 h in B16F10 and A375 cells increased the release of reactive oxygen species compared to the control. In addition, CA and BM isolated or combined with cisplatin chemotherapy (CIS) modulated the purinergic system in B16F10 and A375 cell lines through P2X7, A2AR, CD39, and 5′-nucleotidase. They led to cell apoptosis and immunoregulation by activating A2A receptors and CD73 inhibition. The results disclose that CA and BM from Scenedesmus obliquus exhibit an anti-melanogenic effect, inhibiting melanoma cell growth. Full article

Background/Objectives: The Ca²⁺-activated K⁺ channel K_Ca3.1 is not only involved in physiological processes such as immune reactions and control of vascular tone, but is highly expressed in various tumor entities. Thus, imaging of K_Ca3.1 channels comes into focus for the localization of high channel density, i.e., for tumor diagnosis. In particular, the physicochemical properties of the fluorescent probes should be improved compared to existing probes. Methods: The small molecule inhibitor of the K_Ca3.1 channel, senicapoc, was used as a warhead and was coupled with different fluorescent dyes. After synthesis of the novel probes, their physicochemical properties (lipophilicity, photophysical properties) and their ability to image K_Ca3.1 channels in A549-3R lung tumor cells were determined. Results: In order to increase the polarity and quantum yield of reported fluorescent probes, three strategies were followed: (1) An F-atom at the B-atom of bodipy-labeled senicapoc derivatives 9a, 9b, and 15a was replaced by a OCH₃ moiety, which decreased the logP value by one log-unit. (2) The p-phenylene moiety of the linker was replaced by an aliphatic tetramethylene linker decreasing the lipophilicity by 0.3–0.5 log-units. (3) Instead of bodipy dyes, fluorescein was coupled with the senicapoc warhead resulting in very polar probes 21a and 21b with low logP values of 1.5 and 1.3, respectively. Introduction of an ethyl moiety at the bodipy core increased the quantum yield, which resulted in the best punctate staining pattern of fixed and living A549-3R lung tumor cells with the ethylbodipy-labeled senicapoc derivative 10b. The specificity was shown by various control experiments. Co-staining with 10b and an antibody did not result in overlapping signals. Conclusions: The well-balanced lipophilicity and fluorescent quantum yield render the ethylbodipy-labeled senicapoc derivative 10b a very good probe to image selectively K_Ca3.1 ion channels in fixed and living tumor cells. It was hypothesized that the antibody binds selectively at the closed channel (58.5%), whereas the senicapoc–bodipy conjugate 10b binds selectively at the open channel (41.5%). The ratio 58.5:41.5 reflects the ratio of the ion channel in closed and open conformations. Full article

Satellite remote sensing enables monitoring of regenerative agriculture practices, such as crop rotation, cover cropping, and conservation tillage to allow tracking and quantification at unprecedented scales. The Monitor system presented here capitalizes on the scope and scale of these data by integrating crop identification, cover cropping, and tillage intensity estimations annually at field scales across the contiguous United States (CONUS) from 2014 to 2023. The results provide the first ever mapping of these practices at this temporal fidelity and spatial scale, unlocking valuable insights for sustainable agricultural management. Monitor incorporates three datasets: CropID, a deep learning transformer model using Sentinel-2 and USDA Cropland Data Layer (CDL) data from 2018 to 2023 to predict annual crop types; the living root data, which use Normalized Difference Vegetation Index (NDVI) data to determine cover crop presence through regional parameterization; and residue cover (RC) data, which uses the Normalized Difference Tillage Index (NDTI) and crop residue cover (CRC) index to assess tillage intensity. The system calculates field-scale statistics and integrates these components to compile a comprehensive field management history. Results are validated with 35,184 ground-truth data points from 19 U.S. states, showing an overall accuracy of 80% for crop identification, 78% for cover crop detection, and 63% for tillage intensity. Also, comparisons with USDA NASS Ag Census data indicate that cover crop adoption rates were within 20% of estimates for 90% of states in 2017 and 81% in 2022, while for conventional tillage, 52% and 25% of states were within 20% of estimates, increasing to 75% and 67% for conservation tillage. Monitor provides a comprehensive view of regenerative practices by crop season for all of CONUS across a decade, supporting decision-making for sustainable agricultural management including associated outcomes such as reductions in emissions, long term yield resiliency, and supply chain stability. Full article

This work explores the polymerization of sodium 4-styrenesulfonate (NaSS) inside filter paper using dielectric barrier discharge (DBD) plasma and its application in the environmental field. The plasma-based technique, performed under mild conditions, solves common problems associated with conventional polymerization inside porous materials. The polymerization process was monitored using Fourier-transform infrared (FTIR) spectroscopy, which confirmed the consumption of double bonds, particularly in NaSS samples containing the optimal concentration of crosslinker divinyl benzene (DVB) (0.25% wt). Our work demonstrates the effectiveness and promise of DBD plasma as a substitute polymerization approach, especially for those in porous materials. Full article

Epilepsy is characterized by abnormal neuronal firing in the brain. Several therapeutic strategies exist for epilepsy; however, several patients remain poorly treated. Therefore, the development of effective treatments remains a high priority in the field. Neuroactive steroids can potentiate extra-synaptic and synaptic GABA_A receptors, thereby providing therapeutic benefits relative to benzodiazepines. This research study investigated the therapeutic effectiveness and underlying mechanisms of LPM682000012, a new synthetic neuroactive steroid-positive allosteric modulator (PAM) of GABA_A receptors employed for treating epilepsy. Acute and chronic rat epilepsy models were established to identify the anti-seizure potency of LPM682000012. The dose-dependent sedative effects of LPM682000012 and Ganaxolone in normal rats were evaluated, which revealed that they both dose-dependently alleviated acute epileptic seizure in the pentylenetetrazol (PTZ)-mediated seizure model. Furthermore, LPM682000012 indicated an enhanced safety profile than Ganaxolone. Moreover, LPM682000012 also indicated therapeutic effects in the kainic acid (KA)-induced chronic spontaneous seizure model. Morphologically, LPM682000012 decreased neuronal loss in the hippocampal CA1 and CA3 regions and increased dendritic spine density in the CA1 region. In addition, mechanical analyses, including transcriptomics, Western blot, and proteomics analyses, revealed that the Serpina3n/NF-κB signaling pathway was up-regulated in epileptic rat hippocampal tissue, and LPM682000012 treatment reversed these changes. In summary, this report demonstrated that the novel neurosteroid GABA_A PAM LPM682000012 activated the synaptic and extra-synaptic GABA_A receptors and alleviated KA-induced neuronal loss and synaptic remodeling, potentially by down-regulating the Serpina3n/NF-κB signaling pathways. The results provide evidence that LPM682000012 is a potential anti-seizure pharmacotherapy candidate for epilepsy and warrants further research. Full article

With the increasing awareness of socio-environmental issues, a global trend has emerged emphasizing the valorization of natural ingredients that promote health and well-being within sustainable production systems, such as microalgae-based carotenoids. Currently, little is understood about the correlation between biomass productivity and carotenoid content, which is a fundamental parameter for facilitating the immediate expansion of microalgae bioprocesses and ensuring the availability and industrial viability of these compounds. In this context, this study aims to investigate the carotenoid profile of Chlorella vulgaris through growth curve experiments conducted under photoautotrophic and heterotrophic regimes. Additionally, a trade-off analysis was performed for the production of carotenoids from microalgae. Carotenoids were quantified using high-performance liquid chromatography coupled with diode array and mass spectrometry detectors (HPLC-PDA-MS/MS). The performance of kinetic phases and energy demands across growth regimes was assessed to provide insights into production trade-offs. The results indicated that a total of 22 different carotenoids were identified in all the extracts. The all-trans-lutein and all-trans-β-carotene were the majority compounds. The total carotenoid content of Chlorella vulgaris revealed significant differences in the kinetic phases of carotenoid production, indicating that carotenoid volumetric production is only viable if the cultures are conducted until the log and stationary phases, based on the function of the biomass volumetric production (weight.volume⁻¹). Therefore, the best trade-off for the process was to provide photoautotrophic growth until the exponential phase (log). Under this condition, the maximum carotenoid and lutein content was 2921.70 µg.L⁻¹, reaching a maximum cell biomass of 1.46 g.L⁻¹. From an environmental/economic point of view, the energy demand was 7.74 kWh.L⁻¹. Finally, the scientific advances achieved in this study provide a holistic view of the influence of the main cultivation methods on the production of microalgae carotenoids, suggesting a viable initial direction for different industrial applications. Full article