Search Results (88)

Background: Current sepsis guidelines recommend the best supportive treatment for severe sepsis, but they are limited on the effectiveness of immunomodulatory therapies. Recent data suggest that IgM-enriched immunoglobulin preparations may decrease mortality, but the exact pathomechanism remains unknown. The present experimental study aims to test the hypothesis that IgM-enriched immunoglobulin may improve hemodynamics in E-coli-induced severe sepsis. Subjects and methods: Sepsis was induced in the E. coli bacteriemia (n = 8), E. coli-parallel Pentaglobin treatment (PR-PG; n = 8), and E. coli-delayed Pentaglobin treatment (D-PG; n = 8). Sepsis was induced in the sepsis, PR-PG, and D-PG groups by infusing 38 mL of an E. coli suspension (2.5 × 10⁵/mL) over 3 h. The PR-PG group received a 0.75 g/kg Pentaglobin bolus over 20 min concurrently with the start of E. coli infusion. The D-PG group was given a 0.67 g/kg Pentaglobin bolus one hour after starting E. coli, followed by a continuous infusion at 0.02 g/kg/h for 240 min. Hemodynamic parameters were monitored every 2 h using a pulse contour cardiac output monitoring technique (PiCCo™). Results: Heart rate increased in all groups to varying extents. Mean arterial pressure (MAP) remained stable in controls but declined in untreated sepsis. Both Pentaglobin-treated groups showed higher MAP than untreated septic animals. Mild cardiac index increases occurred in controls and untreated sepsis, whereas the treated groups maintained a consistently elevated CI after Pentaglobin administration. Systemic vascular resistance index (SVRI) transiently increased in controls before normalizing, while untreated septic animals experienced continuous SVRI decline. Treated animals showed an initial transient SVRI rise followed by a decline; yet, SVRI remained higher than in untreated sepsis. Conclusions: IgM-enriched immunoglobulin led to a slight stabilization of some hemodynamic parameters, probably due to the reduced extpnfiravasation of fluids into the interstitium and, hence, had an effect on preload. Full article

Background: Large language models (LLMs) are increasingly used in clinical medicine, yet their ability to interpret advanced intraoperative hemodynamic monitoring—particularly in the context of liver transplantation—remains largely unexplored. In this proof-of-concept study, we evaluated ChatGPT’s capacity to interpret multimodal hemodynamic data derived from both standard anesthesia monitoring and the PiCCO system. The study also employed a structured assessment instrument (ARQuAT), adapted through a Delphi-based process to evaluate LLM-generated clinical interpretations. Methods: Ten key surgical–hemodynamic phases of liver transplantation were identified using a modified Delphi approach to capture the major physiological transitions of the procedure. Sequential screenshots representing these phases were obtained from five liver transplant recipients, yielding a total of 50 images. Each screenshot, along with standardized clinical background information, was submitted to ChatGPT. Five expert anesthesiologists independently assessed the model’s responses using the modified ARQuAT tool, which includes six content-quality domains (Accuracy, Up-to-dateness, Contextual Consistency, Clinical Usability, Trustworthiness, Clarity) and a separate catastrophic Risk item. Descriptive statistics were calculated for domain-level performance. Inter-rater reliability (Kendall’s W) and internal consistency (Cronbach’s alpha, McDonald’s omega) were also analyzed. All statistical analyses and visualizations were performed using NumIQO. Results: ChatGPT demonstrated consistently high performance across all content-quality domains, with median scores ranging from 4.6 to 4.8 and more than 90% of all ratings classified as satisfactory. Lower scores appeared only in a small subset of frames associated with abrupt hemodynamic changes and did not indicate a recurring weakness in any specific domain. Catastrophic Risk exhibited a pronounced floor effect, with 86% of ratings scored as 0 and only three isolated high-risk assessments across the dataset. Internal consistency of the six ARQuAT content domains was excellent, while inter-rater agreement was modest, reflecting ceiling effects and tied ratings among evaluators. Conclusions: ChatGPT generated clinically acceptable, contextually aligned interpretations of complex intraoperative hemodynamic data in liver transplant recipients, with minimal evidence of unsafe recommendations. These findings suggest preliminary promise for LLM-assisted interpretation of advanced monitoring, while underscoring the need for future studies involving larger datasets, dynamic physiological inputs, and expanded evaluator groups. The reliability characteristics observed also provide initial support for further refinement and broader validation of the Delphi-derived ARQuAT framework. Full article

Valued above all others, the white truffle species (Tuber magnatum Picco) is highly dependent on the forest ecosystem and its underground biology. Despite its economic importance, knowledge of its biology and mycorrhizal symbioses remains limited; moreover, natural yields have sharply declined, and cultivation efforts have produced inconsistent results. This study evaluated various forest and mycorrhizal inoculation techniques to promote T. magnatum mycelium development in three Tuscan sites converted to truffle cultivation, using qPCR analysis. Alongside conventional practices like irrigation, mulching, and tillage, an experimental method with a sterile, spore-inoculated soil barrier was tested to improve host root establishment, enhance mycorrhization, and maintain long-term symbiosis for healthy truffle ecosystems. Soil analyses nine months after planting Quercus robur L. seedlings showed significant differences in Tuber magnatum mycelium abundance across sites and treatments. The MA treatment—mycorrhized seedlings combined with a sterile, inoculated substrate and separation diaphragm—produced the highest mycelial levels, underscoring the importance of initial mycorrhization and soil manipulation. These findings provide valuable insights for optimizing forest management and improving truffle cultivation by enhancing mycelial development, a key step toward increasing truffle production. Full article

Background/Objectives: This study aims to investigate the underexplored impact of capsule type on the performances of capsule-based dry powder inhalers (cDPIs). It compares specific properties of hard gelatin-based capsules (Hard Gelatin Capsules (HGC), HGC including polyethylene glycol (HGC + PEG)) and hypromellose-based capsules, (Zephyr^® Vcaps^® (VC), Zephyr^® Vcaps^® Plus (VCP) and Vcaps^® Plus Zephyr Inhance™ (VCP-I)) with aerosolization performances of model carrier-based formulation, providing insights into their impact on pulmonary drug delivery efficacy. Methods: Aerosolization properties of a model phenytoin/lactose blend formulation filled in the different capsules was evaluated using a Next Generation Impactor (NGI) with RS01 device. Capsule shell characteristics were evaluated in terms of water activity, static charges, and inner surface aspect and roughness. Results: Hypromellose-based capsules, especially VC and VCP-I, exhibited significantly higher drug delivery performances compared to gelatin-based capsules. In particular, VCP-I demonstrated good results with excellent batch-to-batch reproducibility and 51% of the nominal dose available for lung absorption. Although capsule inner surface showed clear differences between both polymer families, no clear correlation could be found between cDPI performances and capsule roughness and density of charge. All capsules presented good mechanical properties in the conditions of the tests. Conclusions: Capsule type exerts a significant impact on cDPI performances. These findings highlight the importance of capsule selection as a critical material attribute in the design and optimization of inhalation products. Full article

Variants in CLCN3 and CLCN4, encoding the neuronal endosomal Cl⁻/H⁺ antiporters ClC-3 and ClC-4, are linked to neurodevelopmental disorders with broad phenotypic variability. Over sixty CLCN4 variants have been functionally characterized, showing gain- or loss-of-function (GoF or LoF) effects. While ClC-3 can function as a homodimer, ClC-4 depends on heterodimerization with ClC-3 for efficient endosomal trafficking. CLCN4, located on the X chromosome, exhibits diverse pathogenic outcomes: complete LoF variants often cause non-syndromic presentations in hemizygous males and are asymptomatic in heterozygous females, whereas certain missense variants with partial or complete LoF produce severe syndromic phenotypes in both sexes. Here, we demonstrate dominant effects of three CLCN4 variants within ClC-3/ClC-4 heterodimers using two-electrode voltage-clamp recordings in Xenopus laevis oocytes and whole-cell patch-clamp recordings in mammalian cells co-expressing both proteins via a bicistronic IRES construct. Our findings provide the first evidence of dominant-negative CLCN4 effects within ClC-3/ClC-4 complexes and establish a platform for functional analysis of additional disease-associated variants. Full article

Therapeutic innovation in cardiovascular medicine is rapidly overcoming the limitations of conventional strategies, providing more targeted, durable, and multidimensional solutions. Key advances include next-generation lipid-lowering agents such as PCSK9 inhibitors, inclisiran, and bempedoic acid, as well as metabolic drugs like SGLT2 inhibitors, GLP-1 receptor agonists, and dual GIP/GLP-1 agonists, which offer cardiovascular and renal benefits beyond glucose control. At the same time, gene therapies, RNA-based interventions, genome editing tools, and nanocarriers are paving the way for precision medicine tailored to individual patient profiles. In parallel, digital innovations, including artificial intelligence, remote monitoring, and telehealth platforms, are transforming care delivery by enhancing adherence, enabling earlier intervention, and refining risk stratification. Collectively, these developments signify a paradigm shift toward a more personalized, proactive, and systems-based model of cardiovascular care. Full article

Background/Objectives: Fluid management in shock remains a clinical challenge, with ongoing debate about optimal guidance. Despite advanced technologies, fluid balance assessment is often inadequate. The SkInShock study investigated whether transepidermal water loss (TEWL) measurements could improve fluid balance estimation and serve as a non-invasive marker of vascular tone in patients with septic or cardiogenic shock. Methods: In this prospective single-center feasibility study (DRKS00027981), TEWL was measured daily in eight mechanically ventilated patients using a Tewameter^® (Courage+Khazaka, Cologne, Germany), which quantifies transcutaneous water evaporation. Total daily skin water loss was calculated either via direct TEWL measurements or an estimation formula (6 mL/kg/day + 20%/°C deviation from 37 °C). Systemic vascular resistance index (SVRI) was measured simultaneously using PiCCO^® technology (Pulsion Medical Systems, Munich, Germany) to evaluate the relationship between TEWL and vascular tone. Results: TEWL values were consistent across most body sites, except the forehead. TEWL-based estimates of skin water loss were significantly lower than formula-based estimates (p < 0.01). Formula-based values overestimated water loss at low TEWL levels and underestimated it at higher levels, with deviations reaching ±100%. While absolute TEWL values did not correlate with SVRI, intra-individually normalized values showed a significant negative correlation, indicating that higher skin water loss corresponded to lower vascular tone. Conclusions: TEWL measurement is feasible in ICU patients and may enhance fluid balance assessment and vascular tone monitoring. Our preliminary findings indicate that this non-invasive method could complement current diagnostics but warrants further investigation in larger cohorts. Full article

The Molise region in Central-Southern Italy is a major contributor to national truffle production, particularly of the highly prized Tuber magnatum Picco, accounting for approximately 40% of the country’s total output and hosting the highest density of truffle harvesters. Despite this, research on the Italian white truffle populations from this area remains limited. Therefore, the primary objective of the present study was to address this knowledge gap by characterizing four T. magnatum Picco populations collected from the municipalities of Agnone, Carovilli, Castel del Giudice, and Pietrabbondante, located in “Alto Molise”, through morphological, genetic, and microbiological investigations. The statistical analyses revealed significant differences in peridium thickness and ascocarp-associated microbiota even though pairwise comparisons did not identify statistically significant differences between specific population pairs. No significant variation was observed in ascocarp weight and maturation degree. Furthermore, the presence of a unique haplotype at the single-locus marker SCAR A21-inf was confirmed in a subset of the analyzed fruiting bodies. Collectively, these findings expand current biological knowledge of the Molise white truffle and provide a foundation for future research aimed at identifying specific provenance markers to discriminate truffle populations at both regional and local scales. Full article

Background/Objectives: “Accelerated Recovery after Surgery” (ARAS) programs for esophagectomy aim to shorten the perioperative course without increases in morbidity or mortality. In such programs, the prediction and early detection of perioperative complications is essential, as ICU observation times are limited. We evaluated two potential laboratory markers as predictors for postoperative complications: shedding of the endothelial glycocalyx and the veno-arterial CO₂-gap as indicators of microcirculatory disturbances. Methods: In total, 26 patients undergoing hybrid Ivor Lewis esophagectomy within an ARAS program were included. Macrocirculatory conditions were kept stable by enhanced hemodynamic monitoring (PiCCO). Glycocalyx shedding parameters (Syndecan-1, heparan sulfate, hyaluronic acid) and a panel of inflammatory mediators were measured preoperatively, upon ICU-admission, and on the first postoperative day. The veno-arterial CO₂-gap was calculated at induction of anesthesia, during laparoscopy, and upon admission to the ICU. Results: Complications (Dindo-Clavien ≥3) occurred in n = 16 (62%) patients. From preoperatively to admission to the ICU, Syndecan-1 (29 pre-op to 56 ng/mL at ICU-admission) and Interleukins 1b (1.2 to 1.4 pg/mL), 6 (1.3 to 19.9 pg/mL), 8 (5.2 to 19.9 pg/mL), and 10 (0.50 to 1.33 pg/mL) increased, indicating a temporary increase in inflammation and glycocalyx shedding during surgery. A difference between patients with or without complications could not be detected. There was also no difference in the veno-arterial CO₂-gap between the two groups (median of 6.8 mmHg in all patients, 6.7 in patients with complications, 7.8 in patients without complications). Conclusions: Signs of microcirculatory dysfunctions and inflammation occurred during esophagectomy within an ARAS protocol with tightly controlled hemodynamics. Increases in Syndecan-1 and the veno-arterial CO₂-gap could not predict perioperative complications. Full article

Forest harvesting can alter sedimentary processes in catchments by reducing vegetation cover and exposing the soil surface. To mitigate these effects, post-harvest residue management is commonly used, though its effectiveness needs individual evaluation. This study assessed how windrowed harvest residues influence structural sediment connectivity in two forest catchments in south-central Chile with a Mediterranean climate. Using digital terrain models and the Index of Connectivity, scenarios with and without windrows were compared. Despite similar windrow characteristics, effectiveness varied between catchments. In catchment N01 (12.6 ha, average slope 0.28 m m⁻¹), with 13.6% windrow coverage, connectivity remained unchanged, but in contrast, catchment N02 (14 ha, average slope 0.27 m m⁻¹), with 21.9% coverage, showed a significant connectivity reduction. A key factor was windrows’ orientation: 83.9% aligned with contour lines in N02 versus 58.6% in N01. Distance to drainage channels also played a role, with the decreasing effect of connectivity at 50–60 m in N02. Bootstrap analysis confirmed significant differences between catchments. These results suggest that windrow configuration, particularly contour alignment, may be more critical than coverage percentage. For effective connectivity reduction, especially on moderate to steep slopes, forest managers should prioritize contour-aligned windrows. This study enhances our understanding of structural sediment connectivity and offers practical insights for sustainable post-harvest forest management. Full article

Dissolved oxygen (DO) is a fundamental water quality parameter that directly determines aquaculture productivity. China contributes 57% of the global aquaculture production, with the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) serving as a key contributor. However, this region faces significant environmental challenges due to increasing intensive stocking densities and outdated management practices, while also grappling with the systematic monitoring limitations of large-scale operations. To address these challenges, in this study, a random forest-based model was developed for DO concentration retrieval (R² = 0.82) using Landsat 8/9 OLI imagery. The Lindeman, Merenda, and Gold (LMG) algorithm was applied to field data collected from four cities—Foshan, Hong Kong, Huizhou, and Zhongshan—to identify key environmental drivers to the changes in DO concentration in these cities. This study also employed satellite imagery from multiple periods to analyze the spatiotemporal distribution and trends of DO concentrations over the past decade, aiming to enhance understanding of DO variability. The results indicate that the average DO concentration in fishponds across the GBA was 7.44 mg/L with a statistically insignificant upward trend. Spatially, the DO levels remained slightly lower than those in other waters. The primary environmental factor influencing DO variations was the pH levels, while the relationship between natural factors such as the temperature and DO concentration was significantly hidden by aquaculture management practices. The further analysis of fishpond water quality parameters across land uses revealed that fishponds with lower DO concentrations (7.293 mg/L) are often located in areas with intensive human intervention, particularly in highly urbanized regions. The approach proposed in this study provides an operational method for large-scale DO monitoring in aquaculture systems, enabling the qualification of anthropogenic influences on water quality dynamics. It also offers scalable solutions for the development of adaptive management strategies, thereby supporting the sustainable management of aquaculture environments. Full article

Rose Bengal (RB) holds promise for therapeutic applications in the gastrointestinal (GI) tract but faces significant limitations due to poor bioavailability and stability in the GI environment. This in vitro proof-of-concept study aimed to develop an oral drug delivery system using self-assembled RB–chitosan (RBCS) nanocomposites formed via electrostatic interactions. RBCS nanocomposites exhibited high drug loading efficiency (87%) and a uniform particle size (~443 nm), with physicochemical analyses confirming molecular interactions and structural stability. However, in vitro studies revealed poor and highly variable drug release in simulated gastric fluids (SGFs), underlining the need for further optimization. To address these limitations, RBCS nanocomposites were encapsulated within well-established alginate beads (AlgBs). Among the tested systems, RBCS20-AlgBs were selected as the optimal one, forming a gastroresistant platform. Encapsulation mitigated burst release, enhanced structural integrity, and enabled sustained RB release under intestinal conditions. Swelling studies demonstrated that RBCS20-AlgBs maintained controlled hydration, preventing premature disintegration. Mathematical modeling indicated a matrix relaxation-driven release mechanism, with RBCS20-AlgBs demonstrating improved reproducibility compared to RB-loaded AlgBs (RB-AlgBs). Future studies should focus on evaluating in vivo performance to confirm the system’s efficacy for oral administration. Full article

Selenium (Se) is an essential micronutrient, yet its deficiency remains a global concern. This study investigates the biofortification of alfalfa (Medicago sativa cv. ProINTA Super Monarca GR9) via foliar Se application to enhance Se accumulation and transformation into bioavailable organic forms. A controlled environment experiment in a plant growth chamber and a one-season open-field trial (January 2023, Argentina) were conducted. Treatments included sodium selenate (Se(VI)), sodium selenite (Se(IV)), and a 1:1 mixture, applied at 45 and 90 g Se ha⁻¹, with and without the biostimulant BIOFORGE^®. Treated plants exhibited increased Se content, correlating with the applied doses. X-ray absorption spectroscopy (XAS) confirmed that most inorganic Se was transformed into organic Se forms, with Se(IV) treatments yielding the highest concentrations of organic Se species such as selenocysteine (SeCys) and selenomethionine (SeMet). Open-field trials showed a complete conversion of Se, though total Se accumulation was lower than in controlled conditions. Se treatments did not affect forage quality or biomass production. The biostimulant slightly reduced Se uptake but did not compromise biofortification. These results highlight Se(IV) as the optimal treatment for alfalfa biofortification, presenting a sustainable strategy to enhance dietary Se intake through functional foods. Full article

Herbicide resistance is an emerging phytosanitary threat, causing serious yield and economic losses. Although this phenomenon has been widely studied, only recently has the role of epigenetic factors in its occurrence been considered. In the present study, we analyzed the microRNA-mediated regulation in Echinochloa oryzicola (Vasinger) Vasinger (late-watergrass) of the expression of cytochromes P450, glutathione S-transferase (GST), and eIF4B, all of which are enzymes involved in profoxydim (AURA^®) detoxification. Before and after profoxydim application, the expression profiles of microRNAs (miRNAs) were selected for their ability to target the genes considered, and their targets were assessed by means of RT-qPCR. Susceptible and resistant biotypes showed different responses to this herbicide. After profoxydim application, in resistant biotypes, osa-miR2099-5p, ath-miR396b, osa-miR395f, osa-miR396a-5p, osa-miR166a-5p, osa-miR166d-5p, gra-miR8759, and gma-miR396f were not triggered, allowing the expression of CYP81A, GSTF1, and eIF4B genes and the herbicide’s detoxification. Meanwhile, the transcription of ata-miR166c-5p, ath-miR847, osa-miR5538, and gra-miR7487c was triggered, down-regulating CYP71AK2, CYP72A254, CYP72A122, and EcGST expression. In susceptible biotypes, the herbicide stimulated ata-miR166c-5p, ath-miR847, osa-miR5538, gra-miR7487c, osa-miR166a-5p, and gra-miR8759, down-regulating their respective target genes (CYP72A122, CYP71AK2, EcGST, CYP72A254, CYP81A12, and eIF4B). A better understanding of the role of miRNA-mediated epigenetic regulation in herbicide resistance will be useful in planning more targeted and sustainable methods for controlling this phytosanitary threat. Full article

This research explores how climate change will affect building energy use across the UK by analysing both a conventional reference building design and a net-zero energy (NZEBs) alternative to assess how each would perform under future weather conditions. Using climate projections from databases like Prometheus and Meteonorm, along with simulation tools like EnergyPlus and Freds4Buildings, the study evaluates the energy performance, costs, and GHG emissions of a case study building under current weather conditions, with 2030, 2050, and 2080 forecasts in three different UK locations: Exeter, Manchester, and Aberdeen. Results indicate that heating demand will decrease consistently over time across all locations by as much as 21% by 2080 while cooling demand will rise sharply. NZEBs proved more resilient to these changes, using less energy and producing fewer GHG emissions than conventional buildings, with 89% reductions in emissions even with increased cooling needs. Accounting for future weather helps both understand the risks of conventional design, with a number of scenarios experiencing overheating in 2080 and ensure NZEBs can meet their goals during their entire lifespan despite the increases in energy needs. The study highlights both the impact of accounting for future weather forecasts during design and the increasing relevance of net-zero energy designs in mitigating the effects of climate change while offering practical insights for architects, policymakers, and energy planners, showing why future weather patterns need to be considered in sustainable building design to ensure buildings will achieve their carbon targets throughout their life. Full article