Search Results (1,788)

Lymphovenous anastomosis (LVA) has become an established microsurgical treatment for lymphedema, yet the hemodynamic basis for its efficacy in the lower extremity has not been rigorously examined. Most assessments of anastomotic function are performed in the supine position, where lymphatic pressure exceeds venous pressure, creating a favorable gradient for drainage. However, adults spend 16–18 h daily in upright postures, during which ankle-level venous pressure rises to 80–100 mmHg while lymphatic pressure increases only modestly. This pressure reversal raises questions about whether lower extremity LVA can function during routine daily activities. Several protective mechanisms have been proposed, including careful recipient venule selection, competent venous valves, and calf muscle pump assistance, yet these safeguards are inherently intermittent rather than continuous. Clinical data reveal progressive anastomotic patency decline over time, with some studies reporting 64% occlusion at two years, a pattern consistent with cumulative hemodynamic injury. Notably, clinical improvement sometimes persists despite declining patency, suggesting that concurrent conservative therapy or selection bias may contribute to observed outcomes. This review critically examines the postural hemodynamics relevant to lower extremity LVA, evaluates proposed protective mechanisms, and argues that the fundamental premise of sustained upright-posture drainage remains untested after three decades of clinical practice. Full article

Cardiogenic shock (CS) remains a life-threatening syndrome characterized by reduced cardiac output and end-organ hypoperfusion, most commonly resulting from acute myocardial infarction (AMI). Despite advances in early revascularization and increasing use of percutaneous mechanical circulatory support (MCS), short-term mortality in AMI-related CS (AMI-CS) remains high. This review summarizes the contemporary evidence on short-term percutaneous MCS in AMI-CS, with a focus on intra-aortic balloon pump (IABP), Impella microaxial flow pumps, and venoarterial extracorporeal membrane oxygenation (VA-ECMO), and provides insights into device selection and implementation in clinical practice. We performed a comprehensive analysis of the most relevant randomized controlled trials and key guideline recommendations from European and North American societies concerning the use of MCS. Despite its long-standing, IABP has not demonstrated a mortality benefit in contemporary trials and is no longer recommended for routine use in AMI-CS without mechanical complications. Nevertheless, it remains widely used due to its simplicity, safety profile, and broad availability. In contrast, Impella devices provide active left ventricular unloading and have shown promising hemodynamic effects, with the DanGer Shock trial suggesting a potential survival benefit in carefully selected patients, at the expense of higher complication rates. VA-ECMO offers full cardiopulmonary support but is associated with the highest complication rates and increases left ventricular afterload, often requiring adjunctive unloading with devices such as Impella (ECPELLA). However, recent randomized trials have not demonstrated a clear survival advantage for VA-ECMO, and concerns regarding its complications persist. In conclusion, CS continues to pose major therapeutic challenges, and no single MCS device has consistently shown a survival benefit across all AMI-CS patient populations. Individualized, phenotype-driven strategies that incorporate hemodynamic profiling and timely escalation of support are essential. Further randomized studies are urgently needed to define optimal device selection, the timing of placement, and appropriate patient selection criteria. Institutional protocols guided by clinical stage, etiology, and available expertise will be pivotal in improving outcomes. Full article

Decarbonising the existing residential sector is a central priority of European energy policy, yet masonry buildings from the early 2000s remain significantly underrepresented in net-zero energy building (NZEB) research. This study addresses this critical gap by evaluating a holistic deep retrofit of a representative single-family house in Cracow, Poland, providing a scalable model for the Central European housing stock. The methodology integrated structural and systemic interventions: eliminating thermal bridges via balcony removal, enhancing the envelope with 0.25 m of mineral wool (λ = 0.036 W/m K), and installing innovative active triple-glazed windows (U_w = 0.85 W/m² K) with integrated electric heating foils. The energy system was transformed by replacing a coal-fired boiler with an 8 kW air-to-water heat pump and a 7 kWp photovoltaic array, complemented by a green roof on the western pitch for passive thermal buffering. Verified results demonstrate a radical reduction in the non-renewable primary energy (EP) index from 224.56 kWh/(m²·a) to 0.00 kWh/(m²·a), achieving full compliance with stringent “WT 2021” standards. Economic analysis reveals that the integrated approach is financially viable, with a simple payback time (SPBT) of 7.1 years when supported by available subsidies. This study concludes that the integration of active glazing, high-performance insulation, and nature-based solutions offers a replicable and economically sound roadmap for transforming legacy housing into zero-emission assets. Full article

The impact of climate change (CC) includes a decline in agricultural production due to crop damage caused by flooding and drought, which destroys crops before harvest, particularly in small-scale irrigation areas. This has led farmers to look for alternative irrigation methods, i.e., groundwater through dug-wells. However, the volume of water obtained through dug-wells is limited. This has led farmers to select the crops they would cultivate. This study aimed to examine the factors that influence farmers in selecting the crops to be cultivated through multinomial logistic regression (MLR). A total of 118 farmers in Jember and Lumajang were randomly selected and interviewed regarding the use of wells and the selection of crops to be cultivated. The dependent variables consist of three crop pattern categories. The results showed that water access variables—particularly well depth, pumped water volume, pipe length, and pump power—significantly influence crop pattern selection (p < 0.01). Farmers adopting diversified crop patterns (food-other and mixed crop pattern) extracted substantially higher groundwater volumes (>76,659 m³ ha⁻¹ annually) and relied on deeper wells (>90 m) compared with the food-crop-dominated pattern. In contrast, water-use-efficient strategies were characterized by lower extraction volumes (<56,755.99 m³ ha⁻¹ annually), longer distribution pipes, and shallower wells (<90 m). Future research should examine the impacts of CC on aquifer depletion and the consequent implications for agricultural activities. Full article

Background/Objective: Activity of SGK-1 has been associated with mechanical aspects of vascular remodeling and matrix stiffening has been a known characteristic of AAA. We hypothesis that VSMC-specific SGK-1 activity is vital to growth of AAA and contributes to progressive aortic stiffness. Methods: C57Bl/6 and SMC-SGK-1KO^+/− mice underwent AAA induction vs Sham on day 0. A subset of C57Bl/6 mice had pump implantation to treat with EMD638683. Aortic ultrasound images were obtained on Day 0 and Day 21 and analyzed for mechanical parameters. At terminal procedure the infrarenal aorta was harvested for immunoblot analysis. Results: At Day 21, C57Bl/6+AAA mice showed growth of 72.27% ± 2.2% versus the C57Bl/6+Sham (p < 0.0001) with associated 3.71 ± 1.15-fold increase in SGK-1 activity (p = 0.001). C57Bl/6+AAA+EMD mice demonstrated growth of 23.68% ± 2.82% (p = 0.0452) with no significant change in SGK-1 activity. SMC-SGK1-KO^+/−+AAA mice had growth of 28.20% ± 3.74% compared to SMC-SGK1-KO^+/−+Sham (p = 0.004) with increased SGK-1 activity (p = 0.0303). Radial strain was significantly reduced in the C57Bl/6+AAA (p = 0.0062) and C57Bl/6+AAA+EMD (p = 0.0135) when compared to C57Bl/6+Sham. Distensibility was significantly reduced in C57Bl/6+AAA (p = 0.01). Pulse propagation velocity (PPV) was significantly elevated in C57Bl/6+AAA mice (p < 0.0001) but inhibited by EMD therapy (p = 0.0007 vs. C57Bl/6+AAA). SMC-SGK1-KO^+/− +AAA mice showed significant reductions in radial strain (p = 0.0011) and distensibility (p = 0.0233) with a modest, but significant, increase in PPV (p = 0.0148). Conclusions: SGK-1 inhibition attenuated AAA growth and preserved vascular function. Targeting this pathway may provide a directed medical therapy for AAA and warrants further investigation. Full article

The non-uniform production contribution caused by insufficient reservoir stimulation during initial fracturing significantly constrains the lifecycle and estimated ultimate recovery (EUR) of horizontal wells. Refracturing is therefore urgently required to reconstruct fracture networks and activate undeveloped reserves. In this study, a coupled geomechanics-matrix-fracture-seepage model is developed based on the Unconventional Fracturing Model (UFM) to characterize formation energy evolution and residual oil distribution. Simulation results indicate that initial fracturing creates a limited pressure diffusion radius (5–30 m), resulting in a “strong near-well, weak far-field” pressure distribution and inefficient residual oil utilization. To address this, a synergistic strategy is proposed, integrating “re-pressurization of existing fractures” for energy replenishment with “infill fracturing” for activating bypassed reserves. This strategy significantly outperforms conventional refracturing, increasing the predicted cumulative oil production by 55.86%. Parameter optimization indicates that maintaining a pumping rate of 10–12 m³/min and a fluid intensity of 1700–1900 m³/stage, while optimizing proppant ratios for conductivity, maximizes recovery. This work provides theoretical guidance for sweet spot evaluation and refracturing design in ultra-low permeability reservoirs. Full article

The multiple-transferable resistance protein (MtrR) is a transcriptional repressor of the mtrCDE-encoded drug efflux pump and Type IV pilus biosynthesis (pilM), and an activator of penicillin-binding protein 1 (ponA) expression in Neisseria gonorrhoeae. Previously published microarray data suggested that MtrR is also an activator of ltgA expression in the gonococcus. LtgA is a lytic transglycosylase responsible for approximately half of recycled peptidoglycan fragments and released peptidoglycan-derived cytotoxins, which cause ciliary damage and induce specific inflammatory responses. The fragments generated by LtgA during peptidoglycan remodeling can either be recognized by the permease AmpG for uptake into the bacterial cytoplasm and recycled for new cell wall growth and general metabolism or released into the external milieu. Therefore, we sought to define the capacity of MtrR to regulate LtgA expression in gonococci. We show that MtrR binds to the ltgA promoter region in a concentration-dependent manner, and that this binding results both in increased ltgA mRNA transcription and LtgA protein levels during exponential growth. Deletion of mtrR in N. gonorrhoeae decreased peptidoglycan monomer release from growing cells and increased autolysis. These results suggest that MtrR regulation of ltgA impacts peptidoglycan-derived cytotoxin release and autolysis in the gonococcus. This study suggests a central role of MtrR in coordinating aspects of the cellular envelope that may contribute to gonococcal pathogenesis. Full article

Biofilm-associated infections pose a significant clinical challenge due to their increased antibiotic tolerance and strong association with multidrug-resistant pathogens. The biofilm protects bacteria against antimicrobial agents and host immune response through a complex matrix, altered cell metabolism, activation of quorum sensing, and overexpression of efflux pumps. Despite the availability of numerous therapeutic strategies, the effectiveness of treatment of these infections remains limited, justifying the search for new pharmaceutics, e.g., compounds of natural origin. Berberine, an isoquinoline alkaloid from the plants of the Berberidaceae family, is of growing interest due to its broad spectrum of antimicrobial and antibiofilm activities. This review summarizes the current state of knowledge regarding the molecular mechanisms of action of berberine against the biofilm forming Gram-(+) and Gram-(−) bacteria. Its effect on bacterial cell adhesion, modulation of quorum sensing, inhibition of extracellular matrix synthesis, disruption of biofilm maturation, and the dispersion process are discussed. The role of berberine as an adjuvant to antibiotic therapy was also analyzed, in particular, its ability to restore bacterial sensitivity to different classes of antibiotics. The pharmacokinetic limitations of berberine and the prospects for the use of modern delivery systems are also considered. The collected data indicate that berberine is a promising factor supporting the treatment of biofilm-related infections. Full article

Magnetic bearing hydrogen recirculation pumps enable high-speed, wear-free operation but are sensitive to flow-induced disturbances. This study proposes a cascade-structured disturbance observer (CDOB) that fuses rotor displacement and bearing current signals to achieve robust disturbance estimation under model uncertainties, with low-pass filtering to ensure stability. The proposed method is validated through simulations and repeated experiments at multiple axial positions. Based on raw displacement signals, the CDOB reduces the average peak-to-peak axial displacement by approximately 35% compared with a traditional disturbance observer. Under axial offset conditions of −100 μm and +100 μm, the CDOB consistently achieves average displacement reductions of approximately 23% and 24%, respectively, demonstrating consistent disturbance suppression and robustness across repeated tests. These results indicate that the CDOB provides an effective and practical solution for disturbance suppression in magnetic bearing systems. Full article

Understanding the drivers of soil carbon efflux is critical for predicting forest carbon cycles under climate change. This study investigates how plant roots and phenology govern the spatio-temporal variability of boreal forest floor respiration (Rf) in an ectomycorrhizal-dominated forest. By analyzing stabilized soil carbon fluxes (NEE, Ra, and Rh) one year after root exclusion in northern Sweden, we challenge the passive physicochemical paradigm. Results show that the spatial distribution and magnitude of Rf are primarily driven by plant roots, with Ra accounting for >60% of total efflux. The collapse of respiration in trenched plots confirms the mycorrhizal bridge as the essential conduit for these spatial patterns. Regarding temporal variability, we identified a biological pulse driven by plant phenology. After temperature-normalization, Ra maintained a strong seasonal peak in July and August. Notably, static drivers like fine root biomass failed to explain spatial variation (R < 0.3, p > 0.05), whereas dynamic NEE showed significant positive correlations (R = 0.52, p < 0.0001). This holistic perspective suggests that the forest floor operates as an integrated metabolic continuum, where root activity and phenological pump are the main regulating factors on carbon release. Future models should reposition plant–fungal phenology as the primary engine of soil metabolism. Full article

This study evaluates the feasibility of using a ground-coupled ammonia heat pump as a heat source for the district heating system in Ustka, Poland. A three-dimensional transient thermal model of a 122-borehole field was developed in ANSYS 2023 R1 using local geological data and hourly meteorological inputs. Three extraction loads—0.50, 0.75, and 1.00 MW—were analysed, together with regeneration periods of one month (August) and six months following the heating season. Ground temperatures were assessed across all geological layers down to 250 m. The simulations show that each of the tested loads leads to a noticeable and lasting reduction in ground temperature. For 1.00 MW, the temperature in the main heat-exchange layers remains more than 2 K below the initial value even after six months of regeneration. At 0.75 MW the deficit is smaller but still persists in the layers that dominate heat transfer. Even the 0.50 MW scenario does not return to thermal balance: the active layers stay more than 1 K cooler after the regeneration period, indicating cumulative long-term cooling. Although the model includes standard engineering simplifications, the large-scale thermal behaviour is consistent across all scenarios. The analysis shows that the analysed GSHP (ground-source heat pump) configuration cannot serve as a primary heat source for the Ustka network in the analysed configuration. Alternative low-emission solutions, such as air-source heat pumps supported by renewable electricity, are more suitable for this site. Full article

The global spread of multidrug-resistant (MDR) Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, presents a significant public health challenge by limiting effective antimicrobial treatment options. Cefepime, a fourth-generation cephalosporin with broad-spectrum activity, is increasingly compromised by β-lactamase production, efflux pumps, and porin loss. In response, novel cefepime-based β-lactam/β-lactamase inhibitor (BL/BLI) combinations have been developed to overcome these resistance mechanisms. This review examines preclinical and clinical studies on cefepime-based BL/BLI combinations, specifically cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, and cefepime/nacubactam, as found in the PubMed database. Key findings include the restoration of activity against class A ESBLs with cefepime/enmetazobactam, while cefepime/taniborbactam and cefepime/zidebactam show broader inhibition of serine β-lactamases and selected metallo-β-lactamases. Additionally, zidebactam and nacubactam target penicillin-binding protein 2, enhancing bactericidal potency. Preclinical and early-phase clinical trial data indicate potent in vitro activity and favorable pharmacokinetic/pharmacodynamic (PK/PD) profiles. Specifically, the combination of cefepime with enmetazobactam has demonstrated an optimal Cmax/MIC ratio of 8–10, supporting its efficacy in treating MDR Gram-negative infections. Phase III studies are ongoing to confirm efficacy in complicated infections. Cefepime-based BL/BLI combinations are emerging as promising carbapenem-sparing agents, offering broad-spectrum activity, dual mechanisms of action, and encouraging clinical outcomes. These findings support their inclusion in antimicrobial stewardship strategies aimed at mitigating resistance. Full article

3,4-Dihydroxybenzaldehyde (DBD) is a polyphenolic active constituent derived from Gastrodia elata. Its characteristic phenolic structure is associated with diverse bioactivities, such as anti-inflammatory, antioxidant, and cardioprotective effects. However, its role and underlying mechanisms in combating Alzheimer’s disease (AD) remain inadequately elucidated. In this study, we employed computational and experimental approaches to investigate the anti-AD effects of DBD. Molecular dynamics simulations revealed that DBD binds to Aβ fibrils via π–π stacking, hydrophobic interactions, and hydrogen bonds, suggesting its potential to disrupt Aβ fibril stability and thereby inhibit aggregation. In vivo experiments in an AD C. elegans model demonstrated that 2 mM DBD treatment significantly delayed paralysis and extended lifespan. It also improved locomotor activity and pharyngeal pumping rates, while reducing lipofuscin accumulation. These results collectively suggest that DBD promotes healthspan-associated phenotypes. Broad-targeted metabolomics analysis indicated that DBD significantly altered the metabolic profile of the worms. Further mechanistic investigations suggested that the protective effects of DBD are associated with the activation of the DAF-16/FOXO and SKN-1/Nrf2 signaling pathways, accompanied by enhanced resistance to oxidative and thermal stress in nematodes. These findings suggest that DBD exhibits anti-AD potential through multimodal mechanisms, which involve interference with Aβ toxicity and reinforcement of cellular defense. This study supports DBD as a candidate compound and provides a rationale for its further investigation. Full article

Background: Growing antibiotic resistance and the limited availability of key components in standard Helicobacter pylori treatments have driven the search for effective alternatives. Minocycline, with its broad-spectrum activity and favorable pharmacokinetics, has emerged as a promising substitute. This meta-analysis compares the safety and efficacy of minocycline-containing bismuth quadruple therapy (MBQT) to conventional first-line BQT regimens, incorporating data from the recent study by Lin et al. Methods: The inclusion criteria were randomized controlled trials (RCTs) with a target population of both treatment-naïve and previously treated patients diagnosed with Helicobacter pylori (H. pylori) infection. The intervention received by eligible patients was a minocycline–bismuth quadruple therapy (MBQT) regimen containing bismuth, minocycline, proton pump inhibitors (PPI), and any additional antibiotic with a minimum period of 2 weeks of administration. We excluded study designs other than RCT and clinical trials that include patients without confirmed H. pylori infection, animal populations, in vitro experiments, and reports of other outcomes that did not include a minimum intervention duration of 2 weeks. A comprehensive literature search was conducted on PubMed, EMBASE, Cochrane Library, and ScienceDirect from inception to 20 May 2025. After screening via Rayyan, data were extracted on an Excel spreadsheet. Quality was assessed using the Cochrane RoB 2.0 tool. Eligible randomized controlled trials (RCTs) were included and analyzed using RevMan 5.4. Outcomes assessed were intention-to-treat and per-protocol eradication rates. Adverse effects were compared among therapies. A random-effects model was used; an I² < 50% and p-value < 0.05 indicated homogeneity and significant results respectively. Results: Five RCTs with 7 interventions involving 2812 patients were included. The pooled odds ratio (OR) for MBQT in intention-to-treat (ITT) analysis was 1.25 (95% CI: 0.96–1.61), showing a non-significant trend. No heterogeneity was detected (I² = 0.0%). In the modified ITT (mITT) analysis (2 studies), MBQT showed higher eradication (OR: 1.70, 95% CI: 0.00–1042.90), but wide CI and high heterogeneity (I² = 70.7%) limited interpretation. All studies were included in the per-protocol (PP) analysis, which showed a statistically significant improvement with MBQT (OR: 1.67, 95% CI: 1.14–2.45) and low heterogeneity (I² = 5.2%), suggesting consistent results. Although not statistically significant, MBQT was associated with a slightly lower rate of adverse events compared to standard therapy (OR: 0.81, 95% CI: 0.59–1.12). I² = 50.6% showed moderate heterogeneity in safety outcomes. Discussion: the number of included RCTs was modest, with only five studies meeting eligibility criteria, and only two contributing to the modified intention-to-treat analysis. The risk-of-bias assessment showed variation in methodological quality across the included studies. Several studies exhibited high risk judgments in critical domains. particularly randomization, deviations from intervention, and selective reporting. Patients who completed the treatment benefited more from MBQT, which also had a comparable safety profile to conventional BQT regimens. In the treatment of H. pylori infection, MBQT may be considered a safe alternative for first-line treatment. Full article

Objectives: Connective tissue dysplasia (CTD) is associated with disorders of collagen synthesis and is widely spread among the healthy population and people with disabilities. In the heart, primarily in the left ventricle (LV), CTD manifests itself as the formation of false tendons (LVFTs) to maintain close-to-normal LV pump function. This exploratory work is devoted to the search for general patterns of cardiac response to physical activity in athletes with disabilities, CTD, and LVFTs. The extent to which “the type of sports or the type of disability” determines the involvement of the heart’s functional reserve is the main testable question of the proposed research. Methods: The group under this study included 610 individuals with disabilities aged from 6 to 60 years with at least two transverse and/or oblique FTs per LV. Participants represented different sports disciplines (n = 10) and various forms of disabilities (n = 4). Cardiovascular indicators were obtained by means of standard TTE, impedance cardiography for hemodynamic monitoring in active orthotest, resting, and stress 12-lead ECG. Exercise testing of the athletes was performed with the use of appropriate methods of physical loading. In total, 141 parameters of cardiorespiratory function and exercise performance per participant were recorded. Statistical analysis of the dataset obtained across sports types or disability types was performed using one-way ANOVA or the Kruskal-Wallis test, depending on the assumptions of normality and homogeneity of variance. Results: Most importantly, it was found that only maximum relative oxygen consumption (VO₂max, mL·kg⁻¹·min⁻¹) as a reliable indicator of the heart’s functional reserve and the corrected QT (QTc, ms) interval as an integral measure of the heart’s electrical activity demonstrated statistically significant differences across the sports specialization or the disability type. In particular, significance values (P) for VO₂max across athletic disciplines and nosology categories were equal to 0.00063 and 0.01028 (one-way ANOVA), while for QTc they were 0.00001 and 0.02185 (Kruskal-Wallis), respectively. Furthermore, the type of disability had a lower impact on VO₂max and QTc than the type of athletic activity. Conclusions: In athletes with disabilities and CTD, sport specialization may involve the heart’s functional reserve to a greater extent than the type of disability. To prescribe training loads for people with disabilities and CTD, individual cardiology screening with an emphasis on VO₂max and QTc is necessary. Full article