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Padi4-dependent NETosis enables diet-induced gut hyperpermeability, translating dysbiosis into systemic inflammation and dysmetabolism
No full text: Microbial signals trigger the release of neutrophil extracellular traps (NETs) through peptidyl-arginine-deiminase-4 (PADI4). In turn, NETosis can propagate inflammation to distant tissues. We hypothesize that PADI4 mediates the interactions between diet-modified microbiota and host metabolism. We report that in the adipose tissue of individuals with obesity, NETosis was associated with dysglycemia. In mice, high-fat diet (HFD) induced not only dysmetabolism and meta-inflammation but also local and systemic signs of NETosis. Deleting Padi4 in hematopoietic cells (Padi4KO) blunted liver and adipose inflammation and improved metabolism under HFD. While NETs were able to disrupt gut epithelial integrity, abrogating NETosis preserved intestinal barrier function and mitigated metabolic endotoxemia due to HFD. Padi4 deletion did not prevent diet-induced dysbiosis, but Padi4KO mice were protected from intestinal hyper-permeability and metabolic impairment due to the transfer of HFD-modified microbiota. As Padi4KO did not blunt the dysmetabolic effects of LPS, we conclude that NETosis operates at the microbiota-intestinal interface, inducing hyperpermeability and the systemic spillover of bacterial-derived products, paving the way to the metabolic consequences of HFD. Finally, pharmacologic PADI4 inhibition recapitulated findings obtained in Padi4KO mice on metabolism and liver steatosis, thereby uncovering a druggable role for PADI4 in mediating the metabolic effects of unhealthy microbiota
Solubility and dissolution kinetics of particle-bound metals in a surrogate lung fluid
Get PDFEnvironmental context: Metals in airborne particles can interact with lung fluids once particles are inhaled. Water solubility of particle-bound metals is often used to define their bioavailability. We show that particle-bound metals exhibit a complex dissolution kinetics in a surrogate lung fluid, their solubility and dissolution kinetics are driven by the fluid composition, and only to a minor extent by atmospheric aqueous phase processing of aerosols. Rationale: Metals in airborne particles can interact with lung fluids once particles are inhaled and cause oxidative stress. Their oxidative potential is dependent on their solubility and dissolution kinetics in the lung fluids. Methodology: In this study, we collected PM2.5 samples from the city of Padova (Italy), in the northern Italian Po Valley. We investigated the solubility and dissolution kinetics of particle-bound metals in a surrogate epithelial lining fluid (SELF) and compared the results to those obtained for a fog water. Re..
Neuropsychological awareness in pediatrics (NAP): Proposal of a new cognitive self-report questionnaire for pediatric multiple sclerosis patients
Get PDFBackground: Self-perception of cognitive functioning in pediatric MS (pedMS) needs to be evaluated with specific questionnaires, currently lacking. This study aimed to develop a self-reportwhich investigates cognitive status in pedMS. Methods: Twenty-seven pedMS patients (mean age±standard deviation=15 years±1.5 year; female/male=2:1) and their parents, completed a questionnaire called “Neuropsychological Awareness in Pediatrics - Patient, and Neuropsychological Awareness in Pediatrics - Caregiver” (NAP-P and NAP-C, respectively). Patients underwent a comprehensive neuropsychological assessment and completed self-reports on quality of life (Pediatric Quality of Life Inventory, Peds-QL), fatigue (Multidimensional Fatigue Scale, Peds-QL MFS), and mood disturbances (Children Depression Inventory, CDI-II). Results: Significant positive correlations were observed between NAP-P and the Trial Making Test-B (ρ = 0.470, p ˂ 0.05). Both NAP-P and NAP-C correlated with CDI-II (ρ = 0.776, p < 0.00..
Deprescribing psychoactive drugs in older orthogeriatric patients: findings from the GIOG2.0 Italian survey
No full textBackground: Psychoactive drugs represent a major contributor to falls in older people. This study aims to evaluate the prescribing practice of psychoactive drugs in older people hospitalized for hip fracture (HF) and to explore independent correlates of deprescribing. Methods: Multicenter prospective observational study including patients with HF admitted to 13 Orthogeriatric wards of the Italian Group of Orthogeriatrics (July 2019-August 2022). Patients underwent a comprehensive geriatric assessment. The use of psychoactive drugs associated with a higher risk of falls was assessed using a dedicated checklist. Deprescribing was defined as any reduction in the number of psychoactive drugs upon discharge, and independent correlates of deprescribing were explored using logistic regression analyses. Cluster analysis by Partitioning around Medoids was also performed in the hypothesis that selected clusters of characteristics could be associated with deprescribing. Results: One thousand eight hundred fifty-four older individuals (mean age 84 years, 77% females) were studied; 1190 (64%) were not prescribed any psychoactive drug, while 474 (26%), 129 (7%), and 61 (3%) took 1, 2, 3 or more psychoactive drugs, respectively. Among 664 patients on psychoactive drugs on admission, 177 (27%) had fewer prescriptions at discharge, mainly anxiolytics from 89 to 10 (50-6%), antipsychotics from 49 to 12 (28-7%) and antidepressants from 98 to 28 (55-16%). On the other count, 51 (8%) were prescribed more psychoactive drugs, mostly antidepressants from 25 to 45 (49-88%) and antipsychotics from 7 to 17 (14-17%). Functional autonomy (ADL aOR 0.87 [95%CI 0.78-0.97] p < 0.001), polipharmacy (aOR 1.15 [95%CI 1.03-1.29] p < 0.001) and the occurrence of post-operative delirium (aOR 1.71 [95%CI 1.09-2.66] p < 0.017) were independent correlates of deprescribing. More specifically, the clustering procedure could not improve the characterization of deprescribing; conversely, the deprescribing propensity significantly depended upon the center-specific prescriptive practice, not explained by other clinical-epidemiological factors. Conclusion: Only a small proportion of patients hospitalized for HF undergoes deprescribing of psychoactive drugs, with considerable heterogeneity among centers, suggesting that the physician's attitude rather than patient-related factors affects deprescribing
Socio-economic determinants of Over-Indebtedness of Microfinance Borrowers: insights for Client Protection against modern financial challenges
No full textUnderstanding the socioeconomic challenges faced by poor and vulnerable populations is crucial, as these groups are disproportionately affected by financial instability, inequality, and limited access to finance. Over-indebtedness remains a pressing concern, as excessive borrowing can lead to financial distress, reduced well-being, and long-term economic instability among low-income borrowers. This research examines the issue of borrowers' over-indebtedness in Nepal's microfinance institutions from the standpoint of client protection against the backdrop of global socioeconomic challenges
such as rising inequality and increasing vulnerability of marginalized people. A questionnaire survey was administered among 180 MFI borrowers between August and September 2021, focusing on the sacrifices reported by borrowers as a result of their loans. Over-indebtedness is assessed using a subjective indicator based on reported loan-related sacrifices across 12 dimensions. These sacrifices are evaluated in terms of both acceptability and frequency. Using binary logistic regression, the study found that financial literacy, income level, multiple borrowing, and loan utilization are major predictors of over-indebtedness. The number of dependents in a household was found to be significant only in terms of acceptability, highlighting the role of family burden in financial distress. However, factors such as the type of business, the borrower’s age, and income volatility were not significant predictors of over-indebtedness. The findings suggest that financial literacy programs, improved income-generating opportunities, and responsible loan usage can mitigate over-indebtedness and promote sustainable financial inclusion. The results provide critical insights for microfinance institutions, policymakers, and regulators, emphasizing the need for strengthened client protection mechanisms. By addressing over-indebtedness, microfinance institutions can contribute to long-term financial stability and economic empowerment, ensuring that borrowers benefit from financial services without falling into debt traps. These findings contribute to the broader discourse on responsible microfinance practices, reinforcing the necessity for balanced policies that safeguard both financial inclusion and borrower well-being
The legacy of the Roman pottery production in the alluvial landscape in Italy: traces of relict clay pits and their ancient environmental impact
Get PDFThe topography of alluvial plains in Europe has been strongly affected and overprinted by different diachronic human activities, and modern land use has reworked geomorphological and archaeological traces, often hindering the reconstruction of past landscapes and the assessment of ancient environmental impacts. In this work, set in the distal Venetian-Friulian Plain, in northeastern Italy, we took advantage of the presence of the last remnants of semi-natural lowland forests, and we combined high-resolution remotely sensed data to detect and map a specific type of archaeological trace related to clay quarrying. Analysis of digital terrain models (DTMs) obtained from LiDAR (Light Detection And Ranging) revealed topographic traces underneath forested or recently deforested areas while photointerpretation of satellite and aerial imagery was crucial in detecting levelled traces. Moreover, we used hand augering techniques to assess the depth and infill material of the clay quarry evidence. Our investigation recognized nine Roman sites, consisting of hundreds of quadrangular pits (124.8 m2 size – 1 m depth), which lie on top of Last Glacial Maximum (LGM) alluvial clays. We infer these pits to be Roman quarried workshops connected to nearby kilns, where clays were extracted for ceramic building material (CBM) and pottery production. The unique signature of such traces, coupled with their resilience in the highly anthropized study area, underlines a Roman proto-industrial impact on the landscape, and suggests the existence of similar evidence in other plains under the Roman domain
Development of a Novel Robust Approach for Unveiling the Stretchiness of Cheese
Get PDFThis study proposed a method for objectively measuring the stretchiness of cheese using a texture analyzer equipped with a double-sided fork probe. The method measures the force required to stretch melted cheese samples at a constant speed. Using a central composite design (CCD) experimental approach, the impact of test parameters (i.e., sample quantity, temperature, speed) has been evaluated. Subsequently, an optimal combination of the test parameters (i.e., 66 degrees C, 17.5 mm/s, 6.7 g sample) has been proposed. These aimed to minimize variability and ensure the reproducibility of the results in the stretchiness of the observed cheese. The key stretch descriptors' significance to describe the stretchiness of cheese, namely peak force, force and work at a distance of 40 mm, and breaking distance has also been indicated. With the proposed method, changes in the stretch properties of Mozzarella during storage at 4 degrees C were able to be monitored. An initial decrease was observed up to day 7, followed by a slight increase by day 25, suggesting changes in the cheese protein network. The method was then used to compare the properties of 15 dairy-based cheeses and 6 vegan Mozzarella-style cheese alternatives. The peak force and filament strength (i.e., force at a distance of 40 mm) were used to cluster various cheeses showing distinct stretch profiles. Mozzarella cheeses generally showed lower resistance to filament formation compared to other dairy-based cheeses, while vegan cheeses exhibited minimal to no filament formation and lower meltability. By comparing and clustering the stretchiness properties of dairy cheeses and their vegan alternatives, the present method can be used to guide researchers and product developers on better profiling the stretch properties of target cheese and subsequently producing (new) products with a more desirable stretch profile
In situ tailored confining microenvironment for lung cancer spheroids
No full textThe mechanical properties and physical confinement of the extracellular matrix (ECM) are crucial roles in regulating tumor growth and progression. Extensive efforts have been dedicated to replicating the physical characteristics of tumor tissue by developing two-dimensional (2D) and three-dimensional (3D) in vitro models. However, it remains a significant challenge to modulate the local microenvironment around the specific cells according to the culture progress. In this study, we develop a 3D culture platform for multicellular lung cancer spheroids using a gelatin-based hydrogel with adjustable density and stiffness. Then, by utilizing a two-photon mediated bioprinting technique, we construct 3D confining microstructures with micrometer accuracy to enclose the selected spheroids within the hydrogel matrix. Diverse transcriptional profilings of cells are observed in response to the increased ECM density and stiffness compared to the additional confining stress. In addition, changed confining stress can regulate the tumor cells with contrary impacts on the cell cycle-related pathways. Our model not only allows for modifications to the mechanical microenvironment of the overall matrix but also facilitates localized adjustments throughout the culture evolution. This approach serves as a valuable tool for investigating tumor progression and understanding cell-ECM interactions
Fluvial Geomorphology of Active Volcanoes in Costa Rica
Get PDFCosta Rica, encompassing an area of 51,100 km2, features a complex network of streams shaped by its rugged terrain, active volcanism, and tectonic activity. This dynamic drainage system is characterized by diverse erosive and depositional landforms. This study provides a comprehensive examination of Costa Rica's river environments, focusing on channel morphologies and fluvial dynamics across selected reaches. Utilizing advanced remote sensing techniques, including Unmanned Aerial Vehicles (UAVs), hydraulic modeling, and detailed field observations, we characterized significant river sections within distinct geological contexts, including steep volcanic-mountain settings and low-gradient alluvial fans.
Focusing on rivers draining from the Irazú-Turrialba Volcanic Complex, we observed rapid channel morphology changes influenced by extreme precipitation, high-magnitude earthquakes, and active volcanic processes. Our analysis of the Sucio River over a 60-year period (1961-2023) revealed significant shifts from island-braided to braided and anabranching systems, illustrating a cyclical pattern of channel dynamics. Increased channel width correlated with a reduction in vegetated islands and sediment bar accumulation, while decreased width facilitated bank stabilization and island consolidation.
Additionally, we investigated the Turrialba River, which flows from Turrialba Volcano. This river has a history of causing severe damage to the nearby city, particularly through bank erosion and flooding events, including a significant flood in July 2021 that drastically altered channel morphology. Our analysis of sediment sources and historical evolution highlighted the high hillslope-channel connectivity and sediment load transport characteristics inherent in volcanic environments.
Overall, our findings emphasize the critical role of sediment supply from landslides and volcanic activity in shaping channel dynamics, while also addressing the potential hazards posed by these highly dynamic fluvial systems. Furthermore, vegetation plays a vital role in stabilizing channel banks and islands, supporting rapid recovery in disturbed areas. This work contributes to a novel understanding of fluvial geomorphology in active volcanic environments, underscoring the need for further research into the interactions between vegetation and geomorphic processes in these dynamic landscapes
A Mature Tool to Address New Challenges: Harnessing Coordination Chemistry for The Sustainable Copper Recovery from Industrial and E‐Waste in The Age of Energy Transition
No full textCopper is arguably one of the most strategic metals for the energy transition, particularly in the shift from fossil fuel-based engines to sustainable and renewable energy sources, with related and broader electrification efforts. While global copper mineral resources are far from depleted, their uneven distribution poses significant supply risks, especially in regions like Europe. In 2023, the European Union (EU) recognized this risk by designating copper as a strategic raw material (SRM), highlighting the need for innovative copper recovery processes. Copper recovery from industrial and electronic waste has been approached through various methods, primarily categorized into pyrometallurgy and solvo- and hydrometallurgy. The latter offers greater tunability and potential for sustainability, particularly when leveraging coordination chemistry. This review focuses on the most promising hydrometallurgical processes for copper recovery from industrial and e-waste (i. e., electronic waste), with a special emphasis on the role of coordination chemistry in supporting these methods. We posed particular focus on the adaptability and versatility of the coordination chemistry-based processes to the highly heterogenous composition of the copper-containing wastes