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This review paper examines the hydrogeological characteristics and challenges of urban groundwater management in ten major Italian cities: Turin, Milano, Padova, Bologna, Roma, Pescara, Napoli, Bari, Catania, and Cagliari. Urbanization has placed significant pressure on groundwater systems, highlighting the need for sustainable management. The study categorizes the cities based on their hydrogeological settings and groundwater uses, identifying key issues such as salinization, industrial contamination, and land subsidence. The findings emphasize the importance of urban local aquifers (ULAs) for drinking water, industry, and ecological support, advocating for integrated urban water management and governance to enhance resilience against future water shortages and climate change impacts.

Background Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of the intratumoral microenvironment.Methods We performed a transcriptomic analysis of several NK receptors with a focus on the activating receptor encoded by KLRC2, NKG2C, among bulk and single-cell RNA sequencing GBM data sets. We also evaluated the effects of KLRC2-overexpressing GL261 cells in mice treated with or without programmed cell death protein-1 (PD-1) monoclonal antibody (mAb). Finally, we analyzed samples from two clinical trials evaluating PD-1 mAb effects in patients with GBM to determine the potential of NKG2C to serve as a biomarker of response.Results We observed significant expression of several inhibitory NK receptors on GBM-infiltrating NK and T cells, which contrasts with the strong expression of KLRC2 on tumor cells, mainly at the infiltrative margin. Neoplastic KLRC2 expression was associated with a reduction in the number of myeloid-derived suppressor cells and with a higher level of tumor-resident lymphocytes. A stronger antitumor activity after PD-1 mAb treatment was observed in NKG2Chigh-expressing tumors both in mouse models and patients with GBM whereas the expression of inhibitory NK receptors showed an inverse association.Conclusions This study explored the role of neoplastic NKG2C/KLRC2 expression in shaping the immune profile of GBM and suggests that it is a predictive biomarker for positive responses to immune checkpoint inhibitor treatment in patients with GBM. Future studies could further validate this finding in prospective trials.

The digitization of pathology departments in hospitals around the world is now a reality. The current commercial solutions applied to digitize histopathological samples consist of a robotic microscope with an RGB-type camera attached to it. This technology is very limited in terms of information captured, as it only works with three spectral bands of the visible electromagnetic spectrum. Therefore, we present an automated system that combines RGB and hyperspectral technology. Throughout this work, the hardware of the system and its components are described along with the developed software and a working methodology to ensure the correct capture of histopathological samples. The software is integrated by the controller of the microscope, which features an autofocus functionality, whole slide scanning with a stitching algorithm, and hyperspectral scanning functionality. As a reference, the time to capture and process a complete sample with 20 regions of high biological interest using the proposed method is estimated at a maximum of 79 min, reducing the time required by a manual operator by at least three times. Both hardware and software can be easily adapted to other systems that might benefit from the advantages of hyperspectral technology.

Cultures in Mediterranean climate zones (MCZs) around the world have long been reliant on groundwater and springs as freshwater sources. While their ecology and cultural sustainability are recognized as critically important, inter-relationships between springs and culture in MCZs have received less attention. Here we augmented a global literature review with case studies in MCZ cultural landscapes to examine the diversity and intensity of cultural and socio-economic relationships on spring ecohydrogeology. MCZs are often oriented on western and southern coasts in tectonically active landscapes which control aquifer structure, the prevalence of westerly winds, and aridity, and generally expose associated habitats and cultures to harsh afternoon sunlight. Cultural appreciation and appropriation of springs ranges widely, from their use as subsistence water supplies to their roles in profound traditions such as Greco-Roman nymphalea as well as Asian and Abrahamic spiritual cleansing and baptism. The abandonment of traditional ways of life, such as rural livestock production, for urban ones has shifted impacts on aquifers from local to regional groundwater exploitation. The commoditization of water resources for regional agricultural, industrial (e.g., mining, water bottling, geothermal resorts), and urban uses is placing ever-increasing unsustainable demands on aquifers and spring ecosystems. When the regional economic value of springs approaches or exceeds local cultural values, these irreplaceable aquatic ecosystems are often degraded, over-looked, and lost. Sustainable stewardship of springs and the aquifers that support them is a poorly recognized but central conservation challenge for modern Mediterranean societies as they face impending impacts of global climate change. Solutions to this crisis require education, societal dialogue, and improved policy and implementation.

Abstract Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic’s strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.

The digitization of pathology departments in hospitals around the world is now a reality. The current commercial solutions applied to digitize histopathological samples consist of a robotic microscope with an RGB-type camera attached to it. This technology is very limited in terms of information captured, as it only works with three spectral bands of the visible electromagnetic spectrum. Therefore, we present an automated system that combines RGB and hyperspectral technology. Throughout this work, the hardware of the system and its components are described along with the developed software and a working methodology to ensure the correct capture of histopathological samples. The software is integrated by the controller of the microscope, which features an autofocus functionality, whole slide scanning with a stitching algorithm, and hyperspectral scanning functionality. As a reference, the time to capture and process a complete sample with 20 regions of high biological interest using the proposed method is estimated at a maximum of 79 min, reducing the time required by a manual operator by at least three times. Both hardware and software can be easily adapted to other systems that might benefit from the advantages of hyperspectral technology. [ABSTRACT FROM AUTHOR]

A mechanism shared by most neurodegenerative diseases, like Alzheimer’s disease (AD) and Parkinson’s disease (PD), is neuroinflammation. It has been shown to have a link between cognitive impairment and retinal function under neuroinflammatory conditions, confirming the essential role of the retina as a window to the brain. Here, we characterize a mouse model of LPS-induced neuroinflammation describing the parallel deterioration of both memory and visual function. Then, we demonstrate, using the Novel Object Recognition test (NOR) and electroretinogram (ERG) recordings, that preventive, chronic treatment with saffron Repron® is able to reduce the neuroinflammation process and prevent the impairment of both cognitive and visual function. The improvement in behavioral and visual function is confirmed by the pattern of expression of neuroinflammation-related genes and related proteins where pre-treatment with Repron® saffron presents a positive modulation compared with that obtained in animals treated with LPS alone. These results hold for retinal tissue and partially in the brain, where it appears that the onset of damage was delayed. This trend underlines the critical role of the retina as a most sensitive portion of the central nervous system to LPS-induced damage and could be used as a “sensor” for the early detection of neurodegenerative diseases such as Alzheimer’s.

Abstract not available

Performing a reliable stability analysis of a landslide slope requires a good understanding of the internal geometries and an accurate characterisation of the geotechnical parameters of the identified strata. Geotechnical models are commonly based on geomorphological data combined with direct and intrusive geotechnical investigations. However, the existence of numerous empirical correlations between seismic parameters (e.g., S-wave velocity) and geotechnical parameters in the literature has made it possible to investigate areas that are difficult to reach with direct instrumentation. These correlations are often overlooked even though they enable a reduction in investigation costs and time. By means of geophysical tests, it is in fact possible to estimate the N-SPT value and derive the friction angle from results obtained from environmental seismic noise measurements. Despite the empirical character and a certain level of uncertainty derived from the estimation of geotechnical parameters, these are particularly useful in the preliminary stages of an emergency, when straight data are not available and on all those soils where other direct in situ tests are not reliable. These correlations were successfully applied to the Theilly landslide (Western Alps, Italy), where the geotechnical model was obtained by integrating the results of a multi-parameter geophysical survey (H/V seismic noise and ground-penetrating radar) with stratigraphic and geomorphological observations, digital terrain model and field survey data. The analysis of the triggering conditions of the landslide was conducted by means of hydrological–geotechnical modelling, evaluating the behaviour of the slope under different rainfall scenarios and considering (or not) the stabilisation interventions present on the slope. The results of the filtration analyses for all events showed a top-down saturation mechanism, which led to the formation of a saturated face with a maximum thickness of 5 m. Stability analyses conducted for the same events showed the development of a shallow landslide in the first few metres of saturated soil. The modelling results are compatible with the actual evolution of the phenomenon and allow us to understand the triggering mechanism, providing models to support future interventions.

Saffron treatment is a broad-spectrum therapy used for several retinal diseases, and its effectiveness depends on a particular molecular composition (REPRON® saffron). Its production requires specific crops and procedures that, together with low yields, make this spice expensive. To reduce costs, the use of hydroponic crops is gradually increasing. In this study, we tested the protective properties of a hydroponic saffron (sH) batch in models of retinal pigmented epithelium (RPE) degeneration. ARPE-19 cells were pretreated with 40 µg/mL saffron and exposed to different types of damage: excess light and retinol (LE + RET) or oxidative stress (H2O2). After analyzing the composition of all saffron types with spectroscopy, we performed cell viability and immunofluorescence analysis for both protocols. We compared the sH results with those of a validated batch of saffron REPRON® (sR) and those of a saffron non-REPRON® (sNR) batch. sH and sR, which we found had the same chemical composition, were more effective than sNR in increasing cell survival and attenuating the morphological changes related to apoptosis. In conclusion, hydroponic culturing is a suitable strategy to produce high-quality saffron to reduce costs and increase the accessibility of this promising treatment for retinal degeneration.

Rhodopsin (RHO) mutations are responsible for 25–40% of the dominant cases of retinitis pigmentosa (RP) with different severity and progression rates. The Tvrm4 mice, heterozygous for an I307N dominant mutation of RHO, display a normal retinal phenotype when raised in ambient light conditions, but undergo photoreceptor degeneration when briefly exposed to strong white light. Here, The Tvrm4 mice is pre-treated with naringenin 100 mg/kg/die, quercetin 100 mg/kg/die, naringenin 50 + quercercetin 100 mg/kg/die or vehicle dimethyl sulfoxide (DMSO 0.025%) in the drinking water for 35 days. On the 30th day, retinal degeneration was induced by exposure for 1 min to the white light of 12,000 lux intensity, and the treatment was repeated for another 5 days. At the end of the protocol retinal functionality was tested by recording an electroretinogram (ERG). The retinal tissue was collected and was used for further analyses, including immunohistochemically, biochemical, and molecular biology assays. The data obtained show that treatment with nutraceutical molecules is effective in counteracting retinal degeneration by preserving the functionality of photoreceptors and increasing the antioxidant and anti-apoptotic pathways of retinal cells. The present data confirm that nutraceutical molecules are effective in slowing photoreceptor degeneration in a mutation-independent way by modulating the antioxidant response of the retina at the gene expression level.

The project of interest involving a hydroelectrical diversion tunnel through a crystalline rock massif in the Alps required a detailed hydrogeological study to forecast the magnitude of water inflows within the tunnel and possible effects on groundwater flow. The tunnel exhibits a length of 9.5 km and is located on the right side of the Toce River in Crevoladossola (Verbania Province, Piedmont region, northern Italy). Under the geological framework of the Alps, the tunnel is located within the Lower Penninic Nappes in the footwall of the Simplon Normal Fault, and the geological succession is mostly represented by Antigorio gneiss (meta-granites) and Baceno metasediments (metacarbonates). Due to the presence of important mineralized springs for commercial mineral water purposes, the abovementioned hydrogeological study focused on both quantity and quality aspects via rainfall data analysis, monitoring of major spring flow rates, monitoring of hydraulic heads and pumping rates of existing wells/boreholes, hydrochemical and isotopic analysis of springs and boreholes and hydraulic tests (Lefranc and Lugeon). The resulting conceptual model indicated dominant low-permeability (aquitard) behavior of the gneissic rock masses, except under conditions of intense fracturing due to tectonization, and aquifer behavior of the metasedimentary rocks, particularly when interested by dissolution. Groundwater flow systems are mainly controlled by gravity. The springs located near the Toce River were characterized by high mineralization and isotopic ratios, indicating long groundwater flow paths. Based on all the data collected and analyzed, two parametric methods were applied: 1) the Dematteis method, slightly adapted to the case study and the available data, which allows assessment of both potential inflows within the tunnel and potential impacts on springs (codified as the drawdown hazard index; DHI); 2) the Cesano method, which only allows assessment of potential inflows within the tunnel, thereby discriminating between major and minor inflows. Contemporarily, a groundwater flow model was implemented with the equivalent porous medium (EPM) approach in MODFLOW-2000. This model was calibrated under steady-state conditions against the available data (groundwater levels inside wells/piezometers and elevation and flow rate of springs). The Dematteis method was demonstrated to be more reliable and suitable for the site than was the Cesano method. This method was validated considering a tunnel through gneissic rock masses, and this approach considered intrinsic parameters of rock masses more notably than morphological and geomorphological factors were considered. The Cesano method relatively overestimated tunnel inflows, considering variations in the topography and overburden above the tunnel. Sensitivity analysis revealed a low sensitivity of these parametric methods to parameter values, except for the rock quality designation (RQD) employed to represent the fracturing degree. The numerical model was calibrated under ante-operam conditions, and sensitivity analysis evaluated the influence of uncertainties in the hydraulic conductivity (K) values of the different hydrogeological units. The hydraulic head distribution after tunnel excavation was forecasted considering three scenarios, namely, a draining tunnel, tunnel as a water loss source, and tunnel sealed along its aquifer sectors, considering 3 levels of K reduction. Tunnel impermeabilization was very effective, thus lowering the drainage rate and impact on springs. The model quantitatively defined tunnel inflows and the effects on spring flow at the surface in terms of flow rate decrease. The Dematteis method and numerical model were combined to obtain a final risk of impact on the springs. This study likely overestimated the risk because all the values assigned to the parameters were chosen in a conservative way, and the steady-state numerical simulations were also very conservative (the transient state in this hydrogeological setting supposedly lasts 1–3 years). Monitoring of the tunnel and springs during tunnel boring could facilitate the feedback process.

Aldose reductase is a key enzyme in the development of long term diabetic complications and its inhibition represents a viable therapeutic solution for people affected by these pathologies. Therefore, the search for effective aldose reductase inhibitors is a timely and pressing challenge. Herein we describe the access to a novel class of oxyimino derivatives, obtained by reaction of a 1,5-dicarbonyl substrate with O-(arylmethyl)hydroxylamines. The synthesised compounds proved to be active against the target enzyme. The best performing inhibitor, compound (Z)-8, proved also to reduce both cell death and the apoptotic process when tested in an in vitro model of diabetic retinopathy made of photoreceptor-like 661w cell line exposed to high-glucose medium, counteracting oxidative stress triggered by hyperglycaemic conditions.

Overproduction of reactive oxygen species (ROS) and alterations in metallostasis are common and related hallmarks in several neurodegenerative diseases (NDDs). Nature-based derivatives always represent an attractive tool in MTDL drug design, especially against ROS in NDDs. On this notion, we designed a new series of 8-quinoline-N-substituted derivatives with a natural antioxidant portion (i.e., lipoic, caffeic, and ferulic acids). These compounds were shown to chelate copper, a metal involved in ROS-induced degeneration, and scavenger oxygen radicals in DPPH assay. Then, selected compounds 4 and 5 were evaluated in an in vitro model of oxidative stress and shown to possess cytoprotective effects in 661W photoreceptor-like cells. The obtained results may represent a starting point for the application of the proposed class of compounds in retinal neurodegenerative diseases such as retinitis pigmentosa (RP), comprising a group of hereditary rod–cone dystrophies that represent a major cause of blindness in patients of working age, where the progression of the disease is a multifactorial event, with oxidative stress contributing predominantly.

In the Egyptian deserts, new land reclamation projects have been recently established to meet the increasing-population growth rate and food demand. These projects mainly depend on the different groundwater aquifers. El-Farafra Oasis is one of the “1.5-million-feddan reclamation project” areas recently established in the Western Desert of Egypt where the only available water source is the world’s largest fossil freshwater reservoir “the Nubian Sandstone Aquifer System (NSAS)”. Groundwater-dependent springs, and their artificial counterpart “drilled wells”, are reliable water systems throughout the world. In the present study, hydrochemical parameters were collected in 2015 from 16 different springs and wells of the El-Farafra Oasis, and analyzed using the different water quality indices. The calculated water quality index (WQI), its correlations with the water quality parameters Gibbs, Piper, US Salinity-Lab Staff and Wilcox diagrams, and Principal Component Analysis (PCA) were used to evaluate the groundwater suitability for human drinking and irrigation purposes. WQI values revealed good-to-excellent groundwater quality for human drinking. In addition, the spring and well water samples investigated showed good indices for irrigation activities. Gibbs and Piper’s diagrams were presented, with most samples falling into the rock-dominance category, and belonging to hydrogeochemical facies determining the following water types: Mg(HCO3)2 type water (37.5% of the samples), no dominant ions (mixed water-type category; Ca/MgCl2) (50% of the samples), and, finally, NaCl water type (the remaining 12.5%). The groundwater chemistry in the study area is mainly controlled by rock-water interactions, particularly the dissolution of carbonate rocks and silicate weathering. The elevated nutrient concentrations, in particular nitrates, are most likely due to agricultural activities, indicating substantial anthropogenic activities in the area studied.

Questo documento presenta le Linee Guida per la gestione sostenibile delle venute d’acqua e del calore geotermico nelle gallerie, elaborate dal Gruppo di Lavoro GESTAG (GEstione SosTenibile delle Acque nelle Gallerie), istituito il 20/06/2012 dal Comitato Italiano dell’Associazione Internazionale degli Idrogeologi. Il documento affronta e descrive obiettivi, metodi e casi di studio, ciascuno dei quali richiede di adottare misure tecniche di vario tipo, illustrate nei capitoli seguenti, come studi idrogeologici, modelli predittivi degli impatti, soluzioni tecnologiche di contenimento del drenaggio e di captazione, recupero e valorizzazione delle risorse intercettate, monitoraggi. Sono affrontati anche i così detti temi non tecnici, come la comunicazione, poiché è ormai noto che l’accettabilità sociale di una galleria influenza direttamente la sua sostenibilità economica e finanziaria, per gli effetti che può avere sui tempi di realizzazione e sui costi delle compensazioni. Sulla base delle diverse esperienze dei componenti del Gruppo di Lavoro GESTAG, si è optato per una suddivisione in 11 temi principali, in particolare, in ciascuno dei capitoli successivi a quello introduttivo vengono trattati rispettivamente: Capitolo 2: l’importanza del ritorno di esperienza proveniente da gallerie già scavate, le banche dati disponibili e i criteri di analisi dei dati pregressi; Capitolo 3: come realizzare lo studio idrogeologico di una galleria, la relazione con il modello geologico, le metodiche da adottare nelle differenti fasi del progetto, che sono state distinte in ante-operam, in corso d’opera e post-operam; Capitolo 4: il tema degli impatti che il drenaggio in galleria può avere sull’ambiente circostante, le analisi che devono essere svolte e gli strumenti da adottare per la gestione del rischio, infine gli interventi per la mitigazione degli impatti; Capitoli 5 e 6: le metodiche di progettazione per la valorizzazione rispettivamente delle acque drenate in galleria e del calore; Capitolo 7: i prodotti chimici che vengono utilizzati in fase di scavo per il sostegno e il miglioramento del terreno, e la loro compatibilità con l’utilizzo delle acque drenate; Capitolo 8: i criteri di monitoraggio delle acque in un progetto di galleria; Capitolo 9: la comunicazione, il rapporto con i territori e l’analisi di casi pregressi, nonché una guida sulle buone pratiche da adottare; Capitolo 10: una panoramica sulla normativa europea ed italiana in tema di valutazione di impatto ambientale, monitoraggio e scarichi delle acque drenate; Capitolo 11: la bibliografia ragionata inerente l’argomento trattato, che include pubblicazioni tecnico scientifiche, normative di riferimento e risorse web.

Different forms of neoteny were recorded in some Italian amphibian species: full (absolute or temporary) and partial. However, this physiological phenomenon was never observed in the Italian endemic Salamandrina perspicillata. The authors report the first record of partial neoteny in an individual of this species, a leucistic larva observed in a drinking trough in the Valle del Treja Regional Park (Latium - Central Italy).

The thermal field of Porretta Terme, located in the Alto Reno Terme municipality (Bologna), has always raised interest for its peculiar waters since ancient times. Indeed, the use of the springs dates back to the I-II century A.D. and perhaps even in the Etruscan period. Porretta’s thermal tradition has developed over the centuries. First regulation, issued in 1936, allowed to cultivate the mineral deposit and its natural gas in a 740 000 acres wide land. The thermal waters, a public good, are indeed ruled by specific laws which control their use through a grant where the Public Authority makes the licensee, usually a private, follow a series of accomplishments aimed at not damaging the quantitative and qualitative characteristics (R.D. July 29, 1927 n. 1443). Fourteen thermo-mineral springs out of the nineteen located in the given land are currently exploited. They are divided into two groups, which differentiate either for the chemical properties of the waters and their topographic location. The first group of springs, called salt-bromoiodic, with higher salinity and temperature, is located in the upper part of Porretta along the Rio Maggiore, a tributary on the left bank of the Reno River. This is the portion of the deposit that has been studied. The second group of springs, called sulphurous, characterized by lower temperatures and salinity, is located south-east Porretta on the left side of the Reno River. These thermo-mineral water resources appear to be very worthy and need particular care and protection. By using the results of past research, the essential bibliography of which has been edited in the end-notes, the aim was to develop the hydrogeological parameters of the aquifer that feeds the thermo-mineral sources, identify and understand the conceptual model of the groundwater circulation system, also detecting the interference between the different sources in the area examined. This type of research, which is usually applied to aquifers in sedimentary and granular soils, can be considered original. Indeed, an exhaustive hydrodynamic parameterization of a fractured thermal aquifer system such as that of Porretta has never been conducted. The collection of observational data on the hydrological regime and on the chemical composition of hot waters during the six months of field surveys, which confirmed the substantial constancy of the values over time, was also remarkable.