Background: Laser therapies can cause hyper- and hypopigmentation of the skin. There is little evidence in the literature of effective treatments for these types of problems in Fitzpatrick IV-VI skin phototypes. The main aim of this retrospective study is to evaluate the effects of a new therapy combining the application of electromagnetic fields and vacuum on a subject with Fitzpatrick VI skin phototype, presenting an extensive, laser-induced facial dyschromia. The secondary aim is to test the effectiveness of a free imaging software for assessing skin pigmentation. Methods: The level of improvement after the therapy was evaluated, with a 5-point Likert scale, one month after the end of the treatment by both the subject, and the doctor who performed the treatment, and by two blinded dermatologists. With the free software, a three-dimensional reconstruction of the area treated and the evaluation of colour distribution were performed. Results: Both the subject and the doctors involved in the study positively evaluated the effects of the treatment. The image analysis highlighted the homogenization of the skin colour in the treated area. Conclusions: The combination of electromagnetic fields and vacuum for dyschromia treatments appears promising. The new method of assessing melanin levels resulted particularly efficient.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p<0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p < 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p<0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

Sleep is a fundamental human need: sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms and pro-inflammatory responses. Sci-entific literature is finally starting to pay attention to the central role of sleep-wake rhythm alterations for patients health. Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. This study aims to understand the effects of sleep-wake rhythm alterations on health and quality of life on cancer patients treated with oxaliplatin. Study has been conducted through the creation and distribution of questionnaires to patients to inves-tigate the potential alteration of the sleep-wake quality. Evaluating the influence of the collected variables on sleep quality, only liver and biliary tract and pancreas tumor lo-calization, in males, and previous difficulty sleeping, and anxiety, worries and stress, in females, resulted statistically significant. The results obtained may serve as foundation for designing awareness campaigns and updating of patients, healthcare personnel and caregivers, to improve health and quality of patients life.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

Synthetic Aperture RADAR (SAR) is a radar imaging technique in which the relative motion of the sensor is used to synthesize a very long antenna and obtain high spatial resolution. Standard SAR raw data processing techniques assume uniform motion of the satellite (or aerial vehicle) and a fixed antenna beam pointing sideway orthogonally to the motion path, assumed rectilinear. Despite SAR data processing is a well established imaging technology that has become fundamental in several fields and applications, in this paper a novel approach has been used to exploit coherent illumination, demonstrating the possibility of extracting a large part of the ancillary data information from the raw data itself, to be used in the focusing procedure. In this work an effort has been carried out to try to focus the raw SAR complex data matrix without the knowledge of anyof the parameters needed in standard focusing procedures as Range Doppler (RD) algorithm, ω - K algorithm and Chirp Scaling (CS) algorithm. All the literature references regarding the algorithms needed to obtain a precise image from raw data use such parameters that refer both to the SAR system acquisition geometry and its radiometric specific parameters. In [12], authors introduced a preliminary work dealing with this problem and able to obtain, in the presence of a strong point scatterer in the observed scene, good quality images, if compared to the standard processing techniques. In this work the proposed technique is described and performances parameters are extracted to compare the proposed approach to RD.

Proteins and DNA exhibit key physical chemical properties that make them advantageous for building nanostructures with outstanding features. Both DNA and protein nanotechnology have growth notably and proved to be fertile disciplines. The combination of both types of nanotechnologies is helpful to overcome the individual weaknesses and limitations of each one, paving the way for the continuing diversification of the structural nanotechnologies. Recent studies have implemented a synergistic combination of both biomolecules to assemble unique and sophisticate protein-DNA nanostructures. These hybrid nanostructures are highly programmable and display remarkable features that create new opportunities to build in the nanoscale. This review focuses on the strategies deployed to create hybrid protein-DNA nanostructures. Here, we will discuss strategies such as polymerization, spatial directing and organizing, coating, rigidizing or folding DNA into particular shapes or moving parts. The enrichment of structural DNA nanotechnology by incorporating protein nanotechnology has been clearly demonstrated and still shows a large potential to create useful and advanced materials with cell-like properties or dynamic systems. It can be expected that structural protein-DNA nanotechnology will open new avenues in the fabrication of nano-assemblies with unique functional applications and enrich the toolbox of bionanotechnology.

This study examines the feasibility of using event-related potentials (ERPs) obtained from electroencephalographic (EEG) recordings as biomarkers for long-term memory item classification. Previous studies have identified old/new effects in memory paradigms associated with explicit long-term memory and familiarity. Recent advancements in convolutional neural networks (CNNs) have enabled the classification of ERP trials under different conditions and identification of features related to neural processes at the single-trial level. We employed this approach to compare three CNN models with distinct architectures using experimental data. Participants (N = 25) performed an association memory task while recording ERPs that were used for training and validation of the CNN models. The EEGNET-based model achieved the most reliable performance in terms of precision, recall, and specificity compared with the shallow and deep convolutional approaches. The classification accuracy of this model reached 70% for known items and 62% for unknown items. Good overall accuracy requires a trade-off between recall and specificity and depends on the architecture of the model and the dataset size. These results suggest the possibility of integrating ERP and CNN into online learning tools and identifying the underlying processes related to long-term memorization.

This study is aimed to point out the possible application of the Enzyme-Linked ImmunoSorbent Assay (ELISA) test on table olives. Because olives, like many other foods, are not free from mycotoxin contamination, the main focus of this work was assessing the presence or absence of aflatoxins and ochratoxin A. The work was carried out in two phases. In the first phase, tests were carried out on commercial olives to assess the efficacy of the method and the kit (Veratox® 'Neogen' and AgraQuant® 'Romer Labs') by comparing them with the Liquid Chromatography coupled to a mass-mass spectrometer (LC-MS/MS); in order to understand if there were any interferences in antigen-antibody recognition; subsequently, mycotoxins were inoculated on the same samples with a known quantity, in order to assess the concentrations obtained and compare them to the expected ones. The second step involved modifying the method, so to improve the recovery of inoculated mycotoxins in the samples under study. Afterwards we evaluated the presence of mycotoxins in table olives supplied in the project. The results showed the effectiveness of the ELISA test, especially in the mycotoxin recovery phase. Indeed, after the modification of the mycotoxin extraction method, recoveries increased from 55% to over 70% for aflatoxins, and from 40% to over 55% for ochratoxin A. When analysing the samples provided by the above-mentioned company, the results showed some false positives, in particular in relation to ochratoxin A ’s analysis, mainly related to the first sample submission. Taking this into account, the ELISA test can be considered as an initial screening method applicable as a control programme for the evaluation of mycotoxins in olives which helps by saving time and costs. It should always be kept in mind that, if positive values should emerge, the LC-MS/MS analysis should be carried out.

The objective of this was to evaluate the effects of organic fertilization on biomass production in Urochloa spp. pastures, and the soil biological and physical properties in the Colombian Amazon region. Three pastures crops (Urochloa decumbens, Urochloa humidicola and Urochloa brizantha) with 5 years old were examined in a hill landscape. A randomized complete blocks design covering an area of 5005 m2, with 1 m separation between units to minimize edge effects. Highly significant differences in Urochloa spp. biomass production were observed before and after organic fertilization (i.e., initial time: 992.19±97.66 kg DM ha-1 vs. final time: 1920.94±155.44 kg DM ha-1 vs.), but not between different fertilization treatments. The interaction between the treatment and time was significant for total density (p=0.0300) and richness (p=0.0300) of soil macrofauna. Furthermore, the interaction between treatment and soil depth was significant for bulk density (p=0.0187). The linear mixed effects analysis showed that soil bulk density and penetration resistance were lower in 0 - 10 cm depth than that observed in 10 - 20 depth and 20 - 30 cm depth. Overall, the application of organic fertilizers had a significant and positive effect on Urochloa spp. forage biomass and on the physical and biological properties of soils that had historically been affected by extensive livestock farming in a deforested hill landscape in the Colombian Amazon region.

We previously showed that, based on the frequency and distribution of specific cell types, rainbow trout (RT) intestinal mucosa is divided in two regions that form a complex nonlinear 3D pattern and have a different renewal rate. This work had two aims. First, to investigate whether the unusual distribution of cell populations reflects a similar distribution of functional activities. To this end, we determined the protein expression pattern of three well defined enterocytes functional markers: Peptide Transporter 1 (PepT1), Sodium-Glucose/Galactose Transporter 1 (SGLT-1) and fatty acid-binding protein 2 (Fabp2). Second, to characterize the structure of RT intestinal stem cells (ISC) niche and to determine whether the different proliferative rates correlate with a different organization and/or extension of the stem cells population. We studied the expression and localization of well-characterized mammal ISC markers: LGR5, HOPX, SOX9, NOTCH1, DLL1 and WNT3A. Our results indicate that morphological similarity is associated with similar function only between the first portion of the mid-intestine and the apical part of the complex folds in the second portion. Mammal ISC markers are all expressed in RT but their localization is completely different suggesting also substantial functional differences. Finally, higher renewal rates are supported by a more abundant ISC population.

Background: Trigeminal neuralgia associated to vascular compression, by aberrant or ectopic arterial or venous vessels, is a frequent condition in clinical practice. Management with microvascular decompression through a Minimal invasive retrosigmoidal has shown high rates of pain control, with low complication rates and excellent therapeutic results. Objective: To describe the surgical technique and clinical outcomes in terms of pain relief after microvascular decompression for trigeminal nerve, through a minimal invasive retrosigmoidal parasterional burr-hole technique. Methods: A group of patients with trigeminal neuralgia refractory to medical management who underwent microvascular decompression considering outcomes based on Visual Analogue Scale (VAS), and Barrow Neurological Institute Pain Scale (BNIPS). Added to a technical note of the surgical technique for a minimal invasive retrosigmoidal parasterional burr-hole. Results: Twenty-two patients were evaluated, clinical assessment after surgical intervention showed a decrease pain according to VAS, resulting from an average preoperative state of 9.5 ± 0.37 to a postoperative condition of 1.32 ± 1.28, exhibiting statistically significant changes (p < 0.0001, d = 9.356). On the other hand, in relation to the BNIPS scale, a decrease from an average preoperative status of 4.55 ± 0.25, to a postoperative status at 12 months of 1.73 ± 0.54 was also demonstrated, showing significant changes (p < 0.0001, d = 3.960). Conclusion: Microvascular decompression of the trigeminal nerve through a minimal invasive retrosigmoidal parasterional burr-hole is feasible and can be a safe and effective technique for the management of pain.

Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.

Italy has been defined as the "logistics platform" of the Mediterranean Sea. The Italian port system, with 11,6 million TEUs handled and 61,4 million passengers by 2022 (Assoporti data Jan‐Dec 2022) [1] is the key to guarantee this condition through adequate levels of reliability, safety and sustainability. This contribution addresses port logistics and shipping, focusing on primary issues related to the energy sector with a specific focus on what can be observed in the Italian context. Specifically, decarbonization of the maritime sector and related infrastructural problems (e.g. Cold Ironing or alternative fuels, where the uncertainty about resources availability and related cost do not allow for an easy strategic planning by both the shipowner and the port authority), as well as policies such the Emission Trading System (ETS) will be analyzed. All these issues, if addressed with a critical review, could represent the driving force of the national port sector for its growth and its competitiveness at a global scale.

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

Our world is increasingly challenged by managing the impacts of natural disasters, particularly floods, which are frequent, dangerous, and costly. Traditional flood mapping methods, reliant on Optical satellites (MSI), struggle under cloud cover which is typical during such events. Synthetic Aperture Radar (SAR) offers a promising alternative with its cloud-penetrating capability, though its use has been limited due to complexity and data labeling challenges. This project aims to develop a SAR-based flood segmentation model that can rapidly and accurately map floods globally, with high adaptability to different flood types and regions. By utilizing deep learning and a novel transfer-learning technique that combines the strengths of Optical/MSI and SAR data, the model seeks to bypass the challenges of manual labeling and improve mapping accuracy. Initial results show the model's effective generalization across various flood events, with superior performance indicated by an Intersection over Union (IoU) of 0.72, outperforming existing methods and demonstrating promising capabilities in precise flood mapping.

Experimental studies of degradation of two ribonucleosides (guanosine and uridine) were carried out by making use of mechanochemistry. Mechanochemical experiments reveal the decomposition of guanosine and uridine promoted by nickel(II) and carbonate ions into guanine and uracil, respectively which were identified by HPLC and 1H NMR spectroscopy (this applied only to uracil). Additionally, DFT methodologies were used to probe the energetic viability of several degradation pathways, including in the presence of the same ions. Three mechanisms were analysed via ribose ring-opening: dry, single molecule water- and metal-assisted, which confirmed the mechanochemical degradation of ribonucleosides, with nucleobase preservation. These results can be applied to interpret the organic content of terrestrial and extra-terrestrial samples after mechanochemical treatment.

Pinus patula is one of the most planted wood conifer species worldwide; however, no foliar nutrient standards exist for this species up to date. The objective of the present study was to generate and verify two sets of foliar nutrient standards for nearly ten-year-old P. patula trees: critical nutrient concentrations and DRIS norms. Nutrients studied were N, P, K, Ca, Mg, Fe, Cu, Zn, Mn, and B. The reference standards were verified experimentally by installing two fertilization trials; one of them located in Huayacocotla, state of Veracruz and the other one in Aquixtla, state of Puebla, Mexico. Nutrient status of each fertilization trial was correctly predicted by critical nutrient values and DRIS as well. Both standards were able to detect the secondary growth-limiting nutrient deficiency in the Huayacocotla trial, where the primary limitation for growth was scarcity of solar radiation within tree crowns. The limiting nutrient in both experimental trials was K.

Surgical knots are sequences of half-knots (H) or half-hitches (S), defined by their number of throws, by an opposite or similar rotation compared with the previous one and for half-hitches, whether sliding (s) or blocking (b). Opposite rotation results in (more secure) symmetric (s) knots, similar rotation in asymmetric (a) knots, and changing active and passive ends has the same effect as changing rotation. Loop security is the force to keep tissue together after a first half-knot or sliding half-hitches. With polyfilament sutures H2, H3, SSs and SSsSsSs have a loop security of 10, 18, 28 and 48 Newton (N), respectively. With monofilament sutures, they are only 7, 16, 18 and 25N. Since many knots can reorganise, the definition of knot security as the force at which the knot opens or the suture breaks should be replaced by the clinically more relevant percentage of clinically dangerous and insecure knots. Secure knots with polyfilament sutures require a minimum of 4 or 5 throws, but the risk of destabilisation is high. With monofilament sutures, only 2 symmetric+4 asymmetric blocking half-hitches are secure. In conclusion, half-hitch sequences are recommended since mandatory for monofilament sutures, adding flexibility for loop security with less risk of destabilisation.

Pericyte and their tunnelling nanotubes (P-TNTs) have been described as involved in the early phases of angiogenesis in the human normal developing brain and glioblastoma, being a common feature of combined endothelium/pericyte vessel sprouts. Based on the few data available so far about this ‘alternative’ pericyte-TNT-driven mode of angiogenesis, whose precise function in vessel growth through vascular cells communication, has still to be determined, this study aims to cast light on the regulative molecules involved in this process, governed by intimate pericyte-endothelial interactions. After considering the existence of the sprout guiding pericyte and P-TNT, as shown by pioneering ultrastructural studies as well as by more recent observations with NG2/CD146 pericyte markers and basal lamina molecules, a step-by-step profile of the process has been suggested and an investigation undertaken on ‘unconventional’, pro-angiogenic ligand/receptor systems, that may have a role aside from the canonical pathways. In this context, a possible candidate worthy of investigation is the c-KIT receptor, a member of the tyrosine kinase family of proteins, which also includes the well-known VEGFR and PDGFR. According to the obtained results showing a primary localization of c-KIT on endothelial cells and pointing out a differential distribution of the receptor on normal vs glioblastoma vessels, it seems conceivable to propose the stem cell factor/c-KIT signaling as a key factor in pericyte-TNT-driven angiogenesis, advancing this alternative mode of angiogenesis and the c- KIT pathway as possible targets for devising effective antiangiogenic therapeutic strategies.

Chronic high glucose (HG) exposure increases methylglyoxal (MG)-derived AGEs and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic‐degenerative diseases. Under physiologic condition the harmful effects of MG are contrasted by glyoxalase system that is involved in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. The study aimed at investigating the role of polyphenols extracted from an apple high in polyphenols (Calville White Winter), on glyco-oxidative stress induced by chronic HG-exposure. Intestinal Caco-2 cells were treated in physiological glucose condition (25mM) as a control and in HG condition (50mM) with or without apple extract for one week. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significantly increase in ROS, lipid peroxidation, AGEs and Glyoxalase I (GlxI) activity with a significant decrease in total antioxidant intracellular defense. Treatment with polyphenols under HG condition restores to the control levels GlxI activity, decreases Glyoxalase II (GlxII) in relation to the control and induces a drop of glyco-oxidative damage. This paper seeks to highlight the roles of polyphenols in glyco-oxidative stress.

Quantum cryptography is the field of cryptography that explores the quantum properties of matter. Its aim is to develop primitives beyond the reach of classical cryptography or to improve on existing classical implementations. Although much of the work in this field has been dedicated to quantum key distribution (QKD), some important steps were made towards the study and development of quantum oblivious transfer (QOT). It is possible to draw a comparison between the application structure of both QKD and QOT primitives. Just as QKD protocols allow quantum-safe communication, QOT protocols allow quantum-safe computation. However, the conditions under which QOT is actually quantum-safe have been subject to a great amount of scrutiny and study. In this review article, we survey the work developed around the concept of oblivious transfer in the area of theoretical quantum cryptography, with an emphasis on some proposed protocols and their security requirements. We review the impossibility results that daunt this primitive and discuss several quantum security models under which it is possible to prove QOT security.

One way to increase overall natural gas engine efficiency is to transform exhaust waste heat into useful energy by means of a bottoming cycle. Organic Rankine cycle (ORC) is a promising technology to convert medium and low grade waste heat into mechanical power and electricity. This paper presents an energy and exergy analysis of three ORC-Waste heat recovery configurations by using an intermediate thermal oil circuit: Simple ORC (SORC), ORC with Recuperator (RORC) and ORC with Double Pressure (DORC), and Cyclohexane, Toluene and Acetone have been proposed as working fluids. An energy and exergy thermodynamic model is proposed to evaluate each configuration performance, while available exhaust thermal energy variation under different engine loads was determined through an experimentally validated mathematical model. Additionally, the effect of evaportating pressure on net power output , absolute thermal efficiency increase, absolute specific fuel consumption decrease, overall energy conversion efficiency, and component exergy destruction is also investigated. Results evidence an improvement in operational performance for heat recovery through RORC with Toluene at an evaporation pressure of 3.4 MPa, achieving 146.25 kW of net power output, 11.58% of overall conversion efficiency, 28.4% of ORC thermal efficiency, and an specific fuel consumption reduction of 7.67% at a 1482 rpm engine speed, a 120.2 L/min natural gas Flow, 1.784 lambda, and 1758.77 kW mechanical engine power.

International basins are divided into sub-basins that are managed at the national and local levels, within the territory of each country, before reaching the level of international concern. The management of international basins could be developed using an integrated water management, based on multi-level governance model in which many actors are involved, from local to international scale. However, in the La Plata River Basin this model is not working, even with international agreements such as the La Plata Basin Treaty, which was signed in 1969. The understanding of political interests behind the law helps to explain its inefficiency. Therefore, considering the lack of a systemic view in an international watershed, it could be possible to have accumulating effects caused by the transformations of watercourses in the sub-basins. Then, the 2014 water crisis in the State of São Paulo, Brazil, is an example of the possible consequences arising from the lack of an integrated water management in the La Plata River Basin. Finally, this article demonstrates that the only way to have water resources utilization efficiency in an international basin is considering it as an integrated ecosystem, in order that any local problem may affect the whole basin.

The cultivation of Hevea brasiliensis, the primary commercial source of natural rubber, is strongly impacted by South American Leaf Blight (SALB) disease, caused by the fungus Pseudocercospora ulei. Various management strategies have been implemented, including the selection of resistant genotypes and the identification of escape zones. This study evaluated the growth, early yield, and resistance to SALB of nine Colombian elite genotypes from the ECC-100 series and IAN 873 clone (control) in a large-scale clone trial in a low SALB pressure zone in the Colombian Amazon, 2017 - 2020. Favorable early performance was evident, although there was a significant increase in the severity and sporulation of P. ulei over time, especially in the ECC 35, ECC 60, and IAN 873 genotypes. However, these scores represented a low susceptibility. Genotypes with higher resistance to SALB demonstrated greater growth and early yield compared to higher susceptible genotypes. The ECC 64, ECC 73, ECC 90, ECC 25, and ECC 29 genotypes were more desirable in low SALB pressure zones due to their higher resistance and early performance. It is important to highlight that this research contributes to the selection of new SALB-resistant Colombian genotypes of H. brasiliensis in the growth stage. Therefore, it is necessary to evaluate their productivity in the mature stage and long-term resistance to SALB, before recommending and promoting their commercial adoption in the Colombian Amazon.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

With an increasing demand for quality of care and lower costs, hospitals are looking for industry-based methods to improve efficiency in their processes. This study aims to reduce waste in a public hospital in Mexico by improving the medical supply process for the operating room. To this end, a lean healthcare (LH) implementation following the DMAIC approach (Define-Measure-Analyze-Improve-Control) is carried out. We analyze the value stream of the supply process, including main surgical procedures and their related medical supplies, and identify different causes of inefficiency, which are evaluated and controlled through different tools, including a value stream map, Kanban, and the 5S program. As a result, five types of waste were reduced. Over-processing requests were reduced by 15.3%, defective identification numbers were reduced by 46.5%, redundant processing was improved by 94.8%, near 2.8% of the unnecessary inventory was reduced, and transportation waste was reduced by up to 16.7%. Finally, the lead-time for the main supplies was reduced by 33 days. This work demonstrates that LH and DMAIC are effective in reducing waste and are highly conducive to improving sustainability in healthcare processes. Moreover, it provides practical insights for practitioners regarding the implementation of LH in public hospitals in developing countries.

A partial least squares (PLS) quantitative chemometric method based on the analysis of the MID-FTIR spectrum of polymer inclusion membranes (PIMs) used for the extraction of Cr(VI) from aqueous media is developed. The system previously optimized considering the variables membrane composition, extraction time, and pH, is characterized in terms of its adsorption isotherm, distribution coefficient, extraction percent and enrichment factor. A Langmuir type adsorption behavior with KL = 21.99 L/mg, qmax = 0.242 mmol/g and 0&lt;RL&lt;1, indicates that metal adsorption is favorable. The characterization of the extraction reaction is performed as well showing an 1:1 Cr(VI):Aliquat 336 ratio, in agreement with solvent extraction data. The principal component analysis (PCA) of the PIMs revels a complex pattern, which is satisfactorily simplified and related to Cr(VI) concentrations through the use of a variable selection method (iPLS) in which bands in the ranges 3451–3500 cm-1 and 3751–3800 cm-1 are chosen. The final PLS model including the 100 wavelengths selected by iPLS and 10 latent variables shows excellent parameter values with RMSEC: 3.73115, RMSECV: 6.82685, Bias: -1.91847e-13, CV Bias: 0.185947, R2 Cal: 0.98145, R2 CV: 0.940902, recovery%: 104.02 ± 4.12 (=0.05), sensitivity%: 0.001547 ppb, γ: 3.8 ppb, γ- 1: 0.6 ppb-1, selectivity: 0.0155, linear range: 5.8–100 ppb, LD: 1.9 ppb, and LQ: 5.8 ppb. The developed PIM sensor is easy to implement as it requires few manipulations and reduced number of chemical compounds in comparison to other similar reported systems.

The performance of a small reconfigurable unmanned aerial vehicle (UAV) is evaluated, 1 combining a multidisciplinary approach in computational analysis of additive manufactured struc- 2 tures, fluid dynamics, and experiments. Reconfigurable UAVs promise cost savings and efficiency 3 without sacrificing performance, while demonstrating versatility to fulfill different military mission 4 profiles. The use of computational fluid dynamics (CFD) in UAV design produces higher accuracy 5 aerodynamic data, which is particularly important for complex aircraft concepts such as blended 6 wing bodies. To address challenges relating to anisotropic materials, the Tsai-Wu failure criterion is 7 applied to structural analysis, using CFD solutions as load inputs. Aerodynamic performance results 8 show the low-speed variant attains an endurance of 1 hour, 48 minutes, whereas for its high-speed 9 counterpart, it is 29 minutes at 66.7% higher cruise speed. Each variant serves different aspects of 10 small UAS deployment in combat, with low-speed envisioned for close surveillance, and high-speed 11 for incursions. Experimental and simulation results suggest room for design iteration, in wing area 12 and geometry adjustments. Structural simulations demonstrated the need for airframe improvements 13 in the low-speed configuration. This paper highlights the potential of reconfigurable UAVs to disrupt 14 the industry, advocating for further research and design improvements.

Mast cells (MCs) play a crucial role during infections with Leishmania, that is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response, impacting the susceptibility to infections. Thus, to assess the impact of androgens and salivary proteins of sand fly vectors on the mast cell (MC) response to Leishmania infections, we infected orchiectomized male mice with the parasite in the presence or absence of sand fly salivary proteins and analyzed the inflammatory response of MCs. Our results showed a differential MC response to the parasite and to vector salivary proteins in mice deprived of gonadal hormones, as compared to sham-operated mice. Orchidectomy induced a different pattern of activation in MC of animals infected with Leishmania and vector-salivary proteins. Our results show that during Leishmania infection, androgens modulate the innate immunity response against the parasite and salivary proteins of the sand fly vector.

The emergence of the COVID-19 pandemics prompted a fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the golden standard RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

Male obesity secondary hypogonadism (MOSH) impairs fertility, sexual function, bone mineralization, fat metabolism, cognitive function, deteriorates muscle mass and alters body composition. The aim of this pilot study was to evaluate the effect of dietary intervention and physical activity on the MOSH patient’s hormonal profile after a 10% weight loss compared to baseline. Fourteen male patients were enrolled. Hormonal, lipid, glycemic profiles and body composition were determined at baseline and after a 10% weight loss. Aging Male Symptoms Scale (AMS) and Yale Food Addiction Scale (YFAS) were administered to patients in order to investigate hypogonadal symptoms and food addiction. Compared to baseline, a significant increase of Total Testosterone (TT) (300.2 ± 79.5 ng/dl vs 408.3 ± 125.9, p = 0.002, 95% CI 26.8; 167.7) and a reduction of 17-Beta Estradiol level (48.3 ± 14.9 pg/mL vs 39.2 ± 15.2, p = 0.049, 95% CI 3.1; 0.0) were observed. Total Fat Mass (FM) percentage, android and gynoid fat mass percentage (39.2 ± 6.4% vs 36.2 ± 5.8%, p = 0.0001, 95% CI 22.5; 62.3; 51.5 ± 6.8% vs 47.6 ± 6.8%, p = 0.001, 95% CI 0.6; 1.8, vs 39.2 ± 6.2% vs 36.5 ± 6.3% p= 0.0001, 95% CI 0.9; 2.0 respectively) were significantly decreased after nutritional intervention. In addition, total Fat Free Mass (FFM) in kg was significantly reduced after 10% weight loss (62.3± 2.8 kg vs 60.3± 7.7 kg, p = 0.002, 95% CI 45.0; 93.0). Lifestyle changes, specifically dietotherapy and physical activity, induce positive effects on hypogonadism due to obesity.

The formation of new blood vessels is a critical process for tumor growth and may be achieved through different mechanisms. Angiogenesis represents the first described and most studied mode of vessel formation, but tumors may also use alternative ways to secure blood supply and eventually acquire resistance to anti-angiogenic treatments. These non-angiogenic mechanisms have been described more recently and include intussusceptive microvascular growth (IMG), vascular co-option, and vasculogenic mimicry. Like solid tumors, also in lymphomas angiogenic and non-angiogenic pathways play a fundamental role in tumor growth and progression. In view of the relevant prognostic and therapeutic implications, a comprehensive understanding of these mechanisms is of paramount importance for improving the efficacy of treatment in patients with lymphoma. In this review, we summarize the current knowledge on angiogenic and non-angiogenic mechanisms involved in the formation of new blood vessels in Hodgkin’s and non-Hodgkin’s lymphomas.

The effect of COVID-19 confinement regulations on air quality in the northwestern Alps is here assessed based on measurements at five valley sites in different environmental contexts. Surface concentrations of nitrogen oxides, ozone, particle matter, together with size, chemical, and optical (light absorption) aerosol properties, complemented by observations along the vertical column are considered. The 2020 concentration anomalies relative to previous years’ average are compared with the output of a machine learning algorithm accounting for weather effects and a chemical transport model, their difference being within 10–20 %. Even in the relatively pristine environment of the Alps, the «lockdown effect» is well discernible, both in the early confinement phase and in late 2020, especially in NOx concentrations (NO decreasing by >80 % and NO2 by >50 %). While ozone shows little variation, secondary aerosols increase due to enhanced transport from the neighbouring Po basin and coarse particles decrease due to missing resuspension by traffic and, in the city, to the shutdown of a steel mill. The NO2 vertical column density decreases by >20 %, whereas the aerosol profile is mainly influenced by large-scale dynamics, except a shallow layer about 500 m thick possibly sensitive to curtailed surface emissions.

Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and pre-scribed off-label for several neurological conditions like neuropathic pain, migraine and anxiety. Amitriptyline potentiates the monoaminergic transmission by blocking the reuptake of norepi-nephrine and serotonin. However, antidepressants also act on additional targets that contribute to either therapeutic or adverse effects and may suggest new indications for their repurposing. Furthermore, since depression is often a co-morbidity in patients with chronic conditions (i.e. cancer, neurodegenerative diseases) the use of antidepressants interfering with pathways in-volved in cell homeostasis may affect the progression and outcome of these pathologies. Here we investigate the effects of amitriptyline on proliferation and autophagy in human SH-SY5Y neuroblastoma cells. Dose and time-dependent upregulation of the autophagy markers LC3II and autophagy receptor p62, with accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to amitriptyline. Alteration of autophagy was accompanied by reduced cell viability and decreased clonogenic capacity, without a significant induction of apoptosis. Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5 -/- MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine suggesting that the amitriptyline’s effects on cell proliferation were not caused by the modulation of autophagy. Our findings demonstrate that amitriptyline acts on pathways that are crucial for cell and tissue homeostasis and pose the basis for further studies on the potential application of these effects and the consequences during long-term antidepressant treatment.

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of those asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT) is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. 177 patients performed carotid Doppler-ultrasound. The following data was collected: EMT, intima-media thickness (IMT), presence of carotid plaques, area of the highest plaque, and grade of internal carotid stenosis. From each carotid bifurcation a right and left EMT was determined. We analyzed both the mean EMT (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT, [Median=1.14; IQR=0.66 versus Median=0.97; IQR=0.40; p=.001]. A positive correlation was found between mean EMT and IMT (right: ρ=.20; p=.010; left: ρ=.21; p=.007) and between mean EMT and area of the largest carotid plaque (right: ρ=.17; p=.036; left: ρ=.22; p=.004). Left carotid stenosis ≥ 70% was associated with higher mean EMT. [Median=1.55; IQR=0.68 versus Median=1.00; IQR=0.46; p=.019]. Patients with “acute culprit” carotid stenosis had a higher ipsilateral EMT [Left ipsilateral EMT: Median=1.46; IQR=0.63; “non-acute”: Median=0.94; IQR=0.43; p=.009; Right ipsilateral EMT: Median=2.25; IQR=0.62; “non-acute”: Median=1.00; IQR=0.51; p=.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an “acute culprit” carotid stenosis decreased (p=.036). The amount of peri-carotid adipose tissue, estimated with EMT was associated with atherosclerosis at the carotid arteries. In particularly EMT could be a non-invasive marker of “acute culprit” carotid stenosis, easily determined in clinical practice. These findings may have implications in personalized medicine, for the determination of the best treatment approach.

Zidovudine (AZT) has significantly reduced the mortality and morbidity rates among AIDS patients, but it has been associated with hepatotoxicity. AZT treatment has been linked to disrupted lipid and glucose metabolism, and the enhancement of pro-inflammatory chemokines and other mediators, which can lead to liver steatosis. In contrast, the administration of adenosine (ADO) has proven to be an effective hepatoprotector against both acute and chronic liver damage. Therefore, present study was aimed to investigate the harmful effects of chronic AZT administration and the beneficial effects of the co-administered ADO. Chronic oral AZT administration did not induce hyperglycemia or dyslipidemia, but serum liver marker enzyme activities were increased, as well as evidence of liver steatosis and inflammation. These findings were associated with low insulin and glucagon levels, elevated serum levels of pro-inflammatory cytokines and disruptions in cell redox states in these animals. ADO co-administration attenuated the deleterious effects induced by AZT: blocking the production of inflammatory molecules, increasing serum insulin and glucagon levels, and restoring liver cellular redox state. Then, blood insulin levels seemed to be greatly influenced by the cellular redox state, which was altered by AZT administration. This alteration is likely to be connected to mitochondrial integrity and metabolism.

Glycine is an important neurotransmitter in vertebrates, performing both excitatory and inhibitory actions. Synaptic levels of glycine are tightly controlled by the action of two glycine transporters, GlyT1 and GlyT2, located on the surface of glial cells and glycinergic or glutamatergic neurons, respectively. Glycinergic neurotransmission in invertebrates has so far only been investigated in a very limited number of species, and, although it was suggested that its functions are to some extent conserved with vertebrates, the evolution of glycinergic neurotransmission remains very poorly understood. Here, by combining phylogenetic and gene expression analyses, we characterized the glycine transporter complement of amphioxus, an important invertebrate model for studying the evolution of chordates. We show that amphioxus possesses three glycine transporter genes, two of which (GlyT2.1 and GlyT2.2) are closely related to GlyT2 of vertebrates, while the other (GlyT) is a member of an ancestral clade of deuterostome glycine transporters. While expression of GlyT2.2 is predominantly non-neural, GlyT and GlyT2.1 are widely expressed in the amphioxus nervous system and are characterized by differential expression in neurons and glia, respectively. However, in vertebrates, glycinergic neurons express GlyT2 and glia GlyT1, suggesting that the evolution of the chordate glycinergic system was accompanied by complex genetic remodeling leading to the paralog-specific inversion of gene expression. Albeit this genetic divergence between amphioxus and vertebrates, we found strong evidence for a general conservation of the role of glycinergic neurotransmission during larval swimming, allowing us to hypothesize that the neural networks controlling the rhythmic movement of chordate bodies are homologous.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

The relationship between tissue effects, intensity (I), and voltage (V) of a high-frequency alternative current seems well known. However, the translation of the settings of the electrosurgical unit and their use during surgery seems not to be unanimously understood by all surgeons. This results in many variations of surgical technique and plenty of specific questions asked during live surgery. Above 200 V, the heat of the sparks results in the explosion of superficial cells and a cutting effect. With higher voltages, the associated coagulation is increasing. Voltage and amount of energy (Watt=I*V) are independent since a similar amount of energy can be obtained with a continuous current or an intermittent current half the time and a double voltage. Below 200 V, tissue is heated until the steam from boiling tissue stops the current. Therefore, slower heating with less energy or a larger contact area permits deeper coagulation. The maximal output (W) of the electrosurgical unit results in versatility of use besides being a safety measure. The current intensity increases with the area of contact. Therefore, when I*V exceeds the preset output, V has to drop. A limited maximal output thus permits using the same instrument for non-contact cutting with >200V and sparks and coagulation when the contact area is much larger. In conclusion, the tissue effects of electrosurgery vary with the device’s voltage setting (often indicated as force) and the maximal output. The sur-geon’s choice to cut or coagulate by changing the contact area adds versatility.

Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24-48 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 μM) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation.

Building integrated photovoltaics (BIPV) consists of PV panels that are integrated into the building as part of the construction. This technology has advantages such as the production of electricity without necessary additional land area. This paper provides a literature review about the recent developments in urban building energy modelling, including tools and methods, and how they can be used to predict the effect of PV systems on building outdoor and indoor environments. It is also intended to provide a critical analysis on how PV systems affect the urban environment, both from an energy and a comfort point of view. The microclimate, namelly the urban heat island concept, is introduced and related with the existence of PV systems. It is concluded that urban building energy modelling (UBEM) can be effective to study the performance of PV systems in the urban environment. It allows to simultaneously predict the building energy performance and the microclimate effect. However, there is a need to develop new methodologies to overcome the challenges associated to UBEM, especially in what concerns non-geometric data, which leads to a major source of errors. and to find an effective method to predict the effect of PV systems in the urban environment.

Impulsive noise is the main limiting factor for transmission over channels affected by electromagnetic interference. We study the estimation of (correlated) Gaussian signals in an impulsive noise scenarios. In this work, we analyze some of the existing as well as some novel estimation algorithms. Their performance is compared, for the first time, for different channel conditions, including the Markov-Middleton scenario, where the impulsive noise switches between different noise states. Following a modern approach in digital communications, the receiver design is based on a factor graph model and implements a message passing algorithm. The correlation among signal samples as well as among noise states brings about a loopy factor graph, where an iterative message passing scheme should be employed. As it is well known, approximate variational inference techniques are necessary in these cases. We propose and analyze different algorithms and provide a complete performance comparison among them, showing that both Expectation Propagation, Transparent Propagation, and the Parallel Iterative Schedule approaches reach a performance close to the optimal, at different channel conditions.

The use of modulator drugs that target the cystic fibrosis transmembrane conductance regulator (CFTR) is the final frontier in the treatment of Cystic Fibrosis (CF), a genetic multiorgan disease. F508del is the most common mutation causing defective formation and function of CFTR. Elexacaftor-tezacaftor-ivacaftor is the first triple combination of CFTR modulators. Herein we report on a one-year case-control study that involved 26 patients with at least one F508del mutation. Patients were assigned to two similar groups, with patients with the worse clinical condition receiving treatment with the triple combination therapy. The study aims to define the clinical and especially microbiological implications of treatment administration. The treatment provided significant clinical benefits in terms of respiratory, pancreatic and sweat function. After one year of therapy, airway infection rates decreased and pulmonary exacerbations were dramatically reduced. Finally, treated patients reported a surprising improvement in their quality of life. The use of triple combination therapy has become essential in most CF people carrying the F508del mutation. While the clinical and instrumental benefits of treatment are thoroughly known, further investigations are needed to properly define its microbiological respiratory implications and establish the real advantage of life-long treatment with elexacaftor-tezacaftor-ivacaftor.

Background: Metastasis is a complex process that involves the spread of the tumor to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Soluble factors such as cytokines have been closely related to breast cancer (BC) metastasis. Bisphenol A (BPA) is an endocrine disrupting chemical compound with estrogenic properties, which exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and cellular changes in the tumoral immune microenvironment. Methods: Thus, we used female BALB/c mice that were exposed neonatally to a single dose of BPA. Once sexual maturity was reached, a mammary tumor was induced injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro and micro metastases in the lung, and metastasis-induced cell infiltration. Results: BPA neonatal treatment did not show significant endocrine alterations. Nevertheless, BPA induced a great rate of metastasis to the lung associated with higher intratumoral expression of IL-1b, IL-6, IFN-g, TNF-a and VEGF. Conclusions Our data suggest that cytokines are key players in BC metastasis induction, and that BPA is a risk factor to be considered. This knowledge must be considered with the aim of recognizing environmental pollution in the clinical history of patients to possibly counter BC metastases.

Resveratrol is one of the most investigated natural polyphenolic compounds and is contained in more than 70 types of plants and in red wine. The widespread interest in this polyphenol derives from its antioxidant, anti-inflammatory and anti-aging properties. Several studies have established that resveratrol regulates animal reproduction. However, the mechanisms of action and the potential therapeutic effects are still unclear. This review aims to clarify the role of resveratrol in the male and female reproductive functions, with a focus on animals of veterinary interest. In the female, resveratrol has been considered a phytoestrogen due to its capacity to modulate ovarian function and steroidogenesis via sirtuins, SIRT1, in particular. Resveratrol has also been used to enhance aged oocyte quality, and as a gametes cryo-protectant with mainly antioxidant, and anti-apoptotic effects. In the male, resveratrol enhanced testes function and spermatogenesis through activation of AMPK pathway. Furthermore, resveratrol has been supplemented to semen extenders improving the preservation of sperm quality. In conclusion, resveratrol has potentially beneficial effects for ameliorating ovarian and testes function. However, due to unclear data, further studies are necessary to consolidate these findings.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

Background and aims: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional –and that cohort research– have reported several risk factors associated with the prevalence and incidence of this condition. However, alterations of body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. Methods: This is a secondary analysis in older adults (≥60 years old) derived from the study “Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)” a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. Results: The cohort included 241 subjects. Average age was 75.6±7.8 years; 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in subjects with excess fat mass index, even after adjusting for several covariates. RM was also more likely to occur in subjects with low total lean tissue index, according to both an unadjusted model and after adjusting for the corresponding variables. Regarding the association between RM and gait speed, RM was also more likely to occur in subjects with low gait speed according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. Conclusion: The risk of malnutrition diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, but possibility was significantly higher in those with low total lean tissue and low gait speed after 4.1 years of follow-up in community-dwelling older adults. These results highlight that excess fat mass, low total lean tissue, and low gait speed are first than risk of malnutrition and not vice versa.

In the Valpolicella area (Verona - Italy) Vitis vinifera cv. Corvina is the main grape variety used to produce Amarone wine. Before starting the winemaking process, the Corvina grapes are stored in a withering (i.e., dehydrating) warehouse until about 30% of the berry weight is lost (WL). This practice is followed to have the chemical metabolites concentrate in the berry and enrich the Amarone wine in aroma and antioxidant compounds. In compliance with the guidelines and strict Amarone protocol set by the Consorzio of Amarone-Valpolicella, withering must be carried out by setting the grapes in a suitable environment, either under controlled relative air humidity (RH) conditions and wind speed (WS) – no temperature modification is to be applied – or, following the traditional methods, in open-air natural environmental conditions. In general, the two processes have different dehydration kinetics due to the different conditions in terms of temperature, RH, and WS, which affect the accumulation of sugars and organic acids and the biosynthesis of sec-ondary metabolites such as stilbenes and glycoside aroma precursors. For this study, the two grape-withering processes were carried out under controlled (C) and not-controlled (NC) condi-tions and the final compositions of the Corvina dried grapes were compared also to evaluate the effects on the organoleptic characteristics of Amarone wine. The findings highlighted differences between the two processes mainly in terms of the secondary metabolites of the dried grapes, which affect the organoleptic characteristics of Amarone wine.

The past years have shown the widespread vulnerability of agro-food systems and rural diets to external perturbations such as wars, climate events, and pandemics. Experiencing numerous obstacles, Cuba constitutes an example of success in the transition to agroecological sustainability models. This article characterizes how processes of agricultural change, local development, and industrial degrowth have impacted food availability and dietary diversity among rural livelihoods in the municipality of Yaguajay, Sancti Spíritus, for the past forty years (1980s-2020s). It integrates findings from focus groups, repeated nutritional surveys, and interviews carried out between 2016 and 2022 among residents of the towns of Yaguajay and La Picadora. The goal is to identify effects and response strategies within agro-food systems of rural populations. Distinguishing between periods of abundance and shortage, our findings show two counterpoints: intensive sugar monocrop cultivation which resulted in high dietary variety; and economic crises in 1990s and during the last period of the pandemic, which have led to significant dietary adjustments. The article concludes underscoring the importance of comprehensive assessments of dietary strategies to elicit what agroecological transitions mean for local realities and of the value of food consumption and small-holder production experiences to understand the limits to sustainable transformations.

In this review, we highlight new findings that have deepened our understanding of the mechanisms of leukemogenesis, therapy and resistance in APL. PML-RARa sets the cellular landscape of Acute promyelocytic leukemia (APL) by repressing transcription of RARa target genes and disrupting PML-NBs. RAR receptors control the homeostasis of tissue growth, modeling and regeneration, PML NBs are involved in self-renewal of normal and cancer stem cells, DNA damage response, senescence and stress response. Additional somatic mutations in APL mainly involve FLT3, WT1, NRAS, KRAS, ARID1B and ARID1A genes. Treatment outcomes in patients with newly diagnosed APL improved dramatically since the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). ATRA activates the transcription of blocked genes and degrades PML-RARα, while ATO degrades PML-RARa by promoting apoptosis and has a pro-oxidant effect. Resistance to ATRA and ATO may derive from mutations in the RARa ligand binding domain (LBD) and in the PML-B2 domain of PML-RARa, but such mutations cannot explain the majority of resistances experienced in the clinic, globally accounting for 5-10% of cases. Several studies are ongoing to unravel clonal evolution and resistance, suggesting the therapeutic potential of new retinoid molecules and combinatorial treatments of ATRA or ATO with different drugs acting through alternative mechanisms of action, which may lead to synergistic effects on growth control or induction of apoptosis in APL cells.

This experimental research presents an easier model for fitting experimental results that can be simulate the dynamical behaviour of a single degree freedom system, SDFS, subjected in a forced vibration in a shaking table. The fractional damping using a Kelvin-Voigt fractional derivative rheological model, KVFRdm, to represent a fractional oscillator and compare with the experimental model.

Overweight and Obesity are global health and economic concerns. According to the World Health Organization, the number of individuals with obesity has nearly tripled since 1975. This health issue is currently considered an epidemic, affecting over 1.9 billion adults and 340 million children and adolescents. It contributes to more than 5 million deaths each year and has a global economic burden that will reach $4.32 trillion annually by 2035, according to the World Obesity Federation. This disease can affect every system of the human body and can lead to complications such as metabolic syndrome, diabetes, cancer, dyslipidemia, cardiovascular diseases, and hypertension, among others. Treatment may sometimes include diet, exercise, drugs, and bariatric surgery. Nonetheless, not all people have access to these treatments, and public health strategies consider prevention the most important factor. In this regard, recent investigations are aiming to find alternatives and adjuvants for the treatment of obesity, its prevention, and the reversion of some of its complications, using natural sources of anti-obesogenic compounds like polyphenols, terpenes, alkaloids, saponins, among others. In this review, we gather the most current information using PubMed, Google Scholar, Scopus, Cochrane, and Web of Science. We present and discuss the current information about natural products that have shown anti-obesogenic effects at a molecular level. We also consider the impact of dietary habits and lifestyle in preventing overweight and obesity due to the evidence of the benefits of certain foods and compounds consumed regularly. We discuss mechanisms, pathways, and receptors involved in the modulation of obesity, especially those related to inflammation and oxidative stress linked to this disease, due to the relevance of these two aspects in developing complications.

White adipose tissue (WAT) is distributed in several depots that have distinct metabolic and inflammatory functions. In our body there are subcutaneous (sWAT), visceral (vWAT) and bone marrow fat depots (BFAT). Obesity affects size, function and inflammatory state of WATs. This process can alter the stem cell niches present in these tissues and affect the functions of stem cells residing within. In particular, obesity may affect the activity of mesenchymal stromal cells (MSCs) present in WAT. MSCs are an heterogenous population containing stromal cells, progenitor cells, fibroblasts and stem cells that are able to differentiate in adipocytes, chondrocytes, osteocytes and other mesodermal derivatives. We performed a comparison of the effects of obesity on MSCs obtained from sWAT, vWAT and BFAT. Our study evidenced that obesity affected mainly the biological functions of MSCs obtained from bone marrow and vWAT with a decrease in proliferation rate, reduced percentage of cells in S phase and trigger of senescence. The onset of senescence was confirmed by expression of genes belonging to RB and P53 pathways. Our study evidenced that negative consequences of obesity on body physiology may be related also to impairment in the functions of stromal compartment present in the several adipose tissues. This finding provides new insights on the targets that should be considered for an effective treatment of obesity-related diseases.

Time estimation was investigated in 24 healthy adults, 12 women and 12 men, before and after an exhaustive exercise. We compared the capability of estimating time intervals in the range from 1 to 5 s using tasks requiring mental count and tasks that did not allow the mental count. Time estimation and blood lactate levels were evaluated before and at the end of the exercise. We found that the perception of time intervals between 1 and 5 s was affected at the end of the exercise. The observed effects, associated with a significant increase in blood lactate levels, were different in the two types of time estimation used in the present study. In experimental conditions in which participants had to evaluate duration of the time interval by mental counting, at the end of exercise a significant reduction in the overestimation of time made at rest was observed. On the other hand, when participants had to assess the difference in duration between two events without the possibility to mentally count, at the end of the exercise a significant deterioration in performance was observed. In both cases, no gender differences were seen.

The urban environment induces stress on trees and the impact can be identified by observing the condition of the crown. The aim of this study is to correlate the variables crown density (Cdn), crown transparency (Ctr) and dieback (Cdie) with the following vegetation indices: normalized difference vegetation index (NDVI), enhanced vegetation index (EVI2), blue normalized difference vegetation index (BNDVI), green normalized difference vegetation index (GNDVI), green-red vegetation Index (GRVI) and red-green-blue vegetation index (RGBVI) of the tree crown located in urban green areas, as well as chlorophyll fluorescence (Fv/Fm) as an indirect indicator of tree health condition. A total of 549 trees were evaluated, represented in 24 families, 36 genera and 53 species; the variables had average values of 67.96 % in Cdn, 35.19 % in Ctr and 1 % in Cdie. Correlations were found between Fv/Fm, NDVI and BNDVI. NDVI and BNDVI correlated with variables such as Cdn and Ctr, mainly in species such as Ligustrum lucidum, Jacaranda mimosifolia and Fraxinus uhdei. Therefore, it is possible to evaluate tree health condition of trees in urban green environments through the identification of unfavorable conditions at the crown level by using vegetation indices for some of the species studied.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.

Nonlinear optimization (NOPT) is a meaningful tool for solving complex tasks in fields like engineering, economics, and operations research, among others. However, NOPT has problems when it comes to dealing with data variability and noisy input measurements that lead to incorrect solutions. Furthermore, nonlinear constraints may result in outcomes that are either infeasible or suboptimal, such as non-convex optimization. This paper introduces a novel regularized physics-informed neural network (RPINN) framework as a new NOPT tool for both supervised and unsupervised data-driven scenarios. By using custom activation functions and regularization penalties in an artificial neural network (ANN), RPINN can handle data variability and noisy inputs. Besides, it uses physics principles to build the network architecture, computing the optimization variables based on network weights and learned features. In addition, it uses automatic differentiation training to make the system scalable and cut down on computation time through batch-based back-propagation. The test results for both supervised and unsupervised NOPT tasks show that our RPINN can provide solutions that are competitive compared to state-of-the-art solvers. In turn, RPINN’s robustness against noisy input measurements makes it particularly valuable in environments with fluctuating information. Additionally, RPINN’s ANN-based foundation offers significant flexibility and scalability.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

Maize (Zea mays) is one of the most important staple food and primary source of livestock feed in the world. As the consumption of maize grown on the selenium-enriched soils of Naore Valley is one of the apparent causes of selenosis in the area, this work collected and analyzed total Se, Se fractions, and Se species distributions in maize plant samples, including grains, leaves, stalks, roots, rhizosphere soils, and the most representative parent rock materials from Naore Valley, Ziyang County, China. The Se distribution in soils markedly correlated with the weathered Se-enriched bedrocks, but most of the Se in the analyzed soils is enclosed as recalcitrant residual Se and organic-sulfide bound Se. In contrast, Se in rocks had a comparatively higher bioavailability and is bounded mainly to organic matter and sulfides minerals, with very few of the Se enclosed in the residual fraction. Maize plants might take a large amount of Se from the organic-sulfide bound Se fraction in the Se-rich soils, the weathered products from bedrocks or plant litters. Total Se concentrations in the collected samples were observed in descending order soil>leaf>root>grain>stalk. The predominant Se species detected in maize plants was SeMet. Se inorganic forms, mainly Se(VI), decreased from root to grain and were possibly assimilated into organic forms. Se (IV) was barely present. The natural increases in Se concentration affected mainly leaf and root dry-weight biomass as they are the organs that coped with the highest Se accumulation. This paper offers an insight into the uptake, accumulation, and distribution of Se forms in natural Se-rich maize crops and an opportunity for shifting Se-rich soils from menaces to valuable resources for growing Se-rich agricultural products.

The involvement of NK and other cytotoxic cells is considered the first defense' line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells, the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers, some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. Despite having demonstrated multiple correlations, it should be noted that immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, impaired epidermal barrier function and unbalanced inflammatory response. The pathophysiology involves immune dysregulation, with a predominance of T-helper 2 cells. AD is triggered by many known and unknown factors, including oxidative stress. Reactive oxygen species (ROS) contribute to AD pathogenesis by causing cellular damage and inflammation. Moreover, increased oxidative stress in AD leads to hyperactivation of the MAP kinase pathway, extracellular signal-regulated kinase (ERK) and p38, with DNA damage and subsequent skin barrier dysfunction. This narrative review provides a comprehensive overview of the role of natural antioxidant compounds, highlighting their potential therapeutic value in AD management. They include vitamin D, vitamin E, pyridoxine (vitamin B6), Vitamin C, carotenoids and melatonin, in AD. Despite some studies have shown an association between vitamin D, vitamin E, vitamin C and carotenoids levels and AD course, conflicting results exist. Pyridoxine supplementation has shown mixed results, and melatonin has demonstrated antioxidant and anti-inflammatory properties in AD; in fact, melatonin treatment resulted in a decrease in symptoms in patients with AD, although no significant correlation with changes in sleep latency was reported. In addition, iron and zinc (Zn) supplementation can also improve AD symptoms. Further research is needed to elucidate the optimal use of these natural antioxidants in AD treatment

In recent years, many studies have highlighted the consistent finding of amoxicillin in waters destined for wastewater treatment plants, in addition to superficial waters of rivers and lakes in both Europe and North America. In this paper, the amoxicillin degradation pathway was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants at three different pH values. The structures of 16 isolated degradation byproducts (DPs), one of which was isolated for the first time, were separated on a C-18 column via a gradient HPLC method. Then, combining mass spectrometry (MALDI-MS/TOF) and nuclear magnetic resonance, we compared commercial standards and justified a proposed formation mechanism beginning from the parent drug. Microbial growth inhibition bioassays with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were performed to determine the potential loss of antibacterial activity in isolated degradation byproducts. An increase of antibacterial activity in the DPs was observed compared to the parent compound.

Hydrotalcites (HTlc) represents a class of nanostructured layered materials that may be employed in a variety of applications, from green to bio technologies. In this paper, we report an investigation on HTlc made of Mg and Fe, recently employed to improve the growth in vitro of osteoblasts within a keratin sponge. We have carried out an analysis of powder materials and of HTlc dispersed in keratin and spin-coated on a Si/SiO2 substrate at different temperatures. A DC magnetic study of the powders has been carried out with a Quantum Design Physical Property Measurement System, equipped with a Vibrating Sample Magnetometer. The data gathered prove that these HTlc are fully paramagnetic, and keratin shows a very small magnetic response. Optical and Atomic Force Microscopy analyses of the thin films provide a detailed picture of clusters randomly dispersed in the films with various dimensions. The magnetic properties of these films have been characterized using the Nano Magneto Optical Kerr Effect (NanoMOKE) down to 7.5K. The data collected show that the local magnetic properties can be mapped with a micrometric resolution distinguishing HTlc regions from keratin ones. This approach opens new perspectives in the characterization of these composite materials.

The study conducts a comparative life cycle assessment (LCA) analysis to assess the environmental impact of two different manufacturing processes used to produce transparent dental aligners. The former method consists of thermoforming a polymeric disc over 3D printed, customized models, while the second, more innovative approach involves the direct printing of aligners using additive manufacturing (AM), specifically applying digital light processing (DLP) technology. The analysis results highlight how adopting direct printing through AM brings significant advantages in terms of environmental sustainability, thanks to the substantial reduction in raw materials and electricity consumption. These drops translate into decreased potential environmental impacts across all impact categories considered within the EF 3.1 method. Furthermore, lowering the amount of raw materials needed in the direct printing process contributes to a notable decrease in the overall volume of waste generated, emphasising the environmental benefits of this innovative technique.

Type-2 diabetes mellitus is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage Type 2 diabetes mellitus is widely documented. These dietary compounds exert their beneficial effects by several actions, including the protection of pancreatic islet β-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorating diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type-2 diabetes patients.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for about 40% of all cases NHL. Analysis of the tumour microenvironment is an important aspect of the assessment of the progression of DLBCL. In this review article, we have analyzed the role of different cellular components of the tumour microenvironment, including mast cells, macrophages, lymphocytes, in tumour progression of DLBCL. We examined several approaches to confront the available pieces of evidence; three key points emerged. DLBCL is a disease of malignant B-cells spreading and accumulating both at nodal and in extranodal sites. Both in patients with nodal and extranodal lesions, the subsequent induction of a cancer-friendly environment appears pivotal. DLBCL cell interaction with mature stromal cells and vessels confers tumour protection and inhibition of immune response while delivering nutrients and oxygen supply. Single cells may also reside and survive in protected niches in the nodal and extranodal sites as a source for residual disease and relapse. This review aims to molecularly and functionally recapitulate the DLBCL-milieu crosstalk, to relate niche and pathological angiogenic constitution and interaction factors to DLBCL progression.

The loop and knot securities of 2 braided and 2 monofilament sutures of four diameters (3.0, 2.0, 0, 1) were evaluated with a tensiometer for four 4-throw knots known to be secure with a 2.0 polyfilament suture. Loop security of monocryl 1 is low, being 14.7 + 3.0 Newton (N) for a 3-throw half-knot (H3) and 15.4 + 2.4 N and 28.3+ 10 N for 2 (SSs) and 4-throw (SSsSsSs) symmetrical sliding half-hitches. This is lower than 18, 24, and 46 N for similar knots with vicryl. Polyfilament sutures have excellent knot security for all diameters. Occasionally, some slide to open with slightly lower knot security, especially for larger diameters, although not clinically problematic. Knot se-curity of monofilament sutures was unpredictable for all 4 knots, especially for larger diameters, resulting in many clinically insecure knots. A secure monofilament knot requires a 6-throw knot with 2 symmetrical sliding half-hitches or 2 symmetrical half-knots secured with 4 asymmetric blocking half-hitches. In conclusion, with polyfilament sutures, 4 or 5-throw half-knot or half-hitch sequences result in secure knots. For monofilament sutures, loop and knot security is much less, half-knot combinations should be avoided, and secure knots require 6-throw knots with 4 asym-metric half hitches. This conclusion is valid for gynecologic laparoscopic and open surgery, and for surgery in general.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Ageing of the world population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioural and psychological syndromes known as neuropsychiatric or behavioural and psychological symptoms of dementia remarkably reduce the quality of life of patients. Rising evidence is unraveling the pathophysiology of these symptoms in which all the neurotransmitter systems in the Central Nervous System (CNS) are implicated, with a pivotal role of alterations of the glutamatergic neurotransmission. Pharmacological agents for the treatment of these disorders endowed with efficacy and safety are not available yet; aromatherapy provides the best evidence in the control of agitation, the most resistant symptom. Basic research effort demonstrates that the essential oil of bergamot induces anxyolitic-like effects, devoid of sedation, typical of benzodiazepines, with noteworthy advantage for demented patients. People suffering from dementia often cannot verbalize pain, thus resulting unrelieved and contributing to agitation. Bergamot essential oil provides extensive evidence of analgesic properties independent from the route of administration. Among other mechanisms, modulation of autophagy, a process involved in neuropathic pain, seems to be implicated in the analgesic activity of bergamot essential oil. These data, together with the reported safety profile form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioural and psychological symptoms of dementia.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the province of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. We performed genomic analysis to identify the changes in genetic diversity of SARS-CoV-2 between December 2019 and November 2020, and through molecular surveillance, we monitored the mutations that could be involved in viral fitness. We analyzed 2,213 complete genomes from 6 geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified 7 frequent mutations that resulted in non-synonymous substitutions (dN). Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein emerged recently and have spread in Oceania and Europe. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

The aim of this study was to evaluate the effect of dietary supplementation with Olea europaea L. extract on the animal welfare and milk quality of lactating Italian Holstein-Friesian dairy cows at different calving orders. Cows in mid lactation phase received, for 60 days, the natural olive extract Phenofeed Dry® (500 mg/cow/day) with high antioxidant power. Hormonal and metabolic parameters were determined through ELISA assays, the milk fatty acid profile through gas chromatography, chemical-nutritional and hygienic-sanitary parameters through ultrasonic analyses. The milk lysozyme content was measured through a specific ELISA assay. The administration of the enriched feed did not alter the hormonal balance. Primiparous cows were more sensitive to the treatment and showed a better general health status compared to other calving orders. The enriched feed resulted in a reduction of saturated fatty acids (SFAs) and an increase of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), ensuring an adequate nutritional content and, above all, a significantly higher content of the antibacterial protein, lysozyme. Overall, our study demonstrate that the inclusion of natural bioactive molecules such as Olea europaea L. polyphenols contributes to improving the welfare status of dairy cows and ensuring high nutritional and functional quality of animal productions.

Object of this work is the design and the simulation of a hybrid UAV with VTOL capabilities that has been designed for landing on naval moving platforms. The work is focused on the innovative propulsion layout adopted on the UAV. Authors discuss how adopted low level control strategies can exploit the innovative features of the proposed system assuring a good rejection of transversal wind disturbances. Particular attention is dedicated to low level modelling and control of the system emphasizing how choices regarding low level actuation and control should improve performances and robustness of the system.

Placing the needle inside the epidural space for locoregional anesthesia is a challenging procedure, which even today is left to the expertise of the operator. Recently, we have demonstrated that the use of optically sensorized needles significantly improve the effectiveness of such procedure. Here we propose an optimized configuration, where the optical fiber strain sensor is directly integrated inside the epidural catheter. The new design allows to solve the biocompatibility issues and increases the versatility of the former configuration. Through an in vivo study carried out on a porcine model we confirm the reliability of our approach, which also opens the way to catheter monitoring during its insertion inside biological spaces.

Electrospinning is known to be an effective and straightforward technique to fabricate polymer non woven matrices made of nano and microfibers. Micro patterned morphology of electrospun matrices results to be outmost advantageous in the biomedical field, since it is able to mimic extracellular matrix (ECM), and favors cell adhesion and proliferation. Controlling electrospun fibers alignment is crucial for the regenerative purposes of certain tissues, such as neuronal and vascular. In this study we investigated the impact of electrospinning process parameters on fiber alignment in tubular nanofibrous matrices made of Poly (L-lactide-co-ε-caprolactone) (PLA-PCL); a Design of Experiments (DoE) approach is here proposed in order to statistically set up the process parameters. The DoE was studied keeping constants the previously set material and environmental parameters; voltage, flow rate and mandrel rotating speed were the process parameters here investigated as variables. Orientation analysis was based on ImageJ and plugin Orientation J analysis of SEM images. The results show that voltage combined with flow rate has significant impact on electrospun fiber orientation, and the greatest orientation is achieved when all the three input parameters (voltage, flow rate and mandrel rotation speed) are at their maximum value.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

(1) Background: Mpox was declared an international public health emergency by WHO. Initially, Smallpox vaccine in Italy was offered only to laboratory personnel at direct risk of infection. Currently, Healthcare workers (HCWs) are all considered by European Centre for Disease Prevention and Control (ECDC) to be at low or moderate risk. (2) Methods: To assess smallpox vaccination coverage among HCWs in an Italian hospital with different levels of risk of exposure to Mpox infection and to assess their attitudes toward vaccination, a self-report was administered to HCWs stratified at high and low/moderate risk. (3) Results: Of the 338 HCWs evaluated, 60.36% provided the requested data; among them the percentage of previously vaccinated staff was 38.7%, which corresponds to 23.4% of the total HCWs in the departments considered. Considering those born before 1979 as vaccinated, vaccination coverage increases from 23.4% to 41.4%. The department with the highest percentage of vaccinated is infectious diseases (60.5%); The percentage of HCWs who adhered to vaccination is 23%; only 8.8% of laboratory staff want to vaccinate, compared with 100% of midwives. The department with the highest percentage of vaccination adherence is proctology (85.7%). (4) Conclusions: Given the vaccination adherence rate and the vaccination coverage of the departments analyzed, it would be useful to extend vaccination against Smallpox to frontline HCWs involved in patient care in Italy too.

Amphibians are widely known as a prolific source of bioactive metabolites. In this work we isolated and characterized compounds with antiparasitic activity from the oocytes of the toad Rhinella alata collected in Panama. Bio-guided isolation and structural elucidation was carried out using chromatographic and spectroscopic techniques. The organic crude extract was subjected to solid phase extraction followed by HPLC purification of the fraction with in vitro activity against Trypanosoma cruzi trypomastigotes. Seven steroids (1-7) of the bufadienolide family were isolated and their structures determined using NMR and MS analyses; of these 19-formyl-dyscinobufotalin (3) is reported as a new natural product. Compounds 1, 3-7, resulted with a good anti-trypanosomal activity profile, among these 16β-hydroxyl-hellebrigenin (1) and bufalin (7) showed significant selectivity for T. cruzi. Furthermore, molecular docking analysis showed compounds 1, 3 and 7 interact through H-bonds with the amino acid residues GLN-19, ASP-158, HIS-159 and TRP-177 from cruzipain, at the catalytic site. Given the lack of therapeutic options to currently treat the American trypanosomiasis, this work can serve as the basis for further studies that aim the development of bufadienolides or their derivatives as drugs against Chagas disease.

Selenium (Se) is an essential element of the human diet. Therefore, it is necessary to implement Se in agricultural fertilization, although it is not considered as an essential element for plants, Se provides benefits at the level of redox metabolism, increasing the resistance of plants to various stress factors. The increase of the availability of selenium with the use of biopolymer complexes was sought in Great Lakes lettuce grown in substrate pots treated with SeO₂ (5 mg L Se), Cs-PAA + Se (5 mg L Se), and Cs-PAA. The redox metabolism was modified by increasing the enzymatic activity of glutathione peroxidase. The use of Cs-PAA + Se biopolymer complexes increase selenium up to 24 mg/Kg dry weight (DW) in plant tissues.

In this paper, the experimental results of the thermal sub-system of a reliable and cost-effective polygeneration solar system are presented. This polygeneration system produces heating, cooling and electricity from solar energy, which are used in an existing test-building. Heat is generated in four evacuated tube solar collectors (ETC). The heat may be used for space cooling, through a variable geometry ejector (VGE) heat pump. In order to reduce the mismatches between generation and consumption, two thermal storage tanks were added. The performance of a new thermal storage, with 400 l, able to storage both sensible and latent heat, was tested. Heating performances of the test-building were assessed. Ejector cycle tests were also performed.

The development of storage standards for databases of different nature and origin makes it possible to aggregate and interact with different data sources in order to obtain and show complex and thematic information to the end user. This article aims to analyze some possibilities opened up by new applications and hypothesize their possible developments. With this work, using the currently available Web technologies, we would like to verify the potential of the use of Linked Open Data in the world of WebGIS and illustrate an application that allows the user to interact with Linked Open Data through their representation on a map. Italy has a artistic and cultural heritage unique in the world and the italian Ministry of Cultural Heritage and Activities and Tourism has created and made freely available a dataset in Linked Open Data format that represents it. With the aim of enhancing and making this heritage more usable, the National Research Council (CNR) has created an application that presents this heritage via WebGIS on a map. Following criteria definable by the user, such as the duration, the subject of interest and the style of the trip, tourist itineraries are created through the places that host this heritage. New possibilities open up where the tools made available by the Web can be used together, according to pre-established sequences, to create completely new applications. This can be compared to the use of words, all known in themselves, which, according to pre-established sequences, allow us to create ever new texts.

Surgical neurolysis is a procedure designed to liberate an injured nerve from scar tissue or adjacent structure, thereby facilitating nerve regeneration in cases of brachial plexus neuropathy (BPN). This study presents a case series of patients diagnosed with BPN who underwent surgical neurolysis. The primary focus was on the clinical assessment of recovery using the British Medical Research Council motor grading scale (BMRC). Additionally, a comprehensive literature review was conducted to analyze motor recovery outcomes related to surgical neurolysis for BPN. 18 patients with BPN who underwent surgical neurolysis where included. The results experienced a notable increase of 58% in muscle strength as assessed by the BMRC. The average preoperative state of 2.17±1.15 improved significantly to a postoperative condition of 3.44±1.34 (p = 0.003, d= 0.913) The systematic review identified 2298 articles which were selected for qualitative analysis, demonstrated that surgical neurolysis was associated with favorable motor recovery outcomes in 75.82% of the patients. Both the case series and the literature review reveal significant motor recovery following surgical neurolysis. It is crucial to conduct well-designed, adequately powered, randomized, and blinded clinical trials. Such studies will provide robust evidence to support or refute the utility of this approach in motor recovery.

Ecuador is the world's fifth largest cocoa producer, generating hundreds of annual tons of residues from this fruit. This research aims to value this residual (cocoa pod husk) by using it as raw material to obtain pectin, which is widely used in the food and pharmaceutical industries. For them, the extraction of three different organic acids with GRAS status (and therefore safe for their use), citric, malic and fumaric acids, were studied. In addition, two other factors, temperature (70-90°C) and extraction time (60-90 min), were explored in a central composite design of experiments. Under the conditions of the experiment, it was obtained that the best yields were reached for citric acid, malic acid and fumaric acid and for ~86 min of extraction time. The temperature did not show a significant influence on the yield. The pectins obtained under optimal conditions were characterised, showing their similarity with commercial pectin. However, the equivalent weight and the esterification degree of the pectin obtained with fumaric acid classify it as having a high equivalent weight and a low degree of esterification. It differs significantly from the other two acids, perhaps due to the limited solubility of fumaric acid.

The addition of flaxseed and amaranth on the physicochemical, functional and microstructural changes of instant-extruded cereals was evaluated. Six different mixtures were made with additions of amaranth (30%–50%) and flaxseed (10% and 15%) using maize grits and minor additives as supplementary ingredients and then extruded in a twin-screw extruder. The extrudates evaluated, had insoluble and soluble fiber contents increased with the proportion of amaranth and flaxseed. The mixture 4 (higher flaxseed content) presented highest soluble fiber percentage (1.9%). Extruded cereals had the lowest viscosity (<99.5 cp) and highest hardness values (5.2 N) whereas the dietary fiber content was highest. Fiber content increase, resulted in a higher water solubility index (WSI) (0.5) and decrease the water absorption index (WAI) (2.5). Amaranth and flaxseed incorporation increased crystallinity, resulting in a larger, and more compact laminar structure. Amaranth and flaxseed addition resulted in extruded cereals with acceptable physicochemical and functional properties.

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

Estimates of dog population sizes are a prerequisite for delivering effective canine rabies control. However, dog population sizes are generally unknown in most rabies-endemic areas. Several approaches have been used to estimate dog populations but without rigorous evaluation. We compare post-vaccination transects, household surveys and school-based surveys to determine which most precisely estimates dog population sizes. These methods were implemented across 28 districts in southeast Tanzania, in conjunction with mass dog vaccinations, covering a range of settings, livelihoods and religious backgrounds. Transects were the most precise method, revealing highly variable patterns of dog ownership, with human: dog ratios ranging from 12.4:1 to 181.3:1 across districts. Both household and school-based surveys generated imprecise and sometimes inaccurate estimates, possible due to low sample size. Transect data were subsequently used to develop a predictive model for estimating dog populations in districts lacking transect data. We predicted a dog population of 2,316,000 (95% CI 1,573,000-3,122,000) in Tanzania and an average human: dog ratio of 20.7:1. Our modelling approach has the potential be applied to predicting dog population size in other districts where mass dog vaccination is carried out, given census and livelihood data. We recommend transects as a rapid and effective method to refine dog population estimates across large geographic areas and guide dog vaccination programs.

Bioglasses are highly adoptable bone substitute materials, which can be combined with so-called therapeutic ions. These ions have shown to influence underlying molecular processes of the bone regeneration cascade. Moreover, it is known that bone substitutes induce an immune reaction within their implantation area involving macrophages and their pro- and anti-inflammatory subtypes dependent on their chemical composition. However, only poor knowledge exists regarding the influence of therapeutic ions onto the immune reactions and the associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglasses on the induction of M1- and M2-macrophages as well as the implant bed vascularization. (2) Methods: For this study, two alkali glasses were produced on basis of ICIE-16 bioglass via the melt-quench route with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglasses were used as control materials. The bioactivity (ion release), chemical composition and the surface pattern were investigated, as well as an in vivo experiment was performed using the subcutaneous implantation model in rats. (3) Results: SEM imaging showed different formations of hydroxyapatite on the surfaces of the bioglass systems after submersion in simulated body fluid. EDX analysis confirmed the doping process by showing the release kinetics. Copper-doped bioglass exhibited a higher ion release than strontium-doped bioglass. Copper induced both a low immune cell migration and triggered a low number of M1- and M2-macrophages but also of blood vessels. The strontium-containing bioactive glass induced higher numbers of M1-macrophages after 30 days. Both copper- and strontium-doped bioglasses induced comparable numbers of M2-macrophages as found in the control groups. (4) Conclusions: Bioglass doping with copper and strontium did not exhibit significant influence on the foreign body response or the implantation bed vascularization in vivo. However, the prepared bioglass systems seemed to be biocompatible.

Nowadays, hydropower is the principal renewable; however, climate change increases extreme events such as floods, droughts, erosion, and sedimentation of rivers that produce uncertainty in hydroelectric generation. Thus, this document aims to analyze the climate change projections in the hydropower systems of Ecuador based on data from 14 projects studying the scenarios ac-cording to the Shared Socioeconomic Pathways from the Intergovernmental Panel on Climate Change. The study period starts from 2010 to 2020 with historical data, collects the tendency, defines a database year, and then projects the scenarios to 2050. The quantitative methodology uses a statistic on Ecuador's hydropower obtained inflow time series to calculate the deviation over the last years and develop a model to simulate future generation. The results show that the hydropower in Ecuador is expected to decrease considerably through 2050 due to meteorological changes. In this calculation of the Shared Socioeconomic Pathways, the selected scenarios show a reduction in SSP5 of 11.5%, SP2 of 16.2%, and SSP4 of 18.2% to 2050, concluding that the oppor-tunities for hydroelectric production facing climate change are variable, but the challenges are broad. In Ecuador, the projections of hydropower plants represent a sensitive issue of their re-ductions, especially knowing that the country had an energy grid in 2020 that depended on 87% of hydroelectric production.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair successful vaccination of elderly people. Thus, improved vaccination strategies specifically adapted to an aged immune system are required. We characterized a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein (MVA-ST) in an aged-hamster model for COVID-19. Intramuscular MVA-ST immunization resulted in protection from disease and severe lung pathology. Importantly, protection correlated with potent activation of SARS-CoV-2 specific T-cells and neutralizing antibodies. Our results suggest that MVA vector vaccines merit further evaluation as clinical candidate vaccines in elderly people to overcome limitations of age-dependent immunosenescence.

Risk management for technological hazards mainly focuses on the consequences on human lives. Although technological risk analysis evaluates environmental vulnerability, it does not reflect the consequences on environmentally exposed elements, such as rivers, water springs, flora, and fauna. This paper's objective was to propose a conceptual framework and create a multidisciplinary evaluation model for environmental risk analysis in the oil and gas industry. Initially, the problem was approached from a global perspective to justify the necessity of a holistic environmental risk analysis methodology in the oil industry, using environmental risk factors as well as underlying factors, such as environmental fragility and lack of resilience. The holistic assessment was carried out based on probabilistic risk analysis methodologies to obtain a holistic environmental risk index, HERI. This methodology was applied to an oil and gas industry company in Colombia. This allowed greater disaggregation of the results to establish priorities for risk reduction actions and identify the company's weaknesses.

The advent of immunotherapy and specifically of immune checkpoint inhibitors (ICIs) for the treatment of solid tumors has deeply transformed therapeutic algorithms in medical oncology. Approximately one third of patients treated with ICIs may develop immune-related adverse events, being the gastrointestinal tract often affected with different grades of mucosal inflammation. Checkpoint inhibitors colitis (CIC) presents with watery or bloody diarrhoea and in case of severe activity requires ICIs discontinuation. The pathogenesis of CIC is multifactorial and still partially unknow: anti-tumor activity that collaterally effects the colonic tissue and the upregulation of specific systemic inflammatory pathways (i.e., CD8+ cytotoxic and CD4+ T lymphocytes) are mainly involved. Many open issues remain on treatment timing and options, and biological treatment, above all with anti-TNF alpha, can be offered to these patients aiming to rapidly resume the oncological therapies. This review aims to summarize the pathogenetic mechanisms underlying CIC and to discuss evidenced-based management including the role of biological therapy.

Background: The t (2; 5) chromosomal rearrangement and resulting nucleophosmin (NPM1) -ALK fusion was first observed in 1994 in anaplastic large cell lymphoma (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab-vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK +, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of Brentuximab, still pending allo-SCT after two failed donor selection. Facing of a new therapeutic failure, we requested the Italian drug regulatory agency, and obtained the authorization, to administer 250 mg twice a day of Crizotinib, a drug incomprehensibly not registered for ALCL ALK +. Conclusions: The response to Crizotinib was optimal, since no adverse event occurred, and CT-PET persisted negative; this drug has proved to be a valid bridge to allo-SCT

The present minireview assessed the benefits of using artificial intelligence applications in healthcare at predicting the targets of bioactive small molecules in human. Method. The tool is a tuned algorithm, with novel data in web interface. Results. We used tables to order the information of Swiss Target Prediction that allow predictions on combination of chemotherapies and probable side effects. This tool is useful to understand the molecular mechanisms underlying a given phenotype or bioactivity, to rationalize possible favorable or unfavorable side effects and to predict off-targets of known molecules as well as to clear the way for drug repurposing. Predictions are done using a ligand-based approach to compare the similarity between a query molecule and the known ligands of a large collection of protein targets. Conclusion. This study allowed us to formulate recommendations for the use of some of the chemotherapeutic agent groups in cancer patients at a low cost. It is very important and beneficial for patients that take medicine for a longer period and on whose lives depend on such treatment.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of HR-HPV infection in female population has led to the discovery of several cases of double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate high risk (HR) HPV infections in women with double cervix within the National Cervical Cancer Screening program of the Lazio Region (Italy). From June 2021 to March 2024 a total of 142,437 samples were analyzed by Seegene’s Anyplex TM II HR-HPV method which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervixes and analyzed separately. Twenty-seven women with double cervix were identified (0.019%): 20 women were tested as negative for both cervices, while the remaining four (namely A, B, C and D) resulted positive. By genotyping, the following results were obtained: A) both samples showed genotype 31; B) one cervix was negative while the other showed genotype 58. C) one cervix was positive for HPV 18 and 31 while for 18, 31 and 33 in the other. D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition, where the presence HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common, paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyse available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is one of the most controversial diseases in pediatric rheumatology. Despite its first description being published more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine re-lease in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

The use of botanical extracts of the plant Jatropha curcas (Euphorbiaceae) represents a valuable alternative to control insect pests and avoid the detrimental effects on the environment and health that arise due to synthetic chemical insecticides. Thus, we conducted a systematic review to summarize the published evidence on the bioactivity of J. curcas against insect pests. Electronic databases were searched to identify studies that assessed J. curcas extracts against insect pests in various types of crops. We included 39 articles that reported the insecticidal and insectistatic activity of several botanical extracts from J. curcas against insects of eight different taxonomic orders. The evidence demonstrates that aqueous and methanolic extracts from seeds and leaves, seed oil, and petroleum ether seed extracts were effective against insect pests of stored grains, aphids of cabbage, sorghum, fruit flies, and desert locusts. The extracts caused high mortality, controlled the populations, reduced oviposition, diminished hatchability, and increased the antifeedant effect. However, the type of solvent used to obtain the botanical extract and the method of application (contact or food) are fundamental to increase its bioactivity. Therefore, botanical extracts from seeds and leaves of J. curcas should be considered as an alternative against insect pests and may be incorporated into integrative and sustainable management for insect control.

A scientific consensus is emerging on the benefits of dc distribution in medium voltage power systems of ships and cities. At least 50% space savings and increased power transfer capacity are estimated with enhanced voltage dc operation of electric cables. The goal of this research is to contribute to developing the empirical knowledge on the insulation performance in order to validate the feasibility of such anticipated gains of dc versus ac, and to determine the comparative impact of different operational conditions from a component engineering point of view. The partial discharge (PD) activity in cables is measured under ac and dc conditions as an indicator of insulation performance. Specifically, PDs in defects at the semicon-insulation interface are studied in terms of inception voltage, repetition rate and discharge magnitude. Empirical understanding is drawn for operating voltage and frequency dependence of the discharge behavior in such voids in the range of 10 to 20\,kV and 0 to 0.1\,Hz, respectively. The change in PD activity with void evolution is explored.