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Background/Objectives: Cognitive impairment in spinocerebellar ataxia patients has been reported since the early-disease stage. We aimed to assess cognitive differences in SCA1 and SCA2 patients. Methods: We performed neuropsychological (NPS) and neurophysiological (auditory event-related potentials, aERPs) assessments in 16 SCA1 and 18 SCA2 consecutive patients. Furthermore, clinical information (age at onset, disease duration, motor disability) was collected. Results: NPS tests yielded scores in the normal range in both groups but with lower scores in the Frontal Assessment Battery (p < 0.05) and Visual Analogue Test for Anosognosia for motor impairment (p < 0.05) in SCA1, and the Trail Making Test (p < 0.01), Raven's progressive matrices (p < 0.01), Stroop (p < 0.05), and emotion attribution tests (p < 0.05) in SCA2. aERPs showed lower N100 amplitude (p < 0.01) and prolonged N200 latency (p < 0.01) in SCA1 compared with SCA2. Clinically, SCA2 had more severe motor disability than SCA1 in the Assessment and Rating of Ataxia Scale. Conclusions: SCA2 showed more significant difficulties in attentional, visuospatial, and emotional function, and greater motor impairment. In contrast, SCA1 showed less cognitive flexibility/phasic ability, probably affected by a more severe degree of dysarthria. The same group revealed less neural activity during nonconscious attentional processing (N100-N200 data), suggesting greater involvement of sensory pathways in discriminating auditory stimuli. NFS did not correlate with NPS findings, implying an independent relationship. However, the specific role of the cerebellum and cerebellar symptoms in NPS test results deserves more focus. [ABSTRACT FROM AUTHOR]

Pulmonary vasculitis identifies a heterogeneous group of diseases characterized by inflammation, damage and necrosis of the wall of pulmonary vessels. The most common approach to classify vasculitis is according to etiology, therefore dividing them into primary and secondary, with a further sub-classification of primary vasculitis based on the size of the affected vessels (large, medium, and small). Pulmonary involvement is frequently observed in patients with systemic vasculitis and radiological presentation is not pathognomonic, but may vary between diseases. The main findings using high-resolution computed tomography (HRCT) include small vessel wall thickening, nodular lesions, cavitary lesions, reticular opacities, ground-glass opacities (GGO), consolidations, interlobular septal thickening, tracheobronchial stenosis, and aneurysmal dilatation of pulmonary arteries, with or without pleural effusion. Radiological diagnosis alone is difficult since signs and symptoms of lung vessel involvement are often non-specific and might overlap with other conditions such as infections, connective tissue diseases and neoplasms. Therefore, the aim of this review is to describe the most common radiological features of lung involvement in pulmonary vasculitis so that, alongside detailed clinical history and laboratory tests, a prompt diagnosis can be performed. [ABSTRACT FROM AUTHOR]

The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis. These therapies restore T-cell antitumor immune response by releasing T-lymphocytes from the inhibitory effects of tumor cells. Immune checkpoint therapies have completely changed the management of patients with solid cancers. This therapeutic strategy is less used in hematological malignancies, although good results have been achieved in some settings, such as refractory/relapsed classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Variable results have been obtained in diffuse large B-cell lymphoma and T-cell lymphomas. Immunohistochemistry represents the main technique for assessing PD-L1 expression on tumor cells. This review aims to describe the current knowledge of PD-L1 expression in various types of lymphomas, focusing on the principal mechanisms underlying PD-L1 overexpression, its prognostic significance and practical issues concerning the evaluation of PD-L1 immunohistochemical results in lymphomas. [ABSTRACT FROM AUTHOR]

Featured Application: This software design pattern can be used in OOP programming in order to promote conceptual clarity, reduce coupling, and facilitate system scalability. Object-oriented programming (OOP) has long been a dominant paradigm in software development, but it is not without its challenges. One major issue is the problem of tight coupling between objects, which can hinder flexibility and make it difficult to modify or extend code. Additionally, the complexity of managing inheritance hierarchies can lead to rigid and fragile designs, making it hard to maintain and evolve the software over time. This paper introduces a software development pattern that seeks to offer a renewed approach to writing code in object-oriented (OO) environments. Addressing some of the limitations of the traditional approach, the Puzzle Pattern focuses on extreme modularity, favoring writing code exclusively in building blocks that do not possess a state (e.g., Java interfaces that support concrete methods definitions in interfaces starting from version 8). Concrete classes are subsequently assembled through the implementation of those interfaces, reducing coupling and introducing a new level of flexibility and adaptability in software construction. The highlighted pattern offers significant benefits in software development, promoting extreme modularity through interface-based coding, enhancing adaptability via multiple inheritance, and upholding the SOLID principles, though it may pose challenges such as complexity and a learning curve for teams. [ABSTRACT FROM AUTHOR]

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF. [ABSTRACT FROM AUTHOR]

In the motorsport industry, the choice of material for manufacturing the heat resistant components often falls on titanium alloys. In most cases, the production flow for this kind of part involves CNC machining and subsequent assembly by welding process, to other parts obtained by cold plastic forming and possibly made using different titanium alloys. Hence, the alloying element-content in the joint area can be extremely heterogeneous and variable point-by-point. To investigate this topic further, dissimilar welding of the alpha/beta alloy Ti6Al4V and of the oxidation-resistant alpha alloy KS-Ti 1.2 ASN-EX was made by GTAW technology and using different filler metals. Chemical and mechanical properties of the welds were investigated by XRD, SEM-EDS, microhardness maps, and tensile and bending tests. Results show that, despite the different alloying elements present in the two filler wires investigated, static properties of the welds are similar. Results also show that the local V/Al content ratio affects the microhardness as it is responsible for the creation of supersaturated alpha phases during the cooling of the weld beads. [ABSTRACT FROM AUTHOR]

Additive manufacturing technology has emerged over the past decade as one of the best solutions for building prototypes and components with complex geometries and reduced thicknesses. Its application has rapidly spread to various industries, such as motorsport, automotive, aerospace, and biomedical. In particular, titanium alloy Ti-6Al-4V, due to its exceptional mechanical properties, low density, and excellent corrosion resistance, turns out to be one of the most popular for the production of parts with additive manufacturing technology across all the market segments listed above. However, when producing components using Laser Powder Bed Fusion (LPBF) technology, it is always necessary to perform appropriate heat treatments whose main purpose is to reduce the residual stresses typically generated during the manufacturing process. Post-process heat treatments on Ti6Al4V components obtained by way of additive technology have been extensively studied in the literature, with the aim of identifying optimal thermal cycles, which may allow for the effective reduction of residual stresses combined with proper microstructural conditions. However, despite the usual target of maximizing relevant mechanical properties, it is mandatory for industrial production to achieve a robust process, i.e., minimizing the sensitivity to noise-induced variation. Therefore, the aim of the present work is to compare several post-process heat treatment strategies by performing different thermal cycles in the temperature range of 750–955 °C and investigating how these affect the average mechanical properties and their variance. The treated samples are then analyzed running a complete mechanical and microstructural characterization, and the latter particularly focused on the determination of the typical microstructure present in the treated samples by using the XRD technique. [ABSTRACT FROM AUTHOR]

Anterior segment optical coherence tomography (AS-OCT) allows the explore not only the anterior chamber but also the front part of the vitreous cavity. Our cross-sectional single-centre study investigated whether AS-OCT can distinguish between vitreous involvement due to vitreoretinal lymphoma (VRL) and vitritis in uveitis. We studied AS-OCT images from 28 patients (11 with biopsy-proven VRL and 17 with differential diagnosis uveitis) using publicly available radiomics software written in MATLAB. Patients were divided into two balanced groups: training and testing. Overall, 3260/3705 (88%) AS-OCT images met our defined quality criteria, making them eligible for analysis. We studied five different sets of grey-level samplings (16, 32, 64, 128, and 256 levels), finding that 128 grey levels performed the best. We selected the five most effective radiomic features ranked by the ability to predict the class (VRL or uveitis). We built a classification model using the xgboost python function; through our model, 87% of eyes were correctly diagnosed as VRL or uveitis, regardless of exam technique or lens status. Areas under the receiver operating characteristic curves (AUC) in the 128 grey-level model were 0.95 [CI 0.94, 0.96] and 0.84 for training and testing datasets, respectively. This preliminary retrospective study highlights how AS-OCT can support ophthalmologists when there is clinical suspicion of VRL. [ABSTRACT FROM AUTHOR]

The choroid is the main part of the uvea, the vascular layer of the eye that lies between the retina and the sclera. The high vascular component of the choroid makes this structure susceptible to inflammation in multisystemic diseases, as well as the most common site of metastasis in the eye. Therefore, the choroid is involved in many pathological conditions, from uveitis to intraocular tumors. Differentiating between inflammatory and neoplastic lesions deforming the choroidal profile can sometimes be challenging. In addition, scleral disorders can also deform the choroidal profile. Choroidal imaging includes ophthalmic ultrasonography, indocyanine green angiography, and optical coherence tomography (OCT). Recent advances in choroidal imaging techniques, such as enhanced depth imaging optical coherence tomography (EDI-OCT) and swept-source optical coherence tomography (SS-OCT), have facilitated an in-depth analysis of the choroid. The purpose of this review article is to report on and highlight the most common OCT findings to help in the differential diagnosis between inflammatory and neoplastic lesions deforming the choroidal profile. [ABSTRACT FROM AUTHOR]

Lymphoproliferative lung diseases are a heterogeneous group of disorders characterized by primary or secondary involvement of the lung. Primary pulmonary lymphomas are the most common type, representing 0.5–1% of all primary malignancies of the lung. The radiological presentation is often heterogeneous and non-specific: consolidations, masses, and nodules are the most common findings, followed by ground-glass opacities and interstitial involvement, more common in secondary lung lymphomas. These findings usually show a prevalent perilymphatic spread along bronchovascular bundles, without a prevalence in the upper or lower lung lobes. An ancillary sign, such as a "halo sign", "reverse halo sign", air bronchogram, or CT angiogram sign, may be present and can help rule out a differential diagnosis. Since a wide spectrum of pulmonary parenchymal diseases may mimic lymphoma, a correct clinical evaluation and a multidisciplinary approach are mandatory. In this sense, despite High-Resolution Computer Tomography (HRCT) representing the gold standard, a tissue sample is needed for a certain and definitive diagnosis. Cryobiopsy is a relatively new technique that permits the obtaining of a larger amount of tissue without significant artifacts, and is less invasive and more precise than surgical biopsy. [ABSTRACT FROM AUTHOR]

Aléria was the main city of the island of Corsica in ancient times. Archaeological excavations in the area where ancient Aléria once stood began between the 1950s and 1960s and brought to light numerous inscriptions mainly carved on slabs of white marble; they constitute an important source of knowledge of the city's institutions, urban topography, society, and economy. The provenance of the marbles, on which the inscriptions were carved, can add important information about the history of the city. A first visual examination of the slabs or slab fragments allows us to state that Carrara is probably the provenance of most of the marbles used. Practical reasons lead us to believe that the provenance of these marbles can be traced back to two main quarry areas: Carrara, or somewhere in Corsica. The determination of the stable isotope composition of these marbles could solve this problem. Carrara marble, in fact, has a narrow range of isotopic variability, with values typical of marine carbonates, that allows for a strong characterization. The petrographic method of investigation was used, as a second step, on a reduced number of marble inscriptions to evaluate the effectiveness of the isotopic characterization of Carrara. The results of the analysis confirmed that most of the gray and white marbles studied have Carrara as their quarrying area; they also revealed that in Corsica the presence of ancient local marble quarries is uncertain, even in Roman times. [ABSTRACT FROM AUTHOR]

Twelve Triticum aestivum L. spp. aestivum varieties with pigmented grain, namely one red, six purple, three blue, and two black, were grown in open fields over two consecutive years and screened to investigate their risk to the accumulation of multiple Fusarium-related mycotoxins. Deoxynivalenol (DON) and its modified forms DON3Glc, 3Ac-DON, 15Ac-DON, and T-2, HT-2, ZEN, and Enniatin B were quantified by means of UHPLC-MS/MS, along with 14 different cyanidin, petunidin, delphinidin, pelargonidin, peonidin, and malvidin glycosides. A significant strong influence effect of the harvesting year (p = 0.0002) was noticed for DON content, which was more than doubled between harvesting years growing seasons (mean of 3746 µg kg−1 vs. 1463 µg kg−1). In addition, a striking influence of varieties with different grain colour on DON content (p < 0.0001) emerged in combination with the harvesting year (year×colour, p = 0.0091), with blue grains being more contaminated (mean of 5352 µg kg−1) and red grain being less contaminated (mean of 715 µg kg−1). The trend was maintained between the two harvesting years despite the highly variable absolute mycotoxin content. Varieties accumulating anthocyanins in the pericarp (purple coloration) had significantly lower DON content compared to those in which aleurone was involved (blue coloration). [ABSTRACT FROM AUTHOR]

Background: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio and CRP levels. Methods: This was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan–Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model. Results: In total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO2/FiO2 ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38–0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification. Conclusions: Our data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use. [ABSTRACT FROM AUTHOR]

Simple Summary: An "intelligent agent" based on deep learning solutions is proposed to detect and non-invasively characterize lung lesions on computed tomography (CT) scans. Our retrospective study aimed to assess the effectiveness of Retina U-Net and the convolutional neural network for computer-aided detection (CADe) and computer-aided diagnosis (CADx) purposes. CADe and CADx were trained, validated, and tested on the publicly available LUNA challenge dataset and two local low-dose CT datasets from the IRCCS Humanitas Research Hospital. (1) Background: Once lung lesions are identified on CT scans, they must be characterized by assessing the risk of malignancy. Despite the promising performance of computer-aided systems, some limitations related to the study design and technical issues undermine these tools' efficiency; an "intelligent agent" to detect and non-invasively characterize lung lesions on CT scans is proposed. (2) Methods: Two main modules tackled the detection of lung nodules on CT scans and the diagnosis of each nodule into benign and malignant categories. Computer-aided detection (CADe) and computer aided-diagnosis (CADx) modules relied on deep learning techniques such as Retina U-Net and the convolutional neural network; (3) Results: Tests were conducted on one publicly available dataset and two local datasets featuring CT scans acquired with different devices to reveal deep learning performances in "real-world" clinical scenarios. The CADe module reached an accuracy rate of 78%, while the CADx's accuracy, specificity, and sensitivity stand at 80%, 73%, and 85.7%, respectively; (4) Conclusions: Two different deep learning techniques have been adapted for CADe and CADx purposes in both publicly available and private CT scan datasets. Experiments have shown adequate performance in both detection and diagnosis tasks. Nevertheless, some drawbacks still characterize the supervised learning paradigm employed in networks such as CNN and Retina U-Net in real-world clinical scenarios, with CT scans from different devices with different sensors' fingerprints and spatial resolution. Continuous reassessment of CADe and CADx's performance is needed during their implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Telemedicine requires either the use of digital tools or a minimum technological knowledge of the patients. Digital health literacy may influence the use of telemedicine in most patients, particularly those with frailty. We aimed to explore the association between frailty, the use of digital tools, and patients' digital health literacy. Methods: We prospectively enrolled patients referred to arrhythmia outpatient clinics of our cardiology department from March to September 2022. Patients were divided according to frailty status as defined by the Edmonton Frail Scale (EFS) into robust, pre-frail, and frail. The degree of digital health literacy was assessed through the Digital Health Literacy Instrument (DHLI), which explores seven digital skill categories measured by 21 self-report questions. Results: A total of 300 patients were enrolled (36.3% females, median age 75 (66–84)) and stratified according to frailty status as robust (EFS ≤ 5; 70.7%), pre-frail (EFS 6–7; 15.7%), and frail (EFS ≥ 8; 13.7%). Frail and pre-frail patients used digital tools less frequently and accessed the Internet less frequently compared to robust patients. In the logistic regression analysis, frail patients were significantly associated with the non-use of the Internet (adjusted odds ratio 2.58, 95% CI 1.92–5.61) compared to robust and pre-frail patients. Digital health literacy decreased as the level of frailty increased in all the digital domains examined. Conclusions: Frail patients are characterized by lower use of digital tools compared to robust patients, even though these patients would benefit the most from telemedicine. Digital skills were strongly influenced by frailty. [ABSTRACT FROM AUTHOR]

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-α. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection. [ABSTRACT FROM AUTHOR]

Primary vitreoretinal lymphoma (PVRL), a rare aggressive malignancy primarily involving the retina and/or the vitreous, is a major diagnostic challenge for clinicians (who commonly misdiagnose it as chronic uveitis) as well as for pathologists (for biological and technical reasons). Delays in diagnosis and treatment are responsible for visual impairments and life-threatening consequences, usually related to central nervous system involvement. The identification of lymphoma cells in vitreous fluid, obtained by vitrectomy, is required for diagnosis. Of note, the scarcity of neoplastic cells in small volumes of vitreous sample, and the fragility of lymphoma cells with degenerative changes caused by previous steroid use for presumed uveitis makes diagnosis based on cytology plus immunophenotyping difficult. Interleukin levels, immunoglobulin heavy chain or T-cell receptor gene rearrangements, and MYD88 mutation are applied in combination with cytology to support diagnosis. We aim to describe the current laboratory technologies for PVRL diagnosis, focusing on the main issues that these methods have. In addition, new emerging diagnostic strategies, such as next-generation sequencing analysis, are discussed. The genetic profile of PVRL remains largely unexplored. Better knowledge of genetic alterations is critical for precision medicine interventions with target-based treatments of this lymphoma for which no standardised treatment protocol currently exists. [ABSTRACT FROM AUTHOR]

To identify the best transfer learning approach for the identification of the most frequent abnormalities on chest radiographs (CXRs), we used embeddings extracted from pretrained convolutional neural networks (CNNs). An explainable AI (XAI) model was applied to interpret black-box model predictions and assess its performance. Seven CNNs were trained on CheXpert. Three transfer learning approaches were thereafter applied to a local dataset. The classification results were ensembled using simple and entropy-weighted averaging. We applied Grad-CAM (an XAI model) to produce a saliency map. Grad-CAM maps were compared to manually extracted regions of interest, and the training time was recorded. The best transfer learning model was that which used image embeddings and random forest with simple averaging, with an average AUC of 0.856. Grad-CAM maps showed that the models focused on specific features of each CXR. CNNs pretrained on a large public dataset of medical images can be exploited as feature extractors for tasks of interest. The extracted image embeddings contain relevant information that can be used to train an additional classifier with satisfactory performance on an independent dataset, demonstrating it to be the optimal transfer learning strategy and overcoming the need for large private datasets, extensive computational resources, and long training times. [ABSTRACT FROM AUTHOR]

The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: A cross-sectional single-center study was conducted to investigate the etiology in hypertensive anterior uveitis whose clinical features are not fully distinctive from cytomegalovirus or from rubella virus and to demonstrate the possible coexistence of both these viruses in causing anterior uveitis. Materials and Methods: The clinical charts of a cohort of patients with hypertensive viral anterior uveitis of uncertain origin consecutively seen in a single center from 2019 to 2022 were retrospectively reviewed; data on the clinical features, aqueous polymerase chain reaction, and antibody response to cytomegalovirus and rubella virus were collected. Results: Forty-three eyes of as many subjects with viral anterior uveitis of uncertain origin were included. Thirty-two patients had an aqueous polymerase chain reaction or antibody index positive to cytomegalovirus only, while 11 cases had an aqueous antibody response to both cytomegalovirus and rubella virus. This latter overlapping group had a statistically significant higher rate of hypochromia and anterior vitritis (p-value: 0.02 and < 0.001, respectively). Conclusions: The simultaneous presence of intraocular antibodies against cytomegalovirus and rubella virus could redefine the differential diagnosis of hypertensive viral anterior uveitis, demonstrating a possible "converged" immune pathway consisting in a variety of stimuli. [ABSTRACT FROM AUTHOR]

Specific T cells are crucial to control SARS-CoV-2 infection, avoid reinfection and confer protection after vaccination. We have studied patients with severe or moderate COVID-19 pneumonia, compared to patients who recovered from a severe or moderate infection that had occurred about 4 months before the analyses. In all these subjects, we assessed the polyfunctionality of virus-specific CD4+ and CD8+ T cells by quantifying cytokine production after in vitro stimulation with different SARS-CoV-2 peptide pools covering different proteins (M, N and S). In particular, we quantified the percentage of CD4+ and CD8+ T cells simultaneously producing interferon-γ, tumor necrosis factor, interleukin (IL)-2, IL-17, granzyme B, and expressing CD107a. Recovered patients who experienced a severe disease display high proportions of antigen-specific CD4+ T cells producing Th1 and Th17 cytokines and are characterized by polyfunctional SARS-CoV-2-specific CD4+ T cells. A similar profile was found in patients experiencing a moderate form of COVID-19 pneumonia. No main differences in polyfunctionality were observed among the CD8+ T cell compartments, even if the proportion of responding cells was higher during the infection. The identification of those functional cell subsets that might influence protection can thus help in better understanding the complexity of immune response to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The Heidenhain Variant of Creutzfeldt–Jakob disease (CJD) is an uncommon early clinical syndrome of the otherwise regular sporadic CJD, which belongs to the group of prion diseases caused by a transmissible agent, the misfolded form of the prion protein. The most characteristic symptoms of CJD are rapidly progressive cognitive impairment, typical motor manifestations and mental and behavioural changes. Conversely, in the Heidenhain Variant, different kinds of visual disturbances are observed at onset due to microvacuolar spongiform degeneration or, less frequently, confluent spongiform changes in the parieto-occipital area, detectable through brain MRI with hyperintensity in T2-FLAIR or DWI in the same areas. Since this an extremely rare condition with a heterogeneous clinical presentation, it may easily be misdiagnosed with other diseases at the earlier stages. Here, we describe the case of a patient initially diagnosed with posterior reversible encephalopathy syndrome (PRES), presenting with visual disturbances and headache at onset in a context of poorly controlled arterial hypertension. Subsequently, a rapid worsening of cognitive decline, associated with myoclonus and startle reaction led to further investigations, shifting the diagnosis toward a rapidly evolving neurodegenerative form. This hypothesis was also supported by EEG traces, MRI and CSF analysis. Finally, the clinical–instrumental evolution confirmed the diagnosis of Heidenhain Variant of CJD. [ABSTRACT FROM AUTHOR]

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS. [ABSTRACT FROM AUTHOR]

The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit the advantages of drug repurposing in the search of new drugs, we developed a similar approach for the identification of new hits interfering with TEAD target gene expression. In our study, a 27-member in-house library was assembled, characterized, and screened for its cancer cell growth inhibition effect. In a secondary luciferase-based assay, only seven compounds confirmed their specific involvement in TEAD activity. IA5 bearing a p-quinoid structure reduced the cytoplasmic level of phosphorylated YAP and the YAP–TEAD complex transcriptional activity and reduced cancer cell growth. IA5 is a promising hit compound for TEAD activity modulator development. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet's disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Simple Summary: The Epstein–Barr virus (EBV) is a commonly occurring virus, infecting more than 90% of the world population, often early in life. However, only a minority of individuals develop EBV-driven diseases at some point in their lifetime. EBV is associated with several neoplasms including epithelial, mesenchymal and lymphoid tumors. EBV-driven lymphoid proliferations encompass a wide spectrum of diseases with different biological behaviors, developing frequently, although not always, in conditions of immunosuppression. The diagnosis is often complicated and requires a strict combination of clinical, pathological and molecular findings. The aim of this review, divided into three parts, is to provide an update on EBV-driven lymphoproliferative disorders arising in the gastrointestinal tract. In this review, we discuss the chronic active EBV infection of T-cell and NK-cell type, its systemic form; extranodal NK/T-cell lymphoma, nasal type and post-transplant lymphoproliferative disorders. EBV is the first known oncogenic virus involved in the development of several tumors. The majority of the global population are infected with the virus early in life and the virus persists throughout life, in a latent stage, and usually within B lymphocytes. Despite the worldwide diffusion of EBV infection, EBV-associated diseases develop in only in a small subset of individuals often when conditions of immunosuppression disrupt the balance between the infection and host immune system. EBV-driven lymphoid proliferations are either of B-cell or T/NK-cell origin, and range from disorders with an indolent behavior to aggressive lymphomas. In this review, which is divided in three parts, we provide an update of EBV-associated lymphoid disorders developing in the gastrointestinal tract, often representing a challenging diagnostic and therapeutic issue. Our aim is to provide a practical diagnostic approach to clinicians and pathologists who face this complex spectrum of disorders in their daily practice. In this part of the review, the chronic active EBV infection of T-cell and NK-cell type, its systemic form; extranodal NK/T-cell lymphoma, nasal type and post-transplant lymphoproliferative disorders are discussed. [ABSTRACT FROM AUTHOR]

The Forma Urbis Romae (F.U.) was a 3rd-century-AD monumental map of ancient Rome consisting of 151 rectangular marble slabs. Several efforts have been made to reconstruct it from its current incomplete and fragmentary condition. In this paper, we explore the potential of an archaeometric approach to serve this purpose. Almost a hundred F.U. fragments have been characterized, particularly focusing on cathodoluminescence (CL) microscopy and stable isotopes (δ18O and δ13C). Different statistical methods have been used to quantify the similarity between samples. The central assumption is that samples from a given slab share similar CL colors and isotopic ratios. The assumption has been verified for samples from single fragments and then it has been used to check ten debated reconstruction hypotheses. The measured isotopic ratios confirm the Proconnesian nature of the F.U. marble, except for a fragment. Beyond provenance, the results cast doubts on four out of the ten checked reconstruction hypotheses and support the other six. The reconstruction of the F.U. remains a fascinating challenge, and both isotopic and CL analyses have demonstrated their potential to tackle it. Further research could extend the presented methodology to a higher number of samples. The innovative use of CL to reconstruct a fragmented artwork could be applied to other projects. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2–4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine–kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients´ outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization. [ABSTRACT FROM AUTHOR]

Simple Summary: Epstein–Barr virus (EBV)-associated lymphoproliferative disorders have been garnering attention in recent years. EBV infects people primarily in their first years of life. The viral genome is maintained in a latent phase within the host cells, usually B-lymphocytes. The immunosuppression of different origins alters homeostasis between the virus and the host, enabling EBV-linked lymphoproliferative disorders to appear. Entities with different biological behaviors often share some morphological and phenotypic features, making the diagnosis complicated. Nodal and extra-nodal sites, including the gastrointestinal tract may be involved. This review, divided into three parts, aims to summarize the available clinical, pathological, molecular and therapeutic data on EBV-associated lymphoproliferative disorders involving the gastrointestinal tract. In this part of the review, we discuss plasmablastic lymphoma, extra-cavitary primary effusion lymphoma and Burkitt lymphoma. Epstein–Barr virus (EBV) is a common pathogen infecting people primarily early in life. The virus has the ability to persist throughout a person's life, usually in B lymphocytes. Conditions of immunodeficiency as well as the introduction of immunosuppressive therapies and the advent of transplant technologies has brought immunodeficiency-associated lymphoproliferative disorders into view, which are often driven by EBV. The group of EBV-associated lymphoproliferative disorders includes different entities, with distinct biological features, ranging from indolent disorders, which may even spontaneously regress, to aggressive lymphomas requiring prompt and adequate treatment. These disorders are often diagnostically challenging due to their overlapping morphology and immunophenotype. Both nodal and extra-nodal sites, including the gastrointestinal tract, may be involved. This review, divided in three parts, summarizes the clinical, pathological, molecular features and treatment strategies of EBV-related lymphoproliferative disorders occurring in the gastrointestinal tract and critically analyzes the major issues in the differential diagnosis. In this part of the review, we discuss plasmablastic lymphoma, extra-cavitary primary effusion lymphoma and Burkitt lymphoma. [ABSTRACT FROM AUTHOR]

Interstitial lung diseases (ILDs) that are known as diffuse parenchymal lung diseases (DPLDs) lead to the damage of alveolar epithelium and lung parenchyma, culminating in inflammation and widespread fibrosis. ILDs that account for more than 200 different pathologies can be divided into two groups: ILDs that have a known cause and those where the cause is unknown, classified as idiopathic interstitial pneumonia (IIP). IIPs include idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) known also as bronchiolitis obliterans organizing pneumonia (BOOP), acute interstitial pneumonia (AIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphocytic interstitial pneumonia (LIP). In this review, our aim is to describe the pathogenic mechanisms that lead to the onset and progression of the different IIPs, starting from IPF as the most studied, in order to find both the common and standalone molecular and cellular key players among them. Finally, a deeper molecular and cellular characterization of different interstitial lung diseases without a known cause would contribute to giving a more accurate diagnosis to the patients, which would translate to a more effective treatment decision. [ABSTRACT FROM AUTHOR]

Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the development of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective autophagy. In this work, we investigated the role and mechanism of action of the combination of a ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2), in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone, i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ], in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability in glioma U251 cells (IC50 11.4 μM) via inhibition of the autophagic machinery, most likely acting at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able to impair cellular viability under conditions of glucose deprivation. We thus suggest different mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs, making complex 2 a very attractive candidate for evading the known resistances of brain tumors to chloroquine-based therapies. [ABSTRACT FROM AUTHOR]

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress–strain curve but follows the mechano-elastic models of "squishy balls", where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support. [ABSTRACT FROM AUTHOR]

This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 ± 0.72 logMAR preoperatively to 0.98 ± 0.97 logMAR at 48 months (p = 0.45) in the Non-Biological Group and from 1.55 ± 0.91 logMAR preoperatively to 0.57 ± 0.83 logMAR at 48 months (p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Drug combinations may help overcome drug resistance, a relevant cause of failure of ovarian cancer therapy. However, designing successful combinations requires a lengthy preclinical validation process. We have analyzed combinations of 5-fluorouracil and raltitrexed, two anticancer drugs that target thymidylate synthase, a key enzyme for the nucleotide synthesis. We have observed administration sequence specific and synergistic combined effects of the two drugs against cisplatin sensitive and resistant ovarian cancer cells. However, the focus of this work was to show that a high stability of the complex of the enzyme with the two drugs, as highlighted by X-ray crystallography, and synergistic inhibition of the enzyme represent indicators, if not prerequisites, for this drug combination to be synergistically active against sensitive and resistant ovarian cancer cells. We thus propose that structural and mechanistic information acquired during the preclinical research can help predict a successful therapeutic application of a drug combination. Combining drugs represent an approach to efficiently prevent and overcome drug resistance and to reduce toxicity; yet it is a highly challenging task, particularly if combinations of inhibitors of the same enzyme target are considered. To show that crystallographic and inhibition kinetic information can provide indicators of cancer cell growth inhibition by combinations of two anti-human thymidylate synthase (hTS) drugs, we obtained the X-ray crystal structure of the hTS:raltitrexed:5-fluorodeoxyuridine monophosphate (FdUMP) complex. Its analysis showed a ternary complex with both molecules strongly bound inside the enzyme catalytic cavity. The synergistic inhibition of hTS and its mechanistic rationale were consistent with the structural analysis. When administered in combination to A2780 and A2780/CP ovarian cancer cells, the two drugs inhibited ovarian cancer cell growth additively/synergistically. Together, these results support the idea that X-ray crystallography can provide structural indicators for designing combinations of hTS (or any other target)-directed drugs to accelerate preclinical research for therapeutic application. [ABSTRACT FROM AUTHOR]

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7–15 years as well as the impact of EAAT on the magnitude of stress in the parent–child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p ≤ 0.01) as well as a progressive improvement in the child's abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples. [ABSTRACT FROM AUTHOR]

The mechanisms of acute respiratory failure other than inflammation and complicating the SARS-CoV-2 infection are still far from being fully understood, thus challenging the management of COVID-19 patients in the critical care setting. In this unforeseen scenario, the role of an individual's excessive spontaneous breathing may acquire critical importance, being one potential and important driver of lung injury and disease progression. The consequences of this acute lung damage may impair lung structure, forecasting the model of a fragile respiratory system. This perspective article aims to analyze the progression of injured lung phenotypes across the SARS-CoV-2 induced respiratory failure, pointing out the role of spontaneous breathing and also tackling the specific respiratory/ventilatory strategy required by the fragile lung type. [ABSTRACT FROM AUTHOR]

(1) Background: Due to its richness in chlorogenic acids (CGAs), Maté (Ilex paraguariensis A. St.-Hil.) could be of interest in the prevention of cardiometabolic diseases, however clinical evidence are lacking. This trial aimed to evaluate the impact of maté CGAs, consumed in a daily dose achievable through traditional maté beverages, on parameters related to cardiometabolic risk. (2) Design: Thirty-four male volunteers aged 45–65 years and with at most one criteria of metabolic syndrome, were recruited for a randomized, double-blind, placebo-controlled, and crossover study. The volunteers were assigned to consume an encapsulated dry maté extract for four-weeks, providing 580 mg of caffeoyl quinic acid derivatives (CQAs) daily, or a placebo, with a two weeks washout between intervention periods. Anthropometric variables, blood pressure, plasma glucose, lipids, endothelial, and inflammatory biomarkers were measured in overnight-fasted subjects and after a glucose load. (3) Results: We found no significant effects of treatment on these parameters and the response to the glucose load was also similar between the two interventions. However, a significant decrease in fasting glucose was observed between day 0 and day 28 for the maté group only (−0.57 ± 0.11 mmol/L, p < 0.0002). In subjects with an intermediate to high Framingham risk score, consumption of maté extract induced a 10% increase of high-density lipoprotein (HDL)-c from baseline. In a subgroup representative of the study population, significant decreases in the C-reactive protein (CRP) (−50%) and interleukin-6 (IL-6) (−19%) levels were observed. (4) Conclusions: These clinical observations suggest that maté, naturally rich in CGAs, could improve some cardiometabolic markers in subjects with a higher predisposition to metabolic syndrome, even if that remains to be confirmed in new trials specifically targeting this population. [ABSTRACT FROM AUTHOR]

Nature is often characterized by systems that are far from thermodynamic equilibrium, and rivers are not an exception for the Earth's critical zone. When the chemical composition of stream waters is investigated, it emerges that riverine systems behave as complex systems. This means that the compositions have properties that depend on the integrity of the whole (i.e., the composition with all the chemical constituents), properties that arise thanks to the innumerable nonlinear interactions between the elements of the composition. The presence of interconnections indicates that the properties of the whole cannot be fully understood by examining the parts of the system in isolation. In this work, we propose investigating the complexity of riverine chemistry by using the CoDA (Compositional Data Analysis) methodology and the performance of the perturbation operator in the simplex geometry. With riverine bicarbonate considered as a key component of regional and global biogeochemical cycles and Ca2+ considered as mostly related to the weathering of carbonatic rocks, perturbations were calculated for subsequent couples of compositions after ranking the data for increasing values of the log-ratio ln(Ca2+/HCO3−). Numerical values were analyzed by using robust principal component analysis and non-parametric correlations between compositional parts (heat map) associated with distributional and multifractal methods. The results indicate that HCO3−, Ca2+, Mg2+ and Sr2+ are more resilient, thus contributing to compositional changes for all the values of ln(Ca2+/HCO3−) to a lesser degree with respect to the other chemical elements/components. Moreover, the complementary cumulative distribution function of all the sequences tracing the compositional change and the nonlinear relationship between the Q-th moment versus the scaling exponents for each of them indicate the presence of multifractal variability, thus revealing scaling properties of the fluctuations. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal gynecological malignancy, often because of the frequent insurgence of chemoresistance to the drugs currently used. Thus, new therapeutical agents are needed. We tested the toxicity of 16 new DNA-intercalating agents to cisplatin (cDDP)-sensitive human ovarian carcinoma cell lines and their resistant counterparts. The compounds were the complexes of Pt(II) or Pd(II) with bipyridyl (bipy) and phenanthrolyl (phen) and with four different thiourea ancillary ligands. Within each of the four series of complexes characterized by the same thiourea ligand, the Pd(phen) drugs invariably showed the highest anti-proliferative efficacy. This paralleled both a higher intracellular drug accumulation and a more efficient DNA intercalation than all the other metal-bidentate ligand combinations. The consequent inhibition of topoisomerase II activity led to the greatest inhibition of DNA metabolism, evidenced by the inhibition of the expression of the folate cycle enzymes and a marked perturbation of cell-cycle distribution in both cell lines. These findings indicate that the particular interaction of Pd(II) with phenanthroline confers the best pharmacokinetic and pharmacodynamic properties that make this class of DNA intercalators remarkable inhibitors, even of the resistant cell growth. [ABSTRACT FROM AUTHOR]

3,1,2-Ruthenadicarbadodecaborane complexes bearing the [C2B9H11]2− (dicarbollide) ligand are robust scaffolds, with exceptional thermal and chemical stability. Our previous work has shown that these complexes possess promising anti-tumor activities in vitro, and tend to form aggregates (or self-assemblies) in aqueous solutions. Here, we report on the synthesis and characterization of four ruthenium(II) complexes of the type [3-(η6-arene)-1,2-R2-3,1,2-RuC2B9H9], bearing either non-polar (R = Me (2–4)) or polar (R = CO2Me (7)) substituents at the cluster carbon atoms. The behavior in aqueous solution of complexes 2, 7 and the parent unsubstituted [3-(η6-p-cymene)-3,1,2-RuC2B9H11] (8) was investigated via UV-Vis spectroscopy, mass spectrometry and nanoparticle tracking analysis (NTA). All complexes showed spontaneous formation of self-assemblies (108–109 particles mL−1), at low micromolar concentration, with high polydispersity. For perspective applications in medicine, there is thus a strong need for further characterization of the spontaneous self-assembly behavior in aqueous solutions for the class of neutral metallacarboranes, with the ultimate scope of finding the optimal conditions for exploiting this self-assembling behavior for improved biological performance. [ABSTRACT FROM AUTHOR]

Brazil is one of the world's largest corn producers and is a leader in exportation. Due to intense globalization, corn may be commercialized worldwide and the issue concerning the safety of corn-based products has become a topic of widespread international interest. Dietary exposure evaluation is a relevant criterion for mycotoxin risk assessment. Thus, human exposure to fumonisins were assessed for corn grain and its derivatives (endosperm, cornmeal, and grits; n = 320) sampled from one of the large-scale corn processing plants in Brazil. The total probable daily intake (PDI) for fumonisins in Brazil was 96.9 ng kg−1 body weight day−1, which corresponds to 5% of the provisional maximum tolerable daily intake (PMTDI) of 2000 ng kg−1 b.w. day−1 for fumonisins. In countries that import Brazilian corn, the total PDI is lower in European countries (from 35.7 to 177 ng kg−1 b.w. day−1) and higher in Angola (1553 ng kg−1 b.w. day−1). Taking into account that dietary exposure in populations in Brazil and importing countries was low, the corn-based products were safe for human consumption regarding fumonisins, even for regions with high corn consumption. [ABSTRACT FROM AUTHOR]