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Botulinum toxin is a protein deriving from the bacteria Clostridium botulinum and it is widely used for the treatment of a variety of muscle hyperactivity syndromes and for cosmetic indications. Having a long-lasting effect, Botulinum toxin type A (BTA) is one of the most botulin toxin products used. Even if BTA has shown benefits in reducing the vertical lines between the eyebrows, Adverse Drug Reactions (ADRs) have been experienced as well, of which the most common ones are headache and drooping eyelids. In addition, since other local and systemic risks have been identified, a non-interventional post-authorization safety study (PASS) has been started. The aim of the present study was to report cases of skin toxicity associated with this drug, considering Individual Case Safety Reports (ICSRs) existing on the Eudravigilance website. Among 1464 ICSRs sent to the EV database, 718 ICSRs, including 5154 PTs, reported BTA as a suspected drug associated with cutaneous toxicity. The majority of patients experiencing BTA-induced skin toxicity were female (92.1%) belonging mostly to the age group of 18–64 years. The most serious criteria, when reported, were "Other Medically Important Condition" and "Caused/prolonged hospitalization", although the outcome was mainly reported as "Unknown". The most reported PTs, related to skin disorders, were: "Erythema", "Rash", "Pruritus", "Urticaria", "Swelling face", "Brow ptosis", "Eyelid ptosis", "Injection site pain", and "Angioedema". Considering that in most ICSRs, ADRs related to skin disorders were symptoms of hypersensitivity reactions which in some conditions could be life-threatening, further studies are required to better define the safety profile of BTA used for aesthetic procedures. [ABSTRACT FROM AUTHOR]

Cationic antimicrobial peptides (CAMPs) are powerful molecules with antimicrobial, antibiofilm and endotoxin-scavenging activities. These properties make CAMPs very attractive drugs in the face of the rapid increase in multidrug-resistant (MDR) pathogens, but they are limited by their susceptibility to proteolytic degradation. An intriguing solution to this issue could be the development of functional mimics of CAMPs with structures that enable the evasion of proteases. Peptoids (N-substituted glycine oligomers) are an important class of peptidomimetics with interesting benefits: easy synthetic access, intrinsic proteolytic stability and promising bioactivities. Here, we report the characterization of P13#1, a 13-residue peptoid specifically designed to mimic cathelicidins, the best-known and most widespread family of CAMPs. P13#1 showed all the biological activities typically associated with cathelicidins: bactericidal activity over a wide spectrum of strains, including several ESKAPE pathogens; the ability to act in combination with different classes of conventional antibiotics; antibiofilm activity against preformed biofilms of Pseudomonas aeruginosa, comparable to that of human cathelicidin LL-37; limited toxicity; and an ability to inhibit LPS-induced proinflammatory effects which is comparable to that of "the last resource" antibiotic colistin. We further studied the interaction of P13#1 with SDS, LPSs and bacterial cells by using a fluorescent version of P13#1. Finally, in a subcutaneous infection mouse model, it showed antimicrobial and anti-inflammatory activities comparable to ampicillin and gentamicin without apparent toxicity. The collected data indicate that P13#1 is an excellent candidate for the formulation of new antimicrobial therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic prostate cancer (PCa) may occur as progression after local therapy with curative intent or may be metastatic as newly onset. Approximately 5% of PCa present with metastatic stage at the time of diagnosis. Therapeutic management differs widely according to the site of metastases, the sensitivity to hormonal treatments and the volume of disease. We reported survival outcomes of patients with high-volume metastatic castration-resistant PCa (mCRPC) treated with ARTA in a chemo-naïve setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. In our population of 88 high-volume-disease mCRPC patients, we showed that survival probabilities are comparable between first-line ARTA and upfront chemotherapy-treated cohorts. Therefore, regardless tumor burden, novel antiandrogens can be useful treatment options and could be considered as first-line in order to postpone the use of more toxic treatments such as chemotherapy, in the case of significant disease progression. Registrative trials recommended the use of upfront chemotherapy in high-volume metastatic prostate cancer. We reported survival outcomes of patients with high-volume mCRPC treated with ARTA in a chemo-naïve setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. We retrospectively collected data on mCRPC patients treated at six centers. The dataset was queried for high-volume disease (defined as more than 6 bone lesions or bulky nodes ≥ 5 cm). We compared the main clinical features of chemo-naïve versus chemo-treated patients. The Mann–Whitney U test and Chi-squared test were used to compare continuous and categorial variables, respectively. The Kaplan–Meier method was used to compare differences in terms of progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS) in an upfront ARTA or chemo-treated setting. Survival probabilities were computed at 12, 24, 48, and 60 months. Out of 216 patients, 88 cases with high-volume disease were selected. Sixty-nine patients (78.4%) received upfront ARTA, while 19 patients received chemotherapy as the first-line treatment option. Forty-eight patients received Abiraterone (AA), 21 patients received Enzalutamide (EZ) as the first-line treatment. The ARTA population was older (p = 0.007) and less likely to receive further lines of treatment (p = 0.001) than the chemo-treated cohort. The five-year PFS, CSS and OS were 60%, 73.3%, and 72.9%, respectively. Overall, 28 patients (31.8%) shifted after their first-line therapy to a second-line therapy: EZ was prescribed in 17 cases, AA in seven cases and radiometabolic therapy in four patients. Sixteen cases (18.2%) developed significant progression and were treated with chemotherapy. At Kaplan–Meyer analysis PFS, CSS and OS were comparable for upfront ARTA vs chemo-treated patients (log rank p = 0.10, p = 0.64 and p = 0.36, respectively). We reported comparable survival probabilities in a real-life series of high-volume mCRPC patients who either received upfront ARTA or chemotherapy. Patients primarily treated with chemotherapy were younger and more likely to receive further treatment lines than the upfront ARTA cohort. Our data support the use of novel antiandrogens as first line treatment regardless tumor burden, delaying the beginning of a more toxic chemotherapy in case of significant disease progression. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) are a group of lesions originating from cells of the diffuse neuroendocrine system. NENs may involve different sites, including the gastrointestinal tract (GEP-NENs). The incidence and prevalence of GEP-NENs has been constantly rising thanks to the increased diagnostic power of imaging and immuno–histochemistry. Despite the plethora of biochemical markers and imaging techniques, the prognosis and therapeutic choice in GEP-NENs still represents a challenge, mainly due to the great heterogeneity in terms of tumor lesions and clinical behavior. The concept that biomedical images contain information about tissue heterogeneity and pathological processes invisible to the human eye is now well established. From this substrate comes the idea of radiomics. Computational analysis has achieved promising results in several oncological settings, and the use of radiomics in different types of GEP-NENs is growing in the field of research, yet with conflicting results. The aim of this narrative review is to provide a comprehensive update on the role of radiomics on GEP-NEN management, focusing on the main clinical aspects analyzed by most existing reports: predicting tumor grade, distinguishing NET from other tumors, and prognosis assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania Region, Italy by analysing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The overall percentage of antibiotics prescribed in dogs was 65% and in cats 31.4%. In dogs, 90.5% of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine. The antimicrobials prescribed were mainly metronidazole–spiramycin (29.7%), amoxicillin–clavulanic (19.6%), enrofloxacin and cephalexin in dogs (16.5%) and enrofloxacin (22.6%) and amoxicillin–clavulanic acid (21.4%) in cats. Based on the results, the widespread use of broad-spectrum antimicrobials and the use of molecules for which limitations should be observed according to the EMA guidelines has emerged. Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania Region, Italy by analysing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescriptions were collected according to the drug administration (systemic or topical) and the rationale for the treatment chosen. In the period under investigation, 166,879 drugs were prescribed of which 129,116 (73.4%) were antimicrobial. A total of 83,965 (65%) antibiotics were prescribed to dogs, 40,477 (31.4%) to cats, and 4674 (3.6%) to other companion animals. In dogs, 90.5% of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely prescribed class was fluoroquinolones. The antimicrobials prescribed were mainly metronidazole–spiramycin (29.7%), amoxicillin–clavulanic (19.6%), enrofloxacin and cephalexin in dogs (16.5%) and enrofloxacin (22.6%) and amoxicillin–clavulanic acid (21.4%) in cats. Based on the results, the widespread use of broad-spectrum antimicrobials and the use of molecules for which limitations should be observed according to the EMA guidelines has emerged. [ABSTRACT FROM AUTHOR]

Mycotoxins are a major source of contamination in cereals, posing risks to human health and causing significant economic losses to the industry. A comprehensive strategy for the analysis of 21 mycotoxins in Italian cereal grain samples (n = 200) was developed using a simple and quick sample preparation method combined with ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap HRMS). The proposed method showed some advantages, such as multi-mycotoxin analyses with simple sample preparation, fast determination, and high sensitivity. The analysis of the sample revealed the presence of 11 mycotoxins, with α-zearalenol being the most frequently detected, while deoxynivalenol exhibited the highest contamination level. Furthermore, co-occurrence was identified in 15.5% of the samples under analysis. Among these, 13% of the samples reported the simultaneous presence of two mycotoxins, while 2.5% showed the co-occurrence of three mycotoxins. Currently, there has been a renewed interest in guaranteeing the quality and safety of products intended for human consumption. This study holds significant value due to its ability to simultaneously detect multiple mycotoxins within a complex matrix. Furthermore, it provides findings regarding the occurrence and co-occurrence of emerging mycotoxins that currently lack regulation under the existing European Commission Regulation. [ABSTRACT FROM AUTHOR]

Immunotherapy denotes an exemplar change in an oncological setting. Despite the effective application of these treatments across a broad range of tumors, only a minority of patients have beneficial effects. The efficacy of immunotherapy is affected by several factors, including human immunity, which is strongly correlated to genetic features, such as intra-tumor heterogeneity. Classic imaging assessment, based on computed tomography (CT) or magnetic resonance imaging (MRI), which is useful for conventional treatments, has a limited role in immunotherapy. The reason is due to different patterns of response and/or progression during this kind of treatment which differs from those seen during other treatments, such as the possibility to assess the wide spectrum of immunotherapy-correlated toxic effects (ir-AEs) as soon as possible. In addition, considering the unusual response patterns, the limits of conventional response criteria and the necessity of using related immune-response criteria are clear. Radiomics analysis is a recent field of great interest in a radiological setting and recently it has grown the idea that we could identify patients who will be fit for this treatment or who will develop ir-AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: Lynch syndrome is the most common form of hereditary colorectal cancer associate to variants in Mismatch Repair (MMR) genes. Unfortunately, a large amount of variants identified in these genes remain of uncertain significance. Therefore, many individuals with a clinical suspicion of LS receive a diagnosis of Lynch-like syndrome. This review summarizes the main aspects of Lynch syndrome and recent advances in the molecular diagnosis and, in particular the main factors that determine the loss of expression of MMR genes. Hereditary non-polyposis colorectal cancer is also known as Lynch syndrome. Lynch syndrome is associated with pathogenetic variants in one of the mismatch repair (MMR) genes. In addition to colorectal cancer, the inefficiency of the MMR system leads to a greater predisposition to cancer of the endometrium and other cancers of the abdominal sphere. Molecular diagnosis is performed to identify pathogenetic variants in MMR genes. However, for many patients with clinically suspected Lynch syndrome, it is not possible to identify a pathogenic variant in MMR genes. Molecular diagnosis is essential for referring patients to specific surveillance to prevent the development of tumors related to Lynch syndrome. This review summarizes the main aspects of Lynch syndrome and recent advances in the field and, in particular, emphasizes the factors that can lead to the loss of expression of MMR genes. [ABSTRACT FROM AUTHOR]

The water-based extract of broad bean hulls contains several bioactive molecules, including polyphenols well-known to exert antioxidant activity, which could justify its use in nutraceutical formulations. Hence, the current investigation aimed to establish the polyphenolic profile of water-based extracts from broad bean hulls through UHPLC–Q-Orbitrap HRMS analysis. The findings highlighted that p-coumaric acid, chlorogenic acid, and epicatechin were the most common compounds found in the tested extracts, being quantified at a mean concentration of 42.1, 32.6, and 31.2 mg/100 g, respectively. Moreover, broad bean hull extracts were encapsulated into a nutraceutical formulation, after which the antioxidant properties and the bioaccessibility of phenolic compounds during the simulated gastrointestinal (GI) process were investigated and compared with the digested non-encapsulated extract. The data highlighted that following the GI process, the capsules were able to preserve active compounds from the adverse effects of digestion, resulting in a greater antioxidant capacity and polyphenol bioaccessibility in the duodenal and colonic phases, compared with the non-encapsulated extract. Our results showed that the water extract from broad bean hulls may be considered a valuable source of natural polyphenolic compounds; in addition, the use of a gastric-resistant capsule could be a suitable alternative to transport these bioactive compounds to the target tissues. [ABSTRACT FROM AUTHOR]

Coffee consumption positively influences colon health. Conversely, high levels of tryptophan metabolites such as skatole released from intestinal putrefactive fermentation in the presence of excessive dietary animal protein intake, and gut microbiota alterations, may have several adverse effects, including the development of colorectal cancer. Therefore, this study aimed to elucidate the potential protective effects of coffee in the presence of different skatole levels. The results showed that skatole exposure induced reduced cell viability and oxidative stress in the HT-29 human colon cancer cell line. However, co-treatment of cells with skatole and coffee samples was able to reduce ROS production (up to 45% for espresso) compared to cells not treated with coffee. Real-time PCR analysis highlighted that treating HT-29 cells with skatole increased the levels of inflammatory cytokines and chemokines TNF-α, IL-1β, IL-8, and IL12, whereas exposure to coffee extracts in cells that were pretreated with skatole showed anti-inflammatory effects with decreased levels of these cytokines. These findings demonstrate that coffee may counteract the adverse effects of putrefactive compounds by modulating oxidative stress and exerting anti-inflammatory activity in colonocytes, thus suggesting that coffee intake could improve health conditions in the presence of altered intestinal microbiota metabolism. [ABSTRACT FROM AUTHOR]

Background: "Ricominciare" is a single-center, prospective, pre-/post-intervention pilot study aimed at verifying the feasibility and safety of the ARC Intellicare (ARC) system (an artificial intelligence-powered and inertial motion unit-based mobile platform) in the home rehabilitation of people with disabilities due to respiratory or neurological diseases. Methods. People with Parkinson's disease (pwPD) or post-COVID-19 condition (COV19) and an indication for exercise or home rehabilitation to optimize motor and respiratory function were enrolled. They underwent training for ARC usage and received an ARC unit to be used independently at home for 4 weeks, for 45 min 5 days/week sessions of respiratory and motor patient-tailored rehabilitation. ARC allows for exercise monitoring thanks to data from five IMU sensors, processed by an AI proprietary library to provide (i) patients with real-time feedback and (ii) therapists with information on patient adherence to the prescribed therapy. Usability (System Usability Scale, SUS), adherence, and adverse events were primary study outcomes. Modified Barthel Index (mBI), Barthel Dyspnea Index (BaDI), 2-Minute Walking Test (2MWT), Brief Fatigue Inventory (BFI), Beck Depression or Anxiety Inventory (BDI, BAI), and quality of life (EQ-5D) were also monitored pre- and post-treatment. Results. A total of 21 out of 23 eligible patients were enrolled and completed the study: 11 COV19 and 10 pwPD. The mean total SUS score was 77/100. The median patients' adherence to exercise prescriptions was 80%. Clinical outcome measures (BaDI, 2MWT distance, BFI; BAI, BDI, and EQ-5D) improved significantly; no side effects were reported. Conclusion. ARC is usable and safe for home rehabilitation. Preliminary data suggest promising results on the effectiveness in subjects with post-COVID condition or Parkinson's disease. [ABSTRACT FROM AUTHOR]

In Heritage Science, sampling is frequently performed for the subsequent diagnostics of modern and contemporary paintings using invasive analytical techniques. However, it endangers the integrity of artworks, and thus, it should be carefully planned and carried out only as a last resort by specialists. Pigment mixtures have commonly been employed by modern and contemporary artists due to the ease of combining paints on the color palette. Hence, a painting might include both primary/secondary paints and mixtures of those. Therefore, obtaining a sample from a mixture might be sufficient for the identification of the individual primary-colored paints. This study focused on the creation of a user-friendly computational workflow for the analysis of images of paintings for the identification of mixtures using cluster analysis (K-means and Fuzzy C-means clustering). Sixteen modern and contemporary paintings that belong to the International Gallery of Modern Art Ca' Pesaro in Venice have been selected: seven of them by Guido Cadorin (1892–1976), six by Andreina Rosa (1924–2019), and three by Boris Brollo (b. 1944), and the artworks of the latter being examined for the first time in this study (using Raman and ER–FTIR spectroscopies). It was found that mixtures can be identified in unvarnished paintings that consist of both non-overlapping and vibrant-colored paint layers, like those of Boris Brollo, and overlapping paint layers, like those of Andreina Rosa. Moreover, K-means clustering performs better in the case of non-overlapping colors, whereas Fuzzy C-means in the case of overlapping colors. In contrast, paintings that have been rendered with dark colors and that present a varnish layer, like those of Guido Cadorin, cannot be preliminary investigated in the proposed manner. [ABSTRACT FROM AUTHOR]

Pain is an unpleasant sensory and emotional experience that affects every aspect of a patient's life and which may be treated through different pharmacological and non-pharmacological approaches. Analgesics are the drugs most commonly used to treat pain, and in specific situations, the use of opioids may be considered with caution. These drugs, in fact, do not always induce optimal analgesia in patients, and several problems are associated with their use. The purpose of this narrative review is to describe the pharmacological approaches currently used for the management of chronic pain. We review several aspects, from the pain-scale-based methods currently available to assess the type and intensity of pain, to the most frequently administered drugs (non-narcotic analgesics and narcotic analgesics), whose pharmacological characteristics are briefly reported. Overall, we attempt to provide an overview of different pharmacological treatments while also illustrating the relevant guidelines and indications. We then report the strategies that may be used to reduce problems related to opioid use. Specifically, we focus our attention on therapeutic drug monitoring (TDM), a tool that could help clinicians select the most suitable drug and dose to be used for each patient. The actual potential of using TDM to optimize and personalize opioid-based pain treatments is finally discussed based on recent scientific reports. [ABSTRACT FROM AUTHOR]

In recent years, research on brain cancers has turned towards the study of the interplay between the tumor and its host, the normal brain. Starting from the establishment of a parallelism between neurogenesis and gliomagenesis, the influence of neuronal activity on the development of brain tumors, particularly gliomas, has been partially unveiled. Notably, direct electrochemical synapses between neurons and glioma cells have been identified, paving the way for new approaches for the cure of brain cancers. Since this novel field of study has been defined "cancer neuroscience", anticancer therapeutic approaches exploiting these discoveries can be referred to as "cancer neuromodulation". In the present review, we provide an up-to-date description of the novel findings and of the therapeutic neuromodulation perspectives in cancer neuroscience. We focus both on more traditional oncologic approaches, aimed at modulating the major pathways involved in cancer neuroscience through drugs or genetic engineering techniques, and on electric stimulation proposals; the latter is at the cutting-edge of neuro-oncology. [ABSTRACT FROM AUTHOR]

Climate change is having an increasing effect on the water cycle, hindering the proper management of water resources for different purposes. Veneto, Northern Italy, is a region characterized by various climatic conditions, ranging from the coastal area to the inland, which exhibits significant agricultural productivity with high irrigation demand, up to the mountainous area to the north. This study assesses a key aspect of climate change in Veneto by focusing on a crucial hydrological parameter, the reference evapotranspiration (ETo), which is calculated using the Penman–Monteith equation. The K-means algorithm was employed to divide Veneto into nine homogeneous regions, each characterized by specific evapotranspiration and climatic features. Furthermore, the seasonal Mann–Kendall (MK) test and the innovative trends analysis (ITA) method were used to investigate the trends related to monthly precipitation, ETo, and climate variables. The seasonal MK test revealed negative trends in precipitation for all clusters. In contrast, ETo trends appear to be decreasing for some clusters, both on the coast and inland, and increasing for others. The ITA method indicated more pronounced trends for higher values of ETo and precipitation, highlighting significant variations that primarily impact extreme values. Overall, this study's approach, which incorporates clustering and trends analysis methods, provides a detailed depiction of ETo in Veneto, enabling the identification of distinct homogeneous areas and the assessment of evolutionary trends concerning evapotranspiration and precipitation, from the coastal to the mountainous regions. [ABSTRACT FROM AUTHOR]

Background: Evidence on the risk of sarcopenia and associated factors in older adults with type 2 diabetes (T2D) is lacking. We evaluate (1) the proportion of patients at risk of sarcopenia in older adults with T2D; and (2) the factors associated with the risk of sarcopenia. Methods: We conducted a cross-sectional study on T2D patients over 65 years referred to our outpatient clinic and who carried out the yearly complication assessment visit. Eligible patients were administered questionnaires during phone interviews for the risk evaluation of sarcopenia (SARC-F), the risk evaluation of malnutrition (Mini Nutritional Assessment Short Form (MNA®-SF)), the adherence to the Mediterranean diet (MEDI-quest), and the evaluation of physical activity (the International Physical Activity Questionnaire short form). Results: A total of 138 patients were included in the study, and 12 patients (8.7% (95% CI 4.6–14.7)) were at risk of sarcopenia. The mean SARC-F score was significantly higher in women compared with men (2.1 ± 1.8 vs. 0.9 ± 1.4, respectively; p < 0.001). The majority of patients identified at risk of sarcopenia compared with those not at risk were women (75% vs. 30%, respectively; p = 0.003), had a higher proportion of neuropathy (50% vs. 19%, respectively; p = 0.027), a lower mean MNA®-SF score (11.6 ± 1.5 vs. 13.0 ± 1.4, respectively; p = 0.001), a lower mean MEDI-quest score (5.2 ± 1.5 vs. 5.9 ± 1, respectively; p = 0.037), and were more inactive (92% vs. 61%, respectively; p = 0.032). Conclusions: In a sample of older adults with T2D, the risk of sarcopenia was identified in 8.7% (95% CI: 4.6–14.7) of the sample, and the main factors associated were female gender, neuropathy, a lower MNA®-SF score, low adherence to the Mediterranean diet, and low physical activity. [ABSTRACT FROM AUTHOR]

While intraoperative neurophysiological monitoring (IONM) is considered a standard for intramedullary spinal cord tumor surgery, the effective role of IONM in intradural extramedullary (IDEM) tumors is still debated. We present the results of 60 patients affected by IDEM tumors undergoing surgery with the aid of IONM. Each patient was evaluated according to the modified McCormick scale (MMS) at admission, discharge and at follow-up. During surgery, motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were studied using the Medtronic NIM-eclipse® 32-channel system (Medtronic Xomed, Inc. 6743 Southpoint Drive North Jacksonville FL USA). Patients' age, gender and tumor location did not affect MMS modifications. Tumors involving more than three levels had an increased likelihood of MMS worsening, while meningioma pathology was associated with worse preoperative and 1-year follow-up MMS. No MEP amplitude ratio was able to predict clinical variations, while intraoperative SEP worsening was associated with 100% risk of poor MMS at discharge and with 50% risk of poor MMS at long-term follow-up. In our opinion, SEP monitoring is a valid tool that may contribute to the preservation of the patient's neurological status. MEP monitoring is not mandatory in IDEM surgery while more studies are required to explore the feasibility and the role of D-wave in this kind of surgery. [ABSTRACT FROM AUTHOR]

Daily use of mouthwash is generally recommended to control dental plaque development and limit further adhesion of oral bacteria. To this purpose, Chlorhexidine di-gluconate (CHG)-containing products are still the most used antiseptic in oral health. The aim of this study was to compare the antimicrobial and antibiofilm activity of three different mouthwash commercial formulations containing CHG at the same concentration (0.2%) on the main etiological agent of dental plaque, Streptococcus mutans (S. mutans). Liquid Chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to confirm the CHG concentration in the commercial formulations. The Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal concentration (MBC) were measured to evaluate the antimicrobial activity of mouthwashes on planktonic cells. The biofilm prevention concentration (BPC) and CHG formulation activity towards mature biofilm were investigated. Both total cell titer and viability in S. mutans pregrown biofilms were evaluated after treatment with formulations at different time points and concentrations, using Crystal Violet (CV) and tetrazolium dye assay (MTT). The Shapiro–Wilk and Levene tests were used to evaluate the normality and overall homogeneity of the datasets, respectively. The chi-square test, Fischer's exact test and Student's t-test were used to evaluate the inhibitory capacity of the commercial formulations in CV and MTT assays. Results showed that even though only slight differences in MIC and MBC values were found on planktonic bacteria, the antibiofilm effect of the different formulations exhibited wide variation when mature biofilms were treated. In addition, results were discussed based on the different compositions of the three formulations, suggesting that herbal extracts, when present in mouthwash formulations, may not always have a beneficial effect, especially when mature biofilms are concerned. [ABSTRACT FROM AUTHOR]

Introduction/Aims HyperCKemia is considered a hallmark of neuromuscular diseases. It can be either isolated or associated with cramps, myalgia, weakness, myoglobinuria, or rhabdomyolysis, suggesting a metabolic myopathy. The aim of this work was to investigate possible genetic causes in order to help diagnose patients with recurrent hyperCKemia or clinical suspicion of inherited metabolic myopathy. Methods A cohort of 139 patients (90 adults and 49 children) was analyzed using a custom panel containing 54 genes associated with hyperCKemia. Results A definite genetic diagnosis was obtained in 15.1% of cases, while candidate variants or variants of uncertain significance were found in a further 39.5%. Similar percentages were obtained in patients with infantile or adult onset, with some different causative genes. RYR1 was the gene most frequently identified, either with single or compound heterozygous variants, while ETFDH variants were the most common cause for recessive cases. In one patient, mRNA analysis allowed identifying a large LPIN1 deletion missed by DNA sequencing, leading to a certain diagnosis. Conclusion These data confirm the high genetic heterogeneity of hyperCKemia and metabolic myopathies. The reduced diagnostic yield suggests the existence of additional genes associated with this condition but also allows speculation that a significant number of cases presenting with hyperCKemia or muscle symptoms are due to extrinsic, not genetic, factors. [ABSTRACT FROM AUTHOR]

In the context of the archaeometrical study of Saturnino Gatti's wall paintings, a significant aspect concerned the study of the organic component to understand both the original binders used in the original areas and the products used for pictorial reintegration and restoration of the painted surfaces. Thanks to the results obtained from various non-invasive and multi-band imaging techniques, it was possible to define Gatti's original painting technique and identify the materials subsequently applied in significant samples. To this end, molecular analyses based on mass spectrometry were carried out. Different procedures in gas chromatography–mass spectrometry (GC-MS) and in pyrolysis coupled with gas chromatography–mass spectrometry (Py-GC-MS) were adopted. The analyses revealed a variety of organic materials on the mural paintings, most of which are from past restoration interventions and have synthetic origin. The overspread presence of paraffin is likely due to the application of a mineral wax-based coating/consolidant. In particular, the execution technique encompassed the use of tempera-based paints, while retouched areas were characterised by the presence of oil-based resins. [ABSTRACT FROM AUTHOR]

Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson's disease (PD). Although its efficacy in the early stage of the disease has been confirmed, its complex pharmacokinetics (PK) increases the variability of the intra-individual motor response, thus amplifying the risk of motor/non-motor fluctuations and dyskinesia. Moreover, it has been demonstrated that L-DOPA PK is strongly influenced by several clinical, therapeutic, and lifestyle variables (e.g., dietary proteins). L-DOPA therapeutic monitoring is therefore crucial to provide personalized therapy, hence improving drug efficacy and safety. To this aim, we have developed and validated an ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to quantify L-DOPA, levodopa methyl ester (LDME), and the DDCI carbidopa in human plasma. The compounds were extracted by protein precipitation and samples were analyzed with a triple quadrupole mass spectrometer. The method showed good selectivity and specificity for all compounds. No carryover was observed, and dilution integrity was demonstrated. No matrix effect could be retrieved; intra-day and inter-day precision and accuracy values met the acceptance criteria. Reinjection reproducibility was assessed. The described method was successfully applied to a 45-year-old male patient to compare the pharmacokinetic behavior of an L-DOPA-based medical treatment involving commercially available Mucuna pruriens extracts and an LDME/carbidopa (100/25 mg) formulation. [ABSTRACT FROM AUTHOR]

Food supplements (FS) containing red yeast rice (RYR) are largely employed to reduce lipid levels in the blood. The main ingredient responsible for biological activity is monacolin K (MoK), a natural compound with the same chemical structure as lovastatin. Concentrated sources of substances with a nutritional or physiological effect are marketed in "dose" form as food supplements (FS). The quality profile of the "dosage form" of FS is not defined in Europe, whereas some quality criteria are provided in the United States. Here, we evaluate the quality profile of FS containing RYR marketed in Italy as tablets or capsules running two tests reported in The European Pharmacopoeia 11 Ed. and very close to those reported in the USP. The results highlighted variations in dosage form uniformity (mass and MoK content) compliant with The European Pharmacopoeia 11 Ed. specifications, whereas the time needed for disintegrating tablets was longer for 44% of the tested samples. The bioaccessibility of MoK was also investigated to obtain valuable data on the biological behaviour of the tested FS. In addition, a method for citrinin (CIT) determination was optimized and applied to real samples. None of the analyzed samples demonstrated CIT contamination (LOQ set at 6.25 ng/mL). Considering the widespread use of FS, our data suggest that greater attention should be paid by fabricants and regulatory authorities to ensure the quality profile and the safe consumption of marketed products. [ABSTRACT FROM AUTHOR]

This paper presents the results obtained for the mural paintings (XV century CE) in the church of San Panfilo in Villagrande di Tornimparte (AQ, Italy) by means of noninvasive spectroscopic techniques; this research is a part of the project on the Saturnino Gatti pictorial cycle, promoted and coordinated by the AIAr (the Italian Archaeometry Association). Digital optical microscopy (OM), X-ray fluorescence spectroscopy (XRF), fiber optics reflectance spectroscopy in the UV–Vis–NIR range (FORS), Fourier transform infrared spectroscopy in the external reflection mode (ER-FTIR), and Raman spectroscopy were performed on the points selected based on the image analysis results and the few available records on previous intervention, with the aim of characterizing both the original and restoration organic and inorganic materials. The synergic application of complementary techniques allowed us to obtain a complete picture of the palette and the main alteration products and organic substances (of rather ubiquitous lipid materials and less widespread resin and proteinaceous materials in specific points). The identification of modern compounds permitted the individuation of restoration areas; this was confirmed by the comparison with multiband imaging results, as in the case of specific green and blue pigments, strictly related to the presence of high signals of zinc. This analytical protocol left only very few ambiguities and allowed to minimizing the number of samples taken to clarifying, by sample laboratory analyses, the few doubts still open. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) has been described in COVID-19 patients. Recently, some case reports and US pharmacovigilance analyses described AF onset as a rare adverse event following COVID-19 vaccination. The possible correlation is unclear. We systematically analyzed the reports of AF related to COVID-19 vaccines collected in the European pharmacovigilance database, EudraVigilance (EV), from 2020 to November 2022. We carried out descriptive and disproportionality analyses. Moreover, we performed a sensitivity analysis, excluding the reports describing other possible alternative AF causes (pericarditis, myocarditis, COVID-19, or other drugs that may cause/exacerbate AF). Overall, we retrieved 6226 reports, which represented only 0.3% of all those related to COVID-19 vaccines collected in EV during our study period. AF reports mainly referred to adults (in particular, >65 years old), with an equal distribution in sex. Reports were mainly related to tozinameran (54.04%), elasomeran (28.3%), and ChAdOx1-S (14.32%). The reported AF required patient hospitalization in 35% of cases and resulted in a life-threatening condition in 10% of cases. The AF duration (when reported) was highly variable, but the majority of the events had a short duration (moda = 24 h). Although an increased frequency of AF reporting with mRNA vaccines emerges from our study, other investigations are required to investigate the possible correlation between COVID-19 vaccination and the rare AF occurrence. [ABSTRACT FROM AUTHOR]

Desmoid tumors (DTs), also known as desmoid fibromatosis or aggressive fibromatosis, are rare, locally invasive, non-metastatic soft tissue tumors. Although histological results represent the gold standard diagnosis, imaging represents the fundamental tool for the diagnosis of these tumors. Although histological analysis represents the gold standard for diagnosis, imaging represents the fundamental tool for the diagnosis of these tumors. DTs represent a challenge for the radiologist, being able to mimic different pathological conditions. A proper diagnosis is required to establish an adequate therapeutic approach. Multimodality imaging, including ultrasound (US), computed tomography (CT) and Magnetic Resonance Imaging (MRI), should be preferred. Different imaging techniques can also guide minimally invasive treatments and monitor their effectiveness. The purpose of this review is to describe the state-of-the-art multidisciplinary imaging of DTs; and its role in patient management. [ABSTRACT FROM AUTHOR]

Vanishing bile duct syndrome (VBDS) is a rare condition characterized by progressive loss, destruction, and disappearance of the intra-hepatic bile ducts, leading to cholestasis and ductopenia. The exact mechanism of development of VDBS has not been established yet. Diagnosis of VBDS mainly relies on clinical and disease related presentations, but liver biopsy is compulsory for diagnosis. Due to the low incidence reported in the literature, a standardized treatment of VDBS has not been established; hence, this rare condition must be managed at a tertiary liver referral center. Here, we report the management and treatment of VBDS of an 81-year-old woman without any history of exposure to antibiotics, neoplasms, etc. [ABSTRACT FROM AUTHOR]

In the recent years, the number of liver resections has seen an impressive growth. Usually, hepatic resections remain the treatment of various liver diseases, such as malignant tumors, benign tumors, hydatid disease, and abscesses. Despite technical advancements and tremendous experience in the field of liver resection of specialized centers, there are moderately high rates of postoperative morbidity and mortality, especially in high-risk and older patient populations. Although ultrasonography is usually the first-line imaging examination for postoperative complications, Computed Tomography (CT) is the imaging tool of choice in emergency settings due to its capability to assess the whole body in a few seconds and detect all possible complications. Magnetic resonance cholangiopancreatography (MRCP) is the imaging modality of choice for delineating early postoperative bile duct injuries and ischemic cholangitis that may arise in the late postoperative phase. Moreover, both MDCT and MRCP can precisely detect tumor recurrence. Consequently, radiologists should have knowledge of these surgical procedures for better comprehension of postoperative changes and recognition of the radiological features of various postoperative complications. [ABSTRACT FROM AUTHOR]

Sacubitril/valsartan (Sac/Val) reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril. However, its effects on functional capacity remain uncertain; consequently, we sought to compare Sac/Val vs. standard medical therapy, in terms of effects on prognostically significant CPET parameters, in HFrEF patients during a long follow-up period. We conducted a single-center, observational study in an HF clinic; specifically, we retrospectively identified that 12 patients switched to Sac/Val and 13 patients that managed with standard, optimal medical therapy (control group). At each visit, baseline, and follow-up (median time: 16 months; IQ range: 11.5–22), we collected demographic information, medical history, vital signs, cardiopulmonary exercise testing, standard laboratory data, pharmacological treatment information, and echocardiographic parameters. The study's primary end-point was the change from baseline in peak VO2 (adjusted to body weight). We did not observe significant differences between the two study groups at baseline. Similarly, we did not observe any significant differences during the follow-up in mean values of peak VO2 corrected for body weight: Sac/Val baseline: 12.2 ± 4.6 and FU: 12.7 ± 3.3 vs. control group: 13.1 ± 4.2 and 13.0 ± 4.2 mL/kg/min; p = 0.49. No significant treatment differences were observed for changes in VE/VCO2 slope: Sac/Val baseline: 35.4 ± 7.4 and FU: 37.2 ± 13.1 vs. control group: 34.6 ± 9.1 and 34.0 ± 7.3; p = 0.49. In conclusion, after a median follow-up period of 16 months, there was no significant benefit of Sac/Val on peak VO2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF. [ABSTRACT FROM AUTHOR]

This paper provides the results of a 3D photogrammetric survey of the apsidal conch of St. Panfilo Church in Tornimparte (L'Aquila, Italy). The images were acquired and then processed in order to obtain a three-dimensional model available on Sketchfab platform. The five panels and the vault of the apsidal conch were exported from the 3D model as orthomosaics and then imported into CAD software for the mapping of the main degradation phenomena. The examined surface was almost entirely covered by mural painting and restoring mortars, the latter mainly located in the lower part of the apsidal conch. The whole surface of the apsidal conch was also examined by means of raking light that enabled highlighting of conservation problems and the presence of incision marks and giornata/pontate boundaries indicating the use of the fresco painting technique. Several degradation phenomena, attributable both to the executive technique of wall painting and the microclimate conditions, could be observed. According to the overlapping of weathering forms and the material involved, most of the examined surfaces exhibited moderate to very severe degradation. [ABSTRACT FROM AUTHOR]

The name "Vesuvian apricot" refers to numerous varieties originating from the same production area at the foot of Vesuvius and with a long tradition of cultivation. The importance of the apricot fruit and its derivatives on human health is known thanks to the presence of several secondary metabolites, many of them being active as antioxidants. This study aims to analyze 12 vesuvian apricot accessions by means of chemical-physical (fruits weights, firmness, TSS, TA, pH, and color fruits) and nutraceutical analyses (acid organic and sugar content, antioxidant activities, and polyphenol content). All the accessions analyzed can be defined as superior-quality apricots because they had TSS values ≥ 13 and a pulp strength ≤ 1 kg/0.5 cm2. Another parameter used to express the quality of apricot fruits was TSS-F (soluble solids content-pulp hardness) which showed a value ≥ 12. The total sugar content ranged from 260.40 mg/g d.w in 'VM' to 744.59 mg/g d.w in 'SC'. In all accessions analyzed the sugar content was in the following order: sucrose > glucose > fructose. The antioxidant activity showed a high variability between the different accessions. Our results show that the Vesuvian apricot accessions present a large range with different organoleptic characteristics and offer the possibility to choose according to consumer and processing preferences. [ABSTRACT FROM AUTHOR]

Simple Summary: A key regulator of erythropoiesis is the erythroid transcriptional factor Krüppel-like factor 1 (KLF1). Increased fetal hemoglobin (HbF) and hemoglobin A2 (HbA2) levels have been associated with KLF1 haploinsufficiency mutations and have been shown to mitigate the severity of β-thalassemia. In our study, two novel KLF1 haploinsufficiency mutations that result in enhanced fetal-globin gene expression, C94X and P173fxP236, are described and functionally characterized. Furthermore, our analysis also shows that some in cis KLF1 mutation combinations may aggravate the phenotype of β-thalassemia. Further understanding of the multiple functions of KLF1 in erythropoiesis is achieved by this study, which also emphasizes the possibility that a subset of KLF1 mutations may be responsible for the severity of the thalassemia phenotype. These findings support the relevance of KLF1 screening for genetic counseling and the efficacy of programs for hemoglobinopathies prevention screening. The erythroid transcriptional factor Krüppel-like factor 1 (KLF1) is a master regulator of erythropoiesis. Mutations that cause KLF1 haploinsufficiency have been linked to increased fetal hemoglobin (HbF) and hemoglobin A2 (HbA2) levels with ameliorative effects on the severity of β-thalassemia. With the aim of determining if KLF1 gene variations might play a role in the modulation of β-thalassemia, in this study we screened 17 subjects showing a β-thalassemia-like phenotype with a slight or marked increase in HbA2 and HbF levels. Overall, seven KLF1 gene variants were identified, of which two were novel. Functional studies were performed in K562 cells to clarify the pathogenic significance of these mutations. Our study confirmed the ameliorative effect on the thalassemia phenotype for some of these variants but also raised the notion that certain mutations may have deteriorating effects by increasing KLF1 expression levels or enhancing its transcriptional activity. Our results indicate that functional studies are required to evaluate the possible effects of KLF1 mutations, particularly in the case of the co-existence of two or more mutations that could differently contribute to KLF1 expression or transcriptional activity and consequently to the thalassemia phenotype. [ABSTRACT FROM AUTHOR]

The management of symptomatic lumbar synovial cysts (LSC) is still a matter of debate. Previous systematic reviews did not stratify data according to different treatment techniques or incompletely reported comparative data on patients treated with lumbar posterior decompression (LPD) and lumbar decompression and fusion (LDF). The aim of our study was to compare LPD and LDF via a systematic review and meta-analysis of the existing literature. The design of this study was in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review questions were as follows: among patients suffering from symptomatic lumbar synovial cysts (population) and treated with either posterior lumbar decompression or posterior decompression with fusion (intervention), who gets the best results (outcome), in terms of cyst recurrence, reoperation rates, and improvement of postoperative symptoms (comparison)? The search of the literature yielded a total of 1218 results. Duplicate records were then removed (n = 589). A total of 598 articles were screened, and 587 records were excluded via title and abstract screening; 11 studies were found to be relevant to our research question and were assessed for eligibility. Upon full-text review, 5 were excluded because they failed to report any parameter separately for both LPD and LDF. Finally, 6 studies for a total of 657 patients meeting the criteria stated above were included in the present investigation. Our analysis showed that LDF is associated with better results in terms of lower postoperative back pain and cyst recurrence compared with LPD. No differences were found in reoperation rates and complication rates between the two techniques. The impact of minimally invasive decompression techniques on the different outcomes in LSC should be assessed in the future and compared with instrumentation techniques. [ABSTRACT FROM AUTHOR]

Medical treatment for trigeminal neuralgia (TN) is not always a feasible option due to a lack of full response or adverse effects. Open surgery or percutaneous procedures are advocated in these cases. Several articles have compared the results among different techniques. Nevertheless, the findings of these studies are heterogeneous. Umbrella reviews are studies sitting at the peak of the evidence pyramid. With this umbrella review, we provided a systematic review of the outcomes of the surgical procedures used for TN treatment. Only systematic reviews and meta-analyses were included following the PRISMA guidelines. Ten articles were enrolled for qualitative and quantitative assessment. Level of evidence was quantified using a specific tool (AMSTAR-2). Results were heterogenous in terms of outcome and measurements. Microvascular decompression (MVD) appeared to be the most effective procedure both in the short-term (pain relief in 85–96.6% of cases) and long-term follow-up (pain relief in 64–79% of cases), although showed the highest rate of complications. The results of percutaneous techniques were similar but radiosurgery showed the highest variation in term of pain relief and a higher rate of delayed responses. The use of the AMSTAR-2 tool to quantify the evidence level scored three studies as critically low and seven studies as low-level, revealing a lack of good quality studies on this topic. Our umbrella review evidenced the need of well-designed comparative studies and the utilization of validated scales in order to provide more homogenous data for pooled-analyses and meta-analyses in the field of TN surgical treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Oligometastatic disease is a condition in oncology where cancer affects only a few distant sites. It is associated with a low-burden spread and a more favorable prognosis compared to polymetastatic disease. Recent studies have identified specific molecular and genetic features that underlie the oligometastatic phenotype, including reduced cancer cell migration and invasion ability, and an enhanced immune response in the metastatic microenvironment. Understanding these characteristics could suggest innovative personalized therapies and contribute to improving the understanding of complex cancer–host relationships. This scoping review highlights new clinical, biological, and methodological challenges that characterize this fascinating field from a modern and innovative perspective. By shedding light on the unique features of oligometastatic disease, we aim to promote the development of more effective and tailored treatments for patients with this condition. Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as "oligometastatic disease" (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Associated liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a recent and promising strategy to perform extensive hepatic resection and limit the risk of post-operative liver failure. Significant morbidity and mortality rates in its pioneering stage has limited acceptance of this treatment. The aim of this review is to evaluate the feasibility, safety, and clinical outcomes of this strategy following application of laparoscopic approach and technical modifications. An evaluation of the data has highlighted that a mini-invasive approach, a less invasive technique in first stage and a better selection of patients could account for potentially better results after ALPPS procedure in terms of blood loss, morbidity, and mortality rate in comparison with outcomes of open series. Background: Associated liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a recent strategy to improve resectability of extensive hepatic malignancies. Recent surgical advances, such as the application of technical variants and use of a mini-invasive approach (MI-ALPPS), have been proposed to improve clinical outcomes in terms of morbidity and mortality. Methods: A total of 119 MI-ALPPS cases from 6 series were identified and discussed to evaluate the feasibility of the procedure and short-term clinical outcomes. Results: Hepatocellular carcinoma were widely the most common indication for MI-ALPPS. The median estimated blood loss was 260 mL during Stage 1 and 1625 mL in Stage 2. The median length of the procedures was 230 min in Stage 1 and 184 in Stage 2. The median increase ratio of future liver remnant volume was 87.8%. The median major morbidity was 8.14% in Stage 1 and 23.39 in Stage 2. The mortality rate was 0.6%. Conclusions: MI-ALPPS appears to be a feasible and safe procedure, with potentially better short-term outcomes in terms of blood loss, morbidity, and mortality rate if compared with those of open series. [ABSTRACT FROM AUTHOR]

Background: The recommended protein intake for the elderly is 25–30 g at main meals, with at least 2500–2800 mg of leucine at each meal. There is still little evidence regarding the amount and distribution of protein and leucine intake with meals in the elderly with type 2 diabetes (T2D). In this cross-sectional study, we evaluated protein and leucine intake at each meal in elderly patients with T2D. Methods: A total of 138 patients (91 men and 47 women) with T2D, aged 65 years or older, were included. Participants performed three 24-h dietary recalls for the evaluation of their dietary habits and protein and leucine intake at meals. Results: The average protein intake was 0.9 ± 0.2 g/kg body weight/day, and only 23% of patients complied with the recommendations. The average protein intake was 6.9 g at breakfast, 29 g at lunch, and 21 g at dinner. None of the patients reached the recommended protein intake at breakfast; 59% of patients complied with the recommendations at lunch; and 32% at dinner. The average leucine intake was 579 mg at breakfast, 2195 g at lunch, and 1583 mg at dinner. The recommended leucine intake was not reached by any patient at breakfast, by 29% of patients at lunch, and by 13% at dinner. Conclusions: Our data show that, in elderly patients with T2D, the average protein intake is low, particularly at breakfast and dinner, and that leucine intake is remarkably lower than the recommended levels. These data raise the need to implement nutritional strategies capable of increasing protein and leucine intake in the elderly with T2D. [ABSTRACT FROM AUTHOR]

Pelargonium quercetorum is a medicinal plant traditionally used for treating intestinal worms. In the present study, the chemical composition and bio-pharmacological properties of P. quercetorum extracts were investigated. Enzyme inhibition and scavenging/reducing properties of water, methanol, and ethyl acetate extracts were assayed. The extracts were also studied in an ex vivo experimental model of colon inflammation, and in this context the gene expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) were assayed. Additionally, in colon cancer HCT116 cells, the gene expression of transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), possibly involved in colon carcinogenesis, was conducted as well. The extracts showed a different qualitative and quantitative content of phytochemicals, with water and methanol extracts being richer in total phenols and flavonoids, among which are flavonol glycosides and hydroxycinnamic acids. This could explain, at least in part, the higher antioxidant effects shown by methanol and water extracts, compared with ethyl acetate extract. By contrast, the ethyl acetate was more effective as cytotoxic agent against colon cancer cells, and this could be related, albeit partially, to the content of thymol and to its putative ability to downregulate TRPM8 gene expression. Additionally, the ethyl acetate extract was effective in inhibiting the gene expression of COX-2 and TNFα in isolated colon tissue exposed to LPS. Overall, the present results support future studies for investigating protective effects against gut inflammatory diseases. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is an often underestimated inflammatory pathological condition that can have a serious impact on quality of life. Many therapies have been proposed to deal with CVD, but unfortunately the symptoms recur with increasing frequency and intensity as soon as treatments are stopped. Previous studies have shown that the common inflammatory transcription factor AP-1 (activator protein-1) and nuclear factor kappa-activated B-cell light chain enhancer (NF-kB) play key roles in the initiation and progression of this vascular dysfunction. The aim of this research was to develop a herbal product that acts simultaneously on different aspects of CVD-related inflammation. Based on the evidence that several natural components of plant origin are used to treat venous insufficiency and that magnolol has been suggested as a putative modulator of AP-1, two herbal preparations based on Ruscus aculeatus root extracts, and Vitis vinifera seed extracts, as well as diosmetin and magnolol, were established. A preliminary MTT-based evaluation of the possible cytotoxic effects of these preparations led to the selection of one of them, named DMRV-2, for further investigation. First, the anti-inflammatory efficacy of DMRV-2 was demonstrated by monitoring its ability to reduce cytokine secretion from endothelial cells subjected to LPS-induced inflammation. Furthermore, using a real-time PCR-based protocol, the effect of DMRV-2 on AP-1 expression and activity was also evaluated; the results obtained demonstrated that the incubation of the endothelial cells with this preparation almost completely nullified the effects exerted by the treatment with LPS on AP-1. Similar results were also obtained for NF-kB, whose activation was evaluated by monitoring its distribution between the cytosol and the nucleus of endothelial cells after the different treatments. [ABSTRACT FROM AUTHOR]

The peritoneum is an unusual site of metastases from lung cancer, and optimal management at the moment remains unclear and mostly based on palliative strategies. Therefore, the aim of the study was to investigate demographic characteristics, management and overall survival of patients with peritoneal metastases from lung cancer (PCLC). A PRISMA-compliant systematic review and pooled analysis was performed searching all English studies published until December 2022. PROSPERO, CRD42022349362. Inclusion criteria were original articles including patients with peritoneal carcinomatosis from lung cancer, specifying at least one outcome of interest. Exclusion criteria were being unable to retrieve patient data from articles, and the same patient series included in different studies. Among 1746 studies imported for screening, twenty-one were included (2783 patients). Mean overall survival was between 0.5 and 5 months after peritoneal carcinomatosis diagnosis and 9 and 21 months from lung cancer diagnosis. In total, 27% of patients underwent first-line or palliative chemotherapy and 7% of them surgery. Management differs significantly among published studies. The literature on PCLC is scarce. Its incidence is low but appears to be substantially rising and is likely to be an underestimation. Prognosis is very poor and therapeutic strategies have been limited and used in a minority of patients. Subcategories of PCLC patients may have an improved prognosis and may benefit from an aggressive oncological approach, including cytoreductive surgery. Further investigation would be needed in this regard. [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently recognized form of regulated cell death involving lipid peroxidation. Glutathione peroxidase 4 (GPX4) plays a central role in the regulation of ferroptosis through the suppression of lipid peroxidation generation. Connections have been reported between ferroptosis, lipid metabolism, cancer onset, and drug resistance. Recently, interest has grown in ferroptosis induction as a potential strategy to overcome drug resistance in hematological malignancies. GATA-1 is a key transcriptional factor controlling hematopoiesis-related gene expression. Two GATA-1 isoforms, the full-length protein (GATA-1FL) and a shorter isoform (GATA-1S), are described. A balanced GATA-1FL/GATA-1S ratio helps to control hematopoiesis, with GATA-1S overexpression being associated with hematological malignancies by promoting proliferation and survival pathways in hematopoietic precursors. Recently, optical techniques allowed us to highlight different lipid profiles associated with the expression of GATA-1 isoforms, thus raising the hypothesis that ferroptosis-regulated processes could be involved. Lipidomic and functional analysis were conducted to elucidate these mechanisms. Studies on lipid peroxidation production, cell viability, cell death, and gene expression were used to evaluate the impact of GPX4 inhibition. Here, we provide the first evidence that over-expressed GATA-1S prevents K562 myeloid leukemia cells from lipid peroxidation-induced ferroptosis. Targeting ferroptosis is a promising strategy to overcome chemoresistance. Therefore, our results could provide novel potential therapeutic approaches and targets to overcome drug resistance in hematological malignancies. [ABSTRACT FROM AUTHOR]

One of the major fields of application of ablation treatment is liver tumors. With respect to HCC, ablation treatments are considered as upfront treatments in patients with early-stage disease, while in colorectal liver metastases (CLM), they can be employed as an upfront treatment or in association with surgical resection. The main prognostic feature of ablation is the tumor size, since the goal of the treatment is the necrosis of all viable tumor tissue with an adequate tumor-free margin. Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most employed ablation techniques. Ablation therapies in HCC and liver metastases have presented a challenge to radiologists, who need to assess response to determine complication-related treatment. Complications, defined as any unexpected variation from a procedural course, and adverse events, defined as any actual or potential injury related to the treatment, could occur either during the procedure or afterwards. To date, RFA and MWA have shown no statistically significant differences in mortality rates or major or minor complications. To reduce the rate of major complications, patient selection and risk assessment are essential. To determine the right cost-benefit ratio for the ablation method to be used, it is necessary to identify patients at high risk of infections, coagulation disorders and previous abdominal surgery interventions. Based on risk assessment, during the procedure as part of surveillance, the radiologists should pay attention to several complications, such as vascular, biliary, mechanical and infectious. Multiphase CT is an imaging tool chosen in emergency settings. The radiologist should report technical success, treatment efficacy, and complications. The complications should be assessed according to well-defined classification systems, and these complications should be categorized consistently according to severity and time of occurrence. [ABSTRACT FROM AUTHOR]

To assess Radiomics and Machine Learning Analysis in Liver Colon and Rectal Cancer Metastases (CRLM) Growth Pattern, we evaluated, retrospectively, a training set of 51 patients with 121 liver metastases and an external validation set of 30 patients with a single lesion. All patients were subjected to MRI studies in pre-surgical setting. For each segmented volume of interest (VOI), 851 radiomics features were extracted using PyRadiomics package. Nonparametric test, univariate, linear regression analysis and patter recognition approaches were performed. The best results to discriminate expansive versus infiltrative front of tumor growth with the highest accuracy and AUC at univariate analysis were obtained by the wavelet_LHH_glrlm_ShortRunLowGray Level Emphasis from portal phase of contrast study. With regard to linear regression model, this increased the performance obtained respect to the univariate analysis for each sequence except that for EOB-phase sequence. The best results were obtained by a linear regression model of 15 significant features extracted by the T2-W SPACE sequence. Furthermore, using pattern recognition approaches, the diagnostic performance to discriminate the expansive versus infiltrative front of tumor growth increased again and the best classifier was a weighted KNN trained with the 9 significant metrics extracted from the portal phase of contrast study, with an accuracy of 92% on training set and of 91% on validation set. In the present study, we have demonstrated as Radiomics and Machine Learning Analysis, based on EOB-MRI study, allow to identify several biomarkers that permit to recognise the different Growth Patterns in CRLM. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to assess MRI features of mucinous liver metastases compared to non-mucinous metastases and hepatic hemangioma. Methods: A radiological archive was assessed from January 2017 to June 2021 to select patients subjected to liver resection for CRCLM and MRI in the staging phase. We selected 20 patients with hepatic hemangioma (study group B). We evaluated (a) the maximum diameter of the lesions, in millimeters, on T1-W flash 2D in phase and out phase, on axial HASTE T2-W and on portal phase axial VIBE T1 W; and (b) the signal intensity (SI) in T1-W sequences, in T2-W sequences, Diffusion-Weighted Imaging (DWI) sequences and apparent diffusion coefficient (ADC) maps so as to observe (c) the presence and the type of contrast enhancement during the contrast study. The chi-square test was employed to analyze differences in percentage values of the categorical variable, while the non-parametric Kruskal–Wallis test was used to test for statistically significant differences between the median values of the continuous variables. A p-value < 0.05 was considered statistically significant. Results: The final study population included 52 patients (33 men and 19 women) with 63 years of median age (range 37–82 years) and 157 metastases. In 35 patients, we found 118 non-mucinous type metastases (control group), and in 17 patients, we found 39 mucinous type metastases (study group A). During follow-up, recurrence occurred in 12 patients, and three exhibited mucinous types among them. In the study group, all lesions (100%) showed hypointense SI on T1-W, very high SI (similar to hepatic hemangioma) in T2-W with restricted diffusion and iso-hypointense signals in the ADC map. During the contrast study, the main significant feature is the peripheral progressive enhancement. [ABSTRACT FROM AUTHOR]

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare type of primary liver malignancy. Among the risk factors, hepatitis B and hepatitis C virus infections, cirrhosis, and male gender are widely reported. The clinical appearance of cHCC-CCA is similar to that of HCC and iCCA and it is usually silent until advanced states, causing a delay of diagnosis. Diagnosis is mainly based on histology from biopsies or surgical specimens. Correct pre-surgical diagnosis during imaging studies is very problematic and is due to the heterogeneous characteristics of the lesion in imaging, with overlapping features of HCC and CCA. The predominant histological subtype within the lesion establishes the predominant imaging findings. Therefore, in this scenario, the radiological findings characteristic of HCC show an overlap with those of CCA. Since cHCC-CCAs are prevalent in patients at high risk of HCC and there is a risk that these may mimic HCC, it is currently difficult to see a non-invasive diagnosis of HCC. Surgery is the only curative treatment of HCC-CCA. The role of liver transplantation (LT) in the treatment of cHCC-CCA remains controversial, as is the role of ablative or systemic therapies in the treatment of this tumour. These lesions still remain challenging, both in diagnosis and in the treatment phase. Therefore, a pre-treatment imaging diagnosis is essential, as well as the identification of prognostic factors that could stratify the risk of recurrence and the most adequate therapy according to patient characteristics. [ABSTRACT FROM AUTHOR]

Distal gastrectomy for benign gastroduodenal peptic disease has become rare, but it still represents a widely adopted procedure for advanced and, in some countries, even for early distal gastric cancer. Survival rates following surgery for gastric malignancy are constantly improving, hence the residual mucosa of the gastric stump is exposed for a prolonged period to biliopancreatic reflux and, possibly, to Helicobacter pylori (HP) infection. Biliopancreatic reflux and HP infection are considered responsible for gastritis and metachronous carcinoma in the gastric stump after oncologic surgery. For gastrectomy patients, in addition to eradication treatment for cases that are already HP positive, endoscopic surveillance should also be recommended, for prompt surveillance and detection in the residual mucosa of any metaplastic-atrophic-dysplastic features following surgery. [ABSTRACT FROM AUTHOR]

The paper presents the first archaeometric results on a selection of ancient Roman coins (antoniniani) from a treasure found in the Roman necropolis area of ancient Cumae (Southern Italy) during archaeological campaigns by the Centre Jean Bérard. A multi-analytical approach consisting of non-destructive techniques (stereomicroscopy, FESEM-EDS, pXRF, Raman, μ-CT) was implemented on the better-preserved coins of the treasure in order to investigate the chemical composition of the alloy. Chemical analysis showed that the Roman mint prepared the metal with an argentiferous lead–bronze alloy. A group of coins presents a low content of the precious metal, which is in agreement with the financial crisis of the Roman Empire of the third century. Another group of two coins shows a higher silver content, which is in agreement with their issue or with the Mediolanum mint standards. In addition, the external layers of corroded coins were analysed to explore the state of conservation of the patina and to identify the corrosion products. Some typical corrosion patinas due to post-depositional conditions were identified. The mineralogical characterisation of the corrosion products enables us to implement adequate conservation strategies, and the presence of more aggressive patinas suggests immediate interventions. [ABSTRACT FROM AUTHOR]