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Oral malignant melanoma (OMM) has a prevalence less than 1% of all melanomas and it commonly develops on the oral mucosa following a slow and unspecific transformation of unstable melanocytic lesions, often resulting in a diagnostic delay. The marker PReferentially Expressed Antigen in MElanoma (PRAME) seems to be a valid tool to investigate the biological and histological nature of cutaneous melanocytic lesions, but to date its use to characterize pigmented lesions in the oral cavity is largely unexplored. The aim of this study was to create preliminary knowledge on the PRAME expression in OMM, and to compare its expression respect to other dysplastic pigmented lesions of the oral cavity. Interestingly, PRAME has been demonstrated to be reliable in the clinical conditions investigated in our pilot study; in fact, it has clearly differentiated the cases of Melanoma, which showed diffuse and intense positivity (score 6+/7+) to PRAME, from the other melanocytic nevi, which resulted to be mainly negative to PRAME. This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area.

Background: Internuclear ophthalmoplegia (INO) is a disorder of eye movements caused by a lesion involving the medial longitudinal fasciculus (MLF) within the brainstem, and it is characterized by adduction impairment combined with contralateral dissociated abduction nystagmus. The frequency of acute ischemic stroke (AIS) presenting with INO as a predominant symptom is very low, and many patients suffering from this brainstem AIS are precluded from intravenous thrombolysis (IVT). Objective: To provide for the first time a magnetic resonance imaging (MRI) evidence of response to the IVT in brainstem wake-up stroke presenting with INO as an isolated symptom. Methods: Here, we described a rare case of pons AIS presenting with INO as a unique symptom of awakening. In order to differentiate an ischemic stroke from other stroke mimics, and to determine whether the patient was within the therapeutic window for IVT (wake-up stroke), brain MRI including DWI and FLAIR sequences was acquired. Results: A left paramedian pontine DWI/FLAIR mismatch was detected and the patient was considered eligible for IVT. After IVT, the patient made a full recovery with complete resolution of INO. Follow-up MRI at 1 month demonstrates the absence of ischemic lesions. Conclusion: Our case provides neuroradiological evidence of IVT efficacy in brainstem stroke, and it should prompt clinicians to rapidly perform MRI in wake-up onset INO and to just as quickly administer IVT, since INO is a functionally disabling deficit. Finally, this case demonstrates the value of MRI in diagnostic, prognostic, and therapeutic workup of posterior circulation wake-up stroke.

The history of high-tech regulation is a path studded with incidents. Each adverse event allowed the gathering of more information on high technologies and their impacts on people, infrastructure, and other technologies, posing the bases for their regulation. With the increasing diffusion of artificial intelligence (AI) use, it is plausible that this connection between incidents and high-tech regulation will be confirmed for this technology as well. This study focuses on the role of AI incidents and an efficient strategy of incident data collection and analysis to improve our knowledge of the impact of AI technologies and regulate them better. To pursue this objective, the paper first analyses the evolution of high-tech regulation in the aftermath of incidents. Second, the paper focuses on the recent developments in AI regulation through soft and hard laws. Third, this study assesses the quality of the available AI incident databases and their capacity to provide information useful for opening and regulating the AI black box. This study acknowledges the importance of implementing a strategy for gathering and analysing AI incident data and approving flexible AI regulation that evolves with such a new technology and with the information that we will receive from adverse events—an approach that is also endorsed by the European Commission and its proposal to regulate and harmonise rules on AI.

En tiempos de globalización, es necesario acercase a la realidad en que se encuentra los gobiernos locales, por el cual se plantea la presente investigación, el problema que se abordó esta expresada en la interrogante ¿Qué relación existe entre la actitud laboral del personal administrativo y satisfacción del usuario de la Municipalidad Provincial de La Convención Quillabamba Cusco 2019.?, para logar una respuesta categórica se formuló el objetivo es Determinar la actitud laboral del personal administrativo y satisfacción del usuario. Que permitió proponer un plan de mejora de la calidad de servicio de la Municipalidad Provincial de La Convención Quillabamba Cusco 2019. En la investigación se planteó la hipótesis: La relación que existe entre actitud laboral del personal administrativo y satisfacción del usuario de la Municipalidad Provincial de La Convención Quillabamba Cusco 2019. es positivo, a mayor apreciación positiva la metodología que se asumió es el deductivo analítico corresponde al: Tipo: de investigación transversal, Nivel: Descriptivo-correlacional, Diseño: M = Ox r Oy. Dónde: M = Muestra O = Observación x = apreciación positiva de 168 servicios administrativos de la municipalidad y satisfacción del usuario de una población: 9745 usuarios cuya muestra es 347 usuarios. La conclusión final permitió explicar, la correlación de la actitud laboraldel personal administrativo y satisfacción del usuario de la Municipalidad Provincial de Quillabamba - Cusco 2019.

Radiocarbon assay of charcoal from four sites in Nola, Central African Republic, provide new age estimates from the Sangha River Interval and doubles the number of radiocarbon dates from the center of this important and controversial biogeographical tract. The new age estimates mark the occupation of a village ~575 cal BP, two iron-smelting events about 1550 cal BP, and a ~2750–2520 cal BP iron production feature that represents one of the earliest smelting sites in the Congo Basin. Although the numbers of dated sites in the northcentral Sangha River Interval remain unfortunately small, most represent iron production loci that predate 1550 cal BP and suggest Nola supported widespread Early Iron Age smelting on the cusp of a proposed human population collapse. The extant record also indicates this profusion of smelting occurred hundreds of years before intensification in metallurgy in the neighboring Lobaye River basin.

Fluoroquinolone prophylaxis’s (FQ-P) usefulness in patients with neutropenia is controversial. In recent decades, Italian epidemiological data has shown worrisome rates of FQ resistance. A single-center cohort study on 136 autologous stem cell transplantations (ASCTs) and 223 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) was performed from January 2018 to December 2020. Piperacillin/tazobactam was the first-line therapy for febrile neutropenia (FN). Since February 2019, FQ-P has been omitted. We evaluated the day +30 posttransplant cumulative incidence function (CIF) of gram-negative bacteria pre-engraftment bloodstream infections (PE-BSIs) and any changes in antimicrobial resistance, FN, and infection-related mortality (IRM). In ASCTs, ≥1 FN episode occurred in 74.3% of transplants, without differences among groups (P = .66). CIF of gram-negative bacteria PE-BSI was 10.1%, with a significant difference according to FQ-P (0% [LEVO-group] vs 14.1% [NO-LEVO-group], P = .016). CIF of IRM was 0% in both groups. In allo-HSCTs, ≥1 FN episode occurred in 96.4% of transplants, without differences among groups (P = .72). CIF of gram-negative bacteria PE-BSI was 28%, significantly higher without FQ-P (14.7% [LEVO-group] vs 34.4% [NO-LEVO-group], P = .003). CIF of IRM was 5%, superimposable in both groups (P = .62). Comparing antimicrobial resistance among gram-negative bacteria of allo-HSCT setting, in the group without FQ-P, a significantly higher proportion of pathogens was susceptible to piperacillin/tazobactam (71% vs 30%, P = .026), FQ (49% vs 10%, P = .03), and carbapenems (95% vs 50%, P = .001). FQ-P discontinuation increased gram-negative bacteria PE-BSI but did not impact IRM, both in the ASCT and allo-HSCT settings; importantly, it concurred to significantly decrease antimicrobial resistance in gram-negative bacteria.

Diabetes mellitus (DM) is one of the fastest-growing health emergencies of the 21st century, and one of the chronic diseases with the highest socio-economic impact on health care systems. DM is the main cause of chronic kidney disease, and is associated with a significant increase in cardiovascular risk and clinical and care complexity. The presence of a constellation of cardiac, metabolic, and renal diseases, in a complex patient with DM, constitutes the CardioRenal Metabolic Syndrome (CRMS). The management of these patients should include a paradigm shift from a reactive strategy to a proactive approach, and the integration of territorial, hospital and social assistance services according to the Chronic Care Model (CCM). Complexity science suggests an alternative model in which disease and health arise from complex, dynamic, and unique interactions among the different components of the overall system. The hospital should be viewed as a highly specialized hub of the chronic care system, which interacts with the outpatient specialist and primary care. In order to create effective communication among territorial care units and highly specialized hospitals, levels of clinical complexity are here proposed and included in a multidimensional management model for the complex patient with diabetes and cardiorenal comorbidity.

One billion people worldwide get flu every year, including patients with non–small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on the composition of the tumor microenvironment (TME) and the clinical outcome of patients with NSCLC is largely unknown. We set out to understand how IAV load impacts cancer growth and modifies cellular and molecular players in the TME. Herein, we report that IAV can infect both tumor and immune cells, resulting in a long-term protumoral effect in tumor-bearing mice. Mechanistically, IAV impaired tumor-specific T-cell responses, led to the exhaustion of memory CD8+ T cells and induced PD-L1 expression on tumor cells. IAV infection modulated the transcriptomic profile of the TME, fine-tuning it toward immunosuppression, carcinogenesis, and lipid and drug metabolism. Consistent with these data, the transcriptional module induced by IAV infection in tumor cells in tumor-bearing mice was also found in human patients with lung adenocarcinoma and correlated with poor overall survival. In conclusion, we found that IAV infection worsened lung tumor progression by reprogramming the TME toward a more aggressive state.

This study aimed to collect and analyze the literature data regarding Chiari network (CN) and other right atrium (RA) remnants comprising the Eustachian and Thebesian valves (EV, ThV) as a potential entrapment site during different percutaneous cardiac procedures (PCP).A systematic search was conducted using Pubmed and Embase databases following the PRISMA guidelines to obtain available data concerning PCP associated with entrapment of inserted materials within CN-EV-ThV. The final analysis included 41 patients who underwent PCP with reported material entrapment within these RA remnants. The PCP was atrial septal defect (ASD)/patent foramen ovale (PFO) closure, catheter ablation, and pacemaker/defibrillator implantation in 44%, 22%, and 17% of patients, respectively. The entrapped materials were ASD/PFO devices, multipolar electrophysiology catheters, passive-fixation pacing leads, and J-guidewires in about 30%, 20%, 15%, and 10% of patients, respectively. Intraprocedural transthoracic, transoesophageal and intracardiac echocardiography showed sensitivity to reveal these structures of 20%, ∼95%, and 100%, respectively. A percutaneous approach successfully managed 70% of patients, while cardiovascular surgery was required in 20% and three patients died (7.3%).CN and other RA remnants may cause entrapment of various devices or catheters during PCP requiring right heart access. The percutaneous approach, guided by intraprocedural imaging, appears safe and effective in managing most patients. Prevention includes recognizing these anatomical structures at baseline cardiac imaging and intraprocedural precautions. Further studies are needed to analyze the actual incidence of this condition, its clinical impact and appropriate management.

Active noise control (ANC) has been used in several systems to improve acoustic performance while avoiding increases in the size and weight required by passive noise control solutions. This paper considers an ANC application aimed at controlling the sound field in the cabin of a supersports car with a naturally aspirated engine. This work studies the performance of a system that employs microphones and loudspeakers in the car cabin and uses a reference signal obtained from CANbus data. The controller exploits a multichannel, multi-order Fx-LMS algorithm to control the sound only in the region surrounding the driver's ears. Due to the nature of the car, this ANC application provides an interesting and challenging case study due to the rapidly changing acoustic excitation provided by the engine. The paper therefore describes a system for noise reduction, focusing on engine order reduction, aiming at achieving control during the most representative manoeuvre known as the "Wide-Open Throttle" (WOT). The investigated controller - acting locally and only on some orders simultaneously - shows good sound attenuation over the entire spectrum, with peaks of reduction exceeding 10 dB, and achieving a 5% overall decrease in the loudness, which is calculated according to ISO 532-1.

Sleep impairment is one of the most common comorbidities affecting people with epilepsy (PWE). The bidirectional relation between epilepsy and sleep has been widely established. Several studies investigated subjective sleep quality and daytime vigilance in PWE, highlighting frequent complaints of sleep fragmentation, difficulties in falling asleep, and daytime sleepiness. The present study aimed to deevaluate sleep structure in drug-naive PWE, distributed on the basis of epilepsy type, and compared to controls.This observational study included adult patients newly diagnosed with epilepsy and drug-naive as well as a control group of healthy subjects. All PWE and controls underwent a dynamic 24-hour EEG with signals for sleep recording in order to evaluate sleep architecture, structure, continuity and fragmentation.Twenty-four PWE were included and distributed in two groups based on epilepsy type. Eleven patients were included in the generalized epilepsy group (63.6% male; 34.91 ± 9.80 years) and 13 patients in the focal epilepsy group (53.8% male; 38.69 ± 12.74 years). The control group included 16 subjects (56.3% male; 32.75 ± 12.19 years). Patients with generalized or focal epilepsy had a significantly lower sleep efficiency than controls. Moreover, both patient groups presented the alteration of markers of sleep fragmentation and lack of continuity, with higher indices of sleep stage transitions and arousal. Finally, the two patient groups presented less REM sleep than controls.This study highlighted the alteration of sleep quality, continuity and stability in both patients with focal or generalized epilepsy compared to controls, also in the absence of ictal events. This sleep impairment resulted in the reduction of REM sleep. Therefore, these findings may be explained by the increase in awakenings and sleep stage shifts, which may be attributed to both sleep networks impairment and neurotransmission dysfunction in PWE, and also possibly triggered by paroxysmal interictal abnormalities.

Neuron generation persists throughout life in the hippocampus but is altered in animal models of neurological and neuropsychiatric diseases, suggesting that disease-associated decline in cognitive and emotional hippocampal-dependent behaviours might be functionally linked with dysregulation of post-natal neurogenesis. Depletion of the adult neural stem/progenitor cell (NSPCs) pool and neurogenic decline have been recently described in mice expressing synaptic susceptibility genes associated with autism spectrum disorder (ASDs). To gain further insight into mechanisms regulating neurogenesis in mice carrying mutations in synaptic genes related to monogenic ASDs, we used the R451C Neuroligin3 knock-in (Nlgn3 KI) mouse, which is characterized by structural brain abnormalities, deficits in synaptic functions, and reduced sociability. We show that the number of adult-born neurons, but not the size of the NSPC pool, was reduced in the ventral dentate gyrus in knock-in mice. Notably, this neurogenic decline was rescued by daily injecting mice with 10 mg/Kg of the antidepressant fluoxetine for twenty consecutive days. Sustained treatment also improved KI mice sociability and increased the number of c-Fos active adult-born neurons, compared with vehicle-injected KI mice. Our study uncovers neurogenesis-mediated alterations in the brain of R451C KI mouse, showing that the R451C Nlgn3 mutation leads to lasting, albeit pharmacologically reversible, changes in the brain, affecting neuron formation in the adult hippocampus. Our results suggest that fluoxetine can ameliorate social behaviour in KI mice, at least in part, by rescuing adult hippocampal neurogenesis, which may be relevant for the pharmacological treatment of ASDs.

We assessed the efficacy and safety of ranolazine in real-world patients with hypertrophic cardiomyopathy (HCM).Ranolazine is an anti-anginal drug that inhibits the late phase of the inward sodium current. In a small prospective trial, ranolazine reduced the arrhythmic burden and improved biomarker profile in HCM patients. However, systematic reports reflecting real-world use in this setting are lacking.Changes in clinical and instrumental features, symptoms and arrhythmic burden were evaluated in 119 patients with HCM before and during treatment with ranolazine at a national referral centre for HCM.Patients were treated with ranolazine for 2 [1-4] years; 83 (70%) achieved a dosage ≥1000 mg per day. Treatment interruption was necessary in 24 patients (20%) due to side effects (n = 10, 8%) or disopyramide initiation (n = 8, 7%). Seventy patients (59%) were treated with ranolazine for relief of angina. Among them, 51 (73%) had total symptomatic relief and 47 patients (67%) showed ≥2 Canadian Cardiovascular society (CCS) angina grade improvement. Sixteen patients (13%) were treated for recurrent ventricular arrhythmias, including 4 with a clear ischemic trigger, who experienced no further arrhythmic episodes while on ranolazine. Finally, 33 patients (28%) were treated for heart failure associated with severe diastolic dysfunction: no symptomatic benefit could be observed in this group.Ranolazine was safe and well tolerated in patients with HCM. The use of ranolazine may be considered in patients with HCM and microvascular angina.

Background: Diabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximatelytwice that of patients without foot ulcers. “Metabolic memory” represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing. Methods: The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigenetic changes on miRNA 126, 305, and 217 expression and the frequency of the SNPs of genes encoding inflammatory molecules (e.g., IL-6 and TNF-alpha) and their correlations with serum levels of proangiogenic molecules (e.g., ENOS, VEGF and HIF-1alpha) and several adipokines as well as with endothelial dysfunction, assessed noninvasively by reactive hyperaemia peripheral artery tonometry . Between March 2021 and June 2022, 110 patients were enrolled into the study: 50 diabetic patients with diabetic foot injuries, 40 diabetic patients without ulcerative complications and 20 nondiabetic patients as the control group. Results: Diabetic subjects with lower limb ulcerative lesions exhibited higher levels of inflammatory cytokines, such as VEGF (191.40±200 pg/mL vs. 98.27±56.92 pg/mL vs. 71.01±52.96 pg/mL; p=0.22), HIF-1alpha (40.18±10.80 ng/mL vs. 33.50±6.16 ng/mL vs. 33.85±6.84 ng/mL; p=0.10), and Gremlin-1 (1.72±0.512 ng/mL vs. 1.31±0.21 ng/mL vs. 1.11±0.19 ng/mL; p< 0.0005), than those without lower limb ulcers and healthy controls. Furthermore, we observed that miR-217-5p and miR-503-5p were 2.19-fold (p

Quella tra alimentazione e cambiamenti climatici è una relazione complessa di causa-effetto, trattandosi di due sistemi interconnessi che evolvono nel tempo originando reciproche pressioni. Questa ormai acquisita consapevolezza è alla base delle strategie programmate a livello globale per affrontare le sfide del climate change, ove la tutela del diritto al cibo (rectius sicurezza alimentare) è assunta quale priorità fondamentale dell’azione climatica. In questo quadro, l’intento qui dichiarato è di impostare alcune linee di riflessione sulla logica e sull’efficacia delle soluzioni ad oggi prospettate per giungere a una transizione ecologica idonea a garantire l’effettività del diritto fondamentale al cibo., BioLaw Journal - Rivista di BioDiritto, N. 2 (2023)

In the Mediterranean and occasionally in the Black Sea, low-pressure systems with the character of both mid-latitude and tropical cyclones can form. These hybrid storms are called subtropical storms, subtropical depressions, medistorms/medicanes, or tropical-like cyclones (TLC). A strong low-pressure system given the name Falchion developed in northern part of the Black Sea during 11–20 August 2021. This storm was blamed for damage and more than 30 casualties in the nations bordering the region. At peak intensity, this storm was a as strong as a tropical depression. Falchion developed and moved northeast, reaching peak intensity before becoming nearly stationary. The NCEP reanalyses and satellite data obtained from Eumetsat’s geostationary satellite, Meteosat-8, were used to examine the character of the storm. This study demonstrates that the movement of Falchion was impeded by a blocking event that occurred over central Asia during much of August 2021. The storm did share characteristics with tropical systems, but a comparison of Falchion to tropical depressions and subtropical storms in the North and South Atlantic demonstrated that this storm was more consistent with these types of storms when examining the storm and the proximal environment. This included an examination of integrated water vapor (IVT) plumes, and the plume associated with Falchion did rise to the character of an atmospheric river in spite of the smaller scale.

We present a data-centric deep learning (DL) approach using neural networks (NNs) to predict the thermodynamics of ternary solid solutions. We explore how NNs can be trained with a dataset of Gibbs free energies computed from a CALPHAD database to predict ternary systems as a function of composition and temperature. We have chosen the energetics of the FCC solid solution phase in 226 binaries consisting of 23 elements at 11 different temperatures to demonstrate the feasibility. The number of binary data points included in the present study is 102,000. We select six ternaries to augment the binary dataset to investigate their influence on the NN prediction accuracy. We examine the sensitivity of data sampling on the prediction accuracy of NNs over selected ternary systems. It is anticipated that the current DL workflow can be further elevated by integrating advanced descriptors beyond the elemental composition and more curated training datasets to improve prediction accuracy and applicability.

Few risk factors have been identified for nonsyndromic anotia/microtia (A/M).We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression.We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with less than high school education (PR: 1.3, 95% CI: 1.1-1.5), diabetes (PR: 2.0, 95% CI: 1.6-2.4), or age 30-39 versus 20-29 years (PR: 1.2, 95% CI: 1.0-1.3). The prevalence was decreased among offspring of non-Hispanic Black versus White women (PR: 0.6, 95% CI: 0.4-0.8) but increased among offspring of Hispanic women (PR: 2.9, 95% CI: 2.5-3.4) and non-Hispanic women of other races (PR: 1.7, 95% CI: 1.3-2.3). We observed similar results among cases with isolated and unilateral A/M. Sex disparities were not evident for nonisolated or bilateral phenotypes, nor did birth prevalence differ between offspring of non-Hispanic Black and non-Hispanic White women. Maternal diabetes was more strongly associated with nonisolated (PR: 4.5, 95% CI: 3.2-6.4) and bilateral A/M (PR: 5.0, 95% CI: 3.3-7.7). Crude prevalence rates increased throughout the study period (annual percent change: 1.82).We identified differences in the prevalence of nonsyndromic A/M by maternal race/ethnicity, education, and age, which may be indicators of unidentified social/environmental risk factors.

There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on "CHD-lymphoma" associations.From3 million live births (1988-2004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD-lymphoma through the California BioBank. We performed case-control epigenome-wide association analyses (EWAS) using two comparison groups with reciprocal discovery and validation to identify differential methylation associated with CHD-lymphoma.After correction for multiple testing at the discovery and validation stages, individuals with CHD-lymphoma had differential newborn methylation at six sites relative to two comparison groups. Our top finding was significant in both EWAS and indicates PPFIA1 cg25574765 was hypomethylated among individuals with CHD-lymphoma (mean beta = 0.04) relative to both unaffected individuals (mean beta = 0.93, p = 1.5 × 10We identified associations between molecular changes present in the genome at birth and risk of childhood lymphoma among those with CHD. Our findings also highlight novel perinatal exposures that may underlie methylation changes in CHD predisposing to lymphoma.

Urinary tract infections (UTIs) are among the most common bacterial infections, representing a massive burden on healthcare systems and accounting for significant morbidity and healthcare expenditure. As bacteria generally cause UTIs, the primary therapy is defined by antibiotics, whose wide use can cause antibiotic resistance. In this scenario, using nutraceuticals to manage UTIs is an attractive alternative. This study aims to test the in vitro efficacy of a new food supplement for treating UTIs containing D-mannose, palmitoylethanolamide, HibCyn® (hibiscus extract), N-acetylcysteine and microencapsulated Lactobacillus rhamnosus LR04. The activity of the product was evaluated in terms of antimicrobial, antibiofilm, cytotoxic, antiinflammatory, and synergic activity with fosfomycin with respect to the main microorganisms responsible for UTIs, specifically Klebsiella pneumoniae, Enterococcus faecium, and Escherichia coli. “UTIVAL” food supplement has an action on both the inhibition and eradication of the biofilms formed by all the microorganisms. In the in vitro tests performed in this study, the activity of the product was effective at a concentration of 0.78 g/l. It was also possible to affirm that the product has an inhibiting effect on inflammation mediated by tumor necrosis factor αlfa (TNFα) in a concentration range of 0.04 to 0.625 mg/ml.

Massima Nel giudizio per la dichiarazione di nullità di un vincolo di destinazione ex art. 2645-ter cod. civ. la beneficiaria vitalizia del vincolo è legittimata passiva. È nullo il vincolo di destinazione ex art. 2645-ter cod. civ. istituito al fine di conservare e incrementare il valore dei beni che sono oggetto e assicurare il godimento dei redditi e del capitale al costituente e a sua moglie vita natural durante e, successivamente alla loro morte, ai loro discendenti, in quanto un simile vincolo – insistente sulla totalità del patrimonio immobiliare del costituente – realizza soltanto una segregazione patrimoniale in danno dei creditori, garantendo al costituente stesso la gestione unica del patrimonio vincolato.

Precipitation is a particularly important part of the Earth’s hydrological cycle and, therefore, is a necessary variable for maintaining natural balance. This study investigated past, present, and future changes in precipitation in the Marmara region, and examined the effects of global warming on this variable. The study period was from 1960 to 2020, and the climate data of 15 synoptic stations in the Marmara region were used for this purpose. To achieve the objectives of the study, linear and 6th order polynomial regression, ombrothermic and hythergraph diagrams, geostatistical models, Mann-Kendall test, Pearson correlation, standard Z-scores, and multi-layer perceptron artificial neural network models (MLP-ANN) were used to model and predict precipitation. The results of the linear regression analysis showed that of the 15 stations, 6 stations had an increasing trend, 6 stations had a trendless pattern, and 3 stations had a decreasing trend. In terms of periodic analysis, the main downward trend started in 1964 and continued until 1992, while the main periodic upward trend started in 1992 and continued until 2016. The synoptic stations in the Marmara region showed a lack of precipitation over six to seven months of the year, and the precipitation changes in the region were stronger than the temperature changes. In addition, the highest precipitation was observed on the southeast coast of the Black Sea, and the lowest precipitation was observed in the eastern parts of the region. Moreover, except for the Bilecik and Kocaeli stations, the changes in the long-term trend of precipitation at the other stations were significant. Among the 15 stations, only the Kocaeli and Sarıyer stations showed a positive correlation with global temperature during the annual period. In addition, the developed ANN model was accurate in simulating and predicting precipitation and showed an upward trend over the next seven years.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination.

Zinc clays are commonly found in oxidized Zn deposits and, even though they rarely represent the main target of the ore exploitation, they can be used as a proxy to restore the genetic conditions during ore-forming processes. This work sheds light on the micro- to nano-mineralogy and on the genesis of Zn-clays in the Kihabe and Nxuu prospects (located in the Aha Hills district, Northern Botswana), through an integrated XRD and TEM study of the mineralized facies occurring in the ore system. The Kihabe and Nxuu ores are hosted in a Neoproterozoic metamorphozed quartzwacke unconformably covered by the recent sedimentary rocks, also containing calcretes, of the Kalahari Group. In the analyzed samples, four distinct mineralogical facies have been recognized: (1) vanadate-calcrete facies, poor of Zn-clays; (2) low Zn-clay facies, characterized mostly by clays showing low Zn concentrations; (3) Zn-clay facies, containing proper Zn clay minerals; and (4) sulfide facies, devoid of Zn-clays. In all the facies detrital dioctahedral mica (muscovite and illite) is interstratified with smectite in the form of random (R0) to short-range ordered (R1) I/S, which locally shows significant Zn concentrations. In the sulfide facies kaolinite overgrowing onto mica packets has been detected. The low Zn-clay facies is dominated by Zn-bearing beidellite, with minor kaolinite and fraipontite. The Zn-clay facies consists mostly of a random (R0) interstratified clay between a 7 Å phase corresponding to fraipontite, and a 2:1 swelling clay component identifiable with the dioctahedral smectite, with minor sauconite. The micro- to nano-scale paragenetic study performed by TEM indicates that the above-mentioned clays formed through a multistage process, eventually ending with the genesis of Zn-bearing phyllosilicates assemblages. The main steps were: (1) alteration of detrital mica and dissolution of feldspar clasts, which led to the formation of epitaxial kaolinite and replacive beidellite; (2) fertilization of barren clays and formation of replacive to epitaxial fraipontite/smectite and of Zn-bearing mica, through input of Zn2+ deriving from sphalerite or willemite dissolution by mixed meteoric-hydrothermal fluids; (3) formation of low tetrahedral charge sauconite, either in pores or as replacement of K-feldspars under surficial hypersaline conditions, possibly also linked to the establishment of the arid climate in region. These processes provide insights into genesis of Zn-Pb-V ore deposits in northwest Botswana. Furthermore, the identification of a Zn-smectite species having a stevensite-like stoichiometry is valuable for future studies dealing with the systematics of clay minerals.

While rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents, past epidemiology studies of this malignancy used data that covered30% of the US population. Therefore, we evaluated RMS incidence using data from U.S. Cancer Statistics (USCS) and survival trends using the National Program of Cancer Registries (NPCR), which covers 100% and 94% of the U.S. population, respectively.Incidence and survival were assessed for pediatric patients diagnosed with RMS during 2003-2017 and 2001-2016, respectively. Both demographic and clinical variables were evaluated. Age-adjusted incidence rates, average annual percent change (AAPC), and 5-year relative survival (RS) were calculated, all with corresponding 95% confidence intervals (CIs). Cox regression models were used to evaluate the impact of demographic and clinical variables on survival.We identified 5656 primary RMS cases in USCS during 2003-2017. The age-adjusted incidence rate was 4.58 per 1 million (95% CI: 4.46-4.70) with an AAPC of 0.3% (95% CI: -0.7 to 1.2%). In NPCR, 5-year RS for all cases was 68.0% (95% CI: 66.6-69.3%). In multivariable analyses, non-Hispanic (NH) Black cases had worse survival compared with NH White cases (hazard ratio [HR] = 1.16, 95% CI: 1.01-1.33).The incidence and survival rates were stable in the largest and most comprehensive population-based analysis for pediatric RMS cases in the U.S. Additionally, we observed a survival disparity among NH Black cases. Findings from this study could inform interventions to address disparities, risk stratification strategies, and clinical trial design.

Targeted therapy in lung cancer requires the assessment of multiple oncogenic driver alterations, including fusion genes. This retrospective study evaluated the Idylla GeneFusion prototype, an automated and ease-of-use (