The evolution of the general criteria for the attribution of the legal capacity

The aim of this contribution is to make a brief exam, starting from the Roman legal system, of the criteria adopted to determine the achievement of puberty by the child, which involves the acquisition of the legal capacity in order to validly enter into legal agreements. The reflection, from a critical point of view, focuses on the analysis of the relationship between physical maturity, ascertained therefore with external criteria, and psychological, which is necessary to give the person that awareness that, to date, is regulated and indicated by art. 2 c.c. as "the ability to perform all acts". How is it established what is the right age for a minor to be considered an adult and therefore able to make legally binding choices? From the point of view of the typical approach of the Roman legal system, it is necessary to premise how, regarding a given problematic case, it is always solved, starting from a 'remedial' perspective rather than a defining one: consequently, also concerning the protection of minors, the sources that testify the situation in which the impuber found themselves are concentrated on the actions granted in defence of the latter, more than anything else. In the Roman legal system, therefore, there was no psychological parameter capable of disproving the passage from impubescence to puberty: it turned out to be a mere physical process whereby, when the full sexual maturity was reached, the full legal capacity was also considered automatically reached. The term impuber, therefore, identifies the person that, nowadays, we would call incapable; although the Romans did not leave us a true definition of 'legal capacity' and, therefore, on the contrary, of 'incapacity' in a modern sense, they conceptually distinguished between a legal capacity and a legal personhood. In fact, especially in the classical and postclassical era, legal agreements entered by persons who had not reached a certain age were automatically recognized as invalid, unless they were ratified by the legal guardian with the interposition of the appropriate auctoritas. A further element that must necessarily be taken into consideration in order to understand the evolutionary process concerning the protection of minors in the Roman system is the recognition of protection granted to persons under the age of twenty-five. After the age of puberty, the only obstacle to the child's ability to implement legally binding agreements was represented by inexperience. Having clarified what was the situation in ancient Rome, we can, in broad terms, see how in the Middle Age the term of the impubescent age and the criterion with which it was defined as such changed from the previous era, especially depending on the areas of reference. The passing, therefore, of the medieval age was a sort of connection between the result that the Romans had arrived at in terms of their legal capacity and what would later be provided for in the subsequent codifications. We see how in this period there is a 'maintain' of what was achieved by the Roman legal system without, however, further steps forward towards the criterion of attribution of the ability to act. There remains a formal criterion that guarantees, in essence, a decreasing protection as age grows. It seems to me then possible to notice how a fixed parameter taken as a basis for considering a young person capable of legally binding choices or not was in a certain sense arbitrary and how this methodology has remained unchanged over the centuries. A fact that now seems certain is that the concept of the legal capacity evolves as the legal thought goes on and is susceptible to interpretations and application methods that adapt it to the most diverse needs. The idea behind the concept of the legal capacity also concerns the parameter of relativity: it varies both according to the type of agreement to be performed and according to the age or legal situation of a given subject. The legal capacity, as mentioned above, relates to the possibility to enter into legally valid agreements, letting the legal system protect the choices made by an individual. Drawing on the brief considerations made so far, the question that arises most spontaneously concerns the assessment of the criterion used to give the full legal capacity: is the completion of a certain age really enough for a young person to be able to fully understand the acts that he implements? Would it not be fairer to ascertain the 'maturity' of the individual more substantially and not only formally?Il contributo effettua una breve ricognizione, dall’ordinamento romano, dei criteri adottati per determinare il conseguimento della pubertà da parte del minore. La riflessione, in un’ottica critica, si focalizza sull’analisi del rapporto tra maturità fisica, accertata quindi con criteri esteriori, e psicologica, necessaria a conferire al soggetto quella consapevolezza che, ad oggi, viene disciplinata ed indicata come «la capacità di compiere tutti gli atti». Come si stabilisce qual è l’età più giusta affinché un minore si possa considerare capace di fare scelte giuridicamente vincolanti

Breakage mechanisms of highly porous particles in 1D compression revealed with x-ray tomography

Grain breakage affects a number of geotechnical engineering problems. In this work, breakage of an artificial, porous granular material (Lightweight expanded clay aggregate) has been studied in 1D compression with both standard laboratory techniques and in situ x-ray tomography during loading. X-ray tomography has revealed that there is a wide distribution of internal porosity among LECA particles, and particle tracking has been used, for the first time, to give an objective measurement of each particle’s life expectancy. Links between micro and macro-scale quantities are discussed

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19

Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-β, IL-2 and IL-10, β-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-β, IL-2, IL-6, IL-8) compared to controls; this increase could generate a sort of "protection of the fetus" from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother's body is responding to the viral attack. These results allow us to hypothesize a mechanism of "trafficking" of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress

Management of Low Rectal Cancer Complicating Ulcerative Colitis: Proposal of a Treatment Algorithm

Simple SummaryThis article expresses the viewpoint of the authors' management of low rectal cancer in ulcerative colitis (UC). This subject suffers from a paucity of literature and therefore management decision is very difficult to take. The aim of this paper is to provide a structured approach to a challenging situation. It is subdivided into two parts: a first part where the existing literature is reviewed critically, and a second part in which, on the basis of the literature review and their extensive clinical experience, a management algorithm is proposed by the authors to offer guidance to surgical and oncological practices. This text adds to the literature a useful guide for the treatment of these complex clinical scenarios.Low rectal Carcinoma arising at the background of Ulcerative Colitis poses significant management challenges to the clinicians. The complex decision-making requires discussion at the multidisciplinary team meeting. The published literature is scarce, and there are significant variations in the management of such patients. We reviewed treatment protocols and operative strategies; with the aim of providing a practical framework for the management of low rectal cancer complicating UC. A practical treatment algorithm is proposed

Basal cytokines profile in metastatic renal cell carcinoma patients treated with subcutaneous IL-2-based therapy compared with that of healthy donors

<p>Abstract</p> <p>Background and purpose</p> <p>Metastatic renal cell carcinoma (MRCC) has a poor prognosis with a median overall survival of about one year. Since only a minority of patients experienced therapeutic benefit to current treatments, several studies have attempted to identify factors that may have an impact on response and survival. Cytokines play a crucial role in the host's immune response by regulating the development and function of a lot of biological compartments. Nevertheless, available data on basal cytokine levels in MRCC are very few and no clear profile of serum cytokines has been identified yet in these patients population. Thus, determining the levels of cytokines in MRCC could not only help in understanding the biological mechanisms of the tumor growth, but also in evaluating if different cytokine profiles are correlated with particular clinical behaviors.</p> <p>Materials and methods</p> <p>In 144 healthy donors and 55 MRCC treated with subcutaneous IL-2-based regimens, we analysed a panel of basal cytokines particularly involved in the neoplastic progression (IL-1beta, IL-6, IL-8, IL-10, IL-12, alpha-TNF) and C-reactive protein (CRP) in order to compare their levels in the two groups, and to verify their impact on patient response and survival.</p> <p>We first compared cytokines levels in patients population and healthy donors. Than, in definite patients group, univariate and multivariate analyses were performed to evaluate the correlation existing between each factor considered and clinical outcomes. For these analyses, baseline values were included as dichotomous variables using the median values (above and below) of control group.</p> <p>Results</p> <p>In general, higher levels of cytokines were found in patients with respect to those of healthy donors, both in term of percentage of undetectable levels or median values. The impact on response was insignificant, except for higher levels of CRP that were strongly correlated with a worse response (p < 0.001). Within the patients groups, a worse survival was associated with higher values of CRP (8 vs 31 months, p = 0.0000), IL-6 (9 vs 25 months, p = 0.0295), and IL-8 (9 vs 17 months, p = 0.0371). Conversely, higher levels of IL-12 were associated with a better survival (25 vs 15 months, months p = 0.0882). A correlation was found between CRP and IL-6 (p = 0.009) and between CRP and IL-10 (p = 0.038). After multivariate analysis only CRP (p = 0.0035) and IL-12 (p = 0.0371) maintained an independent impact on survival, while IL-6 showed a borderline value (p = 0.0792).</p> <p>Conclusion</p> <p>Higher cytokines levels characterize patients population with respect to healthy donors. Moreover, higher basal level of some immunosuppressive cytokines (CRP, IL-6, IL-8) result correlated with a poorer survival, whereas higher levels of IL-12, a cytokine with a potent antineoplastic activity, was associated with a better survival. A wider sample of patients is needed to better clarify if our findings are intrinsically related to patients population or if they are simply an epiphenomenon of disease progression.</p

Artificial Intelligence-suggested Predictive Model of Survival in Patients Treated With Stereotactic Radiotherapy for Early Lung Cancer

Background/aim: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting. Patients and methods: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts. Results: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2. Conclusion: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively

EP1 receptor within the ventrolateral periaqueductal grey controls thermonociception and rostral ventromedial medulla cell activity in healthy and neuropathic rat

The aim of this study was to investigate the expression of prostaglandin EP1 receptor within the ventrolateral periaqueductal grey (VL PAG). The role of VL PAG EP1 receptor in controlling thermonociception and rostral ventromedial medulla (RVM) activity in healthy and neuropathic rats was also examined. EP1 receptor was indeed found to be expressed within the VL PAG and co-localized with vesicular GABA transporter. Intra-VL PAG microinjection of ONO-DI-004, a selective EP1 receptor agonist, dose-dependently reduced tail flick latency as well as respectively increasing and decreasing the spontaneous activity of ON and OFF cells. Furthermore, it increased the ON cell burst and OFF cell pause. Intra-VL PAG prostaglandin E2 (PGE2) behaved similarly to ONO-DI-004. The effects of ONO-DI-004 and PGE2 were antagonized by intra-VL PAG L335677, a selective EP1 receptor antagonist. L335677 dose-dependently increased the tail flick latency and ongoing activity of the OFF cells, while reducing the ongoing ON cell activity. It also decreased the ON cell burst and OFF cell pause. In neuropathic rats using spare nerve injury (SNI) of the sciatic nerve model, EP1 receptor expression decreased in the VL PAG. However, ONO-DI-004 and L335677 were able to alter pain responses and ON and OFF cell activity, as they did in healthy animals. Collectively, these data show that within the VL PAG, EP1 receptor has a facilitatory effect on the nociceptive response and consistently affects RVM neuron activity. Thus, the blockade of EP1 receptor in the VL PAG leads to antinociception in neuropathic pain conditions, despite its down-regulation. The expression of EP1 receptor on GABAergic neurons is consistent with an EP1 receptor blockade-induced disinhibition of the antinociceptive descending pathway at VL PAG level

Smad7 Sustains Stat3 Expression and Signaling in Colon Cancer Cells

: Colorectal cancer (CRC) cells contain elevated levels of active signal transducer and the activator of transcription (Stat)-3, which exerts proliferative and anti-apoptotic effects. Various molecules produced in the CRC tissue can activate Stat3, but the mechanisms that amplify such an activation are yet to be determined. In this paper, we assessed whether Smad7, an inhibitor of Transforiming Growth Factor (TGF)-β1 activity, sustains Stat3 expression/activation in CRC cells. Both Smad7 and phosphorylated (p)/activated-Stat3 were more expressed in the tumoral areas of CRC patients, compared to the normal adjacent colonic mucosa of the same patients, and were co-localized in primary CRC cells and CRC cell lines. The knockdown of Smad7 with a Smad7 antisense oligonucleotide (AS) reduced p-Stat3 in both unstimulated and interleukin (IL)-6- and IL-22-stimulated DLD-1 and HCT116 cells. Consistently, reduced levels of BCL-xL and survivin, two downstream signaling targets of Stat3 activation, were seen in Smad7 AS-treated cells. An analysis of the mechanisms underlying Smad7 AS-induced Stat3 inactivation revealed that Smad7 AS reduced Stat3 RNA and protein expression. A chromatin immunoprecipitation assay showed the direct regulatory effect of Smad7 on the Stat3 promoter. RNA-sequencing data from the Tumor, Normal and Metastatic (TNM) plot database showed a positive correlation between Smad7 and Stat3 in 1450 CRC samples. To our knowledge, this is the first evidence supporting the theory that Smad7 positively regulates Stat3 function in CRC

Some Notes on Granular Mixtures with Finite, Discrete Fractal Distribution

Why fractal distribution is so frequent? It is true that fractal dimension is always less than 3? Why fractal dimension of 2.5 to 2.9 seems to be steady-state or stable? Why the fractal distributions are the limit distributions of the degradation path? Is there an ultimate distribution? It is shown that the finite fractal grain size distributions occurring in the nature are identical to the optimal grading curves of the grading entropy theory and, the fractal dimension n varies between-¥ and ¥. It is shown that the fractal dimensions 2.2-2.9 may be situated in the transitional stability zone, verifying the internal stability criterion of the grading entropy theory. Micro computed tomography (μCT) images and DEM (distinct element method) studies are presented to show the link between stable microstructure and internal stability. On the other hand, it is shown that the optimal grading curves are mean position grading curves that can be used to represent all possible grading curves