Il giudizio a cognizione piena innanzi al tribunale

L’Autrice offre una panoramica delle principali novità introdotte dal d.lgs n. 149/2022 con riferimento al giudizio a cognizione piena innanzi al tribunale, fortemente modificato rispetto alla struttura della fase introduttiva e, di conseguenza, di quelle successive, non mancando di evidenziare – purancora senza il confronto della prassi – una certa sfiducia nelle soluzioni prescelte in termini di semplificazione e riduzione dei tempi per l’accertamento

Effect of a novel nutraceutical combination on serum lipoprotein functional profile and circulating PCSK9

BACKGROUND: A beneficial effect on cardiovascular risk may be obtained by improving lipid-related serum lipoprotein functions such as high-density lipoproteins (HDLs) cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) and by reducing proprotein convertase subtilisin kexin type 9 (PCSK9), independently of lipoprotein concentrations. AIM: We aimed to evaluate the effect of an innovative nutraceutical (NUT) combination containing red yeast rice (monacolin K 3.3 mg), berberine 531.25 mg and leaf extract of Morus alba 200 mg (LopiGLIK®), on HDL-CEC, serum CLC and on circulating PCSK9 levels. MATERIALS AND METHODS: Twenty three dyslipidemic subjects were treated for 4 weeks with the above NUT combination. HDL-CEC was measured using specific cell-based radioisotopic assays; serum CLC and PCSK9 concentrations were measured fluorimetrically and by enzyme-linked immunosorbent assay, respectively. RESULTS: The NUT combination significantly reduced plasma level of the total cholesterol and low-density lipoprotein cholesterol (-9.8% and -12.6%, respectively). Despite no changes in HDL-cholesterol, the NUT combination improved total HDL-CEC in 83% of the patients, by an average of 16%, as a consequence of the increase mainly of the ATP-binding cassette A1-mediated CEC (+28.5%). The NUT combination significantly reduced serum CLC (-11.4%) while it did not change PCSK9 plasma levels (312.9±69.4 ng/mL vs 334.8±103.5 mg/L, before and after treatment, respectively). CONCLUSION: The present NUT combination improves the serum lipoprotein functional profile providing complementary beneficial effects, without any detrimental increase of PCSK9 plasma levels

Genotoxicity assessment of piperitenone oxide: an in vitro and in silico evaluation

Piperitenone oxide, a natural flavouring agent also known as rotundifolone, has been studied for the genotoxicity assessment by an integrated in vitro and in silico experimental approach, including the bacterial reverse mutation assay, the micronucleus test, the comet assay and the computational prediction by Toxtree and VEGA tools. Under our experimental conditions, the monoterpene showed to induce both point mutations (i.e. frameshift, base-substitution and/or oxidative damage) and DNA damage (i.e. clastogenic or aneuploidic damage, or single-strand breaks). Computational prediction for piperitenone oxide agreed with the toxicological data, and highlighted the presence of the epoxide function and the α,β-unsaturated carbonyl as possible structural alerts for DNA damage. However, improving the toxicological libraries for natural occurring compounds is required in order to favour the applicability of in silico models to the toxicological predictions. Further in vivo evaluations are strictly needed in order to evaluate the role of the bioavailability of the substance and the metabolic fate on its genotoxicity profile. To the best of our knowledge, these data represent the first evaluation of the genotoxicity for this flavour compound and suggest the need of further studies to assess the safety of piperitenone oxide as either flavour or fragrance chemicals

Multidisciplinary Approaches to the Stimulation of Wound Healing and Use of Dermal Substitutes in Chronic Phlebostatic Ulcers

Research focus: Skin injuries are evolving as an epidemic issue. Chronic skin lesion is a globally widespread disease, often referred to as a “wound difficult to heal” and one which has a strong impact on both overall health and quality of life. Genetic and clinical variables, such as diabetes, smoking and inflammatory/immunological pathologies, are among the important risk factors limiting the regenerative powers of many therapeutic applications. Therefore, optimisation of current clinical strategies is critical. Experimental research: Here we summarise the field’s current state by focusing on the use of stem-cell therapeutic applications in wound healing, placing considerable emphasis on current clinical approaches being developed at Rome’s Sapienza University. These involve protocols for the ex vivo expansion of adipose tissue-derived mesenchyme stem cells using a patented GMP-compliant platelet lysate, Mesengen™, and cellular and acellular dermal substitutes. A combination of multiple strategies, including genetic modifications of stem cells, biomimetic scaffolds or novel vehicles like nanoparticles, is also discussed as future approaches. Case studies: Here we present a report portraying our clinical experience of the treatment of chronic phlebostatic ulcers. The aim of the study reported here was to evaluate the effectiveness of treatment with dermal substitutes of cutaneous lesions originating from chronic venous insufficiency, therapy which took into consideration parameters such as the reduction of wound size and the improvement of quality of life. Chronic skin lesion, a globally widespread disease, is often referred to as a “difficult wound” and has a strong impact on both overall health and quality of life. The difficulties encountered when seeking to heal this ailment have led to a quest for and development of new therapeutic approaches, including dermal substitutes. We can subdivide these into acellular matrices, such as Integra and Hyalomatrix, and cell therapies such as platelet concentrate and mesenchyme cell concentrate. Results: In all the patients treated, elements of improvement were observed: the appearance on the wound bed of small islands of granulation tissue, superficialization of the bottom of the ulcer and a growth of marginal tissue. During the first 30 days, a reduction in more than 25% of the area of the lesion and a reduction in more than 50% at the end of the observation period were recorded in 10 of the patients who underwent preliminary surgical treatment out of the 13 subjects included in the study sample. On the whole, at the end of the observation period, we witnessed an average 57% decrease in the lesion in all the patients; furthermore, during the treatment period, there was a gradual reduction in pain, measured using the NRS numerical scale. An overall average reduction in pain of four points on the NRS numerical scale was achieved. At the end of the 8-week evaluation period, the majority of the patients reported an improvement in the quality of their lives, since, in addition to the reduction of spontaneous pain, there was a diminution of pruritus, secretions—often malodorous and capable of affecting social life negatively—with recovery of functional capacity and almost complete recovery of habitual daily activities. During the period of treatment, no superinfections of the wounds or secondary complications related to the use of the various products were detected. Main conclusions: The numerous technological opportunities provided by regenerative medicine—including advanced dressings and dermal substitutes—if applied correctly, in compliance with a multidisciplinary approach where necessary, seem to offer advantages not only in terms of clinical efficacy and patient life quality but also in terms, it would appear, of healthcare costs, an aspect which should not be either overlooked or underestimated

Multidisciplinary Approaches to the stimulation of Wound Healing and Use of Dermal Substitutes in Chronic Phlebostatic Ulcers

Research focus: Skin injuries are evolving as an epidemic issue. Chronic skin lesion is a globally widespread disease, often referred to as a “wound difficult to heal" and one which has a strong impact on both overall health and quality of life. Genetic and clinical variables, such as diabetes, smoking, and inflammatory/immunological pathologies, are among the important risk factors limiting the regenerative powers of many therapeutic applications. Therefore, optimisation of current clinical strategies is critical. Experimental research: here we summarise the field’s current state by focusing on the use of stem-cell therapeutic applications in wound healing, placing considerable emphasis on current clinical approaches being developed at Rome’s Sapienza University. These involve protocols for the ex-vivo expansion of adipose tissue-derived mesenchyme stem cells using a patented GMP-compliant platelet lysate, Mesengen™, and cellular and a-cellulated dermal substitutes. A combination of multiple strategies, including genetic modifications of stem cells, biomimetic scaffolds, or novel vehicles like nanoparticles, are also discussed as future approaches. Case studies: here we present a report portraying our clinical experience of the treatment of chronic phlebostatic ulcers. The aim of the study reported here was to evaluate the effectiveness of treatment with dermal substitutes of cutaneous lesions originating from chronic venous insufficiency, therapy which took into consideration parameters such as: the reduction of wound size and the improvement of quality of life. Chronic skin lesion, a globally widespread disease, is often referred to as a "difficult wound" and has a strong impact on both overall health and quality of life. The difficulties encountered when seeking to heal this ailment have led to a quest for and development of new therapeutic approaches, including dermal substitutes. We can subdivide these into a-cellular matrices, such as Integra and Hyalomatrix and cell therapies such as Platelet Concentrate and Mesenchyme Cell Concentrate. Results: in all the patients treated, elements of improvement were observed: the appearance on the wound bed of small islands of granulation tissue, superficialization of the bottom of the ulcer and a growth of marginal tissue. During the first 30 days a reduction of more than 25% of the area of the lesion and a reduction of more than 50% at the end of the observation period were recorded in 10 of the patients who underwent preliminary surgical treatment out of the 13 subjects included in the study sample. On the whole, at the end of the observation period we witnessed an average 57% decrease of the lesion in all the patients; furthermore, during the treatment period, there was a gradual reduction of pain, measured using the NRS numerical scale. An overall average reduction in pain of 4 points on the NRS numerical scale was achieved. At the end of the eight-week evaluation period, the majority of the patients reported an improvement in the quality of their lives, since, in addition to the reduction of spontaneous pain, there was a diminution of pruritus, secretions -often malodorous and capable of affecting social life negatively - with recovery of functional capacity and almost complete recovery of habitual daily activities. During the period of treatment, no super-infections of the wounds or secondary complications related to the use of the various products were detected. Main conclusions. The numerous technological opportunities provided by regenerative medicine -including advanced dressings and dermal substitutes- if applied correctly, in compliance with a multidisciplinary approach where necessary, seem to offer advantages in terms of not only of clinical efficacy and patient life-quality but also in terms, it would appear, of health-care costs, an aspect which should not be either overlooked or underestimated

Characterization by length heterogeneity (LH)-PCR of a hydrogen-producing community obtained in dark fermentation using coastal lake sediment as an inoculum

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Nodular cutaneous metastasis of the leg in advanced urothelial bladder carcinoma: a case report and systematic literature review

Cutaneous metastases from urothelial carcinoma (UC) are very rare and indicate advanced disease with a poor prognosis. A 63-year-old female patient with a history of urothelial bladder carcinoma, treated 2 months prior with radical cystectomy and adjuvant gemcitabine and cisplatin (GC) therapy, presented a skin lesion localized in the lower third of the right leg. Punch biopsy revealed carcinomatous metastasis whose urothelial origin was confirmed by immunohistochemical analysis. 18-FDG PET-CT showed the spread of metastases to the lung and left ischium. Our review focuses on the time between surgery and skin metastasis, localization, and prognosis after metastasis diagnosis. In many cases, skin metastases occur within one year of initial UC surgery and in most cases occur on the abdominal wall. Local wide excision of metastasis should be considered in selected cases; however, chemotherapy remains the main treatment

Transcriptional Repressors of Fetal Globin Genes as Novel Therapeutic Targets in Beta-Thalassemia

During development the human β-globin gene cluster undergoes two switching processes at the embryo-fetal and fetal-adult stages, respectively, involving changes in chromatin remodeling and in transcriptional regulatory networks. In particular, during the perinatal period, the switch from fetal-to-adult globin gene expression leads to fetal globin genes silencing and progressive decline of fetal hemoglobin (HbF). Impaired hemoglobin switching is associated with hereditary persistence of HbF (HPFH), a condition in which the fetal globin genes fail to be completely silenced in adult red blood cells. This condition, when co-inherited with hemoglobinopathies, has great therapeutic potential because elevated HbF levels can ameliorate β-thalassemia and sickle cell anemia. Therefore, there is a growing interest about the complex network of factors that regulate fetal globin genes expression. Here we discuss the activity of transcriptional repressors of fetal globin genes and their potential role as novel therapeutic targets in β-thalassemia

The Q-LAMP Method Represents a Valid and Rapid Alternative for the Detection of the BCR-ABL1 Rearrangement in Philadelphia-Positive Leukemias

Molecular detection of the BCR-ABL1 fusion transcripts is necessary for the genetic confirmation of a chronic myeloid leukemia diagnosis and for the risk classification of acute lymphoblastic leukemia. BCR-ABL1 mRNAs are usually identified using a conventional RT-PCR technique according to the BIOMED-1 method. In this study, we evaluated 122 BCR-ABL1-positive samples with the Q-LAMP assay to establish if this technology may represent a valid alternative to the qualitative BIOMED-1 PCR technique usually employed for the detection and the discrimination of the common BCR-ABL1 transcripts (p190 and p210 isoforms). We found a 100% concordance rate between the two methods. Specifically, the p190- and p210-positive samples were amplified by Q-LAMP with a median threshold time (Tt) of 26.70 min (range: 24.45-31.80 min) and 20.26 min (range: 15.25-34.57 min), respectively. A median time of 19.63 was observed in samples displaying both (e13a2/e14a2) p210 isoforms. Moreover, the Q-LAMP assay allowed recognition of the BCR-ABL1 e13a2 and e14a2 isoforms (median Tts 18.48 for e13a2 vs. 26.08 min for e14a2; p < 0.001). Finally, 20 samples harboring rare BCR-ABL1 isoforms (e1a3, e13a3, e14a3, and e19a2) were correctly identified by the Q-LAMP assay. We conclude that the Q-LAMP assay may represent a faster and valid alternative to the qualitative BIOMED-1 RT-PCR for the diagnosis at BCR-ABL1-positive leukemias, especially when samples are analyzed in centers with restricted resources and/or limited technical expertise