Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique

To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients

Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors

In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling

Targeted therapy in severe asthma today: Focus on immunoglobulin E

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard â\u80\u9cone size fits allâ\u80\u9d approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes cur­rent knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma

Once-Weekly Subcutaneous Semaglutide Improves Fatty Liver Disease in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study

Background. Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with type 2 diabetes (T2D). Semaglutide, a glucagon-like peptide 1 receptor agonist, may have a therapeutic role by targeting common mechanisms involved in the pathophysiology of T2D and NAFLD. The study aimed to assess the effectiveness of Semaglutide on NAFLD in patients with T2D. Methods. Forty-eight patients were treated with subcutaneous Semaglutide in add-on to metformin for 52 weeks. After the baseline visit (T0), follow-up was scheduled quarterly (T3, and T6) and then at 12 months of therapy (T12). During each visit, body composition was analyzed by phase-sensitive bio-impedance, and NAFLD was diagnosed and staged by Ultrasound (US) imaging. Surrogate biomarkers of NAFLD were also calculated and followed over time. Results. A significant decrease in anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and laboratory indices of hepatic steatosis was observed during treatment. Similarly, fat mass and visceral adipose tissue (VAT) decreased over time more than skeletal muscle and free-fat mass. US-assessed VAT thickness and the 12-point steatosis score also declined at T3 up to T12. Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging. Conclusion. Besides glucose control and body composition improvements, Semaglutide was effective in ameliorating the clinical appearance and severity of NAFLD in T2D patients

Light and shadows of a new technique: Isphoton total-skin irradiation using helical IMRT feasible, less complex and as toxic as the electrons one?

BACKGROUND: Radiotherapy is one of the standard treatments for cutaneous lymphoma and Total Skin Electrons Beam Irradiation (TSEBI) is generally used to treat diffuse cutaneous lymphoma and some cases of localized disease. Helical IMRT (HI) allows to treat complex target with optimal dose distribution and organ at risk sparing, so helical tomotherapy has been proposed as alternative technique to TSEBI but only one preliminary report has been published. METHODS: Three patients treated (from May 2013 to December 2014) with Helical IMRT, with a total dose between 24 and 30 Gy, were retrospectively evaluated. Data about dosimetric features, response and acute toxicity were registered and analyzed. Planned target coverage was compared with daily in vivo measures and dose calculation based on volumetric images used for set up evaluation as well. RESULTS: The patients had a mean measured surface fraction dose ranging from 1.54 Gy up to 2.0 Gy. A planned target dose ranging from 85 to 120% of prescription doses was obtained. All doses to Organs At Risk were within the required constraints. Particular attention was posed on "whole bone marrow" planned V10Gy, V12Gy and V20Gy values, ranging respectively between 23 and 43%, 20.1 and 38% and 9.8 and 24%. A comparison with the theoretical homologous values obtained with TSEBI has shown much lower values with TSEBI. Even if treatment was given in sequence to the skin of the upper and lower hemi-body, all the patients had anaemia, requiring blood transfusions, leukopenia and thrombocytopenia. CONCLUSION: Based on our limited results TSEBI should still be considered the standard method to treat total skin because of its pattern of acute and late toxicities and the dose distribution. In this particular case the better target coverage obtained with HI can be paid in terms of worse toxicity. Helical IMRT can instead be considered optimal in treating large, convex, cutaneous areas where it is difficult to use multiple electrons fields in relation with the clinical results and the limited and reversible toxicities

Italian Guidelines For The Management Of Non-Functioning Benign And Locally Symptomatic Thyroid Nodules

Aim: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. Methods: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology(AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. Results: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. Conclusion: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated

Characterization of the nuclei identification performances of the plastic scintillator detector prototype for the future HERD satellite experiment

Satellite experiments employ plastic scintillators to discriminate charged from neutral particles and to identify charged nuclei. We have assembled and tested a prototype of Plastic Scintillator Detector (PSD) equipped with Silicon Photomultipliers (SiPMs) for the High Energy Cosmic Radiation Detection facility (HERD) that will be installed onboard the future Chinese Space Station (CSS). The HERD experiment will provide high quality data on charged cosmic rays up to PeV energies and gamma rays above 100 MeV energies. In order to explore the capability of charge identification of nuclei up to iron, a beam test campaign was performed in 2022 at CERN to study the overall performance of the PSD. The PSD prototype is composed of 8 plastic scintillator trapezoidal bars of two different lengths. The PSD prototype was irradiated with an ion beam composed of particles of selected momentum of 150 GeV/n at CERN SPS H8 beam line. Along the beam line two 10x10x0.5 cm3 squared plastic scintillator tiles were also placed to monitor the beam composition and the particle fragmentation upstream and downstream the beam line. In this work the main results of the SPS H8 beam test in terms of nuclei identification performances of the PSD ptototype detector will be shown

Voce: Prelievi e analisi di campioni

Con la legge 30.6.2009 n. 85 l'Italia ha ratificato l'adesione al Trattato di Pr\ufcm, in vista del rafforzamento della cooperazione tra Stati nella lotta al terrorismo, alla criminalit\ue0 transfrontaliera e alla migrazione illegale, tramite lo scambio di informazioni genetiche. La novit\ue0 pi\uf9 saliente che l'adesione al Trattato ha importato nell'ordinamento interno concerne l'introduzione di un'inedita disciplina dei prelievi coattivi di materiale biologico, volta alla tutela dei diritti individuali nell'impiego processuale di strumenti tecnico-scientifici che consentano di non disperdere il materiale probatorio relativo ad un fatto criminoso. Il tema rievoca la tradizionale distinzione che attribuisce all'imputato la duplice funzione di \u201corgano\u201d ed \u201coggetto\u201d nella formazione della prova, a seconda del contributo attivo o passivo che lo stesso apporti alla vicenda processuale. Questi \ue8 considerato \u201corgano\u201d di prova nell'espletamento di attivit\ue0 che costituiscono esercizio del diritto di difesa, nelle due componenti, positiva e negativa, del diritto di difendersi provando e del diritto al silenzio. Viceversa, si parla di imputato come \u201coggetto\u201d di prova allorquando gli sia richiesto un mero pati rispetto all'attivit\ue0 di istruzione probatoria, come accade nelle ispezioni, nelle perquisizioni, nelle ricognizioni personali, nonch\ue9, pi\uf9 in generale, negli accertamenti che si espletano sul corpo del giudicabile, il quale viene in rilievo non come parte processuale, ma come mera entit\ue0 fisica. Il regime di nuovo conio \ue8 intervenuto a colmare la lacuna normativa lasciata dalla sentenza n. 238 del 1996 con cui la Corte costituzionale aveva dichiarato l'illegittimit\ue0 dell'art. 224, comma 2, c.p.p. nella parte in cui consentiva interventi peritali sul corpo della persona, in violazione del principio di riserva di legge che presidia, ex art. 13 Cost., la libert\ue0 personale. La pronuncia ha individuato un \u201cnocciolo duro\u201d rappresentato dalla libert\ue0 corporale, indissolubilmente legata ai principi di libert\ue0 morale, integrit\ue0 psico-fisica e salute della persona, non comprimibili a fini processuali. La Carta fondamentale prevede un'unica ipotesi di lesione del diritto alla salute nell'ambito dei trattamenti sanitari obbligatori, per finalit\ue0 estranee all'accertamento penale; la libert\ue0 morale, peraltro, rappresenta il quid pluris che sopravvive alla compressione del potere statale, persino durante la pi\uf9 intensa restrizione della libert\ue0 personale. Se questo \ue8 il quadro costituzionale di riferimento, \ue8 evidente come il previgente regime in materia di prelievi biologici coattivi abbia disatteso le indicazioni provenienti dalla Consulta. Difatti, a distanza di quasi un decennio dal monito del Giudice delle leggi, il legislatore intervenne (con la legge 31 luglio 2005, n. 155) \uabin un modo persino pi\uf9 imbarazzante dell'inerzia sino ad allora mantenuta\ubb, attribuendo un potere di intrusione corporale (attraverso il prelievo di capelli o saliva nel corso delle indagini) alla polizia giudiziaria, previa autorizzazione - anche orale, purch\ue9 confermata per iscritto - del pubblico ministero, a soli fini identificativi e purch\ue9 sussistesse il pericolo di alterazione o dispersione della res. Non era contemplato il potere giudiziale di disporre un prelievo biologico a fini peritali e l\u2019esclusivo orientamento teleologico dell\u2019atto d\u2019indagine ne limitava fortemente l\u2019utilit\ue0. Veniva, pertanto, inopinatamente elusa la doppia riserva, di legge e di giurisdizione, che presidia la materia. La riforma realizza una netta soluzione di continuit\ue0 rispetto alla normativa precedente, attraverso l'individuazione nell'organo giurisdizionale del baricentro del micro-sistema normativo dedicato ai prelievi biologici coattivi. Se la libert\ue0 personale pu\uf2 subire restrizioni per atto motivato dell'autorit\ue0 giudiziaria, pertanto anche del pubblico ministero, l'intrusione nella sfera corporale esige l'egida di un soggetto super partes, indifferente rispetto all'esito del processo. Il legislatore ha costruito una disciplina minuziosa, concernente sia l'an che il quomodo dei prelievi, in ossequio alla riserva di legge dettagliata (nei \u201cmodi\u201d e nei \u201ccasi\u201d) imposta dalla Consulta. Ne \ue8 derivato un apparato \uabmulti-livello\ubb, calibrato sulla sistematica del codice e diversificato in base all'orientamento teleologico dell'accertamento \u2013istituzionale, probatorio, investigativo o identificativo-, in cui ogni tipologia \ue8 rigidamente separata dalle altre