Antitumour effects of SFX-01 molecule in combination with ionizing radiation in preclinical and in vivo models of rhabdomyosarcoma.

BACKGROUND: Despite a multimodal approach including surgery, chemo- and radiotherapy, the 5-year event-free survival rate for rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in childhood, remains very poor for metastatic patients, mainly due to the selection and proliferation of tumour cells driving resistance mechanisms. Personalised medicine-based protocols using new drugs or targeted therapies in combination with conventional treatments have the potential to enhance the therapeutic effects, while minimizing damage to healthy tissues in a wide range of human malignancies, with several clinical trials being started. In this study, we analysed, for the first time, the antitumour activity of SFX-01, a complex of synthetic d, l-sulforaphane stabilised in alpha-cyclodextrin (Evgen Pharma plc, UK), used as single agent and in combination with irradiation, in four preclinical models of alveolar and embryonal RMS. Indeed, SFX-01 has shown promise in preclinical studies for its ability to modulate cellular pathways involved in inflammation and oxidative stress that are essential to be controlled in cancer treatment. METHODS: RH30, RH4 (alveolar RMS), RD and JR1 (embryonal RMS) cell lines as well as mouse xenograft models of RMS were used to evaluate the biological and molecular effects induced by SFX-01 treatment. Flow cytometry and the modulation of key markers analysed by q-PCR and Western blot were used to assess cell proliferation, apoptosis, autophagy and production of intracellular reactive oxygen species (ROS) in RMS cells exposed to SFX-01. The ability to migrate and invade was also investigated with specific assays. The possible synergistic effects between SFX-01 and ionising radiation (IR) was studied in both the in vitro and in vivo studies. Student's t-test or two-way ANOVA were used to test the statistical significance of two or more comparisons, respectively. RESULTS: SFX-01 treatment exhibited cytostatic and cytotoxic effects, mediated by G2 cell cycle arrest, apoptosis induction and suppression of autophagy. Moreover, SFX-01 was able to inhibit the formation and the proliferation of 3D tumorspheres as monotherapy and in combination with IR. Finally, SFX-01, when orally administered as single agent, displayed a pattern of efficacy at reducing the growth of tumour masses in RMS xenograft mouse models; when combined with a radiotherapy regime, it was observed to act synergistically, resulting in a more positive outcome than would be expected by adding each exposure alone. CONCLUSIONS: In summary, our results provide evidence for the antitumour properties of SFX-01 in preclinical models of RMS tumours, both as a standalone treatment and in combination with irradiation. These forthcoming findings are crucial for deeper investigations of SFX-01 molecular mechanisms against RMS and for setting up clinical trials in RMS patients in order to use the SFX-01/IR co-treatment as a promising therapeutic approach, particularly in the clinical management of aggressive RMS disease.

Predictive value of perilesional edema volume in melanoma brain metastasis response to stereotactic radiosurgery.

BACKGROUND AND AIM: Stereotactic radiotherapy (SRT) is an established treatment for melanoma brain metastases (MBM). Recent evidence suggests that perilesional edema volume (PEV) might compromise the delivery and efficacy of radiotherapy to treat BM. This study investigated the association between SRT efficacy and PEV extent in MBM. MATERIALS AND METHODS: This retrospective study reviewed medical records from January 2020 to September 2023. Patients with up to 5 measurable MBMs, intracranial disease per RANO/iRANO criteria, and on low-dose corticosteroids were included. MRI scans assessed baseline neuroimaging, with PEV analyzed using 3D Slicer. SRT plans were based on MRI-CT fusion, delivering 18-32.5 Gy in 1-5 fractions. Outcomes included intracranial objective response rate (iORR) and survival measures (L-iPFS and OS). Statistical analysis involved decision tree analysis and multivariable logistic regression, adjusting for clinical and treatment variables. RESULTS: Seventy-two patients with 101 MBM were analyzed, with a mean age of 68.83 years. The iORR was 61.4%, with Complete Response (CR) in 21.8% and Partial Response (PR) in 39.6% of the treated lesions. PEV correlated with KPS, BRAF status, and treatment response. Decision tree analysis identified a PEV cutoff at 0.5 cc, with lower PEVs predicting better responses (AUC = 0.82 sensitivity: 86.7%, specificity:74.4%,). Patients with PEV ≥ 0.5 cc had lower response rates (iORR 44.7% vs. 63.8%, p < 0.001). Median OS was 9.4 months, with L-iPFS of 27 months. PEV significantly impacted survival outcomes. CONCLUSIONS: A more extensive PEV was associated with a less favorable outcome to SRT in MBM.

Prevalence of malocclusion and oral health-related factors among pre-school children in Northern Albania.

The aim of the present study was to investigate prevalence and association between malocclusion and caries among pre-school children aged 4-6 years frequenting public kindergartens in Shkodër, the largest city in North Albania. The sample for this descriptive and cross-sectional study included 389 pre-school children aged 4-6 years frequenting 20 public kindergartens in Shkodër, the largest city in North Albania. The participants were divided into two groups according to their caries experience evaluated, as determined by decayed-missing-filled index dmf (World Health Organization criteria) score. Those with dmf score of zero were considered to be free of caries. The prevalence of children with at least one malocclusion trait was 89%. The prevalence of caries was 66% (mean dmf score: 3.63). Increased overbite (43%), followed by increased overjet, were the most prevalent malocclusion traits observed in children with a dmf of zero. Among children with caries, the most prevalent trait was increased overjet (42%) and increased overbite. Almost half of the entire study population had a straight terminal plane and class I canine relationship. There was a similar prevalence of bilateral crossbite. Significant changes (p = 0.008) were observed between the groups with regards to the absence of spacing in the maxillary anterior region. Regression analysis further revealed that children with an absence of maxillary spacing were 2.564-fold more likely to have caries; those with a deepbite were 0.814-fold more likely to have caries. More than half of the children had caries. Increased overjet, overbite, crossbite and maxillary crowding were malocclusion traits observed in the population included in this study. A positive association was identified between maxillary crowding, deepbite and caries. The association between malocclusion and caries, highlights the necessity for an increased awareness of these two conditions that are commonly found among children of pre-school age.

CT-guided cryoablation for management of bone metastases: a single center experience and review of the literature.

Thermal ablation techniques are procedures of growing interest for management of bone metastases. Among these, cryoablation is probably the most advanced. It allows treatment of large and irregular volumes of pathological tissue, real-time evaluation of the area of ablation and appears less painful than heat-based ablative techniques like radiofrequency and microwaves. Literature shows the effectiveness of cryoablation in the management of bone metastases in terms of pain palliation, but also its employment with curative intent is recommended. We reviewed the outcomes of cryoablation procedures performed in our radiology department over the last seven years, confirming the results in terms of pain palliation and local control of disease. We retrospectively evaluated results of 28 procedures of cryoablation, of which 17 treated with palliative and 11 with curative intent. In a 3-month follow-up study, we recorded an overall reduction of pain (evaluated using a VAS 0-10 scale) between pre- and post-treatment. The mean values dropped from 6.9 (SD: ± 1.3) to 3.5 (SD ± 2.6) (p < 0.0001). In the group of patients treated for local tumor control (follow-up: 22.4 months), we recorded a stability and/or reduction in volume of the lesion in 10 out 11 patients. No major complications were recorded.

MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant. HDAC inhibitors (HDACi) radio-sensitize different cancer cells types. Thus, we evaluated MS-275 (Entinostat), a Class I and IV HDACi, in combination with RT on RMS cells in vitro and in vivo. MS-275 reversibly hampered cell survival in vitro in FN-RMS RD (RASmut) and irreversibly in FP-RMS RH30 cell lines down-regulating cyclin A, B, and D1, up-regulating p21 and p27 and reducing ERKs activity, and c-Myc expression in RD and PI3K/Akt/mTOR activity and N-Myc expression in RH30 cells. Further, MS-275 and RT combination reduced colony formation ability of RH30 cells. In both cell lines, co-treatment increased DNA damage repair inhibition and reactive oxygen species formation, down-regulated NRF2, SOD, CAT and GPx4 anti-oxidant genes and improved RT ability to induce G2 growth arrest. MS-275 inhibited in vivo growth of RH30 cells and completely prevented the growth of RT-unresponsive RH30 xenografts when combined with radiation. Thus, MS-275 could be considered as a radio-sensitizing agent for the treatment of intrinsically radio-resistant PAX3-FOXO1 RMS.

Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms.

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 µM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

Skeletal and dental changes after maxillary expansion with a bone-borne appliance in young and late adolescent patients.

INTRODUCTION: Rapid palatal expansion is a common therapy during orthodontic treatment and could be a preliminary step for correcting different malocclusions; furthermore, this treatment could be necessary at any age. Different anchorage approaches have been proposed to obtain an effective skeletal result, although every device produces both dental and skeletal effects. This study aimed to compare the dentoskeletal effects of a bone-borne palatal expander considering 2 groups of patients of different ages. METHODS: Twenty-four patients consecutively treated were included in the study; patients were divided into 2 groups according to their age: group 1 with age ≤16 years and group 2 patients >16 years. All patients had a preexpansion cone-beam computed tomography scan; a second scan was required at the end of activations. All patients received a bone-borne appliance anchored on 4 miniscrews. RESULTS: Significant intragroup differences were found for maxillary width and dental diameters. No significant differences were found between groups with regard to longitudinal changes, except for the maxillary right plane. CONCLUSIONS: The use of bone-borne maxillary expansion was effective in generating palatal widening both in growing and young adult patients. No significant skeletal or dental differences were found between groups.

The obesity paradox and diabetes.

BACKGROUND: Obesity has been proven to be a risk factor for type 2 diabetes mellitus (T2DM) through numerous pathogenetic mechanisms. Unexpectedly, some studies suggest that subjects with overweight/obesity and T2DM have better clinical outcome than their normal weight peers. This finding is described as "obesity paradox" and calls into question the importance of weight loss in this specific population. OBJECTIVE: This article is a narrative overview on the obesity and type 2 diabetes mellitus, particularly regarding the obesity paradox in T2DM patients. METHODS: We used as sources MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library, from inception to March 2020; we chose 30 relevant papers regarding the association of obesity with clinical outcome and mortality of patients affected by T2DM. RESULTS: Many studies report that in patients with T2DM, overweight and obesity are associated with a better prognosis than underweight or normal weight, suggesting the presence of an obesity paradox. However, these studies have numerous limitations due to their mainly retrospective nature and to numerous confounding factors, such as associated pathologies, antidiabetic treatments, smoking habit, lack of data about distribution of body fat or weight history. CONCLUSION: Literature data regarding the phenomenon of obesity paradox in T2DM patients are controversial due to the several limitations of the studies; therefore in the management of patients with overweight/obesity and T2DM is recommended referring to the established guidelines, which indicate diet and physical activity as the cornerstone of the treatment. LEVEL OF EVIDENCE: Level V: narrative review.

Lifestyles and sexuality in men and women: the gender perspective in sexual medicine.

Sexual health is strictly related with general health in both genders. In presence of a sexual dysfunction, the expert in sexual medicine aims to discover the specific weight of the physical and psychological factors can cause or con-cause the sexual problem. At the same time, a sexual dysfunction can represent a marker of the future development of a Non-communicable diseases (NCDss) as cardiovascular or metabolic diseases.In the evaluation phase, the sexual health specialist must focus on these aspects, focusing especially on the risk and protective factors that could impact on both male and female sexuality.This article presents a review of researches concerning healthy and unhealthy lifestyles and their contribute in the development of sexual quality of life in a gender-dependent manner.Among the unhealthy lifestyle, obesity contributes mostly to the development of sexual dysfunctions, due to its negative impact on cardiovascular and metabolic function. Tobacco smoking, alcohol - substance abuse and chronic stress lead to the development of sexual dysfunction in a med-long term.In order to guarantee a satisfying sexual quality of life, sexual health specialists have the responsibility to guide the patient through the adoption of healthy lifestyles, such as avoiding drugs, smoke and excessive alcohol, practicing a regular physical activity, following a balanced diet and use stress-management strategies, even before proposing both pharmaco- and/or psychotherapies.

Clinically relevant radioresistant rhabdomyosarcoma cell lines: functional, molecular and immune-related characterization.

BACKGROUND: The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background. METHODS: Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the "6Rs", which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology. RESULTS: RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-ß, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors. CONCLUSIONS: These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies.

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma.

Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression of ßIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analyses of Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan-Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin's effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.

Correction to: Evaluation of the reliability and validity of the Italian version of the schema mode inventory for eating disorders-short form for adults with dysfunctional eating behaviors.

The article Evaluation of the reliability and validity of the Italian version.

Evaluation of the reliability and validity of the Italian version of the schema mode inventory for eating disorders: short form for adults with dysfunctional eating behaviors.

PURPOSE: To examine the psychometric properties and the factorial structure of the Italian version of the schema mode inventory for eating disorders-short form (SMI-ED-SF) for adults with dysfunctional eating patterns. METHODS: 649 participants (72.1% females) completed the 64-item Italian version of the SMI-ED-SF and the eating disorder examination questionnaire (EDE-Q) for measuring eating disorder symptoms. Psychometric testing included confirmatory factor analysis (CFA) and internal consistency. Multivariate analysis of covariance (MANCOVA) was also run to test statistical differences between the EDE-Q subscales on the SMI-ED-SF modes, while controlling for possible confounding variables. RESULTS: Factorial analysis confirmed the 16-factors structure for the SMI-ED-SF [S-Bχ2 (1832) = 3324.799; p < .001; RMSEA = 0.045; 90% CI 0.043-0.048; CFI = 0.880; SRMR = 0.066; χ2/df = 1.81; < 3]. Internal consistency was acceptable in all scales, with Cronbach's Alpha coefficients ranging from 0.635 to 0.873. CONCLUSIONS: The SMI-ED-SF represents a reliable and valid alternative to the long-form SMI-ED for assessment and conceptualization of schema modes in Italian adults with disordered eating habits. Its use is recommended for clinical and research purposes. LEVEL OF EVIDENCE: Level V, descriptive study.

The Masturbation Erection Index (MEI): validation of a new psychometric tool, derived from the six-item version of the International Index of Erectile Function (IIEF-6) and from the Erection Hardness Score (EHS), for measuring erectile function during masturbation.

OBJECTIVES: To validate a psychometric instrument, the Masturbation Erection Index (MEI) able to evaluate erectile function (EF) during masturbation. In fact, although the evaluation of EF during masturbation is pivotal in evaluating erectile dysfunction (ED), to date no specific psychometric tools have been developed to measure it both in the routine clinical practice and in the experimental setting. PATIENTS AND METHODS: Of 560 men attending our andrological outpatient clinic for the first time, 99 (17.7%) had ED. As a control group, we enrolled 102 sexually healthy men. All the men were requested to complete both the six-item version of the International Index of Erectile Function (IIEF-6) and the MEI. The MEI was used together with a standardised tool, the Erection Hardness Score (EHS). The MEI was validated in terms of content validity. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Internal consistency was evaluated by Cronbach's α. The comparability between the MEI and IIEF-6 in measuring EF was tested by Bland-Altman analysis. The concordance correlation coefficient (CCC) between the two questionnaires was also determined. RESULTS: Internal consistency of the MEI was >0.93. Test-retest reliability was 0.982 (95% confidence interval [CI] 0.975-0.987). Bland-Altman analysis showed a good level of agreement between the IIEF-6 and MEI in the whole ED population, with stronger agreement in the organic-ED subpopulation. The estimated area under the curve of the MEI was 0.983 (P < 0.001; 95% CI 0.954-0.996), with a score of ≤27 as the optimal threshold to discriminate between the presence and absence of ED during self-induced masturbation. The CCC, Pearson ρ and bias correction factor (Cb) were 0.951 (95% CI 0.936-0.962), 0.968, and 0.982, respectively. CONCLUSION: The MEI showed good internal consistency and a good level of agreement with the IIEF-6. Hence, the MEI fulfills the major psychometric requirements for measuring EF during masturbation.

Magnetic-resonance-guided focused ultrasound treatment of non-spinal osteoid osteoma in children: multicentre experience.

BACKGROUND: Osteoid osteoma is a benign and painful musculoskeletal tumour that usually affects children. Current standard treatment is CT-guided radiofrequency ablation, a minimally invasive percutaneous procedure, with clinical success rates ranging between 85% and 98%. Though minimally invasive, however, this type of procedure is not free from complications. OBJECTIVE: To investigate the efficacy and safety of magnetic resonance (MR)-guided focused ultrasound (MRgFUS), a needleless procedure of thermal ablation employed in the treatment of non-spinal osteoid osteoma in paediatric patients. MATERIALS AND METHODS: We report the results of 33 procedures of ablation of osteoid osteoma performed with MRgFUS in three university hospitals. To ablate a lesion on the bone surface, MRgFUS employs the ultrasound energy transduced along the soft tissue. The follow-up studies lasted 24 months and were performed combining clinical and imaging data. RESULTS: Mean age of the children was 13.8 years. The clinical outcome showed a primary success of 97%. One case alone was submitted to repeat treatment because the first one failed (secondary success). No major or minor complications were recorded. During the investigation time, no relapse of symptomatology or delayed complications were observed. CONCLUSION: Although our study is preliminary and limited by a low number of patients, our data show that MRgFUS is effective. This suggests that it might be useful as the first-line treatment in paediatric patients with osteoid osteoma.

Carotid artery plaque characterization with a wide-detector computed tomography using a dedicated post-processing 3D analysis: comparison with histology.

PURPOSE: The characterization of atherosclerotic carotid plaque plays a key role in the identification of patients at risk. The aim of our work was to evaluate the potentialities of carotid computed tomography angiography (CCTA) in assessing composition of atherosclerotic plaque. MATERIALS AND METHODS: We retrospectively evaluated 29 patients (7 women and 22 men, age range 54-81; mean age 69) who underwent carotid endarterectomy. All patients underwent pre-surgical CCTA using a 320-slice scanner. Post-processing reconstructions and analysis were performed using a specific software. Percentage of three different components of the atherosclerotic plaque (adipose, fibrotic and calcific) were classified based on Hounsfield unit values. Post-processing results were compared with histological analysis. Vessel and plaque parameters were compared using the Pearson correlation coefficient (r). Bland-Altman plots with 95% confidence intervals were calculated for correlation. McNemar's test was used for comparison of dichotomous variables. RESULTS: A significant correlation between histology and CCTA was found with respect to the areas corresponding to adipose, fibrotic and calcified plaques. The existence of proportional bias was observed between the two quantifying methods with lower discrepancies found for the adipose and fibrotic plaque areas. The Bland-Altman analyses showed a mean bias of 3.2%, 2.5% and 0.6% between histology and CCTA, for adipose, fibrotic and calcified plaque areas, respectively. CONCLUSIONS: Multi-detector CT angiography represents a valuable technique to assess quantitatively the composition of atherosclerotic plaques, with particular reference to the prevalence of fibrotic tissue, and is a useful diagnostic tool to improve risk stratification of patients for cerebral stroke.

Percutaneous management of bone metastases: state of the art, interventional strategies and joint position statement of the Italian College of MSK Radiology (ICoMSKR) and the Italian College of Interventional Radiology (ICIR).

Interventional radiology provides local management of bone metastases (BM) with a palliative intent in most cases, or with a curative intent in selected patients. Its role has rapidly expanded in the last decade, offering new treatment solutions often in combination with surgery, radiation therapy and medical treatments. The aim of the present paper is to increase awareness, acceptance and adoption of interventional radiology procedures for the treatment of BM; and to present the joint position of the Italian College of Musculoskeletal Radiology and the Italian College of Interventional Radiology.

Dual PI3 K/mTOR inhibition reduces prostate cancer bone engraftment altering tumor-induced bone remodeling.

Morbidity in advanced prostate cancer patients is largely associated with bone metastatic events. The development of novel therapeutic strategies is imperative in order to effectively treat this incurable stage of the malignancy. In this context, Akt signaling pathway represents a promising therapeutic target able to counteract biochemical recurrence and metastatic progression in prostate cancer. We explored the therapeutic potential of a novel dual PI3 K/mTOR inhibitor, X480, to inhibit tumor growth and bone colonization using different in vivo prostate cancer models including the subcutaneous injection of aggressive and bone metastatic (PC3) and non-bone metastatic (22rv1) cell lines and preclinical models known to generate bone lesions. We observed that X480 both inhibited the primary growth of subcutaneous tumors generated by PC3 and 22rv1 cells and reduced bone spreading of PCb2, a high osteotropic PC3 cell derivative. In metastatic bone, X480 inhibited significantly the growth and osteolytic activity of PC3 cells as observed by intratibial injection model. X480 also increased the bone disease-free survival compared to untreated animals. In vitro experiments demonstrated that X480 was effective in counteracting osteoclastogenesis whereas it stimulated osteoblast activity. Our report provides novel information on the potential activity of PI3 K/Akt inhibitors on the formation and progression of prostate cancer bone metastases and supports a biological rationale for the use of these inhibitors in castrate-resistant prostate cancer patients at high risk of developing clinically evident bone lesions.

Validation of the Italian Yale Food Addiction Scale in postgraduate university students.

PURPOSE: This study was aimed to examine the structural and construct validity of the Italian version of the Yale Food Addiction Scale in a multisite sample of postgraduate students. METHODS: Two hundred and fifty-six subjects (78.1% females) aged from 18 to 53 years (mean = 23.93, SD = 4.96) and attending different postgraduate university programs at multiple Italian universities completed the Italian YFAS, the Italian Binge Eating Scale (BES), the Italian Eating Attitudes Test-26 and the Italian Dutch Eating Behavior Questionnaire (DEBQ) online through Qualtrics. RESULTS: Confirmatory Factor Analysis showed that the single-factor model of the Italian YFAS including all original items had adequate fit indexes (χ2252 = 454.183; p < 0.001; normed χ2 = 1.802; RMSEA = 0.056; 90% CI 0.048-0.076; CFI = 0.761; WRMR = 1.592). However, item analysis revealed that item#25 had zero variance (all subjects were assigned the same score after item dichotomization) and item#24 had a low factor loading, and were thus removed. Furthermore, item#10 and item#11 showed to be almost perfectly correlated (r = 0.998) and were thus parceled. The resulting 19-item single-factor model revealed a better fit to the data (χ2152 = 235.69; p < 0.001; normed χ2 = 1.556; RMSEA = 0.046; 90% CI 0.034-0.058; CFI = 0.858; WRMR = 1.236) and its internal consistency was acceptable (KR-20 = 0.72). Also, a single-factor model including the seven diagnostic symptoms was tested and showed adequate fit values (χ220 = 41.911; p < 0.003; normed χ2 = 2.09; RMSEA = 0.065; 90% CI 0.037-0.093; CFI = 0.946; WRMR = 1.132). Statistically significant and small-to-high correlations were found with all convergent measures, in particular with the BES. CONCLUSION: The Italian 19-item YFAS resulted to be a valid and reliable tool for the assessment of food addiction in postgraduate students. LEVEL OF EVIDENCE: Level V, descriptive study.