MEMORIE E PRESENTE DELLA RIFORMA IN ITALIA / MEMORIES AND PRESENT OF THE REFORM IN ITALY

RiassuntoL’autore propone una riflessione sulle definizioni storiografiche della Riforma del XVI secolo, anche alla luce degli studi più recenti, ponendo attenzione sulle forme assunte dalla Riforma in Italia e sul significato per il dialogo ecumenico della nuova riflessione sulla Riforma in vista del 500° anniversario del suo inizio.Parole chiavi: Riforma. Pentecostali. Ecumenismo. Storiografia.AbstractThe author proposes a reflection on the historiographic definitions of the Reformation of the XVI century, even in the light of the most recent studies, paying attention to the forms taken by the Reformation in Italy and the meaning for the ecumenical dialogue of the new reflection on the Reformation reform in view of the 500° anniversary of its beginning.Keywords: Reformation. Pentecostals. Ecumenism. Historiography

TOLLERANZA – INTOLLERANZA – LIBERTÀ RELIGIOSA NELLA PROSPETTIVA PENTECOSTALE

L’autore prende in esame il rapporto tra «intolleranza-tolleranza-libertà religiosa» nell’esperienza delle comunità pentecostali del XX secolo partendo dall’assoluto rifiuto delle armi e del ricorso alla violenza. Vengono poi presentati i rapporti tra le comunità pentecostali, approfondendo due casi, quello italiano e quello ruandese. Infine si affronta il tema della dialettica tra evangelizzazione e libertà, declinato in forme molto diverse da luogo a luogo, ma particolarmente utile per comprendere il livello di intolleranza e libertà religiosa

Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.

Selective degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is initiated by ER-phagy receptors, which facilitate the incorporation of ER fragments into autophagosomes. FAM134 reticulon family proteins (FAM134A, FAM134B, and FAM134C) are ER-phagy receptors with structural similarities and nonredundant functions. Whether they respond differentially to the stimulation of ER-phagy is unknown. Here, we describe an activation mechanism unique to FAM134C during starvation. In fed conditions, FAM134C is phosphorylated by casein kinase 2 (CK2) at critical residues flanking the LIR domain. Phosphorylation of these residues negatively affects binding affinity to the autophagy proteins LC3. During starvation, mTORC1 inhibition limits FAM134C phosphorylation by CK2, hence promoting receptor activation and ER-phagy. Using a novel tool to study ER-phagy in vivo and FAM134C knockout mice, we demonstrated the physiological relevance of FAM134C phosphorylation during starvation-induced ER-phagy in liver lipid metabolism. These data provide a mechanistic insight into ER-phagy regulation and an example of autophagy selectivity during starvation.We thank G. Diez Roux and P. Ashley-Norman for critical reading of the manuscript. We thank the microscopy, MS, advanced histopathology, and FACS facilities at TIGEM Institute. We thank E. Nusco for helping us with AAV injections. Funding: This work was supported by European Research Council (ERC) (714551), Telethon intramural grants, and Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2015 Id 17717) (to C.S.) and Telethon Foundation (TMPGCBX16TT), AFM Telethon (Trampoline Grant), and AIRC (MFAG-2020-24856) (to P.G.). G.D.L. is a recipient of AIRC fellowship “Francesco Alicino” (25407). V.L. acknowledges funding from the ERC (101001784), the Italian MIUR-PRIN 2017 (2017FJZZRC), and the Swiss National Supercomputing Center (CSCS) (project ID u8). The work of A.S. was supported by the German Research Foundation DFG (SFB1177/2 and WO210/20-2) and the Dr. Rolf M. Schwiete Stiftung (13/2017). A.E. is supported by the RETOS projects Programme of Spanish Ministry of Science, Innovation and Universities, Spanish State Research Agency (grants SAF2015-67538-R and PID2019-104012RB-I00), and the ERC (638891). A.B.P.-G. is a recipient of Ph.D. fellowship from MICIU/AEI (BES-2017-081381). A.R. is a recipient of Umberto Veronesi Foundation postdoctoral fellowship. Author contributions: G.D.L. and F.I. performed most of the experiments. F.I. and A.B.P.-G. performed in vivo experiments. M.M. performed mutagenesis experiments. S.A. and V.L. performed LC3-FAM134C binding analysis. C.P.Q.M. performed in vitro phosphorylation assays. L.C. analyzed CK2 substrate phosphorylation. F.S., A.P., C.C., and A.S. analyzed proteomic data. G.N. provided critical suggestions. A.R. performed proteomic experiments. A.E. supervised in vivo experiments. M.R., L.A.P., and O.M. supervised CK2 experiments. C.S. designed the study. P.G. and C.S. conceived and supervised the experiments. C.S., P.G., V.L., and M.R. wrote the paper. G.D.L. and F.I. prepared the figures. All the authors read the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.S

The urokinase/urokinase receptor system in mast cells: effects of its functional interaction with fmlf receptors

Mast cell and basophils express the high affinity receptor for IgE (FcRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)- anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs). We investigated the expression of the uPAuPAR system and its functional interaction with FPRs in human mast cells (MCs). Differently from basophils, MCs produced uPA that was able to induce their chemotaxis. Indeed, MCs also expressed uPAR, both in the intact and in a cleaved form (DIIDIII-uPAR) that can expose, at the N-terminus, the SRSRY sequence, able to interact with FPRs and to mediate cell chemotaxis. MCs also expressed mRNAs for FPRs that were functionally active; indeed, uPA and a soluble peptide (uPAR84-95), containing the SRSRY chemotactic sequence of uPAR and able to interact with FPRs, were able to induce MCs chemotaxis. Thus, uPA is a potent chemoattractant for MCs acting through the exposure of the chemotactic epitope of uPAR, that is an endogenous ligand for FPRs. The same mechanism could be involved in VEGF-A secretion by human MCs, also induced by uPA and uPAR84-95 stimulation

Metastasis-Directed Radiation Therapy with Consolidative Intent for Oligometastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n = 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC

The impact of prostate biopsy on erectile and ejaculatory function: A prospective study

Objective: To evaluate the impact on erectile and ejaculatory function following transrectal ultrasound-guided biopsies of the prostate (TRUS-Bx) in sexually active men. Methods: Monocentric prospective study from May 2021 to January 2022 of consecutive patients with suspected prostate cancer [elevated prostate specific antigen (PSA) level and/or abnormal digital rectal examination] undergoing TRUS-Bx. The 15-item version of the International Index of Erectile Function (IIEF-15), Premature Ejaculation Diagnostic Tool (PDET) and short form of Male Sexual Health Questionnaire (MSHQ-EjD Short Form) were assessed before, one and three months after TRUS-Bx. The primary endpoint was to evaluate the risk of temporary post-biopsy erectile and/or ejaculatory dysfunctions. The statistical significance was set as p value < 0.05. Results: A total of 276 consecutive patients were included in the study. The median age, PSA and biopsy cores were 65 years (IQR 59-69), 7 ng/ml (IQR 5-9.7) and 16 (IQR 12-16), respectively. We compared the IIEF subdomains before TRUS-Bx vs. one or three months: the erectile function (EF) decreased after one month (p<0.001) but recovered after three months (p=0.833); the Orgasmic Function (OF), the Sexual Desire (SD), the Intercourse Satisfaction (IS), the Overall Satisfaction (OS), and Total IIEF decreased significantly after both one and three months compared to pre-biopsy values (p < 0.05). As for ejaculatory function (EjF), PDET, MSHQ-EjD Short Form 1, 2, 3 and MSHQ-EjD Short Form 4 scores decreased significantly after one month (p < 0.001), but they returned to pre-biopsy values after 3 months: p = 0.538, p = 0.071 and p = 0.098, respectively. Conclusions: Our study proved that EF, assessed through IIEF- 15, and ejaculatory function, assessed through PDET and MSHQ-EjD Short Form, were negatively affected by TRUS-Bx one month after the procedure and recovered after three months. Interestingly, the other IIEF-15 subdomains (OF, SD, IS, OS and Total) resulted as significantly reduced also after 3 months: this issue highlights the importance of carefully considering the indication to TRUS-Bx

Preoperative Fibrinogen-to-Albumin Ratio as Potential Predictor of Bladder Cancer: A Monocentric Retrospective Study

: Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors

Could YouTubeTM encourage men on prostate checks? A contemporary analysis

Objectives: To assess YouTube™ videos' quality on prostate checks, especially on the digital rectal exam (DRE), and to investigate if they can inform patients correctly and eradicate their beliefs and myths.Methods: A search using as keywords "digital rectal exam for prostate cancer" was performed on the YouTubeTM platform. We selected the first 100 videos. To assess video quality content, Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V) and Misinformation tool were used.Results: Seventy-three videos were suitable for the analyses. The median PEMAT A/V Understandability score and PEMAT A/V Actionability score were 46.2% (interquartile range [IQR]: 30.8-76.9) and 50.0% (IQR: 25.0-75.0), respectively. The medi-an PEMAT A/V Understandability and Actionability scores were 69.2% (IQR: 46.2-88.5) vs 46.2% (IQR: 30.8-61.5) (p = 0.01) and 100.0% (IQR: 87.5-100.0) vs 25.0% (IQR: 25.0-68.8)(p < 0.001), for healthcare workers vs patients, respectively. According to the Misinformation tool, the median misinforma-tion score of the overall videos was 2.2 (IQR:1.7-2.8). According to the target audience, the misinformation score was 2.8 (IQR: 2.4-3.5) vs 2.0 (IQR: 1.5-2.8) (p = 0.02), for healthcare workers vs patients, respectively. Conclusions: Currently, based on our analyses, YouTubeTM videos' quality on DRE resulted unsatisfactory according to the PEMAT A/V score and the Misinformation tool. Videos targeted to healthcare workers got higher quality scores if compared to videos targeted to patients. Therefore, YouTubeTM videos' may not be considered a reliable source of information on DRE for patients

The commissioning of the CUORE experiment: the mini-tower run

CUORE is a ton-scale experiment approaching the data taking phase in Gran Sasso National Laboratory. Its primary goal is to search for the neutrinoless double-beta decay in 130Te using 988 crystals of tellurim dioxide. The crystals are operated as bolometers at about 10 mK taking advantage of one of the largest dilution cryostat ever built. Concluded in March 2016, the cryostat commissioning consisted in a sequence of cool down runs each one integrating new parts of the apparatus. The last run was performed with the fully configured cryostat and the thermal load at 4 K reached the impressive mass of about 14 tons. During that run the base temperature of 6.3 mK was reached and maintained for more than 70 days. An array of 8 crystals, called mini-tower, was used to check bolometers operation, readout electronics and DAQ. Results will be presented in terms of cooling power, electronic noise, energy resolution and preliminary background measurements