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Author of the Study: The COVID-19 outbreak has brought challenges to the global healthcare community. The management of upper urinary tract stones has been affected even further, with potential severe sequelae for patient’s health. Materials and Methods: We report a multicentric retrospective study involving 9 Centers regularly delivering treatment for upper tract urinary stones across the country. All Centers suffered significant limitations during the pandemic period due to government limitations. We compared the 12 months-period prior to COVID-19 (from march 1st 2019 to February 28th 2020, named as period A) with postCOVID-19 period (from march 1st, 2020 to February 28th, 2021 named as period B). Aim of the study was to compare endourological procedures for upper urinary stones during period A and the period B. This study investigated all types of surgeries delivered in both elective and emergency setting. Results: A total of 4018 procedures were collected, including 2176 procedures in period A. In period B, 1842 procedures were carried out, corresponding to a loss of 15.35% of cases (p < 0.001). Looking into elective cases, 1622 procedures were delivered in period A, compared to 1280 in period B, resulting in a loss of 342 cases corresponding to 21.81% (p = 0.001). All types of stone treatments resulted affected, including ESWL (from 487 cases in period A to 344 in period B, − 29.37%, p = 0.001), PCNLs (from 170 to 125 cases, corresponding to − 26.47%, p:0.008), retrograde surgery for renal stones (from 433 to 387 cases, − 10.63%, p = 0.008) and for ureteric stones (from 614 cases to 484, − 21.18%, p.008). Additionally, waiting lists resulted affected, with significant delays in period B. In particular, for ureteric stones, mean waiting time in period A was 61.5 days compared to 87.5 days in period B (p = 0.008). Regarding renal stones, waiting list increased from 64.74 days in period A to 85.66 days in period B for RIRS. The waiting list for percutaneous surgeries increased from 79 days to 103 days (p = 0.001). We did not find any patient which acquired COVID-19 during hospitalization for elective or urgent surgery. We also found a longer waiting list for pre-stented patients, resulting to be 86.5 days in period B compared to 64 days in period A (p < 0.005). Conclusions: Our study showed how COVID-19 caused a significant disruption in endourological services across the country. Our data underlined how less patients received treatment in a longer time. This can potentially lead to an increased risk of stone- related complications, including sepsis and kidney loss.

Background To understand the presence and impact of social and cultural factors on health vulnerability it is important for improving diabetes care and management. In fact, through the social dimension, it is possible to identify the priorities and attitudes towards diabetes and diabetes care among those living with the condition. Methods The study was carried out as part of the global Cities Changing Diabetes programme, involved a sample of individuals living with diabetes in the Rome metropolitan area and employed mixed-method and qualitative approaches to data collection and analysis (survey, sorting procedure and focus group). Results Four specific sub-groups of participants have been identified, each with distinct but shared priorities and attitudes towards diabetes: Health conscious thanks to the context; Medicalized elderly people; Fatalistic citizens; Worried but undisciplined young people. The connection between the place where you live and the possibility to adopt a healthier lifestyle was confirmed. For these patients, the disease is mainly characterized by its relationship with food and its connections with psychological aspects are also relevant. Conclusions An important issue concerns information and the different understandings of diabetes. A clear need emerged for further elaboration of the various aspects of a disease that tends to be underestimated also by those who have it. Another aspect concerns the importance of the living environment and consequently of the actions on its urban planning, mobility, but also in everyday life organization, as factors that can make a difference in properly managing the disease. These results are very important to promote a joint action, that have to involve public and private stakeholders, in order to improve treatment opportunities and quality of life of people facing diabetes every day in the Rome metropolitan area. Key messages An important issue concerns information. A clear need emerged for further elaboration of the various aspects of a disease that tends to be underestimated also by those who have it. The living environment in important too and the actions on its urban planning, mobility, in everyday life organization, as factors that can make a difference in properly managing the disease.

Background Multiple sclerosis (MS) is usually diagnosed between 20 and 40 years, affecting the most productive and active period of life. Aim To analyse the health perception of young people with MS and to compare the present results with a previous one. Methods A descriptive cross-sectional study was conducted in 2017. A validate and anonymous questionnaire was administered to 613 Italian young, aged 18-40, affected by MS (women 78.5%). Results Analyzing the declared health status, most of young MS defined good health status (76% good or excellent health) with differences between age class (82% at 25-29 years vs 71% at 35-40) and with a reverse trend with the increasing of disability (92% in subject with no disability vs 34% in ones with a medium or severe disability). The comparison against 2004 data highlights an improvement in the health conditions perceived, also for ones with a serious disability. Regarding the time elapsed from diagnosis, the trend was not linear, since respondents with a diagnosis Conclusions Diagnosis and disability constitute a decisive factor in the assessment of the state of health, but the perception goes to stabilize with time, even if the conditions tend to worsen. In this regard, the worst declared conditions in patients with a recent diagnosis seem to be influenced by psychological factors. So, the moment of diagnosis need a better management. Only 30% got adult vaccination (vs 61% in young Italians) due to lack of information on vaccine safety in MS patients. The improvement of perceived health in young with MS is another proof of the progress of MS treatments, which appears transversal to all the conditions of disability. Key messages The perception of health is strongly related to disability and to time elapsed from diagnosis. In the last 15 years the progress of MS management improved well-being of all MS young patients.

Background Public knowledge, awareness and behaviors related to antibiotic use and antimicrobial-resistance (AMR) are vital to ensure the prudent use of these drugs. In this work, we present the top-line results of the first national survey of AMR among the Italian general population aged ≥18 years. Methods From August to September 2019, we conducted a population-based cross-sectional random survey through mixed CATI/CAMI/CAWI methodologies among representative samples of the general population, parents of children aged 0-11 years, adults ≥65 years and pet's owners. Results were summarized using relative frequencies. Results Of 1,400 persons interviewed, 47% and 68% respectively correctly said that it is false that antibiotics kill viruses and are effective at treating colds and flu. More than 80% of respondents considered themselves to be well-informed about antibiotics but only one in two people knew what is meant by AMR. While the vast majority (96%) of respondents said that they obtained the last course of antibiotics that they used from a medical prescription, 11% incorrectly said that they stopped taking antibiotics when they felt better or that they used those left over from a previous course. In addition, 55% of pet's owners said they obtained antibiotics without a prescription from a pharmacy or elsewhere. Almost all respondents (97%) believed that it's everyone's responsibility to use antibiotics wisely, with the 80% who expressed concerns about the potential of AMR to affect themselves and their families; however, 40% did not think that action at an individual level is the most effective way of tackling resistance to antibiotics. Conclusions Our findings show some improvement in Italians' knowledge, awareness and behaviors related to antibiotic use and AMR but there are needs to be a greater sense of responsibility to take charge of the AMR problem. These results may be drivers of structured national awareness campaigns. Key messages In 2019, we conducted the first national survey of AMR among the Italian population: >80% of respondents felt themselves well-informed about antibiotics but only 1/2 people knew what is meant by AMR. Almost all Italian sample believed that it's everyone's responsibility to use antibiotics wisely, but 40% did not think that action at an individual level is effective to tackle AMR.

[Image: see text] Microsomal prostaglandin E(2) synthase-1 (mPGES-1), the terminal enzyme responsible for the production of inducible prostaglandin E(2), has become an attractive target for the treatment of inflammation and cancer pathologies. Starting from an aminobenzothiazole scaffold, used as an unprecedented chemical core for mPGES-1 inhibition, a Combinatorial Virtual Screening campaign was conducted, using the X-ray crystal structure of human mPGES-1. Two combinatorial libraries (6 × 10(4)) were obtained by decorating the aminobenzothiazole scaffold with all acyl chlorides and boronates available at the Merck database. The scientific multidisciplinary approach included virtual screening workflow, synthesis, and biological evaluation and led to the identification of three novel aminobenzothiazoles 1, 3, and 13 acting as mPGES-1 inhibitors. The three disclosed hits are able to inhibit mPGES-1 in a cell-free system (IC(50) = 1.4 ± 0.2, 0.7 ± 0.1, and 1.7 ± 0.2 μM, respectively), and all are endowed with antitumoral properties against A549 human cancer cell lines at micromolar concentrations (28.5 ± 1.1, 18.1 ± 0.8, and 19.2 ± 1.3 μM, respectively).

Introduction: To demonstrate safety of a new internal protocol for patients and health workers adopted for elective urologic surgical activity during COVID-19 pandemic Materials and methods: We have retrospectively evaluated 86 patients who underwent elective surgery in the urology department of IRCCS Policlinico San Donato, from March 9th to May 8th, 2020 Our institution became a first line hospital for COVID-19 patients since March 2020 We identified non-deferrable patients that needed to be treated within one month All patients included have followed a dedicated pathway from the day-hospital till the discharge Clinical data, as nasopharyngeal swabs, chest X-ray, type of anesthesia, type of surgical procedure and days of hospitalization were collected Moreover, individual risk factors for COVID-19 pneumonia, as advanced age, ongoing malignancy, high blood pressure and coronary artery disease, were analyzed All patients were interviewed after a minimum post discharge time of 14 days to find out if any of them had developed general and Covid-related complications Results: The study population included 66 (76 75%) men and 20 (23 25%) women, aged between 17 and 90 years old We have performed eighty-eight (88) preoperative screenings and two (2) patients were excluded, due to exclusion criteria Overall, 63 (71 60%) patients underwent oncological procedures while only 23 (28 40%) patients underwent non-oncological surgery The average number of hospitalization days was 2 39 ± 2 21 After at least 14 days after discharge (25 00 ± 10 35 days), we phone interviewed all patients to check their conditions No patients included in the study showed symptoms related to COVID-19, except for 2 (2 32%) who manifested coryza, 28 and 35 days after discharge respectively We also analyzed clinical characteristics of the study participants in relation to develop SARS CoV-2 None of patient developed Covid-19 postoperatively and in addition, none of hospital workers that were part of this pathway got the Covid-19 infection Conclusions: The duration of pandemic period is undefined;therefore, our protocol could be considered a good model for every type of surgery and its application could ensure a continuous treatment for non-deferrable conditions, even during healthcare emergencies in a safe way for both the patients and health workers

DMRT genes encode a large family of transcription factors which share an unusual cysteine-rich DNA-binding motif, the DM domain. DM family members have been studied in the context of sexual development; in particular, the DMRT1 gene appeared to be the one most directly involved in sex determination, but its activity is largely unexplored and possible downstream targets of this factor have yet to be identified. DMRT1 of the lacertid lizard Podarcis sicula (PsDMRT1) was isolated as a model to study differential gene expression during the seasonal reproductive cycle of an ectothermal species. The adult testis of P. sicula exhibits full activity in spring, complete regression in summer and a slow autumnal recrudescence without spermiation. We cloned a 591-bp partial ORF of the PsDMRT1 fragment, whose putative amino acid sequence contains the conserved DM domain. Northern blot analysis of mRNA from different tissues of P. sicula individuals captured in spring demonstrated DMRT1 transcripts only in testis. Semi-quantitative RT-PCR and in situ hybridization experiments showed peak PsDMRT1 expression in spring, lower expression in autumn and no expression during the period of gonad regression. A possible correlation between androgen level variations and PsDMRT1 transcripts is hypothesized and discussed. Finally, data showed that PsDMRT1 is expressed only in spermatogenic cells, before the second meiotic division, suggesting that its role is confined to the proliferation and maintenance of spermatogonia and spermatocytes.

To assess the feasibility of protein replacement as a potential therapy for cystic fibrosis, we have evaluated the ability of influenza hemagglutinin (HA) to mediate the delivery of purified cystic fibrosis transmembrane conductance regulator (CFTR) to recipient cells in vitro. CFTR was purified from both CHO cells and Sf9 cells and reconstituted into two different types of vesicular delivery vehicles. In one, CFTR and HA were co-reconstituted into the same lipid vesicle. After binding to the cell surface, delivery of CFTR to the recipient cell was achieved by a transient, low-pH activation of the fusion activity of HA. A second delivery strategy used HA virosomes together with purified CFTR that had been reconstituted into vesicles containing gangliosides, a receptor for HA. After binding of the HA virosomes and CFTR-containing vesicles to the recipient cells, delivery to the plasma membrane again was achieved by a transient pH drop. Delivery of functional CFTR was assessed using the SPQ fluorescence assay. Functional CFTR was detected in a fraction (20%) of the recipient cells using this assay. Quantitative binding and fusion assays using radiolabeled virosomes and lipid vesicles showed that on the order of 1,000 of the added CFTR-containing vesicles bound to each C127 cell under the conditions of our delivery protocols. However, only a fraction of these vesicles fused and delivered CFTR to the cell plasma membrane. The two delivery strategies were found to be approximately equivalent in their ability to deliver active CFTR, and there were no significant differences between deliveries using purified CFTR from either cell source. These feasibility studies suggest that purified CFTR can be delivered to a recipient cell in a functional form and therefore represent a significant step in establishing the concept of protein replacement as a therapy for cystic fibrosis.

Biotechnological applications of proteins and enzymes are often hampered by their low stability to heat, pH, organic solvents, and proteolysis. With the aid of protein engineering, however, many attempts are being made to improve the operational stability of current commercial enzymes, and, in a more general sense, to establish guidelines for improving the thermostability of proteins and enzymes (Mozhaev et al. 1988).

Postoperative irradiation of conservatively operated breast carcinoma is one of the most common practice in radiation oncology. In this job we analyze the acute toxicity during treatment.