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Objectives To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk–benefit profiles in clinical practice.Design Retrospective multicentrer cohort study.Setting Four Italian regions (Lombardy, Veneto, Lazio, Sardinia).Methods Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI).Main outcome measures Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use.Results The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk–benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65).Conclusions The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered by the lack of human translational models and limitations of analysis techniques for fibrosis. The MASH three-dimensional (3D) InSight™ human liver microtissue (hLiMT) model recapitulates pathophysiological features of the disease. We established an algorithm for automated phenotypic quantification of fibrosis of Sirius Red stained histology sections of MASH hLiMTs model using a digital pathology quantitative single-fiber artificial intelligence (AI) FibroNest™ image analysis platform. The FibroNest™ algorithm for MASH hLiMTs was validated using anti-fibrotic reference compounds with different therapeutic modalities-ALK5i and anti-TGF-β antibody. The phenotypic quantification of fibrosis demonstrated that both reference compounds decreased the deposition of fibrillated collagens in alignment with effects on the secretion of pro-collagen type I/III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-3 and pro-fibrotic gene expression. In contrast, clinical compounds, Firsocostat and Selonsertib, alone and in combination showed strong anti-fibrotic effects on the deposition of collagen fibers, however less pronounced on the secretion of pro-fibrotic biomarkers. In summary, the phenotypic quantification of fibrosis of MASH hLiMTs combined with secretion of pro-fibrotic biomarkers and transcriptomics represents a promising drug discovery tool for assessing anti-fibrotic compounds.

Resumo Em 2023, o Instituto de Pesquisa Social de Frankfurt completa cem anos. Desde então, a “Escola de Frankfurt” realizou um amplo diagnóstico da perenidade do capitalismo e de suas contradições. Até meados dos anos 1960, entretanto, o mundo anglófono ainda estava relativamente alheio ao importante legado dessa experiência. Amplamente responsável pela reversão dessa situação, surge em 1973 a obra A imaginação dialética: História da Escola de Frankfurt e do Instituto de Pesquisas Sociais 1923-1950, de Martin Jay. Nessa conversa com o autor, discorremos sobre a história e os pressupostos da teoria crítica, a relação dela com outras correntes de pensamento e, por fim, sua atualidade e relevância para se pensar a periférica situação brasileira.

Abstract Non-alcoholic steatohepatitis (NASH) is a progressive and severe liver disease, characterized by lipid accumulation, inflammation, and downstream fibrosis. Despite its increasing prevalence, there is no approved treatment yet available for patients. This has been at least partially due to the lack of predictive preclinical models for studying this complex disease. Here, we present a 3D in vitro microtissue model that uses spheroidal, scaffold free co-culture of primary human hepatocytes, Kupffer cells, liver endothelial cells and hepatic stellate cells. Upon exposure to defined and clinically relevant lipotoxic and inflammatory stimuli, these microtissues develop key pathophysiological features of NASH within 10 days, including an increase of intracellular triglyceride content and lipids, and release of pro-inflammatory cytokines. Furthermore, fibrosis was evident through release of procollagen type I, and increased deposition of extracellular collagen fibers. Whole transcriptome analysis revealed changes in the regulation of pathways associated with NASH, such as lipid metabolism, inflammation and collagen processing. Importantly, treatment with anti-NASH drug candidates (Selonsertib and Firsocostat) decreased the measured specific disease parameter, in accordance with clinical observations. These drug treatments also significantly changed the gene expression patterns of the microtissues, thus providing mechanisms of action and revealing therapeutic potential. In summary, this human NASH model represents a promising drug discovery tool for understanding the underlying complex mechanisms in NASH, evaluating efficacy of anti-NASH drug candidates and identifying new approaches for therapeutic interventions.

The goal of post-transplant immunosuppressive drug therapy is to prevent organ rejection while minimizing drug toxicities. In clinical practice, a multidrug approach is commonly used and involves drugs with different mechanisms of action, including calcineurin inhibitors (CNI) (tacrolimus or cyclosporine), antimetabolite (antimet) (mycophenolate or azathioprine), inhibitors of mechanistic target of rapamycin (mTOR) (sirolimus or everolimus), and/or steroids. Although evidence based on several randomized clinical trials is available, the optimal immunosuppressive therapy has not been established and may vary among organ transplant settings. To improve the knowledge on this topic, a multiregional research network to Compare the Effectiveness and Safety of Immunosuppressive drugs in Transplant patients (CESIT) has been created with the financial support of the Italian Medicines Agency. In this article, we describe the development of this network, the framework that was designed to perform observational studies, and we also give an overview of the preliminary results that we have obtained. A multi-database transplant cohort was enrolled using a common data model based on healthcare claims data of four Italian regions (Lombardy, Veneto, Lazio, and Sardinia). Analytical datasets were created using an open-source tool for distributed analysis. To link the National Transplant Information System to the regional transplant cohorts, a semi-deterministic record linkage procedure was performed. Overall, 6,914 transplant patients from 2009–19 were identified: 4,029 (58.3%) for kidney, 2,219 (32.1%) for liver, 434 (6.3%) for heart, and 215 (3.1%) for lung. As expected, demographic and clinical characteristics showed considerable variability among organ settings. Although the triple therapy in terms of CNI + antimet/mTOR + steroids was widely dispensed for all settings (63.7% for kidney, 33.5% for liver, 53.3% for heart, and 63.7% for lung), differences in the active agents involved were detected. The CESIT network represents a great opportunity to study several aspects related to the use, safety, and effectiveness of post-transplant maintenance immunosuppressive therapy in real practice.

The roadmaps of satellite-based synthetic aperture radar (SAR) systems show a trend that requires a continuous improvement of the active antenna in terms of operating bandwidth, scanning angle capability, and swath width, thus leading to the demand for increased RF power and better power efficiency of the RF transmitter. Moreover, compact size and light weight are relevant objectives for making the overall SAR instrument appealing for future applications. The transmit/receive module (TRM) shown in this paper was developed while combining all these requirements in a cost-effective approach. A careful design of all relevant RF interconnects and passive devices was performed to ensure the largest output power from the last high-power amplifier of the transmitting chain, the lowest noise figure at the input of the receiving chain, and the calibration capability for appropriately tuning the TX and RX signal. The TRM was manufactured and experimentally tested to verify its performances. The measurement results show the superior performances of the proposed compact high-power large-bandwidth TRM. The achieved target objectives make the design of the proposed TRM readily applicable for the development of a compact, high-power, and highly integrated AESAs to be used for next-generation satellite constellations for Earth observation.

Resenha de CARONE, Iray. Adorno em Nova York: Os estudos de Princeton sobre a música no rádio (1938-1941). São Paulo: Alameda, 2019.

Well-differentiated retroperitoneal liposarcomas are slow growing and low-grade tumors, reaching usually huge size before being symptomatic and so diagnosed, therefore with increase of the surgical risk and of the probability of dedifferentiation. Inguinal location of these tumors is unusual and rarely diagnosed.

Seminal vesicle cysts are a very rare condition and its often associated with ipsilateral renal agenesis. The diagnosis of seminal vesicle cysts may be delayed or missed because of the non-specific symptoms of this condition. This article reports a triad of right renal agenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction (Zinner syndrome) in a 56 years old man.

Penile metastasis from prostate cancer represents a rare condition, associated with poor prognosis. In the literature, authors have reported less than 500 cases of secondary penile cancers, and among these cases of metastases, only 33% are from prostate cancer. Overall reported rate of survival is about 1-24 months. Here, we present an uncommon case of penile metastasis from prostatic adenocarcinoma, with particular focus on the role of computed tomography and magnetic resonance imaging in diagnosis and follow-up.

Thyroid ectopia can occur when the process of thyroid embryogenesis fails. Here, we present the case of a 30-year-old woman with thyroid ectopia that was discovered during magnetic resonance imaging of cervical spine for referred neck pain. Imaging revealed the presence of an encapsulated mass at the base of her tongue. The patient was not symptomatic for any compression of the airways. Diagnosis of ectopic lingual thyroid was confirmed by 99mTC scintigraphy. Incidental diagnosis of thyroid ectopia in asymptomatic adult patients is rare, and it should be considered on diagnostic imaging in case of an anterior midline cervical mass.

The aim of this work was to develop multimodal anthropomorphic breast phantoms suitable for evaluating the imaging performance of a recently-introduced Microwave Imaging (MWI) technique in comparison to the established diagnostic imaging modalities of Magnetic Resonance Imaging (MRI), Ultrasound (US), mammography and Computed Tomography (CT). MWI is an emerging technique with significant potential to supplement established imaging techniques to improve diagnostic confidence for breast cancer detection. To date, numerical simulations have been used to assess the different MWI scanning and image reconstruction algorithms in current use, while only a few clinical trials have been conducted. To bridge the gap between the numerical simulation environment and a more realistic diagnostic scenario, anthropomorphic phantoms which mimic breast tissues in terms of their heterogeneity, anatomy, morphology, and mechanical and dielectric characteristics, may be used. Key in this regard is achieving realism in the imaging appearance of the different healthy and pathologic tissue types for each of the modalities, taking into consideration the differing imaging and contrast mechanisms for each modality. Suitable phantoms can thus be used by radiologists to correlate image findings between the emerging MWI technique and the more familiar images generated by the conventional modalities. Two phantoms were developed in this study, representing difficult-to-image and easy-to-image patients: the former contained a complex boundary between the mammary fat and fibroglandular tissues, extracted from real patient MRI datasets, while the latter contained a simpler and less morphologically accurate interface. Both phantoms were otherwise identical, with tissue-mimicking materials (TMMs) developed to mimic skin, subcutaneous fat, fibroglandular tissue, tumor and pectoral muscle. The phantoms’ construction used non-toxic materials, and they were inexpensive and relatively easy to manufacture. Both phantoms were scanned using conventional modalities (MRI, US, mammography and CT) and a recently introduced MWI radar detection procedure called in-coherent Multiple Signal Classification (I-MUSIC). Clinically realistic artifact-free images of the anthropomorphic breast phantoms were obtained using the conventional imaging techniques as well as the emerging technique of MWI.

Objective: evaluate the correlation between skeletal changes in 2D dimensions and volume changes of the upper airways before and after rapid maxillary expansion (RME) therapy in children with obstructive sleep apnoea (OSA) by Cone Beam computed tomography (CBCT) and between volume of the upper airways and clinical data.

Embryonal tumors of the nervous system are the leading cause of childhood cancer-related morbidity and mortality. Medulloblastoma, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumor and neuroblastoma account for more than 20% of childhood malignancies and typify the current neural embryonal tumor model in pediatric oncology. Mechanisms driving the formation of these tumors point towards impaired differentiation of neuronal and neuron-associated cells during the development of the nervous system as an important factor. The importance of microRNAs (miRNAs) for proper embryonic cell function has been confirmed and their aberrant expressions have been linked to tumor development. The role of miRNAs in controlling essential regulators of key pathways implicated in tumor development makes their use in diagnostics a powerful tool to be used for early detection of cancer, risk assessment and prognosis, as well as for the design of innovative therapeutic strategies. In this review we focus on the significance of miRNAs involved in the biology of embryonal neural tumors, delineate their clinical significance and discuss their potential as a novel therapeutic target.

Embryonal tumors include a heterogeneous group of highly malignant neoplasms that primarily affect infants and children and are characterized by a high rate of mortality and treatment-related morbidity, hence improved therapies are clearly needed. G-quadruplexes are special secondary structures adopted in guanine (G)-rich DNA sequences that are often present in biologically important regions, e.g. at the end of telomeres and in the regulatory regions of oncogenes such as MYC. Owing to the significant roles that both telomeres and MYC play in cancer cell biology, G-quadruplexes have been viewed as emerging therapeutic targets in oncology and as tools for novel anticancer drug design. Several compounds that target these structures have shown promising anticancer activity in tumor xenograft models and some of them have entered Phase II clinical trials. In this review we examine approaches to DNA targeted cancer therapy, summarize the recent developments of G-quadruplex ligands as anticancer drugs and speculate on the future direction of such structures as a potential novel therapeutic strategy for embryonal tumors of the nervous system.

Objectives: In the general population, cadmium seems to be responsible for hypertension, atherosclerosis and an increase in acute coronary events. Therefore, the purpose of this meta-analysis was to analyze controlled studies conducted on cadmium and arterial pressure in occupationally-exposed workers. Materials and Methods: After analyzing all the relevant articles found in the literature, 6 publications were selected. Results: A higher prevalence of hypertension and higher values of systolic and diastolic blood pressure were recorded in the exposed subjects. Conclusions: Cadmium in occupationallyexposed individuals appears to induce an increase in systolic and diastolic blood pressure and an increase in the prevalence of hypertension.

Corpus luteum cyst rupture with consequent hemoperitoneum is a common disorder in women in their reproductive age. This condition should be promptly recognized and treated because a delayed diagnosis may significantly reduce women’s fertility and intra-abdominal bleeding may be life-threatening. Many imaging modalities play a key role in the diagnosis of acute pelvic pain from gynecological causes. Ultrasound study (USS) is usually the first imaging technique for initial evaluation. USS is used to confirm or to exclude the presence of intraperitoneal fluid but it has some limitations in the identification of the bleeding source. Contrast-enhanced computed tomography (CT) is the imaging modality which could be used in the acute setting in order to recognize gynecological emergencies and to establish a correct management. Magnetic resonance imaging (MRI) nowadays is the most useful technique for studying the pelvis but its low availability and the long acquisition time of the images limit its usefulness in characterization of acute gynecological complications. We report a case of a young patient with hemoperitoneum from hemorrhagic corpus luteum correctly identified by transabdominal USS and contrast-enhanced CT.

Colovesical fistula (CVF) is an abnormal connection between the enteric and the urinary systems. The rectourethral fistula (RUF) is a possible but extremely rare complication of treatment of prostate cancer with “transrectal High-Intensity Focused Ultrasound (HIFU) treatment.” We present a case of CVF due to HIFU treatment of recurrent prostate cancer. The case was assessed with cystography completed with a pelvic CT scan—with MPR, MIP, and VR reconstruction—before emptying the bladder. Since the CT scan confirmed that the fistula involved solely the urethra and excluded even a minimal involvement of the bladder, it was possible to employ a conservative treatment by positioning a Foley catheter of monthly duration, in order to allow the urethra to rest. Still today, after 6 months, the patient is in a good clinical condition and has not shown yet signs of a recurrence of the fistula.

Studies in scientific literature have proved that urban pollution affects the respiratory system. The aim of our study is to assess the effects that different time of exposure to urban pollution can cause on respiratory function in municipal traffic policemen. The research was carried out on a sample of 120 traffic police officers of both sexes divided into two groups, group A with work service between 1 and 10 years and group B with more than 10 years of service. All subjects included in the study were tested for respiratory functions by a spirometer test. Statistical analysis showed a significant difference between group A and group B (p

The aim of this study is to identify, by a brief ad hoc questionnaire, specific dimensions of perceived occupational stress that could be relevant in two different work conditions of female workers: visual display unit (VDU) operators, for whom the risk of work-related stress is already known in literature, and kindergarten teachers, for whom very few studies have examined this risk. A questionnaire, prepared specifically for workers, was filled in by 70 all-female kindergarten teachers and 70 all-female VDU operators. The two groups were matched for age and length of service. The questionnaire was examined by factor analysis and questionnaire single item scores. Total score and factor scores were examined between group comparison of means analysis. The level of significance was established at p