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The bronze doors of the Basilica of San Zeno in Verona, Italy, are a special case in art history research. They were made by several workshops during the twelfth century: stylistically, two to three workshops were assumed to produce the metal parts of the door. However, it is still unclear when exactly and if this interpretation can be supported by the chemical composition of the metal. In this research we aimed to verify the art history interpretation by identifying the alloy composition of each individual metal plate. The composition of the supporting wooden structures are discussed. A portable ED-XRF instrument and optical microscopes were used to analyse and document the doors non-invasively. The doors were also photographed to produce high resolution orthophotos and 3D models. We can confirm that the metal parts of the doors were made of leaded tin-bronze as well as leaded brass and mounted on a wooden structure mainly made of spruce and oak wood. Chemically, two/three different groups of alloys have been identified, which can be associated with two or three different workshops, and which largely correspond to the stylistic interpretation. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is one of the leading cause of child blindness. Preterm newborns of very low gestational age (GA) and very low birth weight are at the greatest risk. Our objective was to evaluate the role of genetic variants associated with ROP risk and its comorbidities in an Argentinian sample of premature infants., Methods: A sample of 437 preterm infants <33 weeks GA, born at a maternity hospital in Tucumán, Argentina, 2005-2010, was analyzed. Environmental factors, perinatal outcomes, and fourteen single nucleotide polymorphisms associated with ROP were evaluated, comparing ROP with non-ROP newborns. A lasso logistic regression was performed to select variables; then, a conditional logistic regression was used to identify ROP maternal and perinatal risk factors adjusting by maternal and gestational ages, respectively., Results: ROP maternal risk factors were alcohol intake, periodontal infections, and severe stress. Respiratory distress, sepsis, and intracranial hemorrhage were the ROP perinatal risk factors. Markers rs186085 of EPAS1 and rs427832 of AGTR1 were significantly associated with ROP newborns., Conclusion: We identified three maternal and three perinatal risk factors associated with ROP. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP., Impact: Genetic and environmental risk factors associated with ROP and its comorbidities are evaluated in a Latin American population. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. Three maternal and three perinatal risk factors associated with ROP were also identified. A matrix of significant relationships among genetic markers and comorbidities is presented. Reported data may help develop more effective preventive measures for ROP in the Latin American region., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Purpose: Endocrine-disrupting compounds, including bisphenol A (BPA), may promote obesity influencing basal metabolic rate and shifting metabolism towards energy storage. The role of 1,25‑Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of debate. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the pro-adipogenic effect of BPA in two adipocyte models, mouse 3T3-L1 cell line and human adipose-derived mesenchymal stem cells (hAMSC)., Methods: 3T3-L1, mouse pre-adipocytes and human adipose-derived mesenchymal stem cells (hAMSC) were treated with VitD (10 -7  M) and BPA (10 -8  M and 10 -9  M), alone or in combination, throughout the differentiation in mature adipocytes. Cellular lipid droplet accumulation was assessed by Oil Red O staining, mRNA and protein expression of key adipogenic markers, transcription factors, and cytokines were investigated by RT-qPCR and WB, respectively. miRNAs involved in the regulation of adipogenic transcription factors were evaluated by RT-qPCR, and highly potent steric-blocking oligonucleotides (miRNA inhibitors) were used to modulate miRNAs expression., Results: Pre-adipocytes express VitD receptor (VDR) in basal condition, but during the differentiation process VDR expression reduces if not stimulated by the ligand. VitD significantly decreases lipid accumulation, with a consequent reduction in adipogenic marker expression, and counteracts the pro-adipogenic effect of BPA in 3T3-L1 and hAMSC during differentiation. This effect is associated to the increased expression of miR-27a-3p and miR-27b-3p. The blocking of miR-27a-3p and miR-27b-3p through miRNA inhibitors prevents the anti-adipogenic effect of VitD in both cell models., Conclusions: These results suggest that in cultured 3T3-L1 and hAMSC VitD induces an anti-adipogenic effect and prevents BPA pro-adipogenic effect by triggering at least in part epigenetic mechanisms involving miR-27-3p., (© 2024. The Author(s).)

Purpose: To analyze the clinical presentation, management, and outcome of two sisters affected by hereditary transthyretin related amyloidosis (ATTRv) and bilateral severe-to-profound hearing loss treated with cochlear implant., Methods: A description of two patients underwent three cochlear implant (CI) surgery was performed. Age at time of implantation ranged from 48 to 53 years. Both patients were initially equipped with a bilateral hearing aid and subsequently underwent cochlear implant. A bimodal stimulation was maintained thereafter. One case underwent bilateral surgery. Hearing outcomes were assessed by comparing pre- and post-operatively tonal and vocal hearing thresholds and speech perception tests (Common Evaluation Protocol Results in Rehabilitation Audiology)., Results: In both patients, a significant and stable improvement of hearing threshold and speech perception was observed up to the last follow-up. No post-operative complication were observed during the follow-up., Conclusions: ATTRv amyloidosis may be the cause of cochlear function impairment. Restoring the hearing in these group of patients is of paramount importance since the vision is often compromised too. Cochlear implant could be a viable strategy of rehabilitation for selected patients affected by severe-to-profound sensorineural hearing loss caused by ATTRv amyloidosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pancreatic cancer (PC) is an increasing cause of cancer-related death, with a dismal prognosis caused by its aggressive biology, the lack of clinical symptoms in the early phases of the disease, and the inefficacy of treatments. PC is characterized by a complex tumor microenvironment. The interaction of its cellular components plays a crucial role in tumor development and progression, contributing to the alteration of metabolism and cellular hyperproliferation, as well as to metastatic evolution and abnormal tumor-associated immunity. Furthermore, in response to intrinsic oncogenic alterations and the influence of the tumor microenvironment, cancer cells undergo a complex oncogene-directed metabolic reprogramming that includes changes in glucose utilization, lipid and amino acid metabolism, redox balance, and activation of recycling and scavenging pathways. The advent of omics sciences is revolutionizing the comprehension of the pathogenetic conundrum of pancreatic carcinogenesis. In particular, metabolomics and genomics has led to a more precise classification of PC into subtypes that show different biological behaviors and responses to treatments. The identification of molecular targets through the pharmacogenomic approach may help to personalize treatments. Novel specific biomarkers have been discovered using proteomics and metabolomics analyses. Radiomics allows for an earlier diagnosis through the computational analysis of imaging. However, the complexity, high expertise required, and costs of the omics approach are the main limitations for its use in clinical practice at present. In addition, the studies of extracellular vesicles (EVs), the use of organoids, the understanding of host-microbiota interactions, and more recently the advent of artificial intelligence are helping to make further steps towards precision and personalized medicine. This present review summarizes the main evidence for the application of omics sciences to the study of PC and the identification of future perspectives.

Non-O1 and non-O139 Vibrio cholerae (NOVC) are serogroups that do not produce cholera toxin and are not responsible for epidemics. Even though rarely encountered in clinical practice, they can cause a spectrum of different conditions ranging from mild gastrointestinal syndrome to extraintestinal diseases, of which bacteremia and wound infections are the most severe. Risk factors for severe disease are cirrhosis, neoplasms, and diabetes mellitus. The mortality rate of NOVC bacteremia in hospitalized patients ranges from 24 to 61.5%. Incidence of NOVC infections is still rare, and consensus recommendations on treatment are not available. We report a case of NOVC bacteremia associated with severe cellulitis in an immunocompetent 75-year-old man who had eaten raw seafood in a location by the northern Adriatic Sea (Italy). Twenty-four hours after intake, he developed a high fever and vomiting. Afterwards, he started noticing the appearance of cellulitis in his right leg, which worsened in a matter of hours. The patient had a history of compensated type 2 diabetes mellitus. NOVC was isolated from both blood cultures and the leg ulcer. The non-O1, non-O139 serogroup was confirmed, and the detection of the cholera toxin gene was negative. Both tests were performed by the Reference National Laboratory of Istituto Superiore di Sanità (ISS). Multiple antimicrobial regimens were administered, with complete recovery. In conclusion, considering the severity of NOVC-associated manifestations, it is of pivotal importance to reach etiological diagnosis for a target antimicrobial therapy and to consider V. cholerae infection in the differential diagnosis in the presence of risk factors and potential exposure.

Aristolochia plants are emblematic from an ethnopharmacological viewpoint and are know to possess numerous biological properties, including antiseptic. However, the medicinal potential of these species is debatable because of their representative chemical constituents, aristolochic acids (AAs) and aristolactams (ALs), which are associated, for instance, with nephropathy and cancer. These contrasting issues have stimulated the development of approaches intended to detoxification of aristoloquiaceous biomasses, among which is included the bioconversion method using larvae of the specialist phytophagous insect Battus polydamas, previously shown to be viable for chemical diversification and to reduce toxicity. Thus, eleven Aristolochia spp. were bioconverted, and the antimicrobial activities of the plant methanolic extracts and its respective bioconversion products were evaluated. The best results were found for Aristolochia esperanzae, Aristolochia gibertii, and Aristolochia ringens against Bacillus cereus, with MIC ranging from 7.8 to 31.25 μg/mL. These three species were selected for chemical, antioxidant, cytotoxic, hemolytic, and mutagenic analyses. Chemical analysis revealed 65 compounds, 21 of them possible bioconversion products. The extracts showed potential to inhibit the formation and degradation of B. cereus biofilms. Extracts of A. gibertii and its bioconverted biomass showed antioxidant activity comparable to dibutylhydroxytoluene (BHT) standard. Bioconversion decreased the hemolytic activity of A. esperanzae and the cytotoxicities of A. esperanzae and A. gibertii. None of the extracts was found to be mutagenic. The bioactivities of the fecal extracts were maintained, and biocompatibility was improved. Therefore, the results obtained in this study reveal positive expectations about the natural detoxification process of the Aristolochia species., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The epidemiology of psoriasis and cutaneous mycoses is scarce in Brazil. Thus, this cross-sectional study aimed to characterize the distribution of these diseases in Paraná. Data was obtained from the Outpatient Information System (SIA - Sistema de Informações Ambulatoriais), between 2016 and 2020. The procedures were filtered by the International Classification of Diseases (ICD). A total of 201,161 outpatient procedures were registered for psoriasis and psoriatic arthritis. The distribution concerning gender was similar (50.93% feminine; 49.07% masculine). The mean age was 51.55 years. The most frequent procedure was methotrexate dispensing (23.17%), followed by acitretin (14.29%) and adalimumab (12.55%). Adjusting to total population, the prevalence of procedures was 0.35%. Regarding cutaneous mycoses, 1,756 procedures were registered. 65% of them referred to females. White race/color was predominant (82.97%). The mean age was 37.6 years. The distribution concerning age varied according to the type of mycosis. Medical appointments (48.92%) and surgical pathology exam/biopsy (38.71%) were the most frequent procedures. The prevalence of procedures was 0.004%. This is the first epidemiological study using SIA about the population affected by psoriasis, psoriatic arthritis, and cutaneous mycoses in a Brazilian state. We believe that these findings allow relevant contribution to science and public policies in Brazil.

Objective: To evaluate if fusion computed tomography-diffusion-weighted magnetic resonance imaging may have a role in the pre-operative assessment of congenital middle-ear cholesteatoma., Methods: A retrospective chart review of surgically treated congenital middle-ear cholesteatoma patients over a 2-year timespan was conducted. Pre-operative staging was performed on computed tomography and fusion computed tomography-diffusion-weighted magnetic resonance imaging based on extension of the disease according to the ChOLE classification system and the Potsic classification system. Intra-operative staging was compared to imaging findings to evaluate accuracy of the two imaging modalities in predicting congenital middle-ear cholesteatoma extent., Results: Computed tomography was able to correctly predict congenital middle-ear cholesteatoma extent in three out of six cases according to the ChOLE classification system, all of which were staged as Ch1a and Ch1b on pre-operative computed tomography. Cases in which computed tomography was not able correctly to determine congenital middle-ear cholesteatoma extent were staged as Ch3 on pre-operative computed tomography. Fusion scans correctly determined congenital middle-ear cholesteatoma extent in all cases according to the ChOLE classification., Conclusions: Fusion computed tomography-diffusion-weighted magnetic resonance imaging may be helpful in cases of congenital middle-ear cholesteatoma where pre-operative computed tomography shows mastoid and antrum opacification, in which computed tomography alone may overestimate cholesteatoma extension beyond the level of the lateral semi-circular canal.

The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.

Objectives: To describe how the retrotympanic structures could influence the visibility of the round window niche and the round window membrane during cochlear implant surgery, and to investigate if a round window approach is possible even in cases with unfavourable anatomy., Methods: Video recordings from 37 patients who underwent cochlear implantation were reviewed. The visibility of the round window niche and round window membrane at different timepoints was assessed according to a modified version of the Saint Thomas Hospital classification. The structures that concealed the round window niche and round window membrane were evaluated., Results: After posterior tympanotomy, 54 per cent of cases had limited exposure (classes IIa, IIb and III) of the round window niche. After remodelling the retrotympanum, round window niche visibility significantly increased, with 100 per cent class I and IIa cases. Following remodelling of the round window niche, visibility of more than 50 per cent of the round window membrane surface was achieved in 100 per cent of cases., Conclusion: Remodelling the retrotympanum and the round window niche significantly increased exposure of the round window niche and round window membrane respectively, allowing round window insertion in all cases.

This study aimed to determine the antibiotic profile of microorganisms isolated from urine samples of patients with community urine tract infections (UTI) admitted to the University Hospital of the Federal University of Sao Carlos to support an appropriate local empirical treatment. A retrospective cross-sectional study was conducted from October 2018 to October 2020. Data from 1,528 positive urine cultures for bacterial pathogens and antibiograms were tabulated. Bacterial species prevalence and their resistance profile were analyzed and compared by sex and age. For Gram-negative fermenting bacteria, resistance rates were compared between patients with previous hospitalization and the total of infections caused by this group. For comparisons, the Chi-square test was performed, using Fisher's exact test when necessary (BioEstat program, adopting p ≤ 0.05). A multivariate analysis was applied to assess the effect of the studied variables in predicting multidrug resistance. Infections were more prevalent in women and older adults. Gram-negative bacteria represented 90.44% of total cultures. In both sexes, E. coli prevalence was significantly higher in adults compared with older adults (p < 0.0001). For several antibiotics, resistance rates were higher in the older adults compared with other ages and in patients with Gram-negative fermenting infections and previous hospitalization compared with the total of infections by this group of bacteria. The closer to the hospitalization, the higher the number of antibiotics with superior resistance rates. Resistance rates for aminoglycosides, carbapenems, ceftazidime, nitrofurantoin, piperacillin+tazobactam, and fosfomycin were less than 20%, considered adequate for empirical treatment. Only hospitalization in the previous 90 days was statistically significant in predicting infections by multidrug-resistant bacteria.