Cryptococcus neoformans and Cryptococcus gattii Species Complex Isolates on the Slopes of Mount Etna, SICILY, Italy

This study investigated the presence of Cryptococcus neoformans and Cryptococcus gattii species complex isolates on olive trees growing in the Eastern part of Sicily (Italy) characterized by the presence of the volcano Etna and the ability of these fungal pathogens to sexually reproduce on medium containing volcanic soil. Samples from 124 olive trees were collected from 14 different sites around Mount Etna. Eighteen trees (14.5%) resulted colonized by C. neoformans VNI-\u3b1A isolates, one (0.8%) by VNIV-\u3b1D isolates, and two (1.6%) by C. gattii VGI-\u3b1B isolates. The ability of environmental and reference strains belonging to VNI, VNIV, and VGI molecular types to sexually reproduce on a medium containing volcanic soil was also tested. VNI and VNIV strains were able to produce filaments and basiodiospores more vigorously than on the control medium, whereas VGI strains were not fertile. In conclusion, the present study identified which C. neoformans and C. gattii species complex genotypes are circulating in Eastern Sicily and confirmed the ecological role of olive trees as environmental reservoir of these pathogens. It also showed that Cryptococcus is able to colonize and sexually reproduce in inhospitable environments such as the slopes of a volcano

A disulfide bridge allows for site-selective binding in liver bile acid binding protein thereby stabilising the orientation of key amino acid side chains

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First Isolation, Antifungal Susceptibility, and Molecular Characterization of Cryptococcus neoformans from the Environment in Croatia

The purpose of this study was to investigate the presence of Cryptococcus neoformans species complex isolates from environmental sources in Croatia and to determine their molecular types and antifungal susceptibility. Swab samples of tree hollows and bird excreta in the soil beneath trees were collected. Samples included 472 (92.73%) samples obtained from tree hollows and 37 (7.27%) samples from bird excreta. Four C. neoformans species complex isolates were recovered from tree hollow swabs along the Mediterranean coast, while there were no isolates recovered from bird excreta or from the continental area. Three isolates were identified as molecular types VNI and one as VNIV. All tested antifungals showed high in vitro activity against the four isolates. This is the first report proving the presence of C. neoformans species complex in the environment of Croatia. The results of the study suggest a major risk of exposure for inhabitants living along the Croatian coast and that both VNI and VNIV molecular types can be expected in clinical cases of cryptococcosis. Susceptibility to antifungals confirmed that no resistance should be expected in patients with cryptococcosis at the present time

Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: an experimental approach

Background: Articular cartilage, because of its avascular nature, has little capacity for spontaneous healing, and tissue engineering approaches, employing different biomaterials and cells, are under development. Among the investigated biomaterials are the chitosan-based hydrogels. Although thoroughly studied in other mammalian species, studies are scarce in equines. So, the aim of the present study was to investigate the biocompatibility of chitosan-GP in horse joints submitted to high mechanical loads.Results: An osteochondral defect was created by arthroscopy in the medial surface of lateral trochlea of talus of left or right leg, randomly selected, from six healthy geldings. the defect was filled up with chitosan-GP. the contralateral joint received an identical defect with no implant. the chondral fragment removed to produce the defect was collected, processed and used as the Initial sample (normal cartilage) for histology, immunohistochemistry, and metabolic labelling of PGs. After 180 days, the repair tissues were collected, and also analyzed. At the end of the experiment (180 days after lesion), the total number of cells per field in repair tissues was equal to control, and macrophages and polymorphonuclear cells were not detected, suggesting that no significant inflammation was present. These cells were able to synthesize type II collagen and proteoglycans (PGs). Nevertheless, the cell population in these tissues, both in presence of chitosan-GP and in untreated controls, were heterogeneous, with a lower proportion of type II collagen-positives cells and some with a fibroblastic aspect. Moreover, the PGs synthesized in repair tissues formed in presence or absence of chitosan-GP were similar to those of normal cartilage. However, the chitosan-GP treated tissue had an disorganized appearance, and blood vessels were present.Conclusions: Implanted chitosan-GP did not evoke an important inflammatory reaction, and permitted cell growth. These cells were able to synthesize type II collagen and PGs similar to those synthesized in normal cartilage and in healing tissue without implant, indicating its chondrocyte nature.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Fac Med Vet & Zootecnia, Dept Cirurgia, BR-09500900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, BR-04044020 São Paulo, BrazilUniv São Paulo, Fac Med Vet & Zootecnia, Dept Clin Med, BR-09500900 São Paulo, BrazilUniv São Paulo, Fac Med Vet & Zootecnia, Dept Patol, BR-09500900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, BR-04044020 São Paulo, BrazilWeb of Scienc

The effects of anthocyanin-rich Myrtaceae fruits peel powder on fibrosis-associated hepatocarcinogenesisin mice.

Fruits from Myrtaceae family, as jabuticaba (Myrciaria jaboticaba (Vell) O. Berg), jamelão (Syzygium cumini (L.) Skeels) and jambo (Syzygium malaccense), raise interest due to their high levels of anthocyanins, antioxidant compounds, and, thus, potential for chronic disease risk reduction¹. Therefore, the study evaluated whether the ingestion of jabuticaba, jamelão or jambo peel powder attenuates fibrosis-associated hepatocarcinogenesis. Neonatal female C3H/Hej mice were submitted to a diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced fibrosis-associated hepatocarcinogenesis model. Mice also received basal diet or basal diet containing 2% of jabuticaba, jamelão or jambo dehydrated peels for 10 weeks. HPLC analysis of dehydrated fruit peels revealed high levels of anthocyanins in jabuticaba (802.89±22.88 mg/100g), jamelão (575.95±9.42 mg/100g) and jambo (156.05±10.39 mg/100g). These fruits displayed different types of anthocyanins (Figures 1-3). Interestingly, only the ingestion of basal diet containing jamelão peel powder attenuated liver fibrosis compared to DEN/CCl4 (Figure 4). Mechanisms will be evaluated, as well as the effects of these fruits on the development of preneoplasic/neoplastic liver lesions.WTPC. 21 a 26 de abril

Minerva User Manual Version 1.0

MINERVA (Modality-Inclusive Environment for Radiotherapeutic Variable Analysis) is a Java-based patient-centric radiation treatment planning system (RTPS) for computational dosimetry and treatment planning in emerging areas of radiotherapy for cancer and other diseases. MINERVA was primarily developed at the Idaho National Laboratory (INL) and Montana State University (MSU). MINERVA allows the radiotherapist to make side-by-side comparison of plans for multiple treatment modalities with a common anatomical basis for the computational geometry, calculate doses for combinations of different radiotherapy modalities, and perform dose analysis and reporting functions. This provides the therapist with a consistent basis for selecting the modality or combination of modalities to use for treatment of the patient. MINERVA employs an integrated, lightweight plug-in architecture to accommodate multi-modal treatment planning using standard interface components. The MINERVA design facilitates integration of improved or emerging treatment planning technologies. MINERVA consists of the basic radiation treatment planning software modules managed by a consistent patient interface for developing multi-modal radiotherapy patient treatment plans. One of MINERVA's main functions is to provide a graphical environment for constructing and displaying uniform volume-element-based solid models derived from medical images. These solid models form the geometric basis of the target areas for the radiation transport model

Optimal Sensor Placement with Adaptive Constraints for Nuclear Digital Twins

Given harsh operating conditions and physical constraints in reactors, nuclear applications cannot afford to equip the physical asset with a large array of sensors. Therefore, it is crucial to carefully determine the placement of sensors within the given spatial limitations, enabling the reconstruction of reactor flow fields and the creation of nuclear digital twins. Various design considerations are imposed, such as predetermined sensor locations, restricted areas within the reactor, a fixed number of sensors allocated to a specific region, or sensors positioned at a designated distance from one another. We develop a data-driven technique that integrates constraints into an optimization procedure for sensor placement, aiming to minimize reconstruction errors. Our approach employs a greedy algorithm that can optimize sensor locations on a grid, adhering to user-defined constraints. We demonstrate the near optimality of our algorithm by computing all possible configurations for selecting a certain number of sensors for a randomly generated state space system. In this work, the algorithm is demonstrated on the Out-of-Pile Testing and Instrumentation Transient Water Irradiation System (OPTI-TWIST) prototype vessel, which is electrically heated to mimic the neutronics effect of the Transient Reactor Test facility (TREAT) at Idaho National Laboratory (INL). The resulting sensor-based reconstruction of temperature within the OPTI-TWIST minimizes error, provides probabilistic bounds for noise-induced uncertainty and will finally be used for communication between the digital twin and experimental facility

Epidemiological characteristics of cryptococcal meningoencephalitis associated with Cryptococcus neoformans var. grubii from HIV-infected patients in Madagascar : a cross-sectional study

Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts 64200/\u3bcl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10-12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9-20.3) for cryptococcal infection and 10.9% (95% CI 6.1-17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p<0.001). The 13 Cryptococcus strains obtained at baseline were all Cryptococcus neoformans var. grubii, genotypes VNI-\u3b1A (3 isolates), VNII-\u3b1A (4 isolates) or hybrid VNI/VNII-\u3b1AA\u3b1 (6 isolates), suggesting high diversity. Two strains acquired fluconazole resistance after four and five months of exposure, respectively. The prevalence of cryptococcosis is high in Madagascar and this serious condition is life-threatening in HIV-infected patients. These findings will be used to raise the awareness of national authorities to strengthen the national HIV/AIDS control program

Clinical course of Coronavirus Disease-19 in patients with haematological malignancies is characterized by a longer time to respiratory deterioration compared to non-haematological ones: results from a case-control study

Background We evaluated clinical features and risk factors for mortality in patients with haematological malignancies and COVID-19. Methods Retrospective, case-control (1:3) study in hospitalized patients with COVID-19. Cases were patients with haematological malignancies and COVID-19, controls had COVID-19 without haematological malignancies. Patients were matched for sex, age and time of hospitalization. Results Overall, 66 cases and 198 controls were included in the study. Cases had higher prior corticosteroid use, infection rates, thrombocytopenia and neutropenia and more likely received corticosteroids and antibiotics than controls. Cases had higher respiratory deterioration than controls (78.7% vs 65.5%, p = 0.04). Notably, 29% of cases developed respiratory worsening > 10 days after hospital admission, compared to only 5% in controls. Intensive Care Unit admission and mortality were higher in cases than in controls (27% vs 8%, p = 0.002, and 35% vs 10%, p < 0.001). At multivariable analysis, having haematological malignancy [OR4.76, p < 0.001], chronic corticosteroid therapy [OR3.65, p = 0.004], prior infections [OR57.7, p = 0.006], thrombocytopenia [OR3.03, p < 0.001] and neutropenia [OR31.1, p = 0.001], low albumin levels [OR3.1, p = 0.001] and >= 10 days from hospital admission to respiratory worsening [OR3.3, p = 0.002] were independently associated with mortality. In cases, neutropenia [OR3.1, p < 0.001], prior infections [OR7.7, p < 0.001], >= 10 days to respiratory worsening [OR4.1, p < 0.001], multiple myeloma [OR1.5, p = 0.044], the variation of the CT lung score during hospitalization [OR2.6, p = 0.006] and active treatment [OR 4.4, p < 0.001] all were associated with a worse outcome. Conclusion An underlying haematological malignancy was associated with a worse clinical outcome in COVID-19 patients. A prolonged clinical monitoring is needed, since respiratory worsening may occur later during hospitalization

Effect of ceftazidime/avibactam plus fosfomycin combination on 30 day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae. Results from a multicentre retrospective study

Introduction The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Materials and methods From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam +/- other). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score. Results Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam +/- other). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS >= 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective. Conclusions Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens