Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone.

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

Short Review on the Biological Activity of Cyclodextrin-Drug Inclusion Complexes Applicable in Veterinary Therapy.

Cyclodextrins (CDs) are a family of carrier molecules used to improve the pharmacokinetic parameters of therapeutic molecules. These cyclic oligosaccharides have medical and pharmaceutical applications by being able to form inclusion complexes with molecules that are poorly soluble in water. The benefits of these complexes are directed towards improving the chemical and biological properties-i.e., solubility, bioavailability, stability, non-toxicity and shelf life of drug molecules. Since the 1960s, the first inclusion complexes used in therapeutics were those with α-, ß- and γ-CD, which proved their usefulness, but had certain degrees of particularly renal toxicity. Currently, to correct these deficiencies, ß-CD derivatives are most frequently used, such as sulfobutylether-ß-CD, hydroxypropyl-ß-CD, etc. Therefore, it is of interest to bring to the attention of those interested the diversity of current and potential future clinical applications of inclusion complexes in veterinary medicine and to present the contribution of these inclusion complexes in improving drug efficacy. The most important biological activities of ß-CD complexed molecules in the veterinary field are summarized in this short review.

The Effectiveness of Laser Applications and Photodynamic Therapy on Relevant Periodontal Pathogens (Aggregatibacter actinomycetemcomitans) Associated with Immunomodulating Anti-rheumatic Drugs.

Considering the current context of the increasing resistance of bacterial species to antibiotics and other antimicrobial agents, a major objective is to develop other antimicrobial approaches, which would be able to inactivate pathogens with considerable effectiveness. Two such methods are photodynamic disinfection therapy and laser irradiation. In view of the immunocompromised status of some patients under immunosuppressive therapy and potential drug interactions that can be established between systemic antimicrobial agents, the research of local, minimally invasive methods of inactivating periodontal pathogens in the context of these systemic therapies with modifying drugs of the immune response is justified. This in vitro study evaluated the antimicrobial action of a diode laser, wavelength 940 nm, and photodisinfection therapy at 670 nm (photosensitizer, 3,7 dimethyl phenothiazine chloride) on a type strain of Aggregatibacter actinomycetemcomitans, a known periodontal pathogen, in the presence and absence of active substances used in autoimmune disease therapy (Etanercept, Infliximab, Metothrexate). The association of a conventional antirheumatic drug with anti-TNF-α therapy determined a significantly greater inhibition of the strain of A. actinomycetemcomitans compared to monotherapy, in vitro. Photodisinfection caused a significant reduction in bacterial burden after a 30 s exposure in vitro, regardless of the pharmaceutical associations of biological and conventional disease-modifying antirheumatic drugs (DMARDs). Irradiation with a diode laser for 30 s at a power of 5 W caused a greater reduction compared to irradiation with 1 W. The application of laser and photodisinfection induced a significant reduction in Aggregatibacter actinomycetemcomitans in vitro and could be considered important adjunctive measures for the eradication of this oral pathogen in the context of immunomodulating therapy.

Expression of matrix metalloproteinases (MMPs)-2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)-1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection.

Introduction: Bovine papillomaviruses -1/-2 (BPVs) are small non-enveloped double-stranded DNA viruses able to infect the skin of bovids and equids, causing development of neoplastic lesions such as bovine cutaneous fibropapillomas and equine sarcoid. Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that degrade basal membrane and extracellular matrix, whose function is essential in physiological processes such as tissue remodeling and wound healing. MMPs activity is finely regulated by a balancing with expression of tissue inhibitors of MMPs (TIMPs), a process that is impaired during tumour development. BPV infection is associated with upregulation of MMPs and /or their unbalancing with TIMPs, contributing to local invasion and impairment of extracellular matrix remodeling in equine sarcoid; however, studies regarding this topic in bovine fibropapillomas are lacking. Methods: The aim of this study was to perform an immunohistochemical and biochemical analysis on a panel of MMPs and TIMPs in BPV-2 positive bovine cutaneous fibropapillomas vs. normal skin samples. Results: Immunohistochemistry revealed a cytoplasmic expression of MMP-2 (15/19), a cytoplasmic and perinuclear immunoreactivity of MMP-7 (19/19) and MMP-9 (19/19), along with a cytoplasmic and nuclear pattern of MMP-14 (16/19), accompanied by a cytoplasmic expression of TIMP-1 (14/19) and TIMP-2 (18/19) in tumour samples; western blotting revealed an overexpression of MMP-2 (8/9), MMP-7 (9/9) and MMP-9 (9/9), and a decreased level of MMP-14 (9/9), TIMP-1 (9/9) and TIMP-2 (9/9) in tumour versus normal skin samples. Moreover, gelatine zymography confirmed the expression of pro-active MMP-2 (9/9) and MMP-9 (9/9) and, most importantly, indicated the presence and increased activity of their active forms (82 and 62 kDa, respectively) in tumour samples. Discussion: This is the first study describing MMPs and TIMPs in bovine cutaneous fibropapillomas and our results suggest that their unbalanced expression in presence of BPV-2 may play a significant role in tumour development. A further analysis of supplementary MMPs and TIMPs could bring new important insights into the papillomavirus induced tumours.

Amphiphilic Chitosan Porous Membranes as Potential Therapeutic Systems with Analgesic Effect for Burn Care.

Eliminating or at least lessening the pain is a crucial aspect of burns management, as pain can negatively affect mental health and quality of life, and it can also induce a delay on wound healing. In this context, new amphiphilic chitosan 3D porous membranes were developed and investigated as burns therapeutic systems with analgesic effect for delivery of lidocaine as local anesthetic. The highly porous morphology of the membranes and the structural modifications were evidenced by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and infrared spectroscopy (FTIR). Improved compression mechanical properties, long-term hydrolytic degradation (28 days) evaluation and high swelling capacities (ranging from 8 to 22.6 g/g) indicate an increased capacity of the prepared membranes to absorb physiological fluids (burns exudate). Lidocaine in vitro release efficiency was favored by the decreased content of cross-linking agent (reaching maximum value of 95.24%) and the kinetic data modeling, indicating that lidocaine release occurs by quasi-Fickian diffusion. In addition to the in vitro evaluation of analgesic effect, lidocaine-loaded chitosan membranes were successfully investigated and proved antibacterial activity against most common pathogens in burns infections: Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus.

Evaluation of Physically and/or Chemically Modified Chitosan Hydrogels for Proficient Release of Insoluble Nystatin in Simulated Fluids.

To avoid fungal spreading in the bloodstream and internal organs, many research efforts concentrate on finding appropriate candidiasis treatment from the initial stage. This paper proposes chitosan-based physically or chemically cross-linked hydrogels aimed to provide sustained release of micronized nystatin (NYSm) antifungal drug, known for its large activity spectrum. Nystatin was demonstrated itself to provide hydrodynamic/mechanic stability to the chitosan hydrogel through hydrophobic interactions and H-bonds. For chemical cross-linking of the succinylated chitosan, a non-toxic diepoxy-functionalized siloxane compound was used. The chemical structure and composition of the hydrogels, also their morphology, were evidenced by infrared spectroscopy (FTIR), by energy dispersive X-ray (EDX) analysis and by scanning electron microscopy (SEM), respectively. The hydrogels presented mechanical properties which mimic those of the soft tissues (elastic moduli < 1 MPa), necessary to ensure matrix accommodation and bioadhesion. Maximum swelling capacities were reached by the hydrogels with higher succinic anhydride content at both pH 7.4 (429%) and pH 4.2 (471%), while higher amounts of nystatin released in the simulative immersion media (57% in acidic pH and 51% in pH 7.4) occurred from the physical cross-linked hydrogel. The release mechanism by non-swellable matrix diffusion and the susceptibility of three Candida strains make all the hydrogel formulations effective for NYSm local delivery and for combating fungal infections.

Pegylation of phenothiazine - A synthetic route towards potent anticancer drugs.

Introduction: Cancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs. Objectives: The paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs. Methods: Two PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Their antitumor activity has been investigated on five human tumour lines and a mouse tumor line as well, by determination of IC50. The in vivo toxicity was determined by measuring the LD50 in BALB/c mice by the sequential method and the in vivo antitumor potential was measured by the tumours growth test. The antitumor mechanism was investigated by complexation studies of zinc and magnesium ions characteristic to the farnesyltransferase enzyme, by studies of self-aggregation in the cells proximity and by investigation of the antitumor properties of the acid species resulted by enzymatic cleavage of the PEGylated derivatives. Results: The two compounds showed antitumor activity, with IC50 against mouse colon carcinoma cell line comparable with that of the traditional antitumor drugs 5-Fluorouracil and doxorubicin. The phenothiazine PEGylation resulted in a significant toxicity diminishing, the LD50 in BALB/c mice increasing from 952.38 up to 1450 mg/kg, in phenothiazine equivalents. Both compounds inflicted a 92% inhibition of the tumour growth for doses much smaller than LD50. The investigation of the possible tumour inhibition mechanism suggested the nanoaggregate formation and the cleavage of ester bonds as key factors for the inhibition of cancer cell proliferation and biocompatibility improvement. Conclusion: Phenothiazine and PEG building blocks have a synergetic effect working for both tumour growth inhibition and biocompatibility improvement. All these findings recommend the PEGylated phenothiazine derivatives as a valuable workbench for a next generation of antitumor drugs.

Antifungal and anti-virulence activity of six essential oils against important Candida species - a preliminary study.

Opportunistic infections with Candida species are becoming more problematic, considering their increasing virulence and resistance to antifungal drugs. Aim: To assess the antifungal and anti-virulence activity of basil, cinnamon, clove, melaleuca, oregano and thyme essential oils (EOs) on five Candida species (C. albicans, C. auris, C. krusei, C. parapsilosis and C. guillermondii). Methods: The MIC, growth rate, antibiofilm activity, regulation of gene expression (ALS3, SAP2, HSP70) and germ-tube formation were evaluated by specific methods. Results: Most EOs inhibited Candida species growth and reduced the expression of some virulence factors. Cinnamon and clove EO showed the most significant inhibitory effects. Conclusions: The tested EOs are promising agents for facilitating the management of some Candida infections.

The current state of Clinical Mycology in Eastern and South-Eastern Europe.

The ability of medical centers in Eastern and South-Eastern Europe to diagnose and treat fungal infections remains unknown. In order to investigate that, here we conducted a cross-sectional online survey, released at both The International Society for Human & Animal Mycology (ISHAM) and European Confederation of Medical Mycology (ECMM) websites. A total of 31 institutions responded to the questionnaire. Most centers (87.1%, n = 27) had access to Aspergillus spp. ELISA galactomannan testing as well as to Cryptococcus spp. antigen testing (83.9%, n = 26). Serological tests were mostly available for Aspergillus species (80.6%, n = 25); and most institutions reported access to mold-active antifungal drugs (83.9%; n = 26), but 5-flucytosine was available to only 29% (n = 9) of the participant centers. In conclusion, this study represents the first attempt to document the strengths and limitations of the Eastern and South-Eastern European region for diagnosing and treating fungal diseases. LAY SUMMARY: Our article is about the availability of diagnostic and treatments tools related to fungal infections in the countries of Eastern and South-Eastern region. Surveys like these are important to understand the gaps and point towards the fungal infections as a global health issue.

Expression of collagenases (matrix metalloproteinase-1, -8, -13) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in naturally occurring bovine cutaneous fibropapillomas.

Bovine cutaneous fibropapillomas are among the most common skin tumors in cattle; their etiology is associated with infection by bovine papillomavirus (BPV) types-1/-2 which are considered oncogenic. Degradation of the extracellular matrix (ECM), especially collagenolysis, is a key event during a series of relevant physiological processes, including tissue remodeling and repair. Various types of proteins are implicated in the regulation of ECM degradation: among these, matrix metalloproteinases (MMPs), a group of zinc-dependent endoenzymes, and tissue inhibitors of matrix metalloproteinases (TIMPs) are known to play a major role. Previous studies reported that aberrant expression of collagenolytic MMPs (MMP-1/-8/-13) and unbalancing between MMPs and TIMPs represent a critical step in tumor growth and invasion; however, studies regarding this topic in bovine cutaneous fibropapillomas are lacking. The aim of this study was to investigate the expression of the collagenases MMP-1/-8/-13 and TIMP-3 in naturally occurring fibropapillomas harboring BPV-2 DNA and normal skin samples. Here, by immunohistochemistry and western blotting analysis, we demonstrated overexpression of MMP-8/-13 along with a down-regulation of MMP-1, associated with a decrease in TIMP-3 levels in tumor compared with normal skin samples. This is the first study describing MMP-1/-8/-13 and TIMP-3 expression in bovine cutaneous fibropapillomas and our results suggest that an impaired expression of collagenases along with an imbalance between MMPs/TIMPs may contribute to an increased collagenolytic activity, which in turn could be important in ECM changes and tumors development.

Synthesis, Characterization, and Antifungal Activity of Silver Nanoparticles Embedded in Pullulan Matrices.

Steady developments made in nanotechnology-based products have facilitated new perspectives for combating drug-resistant fungi. Silver nanoparticles represent one of the most attractive nanomaterials in biomedicine due to their exclusive optical, electromagnetic, and catalytic properties and antifungal potency compared with other metal nanoparticles. Most studies show that the physicochemical parameters affecting the antifungal potential of AgNPs include the shape, size, surface charge, and concentration and colloidal state. For the present study, pullulan (P) and its oxidized counterpart (PO) have been selected as matrices for the silver nanoparticles' generation and stabilization (AgNPs). The TEMPO (2,2,6,6-tetramethylpiperidin-1-yl radical)-sodium hypochlorite-sodium bromide system was used for the C6 selective oxidation of pullulan in order to introduce negatively charged carboxylic groups in its structure. The structure and morphology of the synthesized AgNPs were analyzed using FTIR and EDX. The main objective of this study was to elucidate the antifungal activity of AgNPs on the clinical yeasts isolates and compare the performance of AgNPs with the conventional antifungals. In this study, different concentrations of AgNPs were tested to examine antifungal activity on various clinical isolates.

Toxicity Assessment of Long-Term Exposure to Non-Thermal Plasma Activated Water in Mice.

Non-thermal plasma activated water (PAW) has recently emerged as a powerful antimicrobial agent. Despite numerous potential bio-medical applications, studies concerning toxicity in live animals, especially after long-term exposure, are scarce. Our study aimed to assess the effects of long-term watering with PAW on the health of CD1 mice. PAW was prepared from distilled water with a GlidArc reactor according to a previously published protocol. The pH was 2.78. The mice received PAW (experimental group) or tap water (control group) daily for 90 days as the sole water source. After 90 days, the following investigations were performed on the euthanatized animals: gross necropsy, teeth mineral composition, histopathology, immunohistochemistry, hematology, blood biochemistry, methemoglobin level and cytokine profile. Mice tolerated PAW very well and no adverse effects were observed during the entire period of the experiment. Histopathological examination of the organs and tissues did not reveal any structural changes. Moreover, the expression of proliferation markers PCNA and Ki67 has not been identified in the epithelium of the upper digestive tract, indicating the absence of any pre- or neoplastic transformations. The results of our study demonstrated that long-term exposure to PAW caused no toxic effects and could be used as oral antiseptic solution in dental medicine.

Total Aseptization of Boar Semen, to Increase the Biosecurity of Reproduction in Swine.

The aim of the study was to establish the complete microbiological profile of boar semen (Sus scrofa domesticus) and to choose the most effective antiseptic measures in order to control and optimize AI reproduction in pig farms. One hundred and one semen samples were collected and analyzed from several pig farms. The microbiological profile of ejaculates was determined by evaluating the degree of contamination of fresh semen and after dilution with specific extenders. The bacterial and fungal load of fresh boar semen recorded an average value of 82.41/0.149 × 103 CFU/mL, while after diluting the ejaculates the contamination value was 0.354/0.140 × 103 CFU/mL. Twenty-four germs (15 bacterial and 9 fungal species) were isolated, the most common being Candida parapsilosis/sake (92%) and Escherichia coli (81.2%). Modification of the sperm collection protocol (HPBC) reduced contamination in raw sperm by 49.85% in bacteria (significant (p < 0.00001) and by 9.67% in fungi (non-significant (p < 0.111491). The load in bacteria and filamentous fungi can be controllable, but not in levuras fungi. Some fluconazole-added extenders (12.5 mg%), ensure fungal aseptization, and even an increase in sperm progressivity (8.39%) for at least a 12 h shelf life after dilution. Validation of sperm aseptization was done by maintaining sow fecundity unchanged after AI (insignificant p > 0.05).

Clinical Profile of 24 AIDS Patients with Cryptococcal Meningitis in the HAART Era: A Report from an Infectious Diseases Tertiary Hospital in Western Romania.

Management of cryptococcal infections among patients suffering from acquired immunodeficiency syndrome (AIDS) represents a medical challenge. This retrospective study aims to describe the disease management and outcomes among 24 AIDS patients who suffered from Cryptococcus neoformans meningitis. The parameters evaluated from our patients' database records include epidemiological data, clinical manifestations, biochemical and microbiological analysis of patients' cerebrospinal fluid (CSF), treatment profiles, and disease outcomes. All patients included in the study had a lymphocyte count of less than 200 CD4/mm3. Of the 24 patients included in this study, five had been diagnosed with HIV infection since childhood, after receiving HIV-infected blood transfusions. The most prominent symptom was fatigue in 62.5% of patients, followed by nausea/vomiting and headache. Seven patients had liver cirrhosis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, while Kaposi sarcoma and cerebral toxoplasmosis were found in two patients. Six out of 24 patients died due to bacterial sepsis and acute respiratory distress syndrome (ARDS). High intracranial pressure was the strongest predictive factor for mortality (OR = 2.9), followed by ARDS (OR = 1.8), seizures at disease onset (OR = 1.4), and diabetes mellitus (OR = 1.2). Interestingly, patients younger than 40 years old had a significantly lower survival rate than that of the older patients. Before developing Cryptococcal meningitis, all patients had low adherence to the early ART treatment scheme and skipped the follow-up visits. All patients received a combination of amphotericin B and flucytosine as induction therapy, adding fluconazole for maintenance. Simultaneously, AIDS HAART was initiated at diagnosis of the cryptococcal infection. A combined regimen of antifungals and highly active antiretroviral therapy showed improved patient recovery with minor side effects.

Geographical Variations in Virulence Factors and Antimicrobial Resistance Amongst Staphylococci Isolated From Dogs From the United Kingdom and Romania.

The objective of this study was to compare virulence and resistance factors of mucosal and cutaneous staphylococci from dogs with pyoderma in the UK and Romania, two countries with different approaches to antimicrobial use in companion animals. Staphylococcal isolates (n = 166) identified to the species level as being Staphylococcus pseudintermedius or coagulase negative (CoNS) were analyzed for their antimicrobial resistance (AMR) profile and presence of resistance and virulence genes. Of the investigated isolates, 26 were methicillin-resistant S. pseudintermedius (MRSP), 89 were methicillin-susceptible S. pseudintermedius (MSSP) and 51 were coagulase negative staphylococci (CoNS). A significantly larger number of isolates originating from Romania were resistant to clindamycin, tetracycline, and chloramphenicol compared to the UK isolates (P < 0.05). Resistance to amoxicillin-clavulanic acid, gentamicin, and trimethoprim-sulphamethoxazole was more evident in UK isolates. Fusidic acid resistance was common in Staphylococcus spp. isolates from both countries. Most isolates carried virulence factors associated with siet (exfoliative toxin) and luk (leucocidin) genes. All MRSP UK isolates exhibited fusidic acid resistance genes whilst this was very rare in the MRSP isolates from Romania. The chlorhexidine resistance gene qacA/B was frequently identified in CoNS isolates from the UK (P < 0.001). The current study documented differences in antimicrobial resistance profiles of Staphylococcus spp. isolates from dogs in two geographical locations in Europe, which could reflect differences in antimicrobial prescribing patterns. The study also highlights the need for further studies and interventions on antimicrobial use, prescribing patterns and AMR surveillance in companion animals in Romania.

Diagnosis of Pneumocystis jirovecii Pneumonia in Pediatric Patients in Serbia, Greece, and Romania. Current Status and Challenges for Collaboration.

Pneumocystis jirovecii can cause fatal Pneumocystis pneumonia (PcP). Many children have been exposed to the fungus and are colonized in early age, while some individuals at high risk for fungal infections may develop PcP, a disease that is difficult to diagnose. Insufficient laboratory availability, lack of knowledge, and local epidemiology gaps make the problem more serious. Traditionally, the diagnosis is based on microscopic visualization of Pneumocystis in respiratory specimens. The molecular diagnosis is important but not widely used. The aim of this study was to collect initial indicative data from Serbia, Greece, and Romania concerning pediatric patients with suspected PcP in order to: find the key underlying diseases, determine current clinical and laboratory practices, and try to propose an integrative future molecular perspective based on regional collaboration. Data were collected by the search of literature and the use of an online questionnaire, filled by relevant scientists specialized in the field. All three countries presented similar clinical practices in terms of PcP prophylaxis and clinical suspicion. In Serbia and Greece the hematology/oncology diseases are the main risks, while in Romania HIV infection is an additional risk. Molecular diagnosis is available only in Greece. PcP seems to be under-diagnosed and regional collaboration in the field of laboratory diagnosis with an emphasis on molecular approaches may help to cover the gaps and improve the practices.

Invasive Scedosporium spp. and Lomentospora prolificans infections in pediatric patients: Analysis of 55 cases from FungiScope® and the literature.

OBJECTIVES: Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections. METHODS: Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected. RESULTS: Fifty-five children (median age 9 years [IQR: 5-14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment. Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3-28] versus 61 days [IQR: 16-148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35-51.40] and HR 6.12 [95% CI 1.52-24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11-0.99] and HR 0.09 [95% CI 0.02-0.40], respectively). CONCLUSIONS: Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome.

Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.

In Vitro and In Vivo Antioxidant Activity of the New Magnetic-Cerium Oxide Nanoconjugates.

BACKGROUND: Cerium oxide nanoparticles present the mimetic activity of superoxide dismutase, being able to inactivate the excess of reactive oxygen species (ROS) correlated with a large number of pathologies, such as stents restenosis and the occurrence of genetic mutations that can cause cancer. This study presents the synthesis and biological characterisation of nanoconjugates based on nanoparticles of iron oxide interconnected with cerium oxide conjugates. METHODS: The synthesis of magnetite-nanoceria nanoconjugates has been done in several stages, where the key to the process is the coating of nanoparticles with polyethyleneimine and its chemical activation-reticulation with glutaraldehyde. The nanoconjugates are characterised by several techniques, and the antioxidant activity was evaluated in vitro and in vivo. RESULTS: Iron oxide nanoparticles interconnected with cerium oxide nanoparticles were obtained, having an average diameter of 8 nm. Nanoconjugates prove to possess superparamagnetic properties and the saturation magnetisation varies with the addition of diamagnetic components in the system, remaining within the limits of biomedical applications. In vitro free-radical scavenging properties of nanoceria are improved after the coating of nanoparticles with polyethylenimine and conjugation with magnetite nanoparticles. In vivo studies reveal increased antioxidant activity in all organs and fluids collected from mice, which demonstrates the ability of the nanoconjugates to reduce oxidative stress. CONCLUSION: Nanoconjugates possess magnetic properties, being able to scavenge free radicals, reducing the oxidative stress. The combination of the two properties mentioned above makes them excellent candidates for theranostic applications.

ECMM CandiReg-A ready to use platform for outbreaks and epidemiological studies.

BACKGROUND: Recent outbreaks of Candida auris further exemplify that invasive Candida infections are a substantial threat to patients and healthcare systems. Even short treatment delays are associated with higher mortality rates. Epidemiological shifts towards more resistant Candida spp. require careful surveillance. OBJECTIVES: Triggered by the emergence of C auris and by increasing antifungal resistance rates the European Confederation of Medical Mycology developed an international Candida Registry (FungiScope™ CandiReg) to allow contemporary multinational surveillance. METHODS: CandiReg serves as platform for international cooperation to enhance research regarding invasive Candida infections. CandiReg uses the General Data Protection Regulation compliant data platform ClinicalSurveys.net that holds the electronic case report forms (eCRF). Data entry is supported via an interactive macro created by the software that can be accessed via any Internet browser. RESULTS: CandiReg provides an eCRF for invasive Candida infections that can be used for a variety of studies from cohort studies on attributable mortality to evaluations of guideline adherence, offering to the investigators of the 28 ECMM member countries the opportunity to document their cases of invasive Candida infection. CandiReg allows the monitoring of epidemiology of invasive Candida infections, including monitoring of multinational outbreaks. Here, we describe the structure and management of the CandiReg platform. CONCLUSION: CandiReg supports the collection of clinical information and isolates to improve the knowledge on epidemiology and eventually to improve management of invasive Candida infections. CandiReg promotes international collaboration, improving the availability and quality of evidence on invasive Candida infection and contributes to improved patient management.