Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of the verITI-8 study.

Inhibitor development remains a major challenge in factor VIII (FVIII) replacement therapy. verITI-8 is the first prospective study of a recombinant FVIII Fc fusion protein (rFVIIIFc; efmoroctocog alfa) for first-time immune tolerance induction (ITI) in males with severe hemophilia A and high-titer inhibitors (historical peak ≥5 Bethesda units [BU]/mL). In this single-arm, open-label, multicenter study, screening was followed by ITI (rFVIIIFc 200 IU/kg per day until tolerization or maximum of 48 weeks). Those who achieved ITI success entered a tapering period, returning to standard prophylaxis, and then entered follow-up. Primary end point was time to tolerization with rFVIIIFc defined by inhibitor titer <0.6 BU/mL, incremental recovery (IR) ≥66% of expected IR (IR ≥1.32 IU/dL per IU/kg), and half-life (t½) ≥7 hours within 48 weeks. Sixteen patients received ≥1 rFVIIIFc dose. Twelve (75%), 11 (69%), and 10 patients (63%), respectively, achieved negative inhibitor titers, an IR ≥66%, and a t½ ≥7 hours (ie, tolerance) within 48 weeks. Median times in weeks to achieve these markers of success were 7.4 (interquartile range [IQR], 2.2-17.8), 6.8 (IQR, 5.4-22.4), and 11.7 (IQR, 9.8-26.2), respectively. All patients experienced ≥1 treatment-emergent adverse event (TEAE), and 1 reported ≥1 related TEAE (injection site pain). Nine patients experienced ≥1 treatment-emergent serious AE. No thrombotic events, discontinuations because of AEs, or deaths were reported during the study. As the first extended half-life rFVIII with prospective data in ITI, rFVIIIFc offered short time to tolerization with durable responses in almost two-thirds of patients and was well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT03093480.

First-line Anti-GD2 Therapy Combined With Consolidation Chemotherapy in 3 Patients With Newly Diagnosed Metastatic Ewing Sarcoma or Ewing-like Sarcoma.

Despite multimodal therapy, the prognosis of patients with metastatic Ewing sarcoma (ES) remains poor, with new treatments urgently needed. The disialoganglioside GD2, a well-established tumor-associated antigen, is expressed in 40% to 90% of ES cells, making it a suitable therapeutic target. Here we report 3 cases with newly diagnosed, metastatic, GD2-positive ES or Ewing-like sarcoma treated with the anti-GD2 antibody dinutuximab beta in addition to standard chemotherapeutic regimens. Treatment was well-tolerated, and all patients achieved complete remission, without evidence of relapse. First-line anti-GD2 immunotherapy in patients with metastatic, GD2-positive ES or Ewing-like sarcoma represents a promising therapeutic option that warrants further clinical evaluation.

Electrospun Polymer Materials with Fungicidal Activity: A Review.

In recent years, there has been special interest in innovative technologies such as polymer melt or solution electrospinning, electrospraying, centrifugal electrospinning, coaxial electrospinning, and others. Applying these electrokinetic methods, micro- or nanofibrous materials with high specific surface area, high porosity, and various designs for diverse applications could be created. By using these techniques it is possible to obtain fibrous materials from both synthetic and natural biocompatible and biodegradable polymers, harmless to the environment. Incorporation of low-molecular substances with biological activity (e.g., antimicrobial, antifungal) is easily feasible. Moreover, biocontrol agents, able to suppress the development and growth of plant pathogens, have been embedded in the fibrous materials as well. The application of such nanotechnologies for the creation of plant protection products is an extremely promising new direction. This review emphasizes the recent progress in the development of electrospun fungicidal dressings and their potential to be applied in modern agriculture.

Treatment of Childhood Acute Myeloid Leukemia in Bulgaria.

BACKGROUND: During the last four decades the prognosis of childhood acute myeloid leukemia (AML) has been substantially improved due to an increase in complete remission (CR) rates, event-free survival (EFS) and reduced early mortality. The relapsed AML still remains a therapeutic challenge. AIM: To report the AML treatment results of the Bulgarian pediatric oncohematological centers. MATERIALS AND METHODS: Retrospective analysis of the treatment results of children and adolescents (age from 0 to 20 years) with primary AML. Unified AML BFM- backbone type treatment protocol is used. RESULTS: This study included 97 newly diagnosed patients (44 girls and 53 boys) with AML in Bulgaria between 2003 and 2016. The median age at diagnosis was 10.2 years. The most frequent FAB-morphologic subtype was M2 followed by M4. First complete remission (CR1) was achieved in 83 patients (85.6%). The 13-year EFS was 49%, while the overall survival (OS) was 54.6%. Twenty seven (27.8%) patients relapsed, with only 5 of them being still alive towards the end of the study period. CONCLUSION: The EFS and OS for the children with AML in Bulgaria are comparable with those reported by other European groups. The prognosis of relapsed AML remains still unfavorable for the past 13 years.

Еlectrospun сellulose acetate membranes decorated with curcumin-PVP particles: preparation, antibacterial and antitumor activities.

Curcumin (Curc) exhibits anti-inflammatory, antibacterial and antitumor activity. However, its clinical application is limited by its poor bioavailability related to its extremely low water solubility. Novel materials allowing enhanced release of Curc in aqueous medium were obtained. The new materials consisted of electrospun fibers from cellulose acetate (CA) (mean fiber diameter ca. 780 nm ± 110 nm) with electrosprayed Curc/polyvinylpyrrolidone (Curc/PVP) particles. Scanning electron microscopy (SEM) showed that separated and evenly distributed particles of Curc/PVP were deposited on the surface of the mats and on the inner layers of the mat. X-ray diffraction studies showed that Curc was in amorphous state. In vitro studies demonstrated that Curc release was facilitated from Curc/PVP-on-CA mats (ca. 78% for 24 h) compared with the materials in which Curc was incorporated in CA fibers (17% for 24 h). Moreover, the curcumin-containing materials exhibited antibacterial activity against Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). Curc/PVP-on-CA fibrous mats exhibited high in vitro cytotoxicity towards HeLa tumor cells. Therefore, the obtained materials are promising for antibacterial wound dressing applications as well as for application in local treatment of cervical tumors.

Immunophenotypic Modulation of the Blast Cells in Childhood Acute Lymphoblastic Leukemia Minimal Residual Disease Detection.

UNLABELLED: Early clearance of leukemic cells during induction therapy of childhood acute lymphoblastic leukemia (ALL) is a basis for treatment optimization. Currently, the most widely used methods for the detection of minute residual malignant cells in the bone marrow and/or peripheral blood, minimal residual disease (MRD), are PCR and flow cytometry (FCM). Immunophenotypic modulation (IM) is a well known factor that can hamper the accurate FCM analysis. AIM: To report the IM detected by 8-color FCM during the BFM-type remission induction in 24 consecutive MRD-positive samples of children with B-cell precursor ALL and the possible implications for MRD detection. PATIENTS AND METHODS: Between 2010 and 2012 we prospectively followed up the MRD on days 15 and 33 of induction treatment in bone marrow (BM) samples and on day 8 in peripheral blood (PB). The IM was assessed by comparative analyses of the changes in the mean fluorescence intensity of 7 highly relevant antigens expressed by the leukemic cells and normal B-lymphocytes. RESULTS: IM occurred, to different extents, in all analyzed day 15 BM and in most day 33 BM samples. Statistically significant changes in the MFI-levels of four CDs expressed by the leukemic blasts were observed: downmodulation of CD10, CD19 and CD34 and upmodulation of CD20. No changes in the expression of CD38, CD58 and CD45 were noticed. CONCLUSIONS: Measuring the MRD by standardized 8-color flow cytometry helps improve the monitoring of the disease, leading to better therapeutic results. However, the IM of the different antigens expressed by the leukemic blasts should be taken into consideration and cautiously analyzed.

Electrospun Materials Based on Cellulose Acetate Loaded with Rosmarinic Acid with Antioxidant and Antifungal Properties.

Fibrous cellulose acetate (CA) materials loaded with rosmarinic acid (RA) were successfully created by one-pot electrospinning. In order to improve the water solubility of the polyphenolic acid and to facilitate its release from the fibrous materials, the non-ionic water-soluble polyethylene glycol (PEG) was added. Detailed characterization of the fabricated fibrous CA/RA and CA/PEG/RA materials was performed using scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), UV-Vis spectroscopy and water contact angle analysis. The optimal ratio between CA, RA and PEG for preparation of defect-free and uniform fibers was accomplished by varying their concentrations. Furthermore, the incorporation of the PEG improved the hydrophilicity and wettability of the fibrous CA materials. Moreover, PEG facilitated the RA release and over 360 min, the amount released from fibrous CA/PEG/RA fibers was 91%, while that released from CA/RA materials was 53%. Both of the RA-containing fibrous materials, with and without PEG, manifested high antioxidant activity as determined by the DPPH free radical-scavenging method. In addition, the electrospun CA/PEG/RA materials displayed good antifungal activity against C. albicans. These features make the fibrous CA/PEG/RA materials promising candidates for treatment of wound infections.

Innovative Bioactive Nanofibrous Materials Combining Medicinal and Aromatic Plant Extracts and Electrospinning Method.

Since antiquity, humans have known about plants as a medicinal cure. Recently, plant extracts are attracting more attention as a result of their natural origin and wide range of desirable features. Nanotechnology's progress and innovations enable the production of novel materials with enhanced properties for a broad range of applications. Electrospinning is a cutting-edge, flexible and economical technique that allows the creation of continuous nano- and microfibrous membranes with tunable structure, characteristics and functionalities. Electrospun fibrous materials are used in drug delivery, tissue engineering, wound healing, cosmetics, food packaging, agriculture and other fields due to their useful properties such as a large surface area to volume ratio and high porosity with small pore size. By encapsulating plant extracts in a suitable polymer matrix, electrospinning can increase the medicinal potential of these extracts, thus improving their bioavailability and maintaining the required concentration of bioactive compounds at the target site. Moreover, the created hybrid fibrous materials could possess antimicrobial, antifungal, antitumor, anti-inflammatory and antioxidant properties that make the obtained structures attractive for biomedical and pharmaceutical applications. This review summarizes the known approaches that have been applied to fabricate fibrous materials loaded with diverse plant extracts by electrospinning. Some potential applications of the extract-containing micro- and nanofibers such as wound dressings, drug delivery systems, scaffolds for tissue engineering and active food packaging systems are discussed.

Physico-Chemical, Mechanical, and Biological Properties of Polylactide/Portulaca oleracea Extract Electrospun Fibers.

Electrospinning was used to create fibrous polylactide (PLA) materials loaded with Portulaca oleracea (P. oleracea) plant extract obtained by supercritical carbon dioxide. Morphological, physico-chemical, mechanical, and biological characteristics of the fibers were studied. According to the SEM results, the diameters of smooth and defect-free fibers fabricated by a one-pot electrospinning method were at micron scale. All the obtained materials possess good mechanical properties. Additionally, it was found that the composite fibers exhibited considerable antioxidant activity. The antimicrobial activity of the fibrous materials against Gram-positive and Gram-negative bacteria was determined as well. In vitro studies showed that the electrospun biomaterials had no cytotoxic effects and that the combination of PLA and the P. oleracea extract in the fiber structure promoted cell survival and proliferation of normal mouse fibroblasts. The obtained results reveal that microfibrous mats containing the polyester-PLA and the plant extract-P. oleracea can be suitable for applications in wound healing.

Electrospun PLA-Based Biomaterials Loaded with Melissa officinalis Extract with Strong Antioxidant Activity.

In the present study, the plant extract Melissa officinalis (M. officinalis) was successfully loaded in polymer fibrous materials on the basis of a biodegradable polyester-poly(L-lactide) (PLA) and biocompatible polyether-polyethylene glycol (PEG) by applying the electrospinning method. The optimal process conditions for the preparation of hybrid fibrous materials were found. The extract concentration was varied-0, 5 or 10 wt% in respect of the polymer weight, in order to study its influence on the morphology and the physico-chemical properties of the obtained electrospun materials. All the prepared fibrous mats were composed of defect-free fibers. The mean fiber diameters of the PLA, PLA/M. officinalis (5 wt%) and PLA/M. officinalis (10 wt%) were 1370 ± 220 nm, 1398 ± 233 nm and 1506 ± 242 nm, respectively. The incorporation of the M. officinalis into the fibers resulted in slight increase of the fiber diameters and in increase of the water contact angle values to 133°. The presence of the polyether in the fabricated fibrous material assisted the wetting of the materials imparting them with hydrophilicity (the value of the water contact angle become 0°). Extract-containing fibrous materials displayed strong antioxidant activity as determined by the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method. The DPPH solution color changed to yellow and the absorbance of the DPPH radical dropped by 88.7% and 91% after being in contact with PLA/M. officinalis and PLA/PEG/M. officinalis mats, respectively. These features revealed the M. officinalis-containing fibrous biomaterials promising candidates for pharmaceutical, cosmetic and biomedical use.

Innovative Fibrous Materials Loaded with 5-Nitro-8-hydroxyquinoline via Electrospinning/Electrospraying Demonstrate Antioxidant, Antimicrobial and Anticancer Activities.

A new type of fibrous mat based on a cellulose derivative-cellulose acetate (CA) or CA and water-soluble polymers (polyvinylpyrrolidone, PVP or poly(vinyl alcohol), PVA)-loaded with the model drug 5-nitro-8-hydroxyquinoline (5N) was fabricated via electrospinning or electrospinning in conjunction with electrospraying. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), water contact angle measurements and ultraviolet-visible spectroscopy (UV-Vis) were used for the complex characterization of the obtained novel material. The decoration of CA fibers with a water-soluble polymer containing the drug resulted in the facilitation of wetting and fast drug release. The 5N-containing fibrous material showed antioxidant activity. Moreover, the proposed materials' antibacterial and antifungal properties were tested against S. aureus, E. coli, P. aeruginosa and C. albicans. Well-distinguished, sterile zones with diameters above 3.5 cm were observed around all 5N-containing mats. The mats' cytotoxicity toward HeLa carcinoma cells and normal mouse BALB/c 3T3 fibroblasts was assessed. The 5N-in-CA, PVP,5N-on-(5N-in-CA) and PVA,5N-on-(5N-in-CA) fibrous mats possessed anticancer efficacies and much lower levels of toxicity against normal cells. Therefore, the as-created novel electrospun materials, which are based on polymers loaded with the drug 5N via electrospinning/electrospraying, can potentially be applied for topical wound healing and for local cancer therapy.

Eco-Friendly Hybrid PLLA/Chitosan/Trichoderma asperellum Nanomaterials as Biocontrol Dressings against Esca Disease in Grapevines.

Fungi constitute the largest number of plant pathogens and are responsible for a range of serious plant diseases. Phaeomoniella chlamydospora (P. chlamydospora) and Phaeoacremonium aleophilum (P. aleophilum) are the main fungal pathogens causing esca disease in grapevines. On the other hand, there are beneficial microorganisms such as Trichoderma spp., which are able to control the growth of many phytopathogens. In the present study, innovative, eco-friendly hybrid nanomaterials were created by electrospinning PLLA, followed by the formation of a film of chitosan/Trichoderma asperellum (T. asperellum) spores on the fibers. The polymer carrier used in this study plays an active role in ensuring the viability of the biological agent during storage and, when placed in contact with moisture, ensures the agent's normal development. Oligochitosan, as well as low molecular weight and high molecular weight chitosan, were used. The effects of chitosan molecular weight on the dynamic viscosity of chitosan solutions, film formation, mechanical properties, spore incorporation and growth were studied. The morphology of the prepared nanomaterials, and the presence of a film based on the formation of chitosan/T. asperellum spores on the PLLA fibers, were examined using scanning electron microscopy (SEM). The surface chemical compositions of the fibrous materials were studied using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The mechanical properties of the obtained materials were also tested. The microbiological screening that was performed revealed that the eco-friendly hybrid nanomaterials incorporated with the beneficial microorganism, T. asperellum, to hamper the growth of the pathogenic P. chlamydospora and P. aleophilum fungi. The suppression rate depended on the viscosity of the chitosan solution used for the film formation. The use of oligochitosan resulted in the most effective infection of the material with T. asperellum spores. The environmentally friendly hybrid nanomaterials obtained in this study-in which the bioagent was embedded-are promising bioactive dressings for protecting grapevines against esca disease.

Electrospun 5-Chloro-7-iodo-8-hydroxyquinoline (Clioquinol)-Containing Poly(3-hydroxybutyrate)/Polyvinylpyrrolidone Antifungal Materials Prospective as Active Dressings against Esca.

Esca is a grapevine disease known for centuries which pertains to the group of so-called vine trunk diseases. Phaeomoniella chlamydospora (P. chlamydospora) and Phaeoacremonium aleophilum (P. aleophilum) are the two main fungal pathogens associated with esca. Novel fibrous materials with antifungal properties based on poly(3-hydroxybutyrate) (PHB), polyvinylpyrrolidone (PVP) and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ) were developed. One-pot electrospinning ("in" strategy) or electrospinning in conjunction with electrospraying ("on" strategy) were applied to obtain the materials. The materials' morphology and their surface chemical composition were examined using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). CQ incorporated in the bulk of the fibers or in PVP particles deposited on the fibers was in the amorphous phase, which was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction analysis (XRD). The in vitro release of CQ depended on the composition of the electrospun materials and on their design. The performed microbiological screening revealed that, unlike the non-loaded mats, the fibrous mats loaded with CQ were effective in inhibiting the growth of the pathogenic P. chlamydospora and P. aleophilum fungi. Therefore, the created materials are promising as active dressings for grapevine protection against esca.

Quercetin- and Rutin-Containing Electrospun Cellulose Acetate and Polyethylene Glycol Fibers with Antioxidant and Anticancer Properties.

Innovative fibrous materials from cellulose derivative, cellulose acetate (CA) and water-soluble polyether, polyethylene glycol (PEG) loaded with natural biologically active compounds (BAC), quercetin (QUE) and rutin (RUT), have been successfully fabricated by blend electrospinning and dual electrospinning. Scanning electron microscopy revealed that the mean fiber diameters of all the obtained fibers were in the nanometer range. QUE and RUT incorporated in the fibrous mats were in the amorphous state, as evidenced by the performed differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The presence of the polyether in the developed fibrous material assisted the in vitro release of the biologically active compounds by improving the hydrophilicity and wettability of the mats. Rutin-containing fibrous materials manifest the highest antioxidative activity, as determined by the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method. The cytotoxicity of the fabricated novel materials was evaluated using a tumor cell line and normal mouse fibroblast cells. The mats containing QUE and QUE/RUT independent of the applied spinning method show a higher cytotoxic effect against cancer cells and 3 to 4.5 times lower cytotoxicity to a noncancer cell line. These features make the quercetin- and rutin-containing fibrous materials promising candidates for pharmaceutical, cosmetic, and biomedical use.

Early Use of Dinutuximab Beta in Patients with High-Risk Neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in children, accounting for 15% of all pediatric cancer deaths. High-risk neuroblastoma (HRNB) is a particularly difficult-to-treat form of the disease that requires aggressive multimodality therapy, including induction chemotherapy, consolidation therapy with high-dose chemotherapy and autologous stem cell transplant, and maintenance therapy with dinutuximab beta. Despite treatment advances, the prognosis of these patients remains poor. As a better response to induction therapy has been associated with prolonged survival in patients with HRNB, we hypothesized that early use of dinutuximab beta-post-induction chemotherapy-may improve patient outcomes. We describe here our experience of administering at least one cycle of dinutuximab beta post-induction and prior to surgery in three children with HRNB who did not demonstrate a complete response to induction chemotherapy. All three patients achieved complete remission. Early use of dinutuximab beta may therefore have the potential to improve outcomes in patients with HRNB.

Cellulose Acetate-Based Electrospun Materials with a Variety of Biological Potentials: Antibacterial, Antifungal and Anticancer.

Novel eco-friendly fibrous materials with complex activities from cellulose acetate and cellulose acetate/polyethylene glycol (CA,PEG) containing 5-chloro-8-hydroxyquinoline as a model drug were obtained by electrospinning. Several methods, including scanning electron microscopy, X-ray diffraction analysis, ultraviolet-visible spectroscopy, water contact angle measurements, and mechanical tests, were utilized to characterize the obtained materials. The incorporation of PEG into the fibers facilitated the drug release. The amounts of the released drug from CA/5-Cl8Q and CA,PEG/5-Cl8Q were 78 ± 3.38% and 86 ± 3.02%, respectively (for 175 min). The antibacterial and antifungal activities of the obtained materials were studied. The measured zones of inhibition of CA/5-Cl8Q and CA,PEG/5-Cl8Q mats were 4.0 ± 0.18 and 4.5 ± 0.2 cm against S. aureus and around 4.0 ± 0.15 and 4.1 ± 0.22 cm against E. coli, respectively. The complete inhibition of the C. albicans growth was detected. The cytotoxicity of the obtained mats was tested toward HeLa cancer cells, SH-4 melanoma skin cells, and mouse BALB/c 3T3 fibroblasts as well. The CA/5-Cl8Q and CA,PEG/5-Cl8Q materials exhibited anticancer activity and low normal cell toxicity. Thus, the obtained fibrous materials can be suitable candidates for wound dressing applications and for application in local cancer treatment.

Electrospun Polymer-Fungicide Nanocomposites for Grapevine Protection.

Nowadays, diseases in plants are a worldwide problem. Fungi represent the largest number of plant pathogens and are responsible for a range of serious plant diseases. Esca is a grapevine disease caused mainly by fungal pathogens Phaeomoniella chlamydospora (P. chlamydospora) and Phaeoacremonium aleophilum (P. aleophilum). The currently proposed methods to fight esca are not curative. In this study, polymer composites based on biodegradable polymer containing chemical fungicides with antifungal activity were successfully prepared by electrospinning. The obtained materials were hydrophobic with good mechanical properties. In vitro studies demonstrated that the fungicide release was higher from PLLA/K5N8Q fibrous mats (ca. 72% for 50 h) compared to the released drug amount from PLLA/5-Cl8Q materials (ca. 52% for 50 h), which is due to the better water-solubility of the salt. The antifungal activity of the fibrous materials against P. chlamydospora and P. aleophilum was studied as well. The incorporation of the fungicide in the biodegradable fibers resulted in the inhibition of fungal growth. The obtained materials are perspective candidates for the protection of vines from the penetration and growth of fungal pathogens.

Polylactide stereocomplex-based electrospun materials possessing surface with antibacterial and hemostatic properties.

Novel fibrous materials of stereocomplex between high-molecular-weight poly(d- or l-)lactide (HMPDLA or HMPLLA) and diblock copolymers consisting of poly(l- or d-)lactide and poly(N,N-dimethylamino-2-ethyl methacrylate) blocks, respectively (PLLA-block-PDMAEMA or PDLA-block-PDMAEMA), were prepared by solution electrospinning. Fibers with mean diameters ranging from 1400 to 1700 nm were obtained. The stereocomplex formation was evidenced by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses. Annealing at 100 degrees C for 8 h resulted in the appearance of crystalline peaks at 2theta values of 12, 21, and 24 degrees for PLA stereocomplex. X-ray photoelectron spectroscopy (XPS) analyses revealed the gradient composition of the fibers with a surface enriched in tertiary amino groups from PDMAEMA blocks. The availability of tertiary amino groups imparts hemostatic and antibacterial properties to the stereocomplex fibrous materials, as indicated by the performed tests on blood cells and on pathogenic microorganisms.

Electrospun Eco-Friendly Materials Based on Poly(3-hydroxybutyrate) (PHB) and TiO2 with Antifungal Activity Prospective for Esca Treatment.

Esca is a type of grapevine trunk disease that severely affects vine yield and longevity. Phaeomoniella chlamydospora (P. chlamydospora) is one of the main fungi associated with esca. The aim of the present study was to obtain eco-friendly materials with potential antifungal activity against P. chlamydospora based on biodegradable and biocompatible poly(3-hydroxybutyrate) (PHB), nanosized TiO2-anatase (nanoTiO2), and chitosan oligomers (COS) by conjunction of electrospinning and electrospraying. One-pot electrospinning of a suspension of nanosized TiO2 nanoparticles in PHB solution resulted in materials in which TiO2 was incorporated within the fibers (design type "in"). Simultaneous electrospinning of PHB solution and electrospraying of the dispersion of nanosized TiO2 in COS solution enabled the preparation of materials consisting of PHB fibers on which TiO2 was deposited on the fibers' surface (design type "on"). Several methods including scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), thermogravimetric analyses (TGA) and water contact angle were utilized to characterize the obtained materials. The incorporation of nanoTiO2 in the PHB fibers, as well as nanoTiO2 deposition onto the surface of the PHB fibers resulted in increased roughness and hydrophobicity of the obtained composite fibrous materials. Moreover, TiO2-on-PHB fibrous material exhibited complete inhibition of fungal growth of P. chlamydospora. Therefore, the obtained eco-friendly fibrous materials based on PHB and nanoTiO2 are promising candidates for protection against esca in agriculture.

Magnetic Resonance Imaging of Hemophilic Joints: Correlations with the Bleeding Phenotype and Physical Examination.

INTRODUCTION: Blood-induced joint damage as a hallmark of haemophilia continues to occur despite the widespread prophylaxis. Pre-cise assessment and follow-up of joint status are crucial for tailoring their treatment. AIM: To study the correlation between the bleeding phenotype, the functional joint status, and the magnetic resonance imaging score in pediatric patients with haemophilia. MATERIALS AND METHODS: Eighty-six joints (ankles, knees, and elbows) in patients aged 10.7±0.5 (range 4 - 20) years with severe/moderate haemophilia A, severe haemophilia B and haemophilia A with inhibitors were included in the study. The joints were assessed by Haemophilia Joint Health Score 2.1 (HJHS2.1) one month after the last hemarthrosis in a non-bleeding state. The magnetic reso-nance imaging was performed on 40 (46.5%) of the examined hemophilic joints (16 ankles, 11 knees and 13 elbows). RESULTS: Joint bleeds were present in 37 (38.9%) of the joints with ankles being the most commonly affected. Sixty joints (69.8%) had normal HJHS2.1 score. Only the loss of flexion score differed significantly between the joints and the ankles had highest score. The cumulative number of hemarthrosis in the joint correlated moderately with hemosiderin deposition and strongly with the formation of subchondral cysts on magnetic resonance imaging. The magnetic resonance imaging scores for soft tissue and osteochondral domains correlated moderately with the cumulative number of hemarthrosis in the joint and only with the presence of pain and crepitus of mo-tion from the physical examination. CONCLUSIONS: Magnetic resonance imaging is more sensitive than the bleeding phenotype and physical examination in detecting early signs of haemophilic arthropathy.