Resilience strengthening in youth with a chronic medical condition: a randomized controlled feasibility trial of a combined app and coaching program.

Youth with a chronic medical condition (CMC) are often affected by comorbid mental disorders. Resilience-strengthening interventions can protect youth's mental health, yet evidence-based programs remain scarce. To address this lack, this study aimed to evaluate the feasibility of a dual approach combining app-based resilience training and cognitive behavioral group coaching. Fifty-one youths with CMC treated at a German university children's hospital aged 12-16 years were recruited. They were randomly assigned to a combined app game and coaching intervention or sole app gameplay. At pre-, post-intervention, and at a 2-month follow-up resilience, automatic negative thoughts and an app and coaching evaluation were assessed. Feasibility was defined as a recruitment rate of 70%, an 85% adherence rate for the REThink game, and 70% participation in both coaching sessions. Feasibility criteria were reached for coaching participation but not for recruitment or app adherence. While both the REThink game app and coaching intervention had high acceptance rates among youth with CMC, participants receiving additional coaching sessions showed higher satisfaction and adherence rates. Participants preferred remote to in-person meetings. The findings support a combination of a gamification app approach with online group coaching. Group coaching can improve adherence while online options increase accessibility. Future research should focus on testing in diverse participant samples, language, and age-adapted updates of the REThink game app. These findings provide guidance for increasing adherence in future intervention studies in youth with CMC cohorts.

Effect of titanium dioxide nanocoating on the colour stability of room temperature vulcanizing maxillofacial silicone-an invitro study.

OBJECTIVE: The aim of this in vitro study was to evaluate the effect of an oxide nanocoating to prevent colour degradation of maxillofacial silicone elastomers following accelerated ageing. MATERIAL AND METHODS: Specimens (N = 40) of specified dimensions were fabricated in Factor II room temperature vulcanizing (RTV) silicone and processed according to the manufacturer's instructions. Two groups were classified with 20 specimens each. Specimens in the first group were coated with titanium dioxide (TiO2) by atomic layer deposition technology. The colour stability test was conducted with a UV-VIS spectrometer (Schimadzu) for both titanium dioxide nanocoated and uncoated specimen groups after subjecting them to accelerated ageing. It was analysed using the CIE L*a*b method. RESULTS: The average colour change was highest for uncoated specimens (2.868), and the average colour change for titanium dioxide-coated specimens was significantly low (1.774). The average colour change of uncoated specimens (2.868) was close to the acceptable threshold value (3), and that of coated specimens (1.774) was far below the acceptable threshold (3). CONCLUSIONS: The colour change that occurred in titanium dioxide nanocoated specimens following accelerated ageing was significantly lower than that in the uncoated group, showing that the TiO2 nanocoating was effective in reducing the colour degradation of silicone elastomers. CLINICAL RELEVANCE: Maxillofacial prostheses fabricated from silicone elastomers go through undesirable colour degradation over time. The development of a scientific technique that retards the colour deterioration of silicone prostheses would be of great clinical significance.

ILC1 drive intestinal epithelial and matrix remodelling.

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor ß1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells.

Mesenchymal stem/stromal cells (MSCs) evoke great excitement for treating different human diseases due to their ability to home inflamed tissues, suppress inflammation, and promote tissue regeneration. Despite great promises, clinical trial results are disappointing as allotransplantation of MSCs trigger thrombotic activity and are damaged by the complement system, compromising their survival and function. To overcome this, a new strategy is presented by the silencing of tissue factor (TF), a transmembrane protein that mediates procoagulant activity. Novel Pluronic-based micelles are designed with the pendant pyridyl disulfide group, which are used to conjugate TF-targeting siRNA by the thiol-exchange reaction. This nanocarrier design effectively delivered the payload to MSCs resulting in ∼72% TF knockdown (KD) without significant cytotoxicity. Hematological evaluation of MSCs and TF-KD MSCs in an ex vivo human whole blood model revealed a significant reduction in an instant-blood-mediated-inflammatory reaction as evidenced by reduced platelet aggregation (93% of free platelets in the TF-KD group, compared to 22% in untreated bone marrow-derived MSCs) and thrombin-antithrombin complex formation. Effective TF silencing induced higher MSC differentiation in osteogenic and adipogenic media and showed stronger paracrine suppression of proinflammatory cytokines in macrophages and higher stimulation in the presence of endotoxins. Thus, TF silencing can produce functional cells with higher fidelity, efficacy, and functions.

Modulating Thiol p Ka Promotes Disulfide Formation at Physiological pH: An Elegant Strategy To Design Disulfide Cross-Linked Hyaluronic Acid Hydrogels.

The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors, and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants, and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the ß-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as l-cysteine indicated disulfide formation at a 2.8-fold higher ( k1 = 5.04 × 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid ( k1 = 1.80 × 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-l-cysteine substrate ( k1 = 0.51 × 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the p Ka value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the ß-position reduced the p Ka of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys); and 8.1 for HA-thiol (HA-SH) derivatives, respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 min or 10 h, respectively, at pH 7.4. After completion of cross-linking reaction, both gels demonstrated a storage modulus G' ≈ 3300-3500 Pa, which indicated comparable levels of cross-linking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.

Insights into siRNA Transfection in Suspension: Efficient Gene Silencing in Human Mesenchymal Stem Cells Encapsulated in Hyaluronic Acid Hydrogel.

Small interfering RNAs (siRNAs) are powerful tools for post-transcriptional gene silencing, which offers enormous opportunities for tissue engineering applications. However, poor serum stability, inefficient intracellular delivery, and inevitable toxicity of transfection reagents are the key barriers for their clinical translation. Thus, innovative strategies that allow safe and efficient intracellular delivery of the nucleic acid drugs at the desired site is urgently needed for a smooth clinical translation of therapeutically appealing siRNA-based technology. In this regard, we have developed an innovative siRNA transfection protocol that employs a short incubation time of just 5 min. This allows easy transfection in suspension followed by transplantation of the cells in a hyaluronic acid (HA) hydrogel system. We also report here the unique ability of siRNA to bind HA that was quantified by siRNA release and rheological characterization of the HA-hydrogel. Such interactions also showed promising results to deliver functional siRNA in suspension transfection conditions within 30 min using native HA, although removal of excess HA by centrifugation seem to be essential. In the 2D experiments, suspension transfection of hMSCs with RNAiMAX resulted in ≈90% gene silencing (with or without removal of the excess reagent by centrifugation), while HA demonstrated a modest ≈40% gene silencing after removal of excess reagent after 30 min. Transplantation of such transfected cells in the HA-hydrogel system demonstrated an improved knockdown (≈90% and ≈60% with RNAiMAX and HA respectively after 48 h), with lower cytotoxicity (up to 5-days) as determined by PrestoBlue assay. The gene silencing efficiency in the 2D and 3D conditions were also confirmed at the protein levels by Western blot analysis. We postulate this novel transfection method could be applied for in vivo applications as it allows minimal manipulation of cells that are to be transplanted and reduce toxicity.

[Evidence-based treatment recommendations for familial Mediterranean fever : A joint statement by the Society for Pediatric and Adolescent Rheumatology and the German Society for Rheumatology]. / Evidenzbasierte Therapieempfehlungen für das familiäre Mittelmeerfieber : Eine gemeinsame Stellungnahme der Gesellschaft für Kinder- und Jugendrheumatologie und der Deutschen Gesellschaft für Rheumatologie.

BACKGROUND: Familial Mediterranean fever (FMF) in Germany is a rare, genetically linked disease of childhood and adolescence, which is characterized by recurrent febrile episodes and clinical signs of peritonitis, pleuritis and arthritis. Treatment with colchicine is effective and well-tolerated in the majority of patients; however, some patients do not sufficiently respond to this treatment or are intolerant to colchicine. For these patients first-line treatment with biologics which block interleukin-1 can be used. OBJECTIVE: The aim was to formulate evidence-based treatment recommendations for patients with an insufficient response and intolerance to colchicine treatment. METHODS: Based on a literature search and the European League Against Rheumatism (EULAR) recommendations on FMF from 2016 the appointed members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German Society for Rheumatology (DGRh) convened to work out and form a consensus in a joint statement on evidence-based treatment recommendations on FMF. RESULTS: After intensive discussions all decisions were in concordance. A total of 5 superordinate principles and 10 recommendations were agreed upon. DISCUSSION: The joint activities of the GKJR and the DGRh were successfully concluded in a timely manner. The recommendations form a good basis for optimal treatment of all age groups of patients with FMF.

An Unexpected Role of Hyaluronic Acid in Trafficking siRNA Across the Cellular Barrier: The First Biomimetic, Anionic, Non-Viral Transfection Method.

Circulating nucleic acids, such as short interfering RNA (siRNA), regulate many biological processes; however, the mechanism by which these molecules enter the cell is poorly understood. The role of extracellular-matrix-derived polymers in binding siRNAs and trafficking them across the plasma membrane is reported. Thermal melting, dynamic light scattering, scanning electron microscopy, and computational analysis indicate that hyaluronic acid can stabilize siRNA via hydrogen bonding and Van der Waals interactions. This stabilization facilitated HA size- and concentration-dependent gene silencing in a CD44-positive human osteosarcoma cell line (MG-63) and in human mesenchymal stromal cells (hMSCs). This native HA-based siRNA transfection represents the first report on an anionic, non-viral delivery method that resulted in approximately 60 % gene knockdown in both cell types tested, which correlated with a reduction in translation levels.

Innovative Strategy for 3D Transfection of Primary Human Stem Cells with BMP-2 Expressing Plasmid DNA: A Clinically Translatable Strategy for Ex Vivo Gene Therapy.

Ex vivo gene therapy offers enormous potential for cell-based therapies, however, cumbersome in vitro cell culture conditions have limited its use in clinical practice. We have optimized an innovative strategy for the transient transfection of bone morphogenetic protein-2 (BMP-2) expressing plasmids in suspended human stem cells within 5-min that enables efficient loading of the transfected cells into a 3D hydrogel system. Such a short incubation time for lipid-based DNA nanoparticles (lipoplexes) reduces cytotoxicity and at the same time reduces the processing time for cells to be transplanted. The encapsulated human mesenchymal stromal/stem cells (hMSCs) transfected with BMP-2 plasmid demonstrated high expression of an osteogenic transcription factor, namely RUNX2, but not the chondrogenic factor (SOX9), within the first three days. This activation was also reflected in the 7-day and 21-day experiment, which clearly indicated the induction of osteogenesis but not chondrogenesis. We believe our transient transfection method demonstrated in primary MSCs can be adapted for other therapeutic genes for different cell-based therapeutic applications.

[Sexuality in adolescents with rheumatic diseases : Contraception, HPV vaccination and pregnancy]. / Sexualität bei Jugendlichen mit rheumatischen Erkrankungen : Verhütung, HPV-Impfung und Schwangerschaft.

Young patients and adolescents with chronic rheumatic diseases have the same desires, fears and needs in terms of sexuality and pregnancy as their healthy peers. In most cases adolescents are already sexually active before transition from pediatric to adult rheumatological care takes place. Pregnancies in women with rheumatic diseases are associated with increased maternal and fetal risks, especially when they occur unplanned in the course of active disease or under teratogenic drugs. Safe contraception is therefore crucial in preventing unwanted pregnancies. The choice of contraception should anticipate the safety of the method of contraception as well as age-dependent practicability. A strategy of "double protection" through the use of condoms for contraception and prevention of sexually transmitted diseases combined with another safe contraception method should be recommended. Women with rheumatic diseases are more susceptible to acquire persisting human papilloma virus (HPV) infections and the subsequent progression to cervical cancer. In women with rheumatic diseases HPV vaccination induces high seroconversion rates, is safe and does not seem to induce disease activity. The care of adolescent women with rheumatic diseases before, during and after medical transition needs to encompass an open, early and continuous counselling regarding these topics in order to retain the individual health-related quality of life and to adapt this care to age-specific needs.

Insights into the mechanism and catalysis of oxime coupling chemistry at physiological pH.

The dynamic covalent-coupling reaction involving α-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ∼14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.

[Juvenile systemic lupus erythematosus with unusual manifestation of lupus-associated panniculitis]. / Juveniler systemischer Lupus erythematodes mit der ungewöhnlichen Manifestation einer Lupus-assoziierten Pannikulitis.

Juvenile systemic lupus erythematosus (JSLE) is a rare multisystem autoimmune disease with broad heterogeneity of clinical manifestations. Diagnosing JSLE is often very challenging. This life-threatening, unpredictable, and relapsing disease, which may affect various organ systems, requires interdisciplinary, lifelong care. Here, we report the case of a 13-year-old patient with JSLE suffering from recurrent arthralgia, lupus panniculitis, and rashes that were successfully treated with hydroxychloroquine and prednisolone.

Glycosaminoglycans' for brain health: Harnessing glycosaminoglycan based biomaterials for treating central nervous system diseases and in-vitro modeling.

Dysfunction of the central nervous system (CNS) following traumatic brain injuries (TBI), spinal cord injuries (SCI), or strokes remains challenging to address using existing medications and cell-based therapies. Although therapeutic cell administration, such as stem cells and neuronal progenitor cells (NPCs), have shown promise in regenerative properties, they have failed to provide substantial benefits. However, the development of living cortical tissue engineered grafts, created by encapsulating these cells within an extracellular matrix (ECM) mimetic hydrogel scaffold, presents a promising functional replacement for damaged cortex in cases of stroke, SCI, and TBI. These grafts facilitate neural network repair and regeneration following CNS injuries. Given that natural glycosaminoglycans (GAGs) are a major constituent of the CNS, GAG-based hydrogels hold potential for the next generation of CNS healing therapies and in vitro modeling of CNS diseases. Brain-specific GAGs not only offer structural and biochemical signaling support to encapsulated neural cells but also modulate the inflammatory response in lesioned brain tissue, facilitating host integration and regeneration. This review briefly discusses different roles of GAGs and their related proteoglycan counterparts in healthy and diseases brain and explores current trends and advancements in GAG-based biomaterials for treating CNS injuries and modeling diseases. Additionally, it examines injectable, 3D bioprintable, and conductive GAG-based scaffolds, highlighting their clinical potential for in vitro modeling of patient-specific neural dysfunction and their ability to enhance CNS regeneration and repair following CNS injury in vivo.

Physically and Chemically Crosslinked Hyaluronic Acid-Based Hydrogels Differentially Promote Axonal Outgrowth from Neural Tissue Cultures.

Our aim was to investigate axonal outgrowth from different tissue models on soft biomaterials based on hyaluronic acid (HA). We hypothesized that HA-based hydrogels differentially promote axonal outgrowth from different neural tissues. Spinal cord sliced cultures (SCSCs) and dorsal root ganglion cultures (DRGCs) were maintained on a collagen gel, a physically crosslinked HA-based hydrogel (Healon 5®) and a novel chemically crosslinked HA-based hydrogel, with or without the presence of neurotrophic factors (NF). Time-lapse microscopy was performed after two, five and eight days, where axonal outgrowth was assessed by automated image analysis. Neuroprotection was investigated by PCR. Outgrowth was observed in all groups; however, in the collagen group, it was scarce. At the middle timepoint, outgrowth from SCSCs was superior in both HA-based groups compared to collagen, regardless of the presence of NF. In DRGCs, the outgrowth in Healon 5® with NF was significantly higher compared to the rest of the groups. PCR revealed upregulation of NeuN gene expression in the HA-based groups compared to controls after excitotoxic injury. The differences in neurite outgrowth from the two different tissue models suggest that axons differentially respond to the two types of biomaterials.

A quality by design approach to optimise disulfide-linked hyaluronic acid hydrogels.

In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.

Mild and efficient strategy for site-selective aldehyde modification of glycosaminoglycans: tailoring hydrogels with tunable release of growth factor.

Aldehydes have been used as an important bioorthogonal chemical reporter for conjugation of large polymers and bioactive substances. However, generating aldehyde functionality on carbohydrate-based biopolymers without changing its native chemical structure has always persisted as a challenging task. The common methods employed to achieve this require harsh reaction conditions, which often compromise the structural integrity and biological function of these sensitive molecules. Here we report a mild and simple method to graft aldehydes groups on glycosaminoglycans (GAGs) in a site-selective manner without compromising the structural integrity of the biopolymer. This regio-selective modification was achieved by conjugating the amino-glycerol moiety on the carboxylate residue of the polymer, which allowed selective cleavage of pendent diol groups without interfering with the C2-C3 diol groups of the native glucopyranose residue. Kinetic evaluation of this reaction demonstrated significant differences in second-order reaction rate for periodate oxidation (by four-orders of magnitude) between the two types of vicinal diols. We employed this chemistry to develop aldehyde modifications of sulfated and nonsulfated GAGs such as hyaluronic acid (HA), heparin (HP), and chondroitin sulfate (CS). We further utilized these aldehyde grafted GAGs to tailor extracellular matrix mimetic injectable hydrogels and evaluated its rheological properties. The composition of the hydrogels was also found to modulate release of therapeutic protein such as FGF-2, demonstrating controlled release (60%) for over 14 days. In short, our result clearly demonstrates a versatile strategy to graft aldehyde groups on sensitive biopolymers under mild conditions that could be applied for various bioconjugation and biomedical applications such as drug delivery and regenerative medicine.

Biomimetic polyelectrolyte coating of stem cells suppresses thrombotic activation and enhances its survival and function.

Mesenchymal stem cells (MSCs) therapy is a promising approach for treating inflammatory diseases due to their immunosuppressive and tissue repair characteristics. However, allogenic transplantation of MSCs induces thrombotic complications in some patients which limits its potential for clinical translation. To address this challenge, we have exploited the bioactivity of heparin, a well-known anticoagulant and immunosuppressive polysaccharide that is widely used in clinics. We have developed a smart layer-by-layer (LbL) coating strategy using gelatin and heparin polymers exploiting their overall positive and negative charges that enabled efficient complexation with the MSCs' glycocalyx. The stable coating of MSCs suppressed complement attack and mitigated thrombotic activation as demonstrated in human whole blood. Gratifyingly, the MSC coating retained its immunosuppressive properties and differentiation potential when exposed to inflammatory conditions and differentiation factors. We believe the simple coating procedure of MSCs will increase allogenic tolerance and circumvent the major challenge of MSCs transplantation.

Unveiling extracellular matrix assembly: Insights and approaches through bioorthogonal chemistry.

Visualizing cells, tissues, and their components specifically without interference with cellular functions, such as biochemical reactions, and cellular viability remains important for biomedical researchers worldwide. For an improved understanding of disease progression, tissue formation during development, and tissue regeneration, labeling extracellular matrix (ECM) components secreted by cells persists is required. Bioorthogonal chemistry approaches offer solutions to visualizing and labeling ECM constituents without interfering with other chemical or biological events. Although biorthogonal chemistry has been studied extensively for several applications, this review summarizes the recent advancements in using biorthogonal chemistry specifically for metabolic labeling and visualization of ECM proteins and glycosaminoglycans that are secreted by cells and living tissues. Challenges, limitations, and future directions surrounding biorthogonal chemistry involved in the labeling of ECM components are discussed. Finally, potential solutions for improvements to biorthogonal chemical approaches are suggested. This would provide theoretical guidance for labeling and visualization of de novo proteins and polysaccharides present in ECM that are cell-secreted for example during tissue remodeling or in vitro differentiation of stem cells.

Epidemiology and clinical characteristics of pandemic (H1N1) 2009 influenza infection in pediatric hemato-oncology and hematopoietic stem cell transplantation patients.

BACKGROUND: For children with hemato-oncologic diseases, especially after hematopoietic stem cell transplantation (HSCT), the risk for developing complications related to pandemic influenza A (H1N1) 2009 (pH1N1) infection is largely unknown. METHODS: A retrospective chart study was performed of pH1N1 cases diagnosed between October 2009 to January 2010 in the hemato-oncologic unit of the University Children's Hospital of Düsseldorf, Germany. FINDINGS: In total, 21 children were diagnosed with laboratory-confirmed pH1N1; in 16 patients with malignancies (acute leukemia 7, lymphoma 4, solid tumors 2, others 3) and in 5 with benign hematologic disorders. Five patients had undergone prior HSCT, although 1 patient was diagnosed during conditioning therapy with high-dose chemotherapy in preparation for haploidentical HSCT. Most frequent symptoms were fever (>38.5°C) and cough (in 100%), and rhinorrhea (57%). The 2 patients acquiring pH1N1 infection under high-dose or intensive chemotherapy did not require intensive care or mechanical ventilation, and both recovered under antiviral therapy. Oseltamivir was administered to 11 patients; in 1 patient, therapy was switched, on a compassionate-use basis, to intravenous zanamivir because of lack of clinical improvement after oseltamivir therapy. Complications were hospitalization (19%), demand of oxygen supplementation, delay/interruption of antineoplastic therapy, and prolonged administration of antibiotics and antipyretics. CONCLUSION: In the investigated patient population, pH1N1 was mild in most cases, but was associated with substantial morbidity in a proportion of patients and led to interruption and delay in anticancer treatment.

Dynamic covalent crosslinked hyaluronic acid hydrogels and nanomaterials for biomedical applications.

Hyaluronic acid (HA), one of the main components of the extracellular matrix (ECM), is extensively used in the design of hydrogels and nanoparticles for different biomedical applications due to its critical role in vivo, degradability by endogenous enzymes, and absence of immunogenicity. HA-based hydrogels and nanoparticles have been developed by utilizing different crosslinking chemistries. The development of such crosslinking chemistries indicates that even subtle differences in the structure of reactive groups or the procedure of crosslinking may have a profound impact on the intended mechanical, physical and biological outcomes. There are widespread examples of modified HA polymers that can form either covalently or physically crosslinked biomaterials. More recently, studies have been focused on dynamic covalent crosslinked HA-based biomaterials since these types of crosslinking allow the preparation of dynamic structures with the ability to form in situ, be injectable, and have self-healing properties. In this review, HA-based hydrogels and nanomaterials that are crosslinked by dynamic-covalent coupling (DCC) chemistry have been critically assessed.