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The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin-CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.
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Antibacterianos/farmacologia , Endopeptidases/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/crescimento & desenvolvimento , Silanos/farmacologia , Antibacterianos/química , Bacteriófagos/metabolismo , Biofilmes/efeitos dos fármacos , Dendrímeros , Composição de Medicamentos , Sinergismo Farmacológico , Interferometria , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia de Fluorescência , Plâncton/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Silanos/químicaRESUMO
BACKGROUND: Chronic stress is one of the leading predisposing factors in bruxism aetiology, but the influence of genetic factors is also suggested. We aimed to study whether sequence variants in genes involved in stress regulation pathways: NTRK2 and BDNF, may be associated with awake bruxism susceptibility, clinical presentation, and patients' perceived stress level. METHODS: The study group included 104 patients with probable awake bruxism and 191 population controls. Patients underwent dental examination concerning the symptoms of bruxism and psychological testing. Genotyping was performed using HRMA and sequencing. Statistical analyses were conducted, and P values below 0.05 were considered statistically significant. RESULTS: We observed a positive correlation of measured stress level and pathological teeth attrition in the anterior segment (r = 0.45, P < 0.001), enamel attritions (r = 0.44, P < 0.001), tongue impressions (r = 0.50, P < 0.001) and posterior teeth attrition (r = 0.27, P = 0.005). Moreover, the c.196A variant (p.66Met) of the BDNF gene and c.1397-31392G allele of the NTRK2 gene were present with elevated frequency, comparing to controls. CONCLUSIONS: This study hence the thesis that perceived stress level is a substantial contributing factor to awake bruxism occurrence and its clinical manifestations. Moreover, sequence variants in genes related to stress coping may be correlated with awake bruxism's susceptibility via elevated perceived stress level.
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Adaptação Psicológica , Fator Neurotrófico Derivado do Encéfalo/genética , Bruxismo , Glicoproteínas de Membrana/genética , Receptor trkB/genética , Atrito Dentário , Alelos , Bruxismo/genética , Humanos , VigíliaRESUMO
Nowadays, the researchers make a big effort to find new alternatives to overcome bacterial drug resistance. One option is the application of bacteriophage endolysins enable to degrade peptidoglycan (PG) what in consequence leads to bacterial cell lysis. In this study we examine phage KP27 endolysin mixed with poly(propyleneimine) dendrimers to evaluate an antimicrobial effect against Pseudomonas aeruginosa. Polycationic compounds destabilize bacterial outer membrane (OM) helping endolysins to gain access to PG. We found out that not only bacterial lipopolysaccharide (LPS) is the main hindrance for highly charged cationic dendrimers to disrupt OM and make endolysin reaching the target but also the dendrimer surface modification. The reduction of a positive charge and concentration in maltose poly(propyleneimine) dendrimers significantly increased an antibacterial effect of endolysin. The application of recombinant lysins against Gram-negative bacteria is one of the future therapy options, thus OM permeabilizers such as cationic dendrimers may be of high interest to be combined with PG-degrading enzymes.
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Antibacterianos/farmacologia , Dendrímeros/farmacologia , Endopeptidases/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/química , Bacteriófagos/enzimologia , Dendrímeros/química , Sinergismo Farmacológico , Endopeptidases/química , Klebsiella/virologia , Maltose/análogos & derivados , Testes de Sensibilidade Microbiana , Estabilidade ProteicaRESUMO
Many bacteria become progressively more resistant to antibiotics and it remains a challenging task to control their overall levels. Polymers combined with active biomolecules come to the forefront for the design of antibacterial materials that can address this encounter. In this work, we investigated the photo-crosslinking approach of UV-sensitive benzophenone molecule (BP) with polyvinylpyrrolidone (PVP) polymer within electrospun fibres. The BP and PVP solutions allowed fabricating polymer mats that were subsequently functionalised with antibacterial lysozyme. The physical properties of the crosslinked electrospun fibres were investigated by scanning electron microscopy and atomic force microscopy. The average diameter of the obtained fibres decreased from 290 ± 50 nm to 270 ± 70 nm upon the addition of the crosslinking molecules and then to 240 ± 80 nm and 180 ± 90 nm after subsequent crosslinking reaction at an increasing time: 3 and 5 h, respectively. The peak force quantitative nanomechanical mapping (PF-QNM) indicated the increase of DMT modulus of obtained cross-linked fibres from 4.1 ± 0.8 GPa to 7.2 ± 0.5 GPa. Furthermore, the successful crosslinking reaction of PVP and BP solution into hydrogels was investigated in terms of examining photo-crosslinking mechanism and was confirmed by rheology, Raman, Fourier transform infrared and nuclear magnetic resonance. Finally, lysozyme was successfully encapsulated within cross-linked PVP-BP hydrogels and these were successfully electrospun into mats which were found to be as effective antibacterial agents as pure lysozyme molecules. The dissolution rate of photo cross-linked PVP mats was observed to increase in comparison to pure PVP electrospun mats which opened a potential route for their use as antibacterial, on-demand, dissolvable coatings for various biomedical applications.
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PURPOSE: The study discusses the value of electrospun cilostazol-loaded (CIL) polymer structures for potential vascular implant applications. METHODS: Biodegradable polycaprolactone (PCL) fibers were produced by electrospinning on a rotating drum collector. Three different concentrations of CIL: 6.25%, 12.50% and 18.75% based on the amount of polymer, were incorporated into the fibers. The fibers were characterized by their size, shape and orientation. Materials characterization was carried out by Fourier Transformed Infrared spectroscopy (FTIR), Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In vitro drug release study was conducted using flow-through cell apparatus (USP 4). RESULTS: Three-dimensional structures characterized by fibers diameter ranging from 0.81 to 2.48 µm were in the range required for cardiovascular application. DSC and XRD confirmed the presence of CIL in the electrospun fibers. FTIR and Raman spectra confirmed CIL polymorphic form. Elastic modulus values for PCL and the CIL-loaded PCL fibers were in the range from 0.6 to 1.1 GPa. The in vitro release studies were conducted and revealed drug dissolution in combination with diffusion and polymer relaxation as mechanisms for CIL release from the polymer matrix. CONCLUSIONS: The release profile of CIL and nanomechanical properties of all formulations of PCL fibers demonstrate that the cilostazol loaded PCL fibers are an efficient delivery system for vascular implant application.
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Prótese Vascular , Cilostazol/administração & dosagem , Sistemas de Liberação de Medicamentos , Inibidores da Agregação Plaquetária/administração & dosagem , Trombose/prevenção & controle , Aterosclerose/cirurgia , Implante de Prótese Vascular/efeitos adversos , Cilostazol/farmacocinética , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Inibidores da Agregação Plaquetária/farmacocinética , Poliésteres/química , Trombose/etiologiaRESUMO
Bacteriophages (phages) are viruses that infect bacteria. The "predator-prey" interactions are recognized as a potentially effective way to treat infections. Phages, as well as phage-derived proteins, especially enzymes, are intensively studied to become future alternative or supportive antibacterials used alone or in combination with standard antibiotic regimens treatment. There are many publications presenting phage therapy aspects, and some papers focused separately on the application of phage-derived enzymes. In this review, we discuss advantages and limitations of both agents concerning their specificity, mode of action, structural issues, resistance development, pharmacokinetics, product preparation, and interactions with the immune system. Finally, we describe the current regulations for phage-based product application.
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Infecções Bacterianas/terapia , Bacteriófagos/crescimento & desenvolvimento , Enzimas/metabolismo , Terapia por Fagos/métodos , HumanosRESUMO
Bacteriophages are bacterial viruses that infect the host after successful receptor recognition and adsorption to the cell surface. The irreversible adherence followed by genome material ejection into host cell cytoplasm must be preceded by the passage of diverse carbohydrate barriers such as capsule polysaccharides (CPSs), O-polysaccharide chains of lipopolysaccharide (LPS) molecules, extracellular polysaccharides (EPSs) forming biofilm matrix, and peptidoglycan (PG) layers. For that purpose, bacteriophages are equipped with various virion-associated carbohydrate active enzymes, termed polysaccharide depolymerases and lysins, that recognize, bind, and degrade the polysaccharide compounds. We discuss the existing diversity in structural locations, variable architectures, enzymatic specificities, and evolutionary aspects of polysaccharide depolymerases and virion-associated lysins (VALs) and illustrate how these aspects can correlate with the host spectrum. In addition, we present methods that can be used for activity determination and the application potential of these enzymes as antibacterials, antivirulence agents, and diagnostic tools.
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Bactérias/virologia , Cápsulas Bacterianas/fisiologia , Infecções Bacterianas/microbiologia , Bacteriófagos/enzimologia , Bacteriófagos/fisiologia , Metabolismo dos Carboidratos , Vírion/enzimologia , Infecções Bacterianas/tratamento farmacológico , Bacteriófagos/genética , Biofilmes/crescimento & desenvolvimento , Carboidratos/química , Humanos , Hidrolases/metabolismo , Hidrolases/uso terapêutico , Peptidoglicano/metabolismo , Polissacarídeos/metabolismo , Vírion/genética , Vírion/metabolismoRESUMO
Lytic bacteriophages and phage-encoded endolysins (peptidoglycan hydrolases) provide a source for the development of novel antimicrobial strategies. In the present study, we focus on the closely related (96 % DNA sequence identity) environmental myoviruses vB_KpnM_KP15 (KP15) and vB_KpnM_KP27 (KP27) infecting multidrug-resistant Klebsiella pneumoniae and Klebsiella oxytoca strains. Their genome organisation and evolutionary relationship are compared to Enterobacter phage phiEap-3 and Klebsiella phages Matisse and Miro. Due to the shared and distinct evolutionary history of these phages, we propose to create a new phage genus "Kp15virus" within the Tevenvirinae subfamily. In silico genome analysis reveals two unique putative homing endonucleases of KP27 phage, probably involved in unrevealed mechanism of DNA modification and resistance to restriction digestion, resulting in a broader host spectrum. Additionally, we identified in KP15 and KP27 a complete set of lysis genes, containing holin, antiholin, spanin and endolysin. By turbidimetric assays on permeabilized Gram-negative strains, we verified the ability of the KP27 endolysin to destroy the bacterial peptidoglycan. We confirmed high stability, absence of toxicity on a human epithelial cell line and the enzymatic specificity of endolysin, which was found to possess endopeptidase activity, cleaving the peptide stem between L-alanine and D-glutamic acid.
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Bacteriófagos/enzimologia , Bacteriófagos/isolamento & purificação , DNA Viral/química , Endopeptidases/metabolismo , Klebsiella oxytoca/virologia , Klebsiella pneumoniae/virologia , Bacteriófagos/classificação , Bacteriófagos/genética , DNA Viral/genética , Ordem dos Genes , Myoviridae/classificação , Myoviridae/enzimologia , Myoviridae/genética , Myoviridae/isolamento & purificação , Filogenia , Homologia de SequênciaRESUMO
Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.
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Anti-Infecciosos/isolamento & purificação , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Complexo Burkholderia cepacia/virologia , Burkholderia/virologia , Genoma Viral , Especificidade de Hospedeiro , Animais , Infecções por Burkholderia/microbiologia , Burkholderia cenocepacia/virologia , Fibrose Cística/microbiologia , Humanos , Lisogenia , Mariposas/virologia , Análise de Sequência de DNA , VirulênciaRESUMO
BACKGROUND Numerous studies have discussed cases of concomitant temporomandibular disorders (TMD) and otologic symptoms (OS). However, attempts to determine the true origin of these symptoms combined with assessments of the condition of the organ of hearing are relatively rare. This study aimed to evaluate the frequency and type of OS in patients with TMD, and attempted to determine the origin of the OS in the studied group of patients. MATERIAL AND METHODS 246 patients, aged 40.08±11.12 years (F=147, M=99) with TMD, from the Department of Oral Rehabilitation of Poznan University of Medical Sciences. METHODS: dental history interviews and clinical examinations. There were 2 groups-G1 and G2-selected on the basis of the presence or absence of OS in the medical history stage. After audiological evaluation, 2 subgroups were identified: G1.1 and G1.2. RESULTS OS were observed in 36.18% (G1). In 48 patients (53.93%), the audiological evaluation found there was no impairment of the organ of hearing (G1.2). Audiological abnormalities were found in 46.07% (n=41) of the patients (G1.1). The OS which differentiated the 2 groups were a plugging sensation as well as otalgia (more frequent in group G1.2) and hearing impairment (more frequent in group G1.1). CONCLUSIONS 1. The OS which most frequently accompany with TMD were fullness and otalgia. 2. It is recommended that a subjective assessment of hearing loss in patients with TMD and concomitant OS should be included in the medical history stage. 3. Clicking and popping are significantly more frequent in patients without concomitant hearing impairment.
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Orelha/fisiopatologia , Audição/fisiologia , Transtornos da Articulação Temporomandibular/epidemiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adulto , Feminino , Humanos , Incidência , MasculinoRESUMO
INTRODUCTION: Human development includes lots of physical and emotional changes. The human voice depends on age. Voice production is a complex physiological and acoustic phenomenon that depends on many factors such as structure, hormone level, degree of fatigue or nutrition and hydration of the body, systemic diseases, and emotional state. All these factors can be present in anorexia nervosa (AN), such as excessive weight loss, generated hydro-electrolytic changes, nutritional deficiencies, hormonal disturbances in the function of the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-ovarian axis, and emotional distress. The prevalence of AN ranges between 0.3% and 3%, and it is the third most common chronic disease affecting adolescent girls. However, voice changes related to AN have not been fully investigated. OBJECTIVE: The purpose of this study was to evaluate the impact of AN on age-related changes in the voice of adolescent women-before and after puberty, particularly through acoustic analysis. An additional objective was to evaluate estrogen substitution in female patients with AN in order to investigate their effect on voice condition. MATERIALS AND METHODS: 126 girls diagnosed with AN (15.32 ± 2.12 years, range 12-19, BMI = 14.38 ± 1.67), were assessed for the condition of the voice such as perceptual voice evaluation on the GRBAS scale, maximal phonation time (MPT), laryngoscopy, with special attention to voice acoustic analysis-Multi-Dimensional Voice Program (MDVP). The control group (B) included 93 girls without eating disturbances (aged 12-19, mean age 15.52 ± 2.40, BMI = 21.50 ± 1.54). Perceptual voice assessment, aerodynamic test MPT, and acoustic parameters were analyzed in age groups (≤16 years and >16 years). The human vocal tract is sensitive to sex hormones, so the analysis was carried out in the group up to the age of 16 and above 16 to check possible effects. RESULTS: GRBAS scale was higher in girls with AN compared to the control group for breathiness (B) (P = 0.0002) and asthenia (A) (P < 0.05). The median GRBAS scale for the older group of anorexic women was the highest (2.0). The mean MPT for group A was significantly lower (15.40 ± 3.51 seconds). Comparing age subgroups there was a prolongation of MPT in the healthy group (in groups ≤16 years and >16 years respectively 21.13 seconds versus 25.40 seconds) and a shortening in the anorectic group (≤16 years versus >16 years: 17.06 seconds versus 14.17 seconds). There was no difference between groups A and C up to 16 years of age, but above 16 years of age appeared (14.17 seconds versus 25.40 seconds). Acoustic analysis revealed lower F0 values in group A and C in older subgroups (215,85 Hz versus 236,01 Hz-statistically significant), as well as between subgroups both groups (A: 251,38 Hz versus 215,85 Hz; C: 248,20 Hz versus 236,01 Hz). A narrowing of the vocal range in girls over 16 years in group A was observed. There were no statistically significant differences in F0 between subgroups ≤16 years in groups A and C (251.38 Hz versus 248.20 Hz). The ENT study found that more than half of the girls (54.55%) over the age of 16 who took hormone supplementation manifested laryngeal structure that was normal for their age, there was no effect of hormone supplementation on any of the MDVP parameters between the drug-taking and non-drug-taking groups. CONCLUSIONS: The acoustic results of the voice in MDVP measurements in adolescent women with AN are not within the normal range and do not mimic the normal developmental changes of the voice. The most important acoustic characteristics of the voice are changes in the fundamental frequency F0 and the range of the voice tended to be more severe in anorectic women >16 years of age and to increase with age, indicating a possible cumulative effect of malnutrition-related disorders as well as hormonal dysfunctions. MDVP can be considered a simple, non-invasive method of assessing the voice organ in AN. MPT differentiated the study groups well: statistically significant differences were noted both between the groups, as well as between age groups. There was no significant effect of oral hormone supplementation on any parameters of the voice. In conclusion, body mass and fat volume in AN may be related to voice production/physiology, affecting voice quality, voice acoustic parameters, voice aerodynamics, and phonatory range in an age-dependent manner. Future studies are needed to assess the long-term efficacy of estrogen treatment in AN.
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Electrospinning has been applied to produce ceramic fibers using sol gel-based spinning solutions consisting of ceramic precursors, a solvent, and a polymer to control the viscosity of the solution. However, the addition of polymers to the spinning solution makes the process more complex, increases the processing time, and results in porous mechanically weak ceramic fibers. Herein, we develop a coelectrospinning technique, where a nonspinnable sol (<10 mPa s) consisting of only the ceramic precursor(s) and solvent(s) is encapsulated inside a polymeric shell, forming core-shell precursor fibers that are further calcined into ceramic fibers with reduced porosity, decreased surface defects, uniform crystal packing, and controlled diameters. We demonstrate the versatility of this method by applying it to a series of nonspinnable sols and creating high-quality ceramic fibers containing TiO2, ZrO2, SiO2, and Al2O3. The polycrystalline TiO2 fibers possess excellent flexibility and a high Young's modulus reaching 54.3 MPa, solving the extreme brittleness problem of the previously reported TiO2 fibers. The single-component ZrO2 fibers exhibit a Young's modulus and toughness of 130.5 MPa and 11.9 KJ/m3, respectively, significantly superior to the counterparts prepared by conventional sol-gel electrospinning. We also report the creation of ceramic fibers in micro- and nanospring morphologies and examine the formation mechanisms using thermomechanical simulations. The fiber assemblies constructed by the helical fibers exhibit a density-normalized toughness of 3.5-5 times that of the straight fibers due to improved fracture strain. This work expands the selection of the electrospinning solution and enables the development of ceramic fibers with more attractive properties.
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Infection with Mycobacterium tuberculosis is accompanied by an intense inflammatory response. Recently, a new mediator of inflammation, HMGB1 protein has been identified that contributes to acute lung injury. However, its role in the systemic inflammatory response in tuberculosis has not been thoroughly investigated. We investigated the systemic levels of HMGB1 and TNF-α in patients with active and latent lung tuberculosis as a prognostic marker of disease activity. The study was performed to 70 patients with confirmed Mycobacterium tuberculosis infection and other than tuberculosis lung diseases and in 20 healthy persons. Serum HMGB1 and TNF-α concentrations were measured by ELISA. The highest concentration of HMGB1 was detected in the bloodstream of people with Mtb infection (latent and active). Its concentration increased significantly in sera of patients with active tuberculosis (47.5 ng/ml), compared to patients with other lung diseases (36.87 ng/ml). TNF-α had significantly higher concentration in a patients group compared to healthy controls, with the highest concentration in the LTBI group of patients (0.136 ng/ml). We observed a strong positive correlation between TNF-α and HMGB1 concentrations in patients with tuberculosis infections. We conclude that HMGB1 is secreted during active and latent tuberculosis in the highest amounts compared to other lung diseases.
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Proteína HMGB1/sangue , Mycobacterium tuberculosis , Tuberculose Pulmonar/sangue , Adulto , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
OBJECTIVES: It has been suggested that dyslexia is linked to a core cognitive deficit in phonological awareness tasks and/or in the processing of auditory stimuli. Auditory evoked potentials are a valid, objective measure of the accuracy of central auditory processing in humans. The aim of this study was to assess auditory evoked potentials in children with dyslexia. PATIENTS AND METHODS: Sixty-six children participated in the study. A set of hearing tests and the recording of complex event-related potentials (ERPs) were performed. RESULTS: Mixmatch negativity (MMN) and P300 waves were significantly more frequent in the healthy children (control group) than in children with dyslexia. The P300 wave was present in all subjects from the control group, the MMN wave in 92% of them. In the dyslexic group, complex ERPs were recorded roughly 33% of the time. Latencies of complex ERPs in children with dyslexia were greater than latencies in children in the control group. MMN and P300 maturation (change with age) was observed only for the control group. A wide range of MMN and P300 responses was observed across children with dyslexia. CONCLUSION: Complex ERPs may be useful in determining the condition of audiologic functions; however, on their own they are not sufficient to recognize dyslexia because of the heterogeneity of nonspecific changes.
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Dislexia/etiologia , Potenciais Evocados P300 , Potenciais Evocados Auditivos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Estimulação Acústica , Adolescente , Criança , Dislexia/fisiopatologia , Feminino , Testes Auditivos , Humanos , Transtornos do Desenvolvimento da Linguagem/complicações , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Masculino , Testes Psicológicos , Tempo de ReaçãoRESUMO
INTRODUCTION: The process of human voice production is a complex physiological and acoustic phenomenon that depends on many structural, physical, and hormonal factors, systemic diseases as well as emotional states. All these factors can be present in eating disorders. However, studies on eating disorders and voice problems have usually been evaluated in terms of bulimia. Chronic starvation and emotional problems in the course of anorexia nervosa (AN) appear to be under-researched, despite various biochemical, metabolic, and hormonal changes. OBJECTIVE: The purpose of this study was to evaluate voice quality, specifically acoustic analysis, in adolescent female with AN from the point of view of the possible influence on the function and structure of the larynx, low body mass accompanying AN, as well as energy deficiency, hormonal and emotional disturbances. MATERIALS AND METHODS: A total of 84 girls diagnosed with AN (Gr.A) (15.32 years, SD = 2.12; range 12-19, BMI = 14.11 ± 1.72) were assessed for the condition of the voice such as perceptual voice evaluation on the GRBAS scale, maximal phonation time (MPT), laryngoscopy, with special attention to voice acoustic analysis - Multi-Dimensional Voice Program (MDVP). The control group (Gr.C) included 62 girls without eating disturbances (aged 12-19, mean age 15.41 ± 2.40, BMI = 21.60 ± 1.92). Perceptual voice assessment, aerodynamic test MPT, and acoustic parameters were analyzed according to girls' age. RESULTS: Total GRBAS scale was higher in girls with AN compared to the control group mainly for two parameters: breathiness (B) (P = 0.00015) and asthenia (A) (P < 0.05). The MPT for Gr.A was significantly shorter compared to Gr.C (15.40 ± 3.51 seconds vs. 23.19 ± 5.17 seconds) (P < 0.001), and a correlation of MPT values with the age of the adolescent female was observed: Spearman's coefficient for Gr.A = (-)0.5378, for Gr.C = 0.5516 (P = 0.0012). Acoustic analysis revealed the decrease in the basic frequency F0 in Gr.A compared to Gr.C (231.08 Hz vs. 242.30 Hz), and narrowing of the voice scale was observed, resulting mainly from a reduction in the upper limit. Significant differences were found for measures of frequency perturbations (Jita, Jitter, RPA, PPQ, sPPR), with Gr.A scoring significantly higher than Gr.C (P < 0.05 for all). Significant changes in voice acoustic analysis parameters were found with age. Negative correlations were found for measures of F0 for Gr.A to a much greater extent compared to Gr.C. Positive correlations were found with measures of tremor assessment (SPI, FTRI, ATRI) for Gr.A.
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To date, there has been limited reporting on the fabrication and properties of macroscopic sheet assemblies (specifically buckypapers) composed of carbon/boron nitride core-shell heteronanotubes (MWCNT@BNNT) or boron nitride nanotubes (BNNTs). Herein we report the synthesis of MWCNT@BNNTs via a facile method involving Atmospheric Pressure Chemical Vapor Deposition (APCVD) and the safe h-BN precursor ammonia borane. These MWCNT@BNNTs were used as sacrificial templates for BNNT synthesis by thermal oxidation of the core carbon. Buckypaper fabrication was facilitated by facile sonication and filtration steps. To test the thermal conductivity properties of these new buckypapers, in the interest of thermal management applications, we have developed a novel technique of advanced scanning thermal microscopy (SThM) that we call piercing SThM (pSThM). Our measurements show a 14% increase in thermal conductivity of the MWCNT@BNNT buckypaper relative to a control multiwalled carbon nanotube (MWCNT) buckypaper. Meanwhile, our BNNT buckypaper exhibited approximately half the thermal conductivity of the MWCNT control, which we attribute to the turbostratic quality of our BNNTs. To the best of our knowledge, this work achieves the first thermal conductivity measurement of a MWCNT@BNNT buckypaper and of a BNNT buckypaper composed of BNNTs not synthesized by high energy techniques.
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IMPORTANCE: In this work, we determined the structure of Klebsiella phage KP34p57 capsular depolymerase and dissected the role of individual domains in trimerization and functional activity. The crystal structure serendipitously revealed that the enzyme can exist in a monomeric state once deprived of its C-terminal domain. Based on the crystal structure and site-directed mutagenesis, we localized the key catalytic residues in an intra-subunit deep groove. Consistently, we show that C-terminally trimmed KP34p57 variants are monomeric, stable, and fully active. The elaboration of monomeric, fully active phage depolymerases is innovative in the field, as no previous example exists. Indeed, mini phage depolymerases can be combined in chimeric enzymes to extend their activity ranges, allowing their use against multiple serotypes.
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Bacteriófagos , Klebsiella , Klebsiella/genética , Bacteriófagos/genética , Klebsiella pneumoniae/genéticaRESUMO
Topographical cues on materials can manipulate cellular fate, particularly for neural cells that respond well to such cues. Utilizing biomaterial surfaces with topographical features can effectively influence neuronal differentiation and promote neurite outgrowth. This is crucial for improving the regeneration of damaged neural tissue after injury. Here, we utilized groove patterns to create neural conduits that promote neural differentiation and axonal growth. We investigated the differentiation of human neural stem cells (NSCs) on silicon dioxide groove patterns with varying height-to-width/spacing ratios. We hypothesize that NSCs can sense the microgrooves with nanoscale depth on different aspect ratio substrates and exhibit different morphologies and differentiation fate. A comprehensive approach was employed, analyzing cell morphology, neurite length, and cell-specific markers. These aspects provided insights into the behavior of the investigated NSCs and their response to the topographical cues. Three groove-pattern models were designed with varying height-to-width/spacing ratios of 80, 42, and 30 for groove pattern widths of 1 µm, 5 µm, and 10 µm and nanoheights of 80 nm, 210 nm, and 280 nm. Smaller groove patterns led to longer neurites and more effective differentiation towards neurons, whereas larger patterns promoted multidimensional differentiation towards both neurons and glia. We transferred these cues onto patterned polycaprolactone (PCL) and PCL-graphene oxide (PCL-GO) composite 'stamps' using simple soft lithography and reproducible extrusion 3D printing methods. The patterned scaffolds elicited a response from NSCs comparable to that of silicon dioxide groove patterns. The smallest pattern stimulated the highest neurite outgrowth, while the middle-sized grooves of PCL-GO induced effective synaptogenesis. We demonstrated the potential for such structures to be wrapped into tubes and used as grafts for peripheral nerve regeneration. Grooved PCL and PCL-GO conduits could be a promising alternative to nerve grafting.
Assuntos
Células-Tronco Neurais , Humanos , Neurônios/fisiologia , Diferenciação Celular , Alicerces Teciduais/química , Dióxido de Silício/farmacologiaRESUMO
Electrospinning technique is well-known for the generation of different fibers. While it is a "simple" technique, it lies in the fact that the fibers are typically produced in the form of densely packed two-dimensional (2D) mats with limited thickness, shape, and porosity. The highly demanded three-dimensional (3D) fiber assemblies have been explored by time-consuming postprocessing and/or complex setup modifications. Here, we use a classic electrospinning setup to directly produce 3D fiber macrostructures only by modulating the spinning solution. Increasing solution conductivity modifies electrodynamic jet behavior and fiber assembling process; both are observed in situ using a high-speed camera. More viscous solutions render thicker fibers that own enhanced mechanical stiffness as examined by finite element analysis. We reveal the correlation between the universal solution parameters and the dimensionality of fiber assemblies, thereof, enlightening the design of more "3D spinnable" solutions that are compatible with any commercial electrospinning equipment. After a calcination step, ultralightweight ceramic fiber assemblies are generated. These inexpensive materials can clean up exceptionally large fractions of oil spillages and provide high-performance thermal insulation. This work would drive the development and scale-up production of next-generation 3D fiber materials for engineering, biomedical, and environmental applications.
RESUMO
Tinnitus is a sensation of ringing in the ears in the absence of any physical source in the environment. Between 9-35% of adults experience some form of tinnitus. Common causes of tinnitus include noise, head injury, ototoxic substances, as well as disorders of blood and blood vessels. Vascular causes include: head-neck tumours, turbulent blood flow, problems with blood supply and inner ear cell damage. The aspect of rheology in terms of tinnitus has not been described yet. In the present study, which comprised 12 patients aged 30 to 74 years presenting with tinnitus, rheological properties of whole blood and plasma were assessed. All the subjects underwent audiological and neurological evaluation. The Quemada model was used to describe the variability of red blood cell shape, as well as their tendency to form aggregates. On the basis of the experimental study, statistically different results of haemorheological measurements were observed in the evaluated group in comparison to a reference group.