Publications

Surface topography at the nanoscale plays a crucial role in modulating the biological properties of dental implants. However, the understanding of how the nanoroughness of zirconia affects cell and bacteria responses remains unclear. In this study, chemical etching of 3Y-TZP was explored to develop a nanotopography capable of favoring eukaryotic cell behavior while simultaneously inhibiting bacterial adhesion. Three topographies of different roughness were created by varying the etching time with hydrofluoric acid (i.e., HF15, HF30, and HF60). The etched surfaces exhibited a nanorough topography with randomly distributed nanopits, and surface roughness increased at longer etching times. Mesenchymal stem cell adhesion, spreading, proliferation and mineralization were enhanced on the etched surfaces, compared to flat controls. The roughest surface (HF60) also inhibited S. aureus adhesion and caused significant damage to P. aeruginosa. This study highlights the potential of chemical etching to produce nanorough zirconia with improved biological outcomes.

JTD Keywords: Attachment, Bacteri, Bacterial adhesion, Biomaterials, Cell response, Chemical etching, Dental implants, Dental zirconia, Integration, Osseointegration, Osteogenic differentiation, Parameter, Roughness, Surface-topography, Titanium implants, Zirconia

Amyloid fibrils, which are aggregates of misfolded proteins characterized by 13-sheet-rich structures, are implicated in several neurodegenerative and systemic pathologies, including Alzheimer's and Parkinson's diseases and type II diabetes mellitus. Traditional amyloid markers, such as Congo Red and Thioflavin T, are widely used for amyloid detection but present limitations, particularly in cellular assays, due to spectral interference and aggregation inhibition. This study investigates YAT2150, a novel fluorescent dye with enhanced amyloid-binding specificity and sensitivity, as a potential alternative to conventional dyes. We evaluated YAT2150's efficacy for detecting amyloid aggregates in both in vitro and in cellula assays. First, we compared its fluorescence intensity and binding specificity to that of Thioflavin Tin amyloid fibril assays, demonstrating that YAT2150 exhibits high affinity and selectivity for amyloid structures, with minimal interference from non-aggregated proteins. Furthermore, we explored YAT2150's utility in Escherichia colt as a model system for studying protein aggregation and amyloid formation in a procaryotic cellular context. Our findings indicate that YAT2150 effectively labels amyloid-like inclusion bodies in E. colt producing a robust fluorescence signal with low background noise. These results suggest that YAT2150 is a promising new tool for amyloid research, offering greater sensitivity compared to traditional dyes, even in complex cellular environments.

JTD Keywords: Aggregation, Amyloid, Amyloid inhibitor, Bacterial inclusion-bodies, Detect, In-vitro, Inclusion bodies, Kinetics, Model, Parameters, Prion, Screening, Silico, Yat2150

The accurate spatial segregation into distinct phases within cell membranes coordinates vital biochemical processes and functionalities in living organisms. One of nature's strategies to localize reactivity is the formation of dynamic raft domains. Most raft models rely on liquid-ordered L-0 phases in a liquid-disordered L-d phase lacking correlation and remaining static, often necessitating external agents for phase separation. Here, we introduce a synthetic system of bicomponent glycodendrimersomes coassembled from Janus dendrimers and Janus glycodendrimers (JGDs), where lactose-lactose interactions exclusively drive lateral organization. This mechanism results in modulated phases across two length scales, yielding raft-like microdomains featuring nanoarrays at the nanoscale. By varying the density of lactose and molecular architecture of JGDs, the nanoarray type and size, shape, and spacing of the domains were controlled. Our findings offer insight into the potential primordial origins of rudimentary raft domains and highlight the crucial role of glycans within the glycocalyx.

JTD Keywords: Article, Artificial cells, Atomic force microscopy, Bicomponents, Bilayer, Bilayer membrane, Biochemical functionality, Biochemical process, Biological-membranes, Cell component, Cell membrane, Cellular parameters, Chemical interaction, Chemical structure, Chemistry, Cytology, Defined janus glycodendrimers, Dehydration, Dendrimer, Dendrimers, Dilution, Dimer, External agents, Fourier transform, Giant vesicles, Glycan, Glycans, Glycocalyx, Glycodendrimers, Janus dendrimer, Janus glycodendrimer, Lactose, Lateral organization, Lectin, Lipid rafts, Living organisms, Membrane damage, Membrane microdomain, Membrane microdomains, Membrane structure, Metabolism, Modulated phases, Molecule, Monomer, Nanoarrays, Oligosaccharide, Organization, Periodicity, Phase separation, Phase-separation, Phospholipids, Polysaccharide, Polysaccharides, Raft like domain, Relative humidity, Spatial segregation, Structure analysis, Sugars, Synthetic systems, Tetramer, Unclassified drug, Unilamellar vesicles, Water

The mutual interaction between reactive species generated by non-thermal plasma and biopolymers in solution causes oxidative modifications that can have an impact in biomedical applications.

JTD Keywords: atmospheric plasma, cellulose, dftb3, gas, oxidation, parameterization, simulations, water, Biopolymers, Hydrogen peroxide, Molecular dynamics simulation, Molecular-dynamics, Nitrites, Reactive oxygen species

3DNA holds promise as a carrier for drugs that can be intercalated into its core or linked to surface arms. Coupling 3DNA to an antibody targeting intercellular adhesion molecule 1 (ICAM-1) results in high lung-specific biodistributions in vivo. While the role of individual parameters on ICAM-1 targeting has been studied for other nanocarriers, it has never been examined for 3DNA or in a manner capable of revealing the hierarchic interplay among said parameters. In this study, we used 2-layer vs. 4-layer anti-ICAM 3DNA and radiotracing to examine biodistribution in mice. We found that, below saturating conditions and within the ranges tested, the density of targeting antibodies on 3DNA is the most relevant parameter driving lung targeting over liver clearance, compared to the number of antibodies per carrier, total antibody dose, 3DNA dose, 3DNA size, or the administered concentration, which influenced the dose in organs but not the lung specific-over-liver clearance ratio. Data predicts that lung-specific delivery of intercalating (core loaded) drugs can be tuned using this biodistribution pattern, while that of arm-linked (surface loaded) drugs requires a careful parametric balance because increasing anti-ICAM density reduces the number of 3DNA arms available for drug loading.

JTD Keywords: 3dna nanocarrier, acid sphingomyelinase, antibody, carrier design parameters, carriers, dna nanostructures, doxorubicin, drug type, icam-1, inflammation, lung targeting, multiparametric hierarchy, nanoparticles, size, 3dna nanocarrier, Intracellular delivery, Multiparametric hierarchy

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A–B Niemann–Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications.

JTD Keywords: active enzymes, encapsulation, enhanced delivery, enzyme therapeutics, formulation parameters, icam-1 targeting, icam-1-targeted nanocarriers, in vivo biodistribution, in-vitro, lysosomal delivery, model, oral delivery, plga nanoparticles, poly(lactic-co-glycolic acid) nanoparticles, protein therapeutics, surface loading, Acid sphingomyelinase, Animals, Encapsulation, Enzyme replacement therapy, Enzyme therapeutics, Icam-1 targeting, In vivo biodistribution, Lysosomal delivery, Lysosomes, Mice, Nanoparticles, Poly(lactic-co-glycolic acid) nanoparticles, Polymers, Surface loading, Surface-active agents

The enhanced catalytic activity of permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, largely depends on both the experimental conditions used to prepare crystalline hydroxyapatite from its calcium and phosphate precursors and the polarization process parameters. A mineral similar to brushite, which is an apatitic phase that can evolve to hydroxyapatite, is found at the surface of highly crystalline hydroxyapatite. It appears after chemical precipitation and hydrothermal treatment performed at 150 degrees C for 24 h followed by a sinterization at 1000 degrees C and a polarization treatment by applying a voltage of 500 Vat high temperature. Both the high crystallinity and the presence of brushite-like phase on the electrophotocatalyst affect the nitrogen and carbon fixation under mild reaction conditions (95 degrees C and 6 bar) and the synthesis of glycine and alanine from a simple gas mixture containing N-2, CO2, CH4 and H2O. Thus, the Gly/Ala ratio can be customized by controlling the presence of brushite on the surface of the catalyst, enabling to develop new strategies to regulate the production of amino acids by nitrogen and carbon fixation. (C) 2021 Elsevier Inc. All rights reserved.

JTD Keywords: Amino acids, Brushite, Carbon, Carbon dioxide fixation, Catalyst activity, Catalytic apatites, Chemical precipitation, Crystalline hydroxyapatite, Crystallinity, Decomposition, Enhanced catalytic activity, Experimental conditions, Heterogeneous catalysis, High crystallinity, Hydrothermal synthesis, Hydrothermal treatments, Hydroxyapatite, Lactic-acid, Mild reaction conditions, Molecular nitrogen fixation, Nitrogen, Nitrogen fixation, Phosphate, Polarization, Precipitation (chemical), Process parameters, Thermally stimulated polarization

Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target cells has been specifically addressed. Additionally, examples are offered with re-spect to changes of TIPS procedure parameters, the combination of TIPS with other techniques and innovations in polymer or filler selection.

JTD Keywords: biodegradable polymer, composites, morphology, pore structure, porosity, processing parameters, thermally induced phase separation, Biodegradable polymer, Composites, Morphology, Pore structure, Porosity, Processing parameters, Thermally induced phase separation, Tissue engineering scaffold

Assessment of the dynamic interactions between cardiovascular signals can provide valuable information that improves the understanding of cardiovascular control. Heart rate variability (HRV) analysis is known to provide information about the autonomic heart rate modulation mechanism. Using the HRV signal, we aimed to obtain parameters for classifying patients with and without chronic heart failure (CHF), and with periodic breathing (PB), non-periodic breathing (nPB), and Cheyne-Stokes respiration (CSR) patterns. An electrocardiogram (ECG) and a respiratory flow signal were recorded in 36 elderly patients: 18 patients with CHF and 18 patients without CHF. According to the clinical criteria, the patients were classified into the follow groups: 19 patients with nPB pattern, 7 with PB pattern, 4 with Cheyne-Stokes respiration (CSR), and 6 non-classified patients (problems with respiratory signal). From the HRV signal, parameters in the time and frequency domain were calculated. Frequency domain parameters were the most discriminant in comparisons of patients with and without CHF: P_Tot (p = 0.02), P_LF (p = 0.022) and fp_HF (p = 0.021). For the comparison of the nPB vs. CSR patients groups, the best parameters were RMSSD (p = 0.028) and SDSD (p = 0.028). Therefore, the parameters appear to be suitable for enhanced diagnosis of decompensated CHF patients and the possibility of developed periodic breathing and a CSR pattern.

JTD Keywords: cardiovascular system, diseases, electrocardiography, frequency-domain analysis, geriatrics, medical signal processing, patient diagnosis, pneumodynamics, signal classification, Cheyne-Stokes respiration patterns, ECG, autonomic heart rate modulation mechanism, cardiovascular control, cardiovascular signals, chronic heart failure, decompensated CHF patients, dynamic interaction assessment, elderly patients, electrocardiogram, enhanced diagnosis, frequency domain parameters, heart rate variability analysis, patient classification, periodic breathing, respiratory flow signal recording, Electrocardiography, Frequency modulation, Frequency-domain analysis, Heart rate variability, Senior citizens, Standards

Ischemic and dilated cardiomyopathy are associated with disorders of myocardium. Using the blood pressure (BP) signal and the values of the ventricular ejection fraction, we obtained parameters for stratifying cardiomyopathy patients as low- and high-risk. We studied 48 cardiomyopathy patients characterized by NYHA ≥2: 19 patients with dilated cardiomyopathy (DCM) and 29 patients with ischemic cardiomyopathy (ICM). The left ventricular ejection fraction (LVEF) percentage was used to classify patients in low risk (LR: LVEF > 35%, 17 patients) and high risk (HR: LVEF ≤ 35%, 31 patients) groups. From the BP signal, we extracted the upward systolic slope (BP_sl), the difference between systolic and diastolic BP (BPA), and systolic time intervals (STI). When we compared the LR and HR groups in the time domain analysis, the best parameters were standard deviation (SD) of 1=STI, kurtosis (K) of BP_sl, and K of BPA. In the frequency domain analysis, very low frequency (VLF) and high frequency (HF) bands showed statistically significant differences in comaprisons of LR and HR groups. The area under the curve of power spectral density was the best parameter in all classifications, and particularly in the very-low-and high- frequency bands (p <; 0.001). These parameters could help to improve the risk stratification of cardiomyopathy patients.

JTD Keywords: blood pressure measurement, cardiovascular system, diseases, medical disorders, medical signal processing, statistical analysis, time-domain analysis, BP signal, HR groups, LR groups, blood pressure signal analysis, cardiomyopathy patients, diastolic BP, dilated cardiomyopathy, frequency domain analysis, high-frequency bands, ischemic cardiomyopathy, left ventricular ejection fraction, low-frequency bands, myocardium disorders, patient characterization, power spectral density curve, standard deviation, statistical significant differences, systolic BP, systolic slope, systolic time intervals, time domain analysis, ventricular ejection fraction, Abstracts, Databases, Parameter extraction, Telecommunication standards, Time-frequency analysis

Some of the most common clinical problems in elderly patients are related to diseases of the cardiac and respiratory systems. Elderly patients often have altered breathing patterns, such as periodic breathing (PB) and Cheyne-Stokes respiration (CSR), which may coincide with chronic heart failure. In this study, we used the envelope of the respiratory flow signal to characterize respiratory patterns in elderly patients. To study different breathing patterns in the same patient, the signals were segmented into windows of 5 min. In oscillatory breathing patterns, frequency and time-frequency parameters that characterize the discriminant band were evaluated to identify periodic and non-periodic breathing (PB and nPB). In order to evaluate the accuracy of this characterization, we used a feature selection process, followed by linear discriminant analysis. 22 elderly patients (7 patients with PB and 15 with nPB pattern) were studied. The following classification problems were analyzed: patients with either PB (with and without apnea) or nPB patterns, and patients with CSR versus PB, CSR versus nPB and PB versus nPB patterns. The results showed 81.8% accuracy in the comparisons of nPB and PB patients, using the power of the modulation peak. For the segmented signal, the power of the modulation peak, the frequency variability and the interquartile ranges provided the best results with 84.8% accuracy, for classifying nPB and PB patients.

JTD Keywords: cardiovascular system, diseases, feature extraction, geriatrics, medical signal processing, oscillations, pneumodynamics, signal classification, time-frequency analysis, Cheyne-Stokes respiration, apnea, cardiac systems, chronic heart failure, classification problems, discriminant band, diseases, elderly patients, feature selection process, frequency variability, interquartile ranges, linear discriminant analysis, nonperiodic breathing, oscillatory breathing pattern, periodic breathing, respiratory How signal, respiratory systems, signal segmentation, time 5 min, time-frequency parameters, Accuracy, Aging, Frequency modulation, Heart, Senior citizens, Time-frequency analysis

Weaning trials process of patients in intensive care units is a complex clinical procedure. 153 patients under extubation process (T-tube test) were studied: 94 patients with successful trials (group S), 38 patients who failed to maintain spontaneous breathing and were reconnected (group F), and 21 patients with successful test but that had to be reintubated before 48 hours (group R). The respiratory pattern of each patient was characterized through the following time series: inspiratory time (T_I), expiratory time (T_E), breathing cycle duration (T_Tot), tidal volume (V_T), inspiratory fraction (T_I/T_Tot), half inspired flow (V_T/T_I), and rapid shallow index (f/V_T), where f is respiratory rate. Using techniques as autoregressive models (AR), autoregressive moving average models (ARMA) and autoregressive models with exogenous input (ARX), the most relevant parameters of the respiratory pattern were obtained. We proposed the evaluation of these parameters using classifiers as logistic regression (LR), linear discriminant analysis (LDA), support vector machines (SVM) and classification and regression tree (CART) to discriminate between patients from groups S, F and R. An accuracy of 93% (98% sensitivity and 82% specificity) has been obtained using CART classification.

JTD Keywords: Accuracy, Indexes, Logistics, Regression tree analysis, Support vector machines, Time series analysis, Autoregressive moving average processes, Medical signal processing, Pattern classification, Pneumodynamics, Regression analysis, Sensitivity, Signal classification, Support vector machines, Time series, SVM, T-tube testing, Autoregressive models-with-exogenous input, Autoregressive moving average models, Breathing cycle duration, Classification-and-regression tree, Expiratory time, Extubation process, Half inspired flow, Inspiratory fraction, Inspiratory time, Intensive care units, Linear discriminant analysis, Logistic regression, Rapid shallow index, Respiratory pattern parameter performance, Sensitivity, Spontaneous breathing, Support vector machines, Tidal volume, Time 48 hr, Time series, Weaning process classifiers

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1_st and 2_nd ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO₂ and periodic breathing cycles significantly increased with acclimatization (p-value <; 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO₂, through a significant negative correlation (p-value <; 0.01). Higher Pm is observed at climbing periods visually labeled as PB with >; 5 periodic breathing cycles through a significant positive correlation (p-value <; 0.01). Our data demonstrate that quantification of the respiratory volum- signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

JTD Keywords: Frequency domain analysis, Frequency modulation, Heart, Sleep apnea, Ventilation, Visualization, Cardiology, Medical disorders, Medical signal processing, Plethysmography, Pneumodynamics, Sensitivity analysis, Sleep, Spectral analysis, Cheyne-Stokes respiration, Climbing periods, Dataset, Heart failure patients, High altitude PB, High altitude periodic breathing, Hypobaric hypoxia, Linear discriminant analysis, Pathophysiologic aspects, Physical activity, Physiologic mechanisms, Power spectral density, Receiver operating characteristic curve, Respiratory control, Respiratory frequency, Respiratory inductive plethysmography, Respiratory pattern, Respiratory volume signal, Sleep apnea, Spectral analysis, Spectral parameters

We have studied the preparation of Cu2O films by copper anodization in a 0.1 M NaOH electrolyte. We identified the potential range at which Cu dissolution takes place then we prepared films with different times of exposure to this potential. The morphology, crystalline structure, band gap. Urbach energy and thickness of the films were studied. Films prepared with the electrode unexposed to the dissolution potential have a pyramidal growth typical of potential driven processes, while samples prepared at increasing exposure times to dissolution potential present continuous nucleation, growth and grain coalescence. We observed a discrepancy in the respective film thicknesses calculated by coulometry, atomic force microscopy and optical reflectance. We propose that anodic Cu2O film formation involves three parallel mechanisms (i) Cu2O nucleation at the surface, (ii) Cu+ dissolution followed by heterogeneous nucleation and (iii) Cu+ and OH- diffusion through the forming oxide and subsequent reaction in the solid state.

JTD Keywords: Cuprous oxide, Anodic films, Reflectance, Thickness, Band gap, Urbach tail parameter, Dissolution, Growth mechanism

Statistical analysis, power spectral density, and Lempel Ziv complexity, are used in a multi-parameter approach to analyze four temporal series obtained from the Electrocardiographic and Respiratory Flow signals of 126 patients on weaning trials. In which, 88 patients belong to successful group (SG), and 38 patients belong to failure group (FG), i.e. failed to maintain spontaneous breathing during trial. It was found that mean values of cardiac inter-beat and breath durations give higher values for SG than for FG; Kurtosis coefficient of the spectrum of the rapid shallow breathing index is higher for FG; also Lempel Ziv complexity mean values associated with the respiratory flow signal are bigger for FG. Patients were then classified with a pattern recognition neural network, obtaining 80% of correct classifications (81.6% for FG and 79.5% for SG).

JTD Keywords: Electrocardiography, Medical signal processing, Neural nets, Pattern recognition, Pneumodynamics, Signal classification, Statistical analysis, ECG, Kurtosis coefficient, Lempel Ziv complexity, Breath durations, Cardiac interbeat durations, Electrocardiography, Multiparameter analysis, Pattern recognition neural network, Power spectral density, Respiratory flow signals, Signal classification, Spontaneous breathing, Statistical analysis, Weaning trials