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Antibiotic resistance genes (ARGs) have been extensively observed in bacterial DNA, and more recently, in phage particles from various water sources and food items. The pivotal role played by ARG transmission in the proliferation of antibiotic resistance and emergence of new resistant strains calls for a thorough understanding of the underlying mechanisms. The aim of this study was to assess the suitability of the prototypical p-crAssphage, a proposed indicator of human fecal contamination, and the recently isolated crAssBcn phages, both belonging to the Crassvirales group, as potential indicators of ARGs. These crAss-like phages were evaluated alongside specific ARGs (blaTEM, blaCTX-M-1, blaCTX-M-9, blaVIM, blaOXA-48, qnrA, qnrS, tetW and sul1) within the total DNA and phage DNA fractions in water and food samples containing different levels of fecal pollution. In samples with high fecal load (>103 CFU/g or ml of E. coli or somatic coliphages), such as wastewater and sludge, positive correlations were found between both types of crAss-like phages and ARGs in both DNA fractions. The strongest correlation was observed between sul1 and crAssBcn phages (rho = 0.90) in sludge samples, followed by blaCTX-M-9 and p-crAssphage (rho = 0.86) in sewage samples, both in the phage DNA fraction. The use of crAssphage and crAssBcn as indicators of ARGs, considered to be emerging environmental contaminants of anthropogenic origin, is supported by their close association with the human gut. Monitoring ARGs can help to mitigate their dissemination and prevent the emergence of new resistant bacterial strains, thus safeguarding public health.
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Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4+ T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8+ T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars.
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Linfócitos B , Vacinas contra COVID-19 , COVID-19 , Mieloma Múltiplo , SARS-CoV-2 , Vacinação , Humanos , Mieloma Múltiplo/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Linfócitos B/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologiaRESUMO
The development of wearable thermoelectric generators (wTEG) represents a promising strategy to replace batteries and supercapacitors required to supply electrical energy for portable electronic devices. However, the main drawback of wTEGs is that the thermal gradient between the skin and the ambient is minimal, reducing the power output produced by the generator. Therefore, it is necessary to improve the thermal management of wTEG in order to increase its efficiency. This work deals with the preparation of a thermoelectric generator that harnesses the plasmonic heating effect to enhance the thermal gradient of the final device. The thermoelectric layer is created through the in situ polymerization of terthiophene (3T) within a polyurethane matrix, utilizing silver (Ag) (I) and copper (II) perchlorate as oxidants. The plasmonic film, composed of Ag-NP (nanoparticles), is formed via photocatalytic reduction of silver nitrate in the presence of titanium oxide. These layers are then meticulously assembled to yield the hybrid plasmonic/thermoelectric generator.
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In this study, we have improved the power factor of conductive polymer nanocomposites by combining layer-by-layer assembly with electrochemical deposition to produce flexible thermoelectric materials based on PEDOT/carbon nanotubes (CNTs)-films. To produce films based on CNTs and PEDOT, a dual approach has been employed: (i) the layer-by-layer method has been utilized for constructing the CNTs layer and (ii) electrochemical polymerization has been used in the synthesis of the conducting polymer. Moreover, the thermoelectric properties were optimized by controlling the experimental conditions including the number of deposition cycles and electropolymerizing time. The electrical characterization of the samples was carried out by measuring the Seebeck voltage produced under a small temperature difference and by measuring the electrical conductivity using the four-point probe method. The resulting values of the Seebeck coefficient S and σ were used to determine the power factor. The structural and morphological analyses of CNTs/PEDOT samples were carried out using scanning electron microscopy (SEM) and Raman spectroscopy. The best power factor achieved was 131.1 (µWm-1K-2), a competitive value comparable to some inorganic thermoelectric materials. Since the synthesis of the CNT/PEDOT layers is rather simple and the ingredients used are relatively inexpensive and environmentally friendly, the proposed nanocomposites are a very interesting approach as an application for recycling heat waste.
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Wastewater-based surveillance constitutes a valuable methodology for the continuous monitoring of viral circulation, with the capacity to function as an early warning system. It holds particular significance in scenarios where respiratory viruses exhibit overlapping clinical presentations, as occurs with SARS-CoV-2, influenza virus (IV), and respiratory syncytial virus (RSV), and allows seasonal virus outbreaks to be distinguished from COVID-19 peaks. Furthermore, sewage sludge, given it harbors concentrated human waste from a large population, serves as a substantial reservoir for pathogen detection. To effectively integrate wastewater-based epidemiology into infectious disease surveillance, the detection methods employed in wastewater samples must be adapted to the distinct characteristics of sludge matrices. In this study, we adapted and applied protocols for the detection of IV and RSV in sewage sludge, comparing their performance with the results obtained in wastewater. To assess the efficiency of these protocols, sludge and wastewater samples were spiked with IV and RSV RNA, either free or incorporated in lentiviral particles. Samples were concentrated using the aluminum hydroxide adsorption-precipitation method before viral RNA extraction. Absolute virus quantification was carried out by RT-qPCR, including an internal control to monitor potential inhibitory factors. Recovery efficiencies for both free IV and RSV RNA were 60 % in sludge, and 75 % and 71 % respectively in wastewater, whereas the values for IV and RSV RNA in lentiviral particles were 16 % and 10 % in sludge and 21 % and 17 % in wastewater respectively. Additionally, the protocol enabled the quantification of naturally occurring IV and RSV in wastewater and sludge samples collected from two wastewater treatment plants during the winter months, thus affirming the efficacy of the employed methodologies.
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Orthomyxoviridae , Vírus , Humanos , Vírus Sinciciais Respiratórios , Esgotos , Águas Residuárias , RNA ViralRESUMO
BACKGROUND: Methylene blue (MB) and flavin mononucleotide (FMN)-mediated photodynamic therapy (PDT) have demonstrated local antimicrobial effect, but no direct comparative study has been published so far for the treatment of toenail onychomycosis. OBJECTIVES: To directly compare the short and medium-term efficacy of MB versus FMN as photosensitizers in PDT for toenail onychomycosis by applying them in a 40% w/w urea cream in two different dye concentrations. METHODS: Forty toenails with distal and lateral subungual moderate onychomycosis due to dermatophyte fungi were randomised to receive 10 weekly sessions of PDT mediated by four topical formulations including MB or FMN at two different concentrations: Group I: 0.1% w/w MB; Group II: 2% w/w MB; Group III: 0.1% w/w FMN; and Group IV: 2% w/w FMN. Photographs were used for onychomycosis severity index (OSI) estimation allowing clinical assessment at any point of the study. Microscopic and microbiological evaluations were carried out at baseline, 27- and 35-week follow-ups. Side effects were recorded along with patient satisfaction. RESULTS: At week 27, mycological cure rates were 60%, 30%, 50% and 40% and complete cure rates were 0%, 20%, 10% and 20%, for Groups I, II, III and IV respectively. At week 35, mycological cure rates were 70%, 70%, 70% and 60% and complete cure rates were 30%, 50%, 70% and 30%, for Groups I, II, III and IV respectively. All cream formulations were safe and patients were fairly satisfied. CONCLUSIONS: Results of the present work confirm PDT as a therapeutic alternative for onychomycosis. Although all cream formulations were safe and effective, with a good degree of satisfaction, higher cure rates were obtained with 2% w/w MB cream and 0.1% w/w FMN cream.
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Dermatoses do Pé , Onicomicose , Humanos , Antifúngicos/uso terapêutico , Onicomicose/tratamento farmacológico , Unhas , Azul de Metileno/uso terapêutico , Mononucleotídeo de Flavina/uso terapêutico , Dermatoses do Pé/tratamento farmacológico , Ureia , Resultado do TratamentoRESUMO
PURPOSE: to determine the yield of Video-Electroencephalogram (VEEG) in the first 24 h in patients with a first unprovoked seizure and normal neurological examination, laboratory findings, and cranial CT scans. METHODS: we analyzed retrospectively the yield of VEEG performed in these patients in the emergency department. All the patients were subsequently seen in the Epilepsy Clinic, and the epilepsy diagnosis was confirmed. RESULTS: we included 19 patients who met the inclusion criteria; all of them underwent VEEG with the 10-20 system within the first 24 h after the seizure. The duration of the recordings averaged at 108.53 min and may or may not have included intermittent photic stimulation and sleep recording; 74% of the recordings were abnormal, with 26% being normal. Among the abnormal cases, epileptogenic activity was found in 47% and seizures in 26% of the patients; because both findings could be present in the same VEEG, 63% of all the VEEG showed epileptogenic alterations or seizures. The VEEG anomalies were recorded before the 20th minute (standard VEEG duration) in 58% of patients who exhibited epileptogenic activity and/or seizures, and after the 20th minute in 42%. CONCLUSION: conducting approximately 100-minute VEEGs within the first 24 h after a first unprovoked seizure can enhance the diagnostic yield in patients with epilepsy. However, the study has the limitations of its sample size and retrospective nature.
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Epilepsia , Convulsões , Humanos , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Eletroencefalografia , Tomografia Computadorizada por Raios XRESUMO
The use of wearable devices has promoted new ways of integrating these devices, one of which is through the development of smart textiles. Smart textiles must possess the mechanical and electrical properties necessary for their functionality. This study explores the impact of polymer-felt microstructure variations on their morphology, electrical, and mechanical properties. The application of thermal treatment, along with an electric field, leads to a substantial structural reorganization of the molecular chains within pristine felt. This results in a system of nanofibrils coated with MWCNT-PEDOT, characterized by highly ordered counterions that facilitate the flow of charge carriers. Both temperature and an electric field induce reversible microstructural changes in pristine felt and irreversible changes in coated felt samples. Furthermore, electropolymerization of PEDOT significantly enhances electrical conductivity, with PEDOT:BTFMSI-coated fabric exhibiting the highest conductivity.
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Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.
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Crassvirales (crAss-like phages) are an abundant group of human gut-specific bacteriophages discovered in silico. The use of crAss-like phages as human fecal indicators is proposed but the isolation of only seven cultured strains of crAss-like phages to date has greatly hindered their study. Here, we report the isolation and genetic characterization of 25 new crAss-like phages (termed crAssBcn) infecting Bacteroides intestinalis, belonging to the order Crassvirales, genus Kehishuvirus and, based on their genomic variability, classified into six species. CrAssBcn phage genomes are similar to ΦCrAss001 but show genomic and aminoacidic differences when compared to other crAss-like phages of the same family. CrAssBcn phages are detected in fecal metagenomes around the world at a higher frequency than ΦCrAss001. This study increases the known crAss-like phage isolates and their abundance and heterogeneity open the question of what member of the Crassvirales group should be selected as human fecal marker.
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Bacteriófagos , Humanos , Heterogeneidade Genética , Genômica , Fezes , Metagenoma/genética , Genoma Viral/genética , FilogeniaRESUMO
SARS-CoV-2, the causal agent of COVID-19, is a new coronavirus that has rapidly spread worldwide and significantly impacted human health by causing a severe acute respiratory syndrome boosted by a pulmonary hyperinflammatory response. Previous data from our lab showed that the newly excysted juveniles of the helminth parasite Fasciola hepatica (FhNEJ) modulate molecular routes within host cells related to vesicle-mediated transport and components of the innate immune response, which could potentially be relevant during viral infections. Therefore, the aim of the present study was to determine whether FhNEJ-derived molecules influence SARS-CoV-2 infection efficiency in Vero cells. Pre-treatment of Vero cells with a tegument-enriched antigenic extract of FhNEJ (FhNEJ-TEG) significantly reduced infection by both vesicular stomatitis virus particles pseudotyped with the SARS-CoV-2 Spike protein (VSV-S2) and live SARS-CoV-2. Pre-treatment of the virus itself with FhNEJ-TEG prior to infection also resulted in reduced infection efficiency similar to that obtained by remdesivir pre-treatment. Remarkably, treatment of Vero cells with FhNEJ-TEG after VSV-S2 entry also resulted in reduced infection efficiency, suggesting that FhNEJ-TEG may also affect post-entry steps of the VSV replication cycle. Altogether, our results could potentially encourage the production of FhNEJ-derived molecules in a safe, synthetic format for their application as therapeutic agents against SARS-CoV-2 and other related respiratory viruses.
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COVID-19 , Fasciola hepatica , Animais , Chlorocebus aethiops , Humanos , SARS-CoV-2 , Células Vero , Antivirais/farmacologiaRESUMO
Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Complementary and alternative therapies are increasingly utilized to address its complex multisystem symptomatology. Art therapy involves motoric action and visuospatial processing while promoting broad biopsychosocial wellness. The process involves hedonic absorption, which provides an escape from otherwise persistent and cumulative PD symptoms, refreshing internal resources. It involves the expression in nonverbal form of multilayered psychological and somatic phenomena; once these are externalized in a symbolic arts medium, they can be explored, understood, integrated, and reorganized through verbal dialogue, effecting relief and positive change. Methods: 42 participants with mild to moderate PD were treated with 20 sessions of group art therapy. They were assessed before and after therapy with a novel arts-based instrument developed to match the treatment modality for maximum sensitivity. The House-Tree-Person PD Scale (HTP-PDS) assesses motoric and visuospatial processing-core PD symptoms-as well as cognition (thought and logic), affect/mood, motivation, self (including body-image, self-image, and self- efficacy), interpersonal functioning, creativity, and overall level of functioning. It was hypothesized that art therapy will ameliorate core PD symptoms and that this will correlate with improvements in all other variables. Results: HTP-PDS scores across all symptoms and variables improved significantly, though causality among variables was indeterminate. Discussion: Art therapy is a clinically efficacious complementary treatment for PD. Further research is warranted to disentangle causal pathways among the aforementioned variables, and additionally, to isolate and examine the multiple, discrete healing mechanisms believed to operate simultaneously in art therapy.
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Wastewater-based surveillance can be a valuable tool to monitor viral circulation and serve as an early warning system. For respiratory viruses that share similar clinical symptoms, namely SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), identification in wastewater may allow differentiation between seasonal outbreaks and COVID-19 peaks. In this study, to monitor these viruses as well as standard indicators of fecal contamination, a weekly sampling campaign was carried out for 15 months (from September 2021 to November 2022) in two wastewater treatment plants that serve the entire population of Barcelona (Spain). Samples were concentrated by the aluminum hydroxide adsorption-precipitation method and then analyzed by RNA extraction and RT-qPCR. All samples were positive for SARS-CoV-2, while the positivity rates for influenza virus and RSV were significantly lower (10.65 % for influenza A (IAV), 0.82 % for influenza B (IBV), 37.70 % for RSV-A and 34.43 % for RSV-B). Gene copy concentrations of SARS-CoV-2 were often approximately 1 to 2 logarithmic units higher compared to the other respiratory viruses. Clear peaks of IAV H3:N2 in February and March 2022 and RSV in winter 2021 were observed, which matched the chronological incidence of infections recorded in the Catalan Government clinical database. In conclusion, the data obtained from wastewater surveillance provided new information on the abundance of respiratory viruses in the Barcelona area and correlated favorably with clinical data.
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COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus , Humanos , Influenza Humana/epidemiologia , Vírus Sinciciais Respiratórios/genética , Águas Residuárias , COVID-19/epidemiologia , SARS-CoV-2 , Vigilância Epidemiológica Baseada em Águas Residuárias , Infecções por Vírus Respiratório Sincicial/epidemiologiaRESUMO
Segmented thermoplastic polyurethanes (PU) were synthetized using a polycarbonatediol macrodiol as a flexible or soft segment with a molar mass of 2000 g/mol, and different diisocyanate molecules and 1,4-butanediol as a rigid or hard segment. The diisocyanate molecules employed are 3,3'-Dimethyl-4,4'-biphenyl diisocyanate (TODI), 4,4'-diphenylmethane diisocyanate (MDI), 4,4'-Methylenebis(phenyl isocyanate) 1-isocyanato-4-[(4-phenylisocyanate)methyl]benzene and 1-isocyanate-4-[(2-phenylisocyanate) methyl]benzene (ratio 1:1) (MDIi), isophorone diisocyanate (IPDI), and hexamethylene diisocyanate (HDI). The polyurethanes obtained reveal a wide variation of microphase separation degree that is correlated with mechanical properties. Different techniques, such as DSC, DMA, and FTIR, have been used to determine flexible-rigid segment phase behavior. Mechanical properties, such as tensile properties, Shore D hardness, and "compression set", have been determined. This work reveals that the structure of the hard segment is crucial to determine the degree of phase miscibility which affects the resulting mechanical properties, such as tensile properties, hardness, and "compression set".
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In the first and limiting step of nitrification, ammonia (NH3) is oxidised to nitrite (NO2-) by the action of some prokaryotes, including bacteria of the Nitrosomonas genus. A potential approach to nitrification inhibition would be through the application of phages, but until now this method has been unexplored and no virulent phages that infect nitrifying bacteria have been described. In this study, we report the isolation of the first phage infecting some Nitrosomonas species. This polyvalent virulent phage (named ΦNF-1) infected Nitrosomonas europaea, Nitrosomonas communis, and Nitrosomonas nitrosa. Phage ΦNF-1 has the morphology of the Podoviridae family, a dsDNA genome of 41,596 bp and a 45.1 % GC content, with 50 predicted open reading frames. Phage ΦNF-1 was found to inhibit bacterial growth and reduce NH4+ consumption in the phage-treated cultures. The application of phages as biocontrol agents could be a useful strategy for nitrification inhibition without the restrictions associated with chemical inhibitors.
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Bacteriófagos , Nitrosomonas europaea , Bacteriófagos/genética , Nitrosomonas , Bactérias , Nitritos , AmôniaRESUMO
Keratolytic properties of urea 40% have long time used for the treatment of onychomycosis. Fractional ablative lasers enhance the delivery of topically applied photosensitizers improving photodynamic therapy (PDT) efficacy. The aim of this study was to compare the short- and medium-term efficacy of a pretreatment with urea 40% and fractional Er:YAG (Fr Er:YAG) laser radiation before PDT mediated by methylene blue (MB) for moderate toenail onychomycosis. Twenty-first-toe toenails were randomized to receive either urea 40% (Group I) or Fr Er:YAG laser (Group II) pretreatment and 9 sessions of MB/PDT over the course of 16 weeks. At baseline, 28- and 40-week follow-ups, clinical efficacy was assessed by digital photographs [allowing determination of the onychomycosis severity index (OSI)], whereas mycological efficacy was assessed by histological examination and fungal culture. Details of the side effects and patients' satisfaction were also recorded. In both groups, a significant decrease in OSI values was observed at the 28-week follow-up and a slight rebound at the 40-week follow-up. The percentage of nail involvement decreased significantly in both groups at the 28-week follow-up, to continue declining gently in Group I at 40 weeks, in contrast to the rebound observed during this period in Group II. The mycological cure rate was 20% and 30% at 28-week follow-up and 70% and 40% at 40-week follow-up, in Group I and II, respectively. Patients reported being fairly satisfied, and no side effects were detected in any groups. Although both pretreatments favor the action of PDT for the treatment of onychomycosis, the use of urea at 40% is more effective in the medium term.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lasers de Estado Sólido , Onicomicose , Fotoquimioterapia , Humanos , Onicomicose/tratamento farmacológico , Unhas/microbiologia , Azul de Metileno/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Ureia , Resultado do Tratamento , AntifúngicosRESUMO
This work focuses on the encapsulation of two organic phase change materials (PCMs), hexadecane and octadecane, through the formation of nanocapsules of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) obtained by oxidative polymerization in miniemulsion. The energy storage capacity of nanoparticles is studied by preparing polymer films on supporting substrates. The results indicate that the prepared systems can store and later release thermal energy in the form of latent heat efficiently, which is of vital importance to increase the efficiency of future thermoelectric devices.