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Soybean is a crucial crop for the Brazilian economy, but it faces challenges from the biotrophic fungus Phakopsora pachyrhizi, which causes Asian Soybean Rust (ASR). In this study, we aimed to identify SNPs associated with resistance within the Rpp1 locus, which is effective against Brazilian ASR populations. We employed GWAS and re-sequencing analyzes to pinpoint SNP markers capable of differentiating between soybean accessions harboring the Rpp1, Rpp1-b and other alternative alleles in the Rpp1 locus and from susceptible soybean cultivars. Seven SNP markers were found to be associated with ASR resistance through GWAS, with three of them defining haplotypes that efficiently distinguished the accessions based on their ASR resistance and source of the Rpp gene. These haplotypes were subsequently validated using a bi-parental population and a diverse set of Rpp sources, demonstrating that the GWAS markers co-segregate with ASR resistance. We then examined the presence of these haplotypes in a diverse set of soybean genomes worldwide, finding a few new potential sources of Rpp1/Rpp1-b. Further genomic sequence analysis revealed nucleotide differences within the genes present in the Rpp1 locus, including the ULP1-NBS-LRR genes, which are potential R gene candidates. These results provide valuable insights into ASR resistance in soybean, thus helping the development of resistant soybean varieties through genetic breeding programs.
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Alelos , Resistência à Doença , Estudo de Associação Genômica Ampla , Glycine max , Phakopsora pachyrhizi , Doenças das Plantas , Polimorfismo de Nucleotídeo Único , Glycine max/genética , Glycine max/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Resistência à Doença/genética , Phakopsora pachyrhizi/fisiologia , Phakopsora pachyrhizi/genética , Haplótipos , Genes de Plantas , Basidiomycota/fisiologiaRESUMO
The highly porous morphology of chitosan cryogels, with submicrometric-sized pore cell walls, provides a large surface area which leads to fast water absorption and elevated swelling degrees. These characteristics are crucial for the applications of nitric oxide (NO) releasing biomaterials, in which the release of NO is triggered by the hydration of the material. In the present study, we report the development of chitosan cryogels (CS) with a porous structure of interconnected cells, with wall thicknesses in the range of 340-881 nm, capable of releasing NO triggered by the rapid hydration process. This property was obtained using an innovative strategy based on the functionalization of CS with two previously synthesized S-nitrosothiols: S-nitrosothioglycolic acid (TGA(SNO)) and S-nitrosomercaptosuccinic acid (MSA(SNO)). For this purpose, CS was previously methacrylated with glycidyl methacrylate and subsequently submitted to photocrosslinking and freeze-drying processes. The photocrosslinked hydrogels thus obtained were then functionalized with TGA(SNO) and MSA(SNO) in reactions mediated by carbodiimide. After functionalization, the hydrogels were frozen and freeze-dried to obtain porous S-nitrosated chitosan cryogels with high swelling capacities. Through chemiluminescence measurements, we demonstrated that CS-TGA(SNO) and CS-MSA(SNO) cryogels spontaneously release NO upon water absorption at rates of 3.34 × 10-2 nmol mg-1 min-1 and 1.27 × 10-1 nmol mg-1 min-1, respectively, opening new perspectives for the use of CS as a platform for localized NO delivery in biomedical applications.
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Quitosana , Criogéis , Óxido Nítrico , Quitosana/química , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Criogéis/química , Porosidade , Processos Fotoquímicos , Reagentes de Ligações Cruzadas/químicaRESUMO
INTRODUCTION AND OBJECTIVES: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.
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Encefalopatia Hepática , Falência Hepática Aguda , Transplante de Fígado , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/etiologia , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/cirurgia , Falência Hepática Aguda/complicações , Homeostase/fisiologiaRESUMO
BACKGROUND: Developmental models suggest that the phenotypes may arise from an immediate or mediated adaptive metabolic response of the perinatal growth. Evidence on the cumulative effects of growth and factors associated with risk of insulin resistance in adolescents is lacking. OBJECTIVE: To investigate the association between birthweight, weight gain during infancy, childhood and adolescence and the triglyceride-glucose index in adolescents. METHODS: This is a cohort of 217 children born at term, followed for the first six months, and reassessed at 8 and 18 years of age. The variables of interest were birthweight, postnatal growth defined as rapid postnatal growth when the weight gain from birth to six months of age was greater than 0.67 z-score, and the same criterion was used for high BMI gain from ages 6 months to 8 years, and from 8 to 18 years. Socioeconomic condition, nutritional status, practice of physical exercises and consumption of ultra-processed foods were verified. Multivariate linear regression analysis was used to verify the effect of the variables on the triglyceride-glucose index. RESULTS: Birthweight was not associated with triglyceride-glucose index in adolescence. Rapid postnatal growth during the first 6 months, higher BMI gain from 8 to 18 years and higher waist circumference contributed significantly to explain higher triglyceride-glucose index. CONCLUSION FOR PRACTICE: Our findings suggest that rapid postnatal growth may be one of the first signs of a higher triglyceride-glucose index in adolescence and that attention should be paid to the greater gain in body mass between childhood and adolescence for the risk of a higher triglyceride-glucose index.
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Glucose , Aumento de Peso , Criança , Feminino , Gravidez , Humanos , Adolescente , Estudos de Coortes , Peso ao Nascer/fisiologia , Brasil , Índice de Massa Corporal , Aumento de Peso/fisiologia , Triglicerídeos , Fatores de RiscoRESUMO
Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1-3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests.
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This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their immune system acts against the invading pathogen, without a pre-established infection rate. Analysis at the microscopic level demonstrates the impact of vaccination on individual immune responses and infection outcomes, providing a more realistic representation of how the humoral response caused by vaccination affects the individual's immune defense. At the macroscopic level, the effects of different population-wide vaccination strategies are explored, including random vaccination, targeted vaccination of specific demographic groups, and spatially focused vaccination. The results indicate that increased vaccination rates are correlated with decreased infection and mortality rates, highlighting the importance of achieving herd immunity. Furthermore, strategies focused on vulnerable populations or densely populated regions prove to be more effective in reducing disease transmission compared to randomly distributed vaccination. The results presented in this work show that vaccination strategies focused on highly crowded regions are more efficient in controlling epidemics and outbreaks. Results suggest that applying vaccination only in the densest region resulted in the suppression of infection in that region, with less intense viral spread in areas with lower population densities. Strategies focused on specific regions, in addition to being more efficient in reducing the number of infected and dead people, reduce costs related to transportation, storage, and distribution of doses compared to the random vaccination strategy. Considering that, despite scientific efforts to consolidate the use of mass vaccination, the accessibility, affordability, and acceptability of vaccines are problems that persist, investing in the study of strategies that mitigate such issues is crucial in the development and application of government policies that make immunization systems more efficient and robust.
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PURPOSES: Due to the popularity and increasing launch of toothpastes with whitening and sensitivity properties on the market, this study aimed to evaluate the fluoride concentrations in these products, since the concentrations of fluoride directly interfere with the anti-caries potential. METHODS: This is an experimental, in vitro study, where 37 samples from different batches (n = 3) purchased in different countries, were analysed in duplicate, via the ion-selective electrode technique to verify the concentration (µg/g or ppm F-) of total fluoride (TF), total soluble fluoride (TSF) and ionic fluoride (IF). For a comparative data analysis, ANOVA was applied followed by a Tukey's test for multiple comparisons. The level of confidence adopted was 95%. RESULTS: In the 37 assessed toothpastes, 45.9% contained NaF and 54.1% sodium monofluorophosphate (MFP). The TF found in the formulations ranged from 902.8 to 1539.4 ppm of F (mean: 1165.2 ± 179.3); fluoride concentration in the TSF fraction ranged from 708.8 to 1306.7 ppm of F (mean: 959.5 ± 162.4); IF results ranged from 101.9 to 1162.3 ppm of F (642.2 ± 294.1). Significant differences (p < 0.05) were found in the concentrations of the 59.5% assessed toothpastes in comparisons between declared and measured total fluoride (TF) concentrations, as well as in 62.2% when total fluoride (TF) and total soluble fluoride (TSF) were compared. CONCLUSIONS: In this study, most of the samples evaluated showed discrepancies when compared to the information declared by the manufacturers. In addition, the soluble concentrations found in half of the samples were lower than total concentrations and this may affect anti-caries effectiveness.
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The application of various density functional approximations (DFAs) and an emphasis on popular methods without any consensus have prevailed in computational studies dedicated to carbocations. More importantly, an extensive and rigorous benchmark investigation on density functionals for the class is still lacking. To close this gap, we present a comprehensive benchmark study of quantum chemical methods on a series of classical and nonclassical carbocations, the CARBO33 dataset. We evaluate a total of 107 DFT methods from all rungs giving particular attention to double hybrid density functionals as the potential of the class has been largely undermined in the context of carbocations. To support our findings, DLPNO-CCSD(T) at the complete basis set (CBS) limit and W1-F12 are used as reference methods. Our results indicate that the composite CBS-QB3 method performs poorly and should not be adopted for target energies. Oftentimes, the tested DFAs of a lower rung perform better than several DFAs in a higher rung of Perdew's "Jacob's ladder". Nonetheless, double hybrids DSD-PBEP86-NL and ωB97X-2-D3(BJ) stand out by showing the overall best performance. Among the hybrids evaluated, about half of them show mean absolute deviation (MAD) below 1.1 kcal mol-1, including the popular hybrids M06-2X and mPW1PW91. In this family, MN15-D3(BJ) performs particularly well (MAD = 0.77 kcal mol-1) displaying reliable results across various tests. Highly popular B3LYP exhibited one of the worst performances (MAD = 4.74 kcal mol-1), and we do not recommend its application to carbocations. We also assess the 24 general-purpose basis sets of single- up to quadruple-ζ quality. The best compromise between accuracy and computational cost is achieved with cc-pVTZ followed by def2-TZVP. Computations on larger structures of general interest, including terpene carbocations, are also presented for selected DFT methods confirming general trends in the results.
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The coronavirus disease 2019 (COVID-19) mortality rates varied among the states of Brazil during the course of the pandemics. The human leukocyte antigen (HLA) is a critical component of the antigen presentation pathway. Individuals with different HLA genotypes may trigger different immune responses against pathogens, which could culminate in different COVID-19 responses. HLA genotypes are variable, especially in the highly admixed Brazilian population. In this ecological study, we aimed to investigate the correlation between HLA haplotypes and the different regional distribution of COVID-19 mortality in Brazil. HLA data was obtained from 4,148,713 individuals registered in The Brazilian Voluntary Bone Marrow Donors Registry. COVID-19 data was retrieved from epidemiological bulletins issued by State Health Secretariats via Brazil's Ministry of Health from February/2020 to July/2022. We found a positive significant correlation between the HLA-A*01~B*08~DRB1*03 haplotype and COVID-19 mortality rates when we analyzed data from 26 states and the Federal District. This result indicates that the HLA-A*01~B*08~DRB1*03 haplotype may represent an additional risk factor for dying due to COVID-19. This haplotype should be further studied in other populations for a better understanding of the variation in COVID-19 outcomes across the world.
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Medula Óssea , COVID-19 , Humanos , Haplótipos , Brasil/epidemiologia , Frequência do Gene , Antígenos HLA-B/genética , COVID-19/genética , Cadeias HLA-DRB1/genética , Alelos , Antígenos HLA/genética , Antígenos HLA-A/genéticaRESUMO
The aim of the study was to evaluate the presence of metal(loid)s in lubricating eye drops used in the treatment of dry eye disease. The concentrations of Al, As, Ba, Cd, Co, Cu, Cr, Pb, Fe, Mg, Mn, Mo, Ni, Se, V, and Zn were determined in 19 eye drop samples using inductively coupled plasma optical emission spectrometry (ICP OES). The limit of detection (LOD) and limit of quantification (LOQ) values for the quantified elements ranged from 0.0002-0.0363 (mg/L) and 0.0007-0.1211 (mg/L), respectively. High values of concentrations of Al (2.382 µg/g), As (0.204 µg/g), Ba (0.056 µg/g), Cd (0.051 µg/g), Co (1.085 µg/g), Cr (0.020 µg/g), Cu (0.023 µg/g), Fe (0.453 µg/g), Mg (24.284 µg/g), Mn (0.014 µg/g), Mo (0.046 µg/g), Ni (0.071 µg/g), Pb (0.049 µg/g), Se (0.365 µg/g), V (0.083 µg/g), and Zn (0.552 µg/g) were quantified in samples of eye drops with and without preservatives. The concentrations of As (5 samples) and Cd (3 samples) were higher than those allowed by the Brazilian Pharmacopoeia for impurities (parenteral use). The value of Co content (µg/g) in a sample was higher than the value established by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH Q3D (R2)) in the parenteral route. The daily eye drop instillation exposure (µg/day) was below the values from the parenteral-permitted daily exposure (PDE) set by the ICH Q3D guideline (R2). The presence of heavy metals in eye drops is an alert to regulatory agencies in several countries so that control and inspections can be carried out.
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Síndromes do Olho Seco , Lubrificantes Oftálmicos , Humanos , Cádmio , Chumbo , Síndromes do Olho Seco/tratamento farmacológico , BrasilRESUMO
Cellulose nanocrystals (CNC)-based foams are promising tissue engineering materials that may facilitate implant-tissue integration and allow localized and controlled drug delivery. Herein, hybrid CNC-based foams, which are ultralightweight (30-100 mg cm-3 ), highly porous (>95%), ominiphilic and superabsorbent (1500-3000 wt% of water and/or toluene uptake) are obtained by the in situ condensation of poly(ethylene glycol) ditriethoxysilyl (TES-PEG-TES) into a 3D network, where silsesquioxane nanoparticles (SS-NP) are the crosslinking nodes, and CNC are entrapped forming ionic interactions, in a supramolecular structure. In a new approach, using 3-mercaptopropyltrimethoxysilane, sulfhydryl groups are inserted on the SS-NP periphery and S-nitrosated to enable the functionalization of SS-NP with S-nitrosothiol groups, which can nitric oxide (NO), in a process triggered by the hydration of the foams and modulated by their supramolecular structure. CNC-SS-PEG foams exhibit elevated thermal and structural stability, compressive strength compatible with various soft human tissues, and NO release rates (1-18 pmol mg-1 min-1 ) within the range of the beneficial NO actions. Thus, the CNC-SS-PEG foams herein described represent a new platform of supramolecular hybrid materials for localized delivery of NO, with potential uses in tissue engineering and other biomedical applications.
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Celulose , Nanopartículas , Celulose/química , Humanos , Nanopartículas/química , Óxido Nítrico , Engenharia Tecidual , Água/químicaRESUMO
Computer vision (CV) feedback could be aimed as a constant tutor to guide ones proficiency during microsurgical practice in controlled environments. Five neurosurgeons with different levels of microsurgical expertise performed simulated vessel dissection and micro-suture in an ex vivo model for posterior computer analysis of recorded videos. A computer program called PRIME (Proficiency Index of Microsurgical Education) used in this research recognized color-labeled surgical instruments, from downloading videos into a platform, with a range of motion greater than 3 mm, for objective evaluation of number of right and left hand movements. A proficiency index of 0 to 1 was pre-established in order to evaluate continuous training improvement. PRIME computer program captured all hand movements executed by participants, except for small tremors or inconsistencies that have a range of motion inferior to 3 mm. Number of left and right hand movements were graphically expressed in order to guide more objective and efficacious training for each trainee, without requiring body sensors and cameras around the operating table. Participants with previous microsurgical experience showed improvement from 0.2 to 0.6 (p < 0.05), while novices had no improvement. Proficiency index set by CV was suggested, in a self-challenge and self-coaching manner. PRIME would offer the capability of constant laboratory microsurgical practice feedback under CV guidance, opening a new window for oriented training without a tutor or specific apparatus regarding all levels of microsurgical proficiency. Prospective, large data study is needed to confirm this hypothesis.
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Internato e Residência , Tutoria , Treinamento por Simulação , Competência Clínica , Computadores , Humanos , Microcirurgia , Estudos ProspectivosRESUMO
This paper documents an increase in the number of observed explosive cyclones (EC) at King George Island, South Shetland Islands, Antarctica, over the 1989â2020 period. In ECs at 60o latitudes the surface atmospheric pressure drops ≥24 hPA in 24 hours. The annual EC frequency time series shows a significant positive trend of ~2.7 cyclones/decade, with a break in 2003 and average numbers of 7.3 and 11.8 events before and after that break, respectively. The increase follows closely earlier documented global sea surface temperature (SST) anomaly trends for the 1981â2018 period, partially attributed to global warming and to the Pacific Decadal Oscillation (PDO). Connections between EC frequency and SST might occur through variations in SST in the southeastern Pacific and southwestern Atlantic, with anomalous cold conditions favoring an increase in ECs. We also found close relations between the number of ECs with simultaneous occurrences of PDO and Atlantic multidecadal oscillation in opposite phases, so that after 2003 they were in the cold and warm phases, respectively, and vice-versa before 2003. Both low-frequency modes seem to modulate the number of ECs. As per the authors knowledge these results have not been discussed before and may help climate modeling studies and weather forecasts.
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Tempestades Ciclônicas , Substâncias Explosivas , Temperatura , Fatores de Tempo , Tempo (Meteorologia)RESUMO
PURPOSE: Sialendoscopy is a minimally invasive procedure considered a paradigm shift in the treatment of obstructive sialadenitis. However, it shows an average need for revision procedure in up to 24% of operated cases. This study analyzed whether patient-related variables could predict the need for a revision during postoperative follow-up. METHODS: From 2012 to 2020, this prospective comparative study analyzed demographic data as well as preoperative responses to the "Manukau Salivary Symptoms Score" (MSSS) questionnaire as predictors of the need for a revision procedure due to symptoms recurrence. RESULTS: 188 sialendoscopies (39.4% for stones/60.6% for stenoses) in 112 parotid (59.6%) and 76 submandibular glands (40.4%) were included in this study. Forty patients (21.3%) required a revision procedure. The variable "Impact on quality of life" in the preoperative period of patients with sialoliths showed that the likelihood of a revision procedure increases by 33.6% with each increase in the 10-point Likert scale presented in the MSSS (p = 0.010, OR = 1336, CI = 1.071 to 1.667). This finding was not influenced by the location of the sialolith in the duct (p = 0.415), size (p = 0.058) or number of stones (P = 0.476). Other demographic variables related to the patient showed no association with the need of a revision procedure. CONCLUSION: Further studies should be performed to exclude the influence of other variables on the results; however, special attention should be given to patients who report a greater pre-operative impact on quality of life due to sialolithiasis. LEVEL OF EVIDENCE: II.
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Cálculos das Glândulas Salivares , Sialadenite , Endoscopia/métodos , Humanos , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Cálculos das Glândulas Salivares/cirurgia , Sialadenite/cirurgia , Resultado do TratamentoRESUMO
AIM: This study aimed to identify medications taken by patients before dental appointments and to simulate and characterize their interactions with medications often prescribed by dental surgeons. MATERIALS AND METHODS: A retrospective cross-sectional study evaluated 320 medical records, 118 from the Emergency Service (ES) archives, and 202 from elective appointments at the Dental Clinic (DC) of a university in southern Brazil. Drug interactions were identified and classified according to severity using the Medscape® application into four grades: (1) Minor, (2) Monitor closely, (3) Serious, or (4) Contraindicated. Descriptive and inferential statistical analyses were carried out (α = 5%). RESULTS: Preexisting systemic conditions were noted in 55.9% of the medical records from the ES and 64.35% from the DC. In the ES records, 47.45% contained information on continuous use medication for treatment of systemic conditions and 59.40% of DC records contained such information. A total of 359 potential interactions were found. Drug interactions with analgesics were most frequent, accounting for 50.41% of the sample. CONCLUSIONS: The most prevalent drug interaction severity was grade 2: monitor or use with caution. Many patients take medications to treat systemic conditions and seek dental care, generating a significant possible source of drug interactions. CLINICAL RELEVANCE: Prescribers must carefully analyze the patients' medical histories and obtain accurate data regarding their use of medications to be able to assess the risk-benefit relationships of possible combinations.
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Odontologia , Prescrições de Medicamentos , Humanos , Estudos Transversais , Estudos Retrospectivos , Interações MedicamentosasRESUMO
Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients' samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-ß, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs' roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.
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Infecções por HTLV-I , Leucemia-Linfoma de Células T do Adulto , MicroRNAs , Biologia Computacional , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/virologia , MicroRNAs/genéticaRESUMO
Hydrogels have been used as matrices for the topical delivery of nitric oxide (NO) for achieving vasodilation, wound healing and analgesic actions. More recently, supramolecular hydrogels comprised of poly(acrylic acid) (PAA) and micellar Pluronic F127 (F127), prepared by thermal reaction, emerged as a suitable matrix for the incorporation of hydrophilic NO donors, such as S-nitrosoglutathione (GSNO). Herein, we describe an innovative method for the three-dimensional (3D) printing of cellulose nanocrystal (CNC)-containing and semi-interpenetrating PAA/F127 hydrogels by PAA photopolymerization via digital light processing (DLP), in the absence of organic solvents. Scanning electron microscopy showed that, differently from typical porous PAA-based hydrogels, the 3D printed PAA/F127/CNC hydrogels have dense morphology. By using transmission electron microscopy we confirmed for the first time the presence of F127 micelles in the printable resin, and their preservation after the photopolymerization process. The F127 micelles conferred compressive recoverability to the 3D printed PAA/F127/CNC hydrogels, widening their potential applications as soft biomaterials. PAA/F127/CNC hydrogels charged with GSNO are shown to release NO spontaneously upon hydration at initial rates that depend on the GSNO charge and are higher in the presence of CNC. As local NO release may exert cell proliferation action, 3D printed PAA/F127/CNC/GSNO hydrogels may serve as a versatile soft biomaterial for local NO delivery in regenerative medicine and other biomedical applications.
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Hidrogéis , Nanopartículas , Resinas Acrílicas , Celulose , Óxido Nítrico , Polietilenos , Polipropilenos , Impressão TridimensionalRESUMO
Several studies have shown that the Brazilian Northeast is a region with high rates of inbreeding as well as a high incidence of autosomal recessive diseases. The elaboration of public health policies focused on the epidemiological surveillance of congenital anomalies and rare genetic diseases in this region is urgently needed. However, the vast territory, socio-demographic heterogeneity, economic difficulties and low number of professionals with expertise in medical genetics make strategic planning a challenging task. Surnames can be compared to a genetic system with multiple neutral alleles and allow some approximation of population structure. Here, surname analysis of more than 37 million people was combined with health and socio-demographic indicators covering all 1794 municipalities of the nine states of the region. The data distribution showed a heterogeneous spatial pattern (Global Moran Index, GMI = 0.58; p < 0.001), with higher isonymy rates in the east of the region and the highest rates in the Quilombo dos Palmares region - the largest conglomerate of escaped slaves in Latin America. A positive correlation was found between the isonymy index and the frequency of live births with congenital anomalies (r = 0.268; p < 0.001), and the two indicators were spatially correlated (GMI = 0.50; p < 0.001). With this approach, quantitative information on the genetic structure of the Brazilian Northeast population was obtained, which may represent an economical and useful tool for decision-making in the medical field.
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Genética Médica/estatística & dados numéricos , Genética Populacional/estatística & dados numéricos , Nomes , Adolescente , Adulto , Idoso , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica Populacional , Adulto JovemRESUMO
During pandemic events, strategies such as social distancing can be fundamental to reduce simultaneous infections and mitigate the disease spreading, which is very relevant to the risk of a healthcare system collapse. Although these strategies can be recommended, or even imposed, their actual implementation may depend on the population perception of the risks associated with a potential infection. The current COVID-19 crisis, for instance, is showing that some individuals are much more prone than others to remain isolated. To better understand these dynamics, we propose an epidemiological SIR model that uses evolutionary game theory for combining in a single process social strategies, individual risk perception, and viral spreading. In particular, we consider a disease spreading through a population, whose agents can choose between self-isolation and a lifestyle careless of any epidemic risk. The strategy adoption is individual and depends on the perceived disease risk compared to the quarantine cost. The game payoff governs the strategy adoption, while the epidemic process governs the agent's health state. At the same time, the infection rate depends on the agent's strategy while the perceived disease risk depends on the fraction of infected agents. Our results show recurrent infection waves, which are usually seen in previous historic epidemic scenarios with voluntary quarantine. In particular, such waves re-occur as the population reduces disease awareness. Notably, the risk perception is found to be fundamental for controlling the magnitude of the infection peak, while the final infection size is mainly dictated by the infection rates. Low awareness leads to a single and strong infection peak, while a greater disease risk leads to shorter, although more frequent, peaks. The proposed model spontaneously captures relevant aspects of a pandemic event, highlighting the fundamental role of social strategies.
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Lung cancer is the most lethal malignant neoplasm worldwide, with an annual estimated rate of 1.8 million deaths. Computed tomography has been widely used to diagnose and detect lung cancer, but its diagnosis remains an intricate and challenging work, even for experienced radiologists. Computer-aided diagnosis tools and radiomics tools have provided support to the radiologist's decision, acting as a second opinion. The main focus of these tools has been to analyze the intranodular zone; nevertheless, recent works indicate that the interaction between the nodule and its surroundings (perinodular zone) could be relevant to the diagnosis process. However, only a few works have investigated the importance of specific attributes of the perinodular zone and have shown how important they are in the classification of lung nodules. In this context, the purpose of this work is to evaluate the impact of using the perinodular zone on the characterization of lung lesions. Motivated by reproducible research, we used a large public dataset of solid lung nodule images and extracted fine-tuned radiomic attributes from the perinodular and intranodular zones. Our best-evaluated model obtained an average AUC of 0.916, an accuracy of 84.26%, a sensitivity of 84.45%, and specificity of 83.84%. The combination of attributes from the perinodular and intranodular zones in the image characterization resulted in an improvement in all the metrics analyzed when compared to intranodular-only characterization. Therefore, our results highlighted the importance of using the perinodular zone in the solid pulmonary nodules classification process.