Traditional methods to incorporate metals into graphene oxide (GO) usually require toxic reagents or high temperatures. This study proposes an innovative and sustainable method to incorporate silver ...(Ag) into graphene oxide using electron beam and evaluate its antibacterial activities. The method is based on green synthesis, without toxic reagents or hazardous wastes, and can be carried out at room temperature, in short reaction times. To synthesize the Ag/rGO nanocomposite, a water/isopropanol solution with dispersed graphene oxide and silver nitrate was submitted to a dose range from 150 to 400 kGy. The product was characterized by thermogravimetry analysis, X-ray diffraction and transmission electron microscopy. The antibacterial activity of Ag/rGO was observed against Gram-negative
Escherichia coli
by plate count method and atomic force microscopy. The results showed that concentrations as low as 100 μg/mL of produced Ag/rGO were enough to inactivate the cells.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
vB_EcoM-UFV13, a member of the T4virus genus, shows lytic activity against Escherichia coli and effectiveness in controlling the biofilm formed by Trueperella pyogenes, which qualifies it as a ...promising component of phage cocktails for mastitis and metritis control.
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with ...other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.
Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these ...associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients.
Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group.
The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1β, MCP 1, and VEGF levels, total lymphocyte counts, and CD8
CD38
mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8
CD38
T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8
HLA-DR
CD38
cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR
CD38
cells.
Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This article aims to analyze residential segregation by race (racial segregation) and income (economic segregation) in Brazil and explore its relationship with socioeconomic and socio-spatial ...factors. Residential segregation was assessed using the dissimilarity index based on the 2010 demographic census and considering urban census tracts since segregation is sociologically considered an urban problem. The results for racial segregation showed that it is more evident in cities in the South and Southeast of Brazil and mainly affects the self-declared black population. The approach used to calculate economic segregation involved examining the income level of different low-income groups. Therefore, we consider families that earned between 0 and 1 minimum wage as the group with the greatest social vulnerability. We did not find significant correlations between racial and income segregation indices with aspects such as urbanization (urban population size). Finally, we present the racial segregation indices stratifying families by income thresholds for the 27 Brazilian capitals and conclude that per capita household income is a preponderant factor for the segregation of the poorest, especially in families whose residents self-identify as black.
Abstract Sildenafil is a potent selective inhibitor of phosphosdiesterase-5 previously used in erectile dysfunction and subsequently approved in 2005 for pulmonary arterial hypertension treatment. ...Since oral administration of sildenafil shows pharmacokinetic problems with mean absolute bioavailability of 41%, the goal of this work was to develop a novel sildenafil self-emulsifying drug delivery system (SEDDS) for oral absorption improvement and management of dosage. One pharmaceutical solution and four SEDDS containing sildenafil were successfully obtained and SEDDS formed O/W nanoemulsion with droplet size less than 300 nm. The stability studies evidenced that the SEDDS containing 3.3% w/w of sildenafil yielded the best results. The safety of 2-pyrrolidone/isobutanol in oral formulations was assessed in mice and no lethality was achieved in the placebo groups with LD50 of 490 mg/Kg for SEDDS II-3.3, suggesting it as a safe excipient for humans. Therewithal, in silico studies using PBPK models provided the pharmacokinetic profile of sildenafil SEDDS. Subsequently, in silico evaluation indicated that the sildenafil SEDDS droplet size influenced its bioavailability, enhancing absorption, assuring a good pharmacokinetic profile. These findings suggest that the formulations developed here presented the potential to enhance drug oral absorption with the possibility to control drug dosage as they are liquid pharmaceutical formulations.
Purpose
Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying ...mechanism has not been fully elucidated.
Methods
All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury.
Results
The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8
+
CD38
+
mean fluorescence intensity (MFI), and percentage of CD8
+
human leukocyte antigen DR isotope (HLA-DR)
+
CD38
–
cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)
+
MFI, percentage of CD8
+
CD38
+
cells, CD8
+
HLA-DR
+
MFI, CD8
+
NKG2A
+
MFI, and percentage of CD8
+
HLA-DR
–
CD38
+
cells. On multivariate regression, the CD8
+
HLA-DR
+
MFI, CD8
+
CD38
+
MFI, and total lymphocyte count were associated significantly with myocardial injury.
Conclusion
Our findings suggest that lymphopenia, CD8
+
CD38
+
MFI, and CD8
+
HLA-DR
+
MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The concern about the risks of viral infections transmission through blood transfusion has led into a search for improvements on screening tests used for the selection of blood donors. Molecular ...biology techniques applied in researches of viral genomes, known as Nucleic Acid-amplification-Test (NAT), represent a technology capable of increasing transfusion safety by shortening the diagnostic window period. In Brazil, the implementation of this technology for the detection of HIV, HCV and HBV occurred due to the implantation of the NAT Kit - produced by Immunobiological Technology Institute (Biomanguinhos-FIOCRUZ), in the Brazilian blood centers. The National Health Surveillance Agency attaches great importance to validation, since it standardizes, disciplines and regulates criteria for the registration of health products. This work aims to establish a protocol of performance validation by real-time PCR method, taking as the object of study the Bio-Manguinhos NAT Kit, in order to update the product registration or to meet any future needs to ensure all regulatory requirements for the performance validation of the real-time PCR diagnostic kit. The protocol developed followed the ICH recommendations. The results revealed that the adopted methodology contemplates the necessary requirements for compliance with the Brazilian legislation, as well as the established validation parameters.
The
genus comprises opportunistic fungi that can become pathogenic when the immune system of the host fails.
is the most important and prevalent species. Polyenes, fluoropyrimidines, echinocandins, ...and azoles are used as commercial antifungal agents to treat candidiasis. However, the presence of intrinsic and developed resistance against azole antifungals has been extensively documented among several
species. The advent of original and re-emergence of classical fungal diseases have occurred as a consequence of the development of the antifungal resistance phenomenon. In this way, the development of new satisfactory therapy for fungal diseases persists as a major challenge of present-day medicine. The design of original drugs from traditional medicines provides new promises in the modern clinic. The urgent need includes the development of alternative drugs that are more efficient and tolerant than those traditional already in use. The identification of new substances with potential antifungal effect at low concentrations or in combination is also a possibility. The present review briefly examines the infections caused by
species and focuses on the mechanisms of action associated with the traditional agents used to treat those infections, as well as the current understanding of the molecular basis of resistance development in these fungal species. In addition, this review describes some of the promising alternative molecules and/or substances that could be used as anticandidal agents, their mechanisms of action, and their use in combination with traditional drugs.
Preeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving ...properties that has been much studied in various animal models of inflammation but poorly studied in the context of human inflammatory diseases. The main objective of this study was to measure AnxA1 levels in PE women and to compare those levels in normotensive pregnant and non-pregnant women. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants.
This study included 40 non-pregnant, 38 normotensive pregnant and 51 PE women. PE women were stratified in early (N = 23) and late (N = 28) subgroups, according to gestational age (GA) at onset of clinical symptoms. Protein AnxA1 and us-CRP plasma levels were determined by ELISA and immunoturbidimetric assays, respectively. Transcript levels of AnxA1 in peripheral blood mononuclear cells (PBMC) were measured by real time RT-PCR.
Increased levels of AnxA1 coincided with higher us-CRP levels in the plasma of PE women. Pregnant women with early PE had higher levels of AnxA1 and us-CRP than normotensive pregnant women with GA <34 weeks. No significant difference was found for AnxA1 and us-CRP, comparing late PE and normotensive pregnant women with GA ≥ 34 weeks. AnxA1 mRNA levels in PBMC were similar among the studied groups. AnxA1 was positively correlated with sTNF-R1, but not with us-CRP.
Our data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis. However, more studies are needed to clarify the role of AnxA1 and other proresolving molecules in the context of the systemic inflammatory response in this intriguing disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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