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.
An outbreak of coronavirus disease began in a large penitentiary complex in Brazil on April 1, 2020. By June 12, there were 1,057 confirmed cases among inmates and staff. Nine patients were ...hospitalized, and 3 died. Mean serial interval was ≈2.5 days; reproduction number range was 1.0-2.3.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The hypnozoite form of
Plasmodium vivax
malaria can lead to recrudescent infection months after primary infection. Primaquine is used as prophylaxis to prevent such relapses. In this report, a higher ...total dose of primaquine (7.0 mg per kilogram over 14 days) was found to be more efficacious than the standard total dose (3.5 mg per kilogram over 7 days).
•A label-free flexible biodevice applicable to COVID-19 was developed.•Flexible transducers were modified with polypyrrole films and gold nanoparticles.•The sensor showed a limit of detection of ...258.01 copies µL−1 with high selectivity.•The resistance variation was associated with the cycle threshold value of RT-PCR.•SARS-CoV-2 diagnosis was correlated with various stages of the viral infection.
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The projection of new biosensing technologies for genetic identification of SARS-COV-2 is essential in the face of a pandemic scenario. For this reason, the current research aims to develop a label-free flexible biodevice applicable to COVID-19. A nanostructured platform made of polypyrrole (PPy) and gold nanoparticles (GNP) was designed for interfacing the electrochemical signal in miniaturized electrodes of tin-doped indium oxide (ITO). Oligonucleotide primer was chemically immobilized on the flexible transducers for the biorecognition of the nucleocapsid protein (N) gene. Methodological protocols based on cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and atomic force microscopy (AFM) were used to characterize the nanotechnological apparatus. The biosensor’s electrochemical performance was evaluated using the SARS-CoV-2 genome and biological samples of cDNA from patients infected with retrovirus at various disease stages. It is inferred that the analytical tool was able to distinguish the expression of SARS-CoV-2 in patients diagnosed with COVID-19 in the early, intermediate and late stages. The biosensor exhibited high selectivity by not recognizing the biological target in samples from patients not infected with SARS-CoV-2. The proposed sensor obtained a linear response range estimated from 800 to 4000 copies µL−1 with a regression coefficient of 0.99, and a detection limit of 258.01 copies µL−1. Therefore, the electrochemical biosensor based on flexible electrode technology represents a promising trend for sensitive molecular analysis of etiologic agent with fast and simple operationalization. In addition to early genetic diagnosis, the biomolecular assay may help to monitor the progression of COVID-19 infection in a novel manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glioblastoma is the most lethal tumor of the central nervous system, presenting a very poor prognostic, with a survival around 16 months. The interaction of mesenchymal stem cells and tumor cells has ...been studied, showing a bias in their role favoring or going against aggressiveness. Natural products such as flavonoids have showed their anticancer properties and the synergic potential with the activation of microenvironment cells to inhibit tumor progression. Agathisflavone is a flavonoid studied in neurodegenerative diseases and cancer. The present study investigated the effect of flavonoid in the viability of heterogeneous glioblastoma (GBM) cells considering a coculture or conditioned medium of mesenchymal stem cells (MSCs) effect, as well as the dose‐dependent effect of this flavonoid in tumor migration and differentiation via STAT3. Agathisflavone (3–10 μM) induced dose‐dependent toxicity to GL‐15 and U373 human GBM cells, since 24 h after treatments. It was not toxic to human MSC but modified the pattern of interaction with GBM cells. Agathisflavone also inhibited migration and increased differentiation of human GBM cells, associated with the reduction on the expression of STAT3. These results demonstrate that the flavonoid agathisflavone had a direct anti‐glioma effect. However, could be observed its effect in MSCs response that may have an impact in controlling GBM growth and aggressiveness, an important factor to consider for new therapies.
Flavonoid agathisflavone selective induces dose‐dependent toxicity in GL‐15 and U373 human glioblastoma (GBM) cells. Agathisflavone inhibits migration and promotes differentiation of human GBM cells. Agathisflavone is not toxic to human mesenchymal stem cells but modifies the pattern of interaction with glioblastoma cells, resulting in resistance.
Highlights
Flavonoid agathisflavone selective induces dose‐dependent toxicity in GL‐15 and U373 human glioblastoma (GBM) cells.
Agathisflavone inhibits migration and promotes differentiation of human GBM cells.
Agathisflavone is not toxic to human mesenchymal stem cells but modifies the pattern of interaction with glioblastoma cells, resulting in resistance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We tested 210 dengue virus‒negative samples collected from febrile patients during a dengue virus type 4 outbreak in Rio de Janeiro in April 2013 and found 3 samples positive for Zika virus. Our ...findings support previously published entomological data suggesting Zika virus was introduced into Brazil during October 2012-May 2013.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rationale, aims and objectives
Literature have showed inconclusive or contradictory results regarding medication review services effectiveness in optimizing process indicators. Thus, this study aimed ...to evaluate the process indicators of a medication review service between pharmacists and physicians.
Method
This quasi‐experimental study was conducted between March 2013 and February 2014 with patients who were receiving care in a medication review service in a teaching hospital in northeastern Brazil. The main process indicators were number of pharmaceutical consultations; identification and resolution of drug‐related problems (DRP) and pharmaceutical interventions that were classified according to type and degree of acceptance. Descriptive statistics were used to report data. The statistical significance of the association between variables was evaluated using the Mantel‐Haenszel chi‐square test. The 95% confidence interval was considered, and differences were deemed statistically significant if P ≤ .05.
Results
A total of 146 patients attended the medication review service. The number of consultations per patient ranged from one to five (2.1 ± 1.1). The service identified 366 DRP, most of which were indication (67.5%). Patients who had four to five pharmaceutical consultations were 1.14 times more likely to have their DRP identified (χ2 = 33.83, P < .0001). Of the DRP identified, 183 (42.33%) were resolved. Patients who had between one and two pharmaceutical consultations were 1.22 times more likely not to have their DRP resolved compared with the group with more than three consultations (χ2 = 3.44, P < .05). Of the 173 pharmaceutical interventions made to the medical students and physicians, the majority (98.7%) was accepted.
Conclusion
The collaborative medication review service optimized the process indicators. Drug‐related problems identification and resolution required more than three pharmaceutical consultations. Most of the pharmaceutical interventions were accepted by prescribers. Thus, collaborative medication review services may be fundamental to the construction of more effective and safe health systems.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
•More than 90% (144/159) of inmates aged >60 were infected with SARS-CoV-2.•Only 2 hospitalisations occurred and no COVID-19 related deaths.•Key actions included periodic health monitoring, active ...case finding and early care.
To assess SARS-CoV-2 prevalence and health outcomes among inmates over 60 years during a COVID-19 outbreak in a major penitentiary complex in the Federal District, Brazil.
A mass test campaign was performed on May 13, 2020, using antibody-detection rapid tests for asymptomatic inmates and reverse transcriptase-polymerase chain reaction testing for those who were symptomatic. Those with negative results were retested on June 16. Inmates were interviewed to characterise background health conditions and the presence of symptoms.
A total of 159 inmates were evaluated. In the first mass testing, 79.9% (127/159) of inmates had been infected, of whom 53.5% (68/127) reported symptoms. In the second testing round, 17 new cases were identified, increasing the total to 90.6% (144/159) of inmates with a positive result. Comorbidities were present in 67.3% of inmates; 2 hospitalisations and no COVID-related deaths were recorded.
More than 90% of inmates aged >60 years were infected with SARS-CoV-2 during the outbreak. Periodic health monitoring, active case finding and early care for symptomatic patients contributed to positive post-infection outcomes. Such measures must be considered essential for the surveillance of COVID-19 in environments with limited capacity to promote social distance, such as penitentiary institutions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chagas disease, caused by the protozoan
Trypanosoma cruzi
, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop ...complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS’s DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.
Introduction
In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug‐resistant strains and HIV subtype distribution in ...the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015.
Methods
The HIV threshold survey methodology (HIV‐THS, WHO) targeting antiretroviral‐naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing.
Results
We analysed samples from 1568 antiretroviral‐naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor‐specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails.
Conclusions
To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK