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1.
Neurosurgery ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912816

RESUMO

BACKGROUND AND OBJECTIVES: The timing of microsurgical treatment (MST) for ruptured brain arteriovenous malformations (bAVM) is a contentious issue in the literature. This study aimed to investigate the impact of MST timing on outcomes in patients with ruptured bAVMs, considering MST with and without preoperative endovascular treatment (EVT). METHOD: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, a comprehensive search was conducted across multiple databases, yielding 15 studies meeting the inclusion criteria. The timing was defined as the duration from the rupture of bAVM to the MST. The patients were divided into 4 different groups based on MST timing: <48 hours, <1 week, <2 weeks, and <1 month. The primary outcome was favorable outcome defined as a modified Rankin Scale score of 0 to 2 or a Glasgow Outcome Scale score of 4 to 5 in the last clinical follow-up. Secondary outcomes included periprocedural mortality and complete excision. RESULTS: MST time >48 hours were associated with a significantly higher favorable outcome rate (odds ratio: 9.71, 95% Cl: 3.09-30.57, P < .01) and a lower mortality rate (OR: 0.15, 95% Cl: 0.02-0.88, P = .04) compared with MST timing ≤48 hours. After exclusion of patients who underwent MST with preoperative EVT, MST time >48 hours had a significantly higher rate of favorable outcome (OR: 9.39, 95% CI: 2.53-34.89, P < .01). CONCLUSION: This meta-analysis suggests that delayed surgical intervention beyond 48 hours may be associated with improved favorable outcomes in patients who underwent MST with and without preoperative EVT for ruptured bAVMs.

2.
J Stroke Cerebrovasc Dis ; 33(2): 107528, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134550

RESUMO

BACKGROUND: The influence of Alberta Stroke Program Early CT Score (ASPECTS) on outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients with low ASPECTS remains unknown. In this study, we compared the outcomes of AIS patients treated with MT for large vessel occlusion (LVO) categorized by ASPECTS value. METHODS: We conducted a retrospective analysis involving 305 patients with AIS caused by LVO, defined as the occlusion of the internal carotid artery and/or the M1 segments of the middle cerebral artery, stratified into two groups: ASPECTS 2-3 and 4-5. The primary outcome was favorable outcome defined as a 90-day modified Rankin Scale (mRS) score of 0-3. Secondary outcomes were 90-day mRS 0-2, 90-day mortality, any intracerebral hemorrhage (ICH), and symptomatic ICH (sICH). We performed multivariable logistic regression analysis to evaluate the impact of ASPECTS 2-3 vs. 4-5 on outcomes. RESULTS: Fifty-nine patients (19.3%) had ASPECTS 2-3 and 246 (80.7%) had ASPECTS 4-5. Favorable outcomes showed no significant difference between the two groups (adjusted odds ratio [aOR]= 1.13, 95% confidence interval [CI]: 0.52-2.41, p=0.80). There were also no significant differences in 90-day mRS 0-2 (aOR= 1.65, 95% CI: 0.66-3.99, p=0.30), 90-day mortality (aOR= 1.14, 95% CI: 0.58-2.20, p=0.70), any ICH (aOR= 0.54, 95% CI: 0.28-1.00, p=0.06), and sICH (aOR= 0.70, 95% CI: 0.27-1.63, p = 0.40) between the groups. CONCLUSIONS: AIS patients with LVO undergoing MT with ASPECTS 2-3 had similar outcomes compared to ASPECTS 4-5.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Estudos Retrospectivos , Alberta , Trombectomia/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/terapia , Hemorragia Cerebral/etiologia , Resultado do Tratamento , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia
3.
Heliyon ; 9(11): e22336, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034697

RESUMO

The Internet-of-Things (IoT)-based healthcare systems are comprised of a large number of networked medical devices, wearables, and sensors that collect and transmit data to improve patient care. However, the enormous number of networked devices renders these systems vulnerable to assaults. To address these challenges, researchers advocated reducing execution time, leveraging cryptographic protocols to improve security and avoid assaults, and utilizing energy-efficient algorithms to minimize energy consumption during computation. Nonetheless, these systems still struggle with long execution times, assaults, excessive energy usage, and inadequate security. We present a novel whale-based attribute encryption scheme (WbAES) that empowers the transmitter and receiver to encrypt and decrypt data using asymmetric master key encryption. The proposed WbAES employs attribute-based encryption (ABE) using whale optimization algorithm behaviour, which transforms plain data to ciphertexts and adjusts the whale fitness to generate a suitable master public and secret key, ensuring security against unauthorized access and manipulation. The proposed WbAES is evaluated using patient health record (PHR) datasets collected by IoT-based sensors, and various attack scenarios are established using Python libraries to validate the suggested framework. The simulation outcomes of the proposed system are compared to cutting-edge security algorithms and achieved finest performance in terms of reduced 11 s of execution time for 20 sensors, 0.121 mJ of energy consumption, 850 Kbps of throughput, 99.85 % of accuracy, and 0.19 ms of computational cost.

4.
J Infect Chemother ; 29(7): 713-717, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37001753

RESUMO

Candida auris is a health hazard because of its antifungal resistance and the potential to cause healthcare-associated outbreaks. To our knowledge, no previous cases of candidemia caused by C. auris have been reported in Japan. Herein, we report the first known case of clade I C. auris candidemia in a Japanese man with coronavirus disease 2019 (COVID-19) infection who was medically evacuated from the Philippines. A 71-year-old Japanese man traveled to Cebu Island in the Philippines 5 months before admission to our hospital. He contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Philippines and was admitted to the intensive care unit (ICU) in a local hospital. During his medical evacuation, we implemented precautions given his history of COVID-19 and pneumonia caused by multi-drug-resistant Acinetobacter baumannii complex. His blood culture revealed that C. auris infection was treated with antifungal agents but he did not survive. No evidence of nosocomial transmission was found among other patients in the ICU. This case study determines that accurate detection of C. auris, appropriate antifungal agent selection, precautions, and patient isolation are crucial to prevent nosocomial outbreaks, especially in patients with a history of multidrug-resistant organism (MDRO) colonization or international hospitalization. Medical professionals should recognize the risk of MDROs in international medical evacuation settings, considering the recent resumption of cross-border travel after the COVID-19 pandemic.


Assuntos
COVID-19 , Candidemia , Infecção Hospitalar , Masculino , Humanos , Idoso , Candidemia/microbiologia , Candida auris , Candida , COVID-19/epidemiologia , Pandemias , Japão , SARS-CoV-2 , Testes de Sensibilidade Microbiana , Filipinas , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Infecção Hospitalar/microbiologia
5.
J Vet Med Sci ; 85(3): 271-278, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36653148

RESUMO

Koalas are iconic mammals indigenous to Australia. These rare animals and their habitats are occasionally associated with pathogenic fungi, including species of Cryptococcus, and consequently, monitoring the mycobiota of areas inhabited by koalas is of considerable importance. In this report, we describe a novel basidiomycetous yeast isolated from a site in Kanazawa Zoo, Japan, associated with captive koalas. Swab samples were collected from koala breeding environments, from which we isolated a novel unencapsulated yeast characterized by ovoid to ellipsoidal cells (3.2-4.9 × 3.5-5 µm). These cells were observed to undergo polar budding and grow as parent bud pairs, with an optimal growth temperature of 28°C. Colonies grown on yeast extract peptone dextrose agar at 28°C have a characteristic coral pink color. On the basis of physiological, morphological, and molecular characters, the new species was placed in the genus Begerowomyces, and the name Begerowomyces aurantius JCM33898T(LSEM1333T=CBS16241T) is proposed.


Assuntos
Basidiomycota , Phascolarctidae , Filogenia , Animais , Ecossistema , Phascolarctidae/microbiologia , Basidiomycota/classificação , Basidiomycota/isolamento & purificação , Animais de Zoológico/microbiologia
6.
J Med Internet Res ; 24(12): e41042, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36542427

RESUMO

BACKGROUND: The introduction of new medical technologies such as sensors has accelerated the process of collecting patient data for relevant clinical decisions, which has led to the introduction of a new technology known as digital biomarkers. OBJECTIVE: This study aims to assess the methodological quality and quality of evidence from meta-analyses of digital biomarker-based interventions. METHODS: This study follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline for reporting systematic reviews, including original English publications of systematic reviews reporting meta-analyses of clinical outcomes (efficacy and safety endpoints) of digital biomarker-based interventions compared with alternative interventions without digital biomarkers. Imaging or other technologies that do not measure objective physiological or behavioral data were excluded from this study. A literature search of PubMed and the Cochrane Library was conducted, limited to 2019-2020. The quality of the methodology and evidence synthesis of the meta-analyses were assessed using AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews 2) and GRADE (Grading of Recommendations, Assessment, Development, and Evaluations), respectively. This study was funded by the National Research, Development and Innovation Fund of Hungary. RESULTS: A total of 25 studies with 91 reported outcomes were included in the final analysis; 1 (4%), 1 (4%), and 23 (92%) studies had high, low, and critically low methodologic quality, respectively. As many as 6 clinical outcomes (7%) had high-quality evidence and 80 outcomes (88%) had moderate-quality evidence; 5 outcomes (5%) were rated with a low level of certainty, mainly due to risk of bias (85/91, 93%), inconsistency (27/91, 30%), and imprecision (27/91, 30%). There is high-quality evidence of improvements in mortality, transplant risk, cardiac arrhythmia detection, and stroke incidence with cardiac devices, albeit with low reporting quality. High-quality reviews of pedometers reported moderate-quality evidence, including effects on physical activity and BMI. No reports with high-quality evidence and high methodological quality were found. CONCLUSIONS: Researchers in this field should consider the AMSTAR-2 criteria and GRADE to produce high-quality studies in the future. In addition, patients, clinicians, and policymakers are advised to consider the results of this study before making clinical decisions regarding digital biomarkers to be informed of the degree of certainty of the various interventions investigated in this study. The results of this study should be considered with its limitations, such as the narrow time frame. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/28204.


Assuntos
Biomarcadores , Tecnologia , Humanos , Viés , Hungria , Revisões Sistemáticas como Assunto
7.
Antimicrob Agents Chemother ; 66(6): e0005922, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35546111

RESUMO

Trichophyton indotineae causes dermatophytosis that is resistant to terbinafine and azole compounds. The aim of this study was to determine the mechanisms of resistance to itraconazole (ITC) and voriconazole (VRC) in strains of T. indotineae. Two azole-sensitive strains (ITC MIC < 0.125 µg/mL; VRC MIC < 0.06 µg/mL) and four azole-resistant strains (ITC MIC ≥ 0.5 µg/mL; VRC MIC ≥ 0.5 µg/mL) were used for the investigation. The expression of MDR genes encoding multidrug transporters of the ABC family for which orthologs have been identified in Trichophyton rubrum and those of CYP51A and CYP51B encoding the targets of azole antifungal compounds were compared between susceptible and resistant strains. TinMDR3 and TinCYP51B were overexpressed in T. indotineae resistant strains. Only small differences in susceptibility were observed between TinMDR3 disruptants and parental strains overexpressing TinMDR3. Whole-genome sequencing of resistant strains revealed the creation of a variable number of TinCYP51B tandem repeats at the specific position of their genomes in three resistant strains. Downregulation of TinCYP51B by RNA interference (RNAi) restored the susceptibility of azole-resistant strains. In contrast, overexpression of TinCYP51B cDNA conferred resistance to a susceptible strain of T. indotineae. In conclusion, the reduced sensitivity of T. indotineae strains to azoles is mainly due to the overexpression of TinCYP51B resulting from additional copies of this gene.


Assuntos
Azóis , Esterol 14-Desmetilase/genética , Trichophyton , Antifúngicos/farmacologia , Azóis/farmacologia , Farmacorresistência Fúngica/genética , Amplificação de Genes , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Trichophyton/genética , Voriconazol
8.
Mycopathologia ; 187(2-3): 225-233, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35347533

RESUMO

INTRODUCTION: Otomycosis is a superficial infection of the external ear caused by fungal pathogens. The genera Aspergillus and Candida are considered the main fungal causative agents, with the predominance of Aspergillus section Nigri. The present study aimed to evaluate the clinical symptoms of patients with otomycosis and predisposing factors and to identify fungal etiological agents using molecular approaches. We also present an overview of published papers on tympanic membrane perforation (TMP) secondary to otomycosis. MATERIALS AND METHODS: An otorhinolaryngologist collected specimens from external ear canals of patients with suspected otomycosis based on the patient's history and clinical examinations. The specimens were collected using sterile swabs. Fungal isolates were confirmed in clinical specimens by direct microscopy and culture methods. Fungal isolates were identified based on molecular approaches. RESULTS: In total, specimens from 211 patients with suspected otomycosis were examined. The presence of fungi was confirmed in about 51% of patients based on fungal elements in direct microscopy and culture-positive fungi. Aspergillus tubingensis was the most commonly isolated species (52.77%), followed by Aspergillus niger (25.92%). Otomycosis due to infection with Candida species was observed in 16% of cases. Of note, in 36.11% of cases, otomycosis was associated with TMP. CONCLUSION: A mycological examination is indispensable for a correct diagnosis in patients with otitis extern. TMP should be considered in patients with otomycosis, as it appears to be relatively common in this population.


Assuntos
Otomicose , Perfuração da Membrana Timpânica , Antifúngicos/uso terapêutico , Candida , Hospitais , Humanos , Irã (Geográfico)/epidemiologia , Otomicose/epidemiologia , Otomicose/microbiologia , Prevalência , Perfuração da Membrana Timpânica/tratamento farmacológico , Perfuração da Membrana Timpânica/epidemiologia
9.
Microbiol Immunol ; 66(6): 292-298, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35229341

RESUMO

Skin colonization by the emerging pathogen Candida auris is common in outbreaks within medical settings. Culture-based screening of patients is an effective management strategy to control the pathogen, and the newly developed CHROMagar™ Candida Plus medium is claimed to enable the presumptive identification of C. auris. Here, we evaluated the use of this medium with 63 C. auris strains comprising its four well-established clades, as well as genetically related comparators, including species from the Metschnikowia clade. The colors and halos of both confluent growth and discrete colonies of all the tested strains were compared. It was found that on CHROMagar™ Candida Plus, C. auris formed characteristic white colonies with blue-green halos that were more evident after 72 hr of incubation at 35°C than after 48 hr. However, distinguishing between closely related species such as Candida haemulonii, Candida pseudohaemulonii, and Candida duobushaemulonii required the consideration of parameters other than color, including colony size and growth ability at 35°C. In conclusion, the novel chromogenic medium CHROMagar™ Candida Plus constitutes an easy screening tool for C. auris.


Assuntos
Candida , Candidíase , Ágar , Antifúngicos , Candida auris , Candidíase/diagnóstico , Humanos
10.
Mycopathologia ; 186(6): 871-876, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34410567

RESUMO

The prevalence of fungal otitis externa, or otomycosis, has been increasing in recent decades. Fungi may act as primary pathogens in this condition, or they may occur as secondary infections after prolonged ototopical treatment with antibiotics, which alters the flora of the external auditory canal (EAC) and enables overgrowth of its fungal inhabitants. We report here a case of otomycosis by Candida parapsilosis, Malassezia obtusa, and Malassezia furfur as a secondary infection following prolonged otic ofloxacin treatment. To the best of our knowledge, although isolation of C. parapsilosis and M. furfur from the EAC is not uncommon, the recovery of M. obtusa has not yet been reported. We also conducted a literature review of the searchable data on PubMed concerning the isolation of Malassezia species from the human EAC.


Assuntos
Malassezia , Otite Externa , Otomicose , Fungos , Humanos , Ofloxacino , Otite Externa/diagnóstico , Otite Externa/tratamento farmacológico
11.
Microbiol Immunol ; 65(11): 463-471, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34251696

RESUMO

The International Space Station (ISS) is a closed facility that orbits the earth carrying not only its crew but also microorganisms. We have participated in microbiota analysis projects for the Japanese Experiment Module KIBO (ISS; operations nomenclature: Microbe-I, II, III, and IV) and were in charge of fungal screening. The interior of KIBO was sampled using swabs and microbe detection sheets (MDSs) for fungal detection. The dominant genera obtained by culture were Aspergillus and Penicillium. DNA analyses of the fungal biota using a clone library showed that KIBO was dominated by Malassezia, a fungal inhabitant of human skin. Three fungal species, Aspergillus sydowii, Penicillium palitans, and Rhodotorula mucilaginosa, which grew under microgravity in KIBO were observed under a field emission-scanning electron microscope on the ground. No novel phenotypic characteristics were noted. The results of antifungal susceptibility testing of all isolates did not differ significantly from previous reports of corresponding fungi. In Microbe-I (August 2009), MDSs were culture negative, while in the next stages the CFU of MDSs were 10 for Microbe-II (February 2011), 24 for Microbe-III (October 2012), and 151 for Microbe-IV (February 2015). These results indicated that fungi inside KIBO are increasing and expanding over time, and therefore continuous surveillance is crucial.


Assuntos
Fungos , Astronave , Aspergillus , Fungos/genética , Humanos , Japão , Penicillium , Rhodotorula
12.
Mycopathologia ; 186(2): 189-198, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33475901

RESUMO

BACKGROUND: Candida auris is an emerging pathogen associated with outbreaks in clinical settings. Isolates of the pathogen have been geographically clustered into four clades with high intra-clade clonality. Pathogenicity varies among the clades, highlighting the importance of understanding these differences. OBJECTIVES: To examine the physiological and biochemical properties of each clade of C. auris to improve our understanding of the fungus. METHODS: Optimal growth temperatures of four strains from three clades, East Asia, South Asia and South Africa, were explored. Moreover, assimilation and antifungal susceptibility properties of 22 C. auris strains from the three clades were studied. RESULTS: The optimal growth temperatures of all strains were 35-37 °C. Assimilation testing demonstrated that the commercial API ID 32 C system can be used to reliably identify C. auris based on the biochemical properties of the yeast. Notably, C. auris can be uniquely differentiated from commonly clinical fungi by its ability to assimilate raffinose and inability to utilize D-xylose, suggesting a useful simple screening tool. The antifungal susceptibility results revealed that all strains are resistant against fluconazole (minimal inhibitory concentration (MIC) 4 to > 64 µg/mL) and miconazole (MIC 8 to > 16 µg/mL), with strains from the Japanese lineage showing relatively lower MIC values (1-4 µg/mL). Conversely, itraconazole, voriconazole, amphotericin B, micafungin and caspofungin were active against most of the tested strains. On the clade level, East Asian strains generally showed lower MICs against azoles comparing to the other clades, while they displayed MICs against flucytosine higher than those of strains from South Africa and South Asia clades. CONCLUSION: Our data suggest a simple identification approach of C. auris based on its physiological and biochemical properties and highlight aspects of C. auris population from various clades.


Assuntos
Antifúngicos , Candida , Anfotericina B , Antifúngicos/uso terapêutico , Ásia , Fluconazol , Testes de Sensibilidade Microbiana
13.
Mycopathologia ; 185(4): 691-698, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32710393

RESUMO

BACKGROUND: Candida albicans is the most frequent pathogenic fungus in oral cavities. It adheres to dental tissues as part of dental plaques and contributes to caries formation. OBJECTIVES: To evaluate the effect of silver diamine fluoride (SDF) on reducing C. albicans adhesion on dentine surfaces. METHODS: Flat dentine surfaces were prepared from bovine dental disks, and samples were divided into three groups. The first and second groups were pretreated for 3 min with 299 mM or 2.99 M SDF, respectively, and the third group (control) did not undergo any SDF pretreatment. All samples were washed, inoculated with C. albicans suspension onto their dentine surface, incubated at 30 °C for 6 h, and washed again to remove any nonadherent cells. The abundance of adherent cells was investigated using colorimetric and real-time polymerase chain reaction approaches. Subsequently, the morphological changes in C. albicans by pretreatment with SDF were observed under a scanning electron microscope (SEM). RESULTS: SDF inhibited candidal growth at concentrations as low as 2.99 µM. Dentine disks pretreated with 299 mM or 2.99 M SDF displayed significantly fewer adhered cells as compared with the control group. Upon pretreatment with SDF, SEM images showed severe morphological changes in the cellular walls, in a dose-dependent manner, suggesting a fungicidal effect of SDF against the yeast. CONCLUSION: SDF should be considered for clinical applications aimed at inhibiting dental plaque caused by C. albicans, particularly in children and elderly individuals.


Assuntos
Candida albicans , Dentina/microbiologia , Compostos de Amônio Quaternário/farmacologia , Compostos de Prata/farmacologia , Animais , Candida albicans/efeitos dos fármacos , Bovinos , Fluoretos Tópicos/farmacologia
14.
Mycoses ; 63(7): 694-703, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32277529

RESUMO

BACKGROUND: Dermatophytes are a group of keratinophilic fungi of medical importance. Despite a relatively long history of molecular taxonomic studies, there is still a need for information on genetic polymorphism in wider variety of genomic loci. OBJECTIVES: Our goal was to study partial DNA topoisomerase 2 gene (TOP2) polymorphism in dermatophytes. METHODS: We performed DNA sequencing of TOP2 in 26 dermatophyte species along with ribosomal internal transcribed spacer (ITS) sequencing. RESULTS: The number of polymorphic sites in TOP2 data set was similar to that one in ITS data set. Nannizzia species formed paraphyletic group in TOP2 tree. Trichophyton simii was paraphyletic in concatenated TOP2-ITS tree, one of its two clades contained solely Iranian isolates. CONCLUSIONS: Our results revealed several unresolved problems in the taxonomy of dermatophytes, including probable polyphyly of the genus Nannizzia and the species T simii.


Assuntos
Arthrodermataceae/enzimologia , Arthrodermataceae/genética , DNA Topoisomerases Tipo II/genética , DNA Fúngico/genética , Polimorfismo Genético , Arthrodermataceae/classificação , DNA Espaçador Ribossômico/genética , Irã (Geográfico) , Filogenia , Análise de Sequência de DNA
15.
Artigo em Inglês | MEDLINE | ID: mdl-31501141

RESUMO

The mechanisms of terbinafine resistance in a set of clinical isolates of Trichophyton rubrum have been studied recently. Of these isolates, TIMM20092 also showed reduced sensitivity to azoles. The azole resistance of TIMM20092 could be inhibited by milbemycin oxime, prompting us to examine the potential of T. rubrum to develop resistance through multidrug efflux transporters. The introduction of a T. rubrum cDNA library into Saccharomyces cerevisiae allowed the isolation of one transporter of the major facilitator superfamily (MFS) conferring resistance to azoles (TruMFS1). To identify more azole efflux pumps among 39 ABC and 170 MFS transporters present within the T. rubrum genome, we performed a BLASTp analysis of Aspergillus fumigatus, Candida albicans, and Candida glabrata on transporters that were previously shown to confer azole resistance. The identified candidates were further tested by heterologous gene expression in S. cerevisiae Four ABC transporters (TruMDR1, TruMDR2, TruMDR3, and TruMDR5) and a second MFS transporter (TruMFS2) proved to be able to operate as azole efflux pumps. Milbemycin oxime inhibited only TruMDR3. Expression analysis showed that both TruMDR3 and TruMDR2 were significantly upregulated in TIMM20092. TruMDR3 transports voriconazole (VRC) and itraconazole (ITC), while TruMDR2 transports only ITC. Disruption of TruMDR3 in TIMM20092 abolished its resistance to VRC and reduced its resistance to ITC. Our study highlights TruMDR3, a newly identified transporter of the ABC family in T. rubrum, which can confer azole resistance if overexpressed. Finally, inhibition of TruMDR3 by milbemycin suggests that milbemycin analogs could be interesting compounds to treat dermatophyte infections in cases of azole resistance.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Antifúngicos/farmacologia , Azóis/farmacologia , Trichophyton/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Antifúngicos/metabolismo , Azóis/metabolismo , Farmacorresistência Fúngica , Humanos , Macrolídeos/metabolismo , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Terbinafina/metabolismo , Terbinafina/farmacologia , Tinha/tratamento farmacológico , Tinha/microbiologia , Trichophyton/metabolismo
16.
Med Mycol ; 57(6): 703-709, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649423

RESUMO

Chronic pulmonary aspergillosis (CPA) is a common subtype of pulmonary aspergillosis and a life-threatening disease. However, its diagnosis remains difficult due to the lack of specific clinical features and radiologic findings, as well as the difficulty of isolating Aspergillus spp. We developed a novel species-specific detection method of medically important aspergilli using a loop-mediated isothermal amplification (LAMP) for CPA. Specific LAMP primer sets for Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, and Aspergillus nidulans were designed. The use of the LAMP assay was validated using respiratory specimens (CPA cases, n = 21; nonaspergillosis cases, n = 23). A total of 15 cases were positive in the CPA group (A. fumigatus, n = 5; A. flavus, n = 1; A. niger, n = 1; A. terreus, n = 7; A. nidulans, n = 1), but only three in the non-CPA group (A. niger, n = 2; A. terreus n = 1). The sensitivity and specificity of the diagnosis of CPA by the LAMP system were 71.4% and 87.0%, respectively. In conclusion, we developed a species-specific detection approach for five medically important aspergilli using the LAMP method. The system showed high sensitivity and specificity for diagnosis of CPA.


Assuntos
Aspergillus/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergillus/classificação , Doença Crônica , Primers do DNA/genética , Feminino , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Especificidade da Espécie
17.
Respiration ; 97(1): 84-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30343287

RESUMO

BACKGROUND: Filamentous basidiomycetes (f-BMs) are involved in some unexplained chronic cough (UCC) cases that can be improved by the administration of antifungal agents. The disease concept was termed fungus-associated chronic cough (FACC). The current diagnostic criteria warrant environmental fungi isolation from respiratory specimens, which is hardly conceivable for such fungi. OBJECTIVES: This study aimed to detect the f-BMs Bjerkandera adusta, the most common pathogen in FACC, from respiratory specimens of patients with UCC using real-time polymerase chain reaction (PCR). It also evaluated the applicability of the PCR system to detect antifungal agent responders among patients with unexplained cough. METHODS: The PCR system specific to B. adusta was developed and its utility was evaluated using sputum samples from 23 patients with chronic cough. RESULTS: B. adusta was detected in 10 out of 14 patients with UCC (71.4%), in contrast to only 2 out of 9 patients with non-UCC (22.2%; p < 0.05 with the Fisher's exact test). The copy number of the samples correlated with the therapeutic impact score for cough symptoms following the oral administration of itraconazole. CONCLUSION: Development of the real-time PCR system enabled us to demonstrate that many patients with UCC might be influenced by B. adusta, a fact evidenced by the improvement of symptoms with itraconazole administration in most PCR-positive patients. This method would help in detecting itraconazole responders among patients with UCC when the isolation of f-BMs is not achievable.


Assuntos
Coriolaceae/genética , Tosse/diagnóstico , DNA Fúngico/análise , Itraconazol/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Escarro/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Doença Crônica , Coriolaceae/isolamento & purificação , Tosse/tratamento farmacológico , Tosse/microbiologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
18.
Sci Rep ; 8(1): 15127, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30310114

RESUMO

Next-generation technologies have prompted efforts towards generating a large repertoire of whole-genome sequences. The dermatophyte Arthroderma vanbreuseghemii has been considered as a good model in which to conduct molecular biological studies on this fungal group. Despite the considerable repertoire of molecular tools developed for this fungus, the lack of genomic data has represented a major limitation, preventing effective implementation of those tools. Herein, the authors report the first draft whole-genome sequence of this dermatophytic species. The size of the draft genome was 23 Mb, exhibiting a GC content of 48.1%. Given the significance of secreted proteases in tissue invasion, a comparative analysis of genes encoding extracellular proteases was performed between A. vanbreuseghemii and other dermatophytes. Furthermore, genes that might be involved in DNA repair also were compared among dermatophytes. Moreover, the complete mitochondrial genome of A. vanbreuseghemii was obtained and shown to consist of 24,287 bp with a GC content of 24%. In conclusion, the availability of genomic data for A. vanbreuseghemii is expected to facilitate the implementation of the molecular tools established for this fungus, enhancing our understanding of the biology of dermatophytes.


Assuntos
Arthrodermataceae/genética , Genoma Fúngico , Genômica , Arthrodermataceae/classificação , Composição de Bases , Reparo do DNA , Evolução Molecular , Tamanho do Genoma , Genômica/métodos , Filogenia , Análise de Sequência de DNA , Sequenciamento Completo do Genoma
20.
Saudi J Kidney Dis Transpl ; 29(1): 107-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29456215

RESUMO

Conventional hemodialysis (HD) is the most common treatment modality used for renal replacement therapy. The concept of HD is based on the diffusion of solutes across a semipermeable membrane. Hemofiltration (HF) is based on convective transport of solutes; hemodiafiltration (HDF) is based on combined convective and diffusive therapies. Data about survival benefit of on-line HDF (OL-HDF) over high-flux HD (HF-HD) is conflicting. We conducted this study to investigate if there is a survival difference between the two treatment modalities. This study is a retrospective, single-center study in which 78 patients were screened; 18 were excluded and 60 patients were analyzed. The study patients were aged 47.5 ± 20.7 years, 33 patients (55%) were on HF-HD, and 27 patients (45%) were on OL-HDF. A total of 24 patients (40%) of both groups were diabetic and, the mean duration on dialysis was 43.5 ±21.3 months in the HF-HD group and 41.2 ± 22.0 months in the OL-HDF group. The mean substitution volume for OL-HDF was 22.3 ± 2.5 L. Survival was 73% [95%, confidence interval (CI) 60-84] in the HF-HD group and 65% (95%, CI 54-75) in the OL-HDF group by the end of the study period. The unadjusted hazard ratio (HR) with 95% CI comparing HF-HD to high-volume postdilution OL-HDF was 0.78 (0.10-5.6; P = 0.810). Kaplan-Meier analysis for patient survival over five years showed no significant difference between the two modalities. Prospective controlled trials with a larger number of patients will be needed to assess the long-term clinical outcome of postdilution OL-HDF over HF-HD.


Assuntos
Hemodiafiltração , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Idoso , Feminino , Hemodiafiltração/efeitos adversos , Hemodiafiltração/mortalidade , Humanos , Rim/fisiopatologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento
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