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Epizootic lymphangitis (EL) is a highly prevalent and contagious infectious disease affecting horses in many parts of Ethiopia caused by Histoplasma capsulatum sensu lato ('var. farciminosum'). In this study, 12 suspected isolates of H. capsulatum sensu lato or yeasts unidentified by conventional biochemical tests isolated from Ethiopian horses with EL were characterised by internal transcribed spacer sequencing. Six of the 12 isolates were identified to be members of H. capsulatum sensu lato and the other six were Pichia kudriavzevii (synonym: Candida krusei) (n = 3), Trichosporon asahii (n = 1), Geotrichum silvicola (n = 1) and Moesziomyces aphidis (n = 1), respectively. The six H. capsulatum sensu lato isolates were further characterised by multilocus sequence analysis. Four distinct gene loci (arf [462 bases], H-anti [410 bases], ole1 [338 bases] and tub1 [272 bases]) of these six isolates as well as those of two H. capsulatum sensu lato ('var. farciminosum') reference strains (ATCC 58332 and ATCC 28798) were polymerase chain reaction (PCR)-amplified and sequenced. Phylogenetic analyses of their concatenated nucleotide sequences showed that three of the isolates and the reference strain ATCC 58332 were identical and belonged to the Eurasia clade within Latin American (LAm) A (H. suramericanum), and those of the other three isolates and the reference strain ATCC 28798 were identical and belonged to the Africa clade. At least two distinct phylogenetic clades of H. capsulatum sensu lato were circulating in Ethiopian horses with EL. Advanced molecular technologies and bioinformatics tools are crucial for the accurate identification and typing of pathogens as well as the discovery of novel microorganisms in veterinary microbiology.
Using multilocus sequence analysis with four concatenated housekeeping gene loci, at least two distinct phylogenetic clades, namely Eurasia clade and Africa clade, of Histoplasma capsulatum sensu lato were confirmed to be circulating in Ethiopian horses with epizootic lymphangitis.
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DNA Fúngico , Histoplasma , Histoplasmose , Doenças dos Cavalos , Tipagem de Sequências Multilocus , Filogenia , Animais , Histoplasma/genética , Histoplasma/classificação , Histoplasma/isolamento & purificação , Etiópia , Histoplasmose/microbiologia , Histoplasmose/veterinária , Cavalos/microbiologia , Doenças dos Cavalos/microbiologia , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Análise de Sequência de DNA , Técnicas de Tipagem MicológicaRESUMO
Electrochemical nitrate reduction (NO3RR) provides a new option to abate nitrate contamination with a low carbon footprint. Restricted by competitive hydrogen evolution, achieving satisfied nitrate reduction performance in neutral media is still a challenge, especially for the regulation of this multielectron multiproton reaction. Herein, facile element doping is adopted to tune the catalytic behavior of IrNi alloy nanobranches with an unconventional hexagonal close-packed (hcp) phase toward NO3RR. In particular, the obtained hcp IrNiCu nanobranches favor the ammonia production and suppress byproduct formation in a neutral electrolyte indicated by in situ differential electrochemical mass spectrometry, with a high Faradaic efficiency (FE) of 85.6% and a large yield rate of 1253 µg cm-2 h-1 at -0.4 and -0.6 V (vs reversible hydrogen electrode (RHE)), respectively. In contrast, the resultant hcp IrNiCo nanobranches promote the formation of nitrite, with a peak FE of 33.1% at -0.1 V (vs RHE). Furthermore, a hybrid electrolysis cell consisting of NO3RR and formaldehyde oxidation is constructed, which are both catalyzed by hcp IrNiCu nanobranches. This electrolyzer exhibits lower overpotential and holds the potential to treat polluted air and wastewater simultaneously, shedding light on green chemical production based on contaminate degradation.
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Nitratos , Oxirredução , Nitratos/química , Técnicas Eletroquímicas , Catálise , Metais/químicaRESUMO
OBJECTIVES: To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia. METHODS: We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics. RESULTS: Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-ß-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved. CONCLUSION: Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.
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Sequenciamento de Nucleotídeos em Larga Escala , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Masculino , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Sistema Respiratório/microbiologia , Adulto Jovem , Técnicas de Diagnóstico Molecular/métodosRESUMO
IMPORTANCE: We report the application of a colorimetric and fluorescent reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to facilitate mass screening for sarbecoviruses in bats. The assay was evaluated using a total of 838 oral and alimentary samples from bats and demonstrated comparable sensitivity and specificity to quantitative reverse transcription PCR (qRT-PCR), with a simple setup. The addition of SYTO9, a fluorescent nucleic acid stain, also allows for quantitative analysis. The scalability and simplicity of the assay are believed to contribute to improving preparedness for detecting emerging coronaviruses by applying it to field studies and surveillance.
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Quirópteros , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Animais , Quirópteros/virologia , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Transcrição ReversaRESUMO
Talaromyces marneffei is a thermally dimorphic fungal pathogen endemic in Southeast Asia. As inhalation of airborne conidia is believed as the major infection route, airway epithelial cells followed by pulmonary macrophages are the first cell types which the fungus encounters inside the host. In this study, we established an in vitro infection model based on human peripheral blood-derived macrophages (hPBDMs) cultured with the supplementation of autologous plasma. Using this model, we determined the transcriptomic changes of hPBDMs in response to T. marneffei infection by quantitative real-time reverse-transcription polymerase chain reaction as well as high-throughput RNA sequencing. Results showed that T. marneffei infection could activate hPBDMs to the M1-like phenotype and trigger a potent induction of chemokine and pro-inflammatory cytokine production as well as the expression of other immunoregulatory genes. In contrast to hPBDMs, there was no detectable innate cytokine response against T. marneffei in human bronchial epithelial cells (hBECs). Using a green fluorescent protein-tagged T. marneffei strain and confocal microscopy, internalization of the fungus by hBECs was confirmed. Live cell imaging further demonstrated that the infected cells exhibited normal cellular physiology, especially that the process of cell division could be observed. Moreover, T. marneffei also survived better inside hBECs than hPBDMs. Our results illustrated a potential role of hBECs to serve as reservoir cells for T. marneffei to evade immunosurveillance by phagocytes, from which the fungus reactivates when the host immunity is weakened and causes infection. Such immunoevasion and reactivation may also help explain the long incubation period observed for talaromycosis, in particular the travel-related cases. IMPORTANCE Talaromyces marneffei is an important fungal pathogen especially in Southeast Asia. To understand the innate immune response to talaromycosis, a suitable infection model is needed. Here, we established an in vitro T. marneffei infection model using human peripheral blood-derived macrophages (hPBDMs). We then examined the transcriptomic changes of hPBDMs in response to T. marneffei infection with this model. We found that contact with T. marneffei could activate hPBDMs to the M1-like phenotype and induced mRNA expressions of five cytokines and eight immunoregulatory genes. Contrary to hPBDMs, such immunoresponse was not elicited in human bronchial epithelial cells (hBECs), despite normal physiology observed in infected cells. We also found that infected hBECs did not eliminate T. marneffei as efficiently as hPBDMs. Our observation suggested that hBECs may potentially serve as reservoir cells for T. marneffei to evade immunosurveillance. When the host immunity deteriorates later, then the fungus reactivates and causes infection.
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Doença Relacionada a Viagens , Viagem , Humanos , Macrófagos/microbiologia , Imunidade Inata , Citocinas/metabolismo , Células Epiteliais/metabolismoRESUMO
Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: -0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children's sleep-wake patterns and sleep problems.
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OBJECTIVES: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). METHODS: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. RESULTS: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). CONCLUSION: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.
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Demência , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Sono REM , Dopamina , Estudos de Casos e Controles , Seguimentos , Estudos Transversais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Polissonografia/métodos , Hipotonia MuscularRESUMO
STUDY OBJECTIVES: This study aimed to examine the effect of sleep-corrected social jetlag (SJLsc) on mental health, behavioral problems, and daytime sleepiness in adolescents. METHODS: This was a cross-sectional study which included 4787 adolescents (Mean age: 14.83±1.6y, 56.0% girls) recruited from 15 secondary schools in Hong Kong. SJLsc was defined as the absolute difference between sleep-corrected midsleep on weekdays and weekends, at which the sleep debt has been considered. It was classified into three groups: low-level ("LSJLsc", <1h), mid-level ("MSJLsc", ≥1h and <2h), and high-level of SJLsc ("HSJLsc", ≥2h). Adolescents' mental health, behavioral problems and daytime sleepiness were measured by the General Health Questionnaire (GHQ-12), the Strengths and Difficulties Questionnaire (SDQ) and the Pediatric Daytime Sleepiness Scale (PDSS). Logistic regression analysis and restricted cubic spline regression (RCS) analysis were applied with consideration of confounders including age, gender, puberty and sleep problems. RESULTS: Nearly half (46.9%) of adolescents had SJLsc for at least 1 h. Greater SJLsc was associated with more behavioral difficulties (MSJLsc: OR: 1.20, p = 0.03; HSJLsc: OR: 1.34, p = 0.02) when controlling for age, sex, puberty, chronotype, insomnia, and time in bed. There was a dose-response relationship in which higher SJLsc had an increased risk of conduct problems and hyperactivity, while only high-level SJLsc was associated with a peer relationship problem. In RCS analysis, SJLsc was associated with a higher likelihood of behavioral difficulties (p = 0.03) but not poor mental health or daytime sleepiness. CONCLUSIONS: Sleep-corrected social jetlag was a unique risk factor for behavioral problems in adolescents. Our findings highlighted the need for interventions to promote healthy sleep-wake patterns in school adolescents.
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Distúrbios do Sono por Sonolência Excessiva , Comportamento Problema , Criança , Feminino , Adolescente , Humanos , Masculino , Saúde Mental , Estudos Transversais , Síndrome do Jet Lag/epidemiologia , Sono/fisiologia , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Inquéritos e Questionários , Ritmo Circadiano/fisiologiaRESUMO
Drug resistance derived from extracellular vesicles (EVs) is an increasingly important research area but has seldom been described regarding fungal pathogens. Here, we characterized EVs derived from a triazole-resistant but amphotericin B-susceptible strain of Candida auris. Nano- to microgram concentrations of C. auris EVs prepared from both broth and solid agar cultures could robustly increase the yeast's survival against both pure and clinical amphotericin B formulations in a dose-dependent manner, resulting in up to 16-fold changes of minimum inhibitory concentration. Meanwhile, this effect was not observed upon addition of these EVs to C. albicans, nor upon addition of C. albicans EVs to C. auris. No change in susceptibilities was observed upon EV treatment for fluconazole, voriconazole, micafungin, and flucytosine. Mass spectrometry indicated the presence of immunogenic-/drug resistance-implicated proteins in C. auris EVs, including alcohol dehydrogenase 1 as well as C. albicans Mp65-like and Xog1-like proteins in high quantities. Based on these observations, we propose a potential species-specific role for EVs in amphotericin B resistance in C. auris. These observations may provide critical insights into treatment of multidrug-resistant C. auris.
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Candidíase , Vesículas Extracelulares , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candida albicans , Candida auris , Candidíase/microbiologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1ß production. The IL-1ß response to T. marneffei yeasts is differently regulated in different cell types; T. marneffei yeasts alone are able to induce IL-1ß production in human PBMCs and monocytes, whereas LPS priming is essential for IL-1ß response to yeasts. We also find that Dectin-1/Syk signaling pathway mediates pro-IL-1ß production, and NLRP3-ASC-caspase-1 inflammasome is assembled to trigger the processing of pro-IL-1ß into IL-1ß. In vivo, mice deficient in NLRP3 or caspase-1 exhibit higher mortality rate and fungal load compared to wild-type mice after systemic T. marneffei infection, which correlates with the diminished recruitment of CD4 T cells into granulomas in knockout mice. Thus, our study first demonstrates that NLRP3 inflammasome contributes to host defense against T. marneffei infection.
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Inflamassomos/imunologia , Micoses/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Infecções Oportunistas/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Caspase 1/genética , Feminino , Humanos , Inflamassomos/genética , Interleucina-1beta/imunologia , Lectinas Tipo C/imunologia , Leucócitos Mononucleares/imunologia , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Micoses/microbiologia , Micoses/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Infecções Oportunistas/microbiologia , Infecções Oportunistas/patologia , Baço/microbiologia , TalaromycesRESUMO
Next-generation sequencing (NGS) technologies have recently developed beyond the research realm and started to mature into clinical applications. Here, we review the current use of NGS for laboratory diagnosis of fungal infections. Since the first reported case in 2014, >300 cases of fungal infections diagnosed by NGS were described. Pneumocystis jirovecii is the predominant fungus reported, constituting ~25% of the fungi detected. In ~12.5% of the cases, more than one fungus was detected by NGS. For P. jirovecii infections diagnosed by NGS, all 91 patients suffered from pneumonia and only 1 was HIV-positive. This is very different from the general epidemiology of P. jirovecii infections, of which HIV infection is the most important risk factor. The epidemiology of Talaromyces marneffei infection diagnosed by NGS is also different from its general epidemiology, in that only 3/11 patients were HIV-positive. The major advantage of using NGS for laboratory diagnosis is that it can pick up all pathogens, particularly when initial microbiological investigations are unfruitful. When the cost of NGS is further reduced, expertise more widely available and other obstacles overcome, NGS would be a useful tool for laboratory diagnosis of fungal infections, particularly for difficult-to-grow fungi and cases with low fungal loads.
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BACKGROUND: Eveningness and insomnia are highly comorbid and closely related to psychopathology in adolescents. We aimed to prospectively investigate the trajectories and associations of eveningness and insomnia with daytime functioning, depression and suicidal risk in adolescents. METHODS: A 3-year longitudinal study was conducted among 414 Chinese adolescents. The associations of eveningness and insomnia with daytime functioning, depression and suicidal ideation were analyzed using logistic regressions. RESULTS: The prevalence rates of eveningness were similar at baseline and follow-up (19.3% vs 22.5%; p = 0.27), while the prevalence of insomnia increased at follow-up (29.2% vs 40.8%; p < 0.001). Among those eveningness adolescents (n=80) at baseline, 46.2% remained as stable evening-type at follow-up, and among those insomnia adolescents (n=121) at baseline, 64.5% had persistent insomnia at follow-up. Logistic regressions showed that stable, incident, and resolved eveningness were associated with excessive daytime sleepiness (EDS) at follow-up, while only persistent and incident insomnia increased the risk of EDS. Persistent and incident insomnia, as well as stable eveningness were independently associated with depression at follow-up. Persistent and incident insomnia, but not eveningness, were associated with suicidal ideation. LIMITATIONS: The outcome assessments were based on self-reported questionnaires and the sample size is modest. CONCLUSIONS: Persistent eveningness and insomnia are significantly associated with greater risks of EDS and depression in adolescents, while both persistent and incident insomnia, but not eveningness, increased the risk of suicidal ideation. These findings underscore the importance of addressing sleep and circadian factors in the management of adolescent mood and daytime functioning.
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Distúrbios do Sono por Sonolência Excessiva , Distúrbios do Início e da Manutenção do Sono , Adolescente , Depressão/epidemiologia , Humanos , Estudos Longitudinais , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Ideação SuicidaRESUMO
In addition to human cases, cases of COVID-19 in captive animals and pets are increasingly reported. This raises the concern for two-way COVID-19 transmission between humans and animals. Here, we developed a SARS-CoV-2 nucleocapsid protein-based competitive enzyme-linked immunosorbent assay (cELISA) for serodiagnosis of COVID-19 which can theoretically be used in virtually all kinds of animals. We used 187 serum samples from patients with/without COVID-19, laboratory animals immunized with inactive SARS-CoV-2 virions, COVID-19-negative animals, and animals seropositive to other betacoronaviruses. A cut-off percent inhibition value of 22.345% was determined and the analytical sensitivity and specificity were found to be 1:64-1:256 and 93.9%, respectively. Evaluation on its diagnostic performance using 155 serum samples from COVID-19-negative animals and COVID-19 human patients showed a diagnostic sensitivity and specificity of 80.8% and 100%, respectively. The cELISA can be incorporated into routine blood testing of farmed/captive animals for COVID-19 surveillance.
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Pleurostoma species are wood-inhabiting fungi and emerging opportunistic pathogens causing phaeohyphomycosis. In this study, we isolated a dematiaceous fungus, HKU44T, from the subhepatic abscess pus and drain fluids of a liver transplant recipient with post-transplant biliary and hepatico-jejunostomy bypass strictures. Histology of the abscess wall biopsy showed abundant fungal hyphae. The patient survived after a second liver transplant and antifungal therapy. On SDA, HKU44T grew initially as white powdery colonies which turned beige upon maturation. Hyphae were septate and hyaline. Phialides were monophialidic and laterally located, generally closely associated to a cluster of conidia which were usually reniform. Phylogenetic analyses showed that HKU44T is most closely related to, but distinct from, Pleurostoma ootheca and Pleurostoma repens. These suggested that HKU44T is a novel Pleurostoma species, for which the name Pleurostoma hongkongense sp. nov. is proposed. Antifungal susceptibility testing showed that Pleurostoma species possessed high MICs/MECs for fluconazole, 5-flucytosine and the echinocandins; whereas they exhibited a high strain-to-strain variability to the susceptibilities to the other triazoles. As for amphotericin B, â¼65% of the Pleurostoma strains had low MICs (≤1â µg/mL). DNA sequencing should be performed to accurately identify fungi with Pleurostoma/Phialophora-like morphologies, so is antifungal susceptibility testing for patients with Pleurostoma infections.
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Antifúngicos/farmacologia , Ascomicetos/classificação , Feoifomicose/microbiologia , Análise de Sequência de DNA/métodos , Abscesso/microbiologia , Idoso , Ascomicetos/genética , Ascomicetos/isolamento & purificação , DNA Fúngico/genética , Equinocandinas/farmacologia , Fluconazol/farmacologia , Flucitosina/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , FilogeniaRESUMO
BACKGROUND: The number of patients infected with Aspergillus rose dramatically in recent years. However, studies on the clinical spectrum and antifungal susceptibilities of non-classical (non-fumigatus, non-flavus, non-niger and non-terreus) pathogenic Aspergillus species are very limited. OBJECTIVES: We examined the clinical spectrum and antifungal susceptibilities of 34 non-duplicated, non-classical Aspergillus isolates collected from Hong Kong, Shenzhen and Shanghai. METHODS: The Aspergillus isolates were identified by internal transcribed spacer, partial BenA and partial CaM sequencing and phylogenetic analyses. Susceptibility testing against eight antifungals was performed following the European Committee for Antimicrobial Susceptibility Testing's methodology. RESULTS: The 34 Aspergillus isolates were identified as 14 different rare/cryptic species of four sections (Flavi [n = 8], Nidulantes [n = 8], Nigri [n = 17] and Restricti [n = 1]). Except for one patient whose clinical history could not be retrieved, 72.7% of the remaining patients had underlying conditions predisposing them to Aspergillus infections. The most common diseases were pulmonary infections (n = 15), followed by skin/nail infections (n = 6), chronic otitis externa and/or media (n = 5), wound infections (n = 2) and mastoiditis/radionecrosis (n = 1), while three were colonisations. Five patients succumbed due to the infections during the admission, and another two died 5 years later because of chronic pulmonary aspergillosis. Antifungal susceptibility testing showed that they possessed different susceptibility profiles compared to the classical Aspergillus species. The majority of isolates characterised were sensitive or wild-type to amphotericin B. The minimum effective concentrations for all the three echinocandins were also low. CONCLUSION: Susceptibility testing should be performed for infections due to these rare/cryptic Aspergillus species to guide proper patient management.
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Antifúngicos/farmacologia , Aspergillus/classificação , Aspergillus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Pré-Escolar , China , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
BACKGROUND: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing. RESULTS: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate. CONCLUSIONS: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.
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Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Simbiose/efeitos dos fármacos , Adolescente , Adulto , Idoso , Bactérias/genética , Fungos/genética , Microbioma Gastrointestinal/genética , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: To investigate the association of insomnia and chronotype preference with daytime impairment and psychopathology in a community sample of adolescents in Hong Kong. METHODS: This was a cross-sectional study that included seven local secondary schools in Hong Kong. A total of 1667 adolescents (mean age: 14.8 ± 1.6 years old; boys: 56.5%) returned a battery of self-report questionnaires including Insomnia Severity Index (ISI) and reduced Horne and Östberg Morningness and Eveningness Questionnaire (rMEQ) for assessing insomnia symptoms and chronotype preference, respectively. A subset of adolescent samples (n = 768) were additionally assessed for suicidal ideation. Potential confounders including age, gender and sleep duration were controlled for in the analyses. RESULTS: The prevalence of insomnia symptoms and eveningness chronotype was 37% and 25.6%, respectively. Regression models indicated that insomnia and eveningness were independently associated with excessive daytime sleepiness (insomnia: adjusted OR [AdjOR] = 3.8; 95% confidence interval [C.I.] = 2.9-5.0; eveningness: AdjOR = 2.6; 95% C.I. = 1.9-3.7), and an increased risk of depression (insomnia: AdjOR = 3.5, 95% C.I. = 2.5-5.0; eveningness: AdjOR = 2.0, 95% C.I. = 1.3-3.2). The odds ratio increased to 8.7 (95% C.I. = 6.1-12.3, p < 0.001) for excessive daytime sleepiness and 4.8 (95% C.I. = 3.2-7.2, p < 0.001) for depression among adolescents with both insomnia and eveningness. Insomnia symptoms, but not eveningness, were associated with anxiety symptoms (AdjOR = 5.8; 95% C.I. = 3.6-9.4) and suicidal ideation (AdjOR = 2.1, 95% C.I. = 1.4-3.2). CONCLUSIONS: The present study provided further evidence that insomnia and eveningness uniquely contributed to poor daytime functioning and mood related outcomes, while the co-existence of these two conditions could confer a greater risk in adolescents. However, insomnia, but not eveningness, was significantly linked to suicidality after controlling for mood symptoms. Our findings highlighted the necessity of timely management of sleep and circadian issues in adolescents.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Distúrbios do Início e da Manutenção do Sono , Suicídio , Adolescente , Ritmo Circadiano , Estudos Transversais , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Hong Kong/epidemiologia , Humanos , Masculino , Sono , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.
Assuntos
Betacoronavirus/genética , Colorimetria/métodos , Infecções por Coronavirus/diagnóstico , Programas de Rastreamento/economia , Pneumonia Viral/diagnóstico , RNA Viral/análise , Betacoronavirus/isolamento & purificação , COVID-19 , Colorimetria/economia , Infecções por Coronavirus/virologia , Humanos , Limite de Detecção , Nasofaringe/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Pandemias , Pneumonia Viral/virologia , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/metabolismo , SARS-CoV-2 , Carga ViralAssuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Farmacorresistência Fúngica , Candida/genética , Candida/fisiologia , Candidíase/microbiologia , Doenças Transmissíveis Emergentes/microbiologia , HumanosRESUMO
The fungus Talaromyces marneffei was described by Professor Gabriel Segretain in 1959, originally as a member of the genus Penicillium. As early as 60 years ago, its peculiarity in exhibiting temperature-dependent morphological dimorphism, its characteristic ability to secrete diffusing red pigment during the mycelial phase and its pathogenicity have already been recognised. Six decades have passed, and our understanding on this intriguing fungus has improved. Apart from the clinical aspect, we have gained a glimpse on its taxonomy, animal or environmental source(s), mechanism of thermal dimorphism, molecular genetics, virulence as well as pathogenesis. However, we are still on our way to get out of the talaromycosis mist. A lot more collective endeavour on T. marneffei research is needed to solve the jigsaw puzzle.