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Leaf mould, caused by Fulvia fulva, is a devastating disease of tomato plants. In many commercial tomato cultivars, resistance to this disease is governed by the Cf-9 locus, which encodes five paralogous receptor-like proteins. Two of these proteins confer resistance: Cf-9C recognises the previously identified F. fulva effector Avr9 and provides resistance during all plant growth stages, while Cf-9B recognises the yet-unidentified F. fulva effector Avr9B and provides mature plant resistance only. In recent years, F. fulva strains have emerged that can overcome the Cf-9 locus, with Cf-9C circumvented through Avr9 deletion. To understand how Cf-9B is circumvented, we set out to identify Avr9B. Comparative genomics, transient expression assays and gene complementation experiments were used to identify Avr9B, while gene sequencing was used to assess Avr9B allelic variation across a world-wide strain collection. A strict correlation between Avr9 deletion and resistance-breaking mutations in Avr9B was observed in strains recently collected from Cf-9 cultivars, whereas Avr9 deletion but no mutations in Avr9B were observed in older strains. This research showcases how F. fulva has evolved to sequentially break down the Cf-9 locus and stresses the urgent need for commercial tomato cultivars that carry novel, stacked resistance genes active against this pathogen.
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Resistência à Doença , Doenças das Plantas , Folhas de Planta , Solanum lycopersicum , Solanum lycopersicum/microbiologia , Solanum lycopersicum/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Resistência à Doença/genética , Folhas de Planta/microbiologia , Folhas de Planta/genética , Loci Gênicos , Alelos , Basidiomycota/fisiologia , Mutação/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: Onychomycoses are difficult-to-treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. OBJECTIVES: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. METHODS: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96-well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. RESULTS: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. CONCLUSIONS: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non-dermatophyte fungus such as S. brevicaulis.
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Morfolinas , Onicomicose , Humanos , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Ciclopirox/farmacologia , Ciclopirox/uso terapêutico , Antifúngicos/uso terapêutico , NaftalenosRESUMO
BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.
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COVID-19 , Coinfecção , Mucormicose , Humanos , COVID-19/complicações , COVID-19/mortalidade , Mucormicose/mortalidade , Mucormicose/epidemiologia , Mucormicose/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prevalência , Coinfecção/mortalidade , Coinfecção/epidemiologia , Coinfecção/microbiologia , Índia/epidemiologia , Adulto , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/mortalidade , Aspergilose Pulmonar/epidemiologia , SARS-CoV-2 , Idoso , Estudos de Casos e Controles , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVES: The mechanisms underlying COVID-19-associated pulmonary mucormycosis (CAPM) remain unclear. We use a transcriptomic analysis of the innate immune cells to investigate the host immune and metabolic response pathways in patients with CAPM. PATIENTS AND METHODS: We enrolled subjects with CAPM (n = 5), pulmonary mucormycosis (PM) without COVID-19 (n = 5), COVID-19 (without mucormycosis, n = 5), healthy controls (n = 5) without comorbid illness and negative for SARS-CoV-2. Peripheral blood samples from cases were collected before initiating antifungal therapy, and neutrophils and monocytes were isolated. RNA sequencing was performed using Illumina HiSeqX from monocytes and neutrophils. Raw reads were aligned with HISAT-2 pipeline and DESeq2 was used for differential gene expression. Gene ontology (GO) and metabolic pathway analysis were performed using Shiny GO application and R packages (ggplot2, Pathview). RESULTS: The derangement of core immune and metabolic responses in CAPM patients was noted. Pattern recognition receptors, dectin-2, MCL, FcRγ receptors and CLEC-2, were upregulated, but signalling pathways such as JAK-STAT, IL-17 and CARD-9 were downregulated; mTOR and MAP-kinase signalling were elevated in monocytes from CAPM patients. The complement receptors, NETosis, and pro-inflammatory responses, such as S100A8/A9, lipocalin and MMP9, were elevated. The major metabolic pathways of glucose metabolism-glycolysis/gluconeogenesis, pentose phosphate pathway, HIF signalling and iron metabolism-ferroptosis were also upregulated in CAPM. CONCLUSIONS: We identified significant alterations in the metabolic pathways possibly leading to cellular iron overload and a hyperglycaemic state. Immune responses revealed altered recognition, signalling, effector functions and a pro-inflammatory state in monocytes and neutrophils from CAPM patients.
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COVID-19 , Mucormicose , Humanos , Mucormicose/microbiologia , SARS-CoV-2 , Perfilação da Expressão Gênica , Imunidade InataRESUMO
Phaseolus vulgaris Linn. is a widely cultivated vegetable throughout the world. From spring 2019 to 2022, green mould symptoms were observed on leaves of P. vulgaris in the greenhouse in Liaoning, China, with disease incidence of 8-75% (plants) and 6-23% (leaves). Symptoms appeared as chlorotic lesions covered with dark green mould. The infections started at the apex or margin of the leaves and then spread inward with a characteristic "V" shape. Lesions exhibited curly morphology. 15 leaf samples with typical symptoms were collected from 5 different greenhouses. A total of 75 (5 replicates of each sample) leaf tissues (0.5 cm × 0.5 cm) were selected from the boundary between diseased and healthy parts. These samples were surface sterilized in 0.5% NaClO formin, rinsed 3 times in sterile distilled water and subsequently incubated at 28â on potato dextrose agar (PDA) supplemented with streptomycin (50 µg/ml). Numerous morphologically uniform colonies had been purified, with no other fungi observed. Afterwards, the strains were subcultured on malt extract agar (MEA). Colonies on MEA reached 70 to 80 mm diam after 14 days, smoke-grey to pale olivaceous-grey, woolly, sometimes radially wrinkled. The mycelia were pale olivaceous-grey, with hyphae measuring 1-5 µm wide (n = 20). The conidiophores were solitary or in groups of 2 to 5, and measured 50-280(-350) × 2.5-4 µm (n = 20), with 2-7 septa. The conidiogenous cells exhibited a cylindrical-oblong morphology and measured 10-44 × 5 µm (n = 20), with 0-2 septa, and the loci frequently thickened. The conidia were catenate in densely branched chains, ellipsoid to obovoid, smooth, and measured 2.5-5 × 2-3 µm (n = 50), with 0-4 septa. The morphological characteristics were similar to Cladosporium tenuissimum (Zhang 2003). The representative isolate KZ-19 was selected for molecular identification. The rDNA-ITS, translation elongation factor 1-α and actin genes were amplified, sequenced, and the resulting sequence data were submitted to GenBank (ITS: OQ931048; EF-1α: OQ954495; ACT: OQ954496). The BLAST results exhibited a 99 to 100% similarity with the sequences of C. tenuissimum type strain CBS 125995(ITS: HM148197; EF-1α: HM148442; ACT: HM148687). Furthermore, a multi-locus phylogenetic tree was constructed using the PhyloSuite (v 1. 2. 2) software, which revealed that the strains were most closely related to C. tenuissimum (Zhang et al. 2020). Based on both morphological and molecular characteristics, KZ-19 was finally identified as C. tenuissimum (Bensch 2012). Pathogenicity testing was performed on healthy 1-month-old P. vulgaris plants by inoculating the spore suspension (1×106 conidia/ml) of KZ-19 onto leaf surfaces, while control plants were simulated inoculated with sterile water, and five pots were used for each treatment. The test was performed under field conditions of 16-28°C (temperature) and 24-56% (relative humidity). Chlorotic lesions became evident within 2 days of inoculation, followed by the appearance of green mold on leaves after 7 days. No symptoms were observed in the control group. To fulfill Koch's postulates, the pathogen was re-isolated from three inoculated leaves. The morphological identification of re-isolated pathogens was similar to that of originally isolated pathogens. No infection was observed in non-inoculated control. To the best of our knowledge, this is the first report of C. tenuissimum causing green mould on P. vulgaris. As a ubiquitous saprobic hyphomycete, C. tenuissimum has been implicated in leaf mold in Punica granatum and Trifolium repens, larch bud blight, and strawberry blossom blight in previous years (He et al. 1987; Zhang et al. 2003; Zheng et al. 2010; Nam et al. 2015), presenting a potential threat to numerous crops. Therefore, an investigation of its distribution and pathogenic potential is essential in addition to the development of effective disease management strategies.
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Since its inception in 2002, the EUCAST Antifungal Susceptibility Testing Subcommittee (AFST) has developed and refined susceptibility testing methods for yeast, moulds and dermatophytes, and established epidemiological cut-off values and breakpoints for antifungals. For yeast, three challenges have been addressed. Interpretation of trailing growth in fluconazole susceptibility testing, which has been proven without impact on efficacy if below the 50% endpoint. Variability in rezafungin MIC testing due to laboratory conditions, which has been solved by the addition of Tween 20 to the growth medium in E.Def 7.4. And third, interpretation of MICs for rare yeast with no breakpoints, where recommendations have been established for MIC-based clinical advice. For moulds, refinements include the validation of spectrophotometer reading for A. fumigatus to facilitate objective MIC determination, and for dermatophytes the establishment of a microdilution method with automated reading and a selective medium to minimise the risk of contaminations. Recent initiatives involve development and validation of agar-based screening assays for detection of potential azole and echinocandin resistance in A. fumigatus and Aspergillus species, respectively, and of terbinafine resistance in Trichophyton species. Moreover, the development of a EUCAST guidance document for molecular resistance testing represents an advancement, particularly for identifying target gene alterations associated with resistance. In summary, EUCAST AFST continues to play a pivotal role in standardizing AFST and facilitating accurate interpretation of susceptibility data for clinical decision-making. Adoption of EUCAST breakpoints for commercial test methods, however, requires thorough validation to ensure concordance with EUCAST reference testing species-specific MIC distributions.
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Antifúngicos , Fungos , Testes de Sensibilidade Microbiana , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Antifúngicos/farmacologia , Humanos , Fungos/efeitos dos fármacos , Farmacorresistência FúngicaRESUMO
Tetraclinis articulata essential oil proved to be effective in controlling tomato grey mould, so we would investigate its effect on some tomato defense mechanisms. The pretreatment of Botrytis cinerea infected tomato plants with TAEO emulsion enhanced the activity of antioxidant enzymes activity SOD, CAT, APX, and GPX, and total polyphenols content and it decreased IC50 of free radical-scavenging activity and H2O2 content. Results showed amelioration in antioxidant status in TAEO emulsion treated and B. cinerea infected plants indicating that treatment decreased infection in tomato plants. The qRT-PCR analysis of defense genes expression Chitinase SlChi, transcription factors SlWRKY and SlAP2/ERF, Lipoxygenase SlLOX, and Thioredoxin SlTRX showed that they were up-regulated as early as 12 hpi sustained with a second increase at 48 hpi in TAEO emulsion pretreated and infected plants. These results suggest the potential use of TAEO emulsion as natural product to induce tomato antioxidant status and activate defense genes.
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Fungicidas Industriais , Óleos Voláteis , Solanum lycopersicum , Fungicidas Industriais/toxicidade , Óleos Voláteis/farmacologia , Peróxido de Hidrogênio , Emulsões , Antioxidantes/farmacologia , Fungos , Doenças das Plantas/prevenção & controle , Doenças das Plantas/genéticaRESUMO
The guidelines published by the German Environment Agency in 2017 on the "Prevention, detection and remediation of mould in buildings" were clarified in two points. First, Chapter 6.1 "Utilisation classes" now includes the definition of an "indoor space" in relation to human use. Second, the previous utilisation class IV - which concerned cavities and building components - was removed. These changes avoid misinterpretations and emphasise the hygiene-preventive approach of the guideline. An English full-text version of this article is available at SpringerLink as Supplementary Information.
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Fungos , Higiene , Humanos , AlemanhaRESUMO
The network-shaped body plan distinguishes the unicellular slime mouldPhysarum polycephalumin body architecture from other unicellular organisms. Yet, network-shaped body plans dominate branches of multi-cellular life such as in fungi. What survival advantage does a network structure provide when facing a dynamic environment with adverse conditions? Here, we probe how network topology impactsP. polycephalum's avoidance response to an adverse blue light. We stimulate either an elongated, I-shaped amoeboid or a Y-shaped networked specimen and subsequently quantify the evacuation process of the light-exposed body part. The result shows that Y-shaped specimen complete the avoidance retraction in a comparable time frame, even slightly faster than I-shaped organisms, yet, at a lower almost negligible increase in migration velocity. Contraction amplitude driving mass motion is further only locally increased in Y-shaped specimen compared to I-shaped-providing further evidence that Y-shaped's avoidance reaction is energetically more efficient than in I-shaped amoeboid organisms. The difference in the retraction behaviour suggests that the complexity of network topology provides a key advantage when encountering adverse environments. Our findings could lead to a better understanding of the transition from unicellular to multicellularity.
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Physarum polycephalum , Physarum polycephalum/fisiologia , Modelos BiológicosRESUMO
The mannose-binding lectin gene MANNOSE-BINDING LECTIN 1 (MBL1) is a member of the G-type lectin family and is involved in defense in strawberry (Fragaria × ananassa). Genome-wide identification of the G-type lectin family was carried out in woodland strawberry, F. vesca, and 133 G-lectin genes were found. Their expression profiles were retrieved from available databases and indicated that many are actively expressed during plant development or interaction with pathogens. We selected MBL1 for further investigation and generated stable transgenic FaMBL1-overexpressing plants of F. ×ananassa to examine the role of this gene in defense. Plants were selected and evaluated for their contents of disease-related phytohormones and their reaction to biotic stresses, and this revealed that jasmonic acid decreased in the overexpressing lines compared with the wild-type (WT). Petioles of the overexpressing lines inoculated with Colletotrichum fioriniae had lower disease incidence than the WT, and leaves of these lines challenged by Botrytis cinerea showed significantly smaller lesion diameters than the WT and higher expression of CLASS II CHITINASE 2-1. Our results indicate that FaMBL1 plays important roles in strawberry response to fungal diseases caused by C. fioriniae and B. cinerea.
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Fragaria , Lectinas , Lectinas/genética , Lectinas/metabolismo , Fragaria/genética , Fragaria/metabolismo , Genes de Plantas , Família , Plantas Geneticamente Modificadas/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologiaRESUMO
The study of comparative cognition bloomed in the 1970s and 1980s with a focus on representations in the heads of animals that undergird what animals can achieve. Even in action-packed domains such as navigation and spatial cognition, a focus on representations prevailed. In the 1990s, I suggested a conception of navigation in terms of navigational servomechanisms. A servomechanism can be said to aim for a goal, with deviations from the goal-directed path registering as an error. The error drives action to reduce the error in a negative-feedback loop. This loop, with the action reducing the very signal that drove action in the first place, is key to defining a servomechanism. Even though actions are crucial components of servomechanisms, my focus was on the representational component that encodes signals and evaluates errors. Recently, I modified and amplified this view in claiming that, in navigation, servomechanisms operate by modulating the performance of oscillators, endogenous units that produce periodic action. The pattern is found from bacteria travelling micrometres to sea turtles travelling thousands of kilometres. This pattern of servomechanisms working with oscillators is found in other realms of cognition and of life. I think that oscillators provide an effective way to organise an organism's own activities while servomechanisms provide an effective means to adjust to the organism's environment, including that of its own body.
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Navegação Espacial , Animais , CogniçãoRESUMO
Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection.
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Feoifomicose Cerebral , Micoses , Feoifomicose , Animais , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feoifomicose/microbiologia , Feoifomicose/veterinária , Feoifomicose Cerebral/diagnóstico , Feoifomicose Cerebral/tratamento farmacológico , Feoifomicose Cerebral/veterinária , Micoses/tratamento farmacológico , Micoses/veterinária , Fatores de Risco , Antifúngicos/uso terapêuticoRESUMO
Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against Aspergillus spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity. Contrary to other broad-spectrum azoles, such as voriconazole and posaconazole, isavuconazole appears to show significant smaller drug-drug interactions with anticalcineurin drugs. We have performed an extensive literature review of the experience with the use of isavuconazole in SOT, which included the SOTIS and the ISASOT studies, and published case reports. More than 140 SOT recipients treated with isavuconazole for IMD were included. Most patients were lung and kidney recipients treated for an Aspergillus infection. Isavuconazole was well tolerated (less than 10% of patients required treatment discontinuation). The clinical responses appeared comparable to that found in other high-risk patient populations. Drug-drug interactions with immunosuppressive agents were manageable after the reduction of tacrolimus and the adjustment of mTOR inhibitors at the beginning of treatment. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IMD in SOT. More clinical studies are warranted.
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Aspergilose , Transplante de Órgãos , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Aspergilose/tratamento farmacológico , Aspergilose/induzido quimicamente , Nitrilas/uso terapêutico , Nitrilas/farmacologia , Transplante de Órgãos/efeitos adversos , Transplantados , Voriconazol/uso terapêuticoRESUMO
BACKGROUND: Few studies exist on environmental risk factors for respiratory infections in Thai school children. AIM: To study associations between home and outdoor environment and respiratory infections among school children in Northern Thailand in dry and wet season. METHODS: A repeated questionnaire survey among the children (N = 1159). Data on ambient temperature and relative air humidity (RH) and PM10 and ozone was collected from nearby monitoring stations. We used logistic regression to calculate odds ratios (OR). RESULTS: 14.1% had current respiratory infections (last 7 days), 32.1% had any respiratory infection last 3 months, and 26.1% had any respiratory infection last 12 months with antibiotic treatment. Students with diagnosed allergy (7.7%) and diagnosed asthma (4.7%) had more often respiratory infections (ORs 1.40-5.40; p < 0.05). Current respiratory infections were more common in dry (18.1%) than in wet season (10.4%) (p < 0.001) and was associated with indoor mould (OR 2.16; p = 0.024) and outdoor RH (OR 1.34 per 10% RH; p = 0.004.) in the total material. In wet season, mould (OR 2.32; p = 0.016), window pane condensation (OR 1.79; p = 0.050), water leakage (OR 1.82; p = 0.018), environmental tobacco smoke (ETS) (OR 2.34; p = 0.003) and outdoor RH (OR 2.70 per 10% RH; p = 0.01) were risk factors for current respiratory infections. In dry season, mould (OR 2.64; p = 0.004) and outdoor RH (OR 1.34 per 10% RH; p = 0.046) were associated with current respiratory infections. Irrespectively of season, biomass burning inside or outside the home was a risk factor for respiratory infections (ORs 1.32-2.34; p < 0.05). Living in a wooden house decreased the risk of respiratory infections (OR 0.56: p = 0.006). CONCLUSIONS: Dry season, high outdoor RH, household dampness, indoor mould and ETS can increase childhood respiratory infections. Living in a traditional wooden house can reduce respiratory infections, possibly due to better natural ventilation. Smoke from biomass burning can increase childhood respiratory infections in northern Thailand.
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Poluição do Ar em Ambientes Fechados , Infecções Respiratórias , Poluição por Fumaça de Tabaco , Criança , Humanos , Poluição do Ar em Ambientes Fechados/análise , Umidade , Biomassa , Tailândia/epidemiologia , Infecções Respiratórias/epidemiologia , Estudantes , FungosRESUMO
BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.
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COVID-19 , Mucormicose , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Mucormicose/tratamento farmacológicoRESUMO
BACKGROUND: Organising pneumonia (OP) is reported in patients with haematologic malignancy suspected of having invasive mould disease, yet little is known about this relationship. OBJECTIVE: To investigate molecular evidence of invasive mould pneumonia in paraffin-embedded lung tissues from histologically diagnosed OP patients with suspected invasive mould pneumonia. PATIENTS/METHODS: Patients with haematologic malignancy suspected to have invasive pulmonary mould disease who underwent lung biopsy at a tertiary hospital, Seoul, South Korea, between 2008 and 2020, were retrospectively reviewed. To find molecular evidence of fungal infection, PCR assay was used to detect Aspergillus- and Mucorales-specific DNA within OP lung tissue sections. RESULTS: Forty-seven patients with suspected invasive mould pneumonia underwent lung biopsy and 15 (32%) were histologically diagnosed as OP without any evidence of fungal hyphae. Of these 15 patients, 3 (20%) received allogenic haematopoietic stem cell transplantation prior to developing OP. Before biopsy, 2 and 13 patients had probably and possible invasive mould disease, respectively. The median antifungal treatment length was 81 [8-114] days, and the median steroid treatment dosage was 0.35 mg/kg/day for 36 days (methylprednisolone equivalent doses), respectively. After biopsy, three patients with possible invasive mould infection revealed probable invasive pulmonary aspergillosis. From the 15 paraffin-embedded lung tissues, 6 (40%) exhibited positive PCR assay results for detecting Aspergillus- and Mucorales-specific DNA. CONCLUSIONS: More than one third of OP cases in patients with suspected invasive mould pneumonia exhibited molecular evidence of invasive mould infection by fungus-specific PCR in lung tissues, likely associated with concurrent or prior fungal infection.
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Neoplasias Hematológicas , Mucorales , Micoses , Pneumonia em Organização , Pneumonia , Humanos , Estudos Retrospectivos , Micoses/tratamento farmacológico , Aspergillus/genética , Neoplasias Hematológicas/complicaçõesRESUMO
Unmanned aerial vehicle (UAV) networks offer a wide range of applications in an overload situation, broadcasting and advertising, public safety, disaster management, etc. Providing robust communication services to mobile users (MUs) is a challenging task because of the dynamic characteristics of MUs. Resource allocation, including subchannels, transmit power, and serving users, is a critical transmission problem; further, it is also crucial to improve the coverage and energy efficacy of UAV-assisted transmission networks. This paper presents an Enhanced Slime Mould Optimization with Deep-Learning-based Resource Allocation Approach (ESMOML-RAA) in UAV-enabled wireless networks. The presented ESMOML-RAA technique aims to efficiently accomplish computationally and energy-effective decisions. In addition, the ESMOML-RAA technique considers a UAV as a learning agent with the formation of a resource assignment decision as an action and designs a reward function with the intention of the minimization of the weighted resource consumption. For resource allocation, the presented ESMOML-RAA technique employs a highly parallelized long short-term memory (HP-LSTM) model with an ESMO algorithm as a hyperparameter optimizer. Using the ESMO algorithm helps properly tune the hyperparameters related to the HP-LSTM model. The performance validation of the ESMOML-RAA technique is tested using a series of simulations. This comparison study reports the enhanced performance of the ESMOML-RAA technique over other ML models.
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Injection moulding (IM) is an important industrial process, known to be the most used plastic formation technique. Demand for faster cycle times and higher product customisation is driving interest in additive manufacturing (AM) as a new method for mould tool manufacturing. The use of AM offers advantages such as greater design flexibility and conformal cooling of components to reduce cycle times and increase product precision. However, shortcomings of metal additive manufacturing, such as porosity and residual stresses, introduce uncertainties about the reliability and longevity of AM tooling. The injection moulding process relies on high volumes of produced parts and a minimal amount of tool failures. This paper reviews the demands for tool condition monitoring systems for AM-manufactured mould tools; although tool failures in conventionally manufactured tooling are rare, they do occur, usually due to cracking, deflection, and channel blockages. However, due to the limitations of the AM process, metal 3D-printed mould tools are susceptible to failures due to cracking, delamination and deformation. Due to their success in other fields, acoustic emission, accelerometers and ultrasound sensors offer the greatest potential in mould tool condition monitoring. Due to the noisy machine environment, sophisticated signal processing and decision-making algorithms are required to prevent false alarms or the missing of warning signals. This review outlines the state of the art in signal decomposition and both data- and model-based approaches to determination of the current state of the tool, and how these can be employed for IM tool condition monitoring. The development of such a system would help to ensure greater industrial uptake of additive manufacturing of injection mould tooling, by increasing confidence in the technology, further improving the efficiency and productivity of the sector.
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When overmoulding optoelectronic devices with optical elements, precise alignment of the overmoulded part and the mould is of great importance. However, mould-integrated positioning sensors and actuators are not yet available as standard components. As a solution, we present a mould-integrated optical coherence tomography (OCT) device that is combined with a piezo-driven mechatronic actuator, which is capable of performing the necessary displacement correction. Because of the complex geometric structure optoelectronic devices may have, a 3D imaging method was preferable, so OCT was chosen. It is shown that the overall concept leads to sufficient alignment accuracy and, apart from compensating for the in-plane position error, provides valuable additional information about the sample both before and after the injection process. The increased alignment accuracy leads to better energy efficiency, improved overall performance and less scrap parts, and thus even a zero-waste production process might be feasible.
RESUMO
The aim of the study was to analyse changes in the physicochemical, rheological, and textural properties occurring during the storage of industrially produced smoked salami and mould salami. Tests on these cold cuts were conducted on the 2nd, 15th, 30th, and 45th days of storage. There was a significant increase in the pH value of the mould salami from 5.16 on the 2nd day to 5.42 on the 45th day (p < 0.05). There was a downward trend in the Aw of the smoked salami sample from 0.892 on the 2nd day to 0.873 on the 45th day. The Aw in the mould salami sample decreased from 0.889 on the 2nd day to 0.847 on the 15th day and then increased to 0.871 on the 45th day (p < 0.05). In the first two test periods, the smoked salami was characterised by a higher modulus of elasticity value than the non-smoked salami but lower loss tangent and dynamic viscosity values. The hardness of the whole bars, as well as the hardness of the salami pieces, was affected by their storage time and the related water content. The texture test results showed that the smoked salami was more resistant to compressive force than the mould salami, which affected the sensory evaluation and ease of slicing of this type of salami.