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1.
Nature ; 597(7878): 660-665, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34588671

RESUMO

The densification of integrated circuits requires thermal management strategies and high thermal conductivity materials1-3. Recent innovations include the development of materials with thermal conduction anisotropy, which can remove hotspots along the fast-axis direction and provide thermal insulation along the slow axis4,5. However, most artificially engineered thermal conductors have anisotropy ratios much smaller than those seen in naturally anisotropic materials. Here we report extremely anisotropic thermal conductors based on large-area van der Waals thin films with random interlayer rotations, which produce a room-temperature thermal anisotropy ratio close to 900 in MoS2, one of the highest ever reported. This is enabled by the interlayer rotations that impede the through-plane thermal transport, while the long-range intralayer crystallinity maintains high in-plane thermal conductivity. We measure ultralow thermal conductivities in the through-plane direction for MoS2 (57 ± 3 mW m-1 K-1) and WS2 (41 ± 3 mW m-1 K-1) films, and we quantitatively explain these values using molecular dynamics simulations that reveal one-dimensional glass-like thermal transport. Conversely, the in-plane thermal conductivity in these MoS2 films is close to the single-crystal value. Covering nanofabricated gold electrodes with our anisotropic films prevents overheating of the electrodes and blocks heat from reaching the device surface. Our work establishes interlayer rotation in crystalline layered materials as a new degree of freedom for engineering-directed heat transport in solid-state systems.

3.
J Clin Densitom ; 27(1): 101455, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38101289

RESUMO

Background Type 2 Diabetes Mellitus (T2DM) frequently coexists with osteoporosis and reduced bone mineral density (BMD). Dipeptidyl peptidase-4 inhibitors (DPP-4i), a class of antihyperglycemic agents, are commonly employed in T2DM treatment. However, the influence of DPP-4i on bone health remains unclear and debated. This meta-analysis is conducted to explore the relationship between the use of DPP-4i and changes in BMD, as well as the prevalence of osteoporosis among T2DM patients. Methods We conducted a comprehensive search in PubMed, Embase, and Cochrane Library and Web of Science databases for relevant studies published up until June 2023. Studies included in the meta-analysis were those investigating T2DM patients under DPP-4i treatment, and examining the effects on BMD and osteoporosis. Random-effects models and fixed-effect models were utilized to compute the pooled effects. Heterogeneity among the included studies was evaluated using I² statistics. Results This meta-analysis incorporated a total of 10 studies, encompassing a combined population of 214,541 individuals. The results from this meta-analysis indicated an increase in BMD following DPP-4i usage (SMD 0.15, 95 % confidence interval 0.03-0.26). Additionally, the risk of osteoporosis was significantly reduced (OR 0.90, 95 % confidence interval 0.86-0.94) with very low heterogeneity, recorded at 0 % and 53.0 % respectively. No publication bias was detected in the funnel plot, and sensitivity analyses affirmed the stability of the study's conclusions. Conclusion Our results offer valuable insights into the positive impact of DPP-4i on bone health in T2DM patients, contributing to informed clinical decision-making. These findings may inform the development of more comprehensive T2DM management strategies that account for bone health.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Osteoporose , Humanos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Densidade Óssea , Hipoglicemiantes/uso terapêutico , Osteoporose/tratamento farmacológico
4.
BMC Infect Dis ; 23(1): 93, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788516

RESUMO

OBJECTIVES: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. METHODS: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI"). RESULTS: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection. CONCLUSIONS: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2/genética , Pandemias , Reinfecção/diagnóstico , Reinfecção/epidemiologia , Estudos Retrospectivos , Singapura/epidemiologia
5.
Phytopathology ; 113(1): 11-20, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35913221

RESUMO

Burkholderia contaminans MS14, isolated from a soil sample in Mississippi, is known for producing the novel antifungal compound occidiofungin. In addition, MS14 exhibits a broad range of antibacterial activities against common plant pathogens. Random mutagenesis and gene complementation indicate that four genes are required for antibacterial activity of strain MS14 against the fire blight pathogen Erwinia amylovora. With the aim of finding the biosynthetic gene cluster for the unknown antibacterial compound, we used RNA-seq to analyze the transcriptome of MS14 wild type and mutants lacking antibacterial activity. The twofold lower expressed genes in all mutants were studied, and a polyketide synthase (PKS) gene cluster was predicted to be directly involved in MS14 antibacterial activities. The nptII-resistance cassette and CRISPR-Cas9 systems were used to mutate the PKS gene cluster. Plate bioassays showed that either insertion or frame-shifting one of the PKS genes resulted in a loss of antibacterial activity. Considering that the antibacterial-defective mutants maintain the same antifungal activities as the wild-type strain, the results suggest that this PKS gene cluster is highly likely to be involved in or directly responsible for the production of MS14 antibacterial activity. Purification efforts revealed that the antibacterial activity of the compound synthesized by the gene cluster is sensitive to UV radiation. Nevertheless, these findings have provided more insights to understand the antibacterial activity of strain MS14.


Assuntos
Burkholderia , Policetídeos , Antifúngicos , Ligases/genética , Doenças das Plantas/microbiologia , Burkholderia/genética , Antibacterianos/farmacologia , Família Multigênica
6.
Ann Hepatol ; 28(2): 100888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36586588

RESUMO

INTRODUCTION AND OBJECTIVES: The Hepamet fibrosis score was introduced for the diagnosis of advanced liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). To date, external validation is limited, and its utility in combination with liver stiffness measurement (LSM) has not been explored. MATERIAL AND METHODS: This is a cross-sectional study on NAFLD patients who had a liver biopsy and LSM on the same day. The diagnostic performance of the Hepamet fibrosis score was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The data for 196 patients were analyzed (mean age 50 ± 11 years old, 50% men, 56.6% Malay, 27.6% Chinese, 15.8% Indian, 67.9% NASH, 15.8% advanced liver fibrosis). The AUROC of Hepamet fibrosis score for the diagnosis of advanced liver fibrosis was 0.85 (95% CI, 0.80 - 0.91). Using the <0.12 and ≥0.47 cut-offs from the original study, the sensitivity, specificity, positive predictive value, negative predictive value, the proportion of indeterminate results and misclassification rate were 81.8%, 91.8%, 47.4%, 98.2%, 32.1% and 6.1%, respectively. Using LSM <10 kPa and ≥15 kPa for the diagnosis of absence and presence of advanced liver fibrosis, respectively, in patients with Hepamet fibrosis score ≥0.47 (i.e., the two-step approach) reduced indeterminate results and misclassification to 16.1% and 3.6%, respectively. CONCLUSIONS: We found the Hepamet fibrosis score to have good diagnostic accuracy in a population that was largely unrepresented in earlier work and demonstrated its utility in a two-step approach with LSM for the diagnosis of advanced liver fibrosis.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Estudos Transversais , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Biópsia/métodos
7.
Food Microbiol ; 115: 104333, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37567623

RESUMO

Natural environment serves as a reservoir for Burkholderia cepacia complex organisms, including the highly transmissible opportunistic human pathogen B. cenocepacia. Currently, there is a lack of an effective and quantitative method for B. cenocepacia detection in fresh food and other environmental niches. A quantitative real-time PCR (qPCR) detection method for B. cenocepacia bacteria was established in this study and validated using artificially inoculated fresh vegetable samples. Genome-wide comparative methods were applied to identify target regions for the design of species-specific primers. Assay specificity was measured with 12 strains of closely related Burkholderia bacteria and demonstrated the primer pair BCF6/R6 were 100% specific for detection of B. cenocepacia. The described qPCR assay evaluated B. cenocepacia with a 2 pg µl-1 limit of detection and appropriate linearity (R2 = 0.999). In 50 samples of experimentally infected produce (lettuce, onion, and celery), the assay could detect B. cenocepacia as low as 2.6 × 102 cells in each sample equal to 1 g. The established qPCR method quantitatively detects B. cenocepacia with high sensitivity and specificity, making it a promising technique for B. cenocepacia detection and epidemiological research on B. cepacia complex organisms from fresh vegetables.


Assuntos
Burkholderia cenocepacia , Complexo Burkholderia cepacia , Humanos , Verduras
9.
Phytopathology ; 112(3): 481-491, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34433293

RESUMO

Aflatoxin is a secondary metabolite produced by Aspergillus fungi and presents a major food safety concern globally. Among the available methods for prevention and control of aflatoxin, the application of antifungal bacteria has gained favor in recent years. An endophytic bacterium MS455, isolated from soybean, exhibited broad-spectrum antifungal activity against economically important pathogens, including Aspergillus flavus. MS455 was identified as a strain of Burkholderia based on genomic analysis. Random and site-specific mutations were used in discovery of the genes that share high homology to the ocf gene cluster of Burkholderia contaminans strain MS14, which is responsible for production of the antifungal compound occidiofungin. RNA sequencing analysis demonstrated that ORF1, a homolog to the ambR1 LuxR-type regulatory gene, regulates occidiofungin biosynthesis in MS455. Additionally, 284 differentially expressed genes, including 138 upregulated and 146 downregulated genes, suggesting that, in addition to its role in occidiofungin production, ORF1 is involved in expression of multiple genes, especially those involved in ornibactin biosynthesis. Plate bioassays showed the growth of A. flavus was significantly inhibited by the wild-type strain MS455 as compared with the ORF1 mutant. Similarly, corn kernel assays showed that growth of A. flavus and aflatoxin production were reduced significantly by MS455 as compared with buffer control and the ORF1 mutant. Collectively, the results demonstrated that production of occidiofungin is essential for antifungal activity of the endophytic bacterium MS455. This research has provided insights about antifungal mechanisms of MS455 and development of biological approaches to prevent aflatoxin contamination in plant production.


Assuntos
Aflatoxinas , Burkholderia , Aflatoxinas/metabolismo , Antifúngicos/metabolismo , Aspergillus flavus/genética , Burkholderia/genética , Glicopeptídeos , Peptídeos Cíclicos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
10.
Eur Arch Otorhinolaryngol ; 279(10): 5025-5032, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35320400

RESUMO

BACKGROUND: Although endoscopic dacryocystorhinostomy (DCR) is a standard procedure for nasolacrimal duct obstruction (NLDO), the failure rate remains approximately 10%. A small lacrimal sac is considered the main reason for surgical failure. We explored the efficacy of endoscopic DCR for the treatment of NLDO with a small lacrimal sac. METHODS: The clinical data of 72 patients (88 eyes) diagnosed with NLDO and undergoing endoscopic DCR from 2012 to 2020, with at least 24 months of follow-up were retrospectively collected. Intraoperatively, the Rosenmüller valves were fully exposed, mucosal flaps were preserved to cover the naked bone, and a silicone tube was implanted if necessary. Postoperative intervention was performed if necessary. The main outcome measures were symptomatic improvement and objective ostium patency. RESULTS: Eighty-eight eyes of 72 patients were divided into two groups: the refractory group (34 patients, 47 eyes), with a small lacrimal sac (≤ 5 mm in diameter), and the simple group (38 patients, 41 eyes). Patients with small lacrimal sacs were more prone to bilateral eye disease than those in the simple group (P = 0.014) and required a longer postoperative follow-up (P < 0.001). Refractory NLDO and simple NLDO had a success rate of 91.5% and 95.1%, respectively, with no significant difference. CONCLUSION: Endoscopic DCR for refractory NLDO with a small lacrimal sac could achieve a beneficial result by exposing the Rosenmüller valves, preserving mucosal flaps, implanting necessary intubation, and intervening postoperatively. Thus, a small lacrimal sac should not be regarded as a contraindication to surgery.


Assuntos
Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Dacriocistorinostomia/métodos , Endoscopia/métodos , Humanos , Intubação , Obstrução dos Ductos Lacrimais/terapia , Ducto Nasolacrimal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Emerg Infect Dis ; 27(5): 1427-1437, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33900180

RESUMO

Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Accurate diagnostic tests to differentiate the 2 infections are necessary for patient management and disease control. Using characterized ZIKV and DENV patient plasma in a blind manner, we validated an ELISA and a rapid immunochromatographic test for ZIKV detection. We engineered the ZIKV nonstructural protein 1 (NS1) for sensitive serologic detection with low cross reactivity against dengue and developed monoclonal antibodies specific for the ZIKV NS1 antigen. As expected, the serologic assays performed better with convalescent than acute plasma samples; the sensitivity ranged from 71% to 88%, depending on the performance of individual tests (IgM/IgG/NS1). Although serologic tests were generally less sensitive with acute samples, our ZIKV NS1 antibodies were able to complement the serologic tests to achieve greater sensitivity for detecting early infections.


Assuntos
Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Humanos , Sensibilidade e Especificidade , Testes Sorológicos , Proteínas não Estruturais Virais
12.
Appl Environ Microbiol ; 87(7)2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33452032

RESUMO

Pseudomonas chlororaphis YL-1 has extensive antimicrobial activities against phytopathogens, and its genome harbors a pyoverdine (PVD) biosynthesis gene cluster. The alternative sigma factor PvdS in Pseudomonas aeruginosa PAO1 acts as a critical regulator in response to iron starvation. The assembly of the PVD backbone starts with peptide synthetase enzyme PvdL. PvdF catalyzes formylation of l-OH-Orn to produce l-N5-hydroxyornithine. Here, we describe the characterization of PVD production in YL-1 and its antimicrobial activity in comparison with that of its PVD-deficient ΔpvdS, ΔpvdF, and ΔpvdL mutants, which were obtained using a sacB-based site-specific mutagenesis strategy. Using in vitro methods, we examined the effect of exogenous iron under low-iron conditions and an iron-chelating agent under iron-sufficient conditions on PVD production, antibacterial activity, and the relative expression of the PVD transcription factor gene pvdS in YL-1. We found that strain YL-1, the ΔpvdF mutant, and the ΔpvdS(pUCP26-pvdS) complemented strain produced visible PVDs and demonstrated a wide range of inhibitory effects against Gram-negative and Gram-positive bacteria in vitro under low-iron conditions and that with the increase of iron, its PVD production and antibacterial activity were reduced. The antibacterial compounds produced by strain YL-1 under low-iron conditions were PVDs based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Moreover, the antibacterial activity observed in vitro was correlated with in vivo control efficacies of strain YL-1 against rice bacterial leaf blight (BLB) disease caused by Xanthomonas oryzae pv. oryzae. Collectively, PVDs are responsible for the antibacterial activities of strain YL-1 under both natural and induced low-iron conditions.IMPORTANCE The results demonstrated that PVDs are essential for the broad-spectrum antibacterial activities of strain YL-1 against both Gram-positive and Gram-negative bacteria under low-iron conditions. Our findings also highlight the effect of exogenous iron on the production of PVD and the importance of this bacterial product in bacterial interactions. As a biocontrol agent, PVDs can directly inhibit the proliferation of the tested bacteria in addition to participating in iron competition.


Assuntos
Antibacterianos/farmacologia , Ferro/metabolismo , Oligopeptídeos/farmacologia , Pseudomonas chlororaphis/metabolismo , Antibacterianos/química , Cromatografia Líquida , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Oligopeptídeos/química , Pseudomonas chlororaphis/química , Pseudomonas chlororaphis/genética , Espectrometria de Massas em Tandem
13.
Epidemiol Infect ; 149: e92, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33814027

RESUMO

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.


Assuntos
Assistência Ambulatorial , Teste para COVID-19/métodos , COVID-19/diagnóstico , Dor Abdominal/fisiopatologia , Adolescente , Adulto , COVID-19/fisiopatologia , Estudos de Casos e Controles , Regras de Decisão Clínica , Tosse/fisiopatologia , Diarreia/fisiopatologia , Progressão da Doença , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Cefaleia/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mialgia/fisiopatologia , Razão de Chances , Seleção de Pacientes , Faringite/fisiopatologia , Rinorreia/fisiopatologia , SARS-CoV-2 , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
14.
Plant Dis ; 105(9): 2704-2707, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33876648

RESUMO

Burkholderia sp. strain MS389, an endophytic bacterium, was isolated from a healthy soybean plant growing adjacent to a patch of plants affected by charcoal rot disease, caused by the fungal pathogen Macrophomina phaseolina. Preliminary studies demonstrated that strain MS389 possesses antimicrobial activities against multiple plant pathogens. Burkholderia sp. strain MS389 was found to have three circular chromosomes of 3,563,380 bp, 3,002,449 bp, and 1,180,421 bp in size, respectively. The 7,746,250-bp genome, with 66.73% G+C content, harbors 6,756 protein coding genes in the predicted 6,985 genes. In total, 18 rRNAs, 68 tRNAs, and four ncRNAs were identified and 139 pseudogenes were annotated as well. The findings of this study will provide valuable data to explore the antimicrobial mechanisms of the endophytic bacterial strain.


Assuntos
Ascomicetos , Burkholderia , Ascomicetos/genética , Burkholderia/genética , Análise de Sequência de DNA , Glycine max
15.
Water Sci Technol ; 83(9): 2087-2099, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33989178

RESUMO

Interspecific competition for substrate and space gives rise to considerable variation in biomass distribution within the microbial community. To study microbial community in depth, we used several research methods as sampling and analytical measurements, and developed a cellular automata (CA) model that would facilitate a description of the microbial growth process based on Anaerobic Digestion Model No. 1 (ADM1) of the International Water Association (IWA). Using the CA model, we aimed to determine whether interspecific competition occurs among acidogens, acetogens and methanogens, and to examine the influence of interspecific competition on the spatial structure of microbial communities. We found that acetogens and methanogens competed for core space, resulting in a multi-layer structure. Butyrate-degrading acetogens increased in number, resulting in inhibition of propionate-degrading acetogens. Hydrogenotrophic methanogens showed stronger competitive advantage than acetotrophic methanogens. The simulation showed that the multi-layer structure of the microbial community was formed by interspecific competition.


Assuntos
Euryarchaeota , Microbiota , Anaerobiose , Reatores Biológicos , Simulação por Computador , Ecologia , Metano
16.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32958713

RESUMO

Occidiofungin is a nonribosomally synthesized cyclic lipopeptide that possesses broad-spectrum antifungal properties at submicromolar concentrations. This report explores multiple routes of administration and formulations of occidiofungin, as well as its toxicity in mice. Further, infection studies were performed in mice to assess the application of occidiofungin for treating systemic and intravaginal yeast infections. Formulations for intravenous and intravaginal administration of occidiofungin were prepared. Pharmacokinetic analyses were performed in a murine model, and a liquid chromatography-mass spectrometry (LC-MS) method was developed and used to quantify occidiofungin in mouse plasma samples. Toxicological and histopathological analyses of two repeat-dose studies using occidiofungin were performed. In these animal models, following intravenous administration, a liposomal formulation of occidiofungin improved the half-life and peak plasma drug concentration over that with a liposome-free formulation. Two long-term repeat-dosing toxicity studies of occidiofungin indicated the absence of toxicity in organ tissues. Murine models of a systemic yeast infection and a vulvovaginal yeast infection were performed. The findings of the systemic infection study revealed limitations in the use of occidiofungin that may be alleviated with the development of novel structural analogs or with further formulation studies. The gel formulation of occidiofungin demonstrated improved efficacy over that of the commercial product Monistat 3 in a vulvovaginal candidiasis study. This report outlines the optimal routes of administration of occidiofungin and demonstrates minimal toxicity following chronic exposure. Further, the results of these studies provide a clear indication for the use of occidiofungin for the treatment of recurrent vulvovaginal candidiasis (RVVC), which is a serious and clinically relevant issue.


Assuntos
Antifúngicos , Candidíase Vulvovaginal , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Feminino , Glicopeptídeos , Humanos , Camundongos , Peptídeos Cíclicos
17.
Eur Arch Otorhinolaryngol ; 277(5): 1369, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32144564

RESUMO

In the original publication of the article, under the experimental protocol of the section "Clinical head position study in postoperative CRS patients", the following sentence "There were 20 CRS patients, 12 male and 8 female across an age range of 19-64 years…" was published incorrectly.

18.
Eur Arch Otorhinolaryngol ; 277(5): 1361-1368, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32055957

RESUMO

PURPOSE: Effective topical medications delivery to the frontal sinus is crucial to recovery from frontal sinusotomy. However, finding a way to deliver local medications to the frontal sinus is still a major challenge. The objective of this study was to evaluate the influence of various head positions on postoperative frontal sinus drug deposition. The safety and efficacy were also evaluated in postoperative chronic rhinosinusitis (CRS) patients. METHODS: Full house surgery was performed on six fresh frozen cadaver heads. The fluorescein solution was dropped into the nasal sinuses in three different head positions, and the fluorescein deposition was evaluated. A prospective cohort study was performed to validate the results in 20 postoperative CRS patients. The cortisol level, symptom VAS and the frontal recess endoscopy scores were evaluated pre- and postoperatively. RESULTS: The frontal recess delivery of fluorescein was better in the Mygind and vertex-to-floor positions than in the head back position. The cortisol level of patients dropped markedly after taking oral methylprednisolone, but returned to baseline when replaced with budesonide drops. The pre- and postoperative symptom VAS scores did not differ significantly between the two groups. Endoscopic scores of the vertex-to-floor group were significantly better than those of the Mygind group. CONCLUSION: Both the Mygind and the vertex-to-floor head positions were optimal for delivery of topical medications to the frontal recess. When applying the steroid drops, both positions were found to be safe and associated with effective relief of symptoms. The vertex-to-floor position can better improve the endoscopic scores of frontal recess and frontal sinus.


Assuntos
Seio Frontal , Preparações Farmacêuticas , Sinusite , Doença Crônica , Endoscopia , Seio Frontal/cirurgia , Humanos , Estudos Prospectivos , Sinusite/tratamento farmacológico , Sinusite/cirurgia
19.
Mikrochim Acta ; 187(7): 373, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504133

RESUMO

A new series of 9-plex chemical isotope-labeling reagents, levofloxacin-based mass tags (LMTs) named as LMT359, 360, 361, 362, 363, 373, 375, 376, and 378, was firstly designed and synthesized for the high-throughput labeling of globotriaosylsphingosine (lyso-Gb3), a disease biomarker of Fabry disease. Creatively based on derivatization strategy-dummy template technique, dummy magnetic molecularly imprinted polymers (DMMIPs) were designed and prepared using LMT387-labeled lyso-Gb3 as a dummy template. The novel DMMIP material was used as sorbents for magnetic dispersive solid-phase extraction of 9-plexed LMT derivatives of lyso-Gb3 from equally mixed derivatization solutions. The enriched 8-plexed lyso-Gb3 derivatives from 8 real samples were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry in a single run using simultaneously extracted LMT359-labeled standard lyso-Gb3 as internal standards. DMMIPs were characterized by using the transmission electron microscope (TEM), Fourier transform infrared, X-ray photoelectron spectroscopy, and some other characterization techniques. TEM micrograph showed that the prepared DMMIPs had an apparent imprinting layer. Triple-recognition abilities of DMMIPs towards LMT-lyso-Gb3 mainly rely on the hydrogen bonding, electrostatic attraction, hydrophobic interaction, and boronate affinity. The imprinting factor of DMMIPs towards LMT-lyso-Gb3 was 5.1. This method shows the advantages of high selectivity (triple recognition), high sensitivity, high accuracy (recovery 93.5-108.8%), and high throughput (8 samples in a single run). The proposed method was successfully applied to the determination of lyso-Gb3 in plasma samples with spiked recoveries in the range of 95.0-102.4%. This indicates that the method is promising in bioanalysis and medical testing of lyso-Gb3 in the future. Graphical abstract Synthesis of multiplexed derivatization reagents and its correlative molecularly imprinted polymers for magnetic extraction of globotriaosylsphingosine.

20.
Nano Lett ; 19(11): 8287-8293, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31661615

RESUMO

Quantum computing based on superconducting qubits requires the understanding and control of the materials, device architecture, and operation. However, the materials for the central circuit element, the Josephson junction, have mostly been focused on using the AlOx tunnel barrier. Here, we demonstrate Josephson junctions and superconducting qubits employing two-dimensional materials as the tunnel barrier. We batch-fabricate and design the critical Josephson current of these devices via layer-by-layer stacking N layers of MoS2 on the large scale. Based on such junctions, MoS2 transmon qubits are engineered and characterized in a bulk superconducting microwave resonator for the first time. Our work allows Josephson junctions to access the diverse material properties of two-dimensional materials that include a wide range of electrical and magnetic properties, which can be used to study the effects of different material properties in superconducting qubits and to engineer novel quantum circuit elements in the future.

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