To study the structure-antifungal activity of vanillin against Aspergillus flavus(A.flavus),the susceptibilities of A.flavus to vanillin and its isomers(o-vanillin,2-hydroxy-4-methoxybenzaldehyde(HMB),2-hydroxy-5-meth...To study the structure-antifungal activity of vanillin against Aspergillus flavus(A.flavus),the susceptibilities of A.flavus to vanillin and its isomers(o-vanillin,2-hydroxy-4-methoxybenzaldehyde(HMB),2-hydroxy-5-methoxybenzaldehyde)and the possible antifungal mechanisms have been investigated.All the four volatile aldehydes could inhibit the germination of spores,and the minimum inhibitory concentrations(MICs)of them were in this order:vanillin(200μg/mL),o-vanillin(100μg/mL),2-hydroxy-5-methoxybenzaldehyde(100μg/mL),HMB(70μg/mL).The minimum fungicidal concentrations(MFCs)of them were in this order:vanillin(240μg/mL),o-vanillin(160μg/mL),HMB(140μg/mL),2-hydroxy-5-methoxybenzaldehyde(140μg/mL).Spore size was arrested at 0 h with the treatment of the four volatile aldehydes.Effects of the four volatile aldehydes on the cell wall and cell membrane integrity of A flavus were observed by calcofluor white(CW)staining and propidium iodide(PI)staining.The results showed that HMB exerted the strongest antifungal and fungicidal effects on the growth of A.flavus.The four volatile aldehydes had little influence on cell wall integrity after 3-hour treatment,however,they could strongly damage the cell membrane integrity.All the four volatile aldehydes could effectively prevent the growth of A.flavus on peanut seeds.The antifungal mechanisms of the four volatile aldehydes provide theoretical foundations for their development of new antifungal agents.展开更多
Several 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl] -2- arylamino - 1,3,4- thiadiazoles were synthesized. The preliminary bio-active test shows that these compounds exhibit high antifungal activity.
Fungal infections have emerged as a worldwide health care problem in recent years, owing to the extensive use of broad-spectrum antibiotics. We screened 104 pregnant women with symptoms of vaginal candidiasis in the a...Fungal infections have emerged as a worldwide health care problem in recent years, owing to the extensive use of broad-spectrum antibiotics. We screened 104 pregnant women with symptoms of vaginal candidiasis in the antenatal clinic of Thika District Hospital, Kenya in order to identify vaginal Candida species and determine their susceptibility profile to commonly used antifungal drugs for treatment of the infection. The drugs tested were fluconazole, ketoconazole, itraconazole, clotrimazole and topical nystatin. Vaginal swabs were collected and subjected to mycological and biochemical tests for Candida species identification. Susceptibility profile of the identified vaginal Candida species to the antifungal drugs was carried out using broth micro-dilution minimum inhibiting concentration method based on the approved National Committee for Clinical Laboratory Standards (NCCLS, 2002) guidelines. Candida albicans was susceptible to most of the azoles drugs while the other species had varying responses. Candida krusei and Candida glabrata species isolated were resistant to fluconazole and ketoconazole. Candida albicans isolates had a high susceptibility to itraconazole (88.33%). Five percent (5%) of the isolates were susceptible in dose dependent (S-DD) with Minimum Inhibitory Concentrations (MICs) of 0.25 - 0.5 μg/ml while 11.67% of C. albicans isolates were resistant (MICs ≥ 1 μg/ml). Itraconazole resistance was highest among C. glabrata isolates (50%) while 32.14% were S-DD (MICs 0.25 - 0.5 μg/ml). Only 17.85% of the C. glabrata isolates were susceptible (MICs of ≤ 0.125 μg/ml). All isolates of Candida isolates were susceptible to itraconazole and clotrimazole except C. krusei which was 100% resistant to clotrimazole. All Candida species isolates had low susceptibility to topical nystatin except Candida parapsilosis that was 100% susceptible. Data also showed an emerging resistance of Candida krusei to most of the drugs used except itraconazole. The results of this study support the continued use of these antifungal drugs for the treatment of vaginal candidiasis in the pregnant women except topical nystatin.展开更多
Fungal infections are increasing and their treatment is difficult,because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore,interest has focused on safely applicable an...Fungal infections are increasing and their treatment is difficult,because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore,interest has focused on safely applicable and clinically introduced non-antifungal drugs,which have potent antifungal activity.Statins were originally used as cholesterol lowering agents in human therapy,but recent studies demonstrated their in vitro antifungal activity against yeasts and filamentous fungi.This indicated their potential application,alone or in combination with other drugs,in the treatment of such diseases.Their effective concentrations are higher than their maximum achievable serum levels;therefore,the application of statins for the treatment of invasive fungal infections is only possible in combination with antifungal agents.These synergistic combinations establish a basis for a new safely applicable therapy.This review focuses on the antifungal activity of statins alone and in combination with antifungal and non-antifungal drugs,and their possible application in clinical therapy.展开更多
Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal St...Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.展开更多
Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where s...Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.展开更多
One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing prom...One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.展开更多
Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical...Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical interventions, its moderate investment and operating costs and its portability. Although the technology is now mature, there is currently the problem of the availability of contrast agents to be injected IV. The aim of this methodology article is to propose an alternative solution to the need for contrast agents for clinical research, particularly in oncology. Methodology: They consist of coupling a fluorescent marker in the form of an NHS derivative, such as IR DYE manufactured in compliance with GMP, with therapeutic monoclonal antibodies having marketing authorization for molecular imaging. For a given antibody, the marking procedure must be the subject of a validation file on the final preparation filtered on a sterilizing membrane at 0.22 μm. Once the procedure has been validated, it would be unnecessary to repeat the tests before each clinical research examination. A check of the marking by thin-layer chromatography (TLC) and place it in a sample bank at +4˚C for 1 month of each injected formulation would be sufficient for additional tests if necessary. Conclusion: Molecular near-infrared fluorescence imaging is experiencing development, the process of which could be accelerated by greater availability of clinical contrast agents. Alternative solutions are therefore necessary to promote clinical research in this area. These methods must be shared to make it easier for researchers.展开更多
Background Physical entity interactions in mixed reality(MR)environments aim to harness human capabilities in manipulating physical objects,thereby enhancing virtual environment(VEs)functionality.In MR,a common strate...Background Physical entity interactions in mixed reality(MR)environments aim to harness human capabilities in manipulating physical objects,thereby enhancing virtual environment(VEs)functionality.In MR,a common strategy is to use virtual agents as substitutes for physical entities,balancing interaction efficiency with environmental immersion.However,the impact of virtual agent size and form on interaction performance remains unclear.Methods Two experiments were conducted to explore how virtual agent size and form affect interaction performance,immersion,and preference in MR environments.The first experiment assessed five virtual agent sizes(25%,50%,75%,100%,and 125%of physical size).The second experiment tested four types of frames(no frame,consistent frame,half frame,and surrounding frame)across all agent sizes.Participants,utilizing a head mounted display,performed tasks involving moving cups,typing words,and using a mouse.They completed questionnaires assessing aspects such as the virtual environment effects,interaction effects,collision concerns,and preferences.Results Results from the first experiment revealed that agents matching physical object size produced the best overall performance.The second experiment demonstrated that consistent framing notably enhances interaction accuracy and speed but reduces immersion.To balance efficiency and immersion,frameless agents matching physical object sizes were deemed optimal.Conclusions Virtual agents matching physical entity sizes enhance user experience and interaction performance.Conversely,familiar frames from 2D interfaces detrimentally affect interaction and immersion in virtual spaces.This study provides valuable insights for the future development of MR systems.展开更多
Grey Wolf Optimization (GWO) is a nature-inspired metaheuristic algorithm that has gained popularity for solving optimization problems. In GWO, the success of the algorithm heavily relies on the efficient updating of ...Grey Wolf Optimization (GWO) is a nature-inspired metaheuristic algorithm that has gained popularity for solving optimization problems. In GWO, the success of the algorithm heavily relies on the efficient updating of the agents’ positions relative to the leader wolves. In this paper, we provide a brief overview of the Grey Wolf Optimization technique and its significance in solving complex optimization problems. Building upon the foundation of GWO, we introduce a novel technique for updating agents’ positions, which aims to enhance the algorithm’s effectiveness and efficiency. To evaluate the performance of our proposed approach, we conduct comprehensive experiments and compare the results with the original Grey Wolf Optimization technique. Our comparative analysis demonstrates that the proposed technique achieves superior optimization outcomes. These findings underscore the potential of our approach in addressing optimization challenges effectively and efficiently, making it a valuable contribution to the field of optimization algorithms.展开更多
Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and wer...Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.展开更多
Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is...Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.展开更多
A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available haloben...A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1 H NMR, 13 C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazolethione and its triazolium derivatives displayed the most potent activities against all the tested strains.展开更多
Twenty-seven novel pyrazole carboxamides with diarylamine-modified scaffold were designed,synthesized and characterized in detail via1 H NMR,^(13) C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the ...Twenty-seven novel pyrazole carboxamides with diarylamine-modified scaffold were designed,synthesized and characterized in detail via1 H NMR,^(13) C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani,Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC_(50) values of 0.013, 1.608 and 1.874 mg/m L, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC_(50) value of 22.21 mg/m L. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.展开更多
A series of 3-substituted quinazolinones,2-substituted quinoxalines and 2-substituted benzopyrans were synthesized and evaluated for their antifungal activity in vitro.The new compounds revealed excellent in vitro ant...A series of 3-substituted quinazolinones,2-substituted quinoxalines and 2-substituted benzopyrans were synthesized and evaluated for their antifungal activity in vitro.The new compounds revealed excellent in vitro antifungal activity with broad spectrum.The structure-activity relationships(SARs) of the derivatives were analyzed.Compound 9A2 exhibits better antifungal activity against 5 tested fungi in vitro than fluconazole,especially against Trichophyton rubrum and Microsporum gypseum.This study provides a series of novel lead compounds for the development of non-azole antifungal agents.展开更多
A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a–i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylamin...A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a–i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine(DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14 ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.展开更多
The present work describes a facile,one-pot three component synthesis of a series of 3-[(4,5-diphenyl-2-substituted aryl/heteryl)-1H-imidazol-1-yl]-1H-1,2,4-triazole-5-carboxylic acid derivatives M(1-15).Benzil,aromat...The present work describes a facile,one-pot three component synthesis of a series of 3-[(4,5-diphenyl-2-substituted aryl/heteryl)-1H-imidazol-1-yl]-1H-1,2,4-triazole-5-carboxylic acid derivatives M(1-15).Benzil,aromatic aldehydes and 3-amino-l,2,4-triazole-5-carboxylic acid was refluxed in ethanol using cerric ammonium nitrate(CAN) as a catalyst to give the title compounds in good yields.The compounds were evaluated for their in vitro antifungal and antibacterial activity.Compounds M1,M9,and M15 were found to be equipotent against Candida albicans when compared with fluconazole.Compounds M2.M5,and M14 showed higher activity against Streptococcus pneumoniae.Escherichia coli and Streptococcus pyogenes,respectively,compared with ampicillin.Docking study of the newly synthesized compounds was performed,and the results showed good binding mode in the active sites of C albicans enzyme cytochrome P450 lanosterol 14α-demethylase.The results of in vitro antifungal activity and docking study showed that synthesized compounds had potential antifungal activity and can be further optimized and developed as a lead compound.展开更多
基金the financial support of the Doctor Research Fund of Henan University of Technology(2019BS019)the Natural Science Research Projects of Education Department of Henan Province(21A550005)the Innovative Funds plan of Henan University of Technology(2020ZKCJ17)。
文摘To study the structure-antifungal activity of vanillin against Aspergillus flavus(A.flavus),the susceptibilities of A.flavus to vanillin and its isomers(o-vanillin,2-hydroxy-4-methoxybenzaldehyde(HMB),2-hydroxy-5-methoxybenzaldehyde)and the possible antifungal mechanisms have been investigated.All the four volatile aldehydes could inhibit the germination of spores,and the minimum inhibitory concentrations(MICs)of them were in this order:vanillin(200μg/mL),o-vanillin(100μg/mL),2-hydroxy-5-methoxybenzaldehyde(100μg/mL),HMB(70μg/mL).The minimum fungicidal concentrations(MFCs)of them were in this order:vanillin(240μg/mL),o-vanillin(160μg/mL),HMB(140μg/mL),2-hydroxy-5-methoxybenzaldehyde(140μg/mL).Spore size was arrested at 0 h with the treatment of the four volatile aldehydes.Effects of the four volatile aldehydes on the cell wall and cell membrane integrity of A flavus were observed by calcofluor white(CW)staining and propidium iodide(PI)staining.The results showed that HMB exerted the strongest antifungal and fungicidal effects on the growth of A.flavus.The four volatile aldehydes had little influence on cell wall integrity after 3-hour treatment,however,they could strongly damage the cell membrane integrity.All the four volatile aldehydes could effectively prevent the growth of A.flavus on peanut seeds.The antifungal mechanisms of the four volatile aldehydes provide theoretical foundations for their development of new antifungal agents.
基金Financial support of this work by the National Natural Science Foundation of China(Projects number 29832050)is gratefully acknowledged.
文摘Several 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl] -2- arylamino - 1,3,4- thiadiazoles were synthesized. The preliminary bio-active test shows that these compounds exhibit high antifungal activity.
文摘Fungal infections have emerged as a worldwide health care problem in recent years, owing to the extensive use of broad-spectrum antibiotics. We screened 104 pregnant women with symptoms of vaginal candidiasis in the antenatal clinic of Thika District Hospital, Kenya in order to identify vaginal Candida species and determine their susceptibility profile to commonly used antifungal drugs for treatment of the infection. The drugs tested were fluconazole, ketoconazole, itraconazole, clotrimazole and topical nystatin. Vaginal swabs were collected and subjected to mycological and biochemical tests for Candida species identification. Susceptibility profile of the identified vaginal Candida species to the antifungal drugs was carried out using broth micro-dilution minimum inhibiting concentration method based on the approved National Committee for Clinical Laboratory Standards (NCCLS, 2002) guidelines. Candida albicans was susceptible to most of the azoles drugs while the other species had varying responses. Candida krusei and Candida glabrata species isolated were resistant to fluconazole and ketoconazole. Candida albicans isolates had a high susceptibility to itraconazole (88.33%). Five percent (5%) of the isolates were susceptible in dose dependent (S-DD) with Minimum Inhibitory Concentrations (MICs) of 0.25 - 0.5 μg/ml while 11.67% of C. albicans isolates were resistant (MICs ≥ 1 μg/ml). Itraconazole resistance was highest among C. glabrata isolates (50%) while 32.14% were S-DD (MICs 0.25 - 0.5 μg/ml). Only 17.85% of the C. glabrata isolates were susceptible (MICs of ≤ 0.125 μg/ml). All isolates of Candida isolates were susceptible to itraconazole and clotrimazole except C. krusei which was 100% resistant to clotrimazole. All Candida species isolates had low susceptibility to topical nystatin except Candida parapsilosis that was 100% susceptible. Data also showed an emerging resistance of Candida krusei to most of the drugs used except itraconazole. The results of this study support the continued use of these antifungal drugs for the treatment of vaginal candidiasis in the pregnant women except topical nystatin.
基金Supported by PannonPharma(Pécsvárad,Hungary)the Hungarian Scientific Research Fund(OTKA),No.PD 83355(to Galgóczy L).
文摘Fungal infections are increasing and their treatment is difficult,because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore,interest has focused on safely applicable and clinically introduced non-antifungal drugs,which have potent antifungal activity.Statins were originally used as cholesterol lowering agents in human therapy,but recent studies demonstrated their in vitro antifungal activity against yeasts and filamentous fungi.This indicated their potential application,alone or in combination with other drugs,in the treatment of such diseases.Their effective concentrations are higher than their maximum achievable serum levels;therefore,the application of statins for the treatment of invasive fungal infections is only possible in combination with antifungal agents.These synergistic combinations establish a basis for a new safely applicable therapy.This review focuses on the antifungal activity of statins alone and in combination with antifungal and non-antifungal drugs,and their possible application in clinical therapy.
文摘Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.
文摘Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.
文摘One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.
文摘Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical interventions, its moderate investment and operating costs and its portability. Although the technology is now mature, there is currently the problem of the availability of contrast agents to be injected IV. The aim of this methodology article is to propose an alternative solution to the need for contrast agents for clinical research, particularly in oncology. Methodology: They consist of coupling a fluorescent marker in the form of an NHS derivative, such as IR DYE manufactured in compliance with GMP, with therapeutic monoclonal antibodies having marketing authorization for molecular imaging. For a given antibody, the marking procedure must be the subject of a validation file on the final preparation filtered on a sterilizing membrane at 0.22 μm. Once the procedure has been validated, it would be unnecessary to repeat the tests before each clinical research examination. A check of the marking by thin-layer chromatography (TLC) and place it in a sample bank at +4˚C for 1 month of each injected formulation would be sufficient for additional tests if necessary. Conclusion: Molecular near-infrared fluorescence imaging is experiencing development, the process of which could be accelerated by greater availability of clinical contrast agents. Alternative solutions are therefore necessary to promote clinical research in this area. These methods must be shared to make it easier for researchers.
基金the Strategic research and consulting project of Chinese Academy of Engineering(2023-HY-14).
文摘Background Physical entity interactions in mixed reality(MR)environments aim to harness human capabilities in manipulating physical objects,thereby enhancing virtual environment(VEs)functionality.In MR,a common strategy is to use virtual agents as substitutes for physical entities,balancing interaction efficiency with environmental immersion.However,the impact of virtual agent size and form on interaction performance remains unclear.Methods Two experiments were conducted to explore how virtual agent size and form affect interaction performance,immersion,and preference in MR environments.The first experiment assessed five virtual agent sizes(25%,50%,75%,100%,and 125%of physical size).The second experiment tested four types of frames(no frame,consistent frame,half frame,and surrounding frame)across all agent sizes.Participants,utilizing a head mounted display,performed tasks involving moving cups,typing words,and using a mouse.They completed questionnaires assessing aspects such as the virtual environment effects,interaction effects,collision concerns,and preferences.Results Results from the first experiment revealed that agents matching physical object size produced the best overall performance.The second experiment demonstrated that consistent framing notably enhances interaction accuracy and speed but reduces immersion.To balance efficiency and immersion,frameless agents matching physical object sizes were deemed optimal.Conclusions Virtual agents matching physical entity sizes enhance user experience and interaction performance.Conversely,familiar frames from 2D interfaces detrimentally affect interaction and immersion in virtual spaces.This study provides valuable insights for the future development of MR systems.
文摘Grey Wolf Optimization (GWO) is a nature-inspired metaheuristic algorithm that has gained popularity for solving optimization problems. In GWO, the success of the algorithm heavily relies on the efficient updating of the agents’ positions relative to the leader wolves. In this paper, we provide a brief overview of the Grey Wolf Optimization technique and its significance in solving complex optimization problems. Building upon the foundation of GWO, we introduce a novel technique for updating agents’ positions, which aims to enhance the algorithm’s effectiveness and efficiency. To evaluate the performance of our proposed approach, we conduct comprehensive experiments and compare the results with the original Grey Wolf Optimization technique. Our comparative analysis demonstrates that the proposed technique achieves superior optimization outcomes. These findings underscore the potential of our approach in addressing optimization challenges effectively and efficiently, making it a valuable contribution to the field of optimization algorithms.
文摘Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.
文摘Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.
基金supported by the National Natural Science Foundation of China (21172181, 81250110089 (The Research Fellowship for International Young Scientists from International (Regional) Cooperation and Exchange Program))the key program from Natural Science Foundation of Chongqing (CSTC2012jjB10026)+1 种基金the Specialized Research Fund for the Doctoral Program of Higher Education of China (SRFDP20110182110007)the Fundamental Research Funds for the Central Universities (XDJK2011D007, XDJK2012B026)
文摘A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1 H NMR, 13 C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazolethione and its triazolium derivatives displayed the most potent activities against all the tested strains.
基金supported by National Key Research and Development Program of China(No.2016YFC0502004-2)Applied Basic Research Program of Sichuan Province(No.2014JY0063)
文摘Twenty-seven novel pyrazole carboxamides with diarylamine-modified scaffold were designed,synthesized and characterized in detail via1 H NMR,^(13) C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani,Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC_(50) values of 0.013, 1.608 and 1.874 mg/m L, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC_(50) value of 22.21 mg/m L. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.
基金supported by the Shandong Natural Science Foundation(No.ZR2012HQ026)the Foundation of Sichuan Provincial Health Department(No.110480)
文摘A series of 3-substituted quinazolinones,2-substituted quinoxalines and 2-substituted benzopyrans were synthesized and evaluated for their antifungal activity in vitro.The new compounds revealed excellent in vitro antifungal activity with broad spectrum.The structure-activity relationships(SARs) of the derivatives were analyzed.Compound 9A2 exhibits better antifungal activity against 5 tested fungi in vitro than fluconazole,especially against Trichophyton rubrum and Microsporum gypseum.This study provides a series of novel lead compounds for the development of non-azole antifungal agents.
文摘A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a–i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine(DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14 ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.
文摘The present work describes a facile,one-pot three component synthesis of a series of 3-[(4,5-diphenyl-2-substituted aryl/heteryl)-1H-imidazol-1-yl]-1H-1,2,4-triazole-5-carboxylic acid derivatives M(1-15).Benzil,aromatic aldehydes and 3-amino-l,2,4-triazole-5-carboxylic acid was refluxed in ethanol using cerric ammonium nitrate(CAN) as a catalyst to give the title compounds in good yields.The compounds were evaluated for their in vitro antifungal and antibacterial activity.Compounds M1,M9,and M15 were found to be equipotent against Candida albicans when compared with fluconazole.Compounds M2.M5,and M14 showed higher activity against Streptococcus pneumoniae.Escherichia coli and Streptococcus pyogenes,respectively,compared with ampicillin.Docking study of the newly synthesized compounds was performed,and the results showed good binding mode in the active sites of C albicans enzyme cytochrome P450 lanosterol 14α-demethylase.The results of in vitro antifungal activity and docking study showed that synthesized compounds had potential antifungal activity and can be further optimized and developed as a lead compound.
