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Microbiology Spectrum Jul 2024To monitor the resistance rate and gain a deeper understanding of the resistance mechanisms, we conducted over a 2-year surveillance focusing on the associated with the...
To monitor the resistance rate and gain a deeper understanding of the resistance mechanisms, we conducted over a 2-year surveillance focusing on the associated with the clinical usage of ceftazidime-avibactam (CZA) in a teaching hospital. A total of 4,641 . isolates were screened to identify the CZA resistance through antimicrobial susceptibility testing. Comprehensive analyses, including homology analysis, conjugation experiments, clone assays, and whole genome sequencing, were furtherly performed on the CZA-resistant strains. In total, four CZA-resistant (CZA-R-Kp) strains were separated from four patients, in which three of them received CZA treatment during the hospitalization, accounting for a 4% (3/75) resistance development rate of under CZA stress. All CZA-R-Kp isolates were found to possess variants of . The identified mutations included , , and a novel variant designated as , all of which were located in the Ω loop of the KPC enzyme. These mutations were found to impact the amino acid sequence and spatial structure of the enzyme's active center, consequently affecting KPC carbapenemase activity. This study underscores the importance of active surveillance to monitor the emergence of resistance to CZA, highlighting the need for ongoing research to develop effective strategies for combating antimicrobial resistance. Understanding the mechanisms behind resistance is crucial in maintaining the efficacy of CZA, a vital tool in the battle against multidrug-resistant infections.IMPORTANCEAs an effective drug for the treatment of carbapenem-resistant , ceftazidime-avibactam (CZA) began to develop resistance in recent years and showed an increasing trend. In order to effectively monitor the resistance rate of CZA and understand its resistance mechanism, we monitored for more than 2 years to find CZA-resistant strains. Through comprehensive analysis of the selected CZA-resistant strains, it was found that all the CZA-resistant strains had mutation, which could affect the activity of KPC carbapenemase. This study highlights the importance of proactive surveillance to monitor the emergence of CZA resistance, which highlights the need for ongoing research to develop effective strategies to combat antimicrobial resistance. Understanding the mechanisms behind resistance is critical to maintaining the effectiveness of CZA, an important tool in the fight against multidrug-resistant infections.
PubMed: 38958437
DOI: 10.1128/spectrum.00258-24 -
Environmental Science & Technology Jul 2024Monitoring of volatile organic compounds (VOCs) in air is crucial for understanding their atmospheric impacts and advancing their emission reduction plans. This study...
Monitoring of volatile organic compounds (VOCs) in air is crucial for understanding their atmospheric impacts and advancing their emission reduction plans. This study presents an innovative integrated methodology suitable for achieving semireal-time high spatiotemporal resolution three-dimensional measurements of VOCs from ground to hundreds of meters above ground. The methodology integrates an active AirCore sampler, custom-designed for deployment from unmanned aerial vehicles (UAV), a proton-transfer-reaction mass spectrometry (PTR-MS) for sample analysis, and a data deconvolution algorithm for improved time resolution for measurements of multiple VOCs in air. The application of the deconvolution technique significantly improves the signal strength of data from PTR-MS analysis of AirCore samples and enhances their temporal resolution by 4 to 8 times to 4-11 s. A case study demonstrates that the methodology can achieve sample collection and analysis of VOCs within 45 min, resulting in >120-360 spatially resolved data points for each VOC measured and achieving a horizontal resolution of 20-55 m at a UAV flight speed of 5 m/s and a vertical resolution of 5 m. This methodology presents new possibilities for acquiring 3-dimensional spatial distributions of VOC concentrations, effectively tackling the longstanding challenge of characterizing three-dimensional VOC distributions in the lowest portion of the atmospheric boundary layer.
PubMed: 38958408
DOI: 10.1021/acs.est.4c05669 -
Turkiye Parazitolojii Dergisi Jun 2024and are enteric protozoa that can cause a variety of gastrointestinal diseases, especially in vulnerable people like children, the elderly, and those with impaired...
OBJECTIVE
and are enteric protozoa that can cause a variety of gastrointestinal diseases, especially in vulnerable people like children, the elderly, and those with impaired immune systems. In order to ascertain the microbiological quality of the recreational water from Araromi Beach in Ilaje Local Government Area, Ondo State, Nigeria. This risk assessment is of great significance to human health protection against waterborne diseases. The aim of this study was to determine the microbial quality of recreational water from Araromi Beach in Ilaje Local Government Area, Ondo State, Nigeria.
METHODS
Microscopic examination of and oocysts were done.
RESULTS
Results revealed maximum occurrence of (20 oocysts/100 mL) of water sample in the month of April and maximum occurrence of (300 cysts/100 mL) of water sample in the month of June. Additionally, according to Kolmogorov-Smirnov tests for normalcy Ho =0.05, and were not regularly distributed in the water samples collected from the beach throughout the study period. The average likelihood of contracting and infections after consuming 100 mL of beach water was 0.96 and 0.35, respectively. The risks of infection associated with was lower than those associated with in water from the beach, but were both above the acceptable risk limit of 10-4.
CONCLUSION
The results of this study indicate that and may represent serious health hazards to people who engage in aquatic activities. Adopting a comprehensive strategy that includes regular inspections, enhanced detection techniques, and the prevention of aquatic environment pollution may provide clean and safe recreational water for all, thereby safeguarding the public's health.
Topics: Cryptosporidium parvum; Giardia lamblia; Nigeria; Humans; Seawater; Risk Assessment; Water Microbiology; Giardiasis; Cryptosporidiosis; Recreation; Oocysts
PubMed: 38958402
DOI: 10.4274/tpd.galenos.2024.69733 -
Journal of Immunology (Baltimore, Md. :... Jul 2024Activation of β-catenin in CD4+CD8+ double-positive (DP) thymocytes halts development before the thymic selection stage and predisposes to transformation....
Activation of β-catenin in CD4+CD8+ double-positive (DP) thymocytes halts development before the thymic selection stage and predisposes to transformation. Leukemogenesis, but not the developmental block, depends on TCF-1, β-catenin's DNA-binding partner. In this study, we show that β-catenin activation directs the DNA-binding protein HEB to block DP thymocyte development. Conditional loss of HEB in DP thymocytes with stabilized β-catenin restores the frequencies of postselection TCRβhi/CCR7+ and TCRβhi/CD69+ DPs and their cell-cycle profile. This recovery is associated with significant reversal of β-catenin-induced expression changes, particularly those related to the CD69+ DP cell signature and to cell-cycle pathways. Stabilizing β-catenin in DP thymocytes directs HEB binding to ≈11,000 novel DNA sites throughout the genome. Novel HEB sites mark most CD69+ DP cell signature genes that change expression upon activation of β-catenin and then revert after loss of HEB. Moreover, many of the novel HEB sites occupy promoter regions of genes enriched in mitotic cell cycle pathways. HEB binding to those regions correlates with downregulation of the associated genes, and HEB inactivation restores expression to physiologic levels. These findings highlight a molecular interplay between HEB and β-catenin that can impair thymic development.
PubMed: 38958395
DOI: 10.4049/jimmunol.2400160 -
Turkiye Parazitolojii Dergisi Jun 2024is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic...
OBJECTIVE
is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of (cinnamon) and (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible strains, and to determine their interaction with metronidazole by checkerboard method.
METHODS
Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method.
RESULTS
According to activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol.
CONCLUSION
It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.
Topics: Acrolein; Thymol; Cymenes; Drug Synergism; Metronidazole; Humans; Oils, Volatile; Thymus Plant; Trichomonas vaginalis; Monoterpenes; Female; Cinnamomum zeylanicum; Antiprotozoal Agents; Microbial Sensitivity Tests; Drug Resistance
PubMed: 38958374
DOI: 10.4274/tpd.galenos.2024.91855 -
Brazilian Journal of Medical and... 2024The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that...
The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.
Topics: Humans; Drug Resistance, Neoplasm; Breast Neoplasms; ATP Binding Cassette Transporter, Subfamily B; Drug Resistance, Multiple; Female; p21-Activated Kinases; Cell Line, Tumor; Blotting, Western
PubMed: 38958364
DOI: 10.1590/1414-431X2024e13357 -
Brazilian Journal of Medical and... 2024Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to...
Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.
Topics: Animals; Azoxymethane; Aberrant Crypt Foci; Proliferating Cell Nuclear Antigen; Male; Arbutin; Rats; bcl-2-Associated X Protein; Colon; Rats, Wistar; Fluorouracil; Carcinogens
PubMed: 38958363
DOI: 10.1590/1414-431X2024e13306 -
Chemistry (Weinheim An Der Bergstrasse,... Jul 2024Taspase 1 is a unique protease not only pivotal for embryonic development but also implicated in leukemias and solid tumors. As such, this enzyme is a promising while...
Taspase 1 is a unique protease not only pivotal for embryonic development but also implicated in leukemias and solid tumors. As such, this enzyme is a promising while still challenging therapeutic target, and with its protein structure featuring a flexible loop preceding the active site a versatile model system for drug development. Supramolecular ligands provide a promising complementary approach to traditional small-molecule inhibitors. Recently, the multivalent arrangement of molecular tweezers allowed the successful targeting of Taspase 1's surface loop. With this study we now want to take the next logic step und utilize functional linker systems that not only allow the implementation of novel properties but also engage in protein surface binding. Consequently, we chose two different linker types differing from the original divalent assembly: a backbone with aggregation-induced emission (AIE) properties to enable monitoring of binding and a calix[4]arene scaffold initially pre-positioning the supramolecular binding units. With a series of four AIE-equipped ligands with stepwise increased valency we demonstrated that the functionalized AIE linkers approach ligand binding affinities in the nanomolar range and allow efficient proteolytic inhibition of Taspase 1. Moreover, implementation of the calix[4]arene backbone further enhanced the ligands' inhibitory potential, pointing to a specific linker contribution.
PubMed: 38958349
DOI: 10.1002/chem.202401542 -
Ciencia & Saude Coletiva Jul 2024Public Health Emergencies (PHE) have had repercussions on health systems on a global scale, and timely access to new health technologies is a challenge for health...
Public Health Emergencies (PHE) have had repercussions on health systems on a global scale, and timely access to new health technologies is a challenge for health policy. The national regulatory authorities (NRA) play a key role in the evaluation and regulation of these technologies. The present study aims to analyze the main strategies and regulatory instruments used to deal with the challenges of regulating new technologies necessary for the health system's effective response during a PHE. This research, based on WHO and Brazilian NRA norms and documents, considered dimensions related to strategies for strengthening regulatory activities and regulatory instruments used to accelerate access to technologies, especially during PHEs. International cooperation between the NRA and the WHO were important strategies for strengthening the NRA, with emphasis on the use of reliance, regionalization, accelerated assessments, and work/information sharing, as well as the processes of regulatory harmonization and convergence. In addition to the use of existing regulatory instruments, efforts were also identified in order to implement new ones.
Topics: Brazil; Health Policy; Public Health; Humans; Emergencies; Biomedical Technology; World Health Organization; International Cooperation; Delivery of Health Care
PubMed: 38958323
DOI: 10.1590/1413-81232024297.03442024 -
Ciencia & Saude Coletiva Jul 2024This article aims to analyze the national scientific production on protective measures aimed at institutional care for at-risk children and adolescents in Brazil. By... (Review)
Review
This article aims to analyze the national scientific production on protective measures aimed at institutional care for at-risk children and adolescents in Brazil. By carrying out an integrative review, we seek to reflect on the main trends, themes, institutional actors, methodologies, and objectives of studies on the aforementioned measure and to analyze how the conditions and the right to health are presented and articulated in these references. Six thematic units were identified in the collection: Perceptions and roles of different actors in institutional reception processes; Processes of autonomy, dismissal, and causes of institutional care; Legislative aspects, evaluation of services, and identification of profiles; Family and community coexistence; Education and professional training; and Physical and mental health of sheltered children and adolescents. In Brazil, specifically, few studies investigate the concepts of the children and adolescents placed in shelters concerning protective measure processes or access to education. The link between poverty and institutionalization appears prominently and the scarcity of activities aimed primarily at family reintegration is evident. A large number of surveys point to the difficulties in implementing legislation.
Topics: Humans; Adolescent; Child; Brazil; Poverty; Child, Institutionalized; Child Health Services; Institutionalization
PubMed: 38958314
DOI: 10.1590/1413-81232024297.02902024