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Brazilian Oral Research 2023The current study aims to assess the effectiveness of e-learning in compliance with the new biosafety recommendations in dentistry in the context of COVID-19 applied to...
The current study aims to assess the effectiveness of e-learning in compliance with the new biosafety recommendations in dentistry in the context of COVID-19 applied to the clinical staff of a dental school in Brazil. A quasi-experimental epidemiological study was carried out by means of a structured, pre-tested online questionnaire, applied before and after an educational intervention, using an e-learning format. After data collection, statistical tests were performed. A total of 549 members of the clinical staff participated in the study in the two collection phases, with a return rate of 26.9%. After the e-learning stage, a reduction was found in the reported use of disposable gloves, protective goggles, and surgical masks. The course had no impact on the staff's knowledge concerning the proper sequence for donning PPE and showed 100% effectiveness regarding proper PPE doffing sequence. Knowledge about avoiding procedures that generate aerosols in the clinical setting was improved. Despite the low rate of return, it can be concluded that online intervention alone was ineffective in significantly improving learning about the new clinical biosafety guidelines. Therefore, the use of hybrid teaching and repetitive training is highly recommended.
Topics: Humans; Computer-Assisted Instruction; COVID-19; Brazil; Diazooxonorleucine; Dentistry
PubMed: 37341233
DOI: 10.1590/1807-3107bor-2023.vol37.0060 -
Frontiers in Public Health 2023The global impact of Coronavirus Disease 2019 (COVID-19) has been profound, affecting public health, the global economy, and overall human life. Past experiences with...
BACKGROUND
The global impact of Coronavirus Disease 2019 (COVID-19) has been profound, affecting public health, the global economy, and overall human life. Past experiences with global pandemics underscored the significance of understanding the perception of HCWs and hospital staff in developing and implementing preventive measures. The World Health Organization (WHO) provided protocols to manage the spread of COVID-19 and assist healthcare workers and health systems globally in maintaining high-quality health services.
OBJECTIVE
This study aims to assess nurses' perception, awareness, and compliance regarding the implementation of COVID-19 protocols and explore factors influencing their perception.
METHODOLOGY
A quantitative cross-sectional survey-based study was conducted, distributing a constructed survey among nurses in the Eastern Province of Saudi Arabia.
RESULTS
Out of 141 participants, most adhered to protocols such as hand sanitization, social distancing, and proper personal protective equipment (PPE) usage. The predominant age group among respondents was 31 to 40 years ( = 71, 50%). A significant portion of participants reported holding a bachelor's degree ( = 86, 61%), with only 14% possessing advanced degrees ( = 19). Nearly a third of the nurses in the study had accumulated 6 to 10 years of professional experience ( = 49, 34.8%). A noteworthy percentage of nurses were engaged in daily shifts exceeding 8 h ( = 98, 70%). Gender differences were observed, with females exhibiting a higher tendency to avoid shaking hands and social gatherings. Saudi nationals were more inclined to shake hands and engage in gatherings. Non-Saudi nurses and those aged between <25 to 40 years demonstrated proper donning/doffing practices. Nurses with over 6 years of experience avoided social gatherings, while those working >8 h adhered better to PPE usage, proper donning/doffing, and disposal of PPE in designated bins.
CONCLUSION
Understanding COVID-19 protocols is crucial for tailoring interventions and ensuring effective compliance with COVID-19 preventive measures among nurses. More efforts should be made toward preparing the healthcare nursing to deal with the outbreak. Preparing healthcare nursing with the right knowledge, attitude, and precautionary practices during the COVID-19 outbreak is very essential to patient and public safety.
Topics: Female; Humans; Adult; Saudi Arabia; Cross-Sectional Studies; COVID-19; Diazooxonorleucine; Perception; Nurses
PubMed: 38249370
DOI: 10.3389/fpubh.2023.1291261 -
British Journal of Anaesthesia Nov 2022Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. Hypoxia exerts extensive pathophysiological effects on the brain; however,...
BACKGROUND
Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood.
METHODS
Mice were acclimated to hypoxia (oxygen 10% for 8 h day) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms.
RESULTS
Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase.
CONCLUSIONS
Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain.
Topics: Animals; Mice; Acetylglucosamine; Sevoflurane; Glutamine; Diazooxonorleucine; Glutamate-Ammonia Ligase; Brain; Hypoxia; Glucose; Anesthetics, General; Oxygen; Glutamates
PubMed: 36031420
DOI: 10.1016/j.bja.2022.06.041 -
Drug Discoveries & Therapeutics Nov 2023This work describes a novel artificial intelligence-based training and monitoring system (AITMS) that was used to control and prevent nosocomial infections (NIs) by...
This work describes a novel artificial intelligence-based training and monitoring system (AITMS) that was used to control and prevent nosocomial infections (NIs) by improving the skills of donning/removing personal protective equipment (PPE). The AITMS has two working modes, namely an AI-based protective equipment surveillance mode and an AI-based training mode, that were used for routine surveillance and training, respectively. Data revealed that the accuracy rate of donning/removing PPE improved as a result of the AITMS. Interestingly, the frequency of NIs decreased with the use of the AITMS. This study suggested the key role of using PPE in controlling and preventing NIs. Data preliminarily proved that appropriate donning/removing PPE may help to reduce the risk of NIs. In addition, the newest computerized technologies, such as AI, have proven to be useful in controlling and preventing NIs. These findings should helpful to formulate a better strategy against NIs in the future.
Topics: Humans; Artificial Intelligence; Pilot Projects; Cross Infection; Diazooxonorleucine; Hospitals
PubMed: 37673650
DOI: 10.5582/ddt.2023.01068 -
International Journal of Molecular... May 2021Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and...
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis.
Topics: Animals; Antimetabolites, Antineoplastic; Cell Cycle; Cell Movement; Cell Proliferation; Cells, Cultured; Diazooxonorleucine; Glutamine; Glycolysis; Immunohistochemistry; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Smooth, Vascular; Neointima; Oxidative Phosphorylation; Platelet-Derived Growth Factor; Rats; Rats, Sprague-Dawley; Serum Albumin, Bovine
PubMed: 34070527
DOI: 10.3390/ijms22115602 -
JAMA Network Open Feb 2024Training on the proper use of personal protective equipment (PPE) is critical for infection prevention among health care workers. Traditional methods, such as... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Training on the proper use of personal protective equipment (PPE) is critical for infection prevention among health care workers. Traditional methods, such as face-to-face and video-based training, can strain resources and present challenges.
OBJECTIVE
To determine the effectiveness of 360° virtual reality (VR) training for PPE donning and doffing compared with face-to-face and video training in enhancing the PPE use skills of prospective health care practitioners.
DESIGN, SETTING, AND PARTICIPANTS
A blinded, prospective, and randomized noninferiority clinical trial was conducted from August to December 2021 at Teikyo University School of Medicine in Tokyo, Japan, with a mixed population of medical students. Participants were second- to fourth-year medicine, medical technology, or pharmacy students aged 20 years or older with no prior PPE training. Participants were randomized into 1 of 3 training groups (VR, face-to-face, or video) based on their enrollment order. An intention-to-treat analysis was conducted.
INTERVENTION
A 30-minute lecture on PPE procedures was delivered to all participants before the training. After the lecture, the VR group trained with an immersive 360° VR tool, the face-to-face group trained with actual PPE, and the video group trained by watching video footage on a computer and a projector. After 3 days, a standardized practical skills test was administered.
MAIN OUTCOMES AND MEASURES
The primary outcome was the mean score on a 20-point practical skills test, and the secondary outcome was the percentage of correct execution.
RESULTS
A total of 91 participants were recruited and randomized into 3 groups: VR (n = 30), face-to-face (n = 30), and video (n = 31) training. After excluding 1 participant due to illness, 90 participants (mean [SD] age, 24.2 [3.15] years; 54 males [60.0%]) completed the assessment. The mean (SD) scores were 17.70 (2.10) points for the VR group, 17.57 (2.45) points for the face-to-face group, and 15.87 (2.90) points for the video group. The VR group demonstrated no significant difference in performance from the face-to-face group. However, the VR group had significantly higher effectiveness than the video group (17.70 vs 15.87 points; P = .02).
CONCLUSIONS AND RELEVANCE
Results of this trial indicate that VR training was as effective as face-to-face training in enhancing PPE donning and doffing skills and was superior to video training. The findings suggest that VR training is a viable resource-conserving training option.
TRIAL REGISTRATION
Japan Registry of Clinical Trials Identifier: jRCT103021029.
Topics: Adult; Humans; Male; Young Adult; Diazooxonorleucine; Health Facilities; Health Personnel; Personal Protective Equipment; Schools; Female
PubMed: 38353953
DOI: 10.1001/jamanetworkopen.2023.55358 -
Bioorganic & Medicinal Chemistry Letters Oct 2021Two distinct diazo precursors, imidazotetrazine and nitrous amide, were explored as promoieties in designing prodrugs of 6-diazo-5-oxo-l-norleucine (DON), a glutamine...
Two distinct diazo precursors, imidazotetrazine and nitrous amide, were explored as promoieties in designing prodrugs of 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist. As a model for an imidazotetrazine-based prodrug, we synthesized (S)-2-acetamido-6-(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)-5-oxohexanoic acid (4) containing the entire scaffold of temozolomide, a precursor of the DNA-methylating agent clinically approved for the treatment of glioblastoma multiforme. For a nitrous amide-based prodrug, we synthesized 2-acetamido-6-(((benzyloxy)carbonyl)(nitroso)amino)-5-oxohexanoic acid (5) containing a N-nitrosocarbamate group, which can be converted to a diazo moiety via a mechanism similar to that of streptozotocin, a clinically approved diazomethane-releasing drug containing an N-nitrosourea group. Preliminary characterization confirmed formation of N-acetyl DON (6), also known as duazomycin A, from compound 4 in a pH-dependent manner while compound 5 did not exhibit sufficient stability to allow further characterization. Taken together, our model studies suggest that further improvements are needed to translate this prodrug approach into glutamine antagonist-based therapy.
Topics: Diazooxonorleucine; Drug Design; Drug Stability; Glutamine; Molecular Structure; Prodrugs
PubMed: 34400301
DOI: 10.1016/j.bmcl.2021.128321 -
Molecules (Basel, Switzerland) Aug 2022Cancer cells change their glucose and glutamine (GLU) metabolism to obtain the energy required to continue growing. Glutaminase (GLS) plays a crucial role in promoting...
Cancer cells change their glucose and glutamine (GLU) metabolism to obtain the energy required to continue growing. Glutaminase (GLS) plays a crucial role in promoting cell metabolism for cancer cell growth; targeting GLU metabolism by inhibiting GLS has attracted interest as a potential cancer management strategy. Herein, we employed a sequential screening of traditional Chinese medicine (TCM) database followed by drug-likeness and molecular dynamics simulations against the active site of GLS. We report 12 potent compounds after screening the TCM database against GLS, followed by a drug-likeness filter with Lipinski and Veber rule criteria. Among them, ZINC03978829 and ZINC32296657 were found to have higher binding energy (BE) values than the control compound 6-Diazo-5-Oxo-L-Norleucine, with BEs of -9.3 and -9.7 kcal/mol, respectively, compared to the BE of 6-Diazo-5-Oxo-L-Norleucine (-4.7 kcal/mol) with GLS. Molecular dynamics simulations were used to evaluate the results further, and a 100 ns MD simulation revealed that the hits form stable complexes with GLS and formed 2-5 hydrogen bond interactions. This study indicates that these hits might be employed as GLS inhibitors in the battle against cancer. However, more laboratory tests are a prerequisite to optimize them as GLS inhibitors.
Topics: Diazooxonorleucine; Early Detection of Cancer; Glutaminase; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Neoplasms; Neoplastic Processes
PubMed: 35956989
DOI: 10.3390/molecules27155042 -
Frontiers in Immunology 2020Transplant tolerance in the absence of long-term immunosuppression has been an elusive goal for solid organ transplantation. Recently, it has become clear that metabolic...
Transplant tolerance in the absence of long-term immunosuppression has been an elusive goal for solid organ transplantation. Recently, it has become clear that metabolic reprogramming plays a critical role in promoting T cell activation, differentiation, and function. Targeting metabolism can preferentially inhibit T cell effector generation while simultaneously promoting the generation of T regulatory cells. We hypothesized that costimulatory blockade with CTLA4Ig in combination with targeting T cell metabolism might provide a novel platform to promote the induction of transplant tolerance.
Topics: Abatacept; Allografts; Animals; Deoxyglucose; Diazooxonorleucine; Glycolysis; Immunosuppression Therapy; Immunosuppressive Agents; Lymphocyte Activation; Metformin; Mice; T-Lymphocytes; Transplantation Tolerance
PubMed: 32328063
DOI: 10.3389/fimmu.2020.00572 -
Clinical Cancer Research : An Official... Oct 2019Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive infantile brain tumors with poor survival. Recent advancements have highlighted significant molecular...
PURPOSE
Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive infantile brain tumors with poor survival. Recent advancements have highlighted significant molecular heterogeneity in AT/RT with an aggressive subgroup featuring overexpression of the proto-oncogene. We perform the first comprehensive metabolic profiling of patient-derived AT/RT cell lines to identify therapeutic susceptibilities in high MYC-expressing AT/RT.
EXPERIMENTAL DESIGN
Metabolites were extracted from AT/RT cell lines and separated in ultra-high performance liquid chromatography mass spectrometry. Glutamine metabolic inhibition with 6-diazo-5-oxo-L-norleucine (DON) was tested with growth and cell death assays and survival studies in orthotopic mouse models of AT/RT. Metabolic flux analysis was completed to identify combination therapies to act synergistically to improve survival in high MYC AT/RT.
RESULTS
Unbiased metabolic profiling of AT/RT cell models identified a unique dependence of high MYC AT/RT on glutamine for survival. The glutamine analogue, DON, selectively targeted high MYC cell lines, slowing cell growth, inducing apoptosis, and extending survival in orthotopic mouse models of AT/RT. Metabolic flux experiments with isotopically labeled glutamine revealed DON inhibition of glutathione (GSH) synthesis. DON combined with carboplatin further slowed cell growth, induced apoptosis, and extended survival in orthotopic mouse models of high MYC AT/RT.
CONCLUSIONS
Unbiased metabolic profiling of AT/RT identified susceptibility of high MYC AT/RT to glutamine metabolic inhibition with DON therapy. DON inhibited glutamine-dependent synthesis of GSH and synergized with carboplatin to extend survival in high MYC AT/RT. These findings can rapidly translate into new clinical trials to improve survival in high MYC AT/RT.
Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Cell Proliferation; Diazooxonorleucine; Female; Glutamine; Humans; Metabolome; Mice; Mice, Nude; Proto-Oncogene Mas; Proto-Oncogene Proteins c-myc; Rhabdoid Tumor; Teratoma; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 31300448
DOI: 10.1158/1078-0432.CCR-19-0189