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In this paper, we study the formation of optical bistability (OB) and optical multistability (OM) in a degenerate four-level atomic system by an external magnetic field that is excited by a probe laser field, a coupling laser field and a signal laser field. The coupling field can cause electromagnetically induced transparency (EIT) for the probe field in the atomic medium, while the signal field and/or external magnetic field can switch between single-EIT and two-EIT regimes. Based on these properties, OB and OM effects can be formed at two different frequency regions of the probe field (two channels). By adjusting the magnetic field or the intensity and the frequency of laser fields, the threshold intensity and the width of OB or OM can also be changed simply. The model can be useful for experimental observations and applications in modern photonic devices.
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The detection of N-nitrosamines in drug products has raised global regulatory interest in recent years due to the carcinogenic potential of some nitrosamines in animals and a need to identify a testing strategy has emerged. Ideally, methods used would allow for the use of quantitative analysis of dose-response data from in vivo genotoxicity assays to determine a compound-specific acceptable intake for novel nitrosamines without sufficient carcinogenicity data. In a previous study we compared the dose-response relationships of N-nitrosodiethylamine (NDEA) in three in vivo genotoxicity endpoints in rats. Here we report a comparison of NDEA's genotoxicity profile in mice. Big Blue® mice were administered NDEA at doses of 0.001, 0.01, 0.1, 1 and 3 mg/kg/day by oral gavage for 28 days followed by 3 days of expression. Statistically significant increases in the NDEA induced mutations were detected by both the transgenic rodent mutation assay (TGR) using the cII endpoint and by duplex sequencing in the liver but not bone marrow of mice. In addition, administration of NDEA for two consecutive days in male C57BL/6N mice caused elevated DNA damage levels in the liver as measured by % tail DNA in comet assay. The benchmark dose (BMD) analysis shows a BMDL50 of 0.03, 0.04 and 0.72 mg/kg/day for TGR, duplex sequencing and comet endpoints, respectively. Overall, this study demonstrated a similar genotoxicity profile of NDEA between mice and rats and provides a reference that can be used to compare the potential potency of other novel nitrosamines for the induction of gene mutations.
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Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary exposures to foods contaminated with aflatoxin-producing molds. Intracellular metabolic activation of aflatoxin B1 (AFB1) to a reactive epoxide generates highly mutagenic AFB1-Fapy-dG adducts. Previously, we demonstrated that repair of AFB1-Fapy-dG adducts can be initiated by the DNA glycosylase NEIL1 and that male Neil1-/- mice were significantly more susceptible to AFB1-induced HCC relative to wild-type mice. To investigate the mechanisms underlying this enhanced carcinogenesis, WT and Neil1-/- mice were challenged with a single, 4 mg/kg dose of AFB1 and frequencies and spectra of mutations were analyzed in liver DNAs 2.5 months post-injection using duplex sequencing. The analyses of DNAs from AFB1-challenged mice revealed highly elevated mutation frequencies in the nuclear genomes of both males and females, but not the mitochondrial genomes. In both WT and Neil1-/- mice, mutation spectra were highly similar to the AFB1-specific COSMIC signature SBS24. Relative to wild-type, the NEIL1 deficiency increased AFB1-induced mutagenesis with concomitant elevated HCCs in male Neil1-/- mice. Our data establish a critical role of NEIL1 in limiting AFB1-induced mutagenesis and ultimately carcinogenesis.
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This paper contains descriptions and illustrations of five new species of the genus Aulacocentrum Brues, 1922, from Vietnam, viz. Aulacocentrumassitum Long & Pham, sp. nov.; A.glabrum Long, sp. nov.; A.imparum Long & van Achterberg, sp. nov.; A.intermedium Long & van Achterberg, sp. nov.; and A.simulatum Long, sp. nov. Additionally, Aulacocentrumseticella van Achterberg & He is newly recorded for Vietnam's braconid fauna. A checklist and a key to the Oriental and East Palaearctic Aulacocentrum species is provided and the in-country distribution of the Vietnamese species is given.
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INTRODUCTION: Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. METHODS: We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. RESULTS: With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). DISCUSSION: HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. CONCLUSION: This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.
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Coinfecção , Infecções por HIV , Hospitalização , Humanos , Infecções por HIV/complicações , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeAssuntos
Botulismo , Humanos , Botulismo/epidemiologia , Botulismo/etiologia , Vietnã/epidemiologia , Fatores de RiscoRESUMO
In this study, the gamma ray-induced Maillard reaction method was carried out for chitosan (CTS) and glucosamine (GA) to improve the water solubility and antibacterial activity. The mixture solution of CTS and GA was exposed to gamma rays at a dose of 25 kGy and freeze-dried to obtain a Maillard reaction product (MRP) powder. The physicochemical and biological properties of the CTS-GA MRP powder were investigated. The CTS-GA MRP powder expressed good solubility at a concentration of 0.05 g/mL. In addition, the result of the antibacterial activity test against Escherichia coli revealed that the CTS-GA MRP powder exhibited highly antibacterial activity at pH 7; in particular, bacterial density was reduced by over 4 logs. Furthermore, the cytotoxicity test of the CTS-GA MRP powder on mouse fibroblast cells (L929) showed non-cytotoxicity with high cell viability (>90%) at concentrations of 0.1-1 mg/mL. Owing to the high antibacterial activity and low cytotoxicity, the water-soluble CTS-GA MRP powder can be used as a favorable natural preservative for food and cosmetics.
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Although the undermining of the nursing profession, time constraints, and the lack of inclusive teaching of evidence-based nursing (EBN) in the nursing school's curriculum have long been identified as being some of the main barriers to the adoption of evidence-based practice (EBP) by nurses, the specific role of nurse leaders in directly influencing and supporting evidence-based nursing is not well demonstrated. This opinion piece discusses potential factors that influence the implementation of EBP into clinical routine practice, as well as how nursing leadership styles can contribute to its promotion in contemporary healthcare settings.
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Enfermagem Baseada em Evidências , Liderança , Humanos , Prática Clínica Baseada em Evidências , CurrículoRESUMO
N-Nitrosodiethylamine (NDEA), a well-studied N-nitrosamine, was tested in rats to compare the dose-response relationship of three genotoxicity endpoints. Mutant / mutation frequencies were determined using the transgenic rodent (TGR) gene mutation assay and error corrected next generation sequencing (ecNGS) (i.e., duplex sequencing (DS)), and genetic damage was detected by the alkaline comet assay. Big Blue® (cII Locus) animals (n = 6 per dose group) were administered doses of 0.001, 0.01, 0.1, 1, 3 mg/kg/day NDEA by oral gavage. Samples were collected for cII mutation and DS analyses following 28-days of exposure and 3 days recovery. In a separate study, male Sprague-Dawley (SD) rats (n = 6 per dose group) were administered the same doses by oral gavage for two consecutive days and then samples collected for the alkaline comet assay. A dose-related increase in mutant / mutation frequencies of the liver but not duodenum was observed using the TGR assay and DS with DS resulting in a slightly more sensitive response, with a lower benchmark dose (BMD). In addition, a dose-related increase in percent tail DNA was observed in the liver using the alkaline comet assay. Therefore, DS and comet assays showed good utility for hazard identification and dose-response analysis of a representative N-nitrosamine comparable to the TGR gene mutation assay.
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Dietilnitrosamina , Nitrosaminas , Ratos , Animais , Masculino , Ensaio Cometa/métodos , Dietilnitrosamina/toxicidade , Roedores , Ratos Sprague-Dawley , Mutação , Animais Geneticamente Modificados , Dano ao DNA , Sequenciamento de Nucleotídeos em Larga Escala , Testes de Mutagenicidade/métodos , Relação Dose-Resposta a DrogaRESUMO
One of the most promising techniques for treating severe peripheral artery disease is the use of cellular tissue-engineered vascular grafts (TEVGs). This study proposes an inverse-gravity (IG) extrusion technique for creating long double-layered cellular TEVGs with diameters over 3 mm. A three-layered coaxial laminar hydrogel flow in an 8 mm-diameter pipe was realised simply by changing the extrusion direction of the hydrogel from being aligned with the direction of gravity to against it. This technique produced an extruded mixture of human aortic smooth muscle cells (HASMCs) and type-I collagen as a tubular structure with an inner diameter of 3.5 mm. After a 21 day maturation period, the maximal burst pressure, longitudinal breaking force, and circumferential breaking force of the HASMC TEVG were 416 mmHg, 0.69 N, and 0.89 N, respectively. The HASMC TEVG was endothelialised with human umbilical vein endothelial cells to form a tunica intima that simulated human vessels. Besides subcutaneous implantability on mice, the double-layered blood vessels showed a considerably lower adherence of platelets and red blood cells once exposed to heparinised mouse blood and were considered nonhaemolytic. The proposed IG extrusion technique can be applied in various fields requiring multilayered materials with large diameters.
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Aorta , Plaquetas , Humanos , Animais , Camundongos , Prótese Vascular , Células Endoteliais da Veia Umbilical Humana , HidrogéisRESUMO
Furan is an important heterocyclic scaffold in natural product, bioorganic, and medicinal chemistry as well as in materials science. The system S8/DABCO/DMSO was found to efficiently mediate the oxidative cyclization of 1,2,3,5-tetraarylpentan-1-ones A, which were obtained in situ as the Michael adducts of chalcones 1 and deoxybenzoins 2, to furan 3. The strategy provided convenient and direct access to tetrasubstituted furans 3 from readily available starting materials with high functional group tolerance.
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This paper describes Monolithic Microwave Integrated Circuits (MMICs) for an X-band radar transceiver front-end implemented in 0.25 µm GaN High Electron Mobility Transistor (HEMT) technology. Two versions of single pole double throw (SPDT) T/R switches are introduced to realize a fully GaN-based transmit/receive module (TRM), each of which achieves an insertion loss of 1.21 dB and 0.66 dB at 9 GHz, IP1dB higher than 46.3 dBm and 44.7 dBm, respectively. Therefore, it can substitute a lossy circulator and limiter used for a conventional GaAs receiver. A driving amplifier (DA), a high-power amplifier (HPA), and a robust low-noise amplifier (LNA) are also designed and verified for a low-cost X-band transmit-receive module (TRM). For the transmitting path, the implemented DA achieves a saturated output power (Psat) of 38.0 dBm and output 1-dB compression (OP1dB) of 25.84 dBm. The HPA reaches a Psat of 43.0 dBm and power-added efficiency (PAE) of 35.6%. For the receiving path, the fabricated LNA measures a small-signal gain of 34.9 dB and a noise figure of 2.56 dB, and it can endure higher than 38 dBm input power in the measurement. The presented GaN MMICs can be useful in implementing a cost-effective TRM for Active Electronically Scanned Array (AESA) radar systems at X-band.
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Error-corrected duplex sequencing (DS) enables direct quantification of low-frequency mutations and offers tremendous potential for chemical mutagenicity assessment. We investigated the utility of DS to quantify induced mutation frequency (MF) and spectrum in human lymphoblastoid TK6 cells exposed to a prototypical DNA alkylating agent, N-ethyl-N-nitrosourea (ENU). Furthermore, we explored appropriate experimental parameters for this application, and assessed inter-laboratory reproducibility. In two independent experiments in two laboratories, TK6 cells were exposed to ENU (25-200 µM) and DNA was sequenced 48, 72, and 96 h post-exposure. A DS mutagenicity panel targeting twenty 2.4-kb regions distributed across the genome was used to sample diverse, genome-representative sequence contexts. A significant increase in MF that was unaffected by time was observed in both laboratories. Concentration-response in the MF from the two laboratories was strongly positively correlated (r = 0.97). C:G>T:A, T:A>C:G, T:A>A:T, and T:A>G:C mutations increased in consistent, concentration-dependent manners in both laboratories, with high proportions of C:G>T:A at all time points. The consistent results across the three time points suggest that 48 h may be sufficient for mutation analysis post-exposure. The target sites responded similarly between the two laboratories and revealed a higher average MF in intergenic regions. These results, demonstrating remarkable reproducibility across time and laboratory for both MF and spectrum, support the high value of DS for characterizing chemical mutagenicity in both research and regulatory evaluation.
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DNA , Mutagênicos , Humanos , Reprodutibilidade dos Testes , Mutação , Mutagênicos/toxicidade , Mutagênese , EtilnitrosoureiaRESUMO
Mutagenicity testing is an essential component of health safety assessment. Duplex Sequencing (DS), an emerging high-accuracy DNA sequencing technology, may provide substantial advantages over conventional mutagenicity assays. DS could be used to eliminate reliance on standalone reporter assays and provide mechanistic information alongside mutation frequency (MF) data. However, the performance of DS must be thoroughly assessed before it can be routinely implemented for standard testing. We used DS to study spontaneous and procarbazine (PRC)-induced mutations in the bone marrow (BM) of MutaMouse males across a panel of 20 diverse genomic targets. Mice were exposed to 0, 6.25, 12.5, or 25 mg/kg-bw/day for 28 days by oral gavage and BM sampled 42 days post-exposure. Results were compared with those obtained using the conventional lacZ viral plaque assay on the same samples. DS detected significant increases in mutation frequencies and changes to mutation spectra at all PRC doses. Low intra-group variability within DS samples allowed for detection of increases at lower doses than the lacZ assay. While the lacZ assay initially yielded a higher fold-change in mutant frequency than DS, inclusion of clonal mutations in DS mutation frequencies reduced this discrepancy. Power analyses suggested that three animals per dose group and 500 million duplex base pairs per sample is sufficient to detect a 1.5-fold increase in mutations with > 80% power. Overall, we demonstrate several advantages of DS over classical mutagenicity assays and provide data to support efforts to identify optimal study designs for the application of DS as a regulatory test.
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Medula Óssea , Taxa de Mutação , Masculino , Camundongos , Animais , Procarbazina/toxicidade , Mutagênicos/toxicidade , Mutação , Testes de Mutagenicidade/métodos , Camundongos Transgênicos , Óperon LacRESUMO
BACKGROUND: Meta-analyses are on top of the evidence-based medicine pyramid, yet many of them are not completed after they are begun. Many factors impacting the publication of meta-analysis works have been discussed, and their association with publication likelihood has been investigated. These factors include the type of systematic review, journal metrics, h-index of the corresponding author, country of the corresponding author, funding sources, and duration of publication. In our current review, we aim to investigate these various factors and their impact on the likelihood of publication. A comprehensive review of 397 registered protocols retrieved from five databases was performed to investigate the different factors that might affect the likelihood of publication. These factors include the type of systematic review, journal metrics, h-index of the corresponding author, country of the corresponding author, funding sources, and duration of publication. RESULTS: We found that corresponding authors in developed countries and English-speaking countries had higher likelihoods of publication: 206/320 (p = 0.018) and 158/236 (p = 0.006), respectively. Factors affecting publications are the countries of corresponding author (p = 0.033), whether they are from developed countries (OR: 1.9, 95% CI: 1.2-3.1, p = 0.016), from English-speaking countries (OR: 1.8, 95% CI: 1.2-2.7, p = 0.005), update status of the protocol (OR: 1.6, 95% CI: 1.0-2.6, p = 0.033), and external funding (OR: 1.7, 95% CI: 1.1-2.7, p = 0.025). Multivariable regression retains three variables as significant predictors for the publication of a systematic review: whether it is the corresponding author from developed countries (p = 0.013), update status of the protocol (p = 0.014), and external funding (p = 0.047). CONCLUSION: Being on top of the evidence hierarchy, systematic review and meta-analysis are the keys to informed clinical decision-making. Updating protocol status and external funding are significant influences on their publications. More attentions should be paid to the methodological quality of this type of publication.
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Medicina Baseada em Evidências , Humanos , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
In 1967, the very first case of the Marburgvirus disease (MVD) was detected in Germany and Serbia sequentially. Since then, MVD has been considered one of the most serious and deadly infectious diseases in the world with a case-fatality rate between 23% and 90% and a substantial number of recorded deaths. Marburgvirus belongs to the family of Filoviridae (filoviruses), which causes severe viral hemorrhagic fever (VHF). Some major risk factors for human infections are close contact with African fruit bats, MVD-infected non-human primates, and MVD-infected individuals. Currently, there is no vaccine or specific treatment for MVD, which emphasizes the seriousness of this disease. In July 2022, the World Health Organization reported outbreaks of MVD in Ghana after two suspected VHF cases were detected. This was followed in February and March 2023 with the emergence of the virus in two countries new to the virus: Equatorial Guinea and Tanzania, respectively. In this review, we aim to highlight the characteristics, etiology, epidemiology, and clinical symptoms of MVD, along with the current prevention measures and the possible treatments to control this virus.
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Quirópteros , Ebolavirus , Doença pelo Vírus Ebola , Doença do Vírus de Marburg , Marburgvirus , Animais , Humanos , Doença do Vírus de Marburg/epidemiologia , Doença do Vírus de Marburg/prevenção & controle , Doença do Vírus de Marburg/diagnóstico , Surtos de Doenças , Fatores de RiscoRESUMO
The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2/genética , Anticorpos Monoclonais , Infecções Irruptivas , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
The public acceptability of a policy is an important issue in democracies, in particular for anti-COVID-19 policies, which require the adherence of the population to be applicable and efficient. Discrete choice experiment (DCE) can help elicit preference ranking among various policies for the whole population and subgroups. Using a representative sample of the French population, we apply DCE methods to assess the acceptability of various anti-COVID-19 measures, separately and as a package. Owing to the methods, we determine the extent to which acceptability depends on personal characteristics: political orientation, health vulnerability, or age. The young population differs in terms of policy preferences and their claim for monetary compensation, suggesting a tailored policy for them. The paper provides key methodological tools based on microeconomic evaluation of individuals' preferences for improving the design of public health policies.