Resistance Factors Research Articles

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes.

Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment. To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM. This was a case-control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12-18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ 2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant. There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112-5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859-2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039-26.279, P = 0.002). Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.

Evaluation of safety of Bifidobacterium and Lactobacillus strains and their synbiotic combination with isomalto-oligosaccharides against LPS-induced inflammation in murine macrophages

In this study, the safety of Bifidobacterium longum Bif10, Bifidobacterium breve Bif11, Lacticaseibacillus rhamnosus LAB3, and Lactiplantibacillus plantarum LAB39 was evaluated using in-vitro, genomics, and in-vivo approaches. In the in-vitro safety studies, mucin degradation, biogenic amine production and cytotoxicity on HEK-293 cells by these strains were evaluated. Whole genome sequencing and bioinformatics analysis were carried out to identify the genes responsible for mucin degradation, biogenic amine production, antibiotic resistance, and virulence factors. In-vivo safety was assessed after acute, subacute, and sub-chronic oral feeding with respective strains to the mice as per revised OECD guidelines. Histopathological examination, gut permeability, hematological, blood biochemistry, and oxidative stress were evaluated after sacrificing the animals. Further, the compatibility of the four strains was assessed and their synbiotic combination with isomaltooligosaccharides (IMOs) was evaluated for its potential in alleviating lipopolysaccharide (LPS) induced inflammation in murine macrophages. In-vitro studies indicated that the strains do not produce biogenic amines and were non-cytotoxic to HEK-293 cells. Whole genome analysis suggested a lack of transferable antibiotic-resistance genes or potentially lethal virulence factors and genes for biogenic amines. In vivo studies showed that the bacterial strains did not affect the health parameters related to blood or induce histological alterations in the vital organs. The four strains were compatible with each other and their synbiotic blend efficiently curtailed LPS-induced oxidative stress, inducible nitric oxide and proinflammatory cytokine production. Given these observations, Bif10, Bif11, LAB3, and LAB39 can be deemed safe and their synbiotic blend with IMOs could impart anti-inflammatory effects.

Virulence and resistance factors of Nakaseomyces glabratus (formerly known as Candida glabrata) in Europe: A systematic review.

Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus. To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years. The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: "Candida glabrata", "Nakaseomyces glabratus", "Europe", "resistance" and "Epidemiology" exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta-analyses and book chapters. Fifty-seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B. The number of candidemia cases associated with triazole-resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options.

Novel hybrid XGBoost-based soft computing models for predicting penetration resistance of buried pipelines in cohesive soils

In this paper, both the finite element limit analysis (FELA) and soft computing techniques of four hybrid XGBoost (XGB) models, namely, GA-XGB, optimized with Genetic Algorithms; SMA-XGB, optimized with Slime Mould Algorithms; PSO-XGB, optimized with Particle Swarm Optimization; ACO-XGB, Ant Colony Optimization; and one Genetic Programing model (GP), are employed to develop surrogate models for predicting the undrained penetration resistance of buried pipelines embedded in clays. The penetration resistance of pipelines is caused by internal and external pressures, resulting in a force that acts on the pipeline in the downward and inclined directions at the same time. The penetration resistance factor (N) of a buried pipeline is determined based on four dimensionless variables, namely, the buried depth ratio (H/D), the inclination angle of the applied load (β), the soil strength or overburden ratio (γH/c), and the adhesion factor at soil-pipeline interfaces (α). The findings of this study are presented and summarized in the form of charts for dimensionless penetration resistance factors (N) and failure mechanisms of pipelines. Furthermore, the results from this study are compared with the results from previous studies and agrees well with those of previous studies. According to the results of the four developed hybrid XGBoost-based models, SMA-XGB outperforms GA-XGB, PSO-XGB, and ACO-XGB with no symptoms of overfitting, while the GP model resulted in an adequately accurate model with the advantage of a closed-form equation; its determination correlation coefficient of training and testing equals 0.98 (R2 = 0.980).

Response surface method-based efficient approach for the load and resistance factors calibration of breakwater foundation considering soil spatial variability

This study aims to propose an efficient approach to calibrate the load and resistance factors (LRFs) for the limit state design of breakwater foundations. The spatial variability of soil was considered by employing the Cholesky decomposition technique. To overcome the low computational efficiency of the Monte Carlo simulation (MCS), a response surface method (RSM) was utilized. Additionally, an efficient algorithm, namely the adaptive boundary-based particle filtering algorithm (ABB-PFA), was proposed with the use of RSM to automatically and quickly search optimal nominal values of random variables in the LRF calibration process. Noticeably, the optimal number of particles and values of the modification factor used in the ABB-PFA were observed to enhance the efficiency of the calibration process. The results showed that the computational efficiency of the calibration process is significantly increased by utilizing the response surface method and the proposed ABB-PFA. The efficiency increases the most if the number of particles is one and the value of the modification factor is 0.5 or 0.6. The influences of the random field element size on the efficiency of the calibration process were also investigated. By using the appropriate size, the efficiency is significantly increased while still obtaining a high accuracy of the LRFs calibration process.

Conventional and unsupervised artificial intelligence analyses identified risk factors for antimicrobial resistance on dairy farms in the province of Québec, Canada

Antimicrobial resistance (AMR) is one of the greatest threats to global health worldwide and is threatening not only humans, but also animal production systems, including dairy farms. The objective of this paper was to describe risks factors associated with AMR on dairy farms in Québec, Canada. This observational cross-sectional study included 101 commercial dairy farms and took place between the springs of 2017 and 2018 for a one-year period. We explored risk factors such as farm practices and producer's knowledge (measured using a questionnaire), antimicrobial use (quantified using veterinary invoices), and the presence of Salmonella Dublin (tested by serology). We evaluated AMR with fecal Escherichia coli retrieved from pre-weaned calves and lactating cows using the following outcomes: the presence of extended-spectrum-β-lactamase/AmpC resistance and the number of resistances to antimicrobial classes. We used logistic regression models to evaluate the association between each risk factor and the 2 outcomes for the 2 types of samples (pre-weaned calves and lactating cows). Furthermore, we explored the relationships between these risk factors utilizing data dimensionality reduction and hierarchical clustering. Outputs of these analyses were used as regressors for AMR in regression models. While the results for univariate analyses were ambiguous, the unsupervised analysis naturally categorized the sample of farms according to their health/treatment status (dimension 1, explaining 12.9% of the variance) and herd size (dimension 2, explaining 7.8%). Three clusters of farms were identified (cluster 1: mainly healthy herds and low ceftiofur users, cluster 2: relatively high ceftiofur users, cluster 3: farms with a higher incidence of diseases and higher antimicrobial treatment rates). Dimension 1 and cluster membership were statistically associated with the presence of extended-spectrum-β-lactamase/AmpC resistance in lactating cows and in pre-weaned calves. Dimension 1 was also statistically associated with the number of resistances in lactating cows and in pre-weaned calves. This study highlights the complexity of analyzing risk factors associated with AMR. Our results suggest that the herd health status and the AMU-related practices used are associated with AMR in dairy farms. However, prospective studies are needed to confirm a causal relation.

Analysis of virus gene subtypes and drug resistance monitoring results of newly reported HIV/AIDS population in Anhui Province from 2020 to 2023

Objective: To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023. Methods: An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University's HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis. Results: A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance (χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4+T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4+T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion: The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4+T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

FLAx‐REinforced Aluminum (FLARE): A Bio‐Based Fiber Metal Laminate Alternative Combining Impact Resistance and Vibration Damping

Fiber metal laminates (FMLs) have mainly been used in aerospace applications with synthetic fibers. To improve their environmental credentials and address issues regarding the end‐of‐life of these materials, a shift to FMLs based on natural fibers can be a promising course of action. However, regarding them as conventional FMLs overlook some of the unique benefits of natural fibers. Therefore, this study pioneers the examination of FLAx‐REinforced aluminum (FLARE) for its combined impact resistance and vibration damping. Dynamic mechanical analysis and vibration beam tests demonstrate that the metallic layer predominantly influences the damping behavior of FLARE. The loss factor notably decreases with aluminum addition (by 80% compared to the flax composite), approximated via an inverse mixture rule. Low‐velocity impact tests highlight the role of aluminum layers in energy absorption and the composite strength as a critical factor in impact resistance. FLARE exhibits 25% less specific energy absorption compared to its glass fiber counterpart. A quasi‐static analytical model suggests the potential of FLARE for practical applications. With its balance of properties and considering its potential advantages at end‐of‐life, allowing recycling of aluminum, and its expected lower carbon footprint, FLARE renders potential beyond the aerospace sector, e.g., in other forms of transportation.

A Reliability-Based Design Approach for the Flexural Resistance of Compression Yielded Fibre-Reinforced Polymer (FRP)-Reinforced Concrete Beams

Fibre-reinforced polymer (FRP) reinforcement has been employed as an alternative to conventional steel reinforcement in concrete structures, which is attributed to its excellent strength and corrosion resistance. However, one drawback is that FRP reinforcements are brittle and affect the ductility of concrete structures. One of the recent effective techniques proposed to overcome ductility issues is the compression yielding (CY) concept. The CY mechanism allows the structure to fail differently than the conventional FRP-reinforced concrete structure. Thus, the existing design recommendations as per the current codes for FRP-reinforced concrete structures are not appropriate. Hence, reliability studies are crucial for the development of a functional CY beam design in order to emphasise the structure’s lifetime performance and to guarantee safety requirements. In this study, a reliability-based design approach is developed for a compression-yielded FRP-reinforced concrete beam (CY beam) using load and resistance factor design (LRFD). Firstly, the flexural failure modes of CY beams are discussed. The uncertainties involved in the development of the probabilistic model for the CY beam are defined. A case study is consequently conducted for a CY beam with random variables that are associated with the statistical characteristics of material properties and load. The reliability analysis method employed in this research is the Hasofer–Lind method. The results suggest the importance of choosing appropriate design variables and stochastic parameters for CY blocks that contribute to a higher level of reliability. The reliability index and resistance factors of a CY beam are then evaluated using the Monte Carlo Simulation computational method. The reliability index value of 3.336 is obtained from the simulation, which indicates that the CY beam demonstrates ductile behaviour. The results not only demonstrate ductile behaviour but also contribute to a possible reduction in material costs and a substantial safety margin. When compared to conventional FRP-reinforced concrete beams, for different load ratios, CY beams showed higher resistance and better reliability levels.

Genomic analysis of &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; strains virulence and antibiotic resistance

Recently, Klebsiella pneumoniae strains have become widespread both in community-acquired infectious processes and in nosocomial infections. There are two pathotypes of K. pneumoniae: classical (cKp) and hypervirulent (hvKp). Representatives of any pathotype are prone to acquire and further transmit genetic factors of antibiotic resistance and virulence. This combination accounts for severity of the infectious process. Therefore, information about whether the strain belongs to either pathotype can help in prescribing proper therapy. Since there is no consensus upon hypervirulence marker, we attempted to find the most significant combinations of genetic markers of virulence and antibiotic resistance in K. pneumoniae strains. The study was aimed to conduct a genomic analysis of virulence and antibiotic resistance of K. pneumoniae clinical isolates. Materials and methods. There were examined 85 strains of K. pneumoniae isolated from diverse clinical material samples from patients in large St. Petersburg hospitals. In our work, we used classical bacteriological methods, including determination of the hypermucoviscous type using the “string test”, the mass spectrometric method (MALDI-ToF MS) for identifying bacteria, molecular methods for studying markers of virulence and antibiotic resistance (multilocus sequence typing, genome sequencing of K. pneumoniae strains). Results. Among the studied K. pneumoniae strains, the most common carbapenemase genes were OXA-48 (18.7%) and NDM-1 genes — 17.3% of strains; in 6.7% of strains, NDM-1 and OXA-48 genes were found simultaneously. The percentage of strains with β-lactamase genes CTX-M-15 was 54.7%, OXA-1 — 17.3%, TEM-1D — 13.3%, and in 17.3% of cases the OXA-1 and TEM-1D genes were simultaneously present in bacterial strains. Quinolone resistance genes were found in 68.4% of strains. The most common genes were qnrS1 (40% of strains) and qnrB1 (22.7%). Phenotypic antimicrobial susceptibility testing showed that 23.5% and 64.7% strains were resistant to colistin and carbapenems, respectively. 32.9% K. pneumoniae strains, isolated in patients with phlegmon, pneumonia, sepsis, and peritonitis, had a hypermucoid phenotype. The most common sequence types were: ST395 (24.3%), ST23 (17.6%) and ST512 (9.5%). 8% and 25.3% of strains belonged to capsule types K1 and K2, respectively. The polyketide synthesis locus ybt, which characterizes virulent strains, was detected in 69.3% isolates, and the clb locus was present in 10.7% of strains. In 73.3% and 14.7% strains, the plasmid-associated virulence loci iuc and iro were identified, which encode the biosynthesis of the siderophores aerobactin and salmochelin. We described 44 cases (58.7% of strains) of genotypic convergence of virulence and antibiotic resistance, as shown by simultaneously detected the aerobactin (iuc) locus and β-lactamase or carbapenemase genes. Thus, identification of hypervirulence may provide valuable information for the clinical management of patients with hvKp infections. Therefore, it is is obviously necessary to develop comprehensive diagnostic test for simultaneous screening of multidrug-resistant hypervirulent K. pneumoniae strains.

Phenolic Compounds in Different Stages of Ontogenesis in Chrysanthemum—A Potential for Thrips-Resistance Characterisation

A number of studies have indicated the potential role of secondary metabolites, referred to as ‘resistance factors’, in plant defence against insect pests. Nevertheless, it remains unclear which metabolites serve as predictors of resistance in chrysanthemum cultivars against thrips. In the present study, the phenolic compounds of chrysanthemum leaves at different ontogenetic stages were analysed using high-performance liquid chromatography (HPLC). Furthermore, the relative epidermal flavonol contents in the leaves were quantified using the Dualex® Scientific 4 sensor, and the suitability of this non-destructive method for the rapid discrimination of resistance levels was evaluated. The results demonstrated that the most notable discrepancies in phenolic metabolite profiles were observed in the older leaves and the vegetative state of the chrysanthemum plants. Multiple discriminant analysis was conducted using HPLC-analysed metabolites to predict the importance of metabolites in resistant, susceptible, or highly susceptible plants in the vegetative stage. The results demonstrated that multiple metabolites, rather than a single metabolite, are responsible for thrips resistance in chrysanthemum. However, the relative flavonol content did not reflect the HPLC-analysed flavonoid glycosides or hydroxycinnamic acid derivatives, indicating that the Dualex® sensor is not a suitable device for determining resistance levels in chrysanthemums. Testing is required to extend and analyse the results in greater depth.

Staphylococcus spp. in Salad Vegetables: Biodiversity, Antimicrobial Resistance, and First Identification of Methicillin-Resistant Strains in the United Arab Emirates Food Supply.

Contamination of leafy greens with Staphylococcus spp. can occur at various supply chain stages, from farm to table. This study comprehensively analyzes the species diversity, antimicrobial resistance, and virulence factors of Staphylococci in salad vegetables from markets in the United Arab Emirates (UAE). A total of 343 salad items were sampled from three major cities in the UAE from May 2022 to February 2023 and tested for the presence of Staphylococcus spp. using standard culture-based methods. Species-level identification was achieved using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antimicrobial susceptibility testing was conducted using the VITEK-2 system with AST-P592 cards. Additionally, whole genome sequencing (WGS) of ten selected isolates was performed to characterize antimicrobial resistance determinants and toxin-related virulence factors. Nine Staphylococcus species were identified in 37.6% (129/343) of the tested salad items, with coagulase-negative staphylococci (CoNS) dominating (87.6% [113/129]) and S. xylosus being the most prevalent (89.4% [101/113]). S. aureus was found in 4.6% (14/343) of the salad samples, averaging 1.7 log10 CFU/g. One isolate was confirmed as methicillin-resistant S. aureus, harboring the mecA gene. It belonged to multi-locus sequence type ST-672 and spa type t384 and was isolated from imported fresh dill. Among the characterized S. xylosus (n = 45), 13.3% tested positive in the cefoxitin screen test, and 6.6% were non-susceptible to oxacillin. WGS analysis revealed that the cytolysin gene (cylR2) was the only toxin-associated factor found in S. xylosus, while a methicillin-sensitive S. aureus isolate harbored the Panton-Valentine Leukocidin (LukSF/PVL) gene. This research is the first to document the presence of methicillin-resistant S. aureus in the UAE food chain. Furthermore, S. xylosus (a coagulase-negative staphylococcus not commonly screened in food) has demonstrated phenotypic resistance to clinically relevant antimicrobials. This underscores the need for vigilant monitoring of antimicrobial resistance in bacterial contaminants, whether pathogenic or commensal, at the human-food interface.

Escherichia coli novel sequence type 11873 harbours a new CTX-M-15–carrying multidrug resistance type 1/2 hybrid IncC plasmid

ObjectiveThe aim of the current study was to determine the genomic map of the resistance genes of two CTX-M-15–carrying Escherichia coli strains belonging to novel sequence type (ST) 11873. Complete, closed genome sequences of the E. coli strains were obtained by applying a combination of short-read Illumina and long-read Oxford Nanopore-based sequencing. MethodsIsolation of E. coli was performed using ECC CHROMagar and antibiotic sensitivity patterns were determined using Sensititre EUVSEC plates. Whole-genome sequencing was performed for two E. coli strains (3–338 and 5–325) using Illumina MiSeq- and Oxford Nanopore MinION-based sequencing. ResultsThe complete genome of strain 3–338 (GenBank accession no. CP130007–17) was assembled into a circular chromosome of 4.65 Mb and 10 plasmids (between 2 and 148 kb). Strain 5–325 (CP130018–27) exhibited a circular chromosome of 4.7 Mb and 9 plasmids (between 2 and 148 kb). Both strains carried an identical type 1/2 hybrid IncC plasmid (∼148 kb) harbouring multiple antibiotic resistance genes (ARGs), including blaCTX−M-15, blaOXA-1, blaTEM-1, qnrS1, sul2, aphA1, aacC2, mph(A) and floR. This plasmid also carried heavy metal resistance genes, such as chrA and arsR. Strain 5–325 carried an additional IncFIB plasmid (∼78 kb) harbouring additional ARGs, including blaTEM-1, qnrS1, tet(A), dfrA14, sul2, strA and strB. ConclusionsOur study shows the emergence of a CTX-M-15–carrying type 1/2 hybrid IncC plasmid in novel E. coli ST11873. These findings emphasise the need for population-based sewage surveillance for understanding the prevalence of antibiotic resistance in pathogens in order to mitigate the further spread of such resistance factors.

Amino acid substitutions in succinate dehydrogenase complex conferring resistance to the SDHI fungicide pydiflumetofen in Cochlibolus heterostrophus causing southern corn leaf blight1

Southern corn leaf blight (SCLB) caused by Cochlibolus heterostrophus, is a widespread foliar disease that has a substantial impact on maize yield in the Huanghuaihai region of China. Pydiflumetofen (Pyd), a new succinate dehydrogenase inhibitor (SDHI), has been found as a promising fungicide for the efficient control of SCLB, however, resistance of C. heterostrophus to Pyd has not been studied well. Here, five Pyd-resistant mutants were generated through fungicide adaptation. Sequence alignment analysis revealed that these mutants primarily mutated in ChSdhB and ChSdhD, with 3 genotypes: ChSdhBH277Y, ChSdhBI279T and ChSdhDH133Y, exhibiting two distinct categories of resistance: high resistance (HR) and moderate resistance (MR), which resistance factors (RF) is 214.22 and 44.33-53.67, respectively. These mutants were more pathogenic than the wild-type parental strains, but there was a significant reduction in mycelial growth rate and sporulation in the resistant mutants, indicating a significant fitness cost associated with resistance to Pyd. In addition, this study revealed a positive cross-resistance between Pyd and another SDHI fungicide cyclobutrifluram. However, no cross-resistance was found between Pyd and other classes of fungicide, including prochloraz, fludioxonil, iprodioneand pyraclostrobin. Homology modeling and molecular docking further confirmed that point mutation of ChSdhBH277Y, ChSdhBI279T, and ChSdhDH133Y could reduce binding affinity between Pyd and its target subunits from −74.07, −74.07, −152.52 kcal mol-1 to −3.90, −4.95, −9.93 kcal/mol, respectively. These findings not only provided valuable insights for managing SCLB caused by C. heterostrophus, but also enhanced our understanding of molecular mechanism underlying plant pathogen resistance to Pyd.

The dynamics of the midgut microbiome in Aedes aegypti during digestion reveal putative symbionts.

Blood-feeding is crucial for the reproductive cycle of the mosquito Aedes aegypti, as well as for the transmission of arboviruses to hosts. It is postulated that blood meals may influence the mosquito microbiome but shifts in microbial diversity and function during digestion remain elusive. We used whole-genome shotgun metagenomics to monitor the midgut microbiome in 60 individual females of A. aegypti throughout digestion, after 12, 24, and 48 h following blood or sugar meals. Additionally, ten individual larvae were sequenced, showing microbiomes dominated by Microbacterium sp. The high metagenomic coverage allowed for microbial assignments at the species taxonomic level, also providing functional profiling. Females in the post-digestive period and larvae displayed low microbiome diversities. A striking proliferation of Enterobacterales was observed during digestion in blood-fed mosquitoes. The compositional shift was concomitant with enrichment in genes associated with carbohydrate and protein metabolism, as well as virulence factors for antimicrobial resistance and scavenging. The bacterium Elizabethkingia anophelis (Flavobacteriales), a known human pathogen, was the dominant species at the end of blood digestion. Phylogenomics suggests that its association with hematophagous mosquitoes occurred several times. We consider evidence of mutually beneficial host-microbe interactions raised from this association, potentially pivotal for the mosquito's resistance to arbovirus infection. After digestion, the observed shifts in blood-fed females' midguts shifted to a sugar-fed-like microbial profile. This study provides insights into how the microbiome of A. aegypti is modulated to fulfil digestive roles following blood meals, emphasizing proliferation of potential symbionts in response to the dynamic midgut environment.

Prevalence of risk factors for venous thromboembolism and aspirin resistance in Australian patients undergoing total hip and knee arthroplasty.

Aspirin is used for venous thromboembolism (VTE) prophylaxis after total hip and knee arthroplasty (THA/TKA). However, its efficacy is unclear in patients with multiple VTE risk factors and at risk of aspirin resistance (AR). To determine the prevalence of risk factors for VTE and AR in patients after THA/TKA and to determine the relationship between risk factors and drugs prescribed for thromboprophylaxis. A retrospective cohort study of elective-THA/TKA in six Australian hospitals over a 1-year period. Medical records were manually reviewed to determine demographics, thromboprophylaxis regimen and presence of risk factors. The relationship between individual and cumulative risk factors with the thromboprophylaxis regimen was determined. In total, 1011 patients were included with a mean (SD) age of 65.9 (±11.0) years, and 56.4% were female. The five most prevalent risk factors were obesity (59.1%), age ≥65 years (58.2%), hypertension (45.3%), dyslipidaemia (35.9%) and diabetes (19.7%). Most patients had ≥1 risk factor for VTE (93.6%) and AR (93.6%), with 49.0% and 35.0% having ≥3 concurrent VTE and AR risk factors, respectively. The only significant relationship between risk factors and drugs was diabetes (P < 0.01). Rivaroxaban was more commonly used as the number of concurrent VTE risk factors increased (P < 0.05). Patients had a high prevalence of VTE and AR risk factors, suggesting aspirin may not be beneficial in many patients. Only diabetes was linked to the selection of thromboprophylaxis. Patients who received rivaroxaban had a greater average number of VTE risk factors. Guidelines should promote individualised prescribing in higher-risk patients.

Microbial Etiology, Antimicrobial Resistance, and Risk Factors of Surgical Site Infections in Gestational Diabetes Mellitus Patients Undergoing Elective Pre-Labor Cesarean Deliveries.

Gestational Diabetes Mellitus (GDM) significantly increases the risk of adverse pregnancy outcomes, including elective pre-labor cesarean deliveries. Postoperative surgical site infections (SSIs) pose a significant concern, underscoring the need for a detailed investigation into their causes and preventative measures. The aim of this study is to systematically identify and analyze the microbial etiology and antimicrobial resistance profiles of pathogens responsible for SSIs in GDM patients undergoing elective pre-labor cesarean deliveries. Additionally, this research aims to elucidate the risk factors contributing to SSIs, with a specific focus on operation duration, amniotic fluid contamination, and genital tract inflammation, and their correlation with the incidence of SSIs. A retrospective analysis was conducted at our Hospital between September 2018 and July 2023, involving 150 GDM patients who underwent elective pre-labor cesarean deliveries. Patients were categorized into infected and uninfected groups based on postoperative SSIs. Clinical data were meticulously collected and analyzed using SPSS software (version 27.0). Independent sample t-tests and chi-square tests were employed for statistical analysis. Microbial profiling revealed that Gram-negative bacteria, primarily E. coli, constituted approximately 59.46% of the isolated strains, exhibiting significant resistance to commonly used antibiotics such as ampicillin and cefotaxime. Elevated levels of biomarkers, including Procalcitonin (PCT) and Hemoglobin A1c (HbA1c), were significantly associated with SSIs. Multivariate logistic regression analysis identified operation time ≥1-hour, amniotic fluid contamination, and genital tract inflammation as significant risk factors. This study highlights the microbial etiology, resistance patterns, and risk factors for SSIs in GDM cesarean patients, emphasizing the need for tailored preoperative evaluations.

Characterizing HIV drug resistance in cases of vertical transmission in the VESTED randomized antiretroviral treatment trial.

VESTED (NCT03048422) compared the safety and efficacy of three antiretroviral treatment (ART) regimens in pregnant and postpartum women: dolutegravir+emtricitabine/tenofovir alafenamide fumarate; dolutegravir+emtricitabine/tenofovir disoproxil fumarate (TDF); efavirenz/emtricitabine/TDF. Vertical HIV transmission (VT) occurred to 4/617 (0.60%) live-born infants, who were evaluated for HIV drug resistance (HIVDR) and other risk factors. In 2018-2020, pregnant (weeks-14-28) women living with HIV and ≤14 days of ART were enrolled at 22 international sites and followed with their infants through 50 weeks postpartum. HIV sequences derived by single genome amplification (SGA) from longitudinally collected specimens were assessed from VT Cases for HIVDR in protease, reverse transcriptase, integrase, and the nef 3'polypurine tract (3'PPT). The four Case mothers were prescribed efavirenz-based-ART for 1-7 days prior to randomization to study ART. Their infants received postnatal nevirapine+/-zidovudine prophylaxis and were breastfed. A total of 833 SGA sequences were derived. The "major" (Stanford HIVDR Score ≥60) non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation (K103N) was detected persistently in one viremic mother, and likely contributed to VT of HIVDR. Major NNRTI HIVDR mutations were detected in all three surviving infants. No integrase, nor high frequencies of 3'PPT mutations conferring dolutegravir HIVDR were detected. The timing of HIV infant diagnosis, plasma HIV RNA levels and HIVDR suggests one in utero, one peripartum, one early, and one late breastfeeding transmission. VT was rare. New-onset NNRTI HIVDR in Case mothers was likely from efavirenz-ART prescribed prior to study dolutegravir-ART, and in one case appeared transmitted to the infant despite nevirapine prophylaxis.

Timing, type, and impact of thromboembolic events caused by flow diversion: a 10-year experience.

Thromboembolic (TE) events are among the most feared complications after flow diversion (FD) and have been reported to occur even with adequate dual antiplatelet therapy. Herein, the authors characterize thrombotic and embolic events that developed after FD, focusing on the morbidity of each of these events and the predisposing factors associated with their development. A retrospective analysis of aneurysms treated with FD at a single institution in the US between 2013 and 2023 was performed. The authors documented the emergence of intraprocedural and postoperative TE events. A survival analysis and a Cox regression model was conducted to identify predictors associated with these events. The authors included 651 procedures performed in 591 patients to treat 746 aneurysms. TE events occurred in 38 of the procedures performed (5.8%), causing permanent deficit in 20 patients and death in 4 patients. Eleven cases presented with acute stent thrombosis, 11 with large-vessel occlusion, and 9 with perforator strokes. At a median follow-up of 9.5 months, 73.0% of patients with an ischemic event had a modified Rankin Scale score ≤ 2. Three of the deaths were secondary to occlusion at the basilar trunk and vertebral artery. In patients with TE events in the anterior circulation, 7 of 11 patients with middle cerebral artery occlusion and 9 of 12 patients with internal carotid artery occlusion achieved independence. Time-to-event Cox regression analysis demonstrated that TE events were more frequent in patients exhibiting aspirin resistance (hazard ratio 2.66; 95% CI 1.10-6.70). TE events after FD result from multiple factors, including age, aneurysm characteristics, aneurysm location, antiplatelet resistance, and procedural factors. In our cohort, we found the highest morbidity for patients with TE events presenting with large-vessel occlusion at the middle cerebral artery, and vertebrobasilar system.

Evaluating Bempedoic Acid for Non-alcoholic Fatty Liver Disease: A Review of Preclinical and Clinical Research.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder globally, characterized by fat accumulation in liver cells, which can progress to inflammation, fibrosis, and cirrhosis. The disease predominantly affects individuals with obesity and high body mass index (BMI). It is a globally prevalent condition, with variations in incidence across different regions. The pathophysiology of NAFLD involves insulin resistance, metabolic disturbances, and genetic and gut microbial factors. Current treatments primarily focus on lifestyle modifications and a limited range of pharmacological options. Bempedoic acid (BA), a novel cholesterol-lowering agent, targets adenosine triphosphate (ATP)-citrate lyase to reduce low-density lipoprotein (LDL) cholesterol and has shown potential in managing NAFLD by decreasing liver fat accumulation and improving lipid profiles. BA's unique mechanism offers a promising add-on therapy, particularly for the patient's intolerant to statins. Despite its potential, comprehensive clinical and preclinical studies are needed to further elucidate its efficacy and safety compared to other NAFLD treatments. Future research should focus on comparing BA with existing and emerging therapies to optimize its role in NAFLD management and enhance patient outcomes.