Evaluating the accuracy of the MBT Lipid Xtract Kit for assessing colistin resistance in comparison to broth microdilution.

Colistin resistance testing methods such as broth microdilution (BMD) are time-consuming and labour intensive for clinical laboratories. MBT Lipid Xtract Kit on MALDI Biotyper Sirius System (Bruker, Billerica, MA, USA) utilizes lipidomic analysis to identify specific cell wall modifications associated with colistin resistance. We compared MBT to BMD (ComASP Colistin, Liofilchem) across 36 Gram-negative isolates (non-resistant MIC ≤2 µg ml-1, resistant MIC ≥4 µg ml-1). All samples were tested twice on MBT with discrepant results repeated before assessing categorical agreement between MBT and BMD. 44.4% (16/36) of isolates were colistin resistant via BMD. MBT Lipid Xtract had 80.6% agreement (29/36) with BMD, with 5/7 discrepancies corrected to match upon repeat testing. There was 100% agreement for Escherichia coli isolates (n=16). The whole-genome sequencing was completed on the two discrepant Klebsiella pneumoniae isolates, with variants within colistin resistance-associated loci identified (MIC 0.5 µg ml-1: arnC S30T, pmrB T246A, lapB N212T, lpxM S253G, crrB Q287K and MIC >16 µg ml-1: arnC S30T, pmrB R90insRN, pmrB T246A, pmrA E57G, lpxM S253G). Further evaluation, particularly for non-E. coli, of MBT is required prior to implementation in clinical laboratories.

O,S,Se-containing Biginelli products based on cyclic ß-ketosulfone and their postfunctionalization.

A one-pot three-component Biginelli synthesis of dihydropyrimidinones/thiones/selenones via acetic acid or solvent-free Yb(OTf)3-catalyzed tandem reaction of ß-ketosulfone (dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide), an appropriate urea, and arylaldehyde has been developed. The reaction proceeds with high chemo- and regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO2-containing analogue of anticancer drug-candidate enastron (SO2 vs C=O) was obtained by using the here reported method in gram scale. We also demonstrate the reactivity of the Biginelli product in various directions - synthesis of condensed thiazoles and tetrazoles. In silico assessment of ADMET parameters shows that most compounds meet the lead-likeness requirements. The biological profiles of new compounds demonstrate high probability levels of activity against the following pathogens/diseases: Candida albicans, Alphis gossypii, Tripomastigote Chagas, Tcruzi amastigota, Tcruzi epimastigota, Leishmania amazonensis, and Dengue larvicida.

In treacherous waters: detection of colistin resistant bacteria in water and plastic litter from a recreational estuary.

Colistin resistance poses a major therapeutic challenge and resistant strains have now been reported worldwide. However, the occurrence of such bacteria in aquatic environments is considerably less understood. This study aimed to isolate and characterize colistin resistant strains from water and plastic litter collected in an urban recreational estuary. Altogether, 64 strains with acquired colistin resistance were identified, mainly Acinetobacter spp. and Enterobacter spp. From these, 40.6% were positive for at least one mcr variant (1-9), 26.5% harbored extended-spectrum beta-lactamases, 23.4%, sulfonamide resistance genes, and 9.3%, quinolone resistance genes. The merA, encoding mercury resistance, was detected in 10.5% of these strains, most of which were also strong biofilm producers. The minimum inhibitory concentration towards colistin was determined for the mcr positive strains and ranged from 2 to ≥ 512 µg.ml-1. Our findings suggest that Gram-negative bacteria highly resistant to a last-resort antimicrobial can be found in recreational waters and plastic litter, thereby evidencing the urgency of the One Health approach to mitigate the antimicrobial resistance crisis.

Sheep and goats as reservoirs of colistin-resistant E. coli: First detection of ETEC ST10 and E. coli ST6396 mcr-1 positive strains in North Africa.

AIM: This study aimed to screen and characterize colistin-resistant strains isolated from different livestock species in Algeria, including sheep, goats, and dromedaries. METHODS & RESULTS: A total of 197 rectal and nasal swabs were screened for colistin-resistant Gram-negative bacilli. 21 isolates were selected, identified, and their antibiotic resistance was phenotypically and genotypically characterized. The majority (15/21) were affiliated to E. coli, from which 4 strains isolated from sheep (n=2) and goats (n=2) and belonging to phylogroup A and ST10 and ST6396 lineages, respectively, carried the mcr-1 gene. The remaining isolates were identified as belonging to the following genera: Raoultella, Enterobacter, Klebsiella, and Pseudomonas. CONCLUSION: This study highlights the presence of virulent and multi-resistant Gram-negative bacilli in farm animals, increasing the risk of transmitting potentially fatal infections to humans.

High-throughput screening identification of apigenin that reverses the colistin resistance of mcr-1-positive pathogens.

The plasmid-mediated gene mcr-1 that makes bacteria resistant to the antibiotic colistin is spreading quickly, which means that colistin is no longer working well to treat Gram-negative bacterial infections. Herein, we utilized a computer-aided high-throughput screening drugs method to identify the natural product apigenin, a potential mcr-protein inhibitor, which effectively enhanced the antimicrobial activity of colistin. Several assays, including a checkerboard minimum inhibitory concentration assay, a time-kill assay, the combined disk test, molecular simulation dynamics, and animal infection models assay, were conducted to verify whether apigenin enhanced the ability of colistin to fight Gram-negative bacterial infections. The results showed that apigenin improved the antimicrobial activity of colistin against multidrug-resistant Enterobacteriaceae infection. Moreover, apigenin not only did not increase the toxic effect of colistin but also had the ability to effectively inhibit the frequency of bacterial resistance mutations to colistin. Studies clearly elucidated that apigenin could interfere with the thermal stability of the protein by binding to the mcr-1 protein. Additionally, the combination of apigenin and colistin could exert multiple effects, including disrupting bacterial membranes, the generation of bacterial nitric oxide and reactive oxygen species, as well as inhibiting bacterial adenosine triphosphate production. Furthermore, the addition of apigenin was able to significantly inhibit colistin-stimulated high expression levels of the bacterial mcr-1 gene. Finally, apigenin exhibited a characteristic anti-inflammatory effect while enhancing the antimicrobial activity of colistin against mcr-1-positive Escherichia coli (E. coli) infected animals. In conclusion, as a potential lead compound, apigenin is promising in combination with colistin in the future treatment of mcr-1-positive E. coli infections.IMPORTANCEThis study found that apigenin was able to inhibit the activity of the mcr-1 protein using a high-throughput virtual screening method. Apigenin effectively enhanced the antimicrobial activity of colistin against multidrug-resistant Enterobacteriaceae, including mcr-1-positive strains, in vitro and in vivo. This study will provide new options and strategies for the future treatment of multidrug-resistant pathogen infections.

Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Fusion event mediated by IS903B between chromosome and plasmid in two MCR-9- and KPC-2-co-producing Klebsiella pneumoniae isolates.

Herein, we first isolated two MCR-9- and KPC-2-co-producing K. pneumoniae isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS903B, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.

Research note: characteristics of blaNDM and mcr-1 co-producing Escherichia coli from retail chicken meat.

Carbapenems and colistin are vital antimicrobials used to treat Enterobacteriaceae-caused infections. The present study aimed to characterize the coexistence mechanism of carbapenem and colistin resistance in an Escherichia coli isolated from retail chicken meat. A total of 4 E. coli isolates co-harboring carbapenem resistance gene blaNDM (2 E. coli isolates with blaNDM-5 and 2 with blaNDM-9) and colistin resistance gene mcr-1. Antimicrobial susceptibility testing exhibited that all the 4 E. coli strains had multidrug resistance profile and consistent with the resistance genes they carried. MLST showed that 3 E. coli isolates belonged to a pathogenic E. coli lineage ST354, which is closely associated with human infections and pose a serious threat to public health. Whole genome sequencing (WGS) showed that 4 mcr-1-positive plasmids with sizes of 60.4 kb to 67.4 kb all belonged to the IncI2 type. A total of 5 blaNDM-harboring plasmids ranged from 99.0 kb to 138.3 kb, among which 4 plasmids belonged to unknow type and only pCS5L-NDM belonged to IncFIA/IncFIB group of hybrid plasmids, a novel carrier for blaNDM. Comparative analysis exhibited that the mcr-1 or blaNDM-carrying plasmids of E. coli strains from chicken meat showed high identity with that from Enterobacteriaceae of human origin, which indicated the risk of mcr-1 or blaNDM dissemination from retail meat to human. The simultaneous occurrence of mcr-1 and blaNDM in E. coli emphasizes the significant of antimicrobial resistance surveillance in retail meat.

Multi-trajectories in different domains of social supports and subjective motoric cognitive risk syndrome: a 16-year group-based multi-trajectory analysis.

OBJECTIVE: The aim of this study was to examine the longitudinal relationships between the trajectories of distinct subtypes of various domains of social supports and risk of subjective motoric cognitive risk (MCR) syndrome. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: 2,279 participants in the Taiwan Longitudinal Study on Aging (TLSA) between 1999 and 2011. METHOD: A group-based multi-trajectory modeling (GBMTM) was implemented to identify distinct trajectory subtypes within various social support domains, encompassing social networks, emotional support, instrumental support, as well as working and economic status. Logistic regression models were then utilized to evaluate the associations between these trajectory subtypes and the risk of subjective MCR. RESULTS: Among 2,279 participants, GBMTM identified four distinct trajectory subtypes: "low social support" (n = 371), "medium social support " (n = 862), "high social support" (n = 292), and "high social support with employment" (n = 754). The incidence rates of subjective MCR for these groups were 9.4%, 9.0%, 4.1%, and 0.8%, respectively. After adjusting for age, sex, education level, and comorbidities, both "low social support" (adjusted odds ratio (aOR) 4.07, 95% CI [1.60-10.34]) and "medium social support" (aOR 3.10, 95% CI [1.26-7.66]) were significantly associated with an increased risk of subjective MCR compared to the "high social support with employment" group. CONCLUSIONS AND IMPLICATIONS: The current study demonstrates that social support significantly reduces the risk of subjective MCR, with lower support levels correlating to higher risk, necessitating further intervention studies to confirm the link between social support and risk of subjective MCR.

Emergence of the mobile colistin resistance gene mcr-1 in a Leclercia adecarboxylata strain isolated from wastewater in Seoul.

Colistin is considered the last resort for treating infections caused by multidrug-resistant bacteria. However, the spread of the plasmid-borne colistin-resistance gene mcr-1 has become a public health threat. In this study, we identified mcr-1-harboring Leclercia adecarboxylata strain (WWCOL-134) isolated from wastewater in Seoul. The strain had a colistin MIC value of 2 µg/ml and was resistant to cefotaxime, gentamicin, tetracycline, trimethoprim, and sulfamethoxazole. The mcr-1 gene, along with an array of resistance genes, was located on a 236-kb plasmid (pCOL134-1), which contained the typical IncHI2 backbone of reported mcr-1-carrying plasmids, and was transferred to an Escherichia coli strain by conjugation. To the best of our knowledge, this is the first study to report the emergence of mcr-1-harboring Leclercia sp. isolate. Our findings demonstrate the ongoing spread of colistin resistance among Enterobacterales species, emphasizing the need for surveillance of antimicrobial resistance in wastewater environments.

Detection of mobile colistin resistance genes mcr-9.1 and mcr-10.1 in Enterobacter asburiae from Ecuadorian children.

Colistin is one of the last-line treatments for multi-drug resistant Gram-negative bacterial infections. The emergence of mobile colistin resistance genes has driven global concern and triggered the need for surveillance. Our report reveals the identification of mcr-9.1 and mcr-10.1 in Ecuador by employing a proximity ligation technique.

Shotgun metagenomic analysis reveals the emergence of plasmid-encoded mcr-5.1 gene in hospital wastewater in Bangladesh.

Colistin is considered the last line therapy for treating multidrug-resistant (MDR) bacterial infections in humans. Therefore, the spread of colistin resistance poses a serious threat to human, and environmental health. Though Bangladesh is known as a hotspot of AMR, limited studies have been carried out regarding the status of colistin resistance. Information on the emerging bacterial resistance is inevitable for protecting public health. Nowadays, wastewater analysis has been prioritized for metagenomics-enabled AMR surveillance. Our study on the metagenomic analysis of untreated hospital effluents first detected the colistin resistance-conferring mcr-5.1 gene in the hospital environment of Bangladesh. Phylogenetic tree and in silico AMR analysis confirmed the detection of this mcr-5 variant, which is located in a plasmid contig. The plasmid was untypeable and belonged to the bacteria from the Enterobacteriaceae family. The mcr-5.1 operon was embedded in a Tn3 transposon, suggesting the mobility of the gene. Tnshfr1 transposon, chromate resistance protein ChrB, DNA invertase hin, and two MFS-type proteins were present in the genetic environment of mcr-5.1. Our findings provide evidence of the occurrence of mcr-5.1 in a hospital environment in Bangladesh, which calls for immediate attention and effective measures to contain the dissemination of colistin resistance in the environment.

Repurposing cetylpyridinium chloride and domiphen bromide as phosphoethanolamine transferase inhibitor to combat colistin-resistant Enterobacterales.

The emergence of plasmid-encoded colistin resistance mechanisms, MCR-1, a phosphoethanolamine transferase, rendered colistin ineffective as last resort antibiotic against severe infections caused by clinical Gram-negative bacterial pathogens. Through screening FDA-approved drug library, we identified two structurally similar compounds, namely cetylpyridinium chloride (CET) and domiphen bromide (DOM), which potentiated colistin activity in both colistin-resistant and susceptible Enterobacterales. These compounds were found to insert their long carbon chain to a hydrophobic pocket of bacterial phosphoethanolamine transferases including MCR-1, competitively blocking the binding of lipid A tail for substrate recognition and modification, resulting in the increase of bacterial sensitivity to colistin. In addition, these compounds were also found to dissipate bacterial membrane potential leading to the increase of bacterial sensitivity to colistin. Importantly, combinational use of DOM with colistin exhibited remarkable protection of test animals against infections by colistin-resistant bacteria in both mouse thigh infection and sepsis models. For mice infected by colistin-susceptible bacteria, the combinational use of DOM and colistin enable us to use lower dose of colistin to for efficient treatment. These properties render DOM excellent adjuvant candidates that help transform colistin into a highly potent antimicrobial agent for treatment of colistin-resistant Gram-negative bacterial infections and allowed us to use of a much lower dosage of colistin to reduce its toxicity against colistin-susceptible bacterial infection such as carbapenem-resistant Enterobacterales.

Global Variation in Escherichia coli mcr-1 Genes and Plasmids from Animal and Human Genomes Following Colistin Usage Restrictions in Livestock.

Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.

Whole genome analysis of multidrug-resistant Escherichia coli isolate collected from drinking water in Armenia revealed the plasmid-borne mcr-1.1-mediated colistin resistance.

The rate of polymyxin-resistant Enterobacteriaceae, as well as human and animal infections caused by them, is increasing worldwide, posing a high epidemiological threat since colistin represents a last-resort antibiotic to treat complicated infections. The study of environmental niches, in particular, aquatic ecosystems in terms of genome analysis of inhabiting antimicrobial-resistant (AMR) microorganisms as reservoirs of acquired resistance determinants (AMR genes), represents a specific concern from a One Health approach. Here, we present a phenotypic AMR analysis and molecular characterization of Escherichia coli isolate found in municipal drinking water after an accident in the water supply system of a residential building in Armenia in 2021. CrieF1144 E. coli isolate was resistant to ampicillin, ampicillin/sulbactam, cefuroxime, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, colistin, and tigecycline, whereas whole genome sequencing (WGS) revealed blaTEM-1B, tet(A), and a combination of dfrA14 with sul1 resistance determinants, which corresponds well with phenotypic resistance above. Moreover, the multidrug-resistant isolate studied harbored mcr-1.1 gene on a conjugative 251 Kb IncHI2 plasmid, whose structure was determined using hybrid short- and long-reads assembly. CrieF1141_p1 plasmid carried all antimicrobial resistance genes revealed in the isolate and did not harbor any virulence determinants, so it could contribute to the spread of AMR genes in the bacterial population. Two copies of ISApl1 transposase-encoding element, which is likely to mediate mcr-1.1 gene mobilization, were revealed surrounding this gene in a plasmid. IMPORTANCE: Evolutionary patterns of Escherichia coli show that they usually develop into highly pathogenic forms by acquiring fitness advantages such as antimicrobial resistance (AMR) and various virulence factors through horizontal gene transfer mediated by mobile elements. This has led to high prevalence of multidrug-resistant (MDR) strains, which highlights the relevancy of enhanced surveillance to monitor and prevent transmission of the MDR bacteria to human and animal populations. However, the limited number of reports regarding the whole genome sequencing (WGS) investigation of MDR E. coli strains isolated from drinking water and harboring mcr genes hampers the adoption of a comprehensive approach to address the relationship between environmental E. coli populations and human and veterinary infections. Our results highlight the relevance of analyzing the environment, especially water, as a part of the surveillance programs to understand the origins and dissemination of antimicrobial resistance within the One Health concept.

CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota.

The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that sfGFP-tagged plasmid-borne mcr-1 can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic resistance.

Two colistin resistance-producing Aeromonas strains, isolated from coastal waters in Zhejiang, China: characteristics, multi-drug resistance and pathogenicity.

Introduction: Aeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals. Results: In this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16-mcr-3-like-dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent. Discussion: Thus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity.

Hyperspectral full-field quick-EXAFS imaging at the ROCK beamline for monitoring micrometre-sized heterogeneity of functional materials under process conditions.

Full-field transmission X-ray microscopy has been recently implemented at the hard X-ray ROCK-SOLEIL quick-EXAFS beamline, adding micrometre spatial resolution to the second time resolution characterizing the beamline. Benefiting from a beam size versatility due to the beamline focusing optics, full-field hyperspectral XANES imaging has been successfully used at the Fe K-edge for monitoring the pressure-induced spin transition of a 150 µm × 150 µm Fe(o-phen)2(NCS)2 single crystal and the charge of millimetre-sized LiFePO4 battery electrodes. Hyperspectral imaging over 2000 eV has been reported for the simultaneous monitoring of Fe and Cu speciation changes during activation of a FeCu bimetallic catalyst along a millimetre-sized catalyst bed. Strategies of data acquisition and post-data analysis using Jupyter notebooks and multivariate data analysis are presented, and the gain obtained using full-field hyperspectral quick-EXAFS imaging for studies of functional materials under process conditions in comparison with macroscopic information obtained by non-spatially resolved quick-EXAFS techniques is discussed.

Enhancing refinery heavy oil fractions analytical performance through real-time predicative modeling.

This study introduces a suite of robust models aimed to advance the determination of physiochemical properties in heavy oil refinery fractions. By integrating real-time analytical technique inside the refinery analysis, we have developed a single analyzer capable of employing six partial least square regression equations. These designed models enable to provide real-time prediction of critical petroleum properties, such as sulfur content, micro carbon residues (MCR), asphaltene content, heating value, and the concentrations of nickel and vanadium metals. Specifically tailored for heavy oil in refinery feeds with an American petroleum institute (API) gravity range of 3° to 32° and sulfur content of 2.8 to 5.5 wt%, the models streamline the analysis process within refinery operations, bridging the gap between catalytic and non-catalytic processes across refinery units. The accuracy of our physiochemical prediction models has been validated against American Society for Testing and Materials (ASTM) standards, demonstrating their capability to deliver precise real-time property values. This approach not only enhances the efficiency of refinery analysis but also sets a new standard for the monitoring and optimization of heavy oil processing in real-time approach.

Predictors for the development of motoric cognitive risk syndrome in older adults.

BACKGROUND: Motoric cognitive risk (MCR) syndrome refers to a condition where both slow gait and memory complaints coexist, which heightens their vulnerability to developing dementia. Considering that the risk factors of MCR are elucidated from cross-sectional studies and also likely vary based on socioeconomic status, we conducted a community-based longitudinal study to determine the predictors of MCR among older adults in Malaysia. METHODS: Out of 1,249 older participants (aged 60 years and above) without MCR at baseline (Wave II of LRGS-TUA cohort study), 719 were successfully followed up after 3.5 years to identify predictors of subsequent MCR development. A comprehensive interview-based questionnaire was administered for sociodemographic information, cognitive function, psychosocial, functional status, and dietary intake. Anthropometric measurements, body composition, and physical performance were assessed. Univariate analyses were performed for each variable, followed by a hierarchical logistic regression analysis to identify the predictors of MCR that accounted for confounding effects between the studied factors. RESULTS: The incidence rate of MCR was 4.0 per 100 person-years. Smoking (Adjusted Odd Ratio (Adj OR) = 1.782; 95% Confidence Interval (CI):1.050-3.024), hypertension (Adj OR = 1.725; 95% CI:1.094-2.721), decreased verbal memory as assessed by the lower Rey Auditory Verbal Learning Test (RAVLT) (Adj OR = 1.891; 95% CI:1.103-3.243), and decreased functional status measured using instrumental activity of daily living (IADL) (Adj OR = 4.710; 95% CI:1.319-16.823), were predictors for MCR incidence. CONCLUSIONS: Our study results provide an initial reference for future studies to formulate effective preventive management and intervention strategies to reduce the growing burden of adverse health outcomes, particularly among Asian older adults.