Analysis of mcr family of colistin resistance genes in Gram-negative isolates from a tertiary care hospital in India.

AIM: Colistin serves as the drug of last resort for combating numerous multidrug-resistant (MDR) Gram-negative infections. Its efficacy is hampered by the prevalent issue of colistin resistance, which severely limits treatment options for critically ill patients. Identifying resistance genes is crucial for controlling resistance spread, with horizontal gene transfer being the primary mechanism among bacteria. This study aimed to assess the prevalence of plasmid-mediated mcr genes associated with colistin resistance in Gram-negative bacteria, utilizing both genotypic and phenotypic tests. METHODS AND RESULTS: The clinical isolates (n=913) were obtained from a tertiary care center in Chennai, India. Colistin resistance was seen among Gram-negative isolates. These strains underwent screening for mcr-1, mcr-3, mcr-4, and mcr-5 genes via conventional PCR. Additionally, mcr-positive isolates were confirmed through Sanger sequencing and phenotypic testing. The bacterial isolates predominantly comprised Klebsiella pneumoniae (62.43%), Escherichia coli (19.71%), Pseudomonas aeruginosa (10.73%), Acinetobacter baumannii (4.81%), along with other species. All isolates exhibited multidrug resistance to three or more antibiotic classes. Colistin resistance, determined via broth microdilution (BMD) using CLSI guidelines, was observed in 13.08% of the isolates studied. Notably, mcr-5 was detected in K. pneumoniae in PCR, despite their absence in Sanger sequencing and phenotypic tests (including the combined-disk test, colistin MIC in the presence of EDTA, and Zeta potential assays). This finding underscores the importance of employing multiple diagnostic approaches to accurately identify colistin resistance mechanisms. CONCLUSION AND IMPACT: The study highlights a concerning prevalence of colistin resistance among Enterobacterales, especially those producing carbapenemase, thereby impacting mortality rates. Nonetheless, further investigations are warranted to elucidate common mechanisms of colistin resistance and to evaluate the efficacy of screening techniques in detecting isolates carrying mcr genes responsible for enzyme-mediated lipopolysaccharide (LPS) modification.

Super-twisting MPPT control for grid-connected PV/battery system using higher order sliding mode observer.

In recent times, photovoltaic (PV) power generation has been growing due to increase in energy demand. In grid-connected mode, achieving maximum power (MP) from the PV array is difficult by using conventional techniques due to various reasons like low tracking efficiency, stability issues, etc. This motivates the design of an appropriate control strategy to obtain the maximum power point tracking (MPPT) to harvest MP from the PV array. This paper proposes a combined higher order sliding mode observer (HOSMO)-super-twisting control (STC) for a grid-connected scenario. A perturb and observe (P &O) technique is employed to generate reference voltage, and a HOSMO is proposed to drive the STC by estimating the inductor current of the PV boost converter. The proposed controller performance is evaluated based on response time across various scenarios, including generation changes, dynamic faults, islanding and resynchronization, and load variations in comparison to other existing controllers. These microgrid test cases have been thoroughly simulated, and their effectiveness has been validated in real-time using OPAL-RT (OP4510).

Accuracy and Consistency of Confidence Limits for Monosyllable Identification Scores Derived Using Simulation, the Harrell-Davis Estimator, and Nonlinear Quantile Regression.

BACKGROUND: Audiological diagnosis and rehabilitation often involve the assessment of whether the maximum speech identification score (PBmax) is poorer than expected from the pure-tone average (PTA) threshold. This requires the estimation of the lower boundary of the PBmax values expected for a given PTA (one-tailed 95% confidence limit, CL). This study compares the accuracy and consistency of three methods for estimating the 95% CL. METHOD: The 95% CL values were estimated using a simulation method, the Harrell-Davis (HD) estimator, and non-linear quantile regression (nQR); the latter two are both distribution-free methods. The first two methods require the formation of sub-groups with different PTAs. Accuracy and consistency in the estimation of the 95% CL were assessed by applying each method to many random samples of 50% of the available data and using the fitted parameters to predict the data for the remaining 50%. STUDY SAMPLE: A total of 642 participants aged 17 to 84 years with sensorineural hearing loss were recruited from audiology clinics. Pure-tone audiograms were obtained and PBmax scores were measured using monosyllables at 40 dB above the speech recognition threshold or at the most comfortable level. RESULTS: For the simulation method, 6.7 to 8.2% of the PBmax values fell below the 95% CL for both ears, exceeding the target value of 5%. For the HD and nQR methods, the PBmax values fell below the estimated 95% CL for approximately 5% of the ears, indicating good accuracy. Consistency, estimated from the standard deviation of the deviations from the target value of 5%, was similar for all the methods. CONCLUSIONS: The nQR method is recommended because it has good accuracy and consistency, and it does not require the formation of arbitrary PTA sub-groups.

Bells and Whistles on Fertilizers: Molecular Hands to Hang Nanoporous Foliar Fertilizer Reservoirs.

Porous materials are highly explored platforms for fertilizer delivery. Among porous materials, metal-organic frameworks (MOFs) are an important class of coordination polymers in which metal ions and organic electron donors as linkers are assembled to form crystalline structures with stable nanoporosity. Selected amino acids were inherently found to have the capacity to hold the leaf cuticle. Hence, MOF synthesis was attempted in the presence of amino acids, which can act as surface terminators and can assist as hands to hold to the leaf for a controlled nutrient supply. By serendipity, the amino acids were found to act as modulators, resulting in well-stabilized porous MOF structures with iron metal nodes, which are often noted to be unstable. Thus, the composite, i.e., (MOF@aa) MOF modulated with amino acids, has efficient nutrient-feeding ability through the foliar route when compared to the control.

A big data scheme for heart disease classification in map reduce using jellyfish search flow regime optimization enabled Spinalnet.

BACKGROUND: The disease related to the heart is serious and can lead to death. Precise heart disease prediction is imperative for the effective treatment of cardiac patients. This can be attained by machine learning (ML) techniques using healthcare data. Several models on the basis of ML predict and identify disease in the heart, but this model cannot manage a huge database because of the deficiency of the smart model. This paper provides an optimized SpinalNet with a MapReduce model to categorize heart disease. OBJECTIVE: The objective is to design a big data approach for heart disease classification using the proposed Jellyfish Search Flow Regime Optimization (JSFRO)-based SpinalNet. METHOD: The binary image conversion is applied on Electrocardiogram (ECG) images for converting the image to binary image. MapReduce model is adapted, in which the mappers execute feature extraction and the reducer performs heart disease classification. In the mapper phase, the features like statistical features, shape features and temporal features are extracted and in reducer, the SpinalNet with JSFRO is considered. Here, the training of SpinalNet is done with JSFRO, which is produced by the unification of Jellyfish Search Optimization (JSO) and Flow Regime Optimization (FRO). METHOD: The JSFRO-based SpinalNet offered effectual performance with the finest accuracy of 90.8%, sensitivity of 95.2% and specificity of 93.6%.

HARNet in deep learning approach-a systematic survey.

A comprehensive examination of human action recognition (HAR) methodologies situated at the convergence of deep learning and computer vision is the subject of this article. We examine the progression from handcrafted feature-based approaches to end-to-end learning, with a particular focus on the significance of large-scale datasets. By classifying research paradigms, such as temporal modelling and spatial features, our proposed taxonomy illuminates the merits and drawbacks of each. We specifically present HARNet, an architecture for Multi-Model Deep Learning that integrates recurrent and convolutional neural networks while utilizing attention mechanisms to improve accuracy and robustness. The VideoMAE v2 method ( https://github.com/OpenGVLab/VideoMAEv2 ) has been utilized as a case study to illustrate practical implementations and obstacles. For researchers and practitioners interested in gaining a comprehensive understanding of the most recent advancements in HAR as they relate to computer vision and deep learning, this survey is an invaluable resource.

Exposure to imipenem at sub-minimum inhibitory concentration leads to altered expression of major outer membrane proteins in Acinetobacter baumannii.

AIMS: Acinetobacter baumannii is a nosocomial pathogen known to be multidrug-resistant (MDR), especially to drugs of the carbapenem class. Several factors contribute to resistance, including efflux pumps, ß-lactamases, alteration of target sites, and permeability defects. In addition, outer membrane proteins (OMPs), like porins are involved in the passage of antibiotics, and their alteration could lead to resistance development. This study aimed to explore the possible involvement of porins and OMPs in developing carbapenem resistance due to differential expression. METHODS AND RESULTS: The antibiotic-susceptible and MDR isolates of A. baumannii were first studied for differences in their transcriptional levels of OMP expression and OMP profiles. The antibiotic-susceptible isolates were further treated with imipenem, and it was found that the omp genes were differentially expressed. Six of the nine genes studied were upregulated at 1 h of exposure to imipenem. Their expression gradually decreased with time, further confirmed by their OMP profile and two-dimensional gel electrophoresis. CONCLUSIONS: This study could identify OMPs that were differentially expressed on exposure to imipenem. Hence, this study provides insights into the role of specific OMPs in antibiotic resistance in A. baumannii.

Braided silk sutures coated with photoreduced silver nanoparticles for eradicating Staphylococcus aureus and Streptococcus mutans infections.

BACKGROUND: Infections resulting from surgical procedures and wound closures continue to pose significant challenges in healthcare settings. To address this issue, the investigators have developed antibacterial non-resorbable braided silk sutures using in situ deposited silver nanoparticles (AgNPs) and investigated their efficacy in eradicating Staphylococcus aureus and Streptococcus mutans infections. METHODS: The braided silk sutures were modified through a simple and efficient in situ photoreduction method, resulting in the uniform distribution of AgNPs along the suture surface. The synthesized AgNPs were characterized using scanning electron microscopy (SEM), dynamic light scattering analysis (DLS) and Fourier Transform Infrared Spectroscopy analysis (FTIR) confirming their successful integration onto the silk sutures. The antibacterial activity of the nanoparticle coated sutures were compared and evaluated with non-coated braided silk sutures through in vitro assays against both S. aureus and S. mutans. RESULTS: The surface and cross-sectional analysis of the treated sutures revealed a uniform and homogeneous distribution of silver particles achieved through the photoreduction of silver solution. This observation confirms the successful coating of silver nanoparticles (AgNPs) on the sutures. The antimicrobial studies conducted, demonstrated significant reductions in bacterial colonies when exposed to the silver nanoparticle-coated sutures. Notably, the width of the inhibition zone surrounding the coated sutures remained consistently wide and stable for duration up to 7 days. This sustained and robust inhibitory effect against gram-positive bacteria, specifically S. aureus and S. mutans, serves as strong evidence of the antibacterial efficacy of the coated sutures. CONCLUSION: The coating of silk sutures with AgNPs provided a significant and effective antibacterial capacity to the surgical sutures, with this activity being sustained for a period of 7 days. This suggests that AgNPs-in situ photoreduction deposited sutures have the potential to effectively manage S. aureus and S. mutans infections.

Caregiver's Quality of Life Among Children with Cerebral Palsy in the Kingdom of Saudi Arabia, and Various Influencing Factors: A Single Cohort Study.

Purpose: Quality of life (QOL) among disabled children and their caregivers is an important concern in healthcare. We aim to evaluate the quality of life among caregivers of children with cerebral palsy and to observe the effects of various demographic factors and affected child-related factors on caregivers' quality of life. Patients and Methods: After ethical approval and written consent was obtained from the participants. One hundred six caregivers of children with cerebral palsy from the Asir region were recruited for the study. Caregivers provided details, including their demographic characteristics, social factors, and information regarding their affected children regarding age, gender, mobility levels, etc. They also completed the Arabic version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire for assessing their QOL. Results: All the caregivers were women; their mean age was 40.38 years and SD7.09, and the overall QOL mean and standard deviations were 66.38 ± 12.88. There was a moderately significant correlation between total QOL in comparison with caregivers' educational level and mobility capacity, with R values of 0.54 (p<0.001) and 0.62 (p<0.001), respectively. Conclusion: All the subdomains of WHOQOL-BREF were found to be very closely related to the total scores for QOL. The caregivers of children with cerebral palsy had better QOL scores than the cutoff scores proposed in the WHOQOL-BREF scale. Factors such as increased mobility and education of the affected child contributed to better total QOL scores.

Identification of resistance to Sugarcane mosaic virus, Sugarcane streak mosaic virus, and Sugarcane bacilliform virus in new elite sugarcane accessions in India.

Sugarcane mosaic and leaf fleck diseases are significant viral diseases affecting sugarcane crops in India. The use of resistant sugarcane varieties is considered the most economical and effective approach to manage viral diseases, especially in vegetatively propagated crops such as sugarcane. Sugarcane mosaic virus (SCMV) and Sugarcane streak mosaic virus (SCSMV) are the primary pathogens responsible for mosaic disease in sugarcane-growing regions of India. Sugarcane bacilliform virus (SCBV), causing leaf fleck disease, is also often found in mixed infections with mosaic symptoms. The study aimed to identify new sources of resistance by screening sugarcane germplasm for resistance to SCMV, SCSMV, and SCBV. The screening was carried out under high inoculum using the infector row method in both plant and ratoon crops. Out of 129 genotypes tested, only 8 were found to be free of mosaic viruses, indicating a rare occurrence of resistant sources. The study revealed that mosaic disease is widespread, with nearly 95% of tested varieties/genotypes being infected with mosaic viruses. SCMV, SCSMV, and SCBV were detected in 121 out of 129 genotypes using the RT-PCR and PCR assays. Based on their response to the viruses, the tested genotypes were categorized into different resistance grades: highly resistant (grade 1), resistant (grade 2), moderately resistant (grade 3), susceptible (grade 4), and highly susceptible (grade 5). The results of the study provide valuable information about elite resistance resources that can be used for the prevention and control of mosaic disease. These resistant genotypes could also serve as potential donors for mosaic and leaf fleck disease resistance in breeding programs.

Layered Potassium Titanium Niobate/Reduced Graphene Oxide Nanocomposite as a Potassium-Ion Battery Anode.

With graphite currently leading as the most viable anode for potassium-ion batteries (KIBs), other materials have been left relatively under-examined. Transition metal oxides are among these, with many positive attributes such as synthetic maturity, long-term cycling stability and fast redox kinetics. Therefore, to address this research deficiency we report herein a layered potassium titanium niobate KTiNbO5 (KTNO) and its rGO nanocomposite (KTNO/rGO) synthesised via solvothermal methods as a high-performance anode for KIBs. Through effective distribution across the electrically conductive rGO, the electrochemical performance of the KTNO nanoparticles was enhanced. The potassium storage performance of the KTNO/rGO was demonstrated by its first charge capacity of 128.1 mAh g-1 and reversible capacity of 97.5 mAh g-1 after 500 cycles at 20 mA g-1, retaining 76.1% of the initial capacity, with an exceptional rate performance of 54.2 mAh g-1 at 1 A g-1. Furthermore, to investigate the attributes of KTNO in-situ XRD was performed, indicating a low-strain material. Ex-situ X-ray photoelectron spectra further investigated the mechanism of charge storage, with the titanium showing greater redox reversibility than the niobium. This work suggests this low-strain nature is a highly advantageous property and well worth regarding KTNO as a promising anode for future high-performance KIBs.

Performance of microscopy compared to conventional PCR in identification of soil-transmitted helminth infections among antenatal women in a low-prevalence setting.

PURPOSE: Traditional microscopy-based methods may provide inaccurate estimates of Soil transmitted helminth (STH) infections in mild intensity of infection. Therefore, we aimed to determine the prevalence of STH infections using molecular diagnostic methods and compare the diagnostic performance of microscopy with polymerase chain reaction (PCR) in stool samples collected from pregnant women in primary care settings in Puducherry, India. METHODOLOGY: A singleplex PCR assay was developed to detect three species of STHs, namely Ascaris lumbricoides, Necator americanus, and Ancylostoma duodenale, by targeting the internal transcribed spacer regions (ITS1 and ITS2) of 5.8S rRNA. The PCR generated 420, 662, and 515 base pairs of DNA for the respective organisms. In addition to singleplex PCR, wet and concentration microscopy techniques were used. The results were expressed as percentages with 95% confidence intervals, and the diagnostic performance of microscopy was compared with PCR in terms of sensitivity, specificity, and positive, negative predictive values and kappa statistics. RESULTS: Among the 650 pregnant women included, 48.8% were aged 25 years or less, 59% were primigravida, and half were from rural areas. The overall prevalence of any STH infection was higher in PCR compared to microscopy (8.9% vs. 7.2%). The prevalence of Ascaris lumbricoides was higher by microscopy (5.4% vs 2.6%), while the prevalence of Necator americanus was higher by PCR (6.3%) than by microscopy (1.8%). No species of Ancylostoma duodenale was detected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microscopy for detecting any STH infection was 22.4%, 94.3%, 27.7%, and 92.5%, respectively. The agreement between microscopy and PCR for the identification is as follows: for any STH infection, k â€‹= â€‹0.12, Ascaris k â€‹= â€‹0.16, and Necator k â€‹= â€‹0.20, respectively. CONCLUSION: The prevalence of any STH infection identified by PCR was higher than microscopy, and the agreement between the two methods was poor.

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy.

Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is Salmonella. The extensive and inappropriate treatments for Salmonella infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in Salmonella. Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in Salmonella. Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system's differential expression and positional mutation in Salmonella may provide insight into developing strategic therapies for one health application.

Integrons as the potential targets for combating multidrug resistance in Enterobacteriaceae using CRISPR- Cas9 technique.

The emergence of multi-drug resistance (MDR) to pan-drug resistance (PDR) in Enterobacteriaceae has made treatment extremely challenging. Genetic mutations and horizontal gene transfer (HGT) through mobile genetic elements (MGEs) were frequently associated mechanisms of drug resistance in pathogens. However, transposons, plasmids, and integrons transfer MDR genes in bacterium via HGT much faster. Integrons are dsDNA segment that plays a crucial role in the adaptation and evolution of bacteria. They contain multiple gene cassettes that code for antibiotic resistance determinants that are expressed by a single promoter (Pc). Integrons are the cause of drug resistance in Enterobacteriaceae. Although alternatives to antibiotics such as bacteriophages, phage proteins, antimicrobial peptides, and natural compounds have been widely used to treat MDR infections, there have been limited efforts to reverse the antibiotic resistance ability of bacteria. Thus, silencing the genes harboured on MGEs achieved by Gene Editing Techniques (GETs) might prevent the spread of MDR. One such GETs, which has a simple design, good repeatability, low cost, and high efficiency, is CRISPR- Cas9 system. Thus, this review is a first of the kind that focuses on utilizing the structure of an integron to make it an ideal target for GETs like CRISPR- Cas9 systems.

Spontaneous Decoration of Ultrasmall Pt Nanoparticles on Size-Separated MoS2 Nanosheets.

Liquid exfoliation can be considered as a viable approach for the scalable production of 2D materials due to its various benefits, although the polydispersity in the obtained nanosheet size hinders their straightforward incorporation. Size-separation can help alleviate these concerns, however a correlation between nanosheet size and property needs to be established to bring about size-specific applicability. Herein, size-selected aqueous nanosheet dispersions have been obtained via centrifugation-based protocols, and their chemical activity in the spontaneous reduction of chloroplatinic acid is investigated. Growth of ultrasmall Pt nanoparticles was achieved on nanosheet surfaces without a need for reducing agents, and stark differences in the nanoparticle coverage were observed as a function of nanosheet size. Defects in the nanosheets were probed via Raman spectroscopy, and correlated to the observed size-activity. Additionally, the effect of reaction temperature during synthesis was investigated. The electrochemical activity of the ultrasmall Pt nanoparticle decorated MoS2 nanosheets was evaluated for the hydrogen evolution reaction, and enhancement in performance was observed with nanosheet size, and nanoparticle decoration density. These findings shine light on the significance of nanosheet size in controlling spontaneous reduction reactions, and provide a deeper insight to intrinsic properties of liquid exfoliated nanosheets.

Multi-stage glaucoma classification using pre-trained convolutional neural networks and voting-based classifier fusion.

Aim: To design an automated glaucoma detection system for early detection of glaucoma using fundus images. Background: Glaucoma is a serious eye problem that can cause vision loss and even permanent blindness. Early detection and prevention are crucial for effective treatment. Traditional diagnostic approaches are time consuming, manual, and often inaccurate, thus making automated glaucoma diagnosis necessary. Objective: To propose an automated glaucoma stage classification model using pre-trained deep convolutional neural network (CNN) models and classifier fusion. Methods: The proposed model utilized five pre-trained CNN models: ResNet50, AlexNet, VGG19, DenseNet-201, and Inception-ResNet-v2. The model was tested using four public datasets: ACRIMA, RIM-ONE, Harvard Dataverse (HVD), and Drishti. Classifier fusion was created to merge the decisions of all CNN models using the maximum voting-based approach. Results: The proposed model achieved an area under the curve of 1 and an accuracy of 99.57% for the ACRIMA dataset. The HVD dataset had an area under the curve of 0.97 and an accuracy of 85.43%. The accuracy rates for Drishti and RIM-ONE were 90.55 and 94.95%, respectively. The experimental results showed that the proposed model performed better than the state-of-the-art methods in classifying glaucoma in its early stages. Understanding the model output includes both attribution-based methods such as activations and gradient class activation map and perturbation-based methods such as locally interpretable model-agnostic explanations and occlusion sensitivity, which generate heatmaps of various sections of an image for model prediction. Conclusion: The proposed automated glaucoma stage classification model using pre-trained CNN models and classifier fusion is an effective method for the early detection of glaucoma. The results indicate high accuracy rates and superior performance compared to the existing methods.

Disease mutations and phosphorylation alter the allosteric pathways involved in autoinhibition of protein phosphatase 2A.

Mutations in protein phosphatase 2A (PP2A) are connected to intellectual disability and cancer. It has been hypothesized that these mutations might disrupt the autoinhibition and phosphorylation-induced activation of PP2A. Since they are located far from both the active and substrate binding sites, it is unclear how they exert their effect. We performed allosteric pathway analysis based on molecular dynamics simulations and combined it with biochemical experiments to investigate the autoinhibition of PP2A. In the wild type (WT), the C-arm of the regulatory subunit B56δ obstructs the active and substrate binding sites exerting a dual autoinhibition effect. We find that the disease mutant, E198K, severely weakens the allosteric pathways that stabilize the C-arm in the WT. Instead, the strongest allosteric pathways in E198K take a different route that promotes exposure of the substrate binding site. To facilitate the allosteric pathway analysis, we introduce a path clustering algorithm for lumping pathways into channels. We reveal remarkable similarities between the allosteric channels of E198K and those in phosphorylation-activated WT, suggesting that the autoinhibition can be alleviated through a conserved mechanism. In contrast, we find that another disease mutant, E200K, which is in spatial proximity of E198, does not repartition the allosteric pathways leading to the substrate binding site; however, it may still induce exposure of the active site. This finding agrees with our biochemical data, allowing us to predict the activity of PP2A with the phosphorylated B56δ and provide insight into how disease mutations in spatial proximity alter the enzymatic activity in surprisingly different mechanisms.