The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years.

BACKGROUND: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. METHODS: In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. RESULTS: We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum ß-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05). CONCLUSIONS: Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.

Biochar imparted constructed wetlands (CWs) for enhanced biodegradation of organic and inorganic pollutants along with its limitation.

The remediation of polluted soil and water stands as a paramount task in safeguarding environmental sustainability and ensuring a dependable water source. Biochar, celebrated for its capacity to enhance soil quality, stimulate plant growth, and adsorb a wide spectrum of contaminants, including organic and inorganic pollutants, within constructed wetlands, emerges as a promising solution. This review article is dedicated to examining the effects of biochar amendments on the efficiency of wastewater purification within constructed wetlands. This comprehensive review entails an extensive investigation of biochar's feedstock selection, production processes, characterization methods, and its application within constructed wetlands. It also encompasses an exploration of the design criteria necessary for the integration of biochar into constructed wetland systems. Moreover, a comprehensive analysis of recent research findings pertains to the role of biochar-based wetlands in the removal of both organic and inorganic pollutants. The principal objectives of this review are to provide novel and thorough perspectives on the conceptualization and implementation of biochar-based constructed wetlands for the treatment of organic and inorganic pollutants. Additionally, it seeks to identify potential directions for future research and application while addressing prevailing gaps in knowledge and limitations. Furthermore, the study delves into the potential limitations and risks associated with employing biochar in environmental remediation. Nevertheless, it is crucial to highlight that there is a significant paucity of data regarding the influence of biochar on the efficiency of wastewater treatment in constructed wetlands, with particular regard to its impact on the removal of both organic and inorganic pollutants.

Effect of different concentrations of resveratrol on nuclear maturation and in-vitro development competence of oocytes of Nili Ravi buffalo.

Buffaloes are considered animals of the future with the ability to survive under unfavorable conditions. However, the lack of access to superior germplasm poses a significant challenge to increasing buffalo production. Resveratrol has been shown to improve oocyte quality and developmental competence in various animals during in vitro embryo development. However, limited information is available on the use of resveratrol to improve the in vitro maturation and development competence of Nili Ravi buffalo oocytes. Therefore, the current study aimed to investigate the influence of different concentrations of resveratrol on the maturation, fertilization, and development of buffalo oocytes under in vitro conditions. Oocytes were collected from ovaries and subjected to in vitro maturation (IVM) using varying concentrations of resveratrol (0 µM, 0.5 µM, 1 µM, 1.5 µM, and 2 µM), and the maturation process was assessed using a fluorescent staining technique. Results indicated no significant differences in oocyte maturation, morula rate, and blastocyst rate among the various resveratrol concentrations. However, the cleavage rate notably increased with 1 µM and 1.5 µM concentrations of resveratrol (p < 0.05). In conclusion, the study suggests that adding 1 µM of resveratrol into the maturation media may enhance the cleavage and blastocyst hatching of oocytes of Nili Ravi buffaloes. These findings hold promise for advancing buffalo genetics, reproductive performance, and overall productivity, offering potential benefits to the dairy industry, especially in Asian countries.

Temporal Trends of Age-Adjusted Mortality Rates for Rheumatic Heart Disease in Brazil From 2000 to 2021.

Background Rheumatic heart disease (RHD) is a chronic cardiovascular condition stemming from an infectious origin, posing a substantial health burden, particularly in economically disadvantaged regions. It starts with acute rheumatic fever (ARF), a complication following group A Streptococcus infection, leading to heart valve damage and, over time, structural heart abnormalities. RHD contributes to premature deaths, especially in low-middle-income countries. Although the incidence and prevalence have generally reduced globally due to antibiotics and improved healthcare, it remains a significant public health concern in Brazil, echoing its prevalence in many developing nations around the world. RHD stands as a poignant testament to the intersection of socio-economic disparities and healthcare challenges within Brazil's diverse population. In Brazil, despite advancements in healthcare, RHD continues to impact communities, highlighting the urgent need for enhanced prevention strategies, access to quality healthcare services, and heightened awareness to combat this preventable, yet persistent, cardiac condition. Understanding the epidemiological landscape and socio-cultural factors influencing RHD in Brazil is crucial for developing targeted interventions aimed at mitigating its burden on individuals, families, and the healthcare system at large. Thus, our study focuses on analyzing age-related mortality rates linked to ARF and chronic RHD (ARHD) in Brazil from 2000 to 2021, particularly examining gender disparities. Materials and methods This retrospective cohort study employed a descriptive time-series approach, utilizing comprehensive nationwide data from Brazil spanning from 2000 to 2021 to assess trends in diverse age groups, among both sexes, enabling a detailed analysis of temporal patterns. Mortality data, extracted and categorized meticulously, were subjected to Joinpoint statistical analyses enabling comparative assessments, with average annual percent change (AAPC) and annual percent change (APC) serving as key metrics to quantify and interpret trends over the analyzed period. Results The acute RHD (ARHD)-related mortality declined over the analyzed years supported by AAPC, with higher mortality reduction in females. The age-adjusted mortality rate for "males and females" decreased from 78 to 67 deaths/100,000 from 2000 to 2021. Female mortality dropped from 85 to 69/100,000, and male mortality decreased from 73 to 63/100,000 over the same period. For ARHD, male age groups (20-29, 60-69, 70-79, 80+) showed declining mortality, while the 30-59 age group exhibited an upward. Females AAMR for chronic RHD (CRHD) decreased across all age groups, with significant reductions in the 80 years and above age group from 2000-2002 (APC: -11.94*) and steadily from 2002 onwards (APC: -1.33). Conclusions Our study revealed an overall decline in mortality rates for both acute and CRHD across both sexes. Females consistently exhibited higher mortality rates and a more pronounced reduction compared to males in both acute and CRHD. In ARHD, males experience the highest mortality in the 50-59 age group, while females have a peak in the 40-49 age group. The 60-69 age group had the highest mortality in CRHD for both sexes. Conversely, the 20-29 age group displayed the lowest mortality in CRHD, and the 80-89 age group had the lowest mortality in ARHD.

Exploring Potentilla nepalensis Phytoconstituents: Integrated Strategies of Network Pharmacology, Molecular Docking, Dynamic Simulations, and MMGBSA Analysis for Cancer Therapeutic Targets Discovery.

Potentilla nepalensis belongs to the Rosaceae family and has numerous therapeutic applications as potent plant-based medicine. Forty phytoconstituents (PCs) from the root and stem through n-hexane (NR and NS) and methanolic (MR and MS) extracts were identified in earlier studies. However, the PCs affecting human genes and their roles in the body have not previously been disclosed. In this study, we employed network pharmacology, molecular docking, molecular dynamics simulations (MDSs), and MMGBSA methodologies. The SMILES format of PCs from the PubChem was used as input to DIGEP-Pred, with 764 identified as the inducing genes. Their enrichment studies have shown inducing genes' gene ontology descriptions, involved pathways, associated diseases, and drugs. PPI networks constructed in String DB and network topological analyzing parameters performed in Cytoscape v3.10 revealed three therapeutic targets: TP53 from MS-, NR-, and NS-induced genes; HSPCB and Nf-kB1 from MR-induced genes. From 40 PCs, two PCs, 1b (MR) and 2a (MS), showed better binding scores (kcal/mol) with p53 protein of -8.6 and -8.0, and three PCs, 3a, (NR) 4a, and 4c (NS), with HSP protein of -9.6, -8.7, and -8.2. MDS and MMGBSA revealed these complexes are stable without higher deviations with better free energy values. Therapeutic targets identified in this study have a prominent role in numerous cancers. Thus, further investigations such as in vivo and in vitro studies should be carried out to find the molecular functions and interlaying mechanism of the identified therapeutic targets on numerous cancer cell lines in considering the PCs of P. nepalensis.

QSAR-driven screening uncovers and designs novel pyrimidine-4,6-diamine derivatives as potent JAK3 inhibitors.

This study presents a robust and integrated methodology that harnesses a range of computational techniques to facilitate the design and prediction of new inhibitors targeting the JAK3/STAT pathway. This methodology encompasses several strategies, including QSAR analysis, pharmacophore modeling, ADMET prediction, covalent docking, molecular dynamics (MD) simulations, and the calculation of binding free energies (MM/GBSA). An efficacious QSAR model was meticulously crafted through the employment of multiple linear regression (MLR). The initial MLR model underwent further refinement employing an artificial neural network (ANN) methodology aimed at minimizing predictive errors. Notably, both MLR and ANN exhibited commendable performance, showcasing R2 values of 0.89 and 0.95, respectively. The model's precision was assessed via leave-one-out cross-validation (CV) yielding a Q2 value of 0.65, supplemented by rigorous Y-randomization. , The pharmacophore model effectively differentiated between active and inactive drugs, identifying potential JAK3 inhibitors, and demonstrated validity with an ROC value of 0.86. The newly discovered and designed inhibitors exhibited high inhibitory potency, ranging from 6 to 8, as accurately predicted by the QSAR models. Comparative analysis with FDA-approved Tofacitinib revealed that the new compounds exhibited promising ADMET properties and strong covalent docking (CovDock) interactions. The stability of the new discovered and designed inhibitors within the JAK3 binding site was confirmed through 500 ns MD simulations, while MM/GBSA calculations supported their binding affinity. Additionally, a retrosynthetic study was conducted to facilitate the synthesis of these potential JAK3/STAT inhibitors. The overall integrated approach demonstrates the feasibility of designing novel JAK3/STAT inhibitors with robust efficacy and excellent ADMET characteristics that surpass Tofacitinib by a significant margin.Communicated by Ramaswamy H. Sarma.

In Silico, In Vitro, and In Vivo Evaluation of Caffeine-Coated Nanoparticles as a Promising Therapeutic Avenue for AML through NF-Kappa B and TRAIL Pathways Modulation.

BACKGROUND: Advancements in nanoscience have led to a profound paradigm shift in the therapeutic applications of medicinally important natural drugs. The goal of this research is to develop a nano-natural product for efficient cancer treatment. METHODS AND RESULTS: For this purpose, mesoporous silica nanoparticles (MSNPs) were formulated, characterized, and loaded with caffeine to develop a targeted drug delivery system, i.e., caffeine-coated nanoparticles (CcNPs). In silico docking studies were conducted to examine the binding efficiency of the CcNPs with different apoptotic targets followed by in vitro and in vivo bioassays in respective animal models. Caffeine, administered both as a free drug and in nanomedicine form, along with doxorubicin, was delivered intravenously to a benzene-induced AML model. The anti-leukemic potential was assessed through hematological profiling, enzymatic biomarker analysis, and RT-PCR examination of genetic alterations in leukemia markers. Docking studies show strong inter-molecular interactions between CcNPs and apoptotic markers. In vitro analysis exhibits statistically significant antioxidant activity, whereas in vivo analysis exhibits normalization of the genetic expression of leukemia biomarkers STMN1 and S1009A, accompanied by the restoration of the hematological and morphological traits of leukemic blood cells in nanomedicine-treated rats. Likewise, a substantial improvement in hepatic and renal biomarkers is also observed. In addition to these findings, the nanomedicine successfully normalizes the elevated expression of GAPDH and mTOR induced by exposure to benzene. Further, the nanomedicine downregulates pro-survival components of the NF-kappa B pathway and upregulated P53 expression. Additionally, in the TRAIL pathway, it enhances the expression of pro-apoptotic players TRAIL and DR5 and downregulates the anti-apoptotic protein cFLIP. CONCLUSIONS: Our data suggest that MSNPs loaded with caffeine, i.e., CcNP/nanomedicine, can potentially inhibit transformed cell proliferation and induce pro-apoptotic TRAIL machinery to counter benzene-induced leukemia. These results render our nanomedicine as a potentially excellent therapeutic agent against AML.

Utilization of ZnFe2O4-Polyaniline (PANI), ZnFe2O4-Polystyrene (PST), and ZnFe2O4-Polypyrrole (PPy) nanocomposites for removal of Red X-GRL and Direct Sky Blue dyes from wastewater: Equilibrium, kinetic and thermodynamic studies.

In this study, ZnFe2O4-Polyaniline (PANI), ZnFe2O4-Polystyrene (PST), and ZnFe2O4-Polypyrrole (Ppy) nanocomposites were synthesized by the adsorption method and characterized by field emission scanning electron microscopy and Fourier transform infrared spectrometer. Batch adsorption experiments were conducted for removing two types of hazardous dyes Red X-GRL and Direct Sky Blue 51 from an aqueous solution and the effect of pH, adsorbent dosage, contact time, and initial concentration of dyes were investigated. Meanwhile, kinetic, isotherm, and thermodynamic parameters were also determined. The electrolyte and surfactant effect was also tested for the prepared nanocomposites. To test the reusability desorption study was also conducted.

The Fabrication of Halogen-Doped FeWO4 Heterostructure Anchored over Graphene Oxide Nanosheets for the Sunlight-Driven Photocatalytic Degradation of Methylene Blue Dye.

Rapid industrialization and urbanization are the two significant issues causing environmental pollution. The polluted water from various industries contains refractory organic materials such as dyes. Heterogeneous photocatalysis using semiconductor metal oxides is an effective remediation technique for wastewater treatment. In this research, we used a co-precipitation-assisted hydrothermal method to synthesize a novel I-FeWO4/GO sunlight-active nanocomposite. Introducing dopant reductive iodine species improved the catalytic activity of FeWO4/GO. I- ions improved the catalytic performance of H2O2 by doping into FeWO4/GO composite. Due to I- doping and the introduction of graphene as a support medium, enhanced charge separation and transfer were observed, which is crucial for efficient heterogeneous surface reactions. Various techniques, like FTIR, SEM-EDX, XRD, and UV-Vis spectroscopy, were used to characterize composites. The Tauc plot method was used to calculate pristine and iodine-doped FeWO4/GO bandgap. Iodine doping reduced the bandgap from 2.8 eV to 2.6 eV. The degradation of methylene blue (MB) was evaluated by optimizing various parameters like catalyst concentration, oxidant dose, pH, and time. The optimum conditions for photocatalysts where maximum degradation occurred were pH = 7 for both FeWO4/GO and I-FeWO4/GO; oxidant dose = 9 mM and 7 mM for FeWO4/GO and I-FeWO4/GO; and catalyst concentration = 30 mg and 35 mg/100 mL for FeWO4/GO and I-FeWO4/GO; the optimum time was 120 min. Under these optimum conditions, FeWO4/GO and I-FeWO4/GO showed 92.0% and 97.0% degradation of MB dye.

Heavy metals in five commonly consumed fish species from River Swat, Pakistan, and their implications for human health using multiple risk assessment approaches.

This study analyzed the levels of heavy metals bioaccumulation in commonly consumed riverine fish species, including G. cavia, T. macrolepis, G. gotyla, S. plagiostomus, and M. armatus from River Swat in Pakistan, and quantify their potential risk to children and adults in general and fisherfolk communities using multiple pollution and risk assessment approaches. The highest metal detected by inductive coupled plasma mass spectrometry (ICP-MS) was Zn, which ranged from 49.61 to 116.83 mg/kg, followed by Fe (19.25-101.33 mg/kg) > Mn (5.25-40.35 mg/kg) > Cr (3.05-14.59 mg/kg) > Ni (4.26-11.80 mg/kg) > Al (1.59-12.25 mg/kg) > Cu (1.24-8.59 mg/kg) > Pb (0.29-1.95 mg/kg) > Co (0.08-0.46 mg/kg) > Cd (0.01-0.29 mg/kg), demonstrating consistent fluctuation with the safe recommendations of global regulatory bodies. The average bioaccumulation factor (BAF) values in the examined fish species were high (BAF > 5000) for Pb, Zn, Mn, Cu, Cr, Ni, and Cd, bioaccumulate (1000 > BAF < 5000) for Co, and probable accumulative (BAF <1000) for Fe, and Al, while the overall ∑heavy metals pollution index (MPI) values were greater than one (MPI > 1) indicating sever heavy metals toxicity in G. cavia, followed by S. plagiostomus, M. armatus, G. gotyla, and T. macrolepis. The multivariate Pearson's correlation analysis identified the correlation coefficients between heavy metal pairs (NiCr, CuCr, PbCr, AlCo, CuNi, and PbNi), the hierarchical cluster analysis (CA) determined the origin by categorizing heavy metal accumulation into Cluster-A, Cluster-B, and Cluster-C, and the principal component analysis (PCA) discerned nearby weathering, mining, industrial, municipal, and agricultural activities as the potential sources of heavy metals bioaccumulation in riverine fish. As per human risk perspective, S.plagiostomus contributed significantly to the estimated daily intake (EDI) of heavy metals, followed by G.cavia > M.armatus > G.gotyla > T.macrolepis in dependent children and adults of the fisherfolk followed by the general population. The non-carcinogenic target hazard quotient (THQ) and hazard index (HI) values for heavy metal intake through fish exposure were < 1, while the carcinogenic risk (CR) for individual metal intake and the total carcinogenic risk (TCR) for cumulative Cr, Cd, and Pb intake were within the risk threshold of 10-6-10-4, suggesting an acceptable to high non-carcinogenic and carcinogenic risk for both children and adults in the fisherfolk, followed by the general population.

Bio-Organically Acidified Product-Mediated Improvements in Phosphorus Fertilizer Utilization, Uptake and Yielding of Zea mays in Calcareous Soil.

The demand for a better agricultural productivity and the available phosphorus (P) limitation in plants are prevailing worldwide. Poor P availability due to the high pH and calcareous nature of soils leads to a lower P fertilizer use efficiency of 10-25% in Pakistan. Among different technologies, the use of biologically acidified amendments could be a potential strategy to promote soil P availability and fertilizer use efficiency (FUE) in alkaline calcareous soils. However, this study hypothesized that an acidified amendment could lower soil pH and solubilize the insoluble soil P that plants can potentially uptake and use to improve their growth and development. For this purpose, the test plant Zea mays was planted in greenhouse pots with a recommended dose rate of 168 kg ha-1 of P for selected phosphatic fertilizers, viz., DAP (diammonium phosphate), SSP (single superphosphate), and RP (rock phosphate) with or without 2% of the acidified product and a phosphorus solubilizing Bacillus sp. MN54. The results showed that the integration of acidified amendments and PSB strain MN54 with P fertilizers improved P fertilizer use efficiency (FUE), growth, yield, and P uptake of Zea mays as compared to sole application of P fertilizers. Overall, organic material along with DAP significantly improved plant physiological-, biochemical-, and nutrition-related attributes over the sole application of DAP. Interestingly, the co-application of RP with the acidified product and MN54 showed a higher response than the sole application of DAP and SSP. However, based on our study findings, we concluded that using RP with organic amendments was a more economically and environmentally friendly approach compared to the most expensive DAP fertilizer. Taken together, the current study suggests that the use of this innovative new strategy could have the potential to improve FUE and soil P availability via pH manipulation, resulting in an improved crop productivity and quality/food security.

Identification of Disalicyloyl Curcumin as a Potential DNA Polymerase Inhibitor for Marek's Disease Herpesvirus: A Computational Study Using Virtual Screening and Molecular Dynamics Simulations.

Marek's disease virus (MDV) is a highly contagious and persistent virus that causes T-lymphoma in chickens, posing a significant threat to the poultry industry despite the availability of vaccines. The emergence of new virulent strains has further intensified the challenge of designing effective antiviral drugs for MDV. In this study, our main objective was to identify novel antiviral phytochemicals through in silico analysis. We employed Alphafold to construct a three-dimensional (3D) structure of the MDV DNA polymerase, a crucial enzyme involved in viral replication. To ensure the accuracy of the structural model, we validated it using tools available at the SAVES server. Subsequently, a diverse dataset containing thousands of compounds, primarily derived from plant sources, was subjected to molecular docking with the MDV DNA polymerase model, utilizing AutoDock software V 4.2. Through comprehensive analysis of the docking results, we identified Disalicyloyl curcumin as a promising drug candidate that exhibited remarkable binding affinity, with a minimum energy of -12.66 Kcal/mol, specifically targeting the DNA polymerase enzyme. To further assess its potential, we performed molecular dynamics simulations, which confirmed the stability of Disalicyloyl curcumin within the MDV system. Experimental validation of its inhibitory activity in vitro can provide substantial support for its effectiveness. The outcomes of our study hold significant implications for the poultry industry, as the discovery of efficient antiviral phytochemicals against MDV could substantially mitigate the economic losses associated with this devastating disease.

Electrochemical Impedance Spectroscopy-Based Sensing of Biofilms: A Comprehensive Review.

Biofilms are complex communities of microorganisms that can form on various surfaces, including medical devices, industrial equipment, and natural environments. The presence of biofilms can lead to a range of problems, including infections, reduced efficiency and failure of equipment, biofouling or spoilage, and environmental damage. As a result, there is a growing need for tools to measure and monitor levels of biofilms in various biomedical, pharmaceutical, and food processing settings. In recent years, electrochemical impedance sensing has emerged as a promising approach for real-time, non-destructive, and rapid monitoring of biofilms. This article sheds light on electrochemical sensing for measuring biofilms, including its high sensitivity, non-destructive nature, versatility, low cost, and real-time monitoring capabilities. We also discussed some electrochemical sensing applications for studying biofilms in medical, environmental, and industrial settings. This article also presents future perspectives for research that would lead to the creation of reliable, quick, easy-to-use biosensors mounted on unmanned aerial vehicles (UAVs), and unmanned ground vehicles (UGVs), utilizing artificial intelligence-based terminologies to detect biofilms.

Global digital divide and environmental degradation in Africa.

ICTs and access to Internet use are considered vital for the achievement of sustainable development goals. So, this study explored the effect of the global digital divide, trade openness, renewable energy consumption, and forestation on greenhouse gas (GHG) emissions in 42 high-income countries (HICs) and high-middle-income (HMICs), low-income countries (LICs), and low-middle-income countries (LMICs) of Africa from 1990 to 2018. TheDumitrescu-Hurlin causality results confirmed a unidirectional causality from GHG emissions to the global digital divide (HICs and HMICs), global digital divide to GHG emissions (LICs), and GHG emission to trade openness (LICs and LMICs). Moreover, the long-run results of the autoregressive distributed lag (ARDL) model showed an increase in GHG due to an increase in the global digital divide in all three panels. Further, ARDL results showed reduced GHG emissions due to increased trade openness in LIC and LMICs, renewable energy consumption, and forestation in all three panels. Thus, to encounter pollution from Internet use, the government should start environment-friendly projects through public and private investment in smart and modern environment-friendly technology and reduce the taxes and tariffs on them. Moreover, the governments of African countries should create public awareness through print and electronic media for raising the forestation area.

Phytochemical Analysis, In Vitro Biological Activities, and Computer-Aided Analysis of Potentilla nepalensis Hook Compounds as Potential Melanoma Inhibitors Based on Molecular Docking, MD Simulations, and ADMET.

Potentilla nepalensis Hook is a perennial Himalayan medicinal herb of the Rosaceae family. The present study aimed to evaluate biological activities such as the antioxidant, antibacterial, and anticancer activities of roots and shoots of P. nepalensis and its synergistic antibacterial activity with antibacterial drugs. Folin-Ciocalteau and aluminium chloride methods were used for the calculation of total phenolic (TPC) and flavonoid content (TFC). A DPPH radical scavenging assay and broth dilution method were used for the determination of the antioxidant and antibacterial activity of the root and shoot extracts of P. nepalensis. Cytotoxic activity was determined using a colorimetric MTT assay. Further, phytochemical characterization of the root and shoot extracts was performed using the Gas chromatography-mass spectrophotometry (GC-MS) method. The TPC and TFC were found to be higher in the methanolic root extract of P. nepalensis. The methanolic shoot extract of P. nepalensis showed good antioxidant activity, while then-hexane root extract of P. nepalensis showed strong cytotoxic activity against tested SK-MEL-28 cells. Subsequently, in silico molecular docking studies of the identified bioactive compounds predicted potential anticancer properties. This study can lead to the production of new herbal medicines for various diseases employing P. nepalensis, leading to the creation of new medications.

Evidence-Based Interventions to Reduce the Incidence of Common Multidrug-Resistant Gram-Negative Bacteria in an Adult Intensive Care Unit.

Background Multidrug-resistant Gram-negative bacteria (MDR-GNB) present a significant and escalating hazard to healthcare globally. Context-specific interventions have been implemented for the prevention and control of MDR-GNB in several healthcare facilities. The objective of this study was to implement and evaluate the effectiveness of evidence-based interventions in the incidence and dissemination of MDR-GNB. Methods This was a pre-and post-intervention study conducted in three phases at King Abdulaziz Medical City Jeddah, Saudi Arabia. During Phase-1, the data on each of the four MDR-GNB (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) were collected prospectively. Genomic fingerprinting was performed on isolates using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) to determine clonality and establish a link between different strains within and between the hospital wards/units. In the second phase, targeted interventions were implemented in the adult intensive care unit (ICU) based on previously determined risk factors and included the education of healthcare workers on hand hygiene, disinfection of patients' surrounding, daily chlorhexidine baths, and disinfection rooms on discharge with hydrogen peroxide fogging after MDR-GNB patients were discharged. An antibiotic restriction protocol was simultaneously implemented as part of the hospital antibiotic stewardship program. In the third phase, the effectiveness of the interventions was evaluated by comparing the incidence rate and clonality (using ERIC-PCR genetic fingerprints) of MDR-GNB before and after the intervention. Results A significant reduction of MDR-GNB was observed in Phase-2 and Phase-3 compared with Phase-1. The mean incidence rate of MDR-GNB per 1000 patient days in Phase-1 (pre-intervention) was 11.08/1000, followed by 6.07 and 3.54/1000 in Phase-2 and Phase-3, respectively. A statistically significant reduction was observed in the incidence rate of MDR-GNB in the adult ICU (P=0.007), whereas no statistically significant decrease (P=0.419) was observed in areas other than the adult ICU. Two A. baumannii strains appear to be circulating within the ICU environment with reduced frequency in Phase-2 and Phase-3 compared to Phase-1. Conclusion  There was a significant reduction in the incidence of MDR-GNB in the adult ICU due to the successful implementation of both infection control and stewardship interventions, albeit challenging to ascertain the relative contribution of each.

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights.

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.

Investigation of boron-doped graphene oxide anchored with copper sulphide flowers as visible light active photocatalyst for methylene blue degradation.

The non-biodegradable nature of waste emitted from the agriculture and industrial sector contaminates freshwater reserves. Fabrication of highly effective and low-cost heterogeneous photocatalysts is crucial for sustainable wastewater treatment. The present research study aims to construct a novel photocatalyst using a facile ultrasonication-assisted hydrothermal method. Metal sulphides and doped carbon support materials work well to fabricate hybrid sunlight active systems that efficiently harness green energy and are eco-friendly. Boron-doped graphene oxide-supported copper sulphide nanocomposite was synthesized hydrothermally and was assessed for sunlight-assisted photocatalytic degradation of methylene blue dye. BGO/CuS was characterized through various techniques such as SEM-EDS, XRD, XPS, FTIR, BET, PL, and UV-Vis DRS spectroscopy. The bandgap of BGO-CuS was found to be 2.51 eV as evaluated through the tauc plot method. The enhanced dye degradation was obtained at optimum conditions of pH = 8, catalyst concentration (20 mg/100 mL for BGO-CuS), oxidant dose (10 mM for BGO-CuS), and optimum time of irradiation was 60 min. The novel boron-doped nanocomposite effectively degraded methylene blue up to 95% under sunlight. Holes and hydroxyl radicals were the key reactive species. Response surface methodology was used to analyze the interaction among several interacting parameters to remove dye methylene blue effectively.

Risk Factors for Infection With Multidrug-Resistant Gram-Negative Bacteria in a Tertiary Care Hospital in Saudi Arabia: A Case-Control Study.

Background The increase in the incidence of multidrug-resistant (MDR) organisms especially Gram-negative bacteria (GNB) in healthcare facilities is a serious cause of concern. This study identified risk factors for the infection with these MDR GNB, such as Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli to inform healthcare workers about strategies for their containment. Methods A case-control study was carried out at a tertiary care hospital where 100 patients with healthcare-associated infections (infections arising 48 hours after admission) caused by MDR GNB were compared with two control groups, i.e., 100 patients with healthcare-associated infections caused by non-MDR GNB (not meeting the criteria of MDR) and 100 patients without infection caused by GNB. MDR bacteria were defined as the ones that were non-susceptible to at least one antibiotic in three or more classes of antibiotics. The data were analyzed using descriptive statistics (frequency and percentage of categorical variables). Multivariate regression analysis was undertaken to identify significant predictors of MDR GNB. Odds ratios with 95% confidence intervals were calculated, and the level of significance was determined at p-value < 0.05. Results A total of 388 organisms were isolated during four months (January-April 2015) from 332 patients. Fifty-six (17%) of the patients were infected with more than one organism. Among the MDR bacteria, the most dominant MDR organism was A. baumannii (38%), followed by K. pneumoniae (31%), P. aeruginosa (20%), and E. coli (11%). Among the non-MDR organisms, the most dominant was P. aeruginosa (47%), followed by E. coli (32%), K. pneumoniae (18%), and A. baumannii (3%). Patients with MDR organisms compared with the first control group (patients with non-MDR organisms) showed that prior antibiotic use (p-value: 0.001), intensive care unit (ICU) admission (p-value: 0.001), and indwelling medical devices (p-value: 0.005) were significant risk factors for MDR infections. It was also found that the risk factors for MDR GNB infection were the same in the second control group (patients without infection): prior antibiotic use (p-value: 0.002), ICU admission (p-value: 0.001), and indwelling medical devices (p-value: 0.03). Based on the comparison of the two control groups, prolonged hospital stays of more than five days (p-value: 0.001), immunosuppressive therapy (p-value: 0.02), and over 60 years of age (p-value: 0.02) were significant risk factors for non-MDR infection. Conclusion  The risk factors identified in our study provide guidance to healthcare workers for the prevention and containment of MDR GNB.

Swellable Array Strategy Based on Designed Flexible Double Hypercross-linked Polymers for Synergistic Adsorption of Toluene and Formaldehyde.

High-capacity adsorption and removal of complex volatile organic compounds (VOCs) from real-world environments is a tough challenge for researchers. Herein, a swellable array adsorption strategy was proposed to realize the synergistic adsorption of toluene and formaldehyde on the flexible double hypercross-linked polymers (FD-HCPs). FD-HCPs exhibited multiple adsorption sites awarded by a hydrophobic benzene ring/pyrrole ring and a hydrophilic hydroxyl structural unit. The array benzene ring, hydroxyl, and pyrrole N sites in FD-HCPs effectively captured toluene and formaldehyde molecules through π-π conjugation and electrostatic interaction and weakened their mutual competitive adsorption. Interestingly, the strong binding force of toluene molecules to the skeleton deformed the pore structure of FD-HCPs and generated new adsorption microenvironments for the other adsorbate. This behavior significantly improved the adsorption capacity of FD-HCPs for toluene and formaldehyde by 20% under multiple VOCs. Moreover, the pyrrole group in FD-HCPs greatly hindered H2O molecule diffusion in the pore, thus efficiently weakening the competitive adsorption of H2O toward VOCs. These fascinating properties enabled FD-HCPs to achieve synergistic adsorption for multicomponent VOC vapor under a highly humid environment and overcame single-species VOC adsorption properties on state-of-the-art porous adsorbents. This work provides the practical feasibility of synergistic adsorption to remove complex VOCs in real-world environments.