Therapeutic drug monitoring of vancomycin in surgical patients through a validated HPLC method.

BACKGROUND: Vancomycin is being used for the treatment of a variety of infections caused by methicillin resistant Staphylococcus aureus and methicillin susceptible Staphylococcus aureus. Therapeutic drug monitoring (TDM) is highly recommended for ensuring the safe and effective therapy with vancomycin. A reliable and cost-effective bioanalytical method is required for TDM as well as pharmacokinetic studies of vancomycin. MATERIALS AND METHODS: A selective, sensitive, and cost effective HPLC method was developed and validated for quantification of vancomycin concentrations in human plasma. The mobile phase was a mixture of buffer (50 mM ammonium dihydrogen phosphate, pH 2.4) and acetonitrile 88 : 12 v/v. The separation was carried on C18 column (125 × 4.6 mm, particle size 5 µm) with isocratic flow rate of 0.370 mL/min at room temperature with UV detection at 215 nm. The method was validated for sensitivity, accuracy, and precision as well as stability of vancomycin in human plasma by following European Medicine Agency (EMA) guideline. Therapeutic drug monitoring of vancomycin was performed by quantifying the trough concentrations of vancomycin in 65 human plasma samples after administration of therapeutically relevant dose. RESULTS: The developed method was sensitive enough to quantify vancomycin concentrations as low as 0.25 mg/L in human plasma. Moreover, the method was proved accurate and precise in terms of quantifying the unknown concentration of vancomycin. The evaluation of short-term, long-term, and freeze-thaw stability proved the stability of vancomycin in human plasma. The TDM of vancomycin by using this method showed that 39 (60%) samples were within the target trough concentration range (TTCR), i.e. 10 - 20 mg/L, while 23 samples (35.4%) were below the TTCR, and 3 samples (4.6%) were above this range. CONCLUSION: The developed method is sensitive and cost effective for quantification of vancomycin in human plasma. The results of sample analysis shows that the developed method can be used reliably for TDM of vancomycin.

Transcriptomics data integration and analysis to uncover hallmark genes in hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease that mainly affects the myocardium. In the current study, we aim to explore HCM-related hub genes through the analysis of differentially expressed genes (DEGs) between HCM and normal sample groups. METHODS: The GSE68316 and GSE36961 expression profiles were obtained from the Gene Expression Omnibus (GEO) database for the identification of DEGs, to explore hub genes, and to perform their expression analysis. Clinical HCM and control tissue samples were taken for expression and promoter methylation validation analysis via RNA-sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) analyses. Then, other different bioinformatics tools were employed to perform STRING, lncRNA-miRNA-mRNA regulatory networks, gene enrichment, and drug prediction analyses. RESULTS: In total, the top 20 DEGs, including 10 up-regulated and 10 down-regulated, were obtained from GSE68316. Out of the 20 DEGs, we subsequently identified the 8 most important hub genes including 5 up-regulated genes (EPB42, UQCRH, CA1, PFDN5, and LSM5) and 3 down-regulated genes (RPS24, TNS1, and RPL26). Expression and promoter methylation dysregulation of these genes were further validated on clinical HCM samples paired with controls. Next, we further investigated hub genes' regulatory 6 miRNAs (has-mir-1-3p, has-mir-129-5p, has-mir-16-5p, has-mir-23b-3p, has-mir-27-3p, and has-mir-182-5p) and miRNAs regulatory 4 lncRNAs (NUTMB2-AS1, NEAT1, XIST, and GABPB1-AS1) in this study via the lncRNA-cricRNA-miRNA-mRNA regulatory network. Later on, gene enrichment analysis revealed that hub genes were enriched in various important pathways including Nitrogen metabolism, Ribosome, RNA degradation, Cardiac muscle contraction, and Coronavirus disease, etc. Finally, the drug prediction analysis highlighted different potential candidate drugs for altering the expression of hub genes in the treatment of HCM. CONCLUSION: In summary, the identification of key hub genes and their enrichment analysis in the current study may shed light on the mechanisms behind the occurrence and development of HCM.

Bone morphogenetic protein 1: a prognostic indicator and potential biomarker in three cancer types.

BACKGROUND: Bone morphogenetic protein 1 (BMP1) is a metalloprotease that plays a role in activating both transforming growth factor-ß (TGF-ß) and BMP signaling pathways. TGF-ß has been identified as a factor initiating and facilitating cancer development. Consequently, we propose the hypothesis that dysregulation of BMP1 could potentially contribute to the onset and advancement of human cancers. METHODS: In this research, we aimed to analyze BMP1 expression level and the associated clinical outcomes across various cancers using online cancer OMICS databases, advanced Bioinformatics tools, and molecular analyses. RESULTS: The outcomes of our web server-based expression analysis indicated an up-regulation of BMP1 in a majority of the human cancers examined. External validation using clinical samples also showed higher expression of BMP1. Moreover, heightened BMP1 expression exhibited a noteworthy correlation with reduced overall survival (OS) duration in Bladder Cancer (BLCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung Adenocarcinoma (LUAD) patients. This suggests a substantial involvement of the BMP1 gene in the development and progression of these three types of cancers. The major signaling pathways related with BMP1 enriched genes were "ECM-receptor interaction, Amoebiasis, Focal adhesion, Protein digestion and absorption, progesterone-mediated, PI3K-Akt signaling pathway, and platelet activation". Moreover, we also explored some interesting correlations among BMP1 expression and its DNA promoter methylation level, CD8+ T immune cells level, and genetic variations. CONCLUSION: In conclusion, our study has provided some solid basis for BMP1 to be used as a reliable common biomarker for BLCA, KIRC, and LUAD patients.

Comparative phenotypic and genotypic analysis of community-acquired and hospital-acquired intra-abdominal infections among liver transplanted patients.

AIM: During liver transplantation, both hospital-acquired (HA) and community-acquired (CA) intra-abdominal infections (IAIs) are involved causing life-threatening diseases. Therefore, comparative studies of aerobic and facultative anaerobic HA-IAIs and CA-IAIs after liver transplantation surgery are necessary. METHODS AND RESULTS: The species of detected isolates (310) from intra-abdominal fluid were identified and classified into hospital-acquired intra-abdominal infections (HA-IAIs) and community-acquired intra-abdominal infections (CA-IAIs). Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were the most commonly detected species. The resistant phenotypes were commonly detected among the HA-IAIs; however, the virulent phenotypes were the predominant strains of CA-IAIs. Regrettably, the resistance profiles were shocking, indicating the inefficacy of monotherapy in treating these isolates. Therefore, we confirmed the use of empirical combination therapies of amikacin and meropenem for treating all IAIs (FICI ≤ 0.5). Unfortunately, the high diversity and low clonality of all identified HA and CA-IAIs were announced with D-value in the range of 0.992-1. CONCLUSION: This diversity proves that there are infinite numbers of infection sources inside and outside healthcare centers.

Revolutionizing and identifying novel drug targets in Citrobacter koseri via subtractive proteomics and development of a multi-epitope vaccine using reverse vaccinology and immuno-informatics.

Citrobacter koseri is a gram-negative rod that has been linked to infections in people with significant comorbidities and immunocompromised immune systems. It is most commonly known to cause urinary tract infections. Thus, the development of an efficacious C. koseri vaccine is imperative, as the pathogen has acquired resistance to current antibiotics. Subtractive proteomics was employed during this research to identify potential antigenic proteins to design an effective vaccine against C. koseri. The pipeline identified two antigenic proteins as potential vaccine targets: DP-3-O-acyl-N-acetylglucosamine deacetylase and Arabinose 5-phosphate isomerase. B and T cell epitopes from the specific proteins were forecasted employing several immunoinformatic and bioinformatics resources. A vaccine was created using a combination of seven cytotoxic T cell lymphocytes (CTL), five helper T cell lymphocyte (HTL), and seven linear B cell lymphocyte (LBL) epitopes. An adjuvant (ß-defensin) was added to the vaccine to enhance immunological responses. The created vaccine was stable for use in humans, highly antigenic, and non-allergenic. The vaccine's molecular and interactions binding affinity with the human immunological receptor TLR3 were studied using MMGBSA, molecular dynamics (MD) simulations, and molecular docking analyses. E. coli (strain-K12) plasmid vector pET-28a (+) was used to examine the ability of the vaccine to be expressed. The vaccine shows great promise in terms of developing protective immunity against diseases, based on the results of these computer experiments. However, in vitro and animal research are required to validate our findings.Communicated by Ramaswamy H. Sarma.

Isolation, preparation and investigation of leaf extracts of Aloe barbadensis for its remedial effects on tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) by in vivo and in silico approaches in experimental rats.

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

Anesthesia and surgery induce changes in endogenous brain protective protein (RNF146) and delirium-like behavior in aged rats.

BACKGROUND: Postoperative delirium (POD) is a common complication after anesthesia and surgery, especially in the elderly. RNF146 has neuroprotective effects in cerebral ischemia, hypoxia, and chronic neurological diseases. However, whether RNF146 expression is related to the occurrence and development of POD remains unclear. Therefore, in this study, we aimed to determine whether RNF146 is involved in the occurrence of POD. METHODS: (Sprague-Dawley) male rats (18 months old) were splenectomized under sevoflurane anesthesia. The cognitive function of rats at 1, 3, and 7 d after anesthesia and surgery was evaluated. Changes in the expression of neuroinflammatory cytokines, IL-6 and IL-10, and RNF146 were measured in the hippocampus in both control group (con) and anesthesia (AS) group. We examined cognitive outcomes and expression of inflammatory factors and RNF146 in con and AS mice using cluster analysis. RESULTS: The cognitive ability and mobility of rats after anesthesia and surgery at day 1, 3, and 7 decreased, especially at day 3. Similarly, the expression of neuroinflammatory factors and RNF146 increased after anesthesia and surgery at day 1, 3, and 7, and the increase was highest at day 3. The clustering and correlation analysis of RNF146 expression in the hippocampi of elderly rats revealed a correlation between POD and neuroinflammation resulting from anesthesia and surgery. CONCLUSION: Anesthesia and surgery can lead to POD and neuroinflammation. The expression of RNF146 correlates with delirium and neuroinflammation caused by anesthesia and surgery.

Therapeutic Potential of Green-Engineered ZnO Nanoparticles on Rotenone-Exposed D. melanogaster (Oregon R+): Unveiling Ameliorated Biochemical, Cellular, and Behavioral Parameters.

Nanotechnology holds significant ameliorative potential against neurodegenerative diseases, as it can protect the therapeutic substance and allow for its sustained release. In this study, the reducing and capping agents of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) extracts were used to synthesize bio-mediated zinc oxide nanoparticles (ZnO-NPs) against bacteria (Staphylococcus aureus and Escherichia coli) and against rotenone-induced toxicities in D. melanogaster for the first time. Their optical and structural properties were analyzed via FT-IR, DLS, XRD, EDS, SEM, UV-Vis, and zeta potential. The antioxidant and antimicrobial properties of the fabricated ZnO-NPs were evaluated employing cell-free models (DPPH and ABTS) and the well diffusion method, respectively. Rotenone (500 µM) was administered to Drosophila third instar larvae and freshly emerged flies for 24-120 h, either alone or in combination with plant extracts (UD, MC, an MK) and their biogenic ZnO-NPs. A comparative study on the protective effects of synthesized NPs was undertaken against rotenone-induced neurotoxic, cytotoxic, and behavioral alterations using an acetylcholinesterase inhibition assay, dye exclusion test, and locomotor parameters. The findings revealed that among the plant-derived ZnO-NPs, MK-ZnO NPs exhibit strong antimicrobial and antioxidant activities, followed by UD-ZnO NPs and MC-ZnO NPs. In this regard, ethno-nano medicinal therapeutic uses mimic similar effects in D. melanogaster by suppressing oxidative stress by restoring biochemical parameters (AchE and proteotoxicity activity) and lower cellular toxicity. These findings suggest that green-engineered ZnO-NPs have the potential to significantly enhance outcomes, with the promise of effective therapies for neurodegeneration, and could be used as a great alternative for clinical development.

In vitro analysis of PI3K pathway activation genes for exploring novel biomarkers and therapeutic targets in clear cell renal carcinoma.

OBJECTIVES: The regulation of various cellular functions such as growth, proliferation, metabolism, and angiogenesis, is dependent on the PI3K pathway. Recent evidence has indicated that kidney renal clear cell carcinoma (KIRC) can be triggered by the deregulation of this pathway. The objective of this research was to investigate 25 genes associated with activation of the PI3K pathway in KIRC and control samples to identify four hub genes that might serve as novel molecular biomarkers and therapeutic targets for treating KIRC. METHODS: Multi-omics in silico and in vitro analysis was employed to find hub genes related to the PI3K pathway that may be biomarkers and therapeutic targets for KIRC. RESULTS: Using STRING software, a protein-protein interaction (PPI) network of 25 PI3K pathway-related genes was developed. Based on the degree scoring method, the top four hub genes were identified using Cytoscape's Cytohubba plug-in. TCGA datasets, KIRC (786-O and A-498), and normal (HK2) cells were used to validate the expression of hub genes. Additionally, further bioinformatic analyses were performed to investigate the mechanisms by which hub genes are involved in the development of KIRC. Out of a total of 25 PI3K pathway-related genes, we developed and validated a diagnostic and prognostic model based on the up-regulation of TP53 (tumor protein 53) and CCND1 (Cyclin D1) and the down-regulation of PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), and GSK3B (Glycogen synthase kinase-3 beta) hub genes. The hub genes included in our model may be a novel therapeutic target for KIRC treatment. Additionally, associations between hub genes and infiltration of immune cells can enhance comprehension of immunotherapy for KIRC. CONCLUSION: We have created a new diagnostic and prognostic model for KIRC patients that uses PI3K pathway-related hub genes (TP53, PTEN, CCND1, and GSK3B). Nevertheless, further experimental studies are required to ascertain the efficacy of our model.

Therapeutic Switching of Rafoxanide: a New Approach To Fighting Drug-Resistant Bacteria and Fungi.

Control and management of life-threatening bacterial and fungal infections are a global health challenge. Despite advances in antimicrobial therapies, treatment failures for resistant bacterial and fungal infections continue to increase. We aimed to repurpose the anthelmintic drug rafoxanide for use with existing therapeutic drugs to increase the possibility of better managing infection and decrease treatment failures. For this purpose, we evaluated the antibacterial and antifungal potential of rafoxanide. Notably, 70% (70/100) of bacterial isolates showed multidrug resistance (MDR) patterns, with higher prevalence among human isolates (73.5% [50/68]) than animal ones (62.5% [20/32]). Moreover, 22 fungal isolates (88%) were MDR and were more prevalent among animal (88.9%) than human (87.5%) sources. We observed alarming MDR patterns among bacterial isolates, i.e., Klebsiella pneumoniae (75% [30/40; 8 animal and 22 human]) and Escherichia coli (66% [40/60; 12 animal and 28 human]), and fungal isolates, i.e., Candida albicans (86.7% [13/15; 4 animal and 9 human]) and Aspergillus fumigatus (90% [9/10; 4 animal and 5 human]), that were resistant to at least one agent in three or more different antimicrobial classes. Rafoxanide had antibacterial and antifungal activities, with minimal inhibitory concentration (MICs) ranging from 2 to 128 µg/mL. Rafoxanide at sub-MICs downregulated the mRNA expression of resistance genes, including E. coli and K. pneumoniae blaCTX-M-1, blaTEM-1, blaSHV, MOX, and DHA, C. albicans ERG11, and A. fumigatus cyp51A. We noted the improvement in the activity of ß-lactam and antifungal drugs upon combination with rafoxanide. This was apparent in the reduction in the MICs of cefotaxime and fluconazole when these drugs were combined with sub-MIC levels of rafoxanide. There was obvious synergism between rafoxanide and cefotaxime against all E. coli and K. pneumoniae isolates (fractional inhibitory concentration index [FICI] values ≤ 0.5). Accordingly, there was a shift in the patterns of resistance of 16.7% of E. coli and 22.5% of K. pneumoniae isolates to cefotaxime and those of 63.2% of C. albicans and A. fumigatus isolates to fluconazole when the isolates were treated with sub-MICs of rafoxanide. These results were confirmed by in silico and mouse protection assays. Based on the in silico study, one possible explanation for how rafoxanide reduced bacterial resistance is through its inhibitory effects on bacterial and fungal histidine kinase enzymes. In short, rafoxanide exhibited promising results in overcoming bacterial and fungal drug resistance. IMPORTANCE The drug repurposing strategy is an alternative approach to reducing drug development timelines with low cost, especially during outbreaks of disease caused by drug-resistant pathogens. Rafoxanide can disrupt the abilities of bacterial and fungal cells to adapt to stress conditions. The coadministration of antibiotics with rafoxanide can prevent the failure of treatment of both resistant bacteria and fungi, as the resistant pathogens could be made sensitive upon treatment with rafoxanide. From our findings, we anticipate that pharmaceutical companies will be able to utilize new combinations against resistant pathogens.

Screening of four signature genes for clinical testing through bioinformatics and in vitro methods in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is the 6th most common cancer around the globe; its underlying molecular mechanisms and accurate molecular markers are still lacking. In this study, we explored hub genes and their potential signaling pathways through which these genes participate in the development of HNSC. The GSE23036 gene microarray dataset was attained from the GEO (Gene Expression Omnibus) database. Hub genes were identified via the Cytohubba plug-in application of the Cytoscape. The Cancer Genome Atlas (TCGA) datasets and cell lines (HOK and FuDu) were used to evaluate expression variations in the hub genes. Moreover, promoter methylation, genetic alteration, gene enrichment, miRNA network, and immunocyte infiltration analysis were also performed to confirm the oncogenic role and biomarker potential of the hub genes in HNSC patients. Based on the hub gene analysis results, four hub genes, including KNTC1 (Kinetochore Associated 1), CEP55 (Centrosomal protein of 55 kDa), AURKA (Aurora A Kinase), and ECT2 (Epithelial Cell Transforming 2), with the highest degree scores were denoted as hub genes. All these four genes were significantly up-regulated in HNSC clinical samples and cell lines relative to their counterparts. Overexpression of KNTC1, CEP55, AURKA, and ECT2 was also associated with poor survival and various clinical parameters of the HNSC patients. Methylation analysis through targeted bisulfite sequencing of HOK and FuDu cell lines revealed that the overexpression of KNTC1, CEP55, AURKA, and ECT2 hub genes was due to their promoter hypomethylation. Moreover, higher expressions of KNTC1, CEP55, AURKA, and ECT2 were positively correlated with the abundance of the CD4+ T cells and macrophage while with the reduction of CD8+ T cells in HNSC samples. Finally, gene enrichment analysis showed that all hub genes are involved in "nucleoplasm, centrosome, mitotic spindle, and cytosol" pathways. In conclusion, the KNTC1, CEP55, AURKA, and ECT2 genes could be potential biomarkers for HNSC patients and provide a novel insight into the diagnosis and treatment of the disease.

Correction: Medication reconciliation on discharge in a tertiary care Riyadh Hospital: An observational study.

[This corrects the article DOI: 10.1371/journal.pone.0265042.].

Isolation and characterization of indigenous bacterial assemblage for biodegradation of persistent herbicides in the soil.

Extensive pesticides (herbicides) use is negatively disturbing the environment and humans. Pesticide bioremediation with eco-friendly techniques bears prime importance. This study aimed to isolate and characterize three different herbicides (metribuzin, clodinafop- propargyl, MCPA (2-methyl, 4 chlorophenoxyacetic acids) and Bromoxynil) degrading bacterial strains from agricultural fields of Punjab University, Pakistan. Among the 12 bacterial isolates, 5 were metribuzin degrading, 3 were clodinafop propargyl degrading and, 4 were MCPA and Bromoxynil degrading bacteria. Morphological, microscopic, and molecular characterization revealed that the majority of these bacterial strains were gram-negative and belonged to Bacillus and Pseudomonas genera. The isolates A6, B3, and C1 were subjected to respective herbicide degradation and the data was confirmed through GC-MS analysis. The effect of herbicide concentrations, pH, and temperature on bacterial growth was determined at OD600. The strain A6 degraded 14.8% metribuzin out of the provided concentration of 50 ppm by following the deamination pathway. While the isolates B3 and C1 degraded 23.2% and 33.9% clodinafop, MCPA and bromo-xynil, respectively, at a spiking concentration of 50ppm. The clodinafop, MCPA and Bromoxynil were metabolized into less toxic products i.e., dicarboxylic acids and 2-methyl phenol respectively, and metabolized via decarboxylation and dehalogenation mechanism. The present study evaluates the herbicides degrading bacterial strains that could potentially be used for bioremediation of agricultural contaminated sites.

Enhancement of shelf-life of food items via immobilized enzyme nanoparticles on varied supports. A sustainable approach towards food safety and sustainability.

This study was designed to extend the shelf life of fruits and vegetables through a novel technique based on utilization of microbially driven enzyme glucose oxidase and casting a fine layer of hydrogen peroxide on the food item that protected the fruit from decay. The produced nanoparticles (ZnO, Ag) were ligated with Glucose Oxidize (GOx) purified from Aspergillus niger. Post ligation studies revealed that ligated enzymes display relatively enhanced activity. Four types of sprays were prepared in order to compare their effectiveness. Glucose oxidase/silver nanoparticles (GOx/AgNPs), glucose oxidase/zinc oxide nanoparticles (GOx/ZnONPs), AgNPs and ZnONPs sprays were applied to guava fruit samples as post-harvest therapeutic agents for a period of 15 days. Fruit quality parameters such as total suspended solids (TSS), pH, weight loss, DPPH free radical capturing performance and firmness confirms that usage of the bioconjugates especially that of GOx/ZnONP was curiously active to maintain the physical appearance of fruit well along with no such deterioration in chemical composition of fruit. Consequently, enzymes ligated on the surface of nanoparticles (ZnONP) are exceptional for extension of post-harvest shelf life of fruits such as guava.

The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain.

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.

Genome Investigation and Functional Annotation of Lactiplantibacillus plantarum YW11 Revealing Streptin and Ruminococcin-A as Potent Nutritive Bacteriocins against Gut Symbiotic Pathogens.

All nutrient-rich feed and food environments, as well as animal and human mucosae, include lactic acid bacteria known as Lactobacillus plantarum. This study reveals an advanced analysis to study the interaction of probiotics with the gastrointestinal environment, irritable bowel disease, and immune responses along with the analysis of the secondary metabolites' characteristics of Lp YW11. Whole genome sequencing of Lp YW11 revealed 2297 genes and 1078 functional categories of which 223 relate to carbohydrate metabolism, 21 against stress response, and the remaining 834 are involved in different cellular and metabolic pathways. Moreover, it was found that Lp YW11 consists of carbohydrate-active enzymes, which mainly contribute to 37 glycoside hydrolase and 28 glycosyltransferase enzyme coding genes. The probiotics obtained from the BACTIBASE database (streptin and Ruminococcin-A bacteriocins) were docked with virulent proteins (cdt, spvB, stxB, and ymt) of Salmonella, Shigella, Campylobacter, and Yersinia, respectively. These bacteria are the main pathogenic gut microbes that play a key role in causing various gastrointestinal diseases. The molecular docking, dynamics, and immune simulation analysis in this study predicted streptin and Ruminococcin-A as potent nutritive bacteriocins against gut symbiotic pathogens.

Myogenesis and Analysis of Antimicrobial Potential of Silver Nanoparticles (AgNPs) against Pathogenic Bacteria.

The widespread and indiscriminate use of broad-spectrum antibiotics leads to microbial resistance, which causes major problems in the treatment of infectious diseases. However, advances in nanotechnology have opened up new domains for the synthesis and use of nanoparticles against multidrug-resistant pathogens. The traditional approaches for nanoparticle synthesis are not only expensive, laborious, and hazardous but also have various limitations. Therefore, new biological approaches are being designed to synthesize economical and environmentally friendly nanoparticles with enhanced antimicrobial activity. The current study focuses on the isolation, identification, and screening of metallotolerant fungal strains for the production of silver nanoparticles, using antimicrobial activity analysis and the characterization of biologically synthesized silver nanoparticles by X-ray diffraction (XRD) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). In total, 11 fungal isolates were isolated and screened for the synthesis of AgNPs, while the Penicillium notatum (K1) strain was found to be the most potent, demonstrating biosynthetic ability. The biologically synthesized silver nanoparticles showed excellent antibacterial activity against the bacteria Escherichia coli (ATCC10536), Bacillus subtilis, Staphylococcus aureus (ATCC9144), Pseudomonas aeruginosa (ATCC10145), Enterococcus faecalis, and Listeria innocua (ATCC13932). Furthermore, three major diffraction peaks in the XRD characterization, located at the 2θ values of 28.4, 34.8, 38.2, 44, 64, and 77°, confirmed the presence of AgNPs, while elemental composition analysis via EDX and spherical surface topology with a scanning electron microscope indicated that its pure crystalline nature was entirely composed of silver. Thus, the current study indicates the enhanced antibacterial capability of mycologically synthesized AgNPs, which could be used to counter multidrug-resistant pathogens.

Region-Based Segmentation and Classification for Ovarian Cancer Detection Using Convolution Neural Network.

Ovarian cancer is a serious sickness for elderly women. According to data, it is the seventh leading cause of death in women as well as the fifth most frequent disease worldwide. Many researchers classified ovarian cancer using Artificial Neural Networks (ANNs). Doctors consider classification accuracy to be an important aspect of making decisions. Doctors consider improved classification accuracy for providing proper treatment. Early and precise diagnosis lowers mortality rates and saves lives. On basis of ROI (region of interest) segmentation, this research presents a novel annotated ovarian image classification utilizing FaRe-ConvNN (rapid region-based Convolutional neural network). The input photos were divided into three categories: epithelial, germ, and stroma cells. This image is segmented as well as preprocessed. After that, FaRe-ConvNN is used to perform the annotation procedure. For region-based classification, the method compares manually annotated features as well as trained feature in FaRe-ConvNN. This will aid in the analysis of higher accuracy in disease identification, as human annotation has lesser accuracy in previous studies; therefore, this effort will empirically prove that ML classification will provide higher accuracy. Classification is done using a combination of SVC and Gaussian NB classifiers after the region-based training in FaRe-ConvNN. The ensemble technique was employed in feature classification due to better data indexing. To diagnose ovarian cancer, the simulation provides an accurate portion of the input image. FaRe-ConvNN has a precision value of more than 95%, SVC has a precision value of 95.96%, and Gaussian NB has a precision value of 97.7%, with FR-CNN enhancing precision in Gaussian NB. For recall/sensitivity, SVC is 94.31 percent and Gaussian NB is 97.7 percent, while for specificity, SVC is 97.39 percent and Gaussian NB is 98.69 percent using FaRe-ConvNN.

Role of polycystic ovarian syndrome in developing psychological burden in Saudi Arabian females: A case control study.

It is well known that polycystic ovarian syndrome (PCOS) may elevate psychological problems in patients, but there is a scarcity of the studies among Saudi Arabian population. This research was designed to investigate the influence of PCOS on the development of psychological load in terms of depression, anxiety, and stress in comparison to normal women who have no PCOS. Further, a correlation of psychological distress in PCOS females was done with their educational level. This is case-control research carried out in one of Riyadh's multispecialty hospitals. In the PCOS patients and control groups (each with 84 samples), samples were collected using convenience sampling and a simple random approach, respectively. The psychological burden was determined using DASS-21. The data obtained were analyzed using SPSS-IBM 25. Most participants (52.9%) were between the ages of 26 and 35 and had a university education (68.4%). A significantly higher percentage of PCOS patients (P = 0.001) had irregular menses, hirsutism, infertility, and acne in comparison to the mothers without PCOS. There was a significantly higher possibility of depression (P = 0.003), anxiety (P = 0.016), and stress (P = 0.001) among PCOS patients than in control subjects. Among the psychological domain tested in the study, the risk of developing stress (odds ratio, OR = 8.32) was high when compared to depression (OR = 3.12) and anxiety (OR = 2.127) in PCOS patients. Furthermore, when compared to PCOS females with less education, a significantly lower number of university-educated PCOS females developed depression. The study demonstrates a high prevalence of psychological burden among the PCOS population. Higher education has been shown to help in alleviating depression in PCOS females. Meeting PCOS women's psychological needs will improve their overall health status.

New Insights into Listeria monocytogenes Antimicrobial Resistance, Virulence Attributes and Their Prospective Correlation.

Listeriosis is one of the most common foodborne diseases caused by Listeria monocytogenes (L. monocytogenes). A poor prognosis has been recorded for the invasive listeriosis, especially neurolisteriosis. In several countries throughout the world, foodborne infections with L. monocytogenes exceeded the legal safety limits in animal sourced foods. Therefore, we decided to investigate the variability, virulence and antimicrobial resistance profiles of this pathogen. Both phenotypic and genotypic methods were used for identifying L. monocytogenes isolates and confirming their virulence profiles. The antimicrobial resistances and their correlation analysis with the existence of virulence genes were detected. Additionally, sequencing and phylogenetic analysis based on L. monocytogenes inlA and inlB genes were undertaken. The prevalence rate (11.9%) and the resistance profiles of L. monocytogenes were shocking. The multi-drug resistance (MDR) phenotypes were common among our isolates (64.9%). Fortunately, the resistance phenotypes were always associated with low virulence arrays and the MDR strains possessed low virulence fitness. Herein, the high genotypic and phenotypic diversity of L. monocytogenes isolates and their weak clonality and adaptability highlighted the difficulty in controlling and managing this pathogen. Therefore, it is important to add more restriction guidelines from national authorities on the consumption of ready to eat foods.