Plasma type IV collagen levels as a potential biomarker for early detection of nephropathy in diabetes mellitus patients.

Diabetic nephropathy represents a microvascular complication related to type 2 diabetes mellitus (T2DM) that ultimately causes end-stage renal disease. Our study aimed to evaluate the association of plasma type IV collagen with albuminuria status and to assess the clinical significance of plasma type IV collagen as a potential biomarker in the early stage of diabetic nephropathy. The study comprised 75 participants diagnosed with T2DM allocated equally (n=25) into three groups: (A) normal albuminuria levels, (B) microalbuminuria, and (C) macroalbuminuria, depending on their urine albumin-to-creatinine ratio. A comparative analysis was conducted between these groups and a control group (D, n=15). The enzyme-linked immunosorbent assay (ELISA) method was employed for measuring plasma type IV collagen levels. The results revealed that plasma type IV collagen levels were significantly higher in T2DM groups than in the control group. Moreover, diabetic patients without albuminuria had significantly higher plasma type IV collagen levels than the control group (p < 0.001). Furthermore, albuminuria levels among diabetic patient groups were significantly increased as albuminuria categories increased (p < 0.001). A significant positive correlation existed between plasma type IV collagen and glycated hemoglobin (HbA1c) levels in the macroalbuminuric diabetic group. Our study employed the receiver operating characteristic (ROC) curve analysis to determine plasma type IV collagen diagnostic utility in macroalbuminuria prediction. The ROC curve analysis revealed that type IV collagen can significantly determine macroalbuminuric patients at a cutoff value of 2.25 with sensitivity, specificity, positive predictive value, and negative predictive value of 68%, 100%, 100%, and 75.8%, respectively (p < 0.001). In conclusion, plasma type IV collagen levels might serve as a valuable predictor of albuminuria onset in patients with T2DM.

Effects of prebiotic (lactoferrin) and diclazuril on broiler chickens experimentally infected with Eimeria tenella.

Introduction: Avian coccidiosis presents a significant challenge to the poultry industry in Egypt, highlighting the urgent need for validating new drug targets offering promising prospects for the development of advanced anticoccidials. Although numerous reports highlight the activity of lactoferrin (LF) against various microorganisms, its potential against Eimeria has not been explored. The present study evaluated the potential anticoccidial effect of LF and diclazuril in broiler chickens experimentally infected with Eimeria tenella. Methods: A total of 100 one-day-old broiler chicks were divided into five equal groups (20 each) as follows: Group 1 (G1) served as the normal healthy control group, Group 2 (G2) consisted of chickens infected with 1 × 105 sporulated E. tenella oocysts at 14 days of age, Group 3 (G3) comprised infected chickens treated with diclazuril (0.5 mL/L in drinking water) for 3 days successively, Group 4 (G4) included infected chickens treated with LF (at a dose of 250 mg/kg of diet) from one day of age until the end of the study, and Group 5 (G5) comprised infected chickens treated with both LF and diclazuril. Results: The positive control group (G2) experienced significant reductions in body weight (BW), BW gain, serum glucose, lipase, amylase, total antioxidant capacity, several hematological indices, and total proteins, along with alterations in various antioxidant enzymes. Conversely, serum levels of aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatases (ALP), urea, creatinine, nitric oxide, mean corpuscular volume (MCV), White blood cells (WBCs), heterophils, alpha 2, beta 1, and liver contents of malondialdehyde were elevated in this group. Moreover, higher oocyst counts and lesion scores, along with histopathological alterations, were observed in G2. Remarkably, treatment with diclazuril and/or LF demonstrated potent antioxidant and anticoccidial effects, resulting in reduced shedding of oocysts, lesion scores, and lymphocytic infiltrates in the cecum. Additionally, these treatments improved the antioxidant and immune systems in chickens and restored all histopathological changes reported in the infected non-treated group (G2). Conclusion: This study offers novel perspectives on the potential anticoccidial effects of the combination of LF and diclazuril in broiler chickens infected with E. tenella, highlighting the potential synergistic actions of LF in treating poultry coccidiosis.

Synthesis, COX-2 inhibition, anti-inflammatory activity, molecular docking, and histopathological studies of new pyridazine derivatives.

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC50 = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1ß. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs.

Association of aerobic fitness and grip strength with cognitive and academic performance in Arab children.

This study investigated the association between aerobic and muscular fitness with the cognitive control and academic performance of preadolescent Arab children. Ninety-three children aged 10-13years (mean=11.5, SD=0.5) representing eight Arab nations (Egypt, Saudi Arabia, Sudan, Syria, Jordan, Lebanon, Yemen, and Morocco) participated in this cross-sectional study. The participants completed tests for aerobic (progressive aerobic cardiovascular endurance run) and muscular (maximum grip strength) fitness, and cognitive control (flanker task). We assessed their academic performance based on their overall grade point average (GPA). Our analyses revealed that greater aerobic fitness was associated with higher GPA scores and greater muscular fitness was associated with a shorter response time in a task condition requiring extensive cognitive control (incongruent condition). No association was found between aerobic fitness and flanker task performance nor between muscular fitness and GPA. These results bridge the knowledge gap on the associations of physical fitness to the cognitive control and academic performance of Arab children, suggesting that the positive associations found in Western and Asian literature can be generalized to the Arab context.

Machine learning optimization for hybrid electric vehicle charging in renewable microgrids.

Renewable microgrids enhance security, reliability, and power quality in power systems by integrating solar and wind sources, reducing greenhouse gas emissions. This paper proposes a machine learning approach, leveraging Gaussian Process (GP) and Krill Herd Algorithm (KHA), for energy management in renewable microgrids with a reconfigurable structure based on remote switching of tie and sectionalizing. The method utilizes Gaussian Process (GP) for modeling hybrid electric vehicle (HEV) charging demand. To counteract HEV charging effects, two scenarios are explored: coordinated and intelligent charging. A novel optimization method inspired by the Krill Herd Algorithm (KHA) is introduced for the complex problem, along with a self-adaptive modification to tailor solutions to specific situations. Simulation on an IEEE microgrid demonstrates efficiency in both scenarios. The predictive model yields a remarkably low Mean Absolute Percentage Error (MAPE) of 1.02381 for total HEV charging demand. Results also reveal a reduction in microgrid operation cost in the intelligent charging scenario compared to coordinated charging.

Association between Young People's Neighbourhoods' Characteristics and Health Risk Factors in Saudi Arabia.

INTRODUCTION: A neighbourhood's environmental characteristics can positively or negatively influence health and well-being. To date, no studies have examined this concept in the context of Saudi Arabian youth. Therefore, this study aimed to evaluate the association between a neighbourhood's environmental characteristics and health risk factors among Saudi Arabian youth. METHODS: A total of 335 secondary-school students (175 males, 160 females), aged 15-19 years old, participated. Body mass index (BMI) and waist circumference measurements were taken, and physical activity (steps) was measured via pedometer. The perceived neighbourhood environment was assessed using the International Physical Activity Questionnaire Environment Module (IPAQ-E). RESULTS: Significant differences were found between the youths from urban, rural farm, and rural desert locations in terms of BMI, waist circumference, daily steps, accessibility, infrastructure, social environment, household vehicles, safety, and access to facilities (p < 0.001). Rural desert youths were less active, and males (26.43 + 8.13) and females (24.68 + 5.03) had higher BMIs compared to the youths from other areas. Chi-square analysis revealed a significant difference (χ21 = 12.664, p < 0.001) between the genders as to social-environment perceptions. Males perceived their neighbourhood as a social environment more than was reported by females (68.39% and 50.28%, respectively). Pearson's correlation revealed negative significant relationships between steps and both safety of neighbourhood (r = -0.235, p < 0.001) and crime rate (r = -0.281, p < 0.001). DISCUSSION: Geographical location, cultural attitudes, lack of facilities, and accessibility impact youth physical-activity engagement and weight status; this includes environmental variables such as residential density, neighbourhood safety, household motor vehicles, and social environment. CONCLUSIONS: This is the first study examining associations with neighbourhood environments in the youths of the Kingdom of Saudi Arabia. Significant associations and geographical differences were found. More research and policy interventions to address neighbourhoods' environmental characteristics and health risk factors relative to Saudi Arabian youth are warranted.

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome.

Background and aim: The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). Materials and methods: The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Results: Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. Conclusions: The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

New insights into the anti-inflammatory and anti-melanoma mechanisms of action of azelaic acid and other Fusarium solani metabolites via in vitro and in silico studies.

Metabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC50 values (2.21 ± 0.06 and 4.81 ± 0.14 µM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC50 value of 8.75 ± 0.18 µM compared to kojic acid (IC50 = 9.27 ± 0.19 µM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3-6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity.

A statistical framework for a new Kavya-Manoharan Bilal distribution using ranked set sampling and simple random sampling.

In survival and stochastic lifespan modeling, numerous families of distributions are sometimes considered unnatural, unjustifiable theoretically, and occasionally superfluous. Here, a novel parsimonious survival model is developed using the Bilal distribution (BD) and the Kavya-Manoharan (KM) parsimonious transformation family. In addition to other analytical properties, the forms of probability density function (PDF) and behavior of the distributions' hazard rates are analyzed. The insights are theoretical as well as practical. Theoretically, we offer explicit equations for the single and product moments of order statistics from Kavya-Manoharan Bilal Distribution. Practically, maximum likelihood (ML) technique, which is based on simple random sampling (SRS) and ranked set sampling (RSS) sample schemes, is employed to estimate the parameters. Numerical simulations are used as the primary methodology to compare the various sampling techniques.

The association of oxidative stress of neonatal hyperbilirubinemia and vitamin E supplementation.

Aim of the study: Jaundice in newborns is a sign of skin and sclera pigmentation. Hyperbilirubinemia and these phenomena do, however, have a relationship. According to many clinical studies, elevated blood bilirubin and low vitamin E (VE) levels in newborns are associated. The aim of the study was to investigate the association of oxidative stress of neonatal hyperbilirubinemia in patients who underwent phototherapy with additional vitamin E supplementation (25 mg/kg/day over the course of three days) and patients without additional vitamin E. Material and methods: A set of 100 neonatal indirect hyperbilirubinemia patients was enrolled at neonatal intensive care units (NICUs) of the pediatric departments at Al Azhar University Hospitals during the period from February 2021 to October 2022 after obtaining signed written informed consent of all neonates' parents with an explanation of the aim of study. Results: Significant differences were found between the studied groups regarding serum bilirubin on the third day of admission (p = 0.039). Patients who were treated with vitamin E had lower serum bilirubin on the third day of admission (8.25 ±3.41) than the control group (11.66 ±3.22). Also, among the VE group, serum bilirubin was significantly decreased on the third day of admission (8.25 ±3.41) compared to zero days of admission (14.10 ±4.39) (p = 0.041). Conclusions: Vitamin E supplementation has an important role in treatment of indirect hyperbilirubinemia in neonates. Early administration of vitamin E in preterm neonates resulted in a significant decrease of serum bilirubin and increased total antioxidant capacity. Vitamin E supplementation in full term decreased the duration of phototherapy.

Veterinary telemedicine: A new era for animal welfare.

Telehealth is a rapidly developing field of veterinary medicine, particularly during and after the coronavirus 2019 (COVID-19) pandemic. The world and animal owners' expectations are changing to the point where veterinary practice will need to adapt due to information technology advancements. This narrative review describes the status, benefits, technology basics, applications, limitations, and legal aspects of veterinary telemedicine over the globe. Veterinary telemedicine is a service alongside other veterinary services that meets client needs, delivers quality medicine, and improves animal welfare. The most frequently utilized veterinary telemedicine applications include teleradiology, telesonography, teledentistry, telecardiology, telerehabilitation, anesthesia teleconsultation, telehospice and telepalliative care, telecytology, tele-endoscpy, teledermatology, tele-ophthalmology, tele-behavior therapy, and veterinary education and training. Veterinary telemedicine has a bright near future and will impact veterinary medicine and animal welfare due to its numerous advantages. These advantages include its low cost, availability, involvement in veterinary health care, online payment, and effectiveness in many clinical situations such as follow-up after an in-person examination, inspection of surgical sites, or mobility. Nevertheless, veterinary telemedicine should receive more attention from veterinary professional regulatory bodies in all countries. Moreover, it is necessary to conduct more studies to evaluate how telehealth is beginning to improve veterinary care, particularly for underserved regions.

Sacubitril/valsartan protective effect on induced intestinal ischemia/reperfusion injury via immune modulation of IL6/STAT1 pathway.

OBJECTIVES: Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury. METHODS: Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR. KEY FINDINGS: SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL. CONCLUSIONS: SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway.

Birnbaum Saunders distribution for imprecise data: statistical properties, estimation methods, and real life applications.

A neutrosophic statistic is a random variable and it has a neutrosophic probability distribution. So, in this paper, we introduce the new neutrosophic Birnbaum-Saunders distribution. Some statistical properties are derived, using Mathematica 13.1.1 and R-Studio Software. Two different estimation methods for parameters estimation are introduced for new distribution: maximum likelihood estimation method and Bayesian estimation method. A Monte-Carlo simulation study is used to investigate the behavior of parameters estimates of new distribution, compare the performance of different estimates, and compare between our distribution and the classical version of Birnbaum-Saunders. Finally, study the validity of our new distribution in real life.

New pyranopyrazole based derivatives: Design, synthesis, and biological evaluation as potential topoisomerase II inhibitors, apoptotic inducers, and antiproliferative agents.

A new series of pyranopyrazole-based derivatives were designed and synthesized. The synthesized compounds were assessed for their cytotoxic efficacy against A549 human lung carcinoma and MCF-7 human breast carcinoma cell lines. Three compounds (1b, 4b, and 7b) exhibited 1.3- to 2.3-fold more antiproliferative activity than that of doxorubicin against the A549 cell line. In comparison to doxorubicin, compounds 1d and 3b were 4.1- and 1.04-fold, respectively more powerful against MCF-7 cancer cells. All the synthesized compounds were found to be more selective toward A549 cancer cells than the normal human fibroblast BJ cells. Of interest, compounds 1b and 7b exhibited promising cytotoxicity and SIs of 27.72 and 25.30, respectively, towards A549 cancer cells, higher than that of doxorubicin (SI 4.81). The most potent compounds 1b, 1d, 3b, 4b, and 7b were then subjected to in vitro Topo II inhibition assay. They showed IC50 values in the range of 2.07 to 8.86 µM. Of particular interest, compound 7b (IC50 = 2.07 µM), exhibited higher Topo II inhibitory activity than that of doxorubicin (IC50 = 2.56 µM). The significant Topo II inhibition of compound 7b was explained by molecular docking simulations into the Topo II active site. Compound 7b halted the cell cycle in the S phase in A549 cancer cells. It induced total apoptosis and necrosis of 20.73- and 4-fold, respectively, greater than the control. This evidence was supported by a 3.59-fold increase in the level of apoptotic caspase-9 and a remarkable elevation of the Bax/BCL-2 ratio. The physiochemical parameters of compound 7b were aligned with Lipinski's rule of five.

Predicting soil cone index and assessing suitability for wind and solar farm development in using machine learning techniques.

This study proposes a novel approach that combines machine learning models to predict soil compaction using the soil cone index values. The methodology incorporates support vector regression (SVR) to gather input data on key soil parameters, and the output data from SVR are used as inputs for additional machine learning techniques such as Gradient Boosting, Decision Tree, Artificial Neural Networks, and Adaptive Neuro-Fuzzy Inference System. Evaluation of Artificial Intelligent techniques shows that the XGBoost model outperforms others, exhibiting high accuracy and reliability with low mean square error and high correlation coefficient. The effectiveness of the XGBoost model has implications for soil management, agricultural productivity, and land suitability evaluations, particularly for renewable energy projects. By integrating advanced AI techniques, stakeholders can make informed decisions about land use planning, sustainable farming practices, and the feasibility of renewable energy installations. Overall, this research contributes to soil science by demonstrating the potential of AI techniques, specifically the XGBoost model, in accurately predicting soil compaction and supporting optimal soil management practices.

Towards improving online learning in physical education: Gender differences and determinants of motivation, psychological needs satisfaction, and academic achievement in Saudi students.

Studies on students' perceptions and expectations during physical education (PE) online learning remain scarce. Centered on self-determination theory, the present cross-sectional study aims to identify gender differences and predictors affecting motivation, psychological needs satisfaction (PNS), and academic achievement during PE online learning. Data were collected from Saudi students' (N = 308, 161 females and 147 males) responses to the PE autonomy, relatedness, competence, and motivation questionnaires. Welch's t-test for unequal sample sizes, multiple linear regression, and binary logistic regression were used to compare means and to predict the relationships between the independent and dependent variables. The results showed higher autonomy and competence perceptions in female than in male students, but no differences were observed in relatedness. Female students presented higher intrinsic motivations, lower amotivation perceptions than males. However, no gender differences were recorded in extrinsic motivation. Students with less experience in online learning and weak grade point averages (GPAs) are more susceptible to having a high level of amotivation. Gender, GPA, and prior experience with online learning are the common predictors for all PNS and amotivation, while GPA and prior experience with online learning are the determinants of intrinsic motivation. GPA is affected by prior experience with online learning, autonomy, competence, intrinsic motivation, and amotivation. Therefore, teachers are encouraged to adapt their didactic-pedagogical behaviors during PE online learning according to students' motivation and autonomy perceptions. Structuring teaching activities with more individualized support for autonomy, competence, intrinsic motivation, and students' online skills/competencies ensures better learning efficiency and academic achievements.

LC-HRMS Profiling and Cytotoxic Potential of Actinomycetes Associated with the Red Sea Soft Coral Sarcophyton glaucum: In vitro and In silico Studies.

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC50 =3.3, 4.2 and 6.8 µg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.

Fuzzy Stress-Strength Model and Mean Remaining Strength for Lindley Distribution: Estimation and Application in Cancer of Benign Endocrine.

This paper is interested in the Bayesian and non-Bayesian estimation of the stress-strength model and the mean remaining strength when there is fuzziness for stress and strength random variables having Lindley's distribution with different parameters. A fuzzy is defined as a function of the difference between stress and strength variables. In the context of Bayesian estimation, two approximate algorithms are used importance sampling algorithm and the Monte Carlo Markov chain algorithm. For non-Bayesian estimation, maximum likelihood estimation and maximum product of spacing method are used. The Monte Carlo simulation study is performed to compare between different estimators for our proposed models using statistical criteria. Finally, to show the ability of our proposed models in real life, real medical application is introduced.

Anti-persister efficacy of colistin and meropenem against uropathogenic Escherichia coli is dependent on environmental conditions.

Antibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure. Furthermore, there is a growing array of evidence that persistence is a 'stepping-stone' for the development of genetic antimicrobial resistance. Urinary tract infections (UTIs) are a major contributor to antibiotic consumption worldwide, and are known to be both persistent (i.e. affecting the host for a prolonged period) and recurring. Currently, in clinical settings, routine laboratory screening of pathogenic isolates does not determine the presence or the frequency of persister cells. Furthermore, the majority of research undertaken on antibiotic persistence has been done on lab-adapted bacterial strains. In the study presented here, we characterized antibiotic persisters in a panel of clinical uropathogenic Escherichia coli isolates collected from hospitals in the UK and Australia. We found that a urine-pH mimicking environment not only induces higher levels of antibiotic persistence to meropenem and colistin than standard laboratory growth conditions, but also results in rapid development of transient colistin resistance, regardless of the genetic resistance profile of the isolate. Furthermore, we provide evidence for the presence of multiple virulence factors involved in stress resistance and biofilm formation in the genomes of these isolates, whose activities have been previously shown to contribute to the formation of persister cells.