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.

The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis.

BACKGROUND: Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to each case. This study aimed to evaluate the therapeutic effects of topical application of miconazole and miconazole-loaded chitosan nanoparticles in treatment of diabetic patients with oral candidiasis. METHODS: In this randomized controlled clinical trial. A total of 80 diabetic patients presenting with symptomatic oral candidiasis were randomly assigned into two treatment groups: miconazole and miconazole-loaded chitosan nanoparticles. The patients were treated for 28 days, and clinical assessments were conducted at baseline, 7, 14, 21 and 28 days. Clinical parameters, including signs and symptoms of oral candidiasis were evaluated and microbiological analysis was performed to determine the Candida species and assess their susceptibility to the antifungal agents. Statistical analysis was done to the categorical and numerical data using chi-square test and Kruskal Wallis test. RESULTS: The antifungal efficacy between the miconazole and miconazole-loaded chitosan nanoparticles (CS-MCZ) groups insignificant difference (P >  0.05) was observed. Both treatment modalities exhibited comparable effectiveness in controlling oral candidiasis symptoms and reducing Candida colonization as miconazole-loaded chitosan nanoparticles group showed a significant difference in the clinical improvement in respect of both signs and symptoms from baseline (70%) until the end of study at 28 days (5%) (P <  0.05) Moreover, miconazole-loaded chitosan nanoparticles, there was a significant reduction in the number of colonies forming units of Candida albicans from baseline until the end of the study at 28-day with P value <  0.000. CONCLUSIONS: This randomized controlled clinical trial and microbiological analysis demonstrate that both miconazole and miconazole-loaded chitosan nanoparticles are effective in the treatment of oral candidiasis in diabetic patients with no adverse reactions. TRIAL REGISTRATION: NCT06072716 with first registration first registration in 10/10/2023.

Formulation, optimization, in-vivo biodistribution studies and histopathological safety assessment of duloxetine HCl-loaded ultra-elastic nanovesicles for antidepressant effect after intranasal and transdermal delivery.

Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL suffers limited bioavailability due to extensive gastric and first-pass metabolism. To improve DUL's bioavailability; DUL-loaded elastosomes were developed, via full factorial design, utilizing various span®60: cholesterol ratios, edge activator types and amounts. Entrapment efficiency (E.E.%), particle size (PS), zeta potential (ZP) and in-vitro released percentages after 0.5 h (Q0.5h) and 8 h (Q8h) were evaluated. Optimum elastosomes (DUL-E1) were assessed for morphology, deformability index, drug crystallinity and stability. DUL pharmacokinetics were evaluated in rats following intranasal and transdermal application of DUL-E1 elastosomal gel. DUL-E1 elastosomes [comprising span®60 and cholesterol (1:1) and brij S2 (edge activator; 5 mg)] were optimum with high E.E.% (81.5 ± 3.2%), small PS (432 ± 13.2 nm), ZP (-30.8 ± 3.3 mV), acceptable Q0.5h (15.6 ± 0.9%), and high Q8h (79.3 ± 3.8%). Intranasal and transdermal DUL-E1 elastosomes revealed significantly higher Cmax (251 ± 18.6 and 248 ± 15.9 ng/mL) at Tmax (2 and 4 h) and improved relative bioavailability (≈ 2.8 and 3.1 folds) respectively, in comparison to oral DUL aqueous solution. In-vivo histopathological studies were conducted to ensure the safety of DUL-E1. Elastosomes are promising novel nano-carriers, capable of enhancing the bioavailability of DUL via various routes of administration.

Evaluation of ABCA1 gene polymorphism as a prognostic index of fibrosis progression in NAFLD patients.

INTRODUCTION: It had been evident that non-alcoholic fatty liver disease (NAFLD) is the new era epidemic. Despite emergence of many drugs on the pipeline that considered candidates to cure NAFLD/NASH, the critical need for defining the cohort liable to fibrosis progression is yet unmet. AIM: Evaluate ABCA1 (rs1800977) genotyping as a noninvasive predictor of liver fibrosis severity. MATERIALS AND METHODS: This study included 118 liver biopsy-proven NAFLD-patients. According to Metavir-fibrosis-staging, cases were divided to early fibrosis (74 cases), and 44 cases with significant fibrosis (>F2), added to 49 healthy control subjects. All patients were subjected to liver function tests, lipids profile, triglyceride TG index, and hepatic steatosis index (HSI) and real-time PCR ABCA1 SNP (rs1800977). RESULTS: Significant differences in transaminases (p > .05), albumin (p < .009), cholesterol (p0.03), low density lipoproteins (LDL) (0.006), triglycerides (p < .001), HSI (p < .001), FIB4 (p < .001) and APRI (p < .001) were reported in those with significant than early fibrosis and control groups. CC was the most prevalent in significant (36.4%) than early fibrosis (13.5%) and control groups (8.2%), with prevalence of C allele in significant fibrosis (p ≤ .003). Univariate analysis revealed that DM (p ≤ .001), TG index (p ≤ .022), cholesterol (p ≤ .03), HSI (p ≤ .006), LDL (p ≤ .02), HDL (p ≤ .01), APRI (p ≤ .02) and CC genotype (p ≤ .005) were the main factors affecting fibrosis progression in NAFLD. However multivariate analysis proved only the role of HSI (p ≤ .005), LDL (p ≤ .02), HDL (p ≤ .003) and CC genotype (p ≤ .03) in predicting fibrosis severity. CONCLUSION: Dyslipidemias, hepatic steatosis index and ABCA1 (rs1800977) gene polymorphism CC genotype; were the only independent predictors of advanced fibrosis in NAFLD-patients.

BioFire FilmArray BCID2 versus VITEK-2 System in Determining Microbial Etiology and Antibiotic-Resistant Genes of Pathogens Recovered from Central Line-Associated Bloodstream Infections.

Central line-associated bloodstream infection (CLABSI) is among the most serious hospital acquired infections. Therefore, the rapid detection of the causative microorganism is of crucial importance to allow for the appropriate antimicrobial therapy. In the present study, we analyzed the clinical performance of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel in the identification of 33 microbial species and 10 antibiotic resistance genes in comparison to the VITEK-2 system. A total of 104 blood specimens were included. The FilmArray BCID2 results were concordant with the VITEK-2 system in 69/97 specimens (71.1%). Non-concordance was either due to the detection of more pathogens by the FilmArray BCID2 23/28 (82%) or microbial species were misidentified 5/28 (18%). Hence, in comparison to the VITEK-2 system, the FilmArray BCID2 panel showed an overall sensitivity of 75.8% (95% CI, 66-83%) and an overall specificity of 98% (95% CI, 97-98.8%) in detecting microbial species. For the resistance genes, the FilmArray BCID was able to detect the presence of blaCTX-M gene in 23 Gram-negative isolates, blaNDM and blaOXA-48- like genes in 14 and 13 isolates, respectively. The mecA and mecC genes were found in 23 Staphylococcus species, while mecA, mecC and MREJ genes were found in 4 Staphylococcus aureus isolates. The sensitivity and specificity for detecting resistance genes by the FilmArray BCID2 was 90% (95% CI, 81.4-95%) and 99.6% (95% CI, 99-100%), respectively. As concluded, the present study emphasizes the high sensitivity and specificity of the FilmArray BCID2 in the rapid and reliable detection of different bacteria and fungi from positive blood culture bottles, as well as the accurate detection of various antibiotic resistance markers.

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients.

Aim of the study: Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients. Material and methods: Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases). Results: Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01). Conclusions: Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.

Synergistic Antiproliferative Effects of Zoledronic Acid and Fluvastatin on Human Pancreatic Cancer Cell Lines: An in Vitro Study.

Bisphosphonates and statins are known to have antitumor activities against different types of cancer cell lines. In the present study, we investigated the antiproliferative effects of the combination of zoledronic acid (ZOL), a bisphophosphonate, and fluvastatin (FLU), a statin, in vitro on two types of human pancreatic cancer cell lines, Mia PaCa-2 and Suit-2. The pancreatic cancer cell lines were treated with ZOL and FLU both individually and in combination to evaluate their antiproliferative effects using WST-8 cell proliferation assay. In this study, we demonstrated a potent synergistic antiproliferative effect of both drugs when used in combination in both cell lines. Moreover, we studied the molecular mechanism behind this synergistic effect, which was inhibited by the addition of the mevalonate pathway products, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Furthermore, we aimed to determine the effect of ZOL and FLU combination on RhoA and Ras guanosine 5'-triphosphate (GTP)-proteins. The combination induced a marked accumulation in RhoA and unprenylated Ras. GGPP and FPP reversed the increase in the amount of both proteins. These results indicated that the combination treatment impaired RhoA and Ras signaling pathway by the inhibition of geranylgeranylation and/or farnesylation. This study provides a potentially effective approach for the treatment of pancreatic cancer using a combination treatment of ZOL and FLU.