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Background Most NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain. Objectives The aim of the study was to estimate population event rates for NSAID-associated ALFT Methods This was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY). Results In the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose). Event rates per MTY were 1.59 (95 % CI 1.1–2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2–3.9) for ibuprofen, 1.9 (95 % CI 0.8–3.7) for nimesulide, 1.6 (95 % CI 0.6–3.4) for diclofenac and 1.6 (95 % CI 0.3–4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6–4.1) without overdoses and 7.8 (95 % CI 6.8–9.0) including overdoses. Conclusions ALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.

Background Several methods have been proposed to assess causality in drug-induced liver injury but none have been tested in the specific context of acute liver failure leading to transplantation (ALFT). Objective We took advantage of the Study of Acute Liver Transplant (SALT), a European case-population study of ALFT, to test different causality scales. Methods Causality was assessed by experts in SALT, a 7-country case-population study from 2005 to 2007 of adult otherwise unexplained ALFT, for all drugs found within 30 days prior to the date of initial symptoms of liver disease (index date), using information content, causality scales, and data circuit determined from a pilot study, Salome. Results The consensus points from Salome were to provide full data on drugs including international non-proprietary name (INN) and doses except for non-steroidal anti-inflammatory drugs (NSAIDs) and to use the World Health Organization (WHO) causality scale. In SALT, among the 9,479 identified patients, 600 (6.3 %) were cases of ALFT, of which 187 had been exposed to drugs within 30 days, without overdose. In 130 (69.5 %) of these the causality score was possible, probable, or highly probable. Conclusion In ALFT cases, once other clinical causes have been excluded and drug exposure established within 30 days, the main discriminant characteristic for causality will be previous knowledge of possible hepatotoxicity.

In the present work, copper oxide nanoparticles have been fabricated by using a biological method. Copper oxide nanoparticles (CuO NPs) have received more attention than other metal oxides due to their distinctive properties and applications. Plant-mediated synthesis of nanoparticles has gained the attention of researchers because of its simple and ecologically sustainable approach. The biosynthesis of CuO NPs included the use of Passiflora edulis leaf extract that acts as a stabilizing and reducing agent. A non-toxic, cost-effective, and ecologically acceptable method was the use of plant leaf extract in the biogenesis of nanoscale materials. UV-vis, SEM, FTIR, and XRD techniques were used to examine the biologically produced copper oxide nanoparticles. The findings of the SEM examination, which gives morphological information, demonstrate that the synthesized NPs have a spherical shape and have an average particle size of between 60 and 65 nm. CuO has been further investigated in the current study as a photo-catalyst in the methylene blue (MB) dye degradation and as an antioxidant in free radical scavenging activities. The decolorization efficiency was approximately 93% after 160 min. Furthermore, CuO nanoparticles were tested for antioxidant performance by scavenging 2, 2-diphenyl-1-picrylhydrazyl hydrate free radicals (DPPH) and evaluated by UV-Vis spectroscopy. The result showed that biologically synthesized CuO NPs can be used as an effective antioxidant. The half maximal inhibitory concentration IC50 of copper oxide nanoparticles was found to be in the range of 0.13–0.20.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by increased red blood cell production, with high risk of venous and arterial thrombosis. Mutations in the JAK2 gene, particularly JAK2 V617F, play a central role in its pathogenesis. Ropeginterferon alfa-2b is a novel long-acting interferon showing promise in managing PV through hematologic and molecular control. This study aimed to evaluate the efficacy and safety of Ropeginterferon alfa-2b in patients with PV based on a systematic review and meta-analysis of available clinical trials. A systematic search was conducted across PubMed, Cochrane Library, Web of Science, Google Scholar, and Scopus on May 8, 2025. Randomized controlled trials (RCTs) assessing Ropeginterferon alfa-2b in PV were included. The PRISMA guidelines were followed, and the protocol was registered in PROSPERO (CRD420251051466). Quality assessment was performed using RoB 2.0 and ROBINS-I tools. A random-effects model was applied using R software. Eight studies involving 761 patients were included and only six studies included in single arm meta-analysis with 328 patients. The pooled proportion of complete hematological response at 12 months was 0.63 (95% CI [0.51–0.73]), with high heterogeneity. Reductions in JAK2 V617F allele burden were significant (MD: 26.57, 95% CI [13.49–39.65]). Molecular response was achieved in 25% (95% CI [0.04–0.70]) of patients. The most common adverse events were elevated liver enzymes (AST: 0.28; ALT: 0.32), influenza-like illness (0.11), and anemia (0.09), with unresolved heterogeneity in all outcomes. Ropeginterferon alfa-2b shows promising efficacy in achieving hematological and molecular responses in patients with PV. However, notable heterogeneity and safety concerns, particularly liver-related adverse effects, warrant further investigation in large-scale trials. Graphical Abstract

Despite the significant milestone of vaccine discovery, the spread of misinformation and pseudoscientific claims has resulted in an increasing number of people refusing vaccination in Syria. In this study, we aimed to explore fears and misconceptions towards COVID-19 vaccines among the Syrian population. We conducted a nationwide cross-sectional study between January and May 2022, using a convenience sample of 10,006 participants aged at least 18 years and living in Syria. We administered a validated online/paper questionnaire and conducted face-to-face interviews. We used SPSS software (version 26) for statistical analysis, assessing our data using frequency and tests, with  < 0.05 considered statistically significant. The majority of the participants were female 6048 (60.4%), university degree holders 7304 (73%), and from urban areas 8015 (80.1%). Approximately half of the participants 5021 (50.2%) belonged to the medical sector (49% had concerns about the vaccine). Females, university degree holders, and participants with a history of symptomatic COVID-19 were more likely to have fears about the vaccines. The main concerns about the vaccines were the rapid development, fears of blood clots, and common side effects. The prevalence of some misconceptions was relatively high, such as the belief that the vaccine is an experiment or a secret plan to reduce the population. Reliable sources are crucial to fight misleading information on social media. COVID-19 vaccine is key to controlling the spread, but acceptance rate is critical. High variability in vaccine acceptance and high vaccine hesitancy can affect the efforts to terminate the COVID-19 pandemic. Addressing the barriers associated with the acceptance of COVID-19 vaccination will be the cornerstone to achieving maximum vaccination coverage. It is important to consider the reasons for refusing the COVID-19 vaccine when interpreting the results of any study on vaccine attitudes among the Syrian population.

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-β) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-β and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines. Methods: Functional study and wound healing assay showed PT-complex significantly reduced cell motility and the migration and invasion of CRC cell lines compared to the untreated control. Western blot performed in the presence and absence of TGF-β demonstrated that PT-complex significantly regulated the TGF-β-mediated altered expressions of EMT markers. Results and Discussion: PT-complex attenuated the migration and invasion by upregulating the protein expression of EMT-suppressing factor E-cadherin and suppressing EMT-inducing factors such as N-Cadherin and Vimentin. Moreover, PT-complex significantly suppressed the activation of SMAD3 in both CRC cell lines. Further, the microarray data analysis revealed differential expression of genes related to invasion and migration. In conclusion, besides displaying antiproliferative activity, the PT complex can decrease the metastasis of CRC cell lines by modulating TGF-β-regulated EMT markers. These findings provide new insight into TGF-β/SMAD signaling as the molecular mechanism involved in the antitumoral properties of novel PT-complex.

The purpose of this study is to examine project performance through the sequential mediation of value co-creation and stakeholder satisfaction, as well as the moderate mediation of stakeholder management in construction companies. The data were collected from project-based organizations using a non-probabilistic, convenience sampling technique. The data were analyzed using structural equation modeling in Smart PLS V. 4. The results suggest that there is a positive and significant association between agile leadership and project performance. Value co-creation and stakeholder satisfaction both separately and sequentially mediate the association between agile leadership and project performance. It was also revealed that stakeholder management moderates this mediation, such that the relationship between agile leadership and project performance is stronger when stakeholder management is high. The implications for theoretical body of knowledge and practices are aligned with stakeholder theory.

Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.

Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.

Background: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Pseudomonas aeruginosa represents a significant challenge to current antibiotic therapies, particularly in immunocompromised patients, leading to severe and potentially fatal infections. Objectives: The present study aims to investigate the association between resistance patterns, the presence of the algD, pelF, and pslD genes, and biofilm formation capabilities among clinical isolates of P. aeruginosa. Methods: A total of 25 clinical strains of P. aeruginosa were isolated from clinical specimens. An antibiotic sensitivity test was conducted to categorize the organisms as resistant (R), MDR, and XDR strains. A biofilm formation assay was performed to evaluate biofilm formation capacity, and the algD, pelF, and pslD genes were detected using a polymerase chain reaction (PCR) technique. Results: All 25 clinical isolates showed the highest resistance against meropenem (MEM) (100%), imipenem (IPM) (96%), and ceftazidime (CAZ) (72%). Antimicrobial resistance (12%) and MDR (12%) strains were more prevalent in the 51 - 60 and 71 - 80 age groups, while the highest MDR (16%) strains were detected in the 81 - 90 age group. In males, R strains (28%) were isolated, and in females, the highest MDR (24%) strains were found, with no significant gender differences. In sepsis diagnosis cases, the highest antimicrobial resistance (16%), MDR (16%), and XDR (8%) strains were isolated. The algD gene was detected in R strains (36%), while pelF (40%) and pslD (40%) were detected in MDR strains. Strong biofilm formation was found in MDR (20%) and XDR (12%) strains, and moderate biofilm formation was observed in R strains (28%). Conclusions: Overall, the study found an association between biofilm formation and MDR/XDR strains. This suggests that the highest biofilm formation and percentage of pelF and pslD gene detection in MDR strains may contribute to the persistence and severity of infections caused by these strains.