Microbiological quality control of nonsterile pharmaceutical products requires reliable detection of Enterobacteriaceae while maintaining operational feasibility in routine laboratory settings. Harmonized pharmacopoeial methods involve sequential procedures, including pre-enrichment, selective enrichment, and differential isolation. These steps increase analytical time and resource requirements. In this study, a simplified culture-based workflow consisting of pre-enrichment in Tryptic Soy Broth, selective enrichment in Mossel Enterobacteria Enrichment broth, and isolation on MacConkey agar was comparatively evaluated against harmonized pharmacopoeial procedures. The assessment was performed using Escherichia coli (ATCC 8739) and Salmonella typhimurium (ATCC 14028) inoculated into finished pharmaceutical products (pravastatin sodium and erlotinib tablets) and a raw material (paracetamol). Qualitative recovery of target microorganisms was observed in the evaluated finished products under both workflows. Comparable qualitative recovery patterns were observed under the experimental conditions evaluated. The simplified approach reduced total analysis time from six to 4 days and decreased estimated culture media costs from USD 340.25 to USD 95.99 per analysis. No recovery of E. coli was observed in paracetamol samples under either workflow. Neutralization also failed to restore microbial growth, suggesting potential matrix-associated inhibitory effects. Within the defined experimental scope, the proposed approach proved practically applicable to the evaluated matrices. However, the study was limited to two finished pharmaceutical products and one pharmaceutical raw material. Therefore, broader applicability requires further evaluation across a wider range of pharmaceutical matrices.

PurposeNon-acetaminophen-induced acute liver failure (NAI-ALF) is associated with high mortality, with limited treatment options beyond supportive care and liver transplantation. While intravenous (IV) N-acetylcysteine (NAC) is the standard of care in acetaminophen-induced ALF, its benefit in NAI-ALF remains uncertain. Therefore, the purpose of this study is to evaluate the effect of IV NAC on in-hospital mortality.MethodsWe conducted a retrospective cohort study that included adult patients with NAI-ALF. Inverse probability of treatment weighting (IPTW) based on baseline demographics, severity of ALF, comorbidity burden, and etiology of ALF was conducted to balance the two groups. The primary outcome was all-cause in-hospital mortality at 21 days. Secondary outcomes included time to INR normalization, time to liver function test (LFT) normalization, and hospital length of stay.ResultsA total of 200 patients were included in the study, with 85 patients in the NAC group and 115 in the non-NAC group. After IPTW, groups were balanced with standardized mean differences of <0.1 for all covariates. IV NAC was associated with lower in-hospital mortality at 21 days (48.9% vs 62.1%, P < .01), with an odds ratio of 0.59 (95% CI 0.39 - 0.88). No difference was observed in time to INR normalization [HR 1.49 (95% CI 0.87 - 2.56, P = .15)], time to LFT normalization [HR 1.12 (95% CI 0.72 - 1.74, P = .61)], and length of hospital stay (11.9 vs 15.1 days, P = .84).ConclusionFor patients with NAI-ALF, IV NAC administration was associated with a reduction in in-hospital mortality at 21 days. These findings suggest NAC could play a role in the management of patients with NAI-ALF. Larger prospective studies are needed to further clarify the role of NAC in this population.

Paracetamol (PARA) is a commonly used analgesic and antipyretic, but overdose can result in severe hepatotoxicity and nephrotoxicity. Aprepitant (APRE), a selective neurokinin-1 receptor (NK-1R) antagonist used clinically as an antiemetic, may offer protective effects against drug-induced organ toxicity. This study aimed to evaluate the renoprotective potential of APRE in a rat model of PARA-induced nephrotoxicity. In this study, 36 male Albino Wistar rats were randomly assigned to six groups: Healthy, PARA (2 g/kg), APRE (20 mg/kg), N-acetylcysteine (NAC) + PARA (140 mg/kg + 2 g/kg), APRE + PARA (10 mg/kg + 2 g/kg), and APRE + PARA (20 mg/kg + 2 g/kg). Twenty-four hours after PARA administration, tissue and blood samples were collected from all groups for biochemical and histopathological analyses. Serum BUN and creatinine levels increased in the PARA group, whereas they improved in the NAC and APRE groups. Renal superoxide dismutase (SOD) activity and glutathione (GSH) levels decreased, but NAC and APRE significantly improved these parameters. Moreover, while malondialdehyde (MDA) levels in kidney tissue increased in the PARA group, they were significantly reduced in the NAC and APRE groups. In addition, histopathological changes supported the biochemical findings. APRE may protect the kidneys against PARA-induced damage by reducing oxidative stress and improving antioxidant defenses.

Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF). We previously observed activation of liver kinase B1 (LKB1) in non-surviving patients with APAP-induced ALF. Thus, we hypothesized LKB1 is detrimental in APAP hepatotoxicity. To test our hypothesis, we overdosed hepatocyte-specific LKB1 knockout (KO) mice and wildtype (WT) littermates with APAP and measured liver injury 2, 6, and 24 h later. Consistent with our hypothesis, LKB1 KO protected against APAP hepatotoxicity. However, the mechanisms of protection were sex-specific. Male KOs had lower NAPQI formation due to lower mitochondrial CYP2E1. In contrast, NAPQI formation was similar between female KO and WT mice, but female KOs still had reduced oxidative stress. The pentose phosphate pathway (PPP) is a major source of NADPH to counter oxidative stress, so we hypothesized that female KO mice have increased PPP enzymes. To test that, we measured hepatic glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the oxidative PPP. Importantly, G6PD was increased in female WT mice compared to male WT animals and even further increased in the female KO mice. Furthermore, 1.5 h post-treatment with the G6PD activator AG1 protected against APAP and increased hepatic NADPH in WT animals. Finally, re-analysis of our prior proteomics data revealed LKB1 activation occurred in both male and female ALF non-survivors, though it was greater in males. We conclude LKB1 regulates CYP2E1 and the PPP, that mitochondrial CYP2E1 is critical in APAP toxicity, and PPP activation is a potential therapeutic approach in liver injury in men and women.

A kaolin-derived Cu(ii)-doped zeolite (Cu-Z1) was synthesized through metakaolin activation, alkaline crystallization, and subsequent Cu2+ ion exchange, and immobilized on nickel foam (Cu-Z1/NiF) for electrochemical determination of paracetamol. The synthesized materials were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM/EDS), X-ray photoelectron spectroscopy (XPS), and thermogravimetric/differential thermogravimetric analysis (TGA/DTGA). The characterization results confirmed preservation of a ZSM-5-type aluminosilicate framework following Cu(ii) incorporation, with accompanying changes in crystallinity, morphology, and surface chemical environment. Electrochemical measurements demonstrated enhanced paracetamol oxidation at Cu-Z1/NiF compared with bare nickel foam and undoped Z1/NiF, giving an anodic peak current of 75.69 µA, a midpoint potential of 355 mV, and reduced charge-transfer resistance. Under optimized conditions, differential pulse voltammetry (DPV) showed a linear response over 5-100 µM paracetamol, with a detection limit of 0.3926 µM, sensitivity of 2.0456 µA µM-1 cm-2, and R 2 = 0.9971. The sensor exhibited good selectivity toward paracetamol in the presence of dopamine, uric acid, and glucose, with repeatability below 0.8% RSD. It retained 95.8% of its initial response after 20 days. Analysis of commercial paracetamol tablets produced recoveries of 95.91-99.29%, demonstrating the applicability of the Cu-Z1/NiF sensor for pharmaceutical paracetamol determination.

Artificial intelligence (AI) and machine-learning models provide powerful data-driven tools for modeling complex nonlinear systems and predicting process behavior from limited experimental data. In this study, an AI-driven predictive framework is developed for modeling paracetamol solubility and solvent density in supercritical carbon dioxide (SC-CO2). A dataset comprising 40 experimental observations was employed, with pressure and temperature used as input variables and paracetamol mole fraction and SC-CO2 density considered as target outputs. Three machine-learning regression algorithms-Gaussian Process Regression (GPR), Tweedie Regression (TDR), and K-Nearest Neighbors (KNN)-were developed and comparatively evaluated. To enhance predictive performance and automate model configuration, the Cheetah Optimizer (CO), a nature-inspired metaheuristic optimization algorithm, was integrated into the modeling framework for hyperparameter optimization. Model performance was assessed using the coefficient of determination (R 2), mean squared error (MSE), and mean absolute error (MAE). The results demonstrated that TDR provided the highest predictive accuracy for paracetamol mole fraction, achieving an R 2 of 0.985, whereas GPR exhibited the best performance for SC-CO2 density prediction, with an R 2 of 0.991. The developed framework successfully captured the nonlinear relationships between operating conditions and the predicted properties while demonstrating that the optimal learning algorithm depends on the target variable. These findings highlight the potential of AI-assisted optimization and machine-learning approaches for data-driven prediction and intelligent modeling of complex supercritical-fluid processes.

A 48-year-old woman presented with acute right-sided neck pain and a trismus. Plain and contrast-enhanced computed tomography revealed prevertebral calcification at the atlantoaxial level and retropharyngeal edema without rim enhancement, consistent with acute calcific tendinitis of the longus colli muscle. Magnetic resonance imaging (MRI) revealed signal hyperintensity in the right lateral pterygoid muscle without diffusion restriction. Moreover, MRI suggested inflammatory involvement of the right lateral pterygoid muscle as a possible mechanism of trismus. Symptoms resolved rapidly following the administration of non-steroidal anti-inflammatory drugs and acetaminophen. MRI may help clarify the mechanism underlying trismus in acute calcific tendinitis of the longus colli.

Surface-enhanced Raman spectroscopy (SERS) substrates require both strong electromagnetic enhancement and efficient access of analyte molecules to field-active hotspots. This study reports a protocol for fabricating entangled plasmonic nanowire substrates that address these requirements through an open network of wire-wire junctions. Vertically aligned carbon nanotube (VACNT) canopies and carbon nanotube buckypaper (CNTBP) provide two scaffold geometries in which numerous crossings are formed before metallization. Au deposition converts the CNT scaffolds into junction-rich plasmonic networks, while an optional alumina interlayer separates Au from the conductive CNT scaffold. Successful fabrication requires continuous metal coverage along individual fibers while preserving repeated crossings and open voids. Representative wire diameters were approximately 60 nm for the Au-coated VACNT-canopy network and approximately 25 nm for the CNTBP-based networks. Both architectures produced picomolar-level SERS responses. In the CNTBP comparison, Au/Al2O3/CNTBP showed an operational detection threshold of 50 pM, one decade lower than the 500 pM threshold of Au/CNTBP under identical acquisition conditions. At 5 pM acetaminophen, 83.1% of the responses in a 33 × 33 map of the Au-coated VACNT-canopy network remained within ±30% of the median, with most of the remaining variation arising from sparse high-response positions. The protocol provides two entangled nanowire scaffold routes for constructing open, junction-rich SERS substrates while preserving molecular access to the plasmonic surface.