A review on reactive oxygen species-induced mechanism pathways of pharmaceutical waste degradation: Acetaminophen as a drug waste model.

Innately designed to induce physiological changes, pharmaceuticals are foreknowingly hazardous to the ecosystem. Advanced oxidation processes (AOPs) are recognized as a set of contemporary and highly efficient methods being used as a contrivance for the removal of pharmaceutical residues. Since reactive oxygen species (ROS) are formed in these processes to interact and contribute directly toward the oxidation of target contaminant(s), a profound insight regarding the mechanisms of ROS leading to the degradation of pharmaceuticals is fundamentally significant. The conceptualization of some specific reaction mechanisms allows the design of an effective and safe degradation process that can empirically reduce the environmental impact of the micropollutants. This review mainly deliberates the mechanistic reaction pathways for ROS-mediated degradation of pharmaceuticals often leading to complete mineralization, with a focus on acetaminophen as a drug waste model.

Novel reduced heteropolyacid nanoparticles for effective treatment of drug-induced liver injury by manipulating reactive oxygen and nitrogen species and inflammatory signals.

With the rapid advancements in biomedicine, the use of clinical drugs has surged sharply. However, potential hepatotoxicity limits drug exploitation and widespread usage, posing serious threats to patient health. Hepatotoxic drugs disrupt liver enzyme levels and cause refractory pathological damage, creating a challenge in the application of diverse first-line drugs. The activation and deterioration of reactive oxygen and nitrogen species (RONS) and inflammatory signals are key pathological mechanisms of drug-induced liver injury (DILI). Herein, a novel reduced heteropolyacid nanoparticle (RNP) has been developed, possessing high RONS-scavenging ability, strong anti-inflammatory activity, and excellent biosafety. These features enable it to swiftly restore the redox and immune balance of the liver. Intravenous administration of RNP effectively scavenged RONS storm, reversing liver oxidative stress and restoring normal mitochondrial membrane potential and function. Furthermore, by inhibiting c-Jun-N-terminal kinase phosphorylation, RNP facilitated the restoration of nuclear factor erythroid 2-related factor 2-mediated endogenous antioxidant signaling, ultimately rescuing the liver function and tissue morphology in acetaminophen-induced DILI mice. Crucially, the high biocompatible RNP exhibited superior efficacy in the DILI mouse model compared to the clinical antioxidant N-acetylcysteine. This targeted therapeutic approach, tailored to address the onset and progression of DILI, offers valuable new insights into controlling the condition and restoring liver structure and function.

A sustainable and green HPLC-PDA technique for the simultaneous estimation of Post-COVID-19 syndrome co-administered drugs with greenness and whiteness assessment.

COVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10-15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors' quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00-45.00 µg/mL, 0.5-50.00 µg/mL, and 0.15-20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55-99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method's greenness. "Non-toxic" ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method's greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety.

Aloperine Ameliorates Acetaminophen-Induced Acute Liver Injury through HMGB1/TLR4/NF-κB and NLRP3/Inflammasome Pathway.

Purpose: Aloperine (ALO), an alkaloid isolated from Sophora alopecuroides L., possesses multiple pharmacological activities and holds a promise potential for the treatment of various clinical conditions, including skin hypersensitivity, cancer, and inflammatory disorders. The purpose of this study was to investigate the role of ALO in acetaminophen (N-acetyl-para-aminophenol (APAP))-induced acute liver injury and its underlying mechanisms. Materials and Methods: An animal model of acute liver injury was induced by intraperitoneal injection of APAP (150 mg/kg). Prior to APAP injection, ALO (40 mg/kg) was administered daily for 7 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were then measured using an automated chemical analyzer. Histopathological changes were evaluated using hematoxylin and eosin staining. Oxidative stress levels were measured by detecting superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). Pro-inflammatory cytokines were detected in serum and liver tissues using ELISA and quantitative real-time polymerase chain reaction (q-PCR). The expression of members of the HMGB1/TLR4/NF-κB signaling pathway and NLRP3 inflammasome were determined by Western blot and/or q-PCR. In addition, the expression and location of NLRP3, cleaved caspase-1, high-mobility group box 1 (HMGB1), and phosphorylated p65 (p-p65) were detected by immunofluorescence. Results: Pretreatment with ALO significantly protected mice from APAP-induced acute liver injury, with decreased MDA content, and significantly increased GSH and SOD activities. Furthermore, ALO pretreatment reduced the release of pro-inflammatory cytokines (IL-1ß and TNF-α) and decreased the expression of caspase-1, cleaved caspase-1, and NLRP3. In addition, ALO pretreatment also inhibited the activation of the HMGB1/TLR4/NF-κB signaling pathway. Conclusion: Taken together, ALO can ameliorate APAP-induced acute liver injury by inhibiting oxidative stress, inflammation by inhibiting the HMGB1/TLR4/NF-κB, and NLRP3/inflammasome pathway.

Exploring the phytochemicals, antioxidant properties, and hepatoprotective potential of Moricandia sinaica leaves against paracetamol-induced toxicity: Biological evaluations and in Silico insights.

Thirteen components were identified in the methanol extract of Moricandia sinaica leaves (MSLE) through analysis utilizing HPLC-ESI-MS/MS., including flavonoids, anthocyanins, phenolic acids, and fatty acids. The methanol extract of M. sinaica leaves contained total phenolics and flavonoids (59.37 ± 2.19 mg GAE/g and 38.94 ± 2.72 mg QE/g), respectively. Furthermore, it revealed in vitro antioxidant properties as determined by the DPPH and FRAP assays, with respective IC50 values of 10.22 ± 0.64 and 20.89 ± 1.25 µg/mL. The extract exhibited a notable hepatoprotective effect in rats who experienced paracetamol-induced hepatotoxicity. When a dose of 250 mg/kg was given, there was a 52% reduction in alanine transaminase and a 30% reduction in aspartate transaminase compared to the group with the disease. Furthermore, it demonstrated a 3.4-fold, 2.2-fold, and 2.6-fold increase in superoxide dismutase, non-protein sulfhydryl, and glutathione peroxidase, respectively. In addition, it demonstrated a 68% decrease in lipid peroxide levels compared to the group with paracetamol-induced condition. The verification was conducted using a histological study, which identified improved liver histology with a small number of distended hepatocytes. Moreover, in silico studies focused on the enzymes NADPH oxidase, butyrylcholinesterase, and tyrosinase as the targets for the major compounds. In conclusion, MSLE showed promising hepatoprotective and antioxidant activities due to its richness in antioxidant metabolites.

Rapid detection of ingested acetaminophen on face mask by ambient ionization tandem mass spectrometry.

BACKGROUND: A regular face mask is comprised of three layers for resisting moisture, filtration, and absorbing oral fluid, respectively. Since the polymers with different polarities are used to make the layers, a face mask can be used as a sampling tool to retain polar or non-polar chemical and biochemical substances in the exhaled breath. In this study, thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS), an ambient ionization mass spectrometric technique, was used to detect trace acetaminophen that were exhaled and retained on the surface of different layers in a face mask. RESULTS: With probe sampling combined with TD-ESI/MS/MS, the acetaminophen ion signal can be detected at the mouth/nostril region of the face mask after taking the acetaminophen tablet. The experimental results were similar to previous studies for the detection of acetaminophen in blood over time using LC/MS/MS. In addition, the intensities of acetaminophen on different layers of the face mask could reveal the differing distributions of exhaled acetaminophen on each layer. To explore the distribution of acetaminophen on the face mask surface, multiple probes were used to collect samples from different locations of the face mask for analysis. The molecular mapping of acetaminophen on the face mask was rendered by scaling the analyte ion signal intensity based on a temperature color gradient. The cartography showed a higher acetaminophen ion signal distribution on the mouth and nostril regions than in other areas of the face mask. SIGNIFICANCE: Owing to the advantages of a simple, sensitive, and non-invasive sampling approach, drug monitoring could be potentially performed to provide useful information for anti-drug of precision medicine in the future.

Exploring the reclamation pathway science of Beachwood powder for pharmaceutical acetaminophen drug effluent management.

High effective low-cost substance derived from agriculture-based waste towards a circular economy concept showed a significant green approach for pharmaceuticals uptake in aqueous solution. Beachwood sawdust was used as the source of cellulose based adsorbents. Cellulose is isolated from the waste and in parallel magnetite nanoparticles are prepared by the simple co-precipitation technique and the two substances are mixed in various proportions to be acetaminophen adsorbent. Characteristics of the prepared magnetite (M)/sawdust (SD) composite in various proportions (M:SD (1:1), M:SD (1:2), M:SD (1:3), M:SD (1:5) and M:SD (2:1) were assessed using scanning electron microscope (SEM) transmission electron microscope (TEM) and X-ray diffractometer (XRD) which revealed the presence magnetite and cellulose. Also, for the object of recoverable adsorbent, vibrating sample magnetometer (VSM) of the adsorbent is investigated to evaluate its sustainability. The highest removal rate was associated with M:SD (1:2) compared to the other composites and the pristine magnetite or sawdust materials within 2 hours of isotherm time. The adsorption parameters are optimized and the maximal yield is attained at pH (7.0), adsorbent dose of 2.0 g/L at room temperature. The adsorption matrix is following Langmuir model and fitted to the second-order kinetic model. The process is exothermic in nature and highlighted physisorption tendency. The highest monolayer adsorption uptake was investigated at 7.0 mg/g which corresponds to the M:SD (1:2) adsorbent.

Application of physiological network mapping in the prediction of survival in critically ill patients with acute liver failure.

Reduced functional connectivity of physiological systems is associated with poor prognosis in critically ill patients. However, physiological network analysis is not commonly used in clinical practice and awaits quantitative evidence. Acute liver failure (ALF) is associated with multiorgan failure and mortality. Prognostication in ALF is highly important for clinical management but is currently dependent on models that do not consider the interaction between organ systems. This study aims to examine whether physiological network analysis can predict survival in patients with ALF. Data from 640 adult patients admitted to the ICU for paracetamol-induced ALF were extracted from the MIMIC-III database. Parenclitic network analysis was performed on the routine biomarkers using 28-day survivors as reference population and network clusters were identified for survivors and non-survivors using k-clique percolation method. Network analysis showed that liver function biomarkers were more clustered in survivors than in non-survivors. Arterial pH was also found to cluster with serum creatinine and bicarbonate in survivors compared with non-survivors, where it clustered with respiratory nodes indicating physiologically distinctive compensatory mechanism. Deviation along the pH-bicarbonate and pH-creatinine axes significantly predicts mortality independent of current prognostic indicators. These results demonstrate that network analysis can provide pathophysiologic insight and predict survival in critically ill patients with ALF.

Effect of fasting-induced headache on calcitonin gene related peptide (CGRP) and other clinical biomarkers on the first day of Ramadan: Sub-analysis from a randomized open label clinical trial.

BACKGROUND: Fasting-induced headaches (FIHs) have been shown to occur on the first day of Ramadan and clearly decline thereafter. Despite the wealth of knowledge about different types of headaches (e.g., migraine-, cluster-, and tension-type headaches), research on the mechanism underlying FIHs, as well as their treatment, remains scarce. Our study aimed to investigate any association between FIHs during the first day of Ramadan and potential headache-related biomarkers, including fasting blood glucose (FBG), C-reactive protein (CRP), magnesium, vitamin B9, vitamin B12, homocysteine, and calcitonin gene related peptide (CGRP), and to assess whether a prophylactic use of paracetamol may influence these biomarkers. METHODS: As part of a randomized, open-label clinical trial that evaluated the effect of paracetamol as a prophylactic therapy for FIH, blood samples from stratified subjects in the prophylaxis and control groups were withdrawn while fasting after the 1st dose of paracetamol (in the prophylaxis group) and prior to reporting headache occurrence. RESULTS: Plasma and serum were separated for 61 subjects; 31 and 30 subjects from the prophylaxis and control groups, respectively. Overall, no significant differences were found in the levels of FBG, CRP, magnesium, vitamin B9, and vitamin B12 in headache-suffering subjects compared to those without headache despite the use of paracetamol for prophylaxis. Homocysteine, however, was significantly reduced in all subjects who experienced FIH compared to those without headache (median 6.9 [1.6] vs. 7.7 [2.7] umol/L; p = 0.041). On the contrary, when the CGRP was measured using immunoassay, it was found to be significantly elevated in all headache-suffering subjects compared to those without headache (median 126.1 [17.7] vs. 105.8 [19.6] pg/mL; p ≤ 0.0001). This difference was maintained upon comparing the headache to non-headache subjects in both the prophylaxis (median 121.5 [15.4] vs. 105.8 [9.4] pg/mL; p < 0.01) and control groups (median 128.5 [28.3] vs. 105.8 [23.8] pg/mL; p < 0.01). Additionally, an elevated CGRP level was found to increase the odds of having a FIH [OR = 1.32; 95%CI 1.06-1.22]. CONCLUSIONS: Our findings revealed the role of CGRP in FIHs for the first time and suggest further investigation in signaling pathways downstream CGRP receptors. Furthermore, the modulation CGRP or CGRP receptors could have a clinical application in the prevention of FIHs. TRIAL REGISTRATION: This study was registered with the Saudi Food and Drug Authority in the Saudi Clinical Trials Registry (SCTR; No. 22122102).

The Influence of Activated Sludge Augmentation on Its Ability to Degrade Paracetamol.

Paracetamol is one of the most commonly used painkillers. Its significant production and consumption result in its presence in the environment. For that reason, paracetamol has a negative impact on the organisms living in ecosystems. Therefore, it is necessary to develop effective methods to remove paracetamol from sewage. One of the methods is the bioaugmentation of activated sludge with organisms with increased degradation potential in relation to paracetamol. This study determined the effectiveness of paracetamol degradation by activated sludge augmented with a free or immobilised Pseudomonas moorei KB4. To immobilise the strain, innovative capsules made of cellulose acetate were used, the structure of which provides an optimal environment for the development of bacteria. Augmentation with both a free and immobilised strain significantly improves the efficiency of paracetamol biodegradation by activated sludge. Over a period of 30 days, examined systems allowed ten doses of paracetamol decomposition, while the unaugmented system degraded only four. At the same time, using the immobilised strain does not significantly affect the functioning of the activated sludge, which was reflected in the stability of processes such as nitrification. Due to the high stability of the preparation, it can become a valuable tool in wastewater treatment processes.

THE PROTECTIVE EFFECTS OF SELENIUM-ENRICHED HYDROPONIC RADISH ON PARACETAMOL-INDUCED LIVER DAMAGE IN RATS.

Paracetamol-induced liver toxicity in rats is a well-studied model for liver damage. The present study investigates the morphological changes in hepatic blood vessels and the protective effects of hydroponically grown Radish (Raphanus sativus L.) pretreatment in rats with paracetamol-induced liver damage. The results indicate significant alterations in vascular morphology and liver enzyme levels, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which serve as indicators of hepatotoxicity. The findings suggest that hydroponic Radish may mitigate the adverse effects of paracetamol on liver health, highlighting the importance of dietary components in preventing micronutrient deficiencies and promoting overall health.

Willow catkin template synthesis of NiS@NSC hollow tubes for highly sensitive dual-function electrochemical detection of acetaminophen and Cu2.

Public health and environmental well-being have become increasingly threatened by the contamination of pharmaceuticals and heavy metal ions. This study focuses on addressing this critical issue by developing a novel electrochemical sensor for the dual-functional detection of acetaminophen (AP) and Cu2+. Utilizing willow catkins as a biomass template, a hollow tubular NiS@NSC composite was prepared by simple nickel salt impregnation combined with calcination and sulfurization. A highly sensitive dual-functional electrochemical sensor was thus constructed that can detect both acetaminophen (AP) and Cu2+. By examining its electrochemical properties, the sensor achieves an impressive detection limit of 1.33 pM for AP, with a linear range of 4.00 pM ~ 0.15 mM. The sensor can also detect Cu2+, with a detection limit of 1.04 µM, and a linear range of 3.13 µM ~ 0.66 mM. The sensor also exhibits strong resistance to interference, and good repeatability and stability. In addition, the sensor has demonstrated good performance in actual sample analysis, including the detection of AP in serum and Cu2+ in wastewater. This excellent electrochemical sensing performance is mainly attributed to the synergistic effect of its unique tubular structure and highly conductive N, S co-doped carbon. This results in the sensor exhibiting minimal charge transfer resistance, an extensive electrochemically active surface area, and a high density of active sites.

Pain after laparoscopic endometriosis-specific vs. hysterectomy surgeries: A retrospective cohort analysis.

OBJECTIVES: To evaluate pain perception and analgesic use between patients who underwent endometriosis-specific laparoscopic surgery compared to laparoscopic hysterectomy. MATERIAL AND METHODS: This retrospective cohort study included women diagnosed with endometriosis who underwent laparoscopic surgery from 1/2019 to 11/2022. The control group consisted of premenopausal women who underwent laparoscopic hysterectomy, which was considered a similarly extensive surgery. Demographics, preoperative and post-operative data were compared between groups. Post-operative pain scores on a visual analogue scale (VAS) between 0 (no pain) and 10 (worst pain) were compared between groups for each post-operative day (POD). Standard pain relief analgesia on POD 0-1 included fixed intravenous treatment with paracetamol and intramuscular diclofenac. The need for additional analgesics (morphine or dipyrone) beyond the standard pain relief protocol was compared between groups. RESULTS: Among 200 patients who underwent laparoscopic surgery, 100 (50%) were in the endometriosis group and 100 (50%) in the hysterectomy group. The endometriosis group was characterized by younger age and lower parity (both, p<0.001). There was no significant difference between the groups in mean VAS scores for each post-operative day. However, among patients who needed additional analgesics beyond the standard protocol on POD 1, a higher percentage of women in the endometriosis group used opioids rather than milder analgesics, as compared to controls (1% vs. 0.2%, respectively, p = 0.03). CONCLUSION: Increased post-operative morphine use was observed in patients with endometriosis following laparoscopic surgery, despite no significant difference in mean VAS scores during the post-operative days. These findings suggest that personalized pain relief protocols should be adjusted for women with endometriosis.

Gardenia jasminoides extract mitigates acetaminophen-induced liver damage in mice.

BACKGROUND: Acetaminophen (APAP)-induced hepatotoxicity is a potentially life-threatening condition. Gardenia jasminoides fruit extract (GJE), which contains geniposide (Gen) as its major active constituent, possesses anti-inflammatory and antioxidant properties and may help address the underlying pathogenesis of APAP-induced hepatotoxicity. This study aimed to evaluate the effects of GJE in a mouse model of APAP-induced hepatotoxicity. METHODS: Twenty-four male ICR mice were divided into 4 groups (n = 6/group): [1] Control group, mice were given distilled water; [2] APAP group, mice received a single dose of 600 mg/kg APAP; [3] APAP + low-dose GJE group, mice received APAP followed 30 min later by 2 doses of low-dose GJE (0.44 g/kg/dose, containing Gen 100 mg/kg/dose) 8 h apart; [4] APAP + high-dose GJE group, mice received APAP followed by 2 doses of high-dose GJE (0.88 g/kg/dose, containing Gen 200 mg/kg/dose). All mice were euthanized 24 h after APAP administration. Liver tissue was used for histological examination and to measure glutathione (GSH) and malondialdehyde (MDA) levels. Serum was used to determine levels of ALT and inflammatory cytokines (tumor necrosis factor- α (TNF-α) and interleukin-6 (IL-6)). RESULTS: Liver histopathology showed moderate to severe hepatic necroinflammation in the APAP group, whereas only mild necroinflammation was observed in both treatment groups. Serum ALT levels were significantly elevated in the APAP group compared to the control group but were significantly reduced after low- and high-dose GJE treatment. Serum TNF- α levels were significantly higher in the APAP group than in the control group and were significantly lower after high-dose GJE treatment (135.5 ± 477.2 vs. 35.5 ± 25.8 vs. 74.7 ± 47.2 vs. 41.4 ± 50.8 pg/mL, respectively). Serum IL-6 followed a similar pattern. Hepatic GSH levels were significantly lower in the APAP group compared to the control group but significantly increased after both low- and high-dose GJE treatment (19.9 ± 4.5 vs. 81.5 ± 12.4 vs. 71.4 ± 7.8 vs. 82.6 ± 6.6 nmol/mg protein, respectively). Conversely, hepatic MDA levels were significantly elevated in the APAP group compared with the control group but significantly decreased after high-dose GJE treatment (108.6 ± 201.5 vs. 40.5 ± 18.0 vs. 40.5 ± 16.8 nmol/mg protein, respectively). CONCLUSIONS: Treatment with G. jasminoides fruit extract can alleviate APAP-induced hepatotoxicity, likely through its anti-inflammatory and antioxidant properties.

Paracetamol-induced hepatotoxicity after normal therapeutic doses in the Hong Kong Chinese population.

INTRODUCTION: Paracetamol is generally safe at normal therapeutic doses of ≤4 g/day in adults. However, paracetamol-induced hepatotoxicity after normal therapeutic doses use has been reported. We investigated the epidemiology of this adverse drug reaction in the Hong Kong Chinese population. METHODS: This territory-wide retrospective observational study included adult patients with suspected paracetamol-induced hepatotoxicity after normal therapeutic doses use from January 2011 to June 2022. We evaluated the demographic characteristics; paracetamol dose, duration, and reason for use; preexisting hepatotoxicity risk factors; laboratory findings; and their relationship with clinical outcomes. RESULTS: We identified 76 patients (median age: 74 years, 23 males) with suspected paracetamolinduced hepatotoxicity after normal therapeutic doses use. There were 14 cases with significant clinical outcomes (five deaths and nine cases of acute hepatic failure), with an incidence of 1.2 cases per year. For patients with significant clinical outcomes, they were significantly older (age >80 years), had a lower body weight (<50 kg), exposed to longer durations (>2 days) and higher daily doses (>3 g), and with higher proportion of malnutrition. CONCLUSION: Paracetamol-induced hepatotoxicity can occur at normal therapeutic doses in the Hong Kong Chinese population. The identified risk factors are consistent with international guidelines regarding susceptible patients. Considering the widespread local use of paracetamol and low incidence of severe hepatotoxicity, the current dosage recommendations are considered safe for the general population. For susceptible patients, a reduced maximum dose of ≤3 g/day is recommended, with liver function and serum paracetamol monitoring in place.

Evaluation, optimization study, and life cycle assessment of novel eco-friendly PVA-based nanocomposite hydrogel adsorbents for methylene blue and paracetamol removal.

In this study, an eco-friendly and novel hydrogel based on a crosslinked polyvinyl alcohol (PVA), iota carrageenan (IC) and polyvinylpyrrolidone (PVP) scaffold, containing a large amount (10-50 wt%) of nanoscale palm fronds (NPF) as additives, for water purification was demonstrated. A life cycle assessment (LCA) findings on NPF as biomass waste incorporated into PVA_PVP_IC polymer matrix was presented, and the results highlight the necessity of focused actions to reduce environmental impact and support the palm waste utilization in a sustainable manner. The multicomponent nanocomposite hydrogels were examined as adsorbents in a system work in batches for methylene blue (MB) and paracetamol (PCT) removal. The results show that, the presence of NPF, which dispersed in the hydrogel PVA_PVP_IC scaffolds containing both covalent and non-covalent cross-linking bonds, greatly enhanced the MB and PCT adsorption efficiency. A response surface methodology (RSM) model was used to find the best operating parameters of contaminant adsorption, including time, adsorbent dose, and starting concentration of pollutants. By using this statistical model, it was found that the optimal conditions for the adsorption reaction to achieve the complete removal of MB are 66.7 h adsorption time duration, 98.5 mg L-1 starting concentration, and an adsorbent dose of 5.9 mg, while for the complete removal of PCT, it is 57.6 h adsorption time duration, 80 mg L-1 starting concentration, and an adsorbent dose of 6 mg. The reusability of the nanocomposite hydrogels were tested for 5 cycles, all showed high adsorption capacity, indicating the potential for practical application of this nanocomposite hydrogel system. This study indicates that the prepared nanocomposite hydrogel raises the standard used for treatment of wastewater and also gives a solution to protect the environment and mitigate global warming.

Self-medication among Basic Science Medical Students of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

INTRODUCTION: Self-medication is using drugs to treat self-diagnosed signs or symptoms of oneself or others. Being closer to pharmacology and pathology, medical students have been more prone to it. The study aimed to determine the prevalence of self-medication among basic sciences medical students in a tertiary care centre in Kathmandu. METHODS: A descriptive cross-sectional study was conducted among basic science students from 15 February 2023 to 14 March 2023 after obtaining ethical approval from the Institutional Review Committee (Reference number: 04122022/04). A convenience sampling method was used. Data were collected online and analysed. Point estimate at 95% confidence interval was calculated. RESULTS: Among 322 basic science medical students the prevalence of self-medication was 218 (67.70%) (64.81-70.59 at 95% Confidence Interval). Fever was the most common condition treated by self-medication 106 (48.62%) and paracetamol was the most common medication 93 (42.66%). Of those who engaged in self-medication, 97 (44.50%) did so to save time. Moreover, within this group, 67 (30.73%) experienced adverse drug reactions, leading 37 (16.97%) of these students to visit a private doctor. Additionally, 138 (63.30%) refrained from prescribing medication to their family and friends. CONCLUSIONS: Self-medication among basic science medical students was found to be lower in comparison to other studies done in similar settings.

The Prophylactic Effect of Acetaminophen and Caffeine on Post Dural Puncture Headache after Spinal Anesthesia for Cesarean Section: A Randomized Double-Blind Clinical Trial.

Background: Post-dural puncture headache (PDPH) is the most common complication following spinal anesthesia among parturients undergoing cesarean section surgery. The purpose of this study was to evaluate the effectiveness of acetaminophen and caffeine in preventing PDPH. Methods: This double-blind, randomized clinical trial was conducted on 96 obstetric women, who were candidates for elective cesarean section. Following the randomization of participants into two groups, participants in the intervention group received tablets of acetaminophen (500 mg)+caffeine (65 mg), and participants in the control group received placebo tablets orally 2 hours before spinal anesthesia induction and then every 6 hours after surgery up to 24 hours. All parturients were evaluated for frequency and intensity of PDPH every 6 hours until 24 hours after surgery and then 48 and 72 hours after surgery. Overall satisfaction during the first 72 hours of postpartum was evaluated. The data were analyzed using SPSS software. P<0.05 was considered statistically significant. Results: Participants in the intervention group were 70% less likely to experience PDPH after spinal anesthesia (OR=0.31 P=0.01, 95% CI [0.12-0.77]). They also experienced significantly milder headaches 18 hours, 48 hours, and 72 hours later. Participants in the intervention group reported higher levels of satisfaction at the end of the study (P=0.01). No side effects related to the intervention were reported. Conclusion: Prophylactic administration of acetaminophen+caffeine decreases 70% the risk of PDPH and significantly attenuates pain intensity in obstetric patients who underwent spinal anesthesia for cesarean section.

Eed-dependent histone modification orchestrates the iNKT cell developmental program alleviating liver injury.

Polycomb repressive complex 2 (PRC2) is an evolutionarily conserved epigenetic modifier responsible for tri-methylation of lysine 27 on histone H3 (H3K27me3). Previous studies have linked PRC2 to invariant natural killer T (iNKT) cell development, but its physiological and precise role remained unclear. To address this, we conditionally deleted Eed, a core subunit of PRC2, in mouse T cells. The results showed that Eed-deficient mice exhibited a severe reduction in iNKT cell numbers, particularly NKT1 and NKT17 cells, while conventional T cells and NKT2 cells remained intact. Deletion of Eed disrupted iNKT cell differentiation, leading to increased cell death, which was accompanied by a severe reduction in H3K27me3 levels and abnormal expression of Zbtb16, Cdkn2a, and Cdkn1a. Interestingly, Eed-deficient mice were highly susceptible to acetaminophen-induced liver injury and inflammation in an iNKT cell-dependent manner, highlighting the critical role of Eed-mediated H3K27me3 marks in liver-resident iNKT cells. These findings provide further insight into the epigenetic orchestration of iNKT cell-specific transcriptional programs.

Material-Sparing Approach to Predict Tablet Capping Under Processing Compression Conditions Based on Mechanical and Molecular Properties Derived from Compaction Simulation and Crystal Structural Analysis.

Present study evaluates the usability of compaction simulation-based mechanical models as a material-sparing approach to predict tablet capping under processing compression conditions using Acetaminophen (APAP) and Ibuprofen (IBU). Measured mechanical properties were evaluated using principal component analysis (PCA) and principal component regression (PCR) models. PCR models were then utilized to predict the capping score (CS) from compression pressure (CP). APAP formulations displayed a quadratic correlation between CS and CP, with CS rank order following CP of 200MPa < 300MPa < 100MPa, indicating threshold compression pressure (TCP) limit between 200 and 300 MPa, resulting in higher CS at 300 than 200 MPa regardless of increased CP. IBU formulations displayed a linear correlation between CS and CP, with CS rank order following CP of 100MPa < 200MPa < 300MPa, indicating TCP limit between 100 and 200 MPa, resulting in higher CS at 200 and 300 than 100 MPa regardless of increased CP. Molecular models were developed as validation methods to predict capping from CP. Measured XRPD patterns of compressed tablets were linked with calculated Eatt and d-spacing of slip planes and analyzed using variable component least square methods to predict TCP triggering cleavage in slip planes and leading to capping. In APAP and IBU, TCP values were predicted at 245 and 175 MPa, meaning capped tablets above these TCP limits regardless of increased CP. A similar trend was observed in CS predictions from mechanical assessment, confirming that compaction simulation-based mechanical models can predict capping risk under desired compression conditions rapidly and accurately.