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Priyanka,1,2 Somdutt Mujwar,3 Ram Bharti,1,2 Thakur Gurjeet Singh,3 Neeraj Khatri1,2 1IMTech Centre for Animal Resources & Experimentation (iCARE), CSIR-Institute of Microbial Technology (CSIR-IMTECH), Chandigarh, 160036, India; 2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; 3Chitkara College of Pharmacy, Chitkara University, Chandigarh, Punjab, 140401, IndiaCorrespondence: Neeraj Khatri, Email neeraj@imtech.res.inPurpose: To elucidate the therapeutic potential of 2,2’-bipyridine derivatives [NPS (1– 6)] on hepatocellular carcinoma HepG2 cells.Methods: The effects on cell survival, colony formation, cellular and nuclear morphology, generation of reactive oxygen species (ROS), change in the integrity of mitochondrial membrane potential (MMP), and apoptosis were investigated. Additionally, docking studies were conducted to analyze and elucidate the interactions between the derivatives and AKT and BRAF proteins.Results: NPS derivatives (1, 2, 5 and 6) significantly impaired cell viability of HepG2 cell lines at nanogram range concentrations - 72.11 ng/mL, 154.42 ng/mL, 71.78 ng/mL, and 71.43 ng/mL, while other derivatives were also effective at concentrations below 1 μg/mL. These compounds reduced the colony formation capacity of HepG2 cells in a dose-dependent manner following treatment. Mechanistic studies revealed that these derivatives induce reactive oxygen species (ROS) accumulation and cause mitochondrial membrane depolarization, ultimately triggering apoptosis in HepG2 cells. In the presence of these derivatives, cells demonstrated that 75% of cells underwent apoptosis, compared to 25% in the control group. Additionally, there was a marked increase in mitochondrial depolarization (95% cells) and a threefold rise in ROS levels compared to the controls. Docking studies revealed interactions between the derivatives and the signaling proteins AKT (PDB ID: 6HHF) and BRAF (PDB ID: 8C7Y) with binding affinities ranging from − 7.10 to − 9.91, highlighting their pivotal role in targeting key players in hepatocellular carcinoma progression.Conclusion: The findings of this study underscore the therapeutic potential of these derivatives against HepG2 cells and offer valuable insights for further experimental validation of their efficacy as inhibitors targeting AKT or BRAF signaling pathways. Keywords: hepatocellular carcinoma, ROS, MMP, apoptosis, AKT, BRAF

Abstract An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16 years; range 9–37 years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12 weeks. Donepezil dosage was started at 2.5 or 5.0 mg based on age and increased by 2.5 mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4 weeks prior for a maximum dosage of 7.5 or 10 mg. Participants

Background: Red man syndrome (RMS) is frequently reported from pediatric ward in patients receiving vancomycin, at the medical store of SGH, Pune. Though common in pediatric patients, not all patients receiving vancomycin developed Red man syndrome. Hence, this study was done to analyse the demographic, pathophysiological, and pharmacological aspects of the subject who experience adverse drug reactions with vancomycin and to determine if this predisposition is associated with any of these factors. Methods: All adverse drug reactions (ADR) to injection vancomycin in the pediatric ward that were reported from April 2018 - January 2022 were included. Controls were a similar number of randomly selected pediatric cases from the same ward who had received Intravenous vancomycin during the same period but did not experience the adverse drug reactions Results: The mean age was 29.91 ± 34.87 months in subjects who experienced ADR and 57.37 ± 41.58 months, in non-ADR group (p=0.0286). 37.4% were infants, 29.69% toddlers in ADR Group. Seventy four percent of patients who manifested with ADR were below age of 3 compared to barely 38% in controls (p=0.03). 66.6% were malnourished in the ADR group compared to 27.6% in controls (p=0.007). There was no association between the ADR and ethnicity, religion, gender, diagnosis, co-morbidities, co-administered drugs, or administered dose of vancomycin among the children. There was no apparent seasonal variation in occurrence of the ADR.Conclusion: RMS is more common in paediatric population than adults and is usually uneventful. Around 75% of the reactions occur within first 4 days of start of Vancomycin and usually occurs within 30 min of the preceding dose. Younger age groups (infants) and malnourishment were the two factors significantly associated with occurrence of RMS. We may also consider using lower than conventional doses and much slower infusions in such at-risk population.

BackgroundHealthcare provider wellness have been reported to correlate with patient care outcomes. It is not understood whether synergistic effects may exist between them.ObjectiveWe aim to investigate three provider wellness markers and determine their associations with provider self-reported medical errors and intent-to-leave outcomes among Emergency Department (ED) providers.DesignThis is a multi-center retrospective study.MethodThree wellness domains include professional fulfillment (PF), burnout (BO), and personal resilience (PR). Two outcomes measured as provider self-reported medical errors and provider intent-to-leave. Correlations between wellness markers and outcomes were analyzed. When adjusted for other confounders (provider demographics, provider experience, and operational environment), a multivariate logistic regression analysis was performed to further determine the interactions among these three domains on provider wellness affecting patient and provider related outcomes.ResultsTotal 242 surveys were collected from providers at 16 different EDs. The median score of PF were 2.83 among physicians and 2.67 among APPs, BO were 1.00 (physicians) and 0.95 (APPs), and PR were 0.88 (physicians) and 0.81 (APPs). The median scores of self-reported medical errors were 1.50 (physicians) and 0.95 (APPs), and intent-to-leave were 1.00 (physicians and APPs). High correlations occurred among PF, BO, and PR. When analyzed together, high PF, low BO, and high PR functioned as a protective effect on provider intent-to-leave (adjusted odds ratios = 0.09, 95% CI 0.03-0.30).ConclusionHigh correlations occurred among three provider wellness markers with no significant difference between physicians and APPs. Providers with high PR, low BO, and high PR tended to be more stable in their jobs.

Background/aims This was a cross-sectional comparative study. We evaluated the ability of three large language models (LLMs) (ChatGPT-3.5, ChatGPT-4, and Google Bard) to generate novel patient education materials (PEMs) and improve the readability of existing PEMs on paediatric cataract. Methods We compared LLMs' responses to three prompts. Prompt A requested they write a handout on paediatric cataract that was 'easily understandable by an average American.' Prompt B modified prompt A and requested the handout be written at a 'sixth-grade reading level, using the Simple Measure of Gobbledygook (SMOG) readability formula.' Prompt C rewrote existing PEMs on paediatric cataract 'to a sixth-grade reading level using the SMOG readability formula'. Responses were compared on their quality (DISCERN; 1 (low quality) to 5 (high quality)), understandability and actionability (Patient Education Materials Assessment Tool (≥70%: understandable, ≥70%: actionable)), accuracy (Likert misinformation; 1 (no misinformation) to 5 (high misinformation) and readability (SMOG, Flesch-Kincaid Grade Level (FKGL); grade level <7: highly readable). Results All LLM-generated responses were of high-quality (median DISCERN ≥4), understandability (≥70%), and accuracy (Likert=1). All LLM-generated responses were not actionable (<70%). ChatGPT-3.5 and ChatGPT-4 prompt B responses were more readable than prompt A responses (p<0.001). ChatGPT-4 generated more readable responses (lower SMOG and FKGL scores; 5.59±0.5 and 4.31±0.7, respectively) than the other two LLMs (p<0.001) and consistently rewrote them to or below the specified sixth-grade reading level (SMOG: 5.14±0.3). Conclusion LLMs, particularly ChatGPT-4, proved valuable in generating high-quality, readable, accurate PEMs and in improving the readability of existing materials on paediatric cataract. [ABSTRACT FROM AUTHOR]

Abstract Direct oxidation of methane to valuable oxygenates like alcohols and acetic acid under mild conditions poses a significant challenge due to high C‒H bond dissociation energy, facile overoxidation to CO and CO2 and the intricacy of C−H activation/C−C coupling. In this work, we develop a multifunctional iron(III) dihydroxyl catalytic species immobilized within a metal-organic framework (MOF) for selective methane oxidation into methanol or acetic acid at different reaction conditions using O2. The active-site isolation of monomeric FeIII(OH)2 species at the MOF nodes, their confinement within the porous framework, and their electron-deficient nature facilitate chemoselective C‒H oxidation, yielding methanol or acetic acid with high productivities of $$38,592\,\upmu {{{\rm{mol}}}}_{{{{\rm{CH}}}}_{3}{{\rm{OH}}}}{{{{\rm{g}}}}_{{{\rm{Fe}}}}}^{-1}{{{\rm{h}}}}^{-1}$$ 38 , 592 μ mol CH 3 OH g Fe − 1 h − 1 and $$81,043\,\upmu {{{\rm{mol}}}}_{{{{\rm{CH}}}}_{3}{{{\rm{CO}}}}_{2}{{\rm{H}}}}{{{{\rm{g}}}}_{{{\rm{Fe}}}}}^{-1}{{{\rm{h}}}}^{-1}$$ 81 , 043 μ mol CH 3 CO 2 H g Fe − 1 h − 1 , respectively. Experiments and theoretical calculations suggest that methanol formation occurs via a FeIII-FeI-FeIII catalytic cycle, whereas CH3CO2H is produced via hydrocarboxylation of in-situ generated CH3OH with CO2 and H2, and direct CH4 carboxylation with CO2.