Accuracy of ChatGPT in Neurolocalization.

Introduction ChatGPT (OpenAI Incorporated, Mission District, San Francisco, United States) is an artificial intelligence (AI) chatbot with advanced communication skills and a massive knowledge database. However, its application in medicine, specifically in neurolocalization, necessitates clinical reasoning in addition to deep neuroanatomical knowledge. This article examines ChatGPT's capabilities in neurolocalization. Methods Forty-six text-based neurolocalization case scenarios were presented to ChatGPT-3.5 from November 6th, 2023, to November 16th, 2023. Seven neurosurgeons evaluated ChatGPT's responses to these cases, utilizing a 5-point scoring system recommended by ChatGPT, to score the accuracy of these responses. Results ChatGPT-3.5 achieved an accuracy score of 84.8% in generating "completely correct" and "mostly correct" responses. ANOVA analysis suggested a consistent scoring approach between different evaluators. The mean length of the case text was 69.8 tokens (SD 20.8). Conclusion While this accuracy score is promising, it is not yet reliable for routine patient care. We recommend keeping interactions with ChatGPT concise, precise, and simple to improve response accuracy. As AI continues to evolve, it will hold significant and innovative breakthroughs in medicine.

MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study.

BACKGROUND: Pick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration. METHODS: In this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically confirmed Pick's disease worldwide. For this analysis, we collected brain samples from individuals with pathologically confirmed Pick's disease from 35 sites (brainbanks and hospitals) in North America, Europe, and Australia between Jan 1, 2020, and Jan 31, 2023. Neurologically healthy controls were recruited from the Mayo Clinic (FL, USA, or MN, USA between March 1, 1998, and Sept 1, 2019). For the primary analysis, individuals were directly genotyped for the MAPT H1-H2 haplotype-defining variant rs8070723. In a secondary analysis, we genotyped and constructed the six-variant-defined (rs1467967-rs242557-rs3785883-rs2471738-rs8070723-rs7521) MAPT H1 subhaplotypes. Associations of MAPT variants and MAPT haplotypes with Pick's disease risk, age at onset, and disease duration were examined using logistic and linear regression models; odds ratios (ORs) and ß coefficients were estimated and correspond to each additional minor allele or each additional copy of the given haplotype. FINDINGS: We obtained brain samples from 338 people with pathologically confirmed Pick's disease (205 [61%] male and 133 [39%] female; 338 [100%] White) and 1312 neurologically healthy controls (611 [47%] male and 701 [53%] female; 1312 [100%] White). The MAPT H2 haplotype was associated with increased risk of Pick's disease compared with the H1 haplotype (OR 1·35 [95% CI 1·12 to 1·64], p=0·0021). MAPT H2 was not associated with age at onset (ß -0·54 [95% CI -1·94 to 0·87], p=0·45) or disease duration (ß 0·05 [-0·06 to 0·16], p=0·35). Although not significant after correcting for multiple testing, associations were observed at p less than 0·05: with risk of Pick's disease for the H1f subhaplotype (OR 0·11 [0·01 to 0·99], p=0·049); with age at onset for H1b (ß 2·66 [0·63 to 4·70], p=0·011), H1i (ß -3·66 [-6·83 to -0·48], p=0·025), and H1u (ß -5·25 [-10·42 to -0·07], p=0·048); and with disease duration for H1x (ß -0·57 [-1·07 to -0·07], p=0·026). INTERPRETATION: The Pick's disease International Consortium provides an opportunity to do large studies to enhance our understanding of the pathobiology of Pick's disease. This study shows that, in contrast to the decreased risk of four-repeat tauopathies, the MAPT H2 haplotype is associated with an increased risk of Pick's disease in people of European ancestry. This finding could inform development of isoform-related therapeutics for tauopathies. FUNDING: Wellcome Trust, Rotha Abraham Trust, Brain Research UK, the Dolby Fund, Dementia Research Institute (Medical Research Council), US National Institutes of Health, and the Mayo Clinic Foundation.

Brucine Entrapped Titanium Oxide Nanoparticle for Anticancer Treatment: An In Vitro Study.

Backgroundand Objective. The public's health has been seriously threatened by cervical cancer during recent times. In terms of newly diagnosed cases worldwide, it ranks as the ninth most prevalent malignancy. Multiple investigations have proven that nanoparticles can effectively combat cancer due to their small dimensions and extensive surface area. In the meantime, bioactive compounds which are biocompatible are being loaded onto nanoparticles to promote cancer therapy. The current study investigates the anticancerous potential of Brucine-entrapped titanium oxide nanoparticles (TiO2 NPs) in cervical cancer cell line (HeLa). Materials and Methods. The physiochemical, structural, and morphological aspects of Brucine-entrapped TiO2 NPs were evaluated by UV-visible spectrophotometer, Fourier transform-infrared spectroscopy (FT-IR), dynamic light scattering (DLS), scanning electron microscopy (SEM), and energy dispersive X-ray (EDAX). The cytotoxic effect against the HeLa cell line was assessed using a tetrazolium-based colorimetric assay (MTT), a trypan blue exclusion (TBE) assay, phase contrast microscopic analysis, and a fluorescence assay including ROS and DAPI staining. Furthermore, estimation of antioxidant markers includes catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD). Results. The UV spectrum at 266 nm revealed the formation of TiO NPs. The FT-IR peaks confirmed the effective entrapment of brucine with TiO2 NPs. The average size (100.0 nm) of Brucine-entrapped TiO2 NPs was revealed in DLS analysis. The micrograph of the SEM revealed the formation of ellipsoidal to tetragonal-shaped NPs. The Ti, O, and C signals were observed in EDAX. In MTT assay, Brucine-entrapped TiO2 NPs showed inhibition of cell proliferation in a dose-wise manner and IC50 was noticed at the concentration of 30 µg/mL. The percentage of viable cells gradually reduced in the trypan blue exclusion assay. The phase contrast microscopic analysis of Brucine-entrapped TiO2 NP-treated cells showed cell shrinkage, cell wall deterioration, and cell blebbing. The intracellular ROS level was increased in a dose-wise manner when compared to control cells in ROS staining. The condensed nuclei and apoptotic cells were increased in treated cells, as noted in DAPI staining. In treated cells, the antioxidant markers such as CAT, GSH, and SOD levels were substantially lower compared to the control cells. Conclusion. The synthesized Brucine entrapped TiO2 NPs exhibited remarkable anticancer activity against the HeLa cell line.

TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury.

During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. Axonal damage includes swelling, defects in transport, and failure to clear damaged intracellular proteins, all of which affect recovery and compromise neuronal integrity. The clearance of damaged cell components is important to maintain normal turnover and restore homeostasis. In this study, we used mass spectrometry to identify insoluble proteins within high-speed/mercaptoethanol/sarcosyl-insoluble pellets from purified white matter plaques isolated from the brains of individuals with relapsing-remitting MS (RRMS). We determined that the transmembrane protein 106B (TMEM106B), normally lysosome-associated, is insoluble in RRMS plaques relative to normal-appearing white matter from individuals with Alzheimer's disease and non-neurologic controls. Relative to wild-type mice, hypomorphic mice with a reduction in TMEM106B have increased axonal damage and lipid droplet accumulation in the spinal cord following myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis. Additionally, the corpora callosa from cuprizone-challenged hypomorphic mice fail to clear lipid droplets efficiently during remyelination, suggesting that when TMEM106B is compromised, protein and lipid clearance by the lysosome is delayed. As TMEM106B contains putative lipid- and LC3-binding sites, further exploration of these sites is warranted.

Corrosion Inhibition of Carbon Steel in a Sour (H2S) Environment by an Acryloyl-Based Polymer.

Corrosion poses safety and operational challenges in the oil and gas field, particularly in a sour environment. Corrosion inhibitors (CIs) are thus employed to protect the integrity of industrial assets. However, CIs have the potential to dramatically impair the effectiveness of other co-additives, such as kinetic hydrate inhibitors (KHIs). Here, we propose an acryloyl-based copolymer, previously used as a KHI, as an effective CI. The copolymer formulation provided a corrosion inhibition efficiency of up to 90% in a gas production environment, implying that it can reduce or even eliminate the need for an additional dedicated CI in the system. It also demonstrated a corrosion inhibition efficiency of up to 60% under field-simulated conditions for a wet sour crude processing environment. Molecular modeling suggests that the enhanced corrosion protection is imparted by the favorable interaction of the heteroatoms of the copolymer with the steel surface, potentially displacing adhered water molecules. All in all, we show that an acryloyl-based copolymer with dual functionalities can potentially overcome issues caused by incompatibilities in a sour environment, resulting in significant cost savings and operational ease.

Preparation and characterization of nanomuscovite by intercalation method for adsorption of heavy metals from polluted water.

In this study, nanomuscovite adsorbents were prepared by intercalation with various organic intercalates (DTAB-TTAB-DTPA-PA-PN) and used to remove Cd2+ and Pb2+ from polluted water. The best nanomuscovite was prepared using DTPA and muscovite (Muc/DTPA) and characterized by XRD, TEM, EDX, FTIR, and BET surface area. The developed nanoadsorbent was used to remove Cd2+ and Pb2+ from polluted water. The effect of various factors, including contact time, adsorbent dosage, solution pH, and temperature, was investigated. The results reveal that the maximum adsorption of Cd2+ and Pb2+ was 91.5% and 97%, respectively, at the initial metal concentration 50 ppm, adsorbent dosage 0.2 g, contact time 60 min, solution temperature 25 °C, and pH 6 for Pb2+ and pH 7 for Cd2+. Adsorption isotherm models (Freundlich, Langmuir, Dubunin-Radushkevich, and Temkin isotherm models) as well as kinetic models (pseudo-first-order, pseudo-second-order, Elovich, and intra-particle diffusion models) were employed to evaluate the experimental results. The adsorption of Cd2+ and Pb2+ on Muc/DTPA fitted well within the Langmuir isotherm model and followed pseudo-second-order kinetics. Thermodynamics parameters of metal adsorption indicated exothermic and spontaneous processes. Results were applied to the real wastewater that showed high Cd2+ and Pb2+ removal.

Design, Development, and Evaluation of Treprostinil Embedded Adhesive Transdermal Patch.

Clinical application of treprostinil in pulmonary arterial hypertension is hampered by adverse effects caused by its high dosing frequency. The objective of this investigation was to Formulate an adhesive-type transdermal patch of treprostinil and evaluate it both in vitro and in vivo. A 32-factorial design was utilized to optimize the selected independent variables (X1: drug amount, X2: enhancer concentration) on the response variables (Y1: drug release, Y2: transdermal flux). The optimized patch was evaluated for various pharmaceutical properties, skin irritation, and pharmacokinetics in rats. Optimization results signify considerable influence (p < 0.0001) of X1 on both Y1 and Y2, as compared to X2. The optimized patch possesses higher drug content (>95%), suitable surface morphology, and an absence of drug crystallization. FTIR analysis revealed compatibility of the drug with excipients, whereas DSC thermograms indicate that the drug exists as amorphous in the patch. The adhesive properties of the prepared patch confirm adequate adhesion and painless removal, while the skin irritation study confirms its safety. A steady drug release via Fickian diffusion and greater transdermal delivery (~23.26 µg/cm2/h) substantiate the potential of the optimized patch. Transdermal therapy resulted in higher treprostinil absorption (p < 0.0001) and relative bioavailability (237%) when compared to oral administration. Overall, the results indicate that the developed drug in the adhesive patch can effectively deliver treprostinil through the skin and could be a promising treatment option for pulmonary arterial hypertension.

Formulation Strategies for Enhancing Pharmaceutical and Nutraceutical Potential of Sesamol: A Natural Phenolic Bioactive.

Natural plants and their products continue to be the major source of phytoconstituents in food and therapeutics. Scientific studies have evidenced the benefits of sesame oil and its bioactives in various health conditions. Various bioactives present in it include sesamin, sasamolin, sesaminol, and sesamol; among these, sesamol represents a major constituent. This bioactive is responsible for preventing various diseases including cancer, hepatic disorders, cardiac ailments, and neurological diseases. In the last decade, the application of sesamol in the management of various disorders has attracted the increasing interest of the research community. Owing to its prominent pharmacological activities, such as antioxidant, antiinflammatory, antineoplastic, and antimicrobial, sesamol has been explored for the above-mentioned disorders. However, despite the above-mentioned therapeutic potential, its clinical utility is mainly hindered owing to low solubility, stability, bioavailability, and rapid clearance issues. In this regard, numerous strategies have been explored to surpass these restrictions with the formulation of novel carrier platforms. This review aims to describe the various reports and summarize the different pharmacological activities of sesamol. Furthermore, one part of this review is devoted to formulating strategies to improve sesamol's challenges. To resolve the issues such as the stability, low bioavailability, and high systemic clearance of sesamol, novel carrier systems have been developed to open a new avenue to utilize this bioactive as an efficient first-line treatment for various diseases.

Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X1, Span 40; X2, and sonication time; X3) on the responses (particle size, Y1, and entrapment efficiency, Y2). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (-49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (p < 0.01) between niosomal gel formulation and control. Greater flux (p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (p < 0.005), with ~3 folds higher Cmax and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.

Intranasal Administration of Dolutegravir-Loaded Nanoemulsion-Based In Situ Gel for Enhanced Bioavailability and Direct Brain Targeting.

Dolutegravir's therapeutic effectiveness in the management of neuroAIDS is mainly limited by its failure to cross the blood-brain barrier. However, lipid-based nanovesicles such as nanoemulsions have demonstrated their potential for the brain targeting of various drugs by intranasal delivery. Thus, the purpose of this study was to develop a Dolutegravir-loaded nanoemulsion-based in situ gel and evaluate its prospective for brain targeting by intranasal delivery. Dolutegravir-loaded nanoemulsions were prepared using dill oil, Tween® 80, and Transcutol® P. Optimization of the nanoemulsion particle size and drug release was carried out using a simplex lattice design. Formulations (F1-F7 and B1-B6) were assessed for various pharmaceutical characteristics. Ex vivo permeation and ciliotoxicity studies of selected in situ gels (B1) were conducted using sheep nasal mucosa. Drug targeting to the brain was assessed in vivo in rats following the nasal delivery of B1. The composition of oil, surfactant, and cosurfactant significantly (p < 0.05) influenced the dependent variables (particle size and % of drug release in 8 h). Formulation B1 exhibits pharmaceutical characteristics that are ideal for intranasal delivery. The mucosal steady-state flux noticed with BI was significantly greater (p < 0.005) than for the control gel. A histopathology of nasal mucosa treated with BI showed no signs of toxicity or cellular damage. Intranasal administration of B1 resulted in greater Cmax (~six-fold, p < 0.0001) and AUC0-α (~five-fold, p < 0.0001), and decreased Tmax (1 h) values in the brain, compared to intravenous administration. Meantime, the drug level in the plasma was relatively low, suggesting less systemic exposure to Dolutegravir through intranasal delivery. In summary, the promising data observed here signifies the prospective of B1 to enhance the brain targeting of Dolutegravir by intranasal delivery and it could be used as a feasible and practicable strategy for the management of neuroAIDS.

Characterization and phylogenetic analysis of the complete mitochondrial genome of Mango tilapia (Sarotherodon galilaeus: Cichlidae).

BACKGROUND: Sarotherodon galilaeus (Linné, 1758) is a member of the family Cichlidae, which is considered the most important aquaculture freshwater species endemic to Africa and the Middle East. The genetics and molecular biology of this species are rare. This requires more comprehensive mitochondrial genomes-based phylogenetics to enhance understanding of the relationship and delineate this species. METHODS AND RESULTS: Here, we assembled the complete mitogenome of S. galilaeus using Illumina high-throughput sequencing technology. The mango tilapia mitogenome was 16,631 bp in length with an AT composition of 53.4% and 46.4% GC content. It encodes 37 genes comprising two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and 13 protein-coding genes (PCGs) as well as the D-loop known as the control region. The phylogenetic tree was conducted to provide a relationship within the haplotilapiine lineage based on the maximum likelihood method, and the newly sequenced S. galilaeus was clustered with other Sarotherodon species. CONCLUSION: Our results provide a new perception of the genetic basis of S. galilaeus species for further research on systematics, evolution, population genetics, and molecular ecology.

Preparation and characterization of activated carbon from agricultural wastes and their ability to remove chlorpyrifos from water.

Chlorpyrifos is an organophosphate insecticide linked to neurological dysfunctions, endocrine disturbance, cardiovascular illness, genotoxicity, histopathological abnormalities, immunotoxicity, and oxidative stress. Therefore, the aim of this study was to prepare activated carbon from agricultural waste to adsorb and remove chlorpyrifos from aqueous solutions, as well as to study the physicochemical characteristics of the prepared activated carbon.Activated carbon was prepared from agricultural waste (banana peels, orange peels, pomegranate peels and date stones). The activated carbon prepared showed an exterior surface that was irregular and full of cavities with Brunauer-Emmett-Teller(BET) surface areas of 94.26, 111.75, 183.89, and 289.86 m2/g for activated carbon prepared from orange peels, date stone, pomegranate peels, and banana peels respectively. The Scanning Electron Microscope (SEM) image revealed that the activated carbon's exterior surface was irregular and full of various shapes and sizes of cavities.The Energy Dispersive X-Ray (EDX) indicated the existence of carbon, oxygen, silicon and potassium in banana peels-derived activated carbon, whereas carbon, oxygen, silicon and potassium, in addition to aluminium, were detected in the pomegranate peels-derived activated carbon. The Fourier-Transform Infrared Spectroscopy (FTIR) analysis of prepared activated carbon revealed several functional groups, including carboxylic acid, carbon dioxide, and aromatic compounds. Results also showed that the activated carbon significantly removed chlorpyrifos from water, recording 97.6%, 90.6%, 71.48%, and 52.00 % for activated carbon prepared from pomegranate peels, banana peels, date stones and orange peels, respectively. The study concluded that agricultural waste-derived activated carbon could be employed as an alternative pesticide adsorbent.

Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges.

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into ß-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (-17 to -26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (ß-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 µg/mL) in comparison to SES (106 µg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.

Tocotrienol in the Treatment of Topical Wounds: Recent Updates.

Healing wounds is an important attempt to keep the internal higher organs safe. Complications in topical wound healing may lead to the formation of scars, which can affect the patient's quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made tocotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds.

Evidence of increased sequestration of pro-resolving lipid mediators within brain esterified lipid pools of multiple sclerosis patients.

BACKGROUND: Unresolved inflammation in multiple sclerosis (MS) is associated with progressive demyelination and symptom worsening. In the brain, both inflammation and resolution pathways are mediated by free lipid mediators (i.e., oxylipins) that can be derived from the enzymatic hydrolysis of esterified oxylipins . It is not known whether disturbances in the turnover of free lipid mediators from esterified pools exist in postmortem brain of MS patients. We hypothesized that resolution pathways are impaired in MS patients because of disturbances in the turnover of free pro-resolving lipid mediators from esterified lipids. The objective was to characterize free and esterified oxylipins in postmortem prefrontal cortex of MS and unaffected control participants. METHODS: Oxylipins in free, neutral lipid and phospholipid pools were extracted from prefrontal cortex of 10 MS participants and 5 unaffected controls, separated by solid phase extraction columns, and quantified by ultra-high-pressure liquid chromatography-tandem mass spectrometry. Significant differences between the control and MS groups were determined by an unpaired t-test with Benjamini and Hochberg False Discovery Rate correction (10%) applied to oxylipins within each lipid pool. RESULTS: The concentration of 7 esterified pro-resolving fatty acid epoxides within neutral lipids were significantly higher by 126%-285% in postmortem prefrontal cortex of MS compared to control participants. The concentration of esterified linoleic acid-derived 9(10)-epoxy-octadecenoic acid, a pro-inflammatory epoxide, was higher by 206% in MS compared to controls. No significant changes were observed in free or phospholipid-bound oxylipins. CONCLUSION: In MS, several pro-resolving lipid mediators are trapped within prefrontal cortex neutral lipids, potentially limiting their supply and availability in the free bioactive form. This may explain why inflammation resolution is impaired in MS patients.

Development of Novel Unfolding Film System of Itopride Hydrochloride Using Box-Behnken Design-A Gastro Retentive Approach.

Currently, gastro-retentive dosage forms achieved a remarkable position among the oral drug delivery systems. This is a broadly used technique to hold the drug delivery systems for a long duration in the gastro intestine (GI) region, slow drug delivery, and overcome other challenges related to typical oral delivery such as low bioavailability. The current work aimed to formulate and characterize a new expandable gastro-retentive system through Itopride Hydrochloride (IH)'s unfolding process for controlled release. The IH-loaded unfolding film formulation was optimized using the Box-Behnken design for folding endurance and length of tested layer (LTL). Initially, the formulation was made using several anti-adhesive additives to promote the unfolding mechanism. Citric acid and sodium bicarbonate were selected as anti-adhesives based on these results. The enfolded film in a capsule shell was shown to unroll in the stomach fluids and render drug delivery up to 12 h in acidic conditions. A fabricated system should have dimensions more than the size of the relaxed pyloric sphincter, and as required, >20 mm LTL was identified. This further confirms that the residence period in the stomach is irrelevant to the fed or fasted condition. Based on desirability criteria, the formulation containing 143.83, 0.7982, and 14.6096 Eudragit L100, PEG, and sodium bicarbonate are selected as optimized formulations (O-IH-UF). The optimized formulation was further analyzed for various parameters such as tensile strength, mechanical strength, unfolding nature, degradability, and in vitro release studies. The pharmacokinetic study revealed greater AUC (area under the curve) and long half-life with the designed O-IH-UF formulation, confirming that the unfolding film type can be a favorable drug system for enhancing the bioavailability of low soluble drugs. The results showed that unfolding types of gastro retentive systems could potentiate the drugs with stability issues in an alkaline medium or those with absorption in acidic conditions.

Formulation-by-Design of Efinaconazole Spanlastic Nanovesicles for Transungual Delivery Using Statistical Risk Management and Multivariate Analytical Techniques.

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett-Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth's analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles.

Adherence to Child Attention-Deficit/Hyperactivity Disorder Treatment Guidelines in Medical Homes-Results from a National Survey.

OBJECTIVE: Having primary care delivered through a medical home is believed to improve mental health care delivery to children. Children with attention-deficit/hyperactivity disorder (ADHD) are commonly treated in pediatric practices, yet little is known about ADHD treatment patterns in medical homes. Our objective was to assess for treatment variation depending on parent-perceived medical home (PPMH) status. We hypothesized that having a PPMH would be associated with receiving ADHD treatments recommended by clinical guidelines. METHODS: We used the 2016 National Survey of Children's Health-a nationally representative cross-sectional survey of children in the United States. Analyses included an unweighted sample of 4,252, representing 5.4 million children aged 3 to 17 years with parent-reported ADHD. Child characteristics were analyzed using descriptive statistics. Associations between ADHD treatment types and PPMH status were assessed using a multinomial logistic regression, adjusting for child characteristics. RESULTS: Having a PPMH was associated with increased prevalence odds of children's receipt of medications alone for ADHD (vs no treatment). The prevalence odds of receiving behavioral treatment alone (vs medications alone) for ADHD decreased by 43% when children had a PPMH (95% confidence interval, 0.38-0.85, p = 0.01). PPMH status was not associated with a statistically significant difference in prevalence odds of receiving combination treatment (vs medications alone) for pediatric ADHD. CONCLUSION: Having a PPMH was associated with children's receipt of ADHD medications alone, but not behavioral treatments. Our findings suggest that medical homes may need further improvement to ensure that children with ADHD receive treatments as recommended by clinical guidelines.

Pulmonary administration of a CSF-1R inhibitor alters the balance of tumor-associated macrophages and supports first-line chemotherapy in a lung cancer model.

Lung cancers remain the leading cause of cancer-related death in both men and women. Infiltrating immune cells in the tumor microenvironment (TME) play a critical role in the formation, progression, and the response of solid tumors to therapy, including in lung cancers. Clinical studies have established that tumor-associated macrophages (TAMs) and their phenotypical composition are critical immune infiltrates in the lung TME, with the abundance of the M2-like phenotype negatively correlating with patient survival. Colony-Stimulating Factor 1 (CSF-1) receptor (CSF-1R) is a type III protein tyrosine kinase receptor that plays an important role in the recruitment and differentiation of monocytes into tumor-promoting M2-like TAMs and their survival. In this work we evaluated the therapeutic potential of PLX 3397 (PLX), a small molecule CSF-1R inhibitor (CSF-1Ri), upon local lung administration in an immune-competent mouse model of lung cancer. The efficacy of local lung delivered PLX as single therapy was investigated first. As assessed by immunofluorescence of sections of lung tumor nodules, a statistically significant reduction in M2-like TAMs and an increase in M1-like TAMs was observed, thus leading to a shift in the (M1/M2) balance. Those changes in abundance of immune infiltrates correlated with a significant decrease in tumor burden when compared to control. When combined with systemically administered cisplatin (CIS) PLX treatment provided further benefits, leading to a significant decrease in tumor burden when compared to either PLX or CIS treatments alone, as measured by bioluminescence intensity (BLI) in vivo (thoracic area) and ex vivo (lung tissue). This combination therapy led to the most pronounced increase in M1/M2 ratio, followed by a significant decrease in M2-like TAMs with the CIS therapy. This work is clinically relevant as it demonstrates the potential of local lung administration of PLX to support standard of care chemotherapy for lung cancer management. This is important as the pulmonary route of administration is a plausible strategy for reducing the total dose of CSF-1Ris as the tissue of interest (lungs) can be locally targeted. Because the major off-target effect of CSF-1Ris is liver toxicity, reducing systemic concentration will support translation of those therapies, especially in combination with standard of care chemotherapy that has significant off-target toxicity and patient attrition itself. This work is scientifically relevant as we demonstrate for the first time that local administration of a CSF-1Ri to the lungs leads to a shift in the balance of TAMs in the TME of a model of lung tumor, adding to the sparse literature of CSF-1Ris related to lung cancers.

Bioenvironmental Trace Elements in Warm Climatic Plant, Pigeon Pea (Cajanus cajan).

Bioenvironmental trace elements play a vital role in plant, animal, and man metabolism. This study aims to determine trace element concentration in different parts (pods, pericarp, seeds, cotyledon, and taste) of the warm climate plant pigeon pea (Cajanus cajan L. Millsp.). The pigeon pea pods were collected from the farms on the shore of the High Dam Lake, Egypt. Elements (Ag, Au, Co, Cr, Sr, Fe, Cu, Ni, Mn, and Zn) in the pods and its different parts were determined by an atomic absorption spectrophotometer. Statistical analysis (cluster, Pearson correlation coefficient, and factor analysis) was applied to trace elements in different parts of pigeon pea. The results reveal that seeds exhibited the highest concentrations of Cu, Ni, Cr, and Zn, while Ag, Co, Pb, and Fe in the pods. Factor and cluster analyses explain a good relationship among the trace elements in pigeon pea. Also, transfer factor of the elements between plant and soil shows that the high transfer factor of most elements was observed for pods and pericarp. The studied elements in the pods and its different parts were in the safety baseline levels for both man and animal uses.