Evidence-based effectiveness of Ozone therapy in the treatment for oral lichen planus - A systematic review.

Oral lichen planus is a common, chronic mucocutaneous condition of uncertain origin. Early treatment of OLP can dramatically reduce the risk of further development, which in turn reduces the risk of developing cancer. Numerous methods can be used to treat OLP. Since the significance of ozone in treating this disease is still uncertain. This systematic review was conducted based on english databases, including PUBMED, SCOPUS, Embase, Ovid, and Journal of Web up to July 2022. We used the search phrases "ozone," "ozone in the treatment of oral lichen planus," "oral lichen planus," and "ozone therapy." Finally, five papers were selected for qualitative analysis. This review included a total of five papers, four of which were clinical trials and one was a longitudinal study. All studies included the erosive form of OLP, also ozone therapy was applied to patients who did not respond to conventional treatment. Ozone showed significant therapeutic effects in terms of reduction in pain and size of the lesion. The signs and symptoms associated with OLP such as burning sensation, lesion size, and scarring all considerably improved with ozone therapy.

Nanoconfinement Effect in Water Processable Discrete Molecular Complex-Based Hybrid Piezo- and Thermo-Electric Nanogenerator.

Water-processable hybrid piezo- and thermo-electric materials have an increasing range of applications. We use the nanoconfinement effect of ferroelectric discrete molecular complex [Cu(l-phe)(bpy)(H2O)]PF6·H2O (1) in a nonpolar polymer 1D-nanofiber to envision the high-performance flexible hybrid piezo- and thermo-electric nanogenerator (TEG). The 1D-nanoconfined crystallization of 1 enhances piezoelectric throughput with a high degree of mechano-sensitivity, i.e., 710 mV/N up to 3 N of applied force with 10,000 cycles of unaffected mechanical endurance. Thermoelectric properties analysis shows a noticeable improvement in Seebeck coefficient (∼4 fold) and power factor (∼6 fold) as compared to its film counterpart, which is attributed to the enhanced density of states near the Fermi edges as evidenced by ultraviolet photoelectric spectroscopy and density functional based theoretical calculations. We report an aqueous processable hybrid TEG that provides an impressive magnitude of Seebeck coefficient (∼793 µV/K) and power factor (∼35 mWm-1K-2) in comparison to a similar class of materials.

Spatio-temporal trends in long-term seasonal groundwater level of South-western Punjab using non-parametric statistical tests.

To manage groundwater resources and develop an action plan, it is crucial to understand the long-term behavior of groundwater level (GWL) fluctuations. In this study, Geographic Information System (GIS) and non-parametric statistical tests were applied for detecting long-term (1973 to 2020) spatio-temporal variations and trends in GWL from 137 observation wells evenly distributed across the south-western part of Punjab. This region has experienced significant changes in GWL over the decades. The non-parametric statistical tests included Mann-Kendall (MK), Sens's Slope Estimator (SSE), and Innovative Trend Analysis (ITA). The study observed significant trends in GWL fluctuations before and after monsoon. The MK and SSE tests showed a statistically increasing trend in observation wells with about 65.7% and 67.2% increase before and after monsoon, respectively. The innovative trend analysis (ITA) also revealed a statistically increasing trend in observation wells with an increase of about 63.5% and 65.7% pre and post-monsoon season, respectively. The results indicate lowering of GWL in the northern districts of southwestern Punjab, while the southern districts experience rising GWLs. This discrepancy can be attributed to diverse agricultural activities and reduced over-exploitation of groundwater in the southern district due to soil salinity and the presence of brackish groundwater. These findings provide valuable insights into the dynamics of GWL in the studied region, highlighting notable trends associated with seasonal variations.

Assessment of Artificial Intelligence Platforms With Regard to Medical Microbiology Knowledge: An Analysis of ChatGPT and Gemini.

The performance of two artificial intelligence (AI) platforms, ChatGPT 3.5 (OpenAI, California, United States) and Gemini (Google AI, California, United States) was assessed by answering 200 questions of microbiology drawn from validated sources. The questions were selected from topics such as General Microbiology, Immunology, and Microbiology Applied to Infectious Diseases. The study was conducted from December 2023 to March 2024, and the responses of the different AI platforms were compared with an answer key. Statistical analysis was performed to assess accuracy. ChatGPT 3.5 and Gemini had comparable accuracy with correct response scores of 71% and 70.5%, respectively. Their performance varied across different sections. Gemini performed better in General Microbiology and Immunology, and ChatGPT 3.5 had a better score in the Applied Microbiology section. The study's findings highlight that AI platforms such as ChatGPT and Gemini can be utilized in microbiology and medical education. The evolution and continuous updating of AI platforms are required to improve their performance.

An appraisal of psychotherapy training during psychiatry residency program in India: A national survey.

Background: The need for psychotherapy training (PT) has been recognized worldwide and is considered an integral component of postgraduate psychiatry training. Our study aims to assess the quality of PT received by psychiatrists during their postgraduate studies and its impact on their current practice. Aim: To evaluate the quality of PT and its effect on the current psychiatry practice. Methodology: An anonymous web-based survey was conducted on registered psychiatrists practicing in India to evaluate the level and quality of PT received during their postgraduate studies. Results: The survey indicates that PT was included in the postgraduate psychiatry curriculum (73.8%). However, more than 50% of responders reported no separate posting, evaluation, logbook, or guidelines related to PT. Most (95.4%) psychiatrists think their PT could have been better. PT was satisfying in medical colleges in terms of inclusion in the curriculum (7.70, P = .021), psychotherapy rotations (16.48, P = <0.001), supervision of sessions (14.80, P = 0.001), lectures on psychotherapy (10.13, P = 0.006), periodic psychotherapy meet/forum (19.35, P = <0.001), maintenance of psychotherapy logbook/records (7.65, P = 0.022), institutional or departmental guideline related to PT (20.55, P = <0.001), and overall quality of PT (22.05, P = .005 and 31.81, P = <.001). Time constraint is the most common (49.9%) barrier in delivering psychotherapy. Conclusion: PT is not well organized, consistent, and uniform in psychiatry training; there is a prevailing sense of inadequacy and dissatisfaction among the country's psychiatrists with a perceived need to improve and learn PT.

Comparative evaluation of cyclic fatigue resistance of thermomechanically treated NiTi rotary instruments in simulated curved canals with two different radii of curvature: An in vitro Study.

Background: This study aimed to compare the effect of heat treatment on the cyclic fatigue resistance of three different nickel-titanium rotary file systems: TruNatomy, HyFlex CM, and NeoEndo flex in simulated curved canals at two different radii of curvatures. Materials and Methods: A total of 60 NiTi rotary files of three types were used, and the samples were divided into three groups TruNatomy, HyFlex CM, and NeoEndo flex. All the instruments were subjected to cyclic fatigue testing using a stainless steel custom-made canal model with a 60° angle of curvature and two radii of curvature 5 mm and 3 mm; the number of cycles to fracture and length of the fractured segment was measured. The separated instruments were subjected to fractographic analysis under scanning electron microscope. Results: The number of cycles to failure to fracture a file at a 3 mm radius of curvature is significantly less as compared to a 5 mm radius of curvature (HCM > TRN > NE). Conclusion: Within the limitation of the present study, there was a positive correlation between the radius of curvature and fatigue life of NiTi files.

System biology approaches for drug repurposing.

Drug repurposing, or drug repositioning, refers to the identification of alternative therapeutic applications for established medications that go beyond their initial indications. This strategy has becoming increasingly popular since it has the potential to significantly reduce the overall costs of drug development by around $300 million. System biology methodologies have been employed to facilitate medication repurposing, encompassing computational techniques such as signature matching and network-based strategies. These techniques utilize pre-existing drug-related data types and databases to find prospective repurposed medications that have minimal or acceptable harmful effects on patients. The primary benefit of medication repurposing in comparison to drug development lies in the fact that approved pharmaceuticals have already undergone multiple phases of clinical studies, thereby possessing well-established safety and pharmacokinetic properties. Utilizing system biology methodologies in medication repurposing offers the capacity to expedite the discovery of viable candidates for drug repurposing and offer novel perspectives for structure-based drug design.

Approaches of pre-clinical and clinical trials of repurposed drug.

Medications that are currently on the market and have proven therapeutic usage can have new therapeutic indications discovered through a process called drug repurposing, which is also called drug repositioning. This approach presents a viable method for drug developers and pharmaceutical companies to discern novel targets for FDA-approved medications. Drug repurposing presents several advantages, including reduced time consumption, lower costs, and diminished risk of failure. Sildenafil, commonly known as Viagra, serves as a notable illustration of a repurposed pharmaceutical agent, initially developed and introduced to the market as an antianginal medication. However, in the current context, its application has been redirected towards serving as a pharmaceutical intervention for the treatment of erectile dysfunction. Comparably, a multitude of pharmaceutical agents exist that have demonstrated efficacy in repurposing for therapeutic management of various clinical conditions. Focusing on the historical use of repurposed pharmaceuticals and their present state of application in disease therapies, this chapter seeks to offer a thorough review of drug repurposing methodologies. Furthermore, the rules and regulations that control the repurposing of drugs will be covered in detail in this chapter.

Repurposing of biologics and biopharmaceuticals.

The field of drug repurposing is gaining attention as a way to introduce pharmaceutical agents with established safety profiles to new patient populations. This approach involves finding new applications for existing drugs through observations or deliberate efforts to understand their mechanisms of action. Recent advancements in bioinformatics and pharmacology, along with the availability of extensive data repositories and analytical techniques, have fueled the demand for novel methodologies in pharmaceutical research and development. To facilitate systematic drug repurposing, various computational methodologies have emerged, combining experimental techniques and in silico approaches. These methods have revolutionized the field of drug discovery by enabling the efficient repurposing of screens. However, establishing an ideal drug repurposing pipeline requires the integration of molecular data accessibility, analytical proficiency, experimental design expertise, and a comprehensive understanding of clinical development processes. This chapter explores the key methodologies used in systematic drug repurposing and discusses the stakeholders involved in this field. It emphasizes the importance of strategic alliances to enhance the success of repurposing existing compounds for new indications. Additionally, the chapter highlights the current benefits, considerations, and challenges faced in the repurposing process, which is pursued by both biotechnology and pharmaceutical companies. Overall, drug repurposing holds great promise in expanding the use of existing drugs and bringing them to new patient populations. With the advancements in computational methodologies and the collaboration of various stakeholders, this approach has the potential to accelerate drug development and improve patient outcomes.

Angiopoietin-like 4 is upregulated by amphiregulin and activates cell proliferation and migration through p38 kinase in head and neck squamous cell carcinoma.

BACKGROUND: Angiopoietin-like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin-like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear. METHODS: Using well-characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia-derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin-like 4-induced head and neck squamous cell carcinoma tumorigenesis. RESULTS: We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin-like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia-inducible factor-1 in this effect. Interestingly, amphiregulin and angiopoietin-like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin-induced activation of cell proliferation was dependent on angiopoietin-like 4. Although both p38 mitogen-activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin-like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin-like 4 promoted the secretion of interleukin 11 (IL-11), interleukin 12 (IL-12), interleukin-1 alpha (IL-1α), vascular endothelial growth factor, platelet-derived growth factor (PDGF), and tumour necrosis factor alpha (TNF-α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis. CONCLUSION: Our results demonstrate that angiopoietin-like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms.

ADME/PK Insights of Crocetin: A Molecule Having an Unusual Chemical Structure with Druglike Features.

Crocetin is a promising phyto-based molecule to treat Alzheimer's disease (AD). The chemical structure of crocetin is incongruent with various standard structural features of CNS drugs. As poor pharmacokinetic behavior is the major hurdle for any candidate to become a drug, we elucidated its druggable characteristics by implementing in silico, in vitro, and in vivo approaches, as limited ADME/PK information is available. Results demonstrate several attributes of crocetin based on rules of drug-likeness, lipophilicity, pKa, P-gp inhibitory activity, plasma stability, RBC partitioning, metabolic stability, CYP inhibitory action, blood-brain barrier (BBB) permeability, oral bioavailability, and pharmacokinetic interaction with marketed anti-Alzheimer's drugs (memantine, donepezil, galantamine, and rivastigmine). However, aqueous solubility, chemical stability, plasma protein binding, and P-gp induction are some concerns associated with this molecule that should be taken into consideration during its further development. Overall results indicate favorable ADME/PK behavior and potential druggable candidature of crocetin.

Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

BACKGROUND: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. METHODS AND FINDINGS: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. CONCLUSIONS: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

Analysis of Laminated Composite Porous Plate under Sinusoidal Load with Various Boundary Conditions.

Bending analysis was carried out for a laminated composite porous plate due to sinusoidal loading with various boundary conditions using improved third-order theory. Zero transverse shear stress provided a free surface at the top and bottom of the plate. Also, the authors developed a finite element formulation based on improved third-order shear deformation theory. To circumvent the C1 continuity requirement associated with improved third-order shear deformation theory, a C0 FE formulation was developed by replacing the out-of-plane derivatives with independent field variables. An in-house FORTRAN code was developed for the bending analysis of the laminated porous plate considering a 2D finite element model. The complete thickness of the plate was covered with different porosity patterns. The impacts of various modulus ratios, boundary conditions, thickness ratios, fiber orientation angles, and material parameters were examined for laminated porous plates. There was an 18.8% reduction in deflection in the case of the square plate as compared to rectangular plates, with a porosity value of 0.1, a thickness ratio of 10, and an orientation angle of 0°/90°/0°. According to the current research, adding porosities causes a relatively greater change in deflection rather than stress, thereby aiding in the development of a lightweight structure.

Optimized submerged batch fermentation for metabolic switching in Streptomyces yanglinensis 3-10 providing platform for reveromycin A and B biosynthesis, engineering, and production.

The cultivation system requires that the approach providing biomass for all types of metabolic analysis is of excellent quality and reliability. This study was conducted to enhance the efficiency and yield of antifungal substance (AFS) production in Streptomyces yanglinensis 3-10 by optimizing operation conditions of aeration, agitation, carbon source, and incubation time in a fermenter. Dissolved oxygen (DO) and pH were found to play significant roles in AFS production. The optimum pH for the production of AFS in S. yanglinensis 3-10 was found to be 6.5. As the AFS synthesis is generally thought to be an aerobic process, DO plays a significant role. The synthesis of bioactive compounds can vary depending on how DO affects growth rate. This study validates that the high growth rate and antifungal activity required a minimum DO concentration of approximately 20% saturation. The DO supply in a fermenter can be raised once agitation and aeration have been adjusted. Consequently, DO can stimulate the development of bacteria and enzyme production. A large shearing effect could result from the extreme agitation, harming the cell and deactivating its products. The highest inhibition zone diameter (IZD) was obtained with 3% starch, making starch a more efficient carbon source than glucose. Temperature is another important factor affecting AFS production. The needed fermentation time would increase and AFS production would be reduced by the too-low operating temperature. Furthermore, large-scale fermenters are challenging to manage at temperatures that are far below from room temperature. According to this research, 28°C is the ideal temperature for the fermentation of S. yanglinensis 3-10. The current study deals with the optimization of submerged batch fermentation involving the modification of operation conditions to effectively enhance the efficiency and yield of AFS production in S. yanglinensis 3-10.

Analysis of Predictive Information From Biomarkers Added to Clinical Models of Preeclampsia: Consideration of PAPP-A2, Activin A, and sFlt-1:PlGF Ratio.

BACKGROUND: Preeclampsia remains a major cause of maternal and fetal adverse outcomes in pregnancy; however, accurate and universally acceptable predictive tools remain elusive. We investigated whether a panel of biomarkers could improve risk prediction for preeclampsia when measured at various pregnancy time points. METHODS: In this prospective cohort study, 192 women with first-trimester high-risk singleton pregnancies were consecutively recruited from tertiary obstetrics clinics in Montréal, Canada. Clinical information (height, pre-pregnancy weight, personal and family medical history, medication use) was collected at baseline. Blood pressure was measured and blood samples collected at each trimester to quantify soluble Fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), pregnancy-associated plasma protein A2 (PAPP-A2), PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. A random-effects hierarchic logistic regression model was used to relate change in biomarker levels to incidence of preeclampsia. RESULTS: When added to a clinical model composed of maternal age, pre-pregnancy body mass index, race, and mean arterial pressure, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% [95% confidence interval (CI) 78.57%-100%] vs 66.67% [57.14%-100%]), while maintaining a comparable high negative predictive value (97.69% [95% CI 95.34%-100%] vs 96.00% [92.19%-99.21%]). CONCLUSIONS: Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and therefore could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies.

A bioactive and biodegradable vitamin C stearate-based injectable hydrogel alleviates experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder affecting nearly 1% of the global population. In RA, synovial joints are infiltrated by inflammatory mediators and enzymes, leading to articular cartilage deterioration, joint damage, and bone erosion. Herein, the 9-aminoacridine-6-O-stearoyl-L-ascorbic acid hydrogel (9AA-SAA hydrogel) was formulated by the heat-cool method and further characterized for surface charge, surface morphology, rheology, and cytocompatibility. Furthermore, we evaluated the therapeutic efficacy of the 9AA-SAA hydrogel, an enzyme-responsive drug delivery system with on-and-off switching capabilities based on disease severity against collagen-induced experimental arthritis in Wistar rats. The anti-inflammatory action of the US FDA-approved drug 9-aminoacridine (9AA) was revealed which acted through nuclear receptor subfamily 4 group A member 1 (NR4A1), an anti-inflammatory orphan nuclear receptor that inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, we have explored the role of ascorbic acid, an active moiety of 6-O-stearoyl-L-ascorbic acid (SAA), in promoting the production of collagen production through ten-eleven translocation-2 (TET2) upregulation. Targeting through NR4A1 and TET2 could be the probable mechanism for the treatment of experimental arthritis. The combination of 9AA and ascorbic acid demonstrated enhanced therapeutic efficacy in the 9AA-SAA hydrogel, significantly reducing the severity of experimental arthritis. This approach, in contrast to existing treatments with limited effectiveness, presents a promising and more effective strategy for RA treatment by mitigating inflammation in experimental arthritis.

Rice false smut pathogen: implications for mycotoxin contamination, current status, and future perspectives.

Rice serves as a staple food across various continents worldwide. The rice plant faces significant threats from a range of fungal, bacterial, and viral pathogens. Among these, rice false smut disease (RFS) caused by Villosiclava virens is one of the devastating diseases in rice fields. This disease is widespread in major rice-growing regions such as China, Pakistan, Bangladesh, India, and others, leading to significant losses in rice plantations. Various toxins are produced during the infection of this disease in rice plants, impacting the fertilization process as well. This review paper lightens the disease cycle, plant immunity, and infection process during RFS. Mycotoxin production in RFS affects rice plants in multiple ways, although the exact phenomena are still unknown.

EIDD-1931 Treatment Tweaks CYP3A4 and CYP2C8 in Arthritic Rats to Expedite Drug Interaction: Implication in Oral Therapy of Molnupiravir.

EIDD-1931 is the active form of molnupiravir, an orally effective drug approved by the United States Food and Drug Administration (USFDA) against COVID-19. Pharmacokinetic alteration can cause untoward drug interaction (drug-drug/disease-drug), but hardly any information is known about this recently approved drug. Therefore, we first investigated the impact of the arthritis state on the oral pharmacokinetics of EIDD-1931 using a widely accepted complete Freund's adjuvant (CFA)-induced rat model of rheumatoid arthritis (RA) after ascertaining the disease occurrence by paw swelling measurement and X-ray examination. Comparative oral pharmacokinetic assessment of EIDD-1931 (normal state vs arthritis state) showed that overall plasma exposure was augmented (1.7-fold) with reduced clearance (0.54-fold), suggesting its likelihood of dose adjustment in arthritis conditions. In order to elucidate the effect of EIDD-1931 treatment at a therapeutic regime (normal state vs arthritis state) on USFDA-recommended panel of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) for drug interaction using the same disease model, we monitored protein and mRNA expressions (rat homologs) in liver tissue by western blotting (WB) and real time-polymerase chain reaction (RT-PCR), respectively. Results reveal that EIDD-1931 treatment could strongly influence CYP3A4 and CYP2C8 among experimental proteins/mRNAs. Although CYP2C8 regulation upon EIDD-1931 treatment resembles similar behavior under the arthritis state, results dictate a potentially reverse phenomenon for CYP3A4. Moreover, the lack of any CYP inhibitory effect by EIDD-1931 in human/rat liver microsomes (HLM/RLM) helps to ascertain EIDD-1931 treatment-mediated disease-drug interaction and the possibility of drug-drug interaction with disease-modifying antirheumatic drugs (DMARDs) upon coadministration. As elevated proinflammatory cytokine levels are prevalent in RA and nuclear factor-kappa B (NF-kB) and nuclear receptors control CYP expressions, further studies should focus on understanding the regulation of affected CYPs to subside unexpected drug interaction.

Influence of obesity on load-transfer mechanism, contact mechanics, and longevity of cemented acetabular cup.

Objective: This investigation aimed to assess the impact of obesity on the load-transfer mechanism, longevity, and contact mechanics of cemented acetabular cups. Methods: Three obesity scenarios were considered: obese case-I (100-110 kg), obese case-II (120-130 kg), and obese case-III (140-150 kg). Utilising six finite element models, the effects of different bodyweights on load transfer, contact mechanics, and cup longevity during normal walking conditions were assessed. Muscle forces and hip joint reaction forces were adjusted and linearly calibrated based on obesity cases. Results: Elevated stresses in cortical and cancellous bones, as well as the cement mantle, were observed in obese cases, suggesting a heightened risk of loosening and failure of the cemented fixation of the acetabular cup. Additionally, increased contact pressure and micromotion between articulating surfaces were noted in obese individuals, with a gradual escalation from obese case-I to obese case-III. Conclusions: These findings highlight the significant negative impact of obesity on the performance of cemented acetabular cups, emphasizing the importance of considering bodyweight variations in the design and assessment of orthopaedic implants for optimal functionality and durability.