Uncovering the Emerging Prospects of Lipid-based Nanoparticulate Vehicles in Lung Cancer Management: A Recent Perspective.

Lung cancer, a leading cause of cancer-related deaths globally, is gaining research interest more than ever before. Owing to the burden of pathogenesis on the quality of life of patients and subsequently the healthcare system, research efforts focus on its management and amelioration. In an effort to improve bioavailability, enhance stability, minimize adverse effects and reduce the incidence of resistance, nanotechnological platforms have been harnessed for drug delivery and improving treatment outcomes. Lipid nanoparticles, in particular, offer an interesting clinical opportunity with respect to the delivery of a variety of agents. These include synthetic chemotherapeutic agents, immunotherapeutic molecules, as well as phytoconstituents with promising anticancer benefits. In addition to this, these systems are being studied for their usage in conjunction with other treatment strategies. However, their applications remain limited owing to a number of challenges, chiefly clinical translation. There is a need to address the scalability of such technologies, in order to improve accessibility. The authors aim to offer a comprehensive understanding of the evolution of lipid nanoparticles and their application in lung cancer, the interplay of disease pathways and their mechanism of action and the potential for delivery of a variety of agents. Additionally, a discussion with respect to results from preclinical studies has also been provided. The authors have also provided a well-rounded insight into the limitations and future perspectives. While the possibilities are endless, there is a need to undertake focused research to expedite clinical translation and offer avenues for wider applications in disease management.

Cholesterol Homeostasis, Mechanisms of Molecular Pathways, and Cardiac Health: A Current Outlook.

The metabolism of lipoproteins, which regulate the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, the authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by 2 biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained in different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

Nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) with repercussions toward apoptosis, necrosis, and cancer necrosis factor (TNF-α) at nano-biointerfaces.

Introduction: Apoptosis, necrosis, and cancer necrosis factor (TNF-a) are all impacted by the nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) at nano-biointerfaces. The creation of multi-functional nanoparticles has had a considerable impact on the transport of drugs and genes, nanotheranostics (in-vivo imaging, concurrent diagnostics), interventions for external healing, the creation of nano-bio interfaces, and the instigation of desired changes in nanotherapeutics. Objectives: The quantitative structure-activity relationships, chemical transformations, biological interactions as well as toxicological analyses are considered as main objectives. Discrete dimensions of SCoNPs-cell interaction interfaces, their characteristic physical features (size, shape, shell structure, and surface chemistry), impact on cell proliferation and differentiation are the key factors responsible for nanotoxicity. Methods: The development of multi-functional nanoparticles has been significant in drug/gene delivery, nanotheranostics (in-vivo imaging, coinciding diagnostics), and external healing interventions, designing a nano-bio interface, as well as inciting desired alterations in nanotherapeutics. Every so often, the cellular uptake of multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoONPs) influences cellular mechanics and initiates numerous repercussions (oxidative stress, DNA damage, cytogenotoxicity, and chromosomal damage) in pathways, including the generation of dysregulating factors involved in biochemical transformations. Results: The concerns and influences of multifunctional SCoNPs on different cell mechanisms (mitochondria impermeability, hydrolysis of ATP, the concentration of Ca2+, impaired calcium clearance, defective autophagy, apoptosis, and necrosis), and interlinked properties (adhesion, motility, and internalization dynamics, role in toxicity, surface hydrophilic and hydrophobicity, biokinetics and biomimetic behaviors of biochemical reactions) have also been summarized. SCoONPs have received a lot of interest among the nanocarriers family because of its advantageous qualities such as biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. Conclusion: Various applications, such as bio-imaging, cell labeling, gene delivery, enhanced chemical stability, and increased biocompatibility, concerning apoptosis, necrosis, and nano-bio interfaces, along with suitable examples. In this analysis, the multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoNPs) intricacies (cytogenotoxicity, clastogenicity, and immunomodulatory), nanotoxicity, and associated repercussions have been highlighted and explained.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

BACKGROUND: Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD. METHODS: A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. RESULTS: Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. CONCLUSION: The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Nanoformulations of quercetin for controlled delivery: a review of preclinical anticancer studies.

One of the well-studied older molecules, quercetin, is found in large quantities in many fruits and vegetables. Natural anti-oxidant quercetin has demonstrated numerous pharmacological properties in preclinical and clinical research, including anti-inflammatory and anti-cancer effects. Due to its ability to control cell signaling pathways, including NF-κB, p53, activated protein-1 (AP-1), STAT3, and epidermal growth response-1 (Egr-1), which is essential in the initiation and proliferation of cancer, it has gained a lot of fame as an anticancer molecule. Recent research suggests that using nanoformulations can help quercetin to overcome its hydrophobicity while also enhancing its stability and cellular bioavailability both in vitro and in vivo. The main aim of this review is to focus on the comprehensive insights of several nanoformulations, including liposomes, nano gels, micelles, solid lipid nanoparticles (SLN), polymer nanoparticles, gold nanoparticles, and cyclodextrin complexes, to transport quercetin for application in cancer.

Genistein: a promising modulator of apoptosis and survival signaling in cancer.

Genistein, a commonly occurring isoflavone, has recently gained popularity owing to its ever-expanding spectrum of pharmacological benefits. In addition to health benefits such as improved bone health and reduced postmenopausal complications owing to its phytoestrogen properties, it has been widely evaluated for its anti-cancer potential. Several studies have established the potential for its usage in the management of breast, lung, and prostate cancers, and its usage has significantly evolved from early applications in traditional systems of medicine. This review offers an insight into its current status of usage, the chemistry, and pharmacokinetics of the molecule, an exploration of its apoptotic mechanisms in cancer management, and opportunities for synergism to improve therapeutic outcomes. In addition to this, the authors have presented an overview of recent clinical trials, to offer an understanding of contemporary studies and explore prospects for a greater number of focused trials, moving forward. Advancements in the application of nanotechnology as a strategy to improve safety and efficacy have also been highlighted, with a brief discussion of results from safety and toxicology studies.

In Silico Biomarkers of Motor Function to Inform Musculoskeletal Rehabilitation and Orthopedic Treatment.

In this review, we elaborate on how musculoskeletal (MSK) modeling combined with dynamic movement simulation is gradually evolving from a research tool to a promising in silico tool to assist medical doctors and physical therapists in decision making by providing parameters relating to dynamic MSK function and loading. This review primarily focuses on our own and related work to illustrate the framework and the interpretation of MSK model-based parameters in patients with 3 different conditions, that is, degenerative joint disease, cerebral palsy, and adult spinal deformities. By selecting these 3 clinical applications, we also aim to demonstrate the differing levels of clinical readiness of the different simulation frameworks introducing in silico model-based biomarkers of motor function to inform MSK rehabilitation and treatment, with the application for adult spinal deformities being the most recent of the 3. Based on these applications, barriers to clinical integration and positioning of these in silico technologies within standard clinical practice are discussed in the light of specific challenges related to model assumptions, required level of complexity and personalization, and clinical implementation.

Antidiabetic agents as a novel treatment for Alzheimer's and Parkinson's disease.

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by several pathological features. In AD and PD, there is an abnormal accumulation of toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, increased astrocyte activation, and perhaps a state of insulin resistance. Epidemiological evidence has revealed a link between AD/PD and type 2 diabetes mellitus, with these disorders sharing some pathological commonalities. Such a link has opened up a promising avenue for repurposing antidiabetic agents in the treatment of neurodegenerative disorders. A successful therapeutic strategy for AD/PD would likely require a single or several agents which target the separate pathological processes in the disease. Targeting cerebral insulin signalling produces numerous neuroprotective effects in preclinical AD/PD brain models. Clinical trials have shown the promise of approved diabetic compounds in improving motor symptoms of PD and preventing neurodegenerative decline, with numerous further phase II trials and phase III trials underway in AD and PD populations. Alongside insulin signalling, targeting incretin receptors in the brain represents one of the most promising strategies for repurposing currently available agents for the treatment of AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists have displayed impressive clinical potential in preclinical and early clinical studies. In AD the GLP-1 receptor agonist, liraglutide, has been demonstrated to improve cerebral glucose metabolism and functional connectivity in small-scale pilot trials. Whilst in PD, the GLP-1 receptor agonist exenatide is effective in restoring motor function and cognition. Targeting brain incretin receptors reduces inflammation, inhibits apoptosis, prevents toxic protein aggregation, enhances long-term potentiation and autophagy as well as restores dysfunctional insulin signalling. Support is also increasing for the use of additional approved diabetic treatments, including intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear receptor γ agonists, amylin analogs, and protein tyrosine phosphatase 1B inhibitors which are in the investigation for deployment in PD and AD treatment. As such, we provide a comprehensive review of several promising anti-diabetic agents for the treatment of AD and PD.

Deep learning for detection of iso-dense, obscure masses in mammographically dense breasts.

OBJECTIVES: To analyze the performance of deep learning in isodense/obscure masses in dense breasts. To build and validate a deep learning (DL) model using core radiology principles and analyze its performance in isodense/obscure masses. To show performance on screening mammography as well as diagnostic mammography distribution. METHODS: This was a retrospective, single-institution, multi-centre study with external validation. For model building, we took a 3-pronged approach. First, we explicitly taught the network to learn features other than density differences: such as spiculations and architectural distortion. Second, we used the opposite breast to enable the detection of asymmetries. Third, we systematically enhanced each image by piece-wise-linear transformation. We tested the network on a diagnostic mammography dataset (2569 images with 243 cancers, January to June 2018) and a screening mammography dataset (2146 images with 59 cancers, patient recruitment from January to April 2021) from a different centre (external validation). RESULTS: When trained with our proposed technique (and compared with baseline network), sensitivity for malignancy increased from 82.7 to 84.7% at 0.2 False positives per image (FPI) in the diagnostic mammography dataset, 67.9 to 73.8% in the subset of patients with dense breasts, 74.6 to 85.3 in the subset of patients with isodense/obscure cancers and 84.9 to 88.7 in an external validation test set with a screening mammography distribution. We showed that our sensitivity exceeded currently reported values (0.90 at 0.2 FPI) on a public benchmark dataset (INBreast). CONCLUSION: Modelling traditional mammographic teaching into a DL framework can help improve cancer detection accuracy in dense breasts. CLINICAL RELEVANCE STATEMENT: Incorporating medical knowledge into neural network design can help us overcome some limitations associated with specific modalities. In this paper, we show how one such deep neural network can help improve performance on mammographically dense breasts. KEY POINTS: • Although state-of-the-art deep learning networks achieve good results in cancer detection in mammography in general, isodense, obscure masses and mammographically dense breasts posed a challenge to deep learning networks. • Collaborative network design and incorporation of traditional radiology teaching into the deep learning approach helped mitigate the problem. • The accuracy of deep learning networks may be translatable to different patient distributions. We showed the results of our network on screening as well as diagnostic mammography datasets.

Association of patent ductus arteriosus with extubation failure among preterm infants.

BACKGROUND: Mechanical ventilation is associated with mortality/morbidities in preterm infants. Nearly a third of these infants fail extubation, and this may increase morbidities. OBJECTIVE: To evaluate the association of moderate to large symptomatic patent ductus arteriosus (PDA) with failure of extubation among preterm infants. METHODS: This was a retrospective study on preterm infants (birth weight <1250 g and gestational age ≥23 weeks) born between January 2009 and December 2016, who were mechanically ventilated and extubated within the first 60 days of age. RESULTS: Three hundred and sixty infants were evaluated, of these, 26% failed, and 74% succeeded in the initial extubation attempt. On adjusted analysis, symptomatic PDA was associated with an increased risk of extubation failure. CONCLUSION: The presence of symptomatic patent ductus arteriosus was associated with extubation failure. Further investigations are needed to establish whether there is a causal relationship between PDA and extubation failure and whether proactive screening for presence of PDA and treatment of the same, before extubation among these infants, improves chances of successful extubation and cardiorespiratory outcomes.

Teaching skills for sustainable health care.

In the context of accelerating concern regarding the climate and ecological crisis and the recognition of this crisis as a health threat, there is growing motivation among the health-care community to reduce the negative environmental impact of health care. Globally, the health-care sector is estimated to be the 5th largest carbon emitter. A health system that is socially, environmentally, and financially sustainable requires clinical leadership, yet few health-care workers possess the conceptual framework or practical skills for creating new models of care. Clinicians can protect planetary health as a core part of professional practice by integrating triple bottom line measures into quality improvement or quality management practices. Initial efforts to integrate sustainability into quality improvement teaching and training have been shown to transform learners' interest in quality improvement and environmental sustainability. Embedding sustainability principles and techniques into established quality improvement education and practice can operationalise planetary health, building the skills necessary for health-care system transformation at the speed and scale required.

Resveratrol and Its Role in the Management of B-Cell Malignancies-A Recent Update.

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, there is a need to explore nanodelivery of this agent, owing to its poor solubility, which in turn may impact its bioavailability. This review aims to offer an overview of the occurrence and pathogenesis of B cell malignancies with a special focus on the inflammatory pathways involved, the mechanism of actions of resveratrol and its pharmacokinetic profile, results from pre-clinical and clinical studies, as well as an overview of the marketed formulations. The authors have also presented their opinion on the various challenges associated with the clinical development of resveratrol and future perspectives regarding therapeutic applications of this agent.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Gut Microbiota-Assisted Synthesis, Cellular Interactions and Synergistic Perspectives of Equol as a Potent Anticancer Isoflavone.

It is well known that, historically, plants have been an important resource of anticancer agents, providing several clinically approved drugs. Numerous preclinical studies have shown a strong anticancer potential of structurally different phytochemicals, including polyphenolic constituents of plants, flavonoids. In this review article, suppressing effects of equol in different carcinogenesis models are unraveled, highlighting the mechanisms involved in these anticancer activities. Among flavonoids, daidzein is a well-known isoflavone occurring in soybeans and soy products. In a certain part of population, this soy isoflavone is decomposed to equol under the action of gut microflora. Somewhat surprisingly, this degradation product has been shown to be more bioactive than its precursor daidzein, revealing a strong and multifaceted anticancer potential. In this way, it is important to bear in mind that the metabolic conversion of plant flavonoids might lead to products that are even more efficient than the parent compounds themselves, definitely deserving further studies.

The implications of quorum sensing inhibition in bacterial antibiotic resistance- with a special focus on aquaculture.

The aquaculture industry is an expanding and demanding industry and due to an increase in urbanization, with rise in income of developing countries population, it offers to provide a sustainable food supply. However, the industry is facing a number of challenges, out of which few needs to be tackled immediately to maximise the productivity. An upcoming problem is the emergence of antibiotic resistant pathogens due to the unchecked use of antibiotics in aquaculture and human clinical practices. A wide variety of aquatic pathogens such as Edwardsiella, Vibrio, and Aeromonas spp. use quorum sensing (QS) systems, a regulatory process involving cell communication via signalling molecules for the collective function of pathogens which regulates the genes expression including virulent genes. Quorum sensing results in bacterial biofilms formation, which leads to their reduced susceptibility towards antimicrobial agents. The usage of quorum sensing inhibitors (QSIs) has been proposed as an attractive strategy to tackle this problem. Due to the modulation of virulence genes expression, QSIs can be used as novel and viable approach to overcome antibiotic resistance in aquaculture. In this review, we direct our attention to the quorum sensing phenomenon and its viability as a target pathway for tackling the ever-growing problem of antimicrobial resistance in aquaculture. This review also provides a concise compilation of the currently available QSIs and investigates possible natural sources for quorum quenching.

Sustainable healthcare in medical education: survey of the student perspectives at a UK medical school.

BACKGROUND: It is now a General Medical Council requirement to incorporate education for sustainable healthcare (ESH) into medical curricula. To date, research has focussed on the perspectives of educators and which sustainable healthcare topics to include in teaching. Therefore, due to this gap in the literature, we have investigated the perspectives of medical students in the UK regarding current and future incorporation of ESH in medical education. METHODS: A survey was circulated to 851 clinical year medical students and students intercalating after completing at least one clinical year in a London University. The anonymous survey consisted of sections on the environmental impact, current teaching and future teaching of ESH. RESULTS: One hundred sixty-three students completed the survey. 93% of participants believed that climate change is a concern in current society, and only 1.8% thought they have been formally taught what sustainable healthcare is. No participants strongly agreed, and only 5 participants (3.1%) agreed, that they would feel confident in answering exam questions on this topic, with 89% agreeing that more ESH is needed. 60% believe that future teaching should be incorporated in both preclinical and clinical years, with 31% of participants preferring online modules as the method of teaching. CONCLUSION: Our study has stressed the lack of current sustainable healthcare teaching in the medical curriculum. There is student demand for ESH, however, uncertainty remains regarding who is best placed to facilitate ESH, how it should be delivered, and whether there is a gender discrepancy regarding sustainable healthcare importance, emphasising the need to close the gap between educational rhetoric and action.

Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications.

Emoxypine and its succinate derivative share a common hydroxypridine structure, which is similar to pyridoxine. These compounds have been utilized therapeutically and industrially, owing to the wide range of properties offered. This includes antihypoxic, neuroprotective and cardioprotective effects, along with pharmacokinetic benefits such as the ability to cross the blood brain barrier (BBB), owing to its relatively small size and low molecular weight. It was observed that emoxypine exhibited iron chelating property in vitro, indicating its usage as a promising therapeutic strategy in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders like thalassemia and hemochromatosis. In addition to this, it has been observed to exert a potent antioxidant effect, therefore, it may be considered for the amelioration of disorders resulting from free radical injury. Studies on its mechanism of action and implications on cellular and molecular levels would help to further the understanding of its benefits, as well as prospects for filing patents for novel applications. The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents.

Finding Emergent Gait Patterns May Reduce Progression of Knee Osteoarthritis in a Clinically Relevant Time Frame.

A high contact force between the medial femoral condyle and the tibial plateau is the primary cause of medial compartment knee osteoarthritis (OA). A high medial contact force (MCF) during gait has been shown to be correlated to both the knee adduction moment (KAM) and knee flexion/extension moment (KFM). In this study, we used OpenSim Moco to find gait kinematics that reduced the peaks of the KAM, without increasing the peaks of the KFM, which could potentially reduce the MCF and, hence, the progression of knee OA. We used gait data from four knee OA participants. Our simulations decreased both peaks of the KAM without increasing either peak of the KFM. We found that increasing the step width was the primary mechanism, followed by simulations of all participants to reduce the frontal plane lever arm of the ground reaction force vector about the knee, in turn reducing the KAM. Importantly, each participant simulation followed different patterns of kinematic changes to achieve this reduction, which highlighted the need for participant-specific gait modifications. Moreover, we were able to simulate emerging gait patterns within 15 min, enhancing the relevance and potential for the application of developed methods in clinical settings.