Therapeutic potential of Buddleja Polystachya Fresen (stem and leaves) extracts: antimicrobial and cytotoxic properties for ocular disease management.

This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant's potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Initial report on the multiple biological and pharmacological properties of hispolon: Exploring stochastic mechanisms.

The development of natural substances derived from nature poses a significant challenge as technologies for the extraction and characterization of active principles advance. Hispolon has received a lot of attention in recent years, ascribable to its wide range of biological activities. It is a phenolic molecule that was extracted from several mushroom species such as Phellinus igniarius, Phellinus linteus, Phellinus lonicerinus, Phellinus merrillii, and Inonotus hispidus. To provide a comprehensive overview of the pharmacological activities of hispolon, this review highlights its anticancer, anti-inflammatory, antioxidant, antibacterial, and anti-diabetic activities. Several scientific research databases, including Google Scholar, Web of Science, PubMed, SciFinder, SpringerLink, Science Direct, Scopus, and, Wiley Online were used to gather the data on hispolon until May 2024. The in vitro and in vivo studies have revealed that hispolon exhibited significant anticancer properties through modifying several signaling pathways including cell apoptosis, cycle arrest, autophagy, and inhibition of angiogenesis and metastasis. Hispolon's antimicrobial activity was proven against many bacterial, fungal, and viral pathogens, highlighting its potential use as a novel antimicrobial agent. Additionally, hispolon displayed potent anti-inflammatory activity through the suppression of key inflammatory mediators, such as inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenases-2 (COX-2), and the modulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The antioxidant potential of hispolon was attributed to its capacity to neutralize reactive oxygen species (ROS) and to increase the activity of antioxidant enzymes, indicating a possible involvement in the prevention of oxidative stress-related illnesses. Hispolon's antidiabetic activity was associated with the inhibition of aldose reductase and α-glucosidase. Studies on hispolon emphasized its potential use as a promising scaffold for the development of novel therapeutic agents targeting various diseases, including cancer, infectious diseases, inflammatory disorders, and diabetes.

Evaluating dasatinib nanocarrier: Physicochemical properties and cytotoxicity activity on cancer cells.

Objective: Dasatinib-(DAS) is a tyrosine kinase inhibitor usually used to treat leukemia. However, DAS is a poorly water-soluble drug. Therefore, oil-in-water emulsions were used for DAS to enhance its solubility and cancer treatment efficacy. This study aims to develop an appropriate DAS nanoemulsion (NE) that can overcome the issue of DAS solubility and provide an effective anticancer effect. Methods: Spherical particles dispersed in an aqueous media approach within an oily phase (oleic acid, Kolliphor RH40, and dipropylene glycol) were used to formulate DAS-NE using high-energy methods. Different formulas were developed and an appropriate formula was analyzed to identify its physicochemical properties. Raw DAS and nonformula cytotoxicity were evaluated through MTT assay against three cancer cell lines, MCF7 (human breast adenocarcinoma), HT29, and SW480 (human colorectal carcinomas), in addition to MRC5 (Normal human fetal lung fibroblast). Results: Different DAS-NEs (1-7) have been developed successfully. Formulas had a droplet size of a diameter ranging from 84.167 ± 10.178 nm to 273.433 ± 45.267 nm. The drug content of the appropriate formula (DAS-NE3) was found to be 83.2%. The drug release result of DAS-NE3 when compared to raw DAS was about 58%, falling to 13% after 24 h. The DAS-NE3 showed cytotoxicity against the three cancer cells below 26.11 µM but showed 30-fold significantly increased selectivity against MRC5 normal cells compared to that of raw DAS. Conclusion: This study shows that the DAS-NE3 formula may provide a potentially effective and sustained drug delivery for cancer treatment. This provides valuable information to the scientific community and the pharmaceutical industry.

Recent advances and molecular mechanisms of TGF-ß signaling in colorectal cancer, with focus on bioactive compounds targeting.

Colorectal cancer (CRC) is one of the most significant forms of human cancer. It is characterized by its heterogeneity because several molecular factors are involved in contiguity and can link it to others without having a linear correlation. Among the factors influencing tumor transformation in CRC, transforming growth factor-beta (TGF-ß) plays a key promoter role. This factor is associated with human colorectal tumors with a very high prognosis: it increases the survival, invasion, and metastasis of CRC cells, thus functioning as an oncogene. The inhibition of this factor can constitute a major therapeutic route for CRC treatment. Various chemical drugs including synthetic molecules and biotherapies have been developed as TGF-ß inhibitors. Moreover, the scientific community has recently shown a major interest in screening natural drugs inhibiting TGF-ß in CRC. In this context, we carried out this review article using computerized databases, such as PubMed, Google Scholar, Springer Link, Science Direct, Cochrane Library, Embase, Web of Science, and Scopus, to highlight the molecular mechanism of TGF-ß in CRC induction and progression and current advances in the pharmacodynamic effects of natural bioactive substances targeting TGF-ß in CRC.

Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases.

Until recently, the main pharmaceuticals used to control cholesterol and prevent cardiovascular disease (CVD) were statin-related drugs, known for their historical side effects. Therefore, there is growing interest in exploring alternatives, such as nutritional and dietary components, that could play a central role in CVD prevention. This review aims to provide a comprehensive understanding of how natural phytosterols found in various diets combat CVDs. We begin with a description of the overall approach, then we explore in detail the different direct and indirect mechanisms that contribute to reducing cardiovascular incidents. Phytosterols, including stigmasterol, ß-sitosterol, ergosterol, and fucosterol, emerge as promising molecules within nutritional systems for protection against CVDs due to their beneficial effects at different levels through direct or indirect cellular, subcellular, and molecular mechanisms. Specifically, the mentioned phytosterols exhibit the ability to diminish the generation of various radicals, including hydroperoxides and hydrogen peroxide. They also promote the activation of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, while inhibiting lipid peroxidation through the activation of Nrf2 and Nrf2/heme oxygenase-1 (HO-1) signaling pathways. Additionally, they demonstrate a significant inhibitory capacity in the generation of pro-inflammatory cytokines, thus playing a crucial role in regulating the inflammatory/immune response by inhibiting the expression of proteins involved in cellular signaling pathways such as JAK3/STAT3 and NF-κB. Moreover, phytosterols play a key role in reducing cholesterol absorption and improving the lipid profile. These compounds can be used as dietary supplements or included in specific diets to aid control cholesterol levels, particularly in individuals suffering from hypercholesterolemia.

In-vitro Cytotoxicity Investigations for Phytoconstituents of Saudi Medicinal Plants With Putative Ocular Effects.

BACKGROUND: Metastatic secondary ocular tumors spread from systemic malignancies, including breast cancer. This study aimed to evaluate the cytotoxicity of extracts from 5 medicinal plants native to Saudi Arabia. METHODS: For preliminary activity screening, cytotoxicity using the MTT assay and selectivity index determinations were made for medicinal plant extracts against various cancer cell-lines. The most promising extract was subjected to GC-MS analysis to determine the phytochemical composition. Clonogenic assays were performed using the most promising extract to confirm the initial results. Finally, western blot analysis was used to determine the modulation in expression of survivin and P27 suppressor genes in the human breast adenocarcinoma (MCF7) cell-line to understand the potential mechanistic properties of the active plant extract. RESULTS: The 5 plant extracts showed various cytotoxic activity levels using IC50. The most active extract was found to be the leaves of Capparis spinosa L. (BEP-07 extract) against the MCF7 breast cancer cell-line (IC50 = 3.61 ± 0.99 µg/ml) and selectivity index of 1.17 compared to the normal human fetal lung fibroblast (MRC5) cells. BEP-07 extract showed a dose dependent clonogenic effect against the MCF7 colonies which was comparable with the effect of doxorubicin. BEP-07 extract caused a significant decrease of survivin and increase in P27 expression compared to control GAPDH at its highest dose (14 µg/ml). The GC-MS chromatogram of Capparis spinosa L. (BEP-07 extract) revealed the existence of 145 compounds, belonging to the diverse classes of phytoconstituents. Fatty acids and their derivatives represent 15.4%, whilst octadecanoic acid, 2,3-dihydroxypropyl ester was the principal component (7.9%) detected. CONCLUSION: Leaves of Capparis spinosa L. (BEP-07 extract) exhibited a significant cytotoxic effect particularly against breast cancer cells. It exhibited this effect through survivin inhibition and via P27 upregulation. The detected phytoconstituents in the plant extract might be involved in tested cytotoxic activity, while further investigations are required to complete the drug candidate profile.

Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein.

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Identification of new potent NLRP3 inhibitors by multi-level in-silico approaches.

Nod-like receptor protein 3 (NLRP-3), is an intracellular sensor that is involved in inflammasome activation, and the aberrant expression of NLRP3 is responsible for diabetes mellitus, its complications, and many other inflammatory diseases. NLRP3 is considered a promising drug target for novel drug design. Here, a pharmacophore model was generated from the most potent inhibitor, and its validation was performed by the Gunner-Henry scoring method. The validated pharmacophore was used to screen selected compounds databases. As a result, 646 compounds were mapped on the pharmacophore model. After applying Lipinski's rule of five, 391 hits were obtained. All the hits were docked into the binding pocket of target protein. Based on docking scores and interactions with binding site residues, six compounds were selected potential hits. To check the stability of these compounds, 100 ns molecular dynamic (MD) simulations were performed. The RMSD, RMSF, DCCM and hydrogen bond analysis showed that all the six compounds formed stable complex with NLRP3. The binding free energy with the MM-PBSA approach suggested that electrostatic force, and van der Waals interactions, played a significant role in the binding pattern of these compounds. Thus, the outcomes of the current study could provide insights into the identification of new potential NLRP3 inflammasome inhibitors against diabetes and its related disorders.

Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Chemistry, Biological Activities, and Pharmacological Properties of Gastrodin: Mechanism Insights.

Gastrodin, a bioactive compound derived from the rhizome of the orchid Gastrodia elata, exhibits a diverse range of biological activities. With documented neuroprotective, anti-inflammatory, antioxidant, anti-apoptotic, and anti-tumor effects, gastrodin stands out as a multifaceted therapeutic agent. Notably, it has demonstrated efficacy in protecting against neuronal damage and enhancing cognitive function in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Additionally, gastrodin showcases immunomodulatory effects by mitigating inflammation and suppressing the expression of inflammatory cytokines. Its cytotoxic activity involves the inhibition of angiogenesis, suppression of tumor growth, and induction of apoptosis. This comprehensive review seeks to elucidate the myriad potential effects of Gastrodin, delving into the intricate molecular mechanisms underpinning its pharmacological properties. The findings underscore the therapeutic potential of gastrodin in addressing various conditions linked to neuroinflammation and cancer.

Transcutaneous auricular vagus nerve stimulation modifies cortical excitability in middle-aged and older adults.

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABAAergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.

Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications.

Bioactive metabolites obtained from fruits and vegetables as well as many drugs have various capacities to prevent or treat various ailments. Nevertheless, their efficiency, in vivo, encounter many challenges resulting in lower efficacy as well as different side effects when high doses are used resulting in many challenges for their application. Indeed, demand for effective treatments with no or less unfavorable side effects is rising. Delivering active molecules to a particular site of action within the human body is an example of targeted therapy which remains a challenging field. Developments of nanotechnology and polymer science have great promise for meeting the growing demands of efficient options. Encapsulation of active ingredients in nano-delivery systems has become as a vitally tool for protecting the integrity of critical biochemicals, improving their delivery, enabling their controlled release and maintaining their biological features. Here, we examine a wide range of nano-delivery techniques, such as niosomes, polymeric/solid lipid nanoparticles, nanostructured lipid carriers, and nano-emulsions. The advantages of encapsulation in targeted, synergistic, and supportive therapies are emphasized, along with current progress in its application. Additionally, a revised collection of studies was given, focusing on improving the effectiveness of anticancer medications and addressing the problem of antimicrobial resistance. To sum up, this paper conducted a thorough analysis to determine the efficacy of encapsulation technology in the field of drug discovery and development.

Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress.

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.

Prospective virtual screening combined with bio-molecular simulation enabled identification of new inhibitors for the KRAS drug target.

Lung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12-14% of non-small cell lung cancers are caused by mutations in KRASG12C. The KRASG12C is one of the most prevalent mutants in lung cancer patients. KRAS was first considered undruggable. The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development is a challenging, expensive, and time-consuming process. Recently, machine-learning-based virtual screening are used for the development of new drugs. In this study, we performed machine-learning-based virtual screening followed by molecular docking, all atoms molecular dynamics simulation, and binding energy calculations for the identifications of new inhibitors against the KRASG12C mutant. In this study, four machine learning models including, random forest, k-nearest neighbors, Gaussian naïve Bayes, and support vector machine were used. By using an external dataset and 5-fold cross-validation, the developed models were validated. Among all the models the performance of the random forest (RF) model was best on the train/test dataset and external dataset. The random forest model was further used for the virtual screening of the ZINC15 database, in-house database, Pakistani phytochemicals, and South African Natural Products database. A total of 100 ns MD simulation was performed for the four best docking score complexes as well as the standard compound in complex with KRASG12C. Furthermore, the top four hits revealed greater stability and greater binding affinities for KRASG12C compared to the standard drug. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at ( https://github.com/Amar-Ajmal/Datasets-for-KRAS ).

Evaluation of the General Population's Knowledge Concerning Liver Health: A Cross-Sectional Study.

INTRODUCTION: Liver disease is among the leading causes of global mortality and morbidity. Given their substantial impact on public health, raising awareness about liver diseases is paramount for their prevention and effective management. This study aimed to evaluate the knowledge, awareness, attitudes, and behaviors of Syrians regarding liver health, chronic liver disorders, and their associated serious and irreversible complications. METHODS: We conducted a cross-sectional study encompassing the adult Syrian population between August 25 and September 29, 2023, excluding non-Syrians and individuals below the age of 18 years. A validated questionnaire, adapted from a previous study, was employed, consisting of 31 questions that covered topics related to knowledge and awareness of liver health and diseases (3-point Likert scale), attitudes towards liver screening, diagnosis, and treatment, and awareness of treatment options and vaccination. Statistical analysis including logistic regression was conducted using Statistical Product and Service Solutions (SPSS, version 28; IBM SPSS Statistics for Windows, Armonk, NY), with statistical significance set established at pp-values below 0.05. RESULTS: This study included 941 participants, with an average age of 26.5 years. While two-thirds of respondents demonstrated awareness of hepatitis B and C as viral diseases (663 (70.4%) and 612 (65.4%), respectively), approximately 66 (7%) were unaware of the potential for hepatitis to induce chronic liver inflammation or lead to liver failure. Over half of the participants were knowledgeable about the non-genetic nature of hepatitis B and C, and 579 (61.7%) were informed about the transmission risks associated with these infections. The most common reason cited for not participating in health screening tests was the perception of being in good health (219, 77.4%), and prescription medication was the most frequently sought treatment for hepatitis (543, 83.9%). Bivariate analysis revealed correlations between participant knowledge and sex, socioeconomic status, educational level, and occupation (P < 0.05). Similarly, the study identified significant associations between participant attitudes and age, gender, economic status, job, and educational level (P < 0.05). Moreover, the multivariate analysis demonstrated that gender, occupation, and educational level significantly influenced both participants' knowledge and attitudes. Specifically, males exhibited lower knowledge and less favorable attitudes than females (P = 0.041 and P < 0.001, respectively). CONCLUSION: The Syrian population possessed moderate knowledge of liver health and liver disorders. To bridge this knowledge gap and enhance preventive measures, it is recommended that additional health programs and awareness initiatives be implemented, involving healthcare providers and leveraging their expertise.

Return to Play Criteria After Adult Lumbar Spinal Fractures: A Review of Current Literature and Expert Recommendations.

PURPOSE OF REVIEW: Understanding the management of lumbar spinal fractures and return to play (RTP) criteria is an essential component of care for adult athletes. Appropriate management of lumbar spinal fractures must balance minimizing time away from physical activity while also minimizing risk of reinjury. The purpose of this review is to summarize current recommendations on lumbar spinal fracture management and RTP guidelines and to provide expert opinion on areas of discrepancy in the field. RECENT FINDINGS: There is a paucity of high-level evidence on the management and return to play criteria for adult lumbar spine fractures in athletes. Much of the data and recommendations are based on expert opinion and studies in pediatric or osteoporotic patients, which may not be applicable to adult athletes. These data presented here may be used to aid patient-physician conversations and provide guidance on expectations for patients, coaches, and athletic trainers. In general, we recommend that patients be free of lumbar pain, neurologically intact, and have full strength and motion of the lumbar spine and lower extremities before returning to play. Adequate protective equipment is recommended to be worn at all times during practice and play.

Fluoroscopic images of the sacroiliac joint alone are unable to identify simulated flexion or extension malreduction of the anterior pelvic ring in AO/OTA 61-B2.3 pelvic injuries.

PURPOSE: Reduction of AO/OTA 61-B2.3 (APC2) pelvic fractures is challenging in the setting of anterior ring comminution. The anterior ring is visually much simpler to evaluate for flexion or extension hemipelvis deformity than the posterior ring, except in the setting of comminution, necessitating some other visual reference to judge hemipelvis reduction. We sought to test whether pelvic inlet and outlet fluoroscopy of the contours of the sacroiliac joint could be used in isolation to judge hemipelvis flexion or extension. METHODS: Symphyseal and anterior SIJ ligaments were cut (6 cadaveric pelvis). The symphysis was held malreduced to produce one centimeter flexion and extension deformity: 1 cm was selected to mimic a maximum clinical scenario. The SIJ was assessed using inlet and outlet fluoroscopy. The scaled width of the SIJ was assessed at the joint apertures and midjoint on both inlet and outlet views. Joint widths in flexion and extension were compared against joint widths measured on the reduced SIJ using paired t-tests. RESULTS: There was no statistical difference in the superior (p = 0.227, 0.675), middle (p = 0.203, 0.693), and inferior (p = 0.232, 0.961) SIJ widths between hemipelvis flexion or extension models against reduced SIJ on outlet views. There was no statistical difference in the anterior (p = 0.731, 0.662), middle (p = 0.257, 0.655), and posterior (p = 0.657, 0.363) SIJ widths between flexion or extension models against reduced SIJ on inlet views. CONCLUSION: Inspection of SIJ width on inlet and outlet fluoroscopy cannot detect up to one centimeter of hemipelvis flexion or extension malreduction in the setting of AO/OTA 61-B2.3 (APC2) pelvic fractures with complex anterior injuries.

Association between opioid utilization and patient-reported outcome measures following lumbar spine surgery.

BACKGROUND CONTEXT: The patient-reported outcomes measurement information system (PROMIS), created by the National institute of Health, is a reliable and valid survey for patients with lumbar spine pathology. Preoperative opioid use has been shown to be an important predictor variable of self-reported health status in legacy patient-reported outcome measures. PURPOSE: To investigate the impact of chronic preoperative opiate use on PROMIS survey scores. STUDY DESIGN: Retrospective database analysis. PATIENT SAMPLE: Between March 2019 and November 2021, 227 patients underwent lumbar decompression ± ≤ 2 level fusion. Fifty-seven patients (25.11%) had chronic preoperative opioid use. OUTCOME MEASURES: Oswestry disability index (ODI) and PROMIS survey scores. METHODS: A retrospective analysis of a prospectively maintained single center patient-reported outcome database was performed with a minimum of 2 year follow-up. PROMIS Anxiety, Depression, Fatigue, Pain Interference (PI), Physical Function (PF), Sleep disturbance (SD), and Social Roles (SR) surveys were recorded at preoperative intake with subsequent follow-up at 6, 12, and 24 months postoperatively. Patients were grouped into chronic opioid users as defined by >6-month duration of use. Differences in mean survey scores were evaluated using Welch t-tests. RESULTS: Two hundred and twenty-seven patients met our inclusion criteria of completed PROMIS surveys at the designated timepoints. A total of 57 (25.11%) were chronic opioid users (COU) prior to surgery. Analysis of patient-reported health outcomes shows that long term opioid use correlated with worse ODI and PROMIS scores at baseline compared to nonchronic users (NOU). At 1 and 2 year follow-up, the COU cohort continued to have significantly worse ODI, PROMIS Fatigue, PF, PI, SD, and SR scores. There is a statistical difference in the magnitude of change in health status between the 2 cohorts at 1 year follow-up in PROMIS Depression (-5.04±7.88 vs -2.49±8.73, p=.042), PF (6.25±7.11 vs 9.03±9.04, p=.019), and PI (-7.40±7.37 vs -10.58±9.87, p=.011) and 2 year follow-up in PROMIS PF (5.58±6.84 vs 7.99±9.64, p=.041) and PI (-6.71±8.32 vs -9.62±10.06, p=.032). Mean improvement in PROMIS scores for the COU cohort at 2 year follow-up exceeded minimal clinically important difference (MCID) in all domains except PROMIS Depression, SR and SD. CONCLUSION: Patients with chronic opioid use status have worse baseline PROMIS scores compared with patients who had nonchronic use. However, patients in the COU cohort displayed clinically significant postoperative improvement in multiple PROMIS domains. These results show that patients with chronic opioid use can benefit greatly from surgical intervention and will allow physicians to better set expectations with their patients.

Clinical application of transcutaneous auricular vagus nerve stimulation: a scoping review.

PURPOSE: Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging non-invasive neuromodulation therapy. This study aimed to explore the therapeutic use of taVNS, optimal stimulation parameters, effective sham protocols, and safety. METHODS: A scoping review was conducted. Five databases and grey literature were searched. The data extracted included stimulation parameters, adverse events (AEs), and therapeutic effects on clinical outcomes. RESULTS: 109 studies were included. taVNS was used across 21 different clinical populations, most commonly in psychiatric, cardiac, and neurological disorders. Overall, 2,214 adults received active taVNS and 1,017 received sham taVNS. Reporting of stimulation parameters was limited and inconsistent. taVNS appeared to have a favourable therapeutic effect across a wide range of clinical populations with varied parameters. Three sham protocols were reported but their effectiveness was documented in only two of the 54 sham-controlled studies. Most reported adverse events were localised to stimulation site. CONCLUSION: There is growing evidence for taVNS therapeutic effect. taVNS appears safe and tolerable. Sham protocols need evaluation. Standardised and comprehensive reporting of both stimulation parameters and adverse events is required. Two different questionnaires have been proposed to evaluate adverse events and the effectiveness of sham methods in blinding participants.

Transcutaneous auricular vagus nerve stimulation (taVNS) showed therapeutic effect across a wide range of clinical populations including depression, epilepsy, and strokeThere is a preliminary indication that daily/weekly dose and overall duration of treatment are important to show therapeutic effectivenessWhen using taVNS as an intervention, the questionnaires proposed in this review should be used to evaluate blinding effectiveness and adverse events.

Identification of subtle residual sacroiliac joint flexion and extension malreductions in AO/OTA 61-C1.2 (APC3) pelvic injuries after provisional anterior ring reduction.

PURPOSE: Hemipelvis reduction in the setting of AO/OTA 61-C1.2 (APC3) pelvic injuries can be challenging. A common strategy is to provisionally reduce or fix the anterior ring prior to definitive fixation of the posterior ring. In this scenario, it is difficult to assess whether residual sacroiliac joint (SIJ) widening is due to hemipelvis flexion/extension or lateral displacement. This simulation sought to identify a radiographic marker for posterior ilium flexion or extension malreduction in the setting of a reduced anterior ring. METHODS: Symphyseal and both anterior and posterior SIJ ligaments were cut in 8 cadaveric pelvis. The symphysis was reduced and wired. One centimeter of posterior flexion or extension at the SIJ was created to mimic the clinical scenario of hemipelvis flexion or extension malreduction, and a lateral compressive force was applied. SIJ widening and the direction of anterior or posterior ileal displacement relative to the contralateral joint were assessed via inlet views. SIJ widening and the direction of cranial or caudal ileal displacement were assessed using outlet views. Comparisons between flexion and extension models used Fisher's exact test. RESULTS: On outlet views, all flexed hemipelvis demonstrated caudal ileal translation at the superior SIJ, in contrast to all extended hemipelvis demonstrated cranial translation (p < 0.0005); the scenarios were easily distinguishable. Conversely, inlet imaging was unable to identify the direction of malreduction. Flexion/extension scenarios resulted in similar amounts of SIJ widening. CONCLUSION: Residual flexion and extension hemipelvis malreductions in APC3 injuries after provisional anterior fixation can be differentiated by the direction of ileal displacement at the superior SIJ on the outlet view.