The impact of diabetes status on pain and physical function following total joint arthroplasty for hip and knee osteoarthritis: variation by sex and body mass index.

Few studies have examined diabetes impact on total joint arthroplasty (TJA) outcomes, with variable findings. We investigated the association between diabetes and post-TJA physical function and pain, examining whether diabetes impact differs by sex and BMI. Patient sample completed questionnaires within 3 months prior to hip or knee TJA for osteoarthritis (OA) and 1-year post-surgery. Surgical 'non-response' was defined as < 30% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function at 1-year. Two adjusted logistic regression models were estimated: (1) excluding, (2) including an interaction between diabetes, sex and BMI. The sample (626 hip, 754 knee) was 54.9% female, had mean BMI of 30.1, 13.0% reported diabetes. In adjusted models excluding an interaction, diabetes was not associated with non-response. However, a significant 3-way interaction (physical function: p = 0.003; pain: p = 0.006) between diabetes, sex, and BMI was found and was associated with non-response: non-response probability increased with increasing BMI in men with diabetes, but decreased with increasing BMI in women in diabetes. Findings suggest uncertainty in diabetes impact may be due to differential impacts by sex and BMI. A simple consideration of diabetes as present vs. absent may not be sufficient, with implications for the large TJA population.

Total Hip Arthroplasty Versus Education and Exercise: A Propensity-Matched Analysis of 266 Patients Who Have Hip Osteoarthritis.

BACKGROUND: Total hip arthroplasty (THA) for osteoarthritis (OA) is a major health system cost. Education and exercise (Edu+Ex) programs may reduce the number of THAs needed, but supporting data is limited. This study aimed to estimate the treatment effect of THA versus Edu+Ex on pain, function, and quality of life outcomes 3- and 12-months after treatment initiation for hip OA. METHODS: Patients who had hip OA who underwent THA or an Edu+Ex program were included in this propensity-matched study. In 778 patients (Edu+Ex n = 303; THA n = 475), propensity scores were based on pre-treatment characteristics, and patients were matched on a 1:1 ratio. Between-group treatment effects (pain, function, and quality of life) were estimated as the mean difference in change from pre-treatment to 3- and 12-month follow-up using linear mixed models. RESULTS: The matched sample consisted of 266 patients (Edu+Ex n = 133; THA n = 133) that were balanced on all pre-treatment characteristics except opioid use. At 12-month follow-up, THA resulted in significantly greater improvements in pain (mean difference [MD] 35.4; 95% CI [confidence interval] 31.4 to 39.4), function (MD 30.5; 95% CI 26.3 to 34.7), and quality of life (MD 33.6; 95% CI 28.8 to 38.4). Between 17 and 30% of patients receiving Edu+Ex experienced a surgical threshold for clinically meaningful improvement in outcomes, compared to 84 and 90% of THA patients. CONCLUSIONS: A THA provides greater improvements in pain, function, and quality of life. A significant proportion of Edu+Ex patients had clinically meaningful improvements, suggesting Edu+Ex may result in THA deferral in some patients, but confirmatory trials are needed.

The impact of diabetes on physical and mental health status and patient satisfaction after total hip and knee arthroplasty.

OBJECTIVE: To assess the impact of diabetes on physical and mental health status, as well as patient satisfaction, one-year following knee and hip total joint arthroplasty (TJA) for osteoarthritis (OA). METHODS: Participants were 626 hip and 754 knee TJA patients. Pre-surgery data were collected on socio-demographics and health status. The 12-item Short Form Health Survey (SF-12) was collected pre- and one year post-surgery, and physical (PCS) and mental component (MCS) summary scores computed. One-year patient satisfaction was also recorded. Four regression models tested the effect of diabetes on: 1) PCS change score; 2) MCS change score; 3) achieving minimal clinically important improvement (MCII) on PCS; and 4) patient satisfaction ('Somewhat or Very Satisfied' vs. 'Somewhat or Very Dissatisfied'). An interaction between surgical joint and diabetes was tested in each model. RESULTS: Self-reported diabetes prevalence was 13.0% (95% CI: 11.2%-14.7%) and was more common in knee 16.1% (95% CI: 13.4%-18.7%) than hip 9.3% (95% CI: 7.0%-11.5%) patients. In adjusted analyses, change scores were 2.3 units less on the PCS for those with diabetes compared to those without (p = 0.005). Patients with diabetes were about half as likely to achieve MCII as patients without diabetes (p = 0.004). Diabetes was not significantly associated with satisfaction or changes in MCS scores. Diabetes effects did not differ by surgical joint. CONCLUSIONS: Findings support that diabetes has a negative impact on improvements in physical health after TJA. Considering the growing prevalence of OA and diabetes in the population, our findings support the importance of perioperative screening and management of diabetes in patients undergoing TJA.

Optimum Working Hours for College of Physicians and Surgeons Pakistan Fellowship Residents of General Medicine and General Surgery Disciplines.

OBJECTIVE: To determine the optimum working hours per week for CPSP trainees of Fellowship Programmes in the disciplines of General Surgery and General Medicine. STUDY DESIGN: Mixed-methods, explanatory study. Place and Duration of the Study: Department of General Medicine and Department of General Surgery, Abbasi Shaheed Hospital, Karachi, from February to August 2023. METHODOLOGY: The total number of subjects included were 33 residents, 7 supervisors (4 from General Medicine and 3 from Geneneral Surgery), and 3 hospital managers (from private sector), constituting a representative sample. Postgraduate trainees (PGTs) of third-and fourth-year FCPS training programme who showed willingness to participate were included as were all supervisors and hospital managers involved in the training programme. FCPS residents, who were not willing, on leave, and on rotation to other departments were excluded, as were PGTs enrolled in university and other programmes. For quantitative analysis, survey forms were distributed to the selected participants. For qualitative analysis, one-to-one interviews were conducted in-person and through video-link. Data collection procedure included distribution by hand and via email. SPSS was used for the data analysis. RESULTS: All residents recorded that duty stress, fatigue, and burnout resulted in poor quality of family and social life. All the stakeholders were convinced that acquisition of skills, learning outcomes, and patient safety with optimum care is compromised. The duration of emergency calls varied from 30 to 36 hours. There were 19 out of 33 residents (57.5%) who recommended 24 hours of rest after each emergency call. All the supervisors recommended six to eight daily duty hours and 66 to 90 weekly working hours. Four out of seven supervisors (57.1%) suggested emergency duty of 30 hours with post-call rest of 24 hours at every 3rd  day. CONCLUSION: There is a need for a comprehensive approach that caters to the patient care as well as learning outcomes and residents' well-being when devising the duty schedules. KEY WORDS: Training hours, Fellowship programme, Fatigue, Learning outcomes.

Advancements in biosensors for cancer detection: revolutionizing diagnostics.

Cancer stands as the reigning champion of life-threatening diseases, casting a shadow with the highest global mortality rate. Unleashing the power of early cancer treatment is a vital weapon in the battle for efficient and positive outcomes. Yet, conventional screening procedures wield limitations of exorbitant costs, time-consuming endeavors, and impracticality for repeated testing. Enter bio-marker-based cancer diagnostics, which emerge as a formidable force in the realm of early detection, disease progression assessment, and ultimate cancer therapy. These remarkable devices boast a reputation for their exceptional sensitivity, streamlined setup requirements, and lightning fast response times. In this study, we embark on a captivating exploration of the most recent advancements and enhancements in the field of electrochemical marvels, targeting the detection of numerous cancer biomarkers. With each breakthrough, we inch closer to a future where cancer's grip on humanity weakens, guided by the promise of personalized treatment and improved patient outcomes. Together, we unravel the mysteries that cancer conceals and illuminate a path toward triumph against this daunting adversary. This study celebrates the relentless pursuit of progress, where electrochemical innovations take center stage in the quest for a world free from the clutches of carcinoma.

Total Knee Arthroplasty Versus Education and Exercise for Knee Osteoarthritis: A Propensity-Matched Analysis.

OBJECTIVE: We estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA). METHODS: Patients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between-group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12-item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching. RESULTS: The matched sample consisted of 522 patients (Edu+Ex, n = 261; TKA, n = 261) who were balanced on all pretreatment characteristics. At 12-month follow-up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7-25.8), function (MD 21.2; 95% CI 17.7-24.4), and quality of life (MD 18.3; 15.0-21.6). Even so, at least one-third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA. CONCLUSION: TKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed.

Mind Matters: Exploring the Intersection of Psychological Factors and Cognitive Abilities of University Students by Using ANN Model.

Purpose: While previous studies have suggested close association of psychological variables of students withtheir higher-order cognitive abilities, such studies have largely been lacking for third world countries like India, with their unique socio-economic-cultural set of challenges. We aimed to investigate the relationship between psychological variables (depression, anxiety and stress) and cognitive functions among Indian students, and to predict cognitive performance as a function of these variables. Patients and Methods: Four hundred and thirteen university students were systematically selected using purposive sampling. Widely used and validated offline questionnaires were used to assess their psychological and cognitive statuses. Correlational analyses were conducted to examine the associations between these variables. An Artificial Neural Network (ANN) model was applied to predict cognitive levels based on the scores of psychological variables. Results: Correlational analyses revealed negative correlations between emotional distress and cognitive functioning. Principal Component Analysis (PCA) reduced the dimensionality of the input data, effectively capturing the variance with fewer features. The feature weight analysis indicated a balanced contribution of each mental health symptom, with particular emphasis on one of the symptoms. The ANN model demonstrated moderate predictive performance, explaining a portion of the variance in cognitive levels based on the psychological variables. Conclusion: The study confirms significant associations between emotional statuses of university students with their cognitive abilities. Specifically, we provide evidence for the first time that in Indian students, self-reported higher levels of stress, anxiety, and depression are linked to lower performance in cognitive tests. The application of PCA and feature weight analysis provided deeper insights into the structure of the predictive model. Notably, use of the ANN model provided insights into predicting these cognitive domains as a function of the emotional attributes. Our results emphasize the importance of addressing mental health concerns and implementing interventions for the enhancement of cognitive functions in university students.

Synthesis, spectrophotometric, pharmacology and theoretical investigation of a new electron transfer complex of 8-hydroxyquinoline with oxalic acid in different polar solvents.

Preparation, characterization, and investigation of a novel organic charge transfer (CT) complex were carried out, with a focus on exploring its antibacterial and antifungal characteristics. Theoretical analysis backs up the experimental findings. CT complex formed was synthesized between 8-hydroxyquinoline (8HQ) and oxalic acid (OA) at RT (room temperature). Different analyses were used to describe the CT complex, including 1H-NMR, FTIR, TGA/DTA, and UV-vis spectra (in different solvents). These indicate that the CT interaction is linked to proton transfer from OA to 8HQ and the subsequent development of 'N+__H…O-" type bonding. On the basis of wave number, the CT complex and reactants are distinguished in FTIR spectra. By using Thermo gravimetric Analysis/Differential Thermal Analysis (TGA/DTA) tests, the thermal stability of complicated and thorough corrosion was examined. Through UV-visible spectroscopy, physical characteristics like ECT (interaction energy), RN (resonance energy), ID (ionization potential), f (oscillator strength) and ΔG (free energy) were calculated. The εCT (molar extinction coefficient), the KCT (formation constant), and additional physical properties of this complex were calculated by the Benesi-Hildebrand equation in order to determine its 1:1 stoichiometry. The biological properties are also supported by theoretical study. The protein, Human Serum Albumin (HSA), is observed to bind with CT complex, as shown by molecular docking and the observed binding energy value is -167.04 kcal/mol. Molecular dynamics (MD) simulation 100 ns run was used to refine docking results and binding free energy was calculated using MM-PBSA. This study introduces a novel CT complex, offering fresh perspectives on molecular interactions.Communicated by Ramaswamy H. Sarma.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

BACKGROUND: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries. METHODS: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors. RESULTS: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs. CONCLUSIONS: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system.

A peptide-binding domain shared with an Antarctic bacterium facilitates Vibrio cholerae human cell binding and intestinal colonization.

Vibrio cholerae, the causative agent of the disease cholera, is responsible for multiple pandemics. V. cholerae binds to and colonizes the gastrointestinal tract within the human host, as well as various surfaces in the marine environment (e.g., zooplankton) during interepidemic periods. A large adhesin, the Flagellar Regulated Hemagglutinin A (FrhA), enhances binding to erythrocytes and epithelial cells and enhances intestinal colonization. We identified a peptide-binding domain (PBD) within FrhA that mediates hemagglutination, binding to epithelial cells, intestinal colonization, and facilitates biofilm formation. Intriguingly, this domain is also found in the ice-binding protein of the Antarctic bacterium Marinomonas primoryensis, where it mediates binding to diatoms. Peptide inhibitors of the M. primoryensis PBD inhibit V. cholerae binding to human cells as well as to diatoms and inhibit biofilm formation. Moreover, the M. primoryensis PBD inserted into FrhA allows V. cholerae to bind human cells and colonize the intestine and also enhances biofilm formation, demonstrating the interchangeability of the PBD from these bacteria. Importantly, peptide inhibitors of PBD reduce V. cholerae intestinal colonization in infant mice. These studies demonstrate how V. cholerae uses a PBD shared with a diatom-binding Antarctic bacterium to facilitate intestinal colonization in humans and biofilm formation in the environment.

Age Estimation using Cephalometrics-A Cross-Sectional Study among Teenagers of Salem District, Tamil Nadu.

Background: Age estimation is important not only in identifying dead body of a person but also in living persons since there is an increasing rate of juvenile delinquencies recorded every year. To avoid foul play by age fabrication, legal age estimation becomes important. Facial growth alteration takes place in the jawbones as age advances which can be observed with lateral cephalometry. Thus, the aim of the study is to create a regression formula for age estimation using cephalometrics of teenagers in Salem population. Materials and Methods: A cross-sectional study was done using 770 lateral cephalometrics of teenagers (13-19 yrs) in Salem population. Nine cephalometric points with two linear hard tissue measurements (condylion to mandibular plane (AFH) and palatal plane to menton (PFH)) and one angular soft tissue measurement (z angle) were recorded as predictor variables using a digital lateral cephalometric software (Carestream CS8100 SC) which were subjected to regression analysis using SPSS version 21.0 to develop a formula for age estimation. Results: Significant association on age was obtained for the two linear measurements. The regression formula generated for estimating the age was Age = 7.146 + 0.044 (AFH) + 0.146 (PFH) with R2 value = 0.674. Conclusion: Within the limitations of the present study, age estimation of teenagers in Salem population can be estimated. The predictability of the age can be increased by taking more cephalometric variables in generating the formula with increase in sample size.

Long non-coding RNAs modulate tumor microenvironment to promote metastasis: novel avenue for therapeutic intervention.

Cancer is a devastating disease and the primary cause of morbidity and mortality worldwide, with cancer metastasis responsible for 90% of cancer-related deaths. Cancer metastasis is a multistep process characterized by spreading of cancer cells from the primary tumor and acquiring molecular and phenotypic changes that enable them to expand and colonize in distant organs. Despite recent advancements, the underlying molecular mechanism(s) of cancer metastasis is limited and requires further exploration. In addition to genetic alterations, epigenetic changes have been demonstrated to play an important role in the development of cancer metastasis. Long non-coding RNAs (lncRNAs) are considered one of the most critical epigenetic regulators. By regulating signaling pathways and acting as decoys, guides, and scaffolds, they modulate key molecules in every step of cancer metastasis such as dissemination of carcinoma cells, intravascular transit, and metastatic colonization. Gaining a good knowledge of the detailed molecular basis underlying lncRNAs regulating cancer metastasis may provide previously unknown therapeutic and diagnostic lncRNAs for patients with metastatic disease. In this review, we concentrate on the molecular mechanisms underlying lncRNAs in the regulation of cancer metastasis, the cross-talk with metabolic reprogramming, modulating cancer cell anoikis resistance, influencing metastatic microenvironment, and the interaction with pre-metastatic niche formation. In addition, we also discuss the clinical utility and therapeutic potential of lncRNAs for cancer treatment. Finally, we also represent areas for future research in this rapidly developing field.

Three-Dimensional Finite Element Analysis of Maxillary Protraction Using Diverse Modes of Rapid Palatal Expansion.

INTRODUCTION: Three-dimensional finite elemental analysis (FEA) is a contemporary research instrument for the numeric simulation of a real physical system's mechanical process. FEA can be used as a very effective tool to analyze and compare various aspects of rapid palatal expanders and to determine the stress distribution in maxillofacial bones and displacement and the biomechanical effects it has on the circummaxillary sutures. This study evaluates the effects of different modes of rapid palatal expansion on maxillary protraction as a treatment modality in skeletal Class III malocclusion by determining the stress and displacement along the circummaxillary sutures using the FEA. MATERIALS AND METHODS: Initially, a three-dimensional finite element simulation of the maxillofacial skeleton and sutures was obtained by Mimics software (Leuven, Belgium) from the cone-beam computed tomography (Dentsply Sirona, USA) images of a 30-year-old adult with normal occlusion. A geometrical preparation of the three expansion appliances, (A) hybrid MARPE (miniscrew-assisted rapid palatal expander) appliance (Fav anchor, India), (B) tooth-borne HYRAX (hygenic rapid expander) appliance (Welcare orthodontics, Kerela), and (C) bone-borne modified MARPE appliance (Biomaterials, Korea), was transferred to ANSYS WORKBENCH, 2020 R1 software (ANSYS, Inc., USA), and three finite element models with each appliance were prepared. A protraction force of 500g was applied to the occlusal plane that is directed 20 degrees inferiorly. The tensile stress, compressive stress, and the amount of displacement on the circummaxillary sutures were assessed and compared in all the three appliances. Young's modulus (kg/mm2) and Poisson's ratio (V) were used to calculate the stress and displacement in sutures adjacent to the maxilla in different aspects. RESULTS: On analyzing the stress distribution, the tensile stress was found to be maximum in the medial aspect of the frontomaxillary suture of the bone-borne modified MARPE appliance (C), and the minimum tensile stress was found in the lateral aspect of the sphenozygomatic suture in hybrid MARPE (A). Again, the compressive stress distribution was found to be maximum in the medial aspect of the frontomaxillary suture in all three simulations and the minimum compressive stress in the superior aspect of the internasal suture in hybrid MARPE (A) along with the frontonasal suture at its medial aspect for tooth-borne HYRAX (B) and bone-borne modified MARPE (C). Displacement of the maxilla in all the planes was observed to be the largest for the bone-borne modified MARPE (C) appliance. On the contrary, the minimum displacement was found in the tooth-borne HYRAX (B) appliance.  Conclusion: The findings reveal that all three modes of rapid palatal expanders produced stress and displacement along the circummaxillary sutures on the application of protraction force with bone-borne modified MARPE being more effective in treating posterior crossbites thereby correcting the skeletal Class III malocclusions successfully.

Effects of Mediterranean diets and nutrigenomics on cardiovascular health.

The field of nutrigenomics studies the interaction between nutrition and genetics, and how certain dietary patterns can impact gene expression and overall health. The Mediterranean diet (MedDiet), characterized by a high intake of fruits, vegetables, whole grains, and healthy fats, has been linked to better cardiovascular health (CVH) outcomes. This review summarizes the current state of research on the effects of nutrigenomics and MedDiet on cardiovascular health. Results suggest that MedDiet, through its impact on gene expression, can positively influence CVH markers such as blood pressure, lipid profile, and inflammation. However, more research is needed to fully understand the complex interactions between genetics, nutrition, and CVH, and to determine the optimal dietary patterns for individualized care. The aim of this scientific review is to evaluate the current evidence on the effects of nutrigenomics and MedDiet on cardiovascular health. The review summarizes the available studies that have investigated the relationship between nutrition, genetics, and cardiovascular health, and explores the mechanisms by which certain dietary patterns can impact CVH outcomes. The review focuses on the effects of MedDiet, a dietary pattern that is rich in whole foods and healthy fats, and its potential to positively influence CVH through its impact on gene expression. The review highlights the limitations of current research and the need for further studies to fully understand the complex interplay between nutrition, genetics, and cardiovascular health.

One-pot microwave synthesis of chitosan-stabilized silver nanoparticles entrapped polyethylene oxide nanofibers, with their intrinsic antibacterial and antioxidant potency for wound healing.

Different physical and chemical techniques could be used to prepare chitosan/Silver nanoparticle (CHS/AgNPs) nanocomposite. The microwave heating reactor was rationally adopted as a benign tool for preparing CHS/AgNPs owing to less energy consumption and shorter time required for completing the nucleation and growth particles. UV-Vis, FTIR, and XRD, provided conclusive evidence of the AgNPs creation, while TEM micrographs elucidated that the size was spherical (20 nm). CHS/AgNPs were embedded in polyethylene oxide (PEO) nanofiber via electrospinning, and their biological properties, cytotoxicity evaluation, antioxidant, and antibacterial activity assays were investigated. The generated nanofibers have mean diameters of 130.9 ± 9.5, 168.7 ± 18.8, and 186.8 ± 8.19 nm for PEO, PEO/ CHS, and PEO/ CHS (AgNPs), respectively. Because of the tiny AgNPs particle size loaded in PEO/CHS (AgNPs) fabricated nanofiber, good antibacterial activity with ZOI against E. coli was 51.2 ± 3.2, and S. aureus was 47.2 ± 2.1 for PEO/ CHS (AgNPs) nanofibers. Non-toxicity was observed against Human Skin Fibroblast and Keratinocytes cell lines (>93.5 %), which justifies its great antibacterial potential to remove or prevent infection in wounds with fewer adverse effects.

TFA-mediated stereoselective aza-Michael addition for the synthesis of 3ß-arylamine derivatives of withaferin A and evaluation of their anticancer potential.

A simple and efficient protocol for the aza-Michael addition of various aromatic anilines to ring A of withaferin A has been developed. Stereoselectivity, functional group tolerance, broad substrate scope, short reaction time and moderate to high yield are the merits of the protocol. One of the synthesized compounds 11 shows an IC 50 value of 3.8 µM against aggressive, highly metastatic triple-negative breast cancer cell line MDA-MB-231.

Identification of a differential metabolite-based signature in patients with late-stage knee osteoarthritis.

Objective: Multiple disease phenotypes have been identified in knee osteoarthritis (OA) patients based on anthropometric, sociodemographic and clinical factors; however, differential systemic metabolite-based signatures in OA patients are not well understood. We sought to identify differential plasma metabolome signatures in a cross-sectional sample of late-stage knee OA patients. Methods: Plasma from 214 (56.5% female; mean age â€‹= â€‹67.58 years) non-diabetic, non-obese (BMI <30 â€‹kg/m2, mean â€‹= â€‹26.25 â€‹kg/m2), radiographic KL 3/4 primary knee OA patients was analyzed by metabolomics. Patients with post-traumatic OA and rheumatoid arthritis were excluded. Hierarchical clustering was used to identify patient clusters based on metabolite levels. A refined metabolite signature differentiating patient clusters was determined based on ≥ 10% difference, significance by FDR-adjusted t-test (q-value < 0.05), and random forests importance score ≥1, and analyzed by AUROC. Bioinformatics analysis was used to identify genes linked to ≥2 annotated metabolites. Associated enriched pathways (q â€‹< â€‹0.05) were determined. Results: Two patient clusters were determined based on the levels of 151 metabolites identified. Metabolite signature refinement found 24 metabolites could accurately predict cluster classification within the sample (AUC â€‹= â€‹0.921). Fifty-six genes were linked to at least 2 â€‹KEGG annotated metabolites. Pathway analysis found 26/56 genes were linked to enriched pathways including tRNA acylation and B-vitamin metabolism. Conclusion: This study demonstrates systemic metabolites can classify a cross-sectional cohort of OA patients into distinct clusters. Links between metabolites, genes and pathways can help determine biological differences between OA patients, potentially improving precision medicine and decision-making.

A Comparison on Efficiency and Aerosol Generation between "Modified and Conventional Technique of Bracket Bonding".

Introduction: The novel COVID-19 which spread's primarily through oral and nasal passage poses a major threat of spread during dental treatments. It is important for dental practitioners to use minimal aerosol techniques. The aim of this study is to compare the time taken, efficiency and aerosol generated between modified and conventional technique (CT) of bracket bonding. Methods: This study includes 40 patients who required complete orthodontic treatment. In all 40 patients, one of the arches was bonded with modified technique (MT) and the opposing with CT. The time taken to prepare tooth in both the techniques were accessed. The efficiency of bond was seen over a period of 6 months. The amount of aerosol particulate matter generated during CT and MT was observed using a laser air quality monitor. Conclusion: There is no significant difference in the bond failure and time taken between both the techniques. The aerosol generated in MT was minimal or almost negligible when compared to the use of CT.

High Pain Catastrophizing Scale Predicts Lower Patient-Reported Outcome Measures in the Foot and Ankle Patient.

BACKGROUND: Postoperative outcomes may be affected by the patient's preoperative morbidity. It is hypothesized that patient's pain catastrophization prior to foot and ankle surgery may affect their patient-reported outcomes. Methods: This study prospectively assessed a consecutive cohort of 46 patients undergoing foot and ankle reconstruction to describe the relationship between Pain Catastrophizing Scale (PCS) and patient-reported outcomes measured by 12-item Short Form Health Survey and Foot and Ankle Outcome Score (FAOS). RESULTS: The 1-year postoperative FAOS pain, activities of daily living, and quality of life scores correlated significantly with all baseline PCS subcategories. We found that the mental domain of the SF-12 had a statistically significant correlation with the rumination and helplessness PCS subcategories. CONCLUSION: This study showed a significant association between a high preoperative PCS and a worse 1-year FAOS. As such, catastrophization could be screened for and potentially treated preoperatively to improve patient-reported outcomes in elective foot and ankle surgery. LEVEL OF EVIDENCE: Therapeutic, Level III Evidence.