Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration.

The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.

Performance evaluation of E-VGG19 model: Enhancing real-time skin cancer detection and classification.

Skin cancer is a pervasive and potentially life-threatening disease. Early detection plays a crucial role in improving patient outcomes. Machine learning (ML) techniques, particularly when combined with pre-trained deep learning models, have shown promise in enhancing the accuracy of skin cancer detection. In this paper, we enhanced the VGG19 pre-trained model with max pooling and dense layer for the prediction of skin cancer. Moreover, we also explored the pre-trained models such as Visual Geometry Group 19 (VGG19), Residual Network 152 version 2 (ResNet152v2), Inception-Residual Network version 2 (InceptionResNetV2), Dense Convolutional Network 201 (DenseNet201), Residual Network 50 (ResNet50), Inception version 3 (InceptionV3), For training, skin lesions dataset is used with malignant and benign cases. The models extract features and divide skin lesions into two categories: malignant and benign. The features are then fed into machine learning methods, including Linear Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Decision Tree (DT), Logistic Regression (LR) and Support Vector Machine (SVM), our results demonstrate that combining E-VGG19 model with traditional classifiers significantly improves the overall classification accuracy for skin cancer detection and classification. Moreover, we have also compared the performance of baseline classifiers and pre-trained models with metrics (recall, F1 score, precision, sensitivity, and accuracy). The experiment results provide valuable insights into the effectiveness of various models and classifiers for accurate and efficient skin cancer detection. This research contributes to the ongoing efforts to create automated technologies for detecting skin cancer that can help healthcare professionals and individuals identify potential skin cancer cases at an early stage, ultimately leading to more timely and effective treatments.

Multi-modal imaging for dynamic visualization of osteogenesis and implant degradation in 3D bioprinted scaffolds.

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Integrating Fluorescence and Magnetic Resonance Imaging in Biocompatible Scaffold for Real-Time Bone Repair Monitoring and Assessment.

In situ monitoring of bone tissue regeneration progression is critical for the development of bone tissue engineering scaffold. However, engineered scaffolds that can stimulate osteogenic progress and allow for non-invasive monitoring of in vivo bone regeneration simultaneously are rarely reported. Based on a hard-and-soft integration strategy, a multifunctional scaffold composed of 3D printed microfilaments and a hydrogel network containing simvastatin (SV), indocyanine green-loaded superamphiphiles, and aminated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NH2 ) is fabricated. Both in vitro and in vivo results demonstrate that the as-prepared scaffold significantly promotes osteogenesis through controlled SV release. The biocomposite scaffold exhibits alkaline phosphatase-responsive near-infrared II fluorescence imaging. Meanwhile, USPIO-NH2 within the co-crosslinked nanocomposite network enables the visualization of scaffold degradation by magnetic resonance imaging. Therefore, the biocomposite scaffold enables or facilitates non-invasive in situ monitoring of neo-bone formation and scaffold degradation processes following osteogenic stimulation, offering a promising strategy to develop theranostic scaffolds for tissue engineering.

Amelioration of physicochemical, pharmaceutical, and pharmacokinetic properties of lornoxicam by cocrystallization with a novel coformer.

OBJECTIVE: The present study was aimed to prepare and characterize new cocrystals of lornoxicam (LORX), a BCS class II drug employing 1,3-dimethyl urea (DMU) as a coformer to improve physicochemical, pharmaceutical, and pharmacokinetic performance. METHODS: A screening study was conducted by employing three techniques viz. neat grinding, liquid-assisted grinding (LAG), and solvent evaporation (SE) using different drug-coformer molar ratios (1:1, 1:2, and 1:3). Samples were characterized by DSC, PXRD, ATR-FTIR, SEM, intrinsic dissolution rate (IDR) studies, compressional studies, and pharmacokinetic studies. In vitro dissolution and stability studies (25 °C/60%RH and 40 °C/75%RH for three months) were carried out for cocrystal tablets. RESULTS: LAG and SE were found successful in ratio 1:3 and IDR showed approximately 28- and 19-fold increase, respectively in 0.1 N HCl (pH 1.2) and buffer (pH 7.4) as compared to pure LORX. The cocrystal exhibited good tabletability and was ∼2.5 times that of LORX at 6000 Psi. Dissolution profiles of tablets of cocrystal increased (56% and 100% at pH 1.2 and 7.4, respectively in contrast to those of physical mixture (PhyMix) (∼35% and ∼10%) and pure LORX (∼17% and ∼7%) within 60 min. The Cmax and AUC0-∞ for the selected cocrystal were significantly increased (p < 0.05) which was 2.4 and 2.5 times, respectively, that of LORX in a single dose oral pharmacokinetic study executed in rabbits. Tablets of cocrystal were found stable at both conditions. CONCLUSION: The study indicates that cocrystallization with DMU can concomitantly improve tabletability, dissolution rate, and in vivo performance of dissolution limited drug LORX.

Physicomechanical, stability, and pharmacokinetic evaluation of aceclofenac dimethyl urea cocrystals.

Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties, aceclofenac (ACE) was cocrystallized with dimethyl urea (DMU) in 1:2 molar ratio by dry and solvent assisted grinding. The cocrystals were characterized by ATR-FTIR, DSC, and PXRD, and their surface morphology was studied by SEM. There was enhancement in intrinsic dissolution rate (IDR) (~eight- and ~fivefold in cocrystals prepared by solvent assisted grinding (SAG) and solid state grinding (SSG), respectively, in 0.1 N HCl, pH 1.2) and similarly (~3.42-fold and ~1.20-fold in phosphate buffer, pH 7.4) as compared to pure drug. Additionally, mechanical properties were assessed by tabletability curves. The tensile strength of ACE was < 1 MPa in contrast to the cocrystal tensile strength (3.5 MPa) which was ~1.98 times higher at 6000 psi. The tablet formulation of cocrystal by direct compression displayed enhanced dissolution profile (~36% in 0.1 N HCl, pH 1.2, and ~100% in phosphate buffer, pH 7.4) in comparison to physical mixture (~ 30% and ~ 80%) and ACE (~18% and ~50%) after 60 min, respectively. Stability studies of cocrystal tablets for 3 months indicated a stable formulation. Pharmacokinetic studies were performed by using rabbit model. The AUC0-∞ (37.87±1.3 µgh/ml) and Cmax (6.94±2.94 µg/ml) of the selected cocrystal C1 prepared by SAG were significantly enhanced (p < 0.05) and were ~3.43 and ~1.63-fold higher than that of ACE. In conclusion, new cocrystal of ACE-DMU was successfully prepared with improved tabletability, in vitro and in vivo properties.

Acute appendicitis: diagnostic accuracy of Alvarado scoring system.

OBJECTIVE: To evaluate the usefulness of the Alvarado scoring system in reducing the percentage of negative appendectomy in our unit. MATERIALS AND METHODS: A cross-sectional study was conducted, comprising 110 patients, admitted to Surgical Unit I, Civil Hospital, Karachi, in 2011 with a preliminary diagnosis of acute appendicitis. Patients of both sexes and all age groups except younger than 10 years were included in the study and their Alvarado scores calculated, on the basis of which patients were divided into two groups: Group A (Alvarado score <6) and Group B (Alvarado score ≥6). The signs, symptoms, laboratory values, surgical interventions, and pathology reports of each patient were evaluated. Diagnosis was confirmed by histopathological examination. Sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Out of 110 cases (79 males, 31 females), 31 belonged to Group A (28.2%) and 79 belonged to Group B (71.8%). Surgical procedures were performed in 98.2% of cases, along with conservative treatment. Final diagnosis by histopathology was confirmed in 77 cases (71.3%). The overall negative appendectomy rate was 28.7% (males: 28.2%, females: 30%). Sensitivity and specificity of the Alvarado scoring system were found to be 93.5% and 80.6% respectively. Positive and negative predictive values were 92.3% and 83.3%, respectively, and accuracy was 89.8%. CONCLUSION: Alvarado score can be used effectively in our setup to reduce the incidence of negative appendectomies. However, its role in females was not satisfactory and needs to be supplemented by other means.

Enteric fever in Karachi: current antibiotic susceptibility of Salmonellae isolates.

OBJECTIVE: To determine the current sensitivity and resistance profile of Salmonellae (S.) isolates in a laboratory setting. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Dr. Essa`s Laboratory and Diagnostic Centre, Karachi, Pakistan, from November 2008 - October 2010. METHODOLOGY: Isolates from blood culture specimens of 481 bacteraemic patients were identified using conventional biochemical tests. Salmonellae was confirmed with specific antisera and their antibiograms determined by Kirby-Bauer Disc Diffusion method using 12 relevant antibiotics. Inclusions of the study were bacteraemia documented in all blood samples positive for S. typhi, S. paratyphi-A and B. Exclusions were all samples other than blood and blood samples negative for S. typhi and S. paratyphi-A and B during the same period. Multidrug resistance (MDR) of isolates was defined as the isolates showing resistance to all conventional anti-typhoid medicines i.e., Chloramphenicol, Ampicillin and Co-trimoxazole. RESULTS: Specimens (n=217) yielded 131 Salmonellae typhi (60.36%), 71 S. paratyphi-A (32.71%), and 15 S. paratyphi-B (6.9%); these were sensitive to the Quinolones [Enoxacin: 94.96% (n=91), Ciprofloxacin, 96.47% (n=182), Ofloxacin: 95.74% (n=203)], and Cephalosporins [Cefixime: 96.62% (n=202), Cefotaxime: 99.17% (n=206), Ceftriaxone: 98.79% (n=208)]. Resistance to Amoxicillin was 96.48% (n=128) and 29.91% (n=78) to Co-trimoxazole. About 62.64% (n=136) of the isolates were MDR strains. CONCLUSION: Ciprofloxacin is currently a suitable empirical choice in presumed enteric fever cases, but culture and sensitivity analysis should be encouraged and results incorporated in prescription strategy. Increasing frequency of S. paratyphi-A isolates possibly suggests incomplete coverage employing monovalent vaccine.