Engineered microbubbles decorated with red emitting carbon nanoparticles for efficient delivery and imaging.

Altering the route of uptake by the cells is an attractive strategy to overcome drug-receptor adaptation problems. Carbon nanoparticles (CNPs) with emission beyond tissue autofluorescence for imaging biological tissues were used to study the phenomenon of uptake by the cells. In this regard, red-emitting carbon nanoparticles (CNPs) were synthesized and incorporated onto lipid microbubbles (MBs). The CNPs showed red emissions in the range of 640 nm upon excitation with 480 nm wavelength of light. Atomic force microscopic and confocal microscopic images showed the successful loading of CNPs onto the MB. Carbon nanoparticle loaded microbubbles (CNP-MBs) were treated with NIH 3 T3 cells at different concentrations. Confocal microscopic imaging studies confirm the presence of CNPs inside the treated cells. Cytotoxicity studies revealed that the CNPs showed minimal toxicity towards cells after loading onto MBs. The CNPs are usually taken up by the cells through the clathrin-mediated (CME) pathway, but when loaded onto MBs, the mechanism of uptake of CNPs is altered, and the uptake by the cells was observed even in the presence of inhibitors for the CME pathway. Loading CNPs onto MBs resulted in the uptake of CNPs by the cell through micropinocytosis and sonophoresis in the presence of ultrasound. The in vivo uptake CNP-MBs were performed in Danio rerio (Zebrafish larvae). This study provides insights into altering the uptake pathway through reformulation by loading nanoparticles onto MBs.

Self-regulated cobalt zinc ferrite system as a potential nanoplatform for the synergistic effect of hyperthermia-chemo agent for cancer therapy.

Magnetic hyperthermia (MH) has been studied for almost seventy-five years, but its efficacy in clinical applications is still fiercely contested. Despite this, few magnetic nanosystems are approved for clinical usage due to their strong affinity as drug carriers. The most important condition for hyperthermia applications for successful cancer therapy is magnetic nanoparticles with a controlled heating pattern (42-46 °C) for a prolonged timeframe. In the current study, cobalt-zinc nanoferrites (MNPs) having a Curie temperature of 46 â„ƒ with a tunable heating profile was loaded with Doxorubicin (DOX) through a surface conjugation technique (DOX-Cs-MNPs), and characterized by using multiple techniques. The magnetic hyterises (M-H) curves revealed the occurrence of superparamagnetism in the MNPs with extremely low coercivity; further, the DOX-loaded nanoparticles exhibited enhanced saturation magnetization. More importantly, the MNPs showed that they could maintain a therapeutic temperature for an indefinite amount of time. High drug loading affinity (86 %) was observed on MNPs with pH and temperature-controlled release. Under in vitro conditions, the biocompatible DOX-Cs-MNPs caused substantial apoptosis in MCF-7 cells (72 %) with overall cell death of < 95 %. The distinctive MNPs thus have the potential to be used in clinical applications.

Effect of pedicle screw placement into the fractured vertebra in management of unstable thoracolumbar and lumbar fractures.

BACKGROUND: Pedicle screw insertion at the level of the fractured vertebra has been shown to improve clinical and radiological outcomes in unstable thoracolumbar and lumbar fractures, albeit this requires further evidence. The study aims to evaluate the effect of pedicle screw placement on the fractured vertebra in such cases. METHODS: A prospective study included adult patients with thoracolumbar and lumbar fractures treated with short-segment posterior instrumentation with a pedicle screw into the fractured vertebra. Anterior vertebral body height loss, kyphotic angle and degree of spinal canal compromise were measured preoperatively and postoperatively in radiographs and CT scans. The neurological status was followed up for one year of the postoperative period. RESULTS: The study included a total of 30 patients. Five patients (16.7%) had grade C, three patients (10%) had grade D, and 22 patients (73.3%) had grade E neurological status. The mean (SD) preoperative kyphotic angle, vertebral body height and canal compromise were 5.54 (5.35), 39.67% (8.04), and 31.59% (10.62), respectively. Postoperatively there was a significant canal decompression, with a mean postoperative spinal canal compromise of 5.53% (SD=7.70; p-value <0.001). At the end of one year of follow-up, the radiological evaluation showed a correction of the kyphotic angle to 6.62 (SD=2.57; p-value <0.001), and the mean anterior vertebral body height was 70.38% (SD=11.25; p-value <0.001). At the end of one year, there was a significant overall neurological recovery with a final neurological status of grade D in 5 (16.7%) and grade E in 25 patients (83.3%). There was no significant association between canal decompression and neurology at the end of the one-year follow-up. CONCLUSION: Unstable thoracolumbar and lumbar fractures surgically treated with short-segment fixation with an additional intermediate screw can achieve significant restoration of vertebral body height and correction of kyphotic angle without any added complications.

NIR-Active Porphyrin-Decorated Lipid Microbubbles for Enhanced Therapeutic Activity Enabled by Photodynamic Effect and Ultrasound in 3D Tumor Models of Breast Cancer Cell Line and Zebrafish Larvae.

Porphyrin is known to enable the photodynamic effect during cancer drug delivery and molecular imaging. However, its hydrophobicity and tendency to aggregate in an aqueous medium create a significant hurdle for its use as an anticancer drug. Loading porphyrin onto biocompatible delivery vehicles can enhance its efficacy. This can be achieved by using gas-filled microbubbles that can be administered intravenously. This study aimed at developing near-infrared (NIR)-active porphyrin-loaded lipid microbubbles with anticancer activity enhanced by sonodynamic and photodynamic effects. The porphyrin-loaded microbubbles were studied for their cell toxicity, cellular uptake of porphyrin, and effect on cellular three-dimensional (3D) invasion of breast cancer cells (MDA-MB-231) in cellulo. Toxicity studies in zebrafish larvae (Danio rerio) in the presence and absence of photodynamic and sonodynamic therapy were also conducted. The results suggest that with a higher concentration of porphyrin loaded on microbubbles, the porphyrin-loaded microbubbles display a higher therapeutic effect facilitated by photodynamic and sonodynamic therapy, which results in enhanced cellular uptake and cellular toxicity. A lower concentration of loaded porphyrin microbubbles exhibits high cellular viability and good fluorescence intensity in the NIR region, which can be exploited for bioimaging applications.

Structural features regulated photoluminescence intensity and cell internalization of carbon and graphene quantum dots for bioimaging.

Carbon-based nanostructures with nanometer dimensions have been identified as potential photoluminescence probes for bioimaging due to their biocompatibility, tunable bandgap, and resistance to photobleaching. However, the influence of structural features of carbon quantum dots (CQDs) and graphene quantum dots (GQDs) in bioimaging has not been explored previously. In the present investigation, we elucidated the mechanism of higher PL in GQDs as compared to CQDs as a function of their structural features. TEM and AFM studies revealed that CQDs were spherical (size ~5 nm), while GQDs showed zigzag edges (size ~3 nm). Further, XRD and NMR studies confirmed that CQDs and GQDs show amorphous and crystalline structures with greater sp2 clusters, respectively. While both the QDs demonstrated multicolor fluorescence against variable excitations with similar lifetime, GQDs showed 7-fold higher QY than CQDs. Bioimaging studies in 2D cell culture, 3D tumoroids, and in vivo suggested a greater intensity of fluorescence in GQDs than CQDs. Additionally, rapid cell internalization was observed in GQDs owing to their positive surface potential by heterogeneous atomic (N and S) doping. Moreover, both CQDs and GQDs have demonstrated better time dependent stability for fluorescence properties. Taken together, the proposed mechanism elucidates the greater PL intensity in GQDs due to quantum confinement effect, crystallinity, and surface edge effects and is a better candidate for bioimaging amongst the carbon family.

Modified cerclage wiring in comminuted transolecranon fracture-dislocations of the elbow.

Transolecranon fracture-dislocations are a result of high-energy trauma, caused due to axial loading of the flexed forearm, with associated anterior dislocation of the ulna with respect to the distal humerus. The usual management of these comminuted and unstable fractures is by using locking compression plates via the dorsal approach. However, plating in cases of poor soft tissue coverage and open wounds can be precarious. In this study, we aimed to evaluate outcomes of cerclage wiring in the management of comminuted trans-olecranon fracture-dislocations in such scenario. A total of seven patients diagnosed with trans-olecranon fracture-dislocation with poor soft tissue coverage who underwent cerclage wiring were included in the study. The aim was to realign the proximal portion of the olecranon to the trochlea and restore the normal ulnohumeral articular relationships accomplished by the anatomical reconstruction of the greater sigmoid notch. Reconstruction of the proximal ulna was started from the distal to the proximal direction so as to convert an unstable fracture into a stable one. After the reduction of the proximal fragment, two long 2 mm K wires were inserted from the tip of the olecranon into the intramedullary canal (with at least 1 wire passed subchondrally), and later cerclage was done. Postoperatively the patient was immobilized for a duration of two weeks and was later started on active assisted mobilization of the elbow. All patients showed fair-to-excellent outcome on the Mayo elbow performance score (MEPS) at the final follow-up (five patients had an excellent score, one had a good score, and one had a fair score). At the final follow-up, the mean extension, flexion, pronation and supination were -20, 117.14, 82.85 and 78.57 degrees respectively. The key components of such management are the restoration of articular congruity, including continuity of the sigmoid cavity, ulnar length, and early initiation of active elbow movements to avoid joint stiffness. Optimal functional results can be achieved with K wire and cerclage when a stable anatomic reconstruction is accomplished, as a feasible alternative to plating.

Recurrent Ganglion Cyst In Peroneus Longus.

Ganglion cysts are benign cystic lesions that are lined by a synovium and are filled with a gelatinous mucoid material. Ganglion cysts are most commonly located in the hand and the wrist. We present a rare case report of a 45-year-old male with a recurrent intramuscular ganglion cyst in the peroneus longus for two years. The patient underwent drainage one year back, but the swelling recurred one month after surgery. Magnetic resonance imaging showed a delineated, round, lobulated fluid collection consistent with the appearance of a ganglion cyst that was present within the proximal part of peroneus longus. Surgical exploration revealed an encapsulated mass present within the peroneus longus muscle belly. The complete excision of the ganglion cyst was performed, and the diagnosis was confirmed by histology. Postoperatively, at a two-month and six-month follow-up, he was completely asymptomatic with no recurrence and a normal neurological function. Ganglion, which arises from the peroneus longus muscle or tendon, presents with swelling over the lateral aspect of leg due to compression of the common peroneal nerve. Careful preservation of the nerve with complete ganglion excision gives excellent results.

An Unusual Complex Posterolateral Osteoligamentous Injury of the Knee in an Adolescent.

We present an unusual and complex case of a 16-year-old adolescent male who injured his right knee and sustained combined avulsion injuries of posterior cruciate ligament (PCL) at the tibial insertion site, iliotibial band at lateral tibial condyle, and lateral collateral ligament (LCL) at femoral insertion site akin to osteoligamentous posterolateral corner injury. Anatomical reduction of the femoral LCL avulsion fragment was performed and fixed with a two 4-mm partially threaded cancellous screw. Iliotibial band avulsion was buttressed using Ellis t-plate and fixed with two 4-mm partially threaded cancellous screws. PCL avulsion fracture was conservatively treated owing to minimal displacement. At one-year follow-up, the patient was pain free with a range of motion of 0 to 150 degrees of flexion and had a pain free knee with no instability. Posterolateral corner injury in the patient was very significant as it involved LCL avulsion and iliotibial band avulsion, both of which are part of the posterolateral structures of the knee and also involve the growth plate. Fixation of the avulsion of Gerdy's tubercle with the buttress plate helps to provide additional stability to counteract the deforming forces of the iliotibial band. LCL is also the major stabilizer against varus forces, and hence fixation is required for stability while preventing growth disturbance. PCL avulsion can be treated conservatively in those patients where the fragment is undisplaced or minimally displaced. A good outcome can be achieved in skeletally immature patients who have osteoligamentous posterolateral corner injuries with associated avulsion fractures by using appropriate anatomical reduction and surgical fixation.