To Evaluate the Efficacy of Biomarkers as Monitoring Tool in Patients with Fascial Space Infections of Odontogenic Origin: A Clinical Study.

Introduction: The objective was to evaluate the efficacy of biochemical markers (WBC, CRP and fibrinogen) and the course of odontogenic space infections in 50 patients. Material and Methods: Blood samples were taken preoperatively and postoperatively at day 0, day 4, day 8 and day 12 for measuring the levels of all three biomarkers. The trends of the biomarkers were observed and compared with assessment parameters such as dental etiology, number of teeth involved, number of spaces involved, mouth opening and pain. Active pus discharge, dysphagia, hoarseness and swelling were assessed and scored accordingly. Results: The data were subjected to paired 't' test, McNemar's and Pearson's bivariate correlation as appropriate. Statistical analysis found strong correlation between laboratory values of markers and parameters used to measure severity of infection. All three biomarkers (WBC, CRP and fibrinogen) are significant markers for hospital stay (p < 0.01). Prospective analysis indicates that only one biomarker cannot be used to rule out specific diagnosis. Conclusion: The combination of three biochemical markers assessed in the present study (WBC, CRP and fibrinogen) should be used as prognostic factor in assessment, clinical severity and efficacy of treatment regime for patients as these can reliably predict the clinical course of odontogenic infection.

Post-COVID Fungal Osteomyelitis-Another Killer.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe as a pandemic. Based on a retrospective analysis of SARS data from worldwide, it is summarized that the fungal co-infections associated with global COVID-19 might be missed or misdiagnosed. Along with, we report case series of fungal infections in the maxilla and in the orbit, who were successfully treated for covid-19 and are on regular follow-up.

Activatable Nanoreporters for Real-Time Tracking of Macrophage Phenotypic States Associated with Disease Progression.

Diagnosis of inflammatory diseases is characterized by identifying symptoms, biomarkers, and imaging. However, conventional techniques lack the sensitivities and specificities to detect disease early. Here, it is demonstrated that the detection of macrophage phenotypes, from inflammatory M1 to alternatively activated M2 macrophages, corresponding to the disease state can be used to predict the prognosis of various diseases. Activatable nanoreporters that can longitudinally detect the presence of the enzyme Arginase 1, a hallmark of M2 macrophages, and nitric oxide, a hallmark of M1 macrophages are engineered, in real-time. Specifically, an M2 nanoreporter enables the early imaging of the progression of breast cancer as predicted by selectively detecting M2 macrophages in tumors. The M1 nanoreporter enables real-time imaging of the subcutaneous inflammatory response that rises from a local lipopolysccharide (LPS) administration. Finally, the M1-M2 dual nanoreporter is evaluated in a muscle injury model, where an initial inflammatory response is monitored by imaging M1 macrophages at the site of inflammation, followed by a resolution phase monitored by the imaging of infiltrated M2 macrophages involved in matrix regeneration and wound healing. It is anticipated that this set of macrophage nanoreporters may be utilized for early diagnosis and longitudinal monitoring of inflammatory responses in various disease models.

Structural Engineering of Star Block Biodegradable Polymer Unimolecular Micelles for Drug Delivery in Cancer Cells.

The present investigation reports the structural engineering of biodegradable star block polycaprolactone (PCL) to tailor-make aggregated micelles and unimolecular micelles to study their effect on drug delivery aspects in cancer cell lines. Fully PCL-based star block copolymers were designed by varying the arm numbers from two to eight while keeping the arm length constant throughout. Multifunctional initiators were exploited for stepwise solvent-free melt ring-opening polymerization of ε-caprolactone and γ-substituted caprolactone to construct star block copolymers having a PCL hydrophobic core and a carboxylic PCL hydrophilic shell, respectively. A higher arm number and a higher degree of branching in star polymers facilitated the formation of unimolecular micelles as opposed to the formation of conventional multimicellar aggregates in lower arm analogues. The dense core of the unimolecular micelles enabled them to load high amounts of the anticancer drug doxorubicin (DOX, ∼12-15%) compared to the aggregated micelles (∼3-4%). The star unimolecular micelle completely degraded leading to 90% release of the loaded drug upon treatment with the lysosomal esterase enzyme in vitro. The anticancer efficacies of these DOX-loaded unimolecular micelles were tested in a breast cancer cell line (MCF-7), and their IC50 values were found to be much lower compared to those of aggregated micelles. Time-dependent cellular uptake studies by confocal microscopy revealed that unimolecular micelles were readily taken up by the cells, and enhancement of the drug concentration was observed at the intracellular level up to 36 h. The present work opens new synthetic strategies for building a next-generation biodegradable unimolecular micellar nanoplatform for drug delivery in cancer research.

Fluorescent ABC-Triblock Polymer Nanocarrier for Cisplatin Delivery to Cancer Cells.

Monitoring intracellular administration of non-luminescent anticancer drugs like cisplatin is a very challenging task in cancer research. Perylenebisimide (PBI) chromophore tagged fluorescent ABC-triblock polycaprolactone (PCL) nanoscaffold was engineered having carboxylic acid blocks for the chemical conjugation of cisplatin at the core and hydrophilic PEG blocks at the periphery. The amphiphilic ABC triblock Pt-prodrug was self-assembled into <200 nm nanoparticles and exhibited excellent shielding against drug detoxification by the glutathione (GSH) species in the cytosol. In vitro drug release studies confirmed that the Pt-prodrug was stable at extracellular conditions and the PCL block exclusively underwent lysosomal-enzymatic biodegradation at the intracellular level to release the cisplatin drug in the active-form for accomplishing more than 90% cell growth inhibition. Confocal microscopic imaging of the red-fluorescence signals from the perylene chromophores established the simultaneous monitoring and delivery aspects of the Pt-prodrug, and the proof-of-concept was successfully demonstrated in breast and cervical cancer cell lines.

Biodegradable Polymer Theranostic Fluorescent Nanoprobe for Direct Visualization and Quantitative Determination of Antimicrobial Activity.

We report a biodegradable fluorescent theranostic nanoprobe design strategy for simultaneous visualization and quantitative determination of antibacterial activity for the treatment of bacterial infections. Cationic-charged polycaprolactone (PCL) was tailor-made through ring-opening polymerization methodology, and it was self-assembled into well-defined tiny 5.0 ± 0.1 nm aqueous nanoparticles (NPs) having a zeta potential of +45 mV. Excellent bactericidal activity at 10.0 ng/mL concentration was accomplished in Gram-negative bacterium Escherichia coli (E. coli) while maintaining their nonhemolytic nature in mice red blood cells (RBC) and their nontoxic trend in wild-type mouse embryonic fibroblast cells with a selectivity index of >104. Electron microscopic studies are evident of the E. coli membrane disruption mechanism by the cationic NP with respect to their high selectivity for antibacterial activity. Anionic biomarker 8-hydroxy-pyrene-1,3,6-trisulfonic acid (HPTS) was loaded in the cationic PCL NP via electrostatic interaction to yield a new fluorescent theranostic nanoprobe to accomplish both therapeutics and diagnostics together in a single nanosystem. The theranostic NP was readily degradable by a bacteria-secreted lipase enzyme as well as by lysosomal esterase enzymes at the intracellular compartments in <12 h and support their suitability for biomedical application. In the absence of bactericidal activity, the theranostic nanoprobe functions exclusively as a biomarker to exhibit strong green-fluorescent signals in live E. coli. Once it became active, the theranostic probe induces membrane disruption on E. coli, which enabled the costaining of nuclei by red fluorescent propidium iodide. As a result, live and dead bacteria could be visualized via green and orange signals (merging of red+green), respectively, during the course of the antibacterial activity by the theranostic probe. This has enabled the development of a new image-based fluorescence assay to directly visualize and quantitatively estimate the real-time antibacterial activity. Time-dependent bactericidal activity was coupled with selective photoexcitation in a confocal microscope to demonstrate the proof-of-concept of the working principle of a theranostic probe in E. coli. This new theranostic nanoprobe creates a new platform for the simultaneous probing and treating of bacterial infections in a single nanodesign, which is very useful for a long-term impact in healthcare applications.