Tramadol-Induced Fatal Angioedema: A Rare Case.

Angioedema is a non-pitting edema that involves the subcutaneous and submucosal layers of the face, lips, neck, oral cavity, larynx, and gut. It may become life-threatening when it involves tissues of the larynx. Angioedema can be triggered by exposure to drugs such as angiotensin-converting enzyme inhibitors (ACE inhibitors), opioid drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs). Tramadol is an opioid analgesic medication that may also induce angioedema, but the incidence of tramadol-induced angioedema is very rare in literature to date. It has been postulated that tramadol may cause fatal angioedema in the presence of underlying diseases such as systemic lupus erythematosus (SLE) or concomitant drugs such as NSAIDs. We describe the case of a patient with SLE who experienced fatal angioedema following tramadol intake.

Unravelling the mystery of the central dentinogenic ghost cell tumor- a rare case report and recurrent insights.

Dentinogenic ghost cell tumor (DGCT) is a rare benign neoplasm form of calcifying odontogenic cyst (COC) characterized by ghost cells. Although benign, it presents an aggressive behavior. DGCT accounts for 2% to 14% of all COCs and less than 0.5% of all odontogenic tumors. It is a benign odontogenic tumor despite its local invasion and the likelihood of recurrence. To detect recurrence, central DGCT patients must be monitored long-term. We present the case of a 51-year-old male who reported pain in the right upper back tooth region. On examination, a soft to firm, bright red swelling was present in the buccal vestibule and gingival margin of the maxillary right first and second molar, which extended up to the palate. Histopathological analysis confirmed the diagnosis of a DGCT, which occurred in a previously treated calcifying odontogenic cyst. The case is reported here, along with a review of the literature update of such recurred instances in the past.

Nanodroplets Engineered with Folate Carbon Dots for Enhanced Cancer Cell Uptake toward Theranostic Application.

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.

Evaluation of risk factors, clinico-radiographic presentations of COVID-associated mucormycosis in the maxillofacial region reporting to a tertiary care dental facility.

Purpose: To evaluate the prevalence of risk factors associated with COVID-associated mucormycosis (CAM) in the maxillofacial region with emphasis on clinical and radiological characteristics of the disease reporting to the dentists. Methods: Archival records of the patients diagnosed with rhino-cerebral mucormycosis through histopathology or culture, were screened and 266 records were included. These records were divided into three groups-previously diabetic (PD, n = 122), recently diagnosed diabetic (RD, n = 105) and non-diabetic (ND, n = 39). All the records were evaluated and compared among the three groups for the duration of presentation, history of co-existing medical conditions, the association of treatment given during COVID-19, and the clinical and radiographic presentations of the disease. Results: The results confirmed uncontrolled diabetes mellitus as the major risk factor for the disease. The prevalence of steroid administration was lower in our study in contrast to previous literature. The risk factors and treatment rendered during COVID-19 did not differ significantly among the three groups (p > 0.05). The findings indicate that the disease was milder and progressed more slowly in the ND group, both clinically and radiographically, and it had close resemblance to odontogenic infection. Conclusion: Patients with early CAM mimicked the odontogenic infection and were more likely to report in a dental setup. Hence, a multidisciplinary and holistic management approach is necessary.

Biomolecular Condensates Regulate Enzymatic Activity under a Crowded Milieu: Synchronization of Liquid-Liquid Phase Separation and Enzymatic Transformation.

Cellular crowding plays a key role in regulating the enzymatic reactivity in physiological conditions, which is challenging to realize in the dilute phase. Enzymes drive a wide range of complex metabolic reactions with high efficiency and selectivity under extremely heterogeneous and crowded cellular environments. However, the molecular interpretation behind the enhanced enzymatic reactivity under a crowded milieu is poorly understood. Herein, using the horseradish peroxidase (HRP) and glucose oxidase (GOx) cascade pair, we demonstrate for the first time that macromolecular crowding induces liquid-liquid phase separation (LLPS) via the formation of liquid-like condensates/droplets and thereby increases the intrinsic catalytic efficiencies of HRP and GOx. Both these enzymes undergo crowding induced homotypic LLPS via enthalpically driven multivalent electrostatic as well as hydrophobic interactions. Using a set of kinetic and microscopic experiments, we show that precise synchronization of spontaneous LLPS and enzymatic transformations is key to realize the enhanced enzymatic activity under the crowded environments. Our findings reveal an unprecedented enhancement (91- to 205-fold) in the catalytic efficiency (kcat/Km) of HRP at pH 4.0 within the droplet phase relative to that in the bulk aqueous phase in the presence of different crowders. In addition, we have shown that other enzymes also undergo spontaneous LLPS under macromolecular crowding, signifying the generality of this phenomenon under the crowded environments. More importantly, coalescence driven highly regulated GOx/HRP cascade reactions within the fused droplets have been demonstrated with enhanced activity and specificity under the crowded environments. The present discovery highlights the active role of membraneless condensates in regulating the enzymatic efficacy for complex metabolic reactions under the crowded cellular environments and may find significant importance in the field of biocatalysis.

Tenofovir-based first-line regimen in newly diagnosed HIV-patients: An experience from a Tertiary Care Hospital in India.

Introduction: India has a huge burden of HIV/AIDS infection. Tenofovir-based first-line therapy is the preferred treatment for newly diagnosed cases of HIV infection. Materials and Methods: The present prospective study was done among newly diagnosed cases of HIV infection. The patients were followed up for 6 months from the day of enrollment. Sociodemographic parameters, CD4 counts, and adverse drug reactions (ADRs) were analyzed at baseline and after 6 months. Bivariate and multivariate logistic regression was performed with the occurrence of ADRs as outcome variable. Results: In this study, 67 patients were enrolled with a mean age of 32.75 (±14.39) years. Mean CD4 count at the start of treatment was 241.5/mm3. The mean difference in CD4 count was 383.05/mm3 (standard deviation = 274.9). Dizziness, tingling, numbness of extremities, and muscle cramps were the most common adverse effects. On multivariate logistic regression, the occurrence of ADRs was seen to be significantly higher only in illiterate patients. Conclusion: The present study highlights the importance of long-term follow-up of the patients on antiretroviral therapy. Adequate monitoring of the treatment parameters is of utmost importance.

Synthetic Protocell as Efficient Bioreactor: Enzymatic Superactivity and Ultrasensitive Glucose Sensing in Urine.

It is believed that membraneless cellular condensates play a critical role in accelerating various slow and thermodynamically unfavorable biochemical processes. However, the exact mechanisms behind the enhanced activity within biocondensates remain poorly understood. Here, we report the fabrication of a high-performance integrated cascade bioplatform based on synthetic droplets for ultrasensitive glucose sensing. Using a horseradish peroxidase (HRP) and glucose oxidase (GOx) cascade pair, we report an unprecedented enhancement in the catalytic activity of HRP inside the synthetic membraneless droplet. Liquidlike membraneless droplets have been prepared via multivalent electrostatic interactions between adenosine triphosphate (ATP) and poly(diallyldimethylammonium chloride) (PDADMAC) in an aqueous medium. Compartmentalized enzymes (GOx/HRP@Droplet) exhibit high encapsulation efficiency, low leakage, prolong retention of activity, and exceptional stability toward protease digestion. Using an HRP@Droplet composite, we have shown that the enzymatic reaction within the droplet follows the classical Michaelis-Menten model. Our findings reveal remarkable enhancement in the catalytic activity of up to 100- and 51-fold for HRP@Droplet and GOx/HRP@Droplet, respectively. These enhanced activities have been explained on the basis of increased local concentrations of enzymes and substrates, along with altered conformations of sequestered enzymes. Furthermore, we have utilized highly efficient and recyclable GOx/HRP@Droplet composite to demonstrate ultrasensitive glucose sensing with a limit of detection of 228 nM. Finally, the composite platform has been exploited to detect glucose in spiked urine samples in solution and filter paper. Our present study illustrates the unprecedented activity of the compartmentalized enzymes and paves the way for next-generation composite bioreactors for a wide range of applications.

Macromolecular Crowding-Induced Unusual Liquid-Liquid Phase Separation of Human Serum Albumin via Soft Protein-Protein Interactions.

Macromolecular crowding has a profound impact on the conformational dynamics and intermolecular interactions of biological macromolecules. In this context, the role of inert synthetic crowders in the protein-protein interactions of globular proteins is poorly understood. Here, using native human serum albumin (HSA) under physiological conditions, we show that macromolecular crowding induces liquid-liquid phase separation (LLPS) via liquid-like membrane-less droplet formation in a concentration- and time-dependent manner. Circular dichroism measurements reveal significant alteration in the secondary structure of HSA inside the droplet during aging. In contrast, at a high protein concentration, a liquid-to-solid-like phase transition has been observed upon maturation. Our findings reveal that the LLPS of HSA is mainly driven by enthalpically controlled intermolecular protein-protein interactions via hydrophobic contacts involving aromatic and/or nonaromatic residues. Moreover, modulation of LLPS of HSA has been demonstrated upon denaturation and ligand binding. This study highlights the importance of soft protein-protein interactions of globular proteins in a crowded cellular environment in driving the LLPS.

Kinetic and Mechanistic Insight into the Surfactant-Induced Aggregation of Gold Nanoparticles and Their Catalytic Efficacy: Importance of Surface Restructuring.

Understanding the fundamental interactions between plasmonic metal nanoparticles (MNPs) and small molecules is of utmost importance in various applications such as catalysis, sensing, drug delivery, optoelectronics, and surface-enhanced Raman spectroscopy. Herein, we have investigated the early stage of the aggregation pathway of citrate-stabilized Au NPs with surfactants and explored their catalytic efficacy. Our findings reveal that (17 ± 2)-nm-sized citrate-stabilized Au NPs undergo concentration and time-dependent aggregation with positively charged cetyltrimethylammonium bromide (CTAB). Kinetic analyses revealed the presence of two distinct kinds of aggregates, namely, smaller clusters and a larger branched network of Au nanochains. At longer times and in the presence of higher concentrations of CTAB, these branched networks of Au nanochains transform into dense compact globular aggregates. The catalytic efficacy of Au NPs, branched Au nanochains, and dense compact aggregates has been explored with respect to the reductive hydrogenation of 4-nitophenol in the presence of excess NaBH4. Our study revealed that the catalytic rate decreases in the order of Au NPs > branched Au nanochains > compact aggregates. Interestingly, pre-equilibrating different Au NP samples with excess NaBH4 prior to the onset of the reaction results in similar catalytic activity irrespective of the aggregation state of Au NPs. This observation has been explained by considering efficient surface restructuring via ligand exchange with H- ions and the subsequent disruption of CTAB-induced aggregates of Au NPs. Moreover, the aggregated Au NPs can be recycled over several consecutive cycles for the reductive hydrogenation of 4-NP upon ligand exchange with H- ions. Taken together, our present study highlights the early-stage aggregation kinetics of Au NPs with CTAB surfactants and demonstrates the importance of the surface restructuring of Au NPs on their catalytic efficacy.

Nanocatalysis under Nanoconfinement: A Metal-Free Hybrid Coacervate Nanodroplet as a Catalytic Nanoreactor for Efficient Redox and Photocatalytic Reactions.

Nature utilizes cellular and subcellular compartmentalization to efficiently drive various complex enzymatic transformations via spatiotemporal control. In this context, designing of artificial nanoreactors for efficient catalytic transformations finds tremendous importance in recent times. One key challenge remains the design of multiple catalytic centers within the confined space of a nanoreactor without unwanted agglomeration and accessibility barrier for reactants. Herein, we report a unique blend of nanoscience and chemical catalysis using a metal-free hybrid synthetic protocell as a catalytic nanoreactor for redox and photocatalytic transformations, which are otherwise incompatible in bulk aqueous medium. Hybrid coacervate nanodroplets (NDs) fabricated from 2.5 nm-sized carbon dots (CDs) and poly(diallyldimethyl)ammonium chloride have been utilized toward reductive hydrogenation of nitroarenes in the presence of sodium borohydride (NaBH4). It has been found that the reduction mechanism follows the classical Langmuir-Hinshelwood (LH) model at the surface of embedded CDs inside the NDs via the generation of reactive surface hydroxyl groups. These NDs show excellent recyclability without any compromise on reaction kinetics and conversion yield. Importantly, spatiotemporal control over the hydrogenation reaction has been achieved using two mixed populations of coacervates. Moreover, efficient visible light-induced photoredox conversion of ferricyanide to ferrocyanide and artificial peroxidase-like activity have also been demonstrated inside these catalytic NDs. Our findings indicate that the individual polymer-bound CD inside the NDs acts as the catalytic center for both the redox and photocatalytic reactions. The present study highlights the unprecedented catalytic activity of the metal-free CD-based coacervate NDs and paves the way for next-generation catalytic nanoreactors for a wide range of chemical and enzymatic transformations.