Development of nanoemulgel of 5-Fluorouracil for skin melanoma using glycyrrhizin as a penetration enhancer.

The purpose of this study was to enhance the topical delivery of 5-Fluorouracil (5-FU), a cancer treatment, by developing a nanoemulgel formulation. Glycyrrhizin (GLY), a natural penetration enhancer has been investigated to exhibit synergistic effects with 5-FU in inhibiting melanoma cell proliferation and inducing apoptosis, Hence, GLY, along with suitable lipids was utilized to create an optimized nanoemulsion (NE) based gel. Solubility studies and ternary phase diagram revealed isopropyl myristate (IPM), Span 80, Tween 80 as Smix and Transcutol P as co-surfactant. IPM demonstrates excellent solubilizing properties facilitates higher drug loading, ensuring efficient delivery to the target site.,The optimized formulation consisting of 40 % IPM, 30 % of mixture of Tween80: Span80 (Smix) and 15 % Transcutol P provides with a nanometric size of 64.1 ± 5.13 nm and drug loading of 97.3 ± 5.83 %. The optimized formulation observed with no creaming and breakeing of NE and found thermodynamically stable during different stress conditions (temperatures of 4.0 °C and 45.0 °C) and physical thawing (-21.0 ± 0.50 °C to 20.0 ± 0.50 °C). The NE was then transformed into a nanoemulgel (NEG) using 1.5 % w/w Carbopol base and 0.1 % w/w glycyrrhizin. The ex vivo permeability studies showed significant enhancements in drug permeability with the GLY-based 5-FU-NEG formulation compared to pure 5-FU gel in excised pig skin upto1440 min in PBS 7.4 as receptor media. The IC50 values for Plain 5-FU gel, 5-FU-NEG, and GLY-based 5-FU-NEG were found to be 20 µg/mL, 1.1 µg/mL, and 0.1 µg/mL, respectively in B16F10 cell lines. The percentage intracellular uptake of GLY-5-FU-NEG and 5-FU-NEG was found to be 44.3 % and 53.6 %, respectively. GLY-based 5-FU-NEG formulation showed alterations in cell cycle distribution, in compared to 5-FU-NE gel. The overall findings suggest that the GLY-based 5-FU-NEG holds promise for improving anti-melanoma activity.

A Critical Appraisal of Functionalized 2-Dimensional Carbon-Based Nanomaterials for Drug Delivery Applications.

The development of an efficient and innovative drug delivery system is essential to improve the pharmacological parameters of the medicinal compound or drug. The technique or manner used to improve the pharmacological parameters plays a crucial role in the delivery system. In the current scenario, various drug delivery systems are available where nanotechnology has firmly established itself in the field of drug delivery. One of the most prevalent elements is carbon with its allotropic modifications such as graphene-based nanomaterials, carbon nanotubes, carbon dots, and carbon fullerenes, these nanomaterials offer notable physiochemical and biochemical properties for the delivery applications due to their smaller size, surface area, and ability to interact with the cells or tissues. The exceptional physicochemical properties of carbon-based 2D nanomaterials, such as graphene and carbon nanotubes, make them attractive candidates for drug delivery systems. These nanomaterials offer a large surface area, high drug loading capacity, and tunable surface chemistry, enabling efficient encapsulation, controlled release, and targeted delivery of therapeutic agents. These properties of the nanomaterials can be exploited for drug delivery applications, like assisting the target delivery of drugs and aiding combination molecular imaging. This review emphasizes the drug delivery system and the role of carbon-based nanomaterials in drug delivery systems. Carbon-based 2D nanomaterials present a wealth of opportunities for advanced drug delivery systems. Their exceptional properties and versatility offers great potential in improving therapeutic efficacy, minimizing side effects, and enabling personalized medicine.

COVID-19: Operational Measures from a Surgeon's Perspective.

Novel corona virus, named as SARS-Cov-2 is the seventh coronavirus causing Corona Virus Disease (COVID-19) in human. It is one of the very few rare events in history of mankind to affect public health at such an enormous scale globally. Whole world is on standstill with this outbreak, which was declared pandemic by WHO in March 2020. All healthcare workers and especially the ones working in vicinity of nasal/oral regions are high risk group to be infected by this airborne virus. Recently, a 62 years old ENT specialist Liang Wudong died while treating patients with COVID in Wuhan city. Numerous reports of health care workers getting infected while serving their patients are coming from all parts of world. As health care providers are struggling to ensure safety and survival of people, their own wellbeing and preventing further spread of infection is also their responsibility. As head and neck surgical specialties are uniquely vulnerable to infection transmission, this communication highlights various instructions and suggestions given by International & National health agencies to safeguard the patient, surgical team, health workers and community. Though the decision regarding treatment is surgeon's discretion, we hope these guidelines will help in decision making.

Correction to: Retransplantation after post transplant lymphoproliferative disorder: overcoming the obstacles!

In the original publication of the article, while submitting the case report.

The Effect of Bariatric Surgery on Patients with Chronic Kidney Disease.

The effect of bariatric surgery on renal functions of patients with chronic kidney disease (CKD) is not well characterized. This prospective study included 13 adult patients having chronic kidney disease who underwent bariatric surgery. The primary objective was to examine the change in glomerular filtration rate (GFR) at 6 months post-bariatric surgery. Median GFR (measured by creatinine clearance) did not change significantly (55 ml/min vs 59 ml/min, p = 0.345) although there was a significant decrease in the protein excretion rate (1700 mg/day vs 900 mg/day, p = 0.001) at 6 months. An improvement in the KDIGO CKD risk category was seen in 30.7% patients. In CKD patients undergoing bariatric surgery, renal function improves over the first 6 months with a decrease in proteinuria and a stable GFR.

Three-Dimensional Bioprinting: Role in Craniomaxillary Surgery Ethics and Future.

Three-dimensional (3D) printing and bioprinting is gaining lot of momentum, especially in surgical specialties. These two technologies have wide array of applications in presurgical, surgical, and in vitro scenarios. Bioprinting can generate customized patient specific tissue engineered from specialized cells. This technology can be a gold standard in reconstructive and regenerative surgeries, if used in regulated and ethical environment. This communication focuses on basics of these technologies, their role in surgical specialties, ethical issues specific to these technologies, and its future.

Rare Occurrence of PLA2R-Positive Membranous Nephropathy in a Patient with Sjogren's Syndrome and CIDP.

Membranous nephropathy is known to be associated with number of autoimmune diseases. Occurrence of PLA2R positive membranous nephropathy with sjogren's syndrome and chronic inflammatory demyelinating neuropathy (CIDP) is quite rare. Role of PLA2R antigen in autoimmune diseases like sjogren's syndrome and CIDP is largely unknown. Choice and initiation of immunosuppression if required may also be governed by the presence of other autoimmune diseases along with PLA2R positive membranous nephropathy.

Retransplantation after post transplant lymphoproliferative disorder: overcoming the obstacles!

Post transplant lymphoproliferative disorder (PTLD) is a rare complication after kidney transplantation. Graft dysfunction is often encountered during the course of the treatment of PTLD, at times leading to need for retransplantation. We describe here the case of a young boy who underwent retransplantation after treatment of early Epstein Barr virus (EBV) related post transplant lymphoproliferative disorder. Our case highlights the various factors needing deliberation before retransplantation including time from remission of PTLD, EBV serostatus and choice of induction and maintenance immunosuppression agents.

Author Correction: Computationally designed antibody-drug conjugates self-assembled via affinity ligands.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tongue flap: a "workhorse flap" in repair of recurrent palatal fistulae.

AIM AND OBJECTIVE: A prospective study done to evaluate the efficacy of tongue flaps in secondary palatal defects, in terms of functionality, esthetics, and donor site morbidity, and to clarify the technique of elevating and insetting of tongue flap. MATERIALS AND METHOD: Twenty patients having recurrent secondary palatal fistula, post cleft treatment were treated with anteriorly and posteriorly based dorsal tongue flaps. Patients were evaluated for outcome in terms of flap uptake and effectiveness, correction of oronasal regurgitation, speech and articulation, donor site morbidity, and esthetics. RESULTS: Twenty patients in age range of 11-24 years, with secondary palatal fistulae, were treated with anteriorly/posteriorly based tongue flap. There were two recurrences as the flap got detached in one patient and necrosis of flap in another. In other patients, healing was uneventful. The flap showed good success rate in terms of uptake and correction of oronasal regurgitation, with imperceptible donor site morbidity. With speech therapy assistance and periodic evaluation by a therapist, significant improvement in speech and articulation was noted over time in all successfully healed patients. CONCLUSION: Use of tongue flap for repair of palatal fistulae is a successful technique as it provides appreciable quality and quantity of well-vascularized tissue for fistula closure with negligible functional and esthetic morbidity associated with donor site. As per our study, it is a reliable technique for palatal fistula closure. It even provides good speech improvement over time.

Computationally designed antibody-drug conjugates self-assembled via affinity ligands.

Antibody-drug conjugates (ADCs) combine the high specificity of antibodies with cytotoxic payloads. However, the present strategies for the synthesis of ADCs either yield unstable or heterogeneous products or involve complex processes. Here, we report a computational approach that leverages molecular docking and molecular dynamics simulations to design ADCs that self-assemble through the non-covalent binding of the antibody to a payload that we designed to act as an affinity ligand for specific conserved amino acid residues in the antibody. This method does not require modifications to the antibody structure and yields homogenous ADCs that form in less than 8 min. We show that two conjugates, which consist of hydrophilic and hydrophobic payloads conjugated to two different antibodies, retain the structure and binding properties of the antibody and its biological specificity, are stable in plasma and improve anti-tumour efficacy in mice with non-small cell lung tumour xenografts. The relative simplicity of the approach may facilitate the production of ADCs for the targeted delivery of cytotoxic payloads.

A safe and efficacious Pt(ii) anticancer prodrug: design, synthesis, in vitro efficacy, the role of carrier ligands and in vivo tumour growth inhibition.

Diaminocyclohexane-Pt(ii)-phenalenyl complexes (1 and 2) showed an appropriate balance between efficacy and toxicity. Compound 2 showed nearly two-fold higher tumour growth inhibition than oxaliplatin in a murine NSCLC tumour model, when a combined drug development approach was used. The fluorescent properties of phenalenone were utilized to understand the mechanistic details of the drug.

Modelling landscape dynamics with LST in protected areas of Western Ghats, Karnataka.

Forest ecosystems sustain biota on the earth as they are habitat to diverse biotic species, arrests soil erosion, play a crucial role in water cycle, sequester carbon, and helps in mitigating the impacts of global warming. Large scale land use land cover (LULC) change leading to deforestation is one of the drivers of global climate changes and alteration of biogeochemical cycles with significant consequences in ecosystem services and biodiversity. This has necessitated the investigation of LULC by mapping, monitoring and modelling spatio-temporal patterns and evaluating these in the context of human-environment interactions. The current work investigates LULC changes with temperature dynamics of select protected areas in Western Ghats. The land use analyses reveal changes in the forest cover across Kudremukh National Park (KNP), Rajiv Gandhi Tiger Reserve (RTR), Bandipur Tiger Reserve (BTR). KNP region has lost evergreen forest cover during 1973-2016 from 33.46 to 27.22%, while BTR lost deciduous cover from 61.69 to 47.3% due to mining, horticulture plantations, human habitations, etc. The LST increase has impacted regeneration of species with the induced water stress, etc. CA-Markov modelling was used for forecasting the likely land uses in 2026 and validation was done through Kappa indices. Results highlight decline of evergreen cover in KNP (9%) and deciduous cover in RTR (2%) followed by BTR (3%) with further expansion of plantations, which will impact biodiversity, hydrology and ecology. Insights of LULC dynamics help natural resource managers in evolving appropriate strategies to ensure conservation of threatened biota in Western Ghats.

Development of a facile antibody-drug conjugate platform for increased stability and homogeneity.

Despite the advances in the design of antibody-drug conjugates (ADCs), the search is still ongoing for novel approaches that lead to increased stability and homogeneity of the ADCs. We report, for the first time, an ADC platform technology using a platinum(ii)-based linker that can re-bridge the inter-chain cysteines in the antibody, post-reduction. The strong platinum-sulfur interaction improves the stability of the ADC when compared with a standard maleimide-linked ADC thereby reducing the linker-drug exchange with albumin significantly. Moreover, due to the precise conserved locations of cysteines, both homogeneity and site-specificity are simultaneously achieved. Additionally, we demonstrate that our ADCs exhibit increased anticancer efficacy in vitro and in vivo. The Pt-based ADCs can emerge as a simple and exciting proposition to address the limitations of the current ADC linker technologies.

Platelet rich fibrin: a novel approach for osseous regeneration.

UNLABELLED:  : To evaluate the efficacy of autologous platelet rich fibrin in soft tissue healing and bone regeneration in mandibular third molar extraction sockets. METHOD: The study was conducted in 20 patients visiting in outpatient department of Oral and Maxillofacial Surgery, requiring extraction of bilateral mandibular third molar, following extraction platelet rich fibrin (PRF) was placed in one extraction sockets, the other socket was studied as the control sites with no PRF. The patient were assessed for post operative pain, soft tissue healing and trabecular pattern in healing bone. Radiological assessment of the extraction site was done for period of 3 months to evaluate the change in bone density. RESULTS: Pain was less in study side compare to control site soft tissue was healing was better in study site. Evaluation of trabecular bone formation started earlier in PRF site compare to control site. The evaluation of bone density by radiological assessment showed the grey level value calculated after 3 months at the PRF site well comparatively higher than the average baseline value of the bone density at the extraction site in control site. CONCLUSION: The study showed that autologous PRF is biocompatible and has significantly improved soft tissue healing. Bone regeneration and increase in bone density in extraction sockets. However, a more elaborate study with a large number of clinical cases is essential to be more conclusive regarding its efficacy.

Comparison of circummandibular wiring with resorbable bone plates in pediatric mandibular fractures.

Pediatric patients present a unique challenge to maxillofacial surgeons in terms of their treatment planning as well as in their functional and nutritional needs which are different from that of adult patients. Early literature has advocated conservative closed management of pediatric fractures to prevent complications. However recent advances in maxillofacial surgery has enabled us to use biodegradable plates and screws, which overcomes the limitations of metallic plates. We present a comparison of two cases of parasymphysis fracture treated with circum-mandibular wiring and biodegradable plate fixation their outcome in terms of fracture healing and functional stability.

"Tension band wiring" a simplified approach for fracture reduction and intermittent stabilization.

INTRODUCTION: Development in plating systems and technical knowledge regarding the osteosynthesis has made open reductions and rigid internal fixation as the most frequently used mode of treatment in facial skeleton fractures. Various modalities for fracture reduction/stabilization during fixation have been mentioned in literature, describing the use of custom made instruments or reduction forceps etc. MATERIAL AND METHOD: We have used a method of "TENSION BAND WIRING" as a means of reducing and temporarily stabilizing the fracture segments in the mandible during rigid fixation. TENSION BAND WIRING method has been used in eighty patients having fractures in relation to mandibular symphysis, parasymphysis and body region. CONCLUSION: In our opinion, this method is quick, simple and effective way of achieving initial reduction and stabilization of bone prior to final rigid fixation. The added advantages are reduced operating time, reduced instrumentation and assistance which in turn provide clear and more accessible surgical field.