Exploring the Biofilm Inhibition Potential of a Novel Phytic Acid-Crosslinked Chitosan Nanoparticle: In Vitro and In Vivo Investigations.

The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.

Implementation of Silver Nanoparticles Green Synthesized with Leaf Extract of Coccinia grandis as Antimicrobial Agents Against Head and Neck Infection MDR Pathogens.

BACKGROUND: Head and neck infections (HNI) associated with multidrug resistance (MDR) offer several health issues on a global scale due to inaccurate diagnosis. OBJECTIVES: This study aimed to identify the bacteria and Candidal isolates and implement the silver nanoparticles green synthesized with leaf extract of Coccinia grandis (Cg-AgNPs) as a therapeutic approach against HNI pathogens. METHODS: The Cg-AgNPs were characterized by the UV-visible spectrophotometer, FT-IR analysis, Zeta particle size, Zeta potential, and field emission scanning electron microscope (FESEM) analysis to validate the synthesis of nanoparticles. Additionally, the antimicrobial activity of Cg-AgNPs was presented by the zone of inhibition (ZOI), minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and antibiofilm assay. Moreover, the cell wall rupture assay was visualized on SEM for the morphological study of antimicrobial activities, and the in-vivo toxicity was performed in a swiss mice model to evaluate the impact of Cg-AgNPs on various biological parameters. RESULTS: Different bacterial strains (Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Candida sp. (Candida albicans, Candida tropicalis, Candida orthopsilosis, and Candida glabrata) were identified. The MIC, MBC, and antibiofilm potential of Cg-AgNPs were found to be highest against A. baumannii: 1.25 µg/ml, 5 µg/ml, and 85.01±5.19% respectively. However, C. albicans and C. orthopsilosis revealed 23mm and 21mm of ZOI. Subsequently, the micromorphology of the cell wall rupture assay confirmed the efficacy of Cg-AgNPs, and no significant alterations were seen in biochemical and hematological parameters on the swiss mice model in both acute and subacute toxicity studies. CONCLUSION: The green synthesized Cg-AgNPs have multifunctional activities like antibacterial, anticandidal, and antibiofilm activity with no toxicity and can be introduced against the HNI pathogens.

Development and Evaluation of Dutasteride Nanoemulgel for the Topical Delivery against Androgenic Alopecia.

BACKGROUND: Dutasteride is approximately three times more potent than finasteride in treating alopecia. For reducing systemic exposure to dihydrotestosterone (DHT), researchers have shown special interest in developing topical formulations for treating androgenic alopecia. Dutasteride emulsification may lead to good skin penetration and improved availability in different lipophilic skin environments. OBJECTIVES: This study aimed to encapsulate the drug into the lipidic carrier system for better local availability in the scalp skin, develop and evaluate nanoemulgel of dutasteride to ensure efficient topical administration, and perform the in-vivo activity of the developed gel for improved efficacy against alopecia. METHODS: Dutasteride-loaded nanoemulsion was prepared by a high-speed homogenizer, followed by thickening of the dispersion using Carbopol 934. Skin permeation and accumulation were investigated in the excised skin of male Swiss albino mice. The nanoemulgel was characterized based on pH, stress stability, viscosity, and hardness. RESULTS: The optimized dutasteride-loaded nanoemulsion had a size of 252.33 ± 8.59 nm, PDI of 0.205 ± 0.60, and drug content of 98.65 ± 1.78%. Stress stability was performed was well observed in nanoemulsion formulation. Nanoemulgel evaluation results were as follows: pH 5-6 was desirable for topical application, hardness was 43 gm, and spreadability was 79 gm with in vitro release of nanoemulgel at 91.98% and permeation study at 13.67%. CONCLUSION: The in vivo studies demonstrated the growth of newer hair follicles and increased hair diameter and length in dutasteride-loaded nanoemulgel-treated alopecia animals compared to the marketed sample and testosterone-treated group. Provided with the same and long-term storage stability, the developed formulation is supposed to offer a good option for the topical administration of dutasteride in treating androgenic alopecia.

Role of Textural Analysis of Pretreatment 18F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Prediction in Esophageal Carcinoma Patients.

Introduction: Positron emission tomography/computed tomography (PET/CT) is routinely used for staging, response assessment, and surveillance in esophageal carcinoma patients. The aim of this study was to investigate whether textural features of pretreatment 18F-fluorodeoxyglucose (18F-FDG) PET/CT images can contribute to prognosis prediction in carcinoma oesophagus patients. Materials and Methods: This is a retrospective study of 30 diagnosed carcinoma esophagus patients. These patients underwent pretreatment 18F-FDG PET/CT for staging. The images were processed in a commercially available textural analysis software. Region of interest was drawn over primary tumor with a 40% threshold and was processed further to derive 92 textural and radiomic parameters. These parameters were then compared between progression group and nonprogression group. The original dataset was subject separately to receiver operating curve analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff values for textural features with a P < 0.05 for statistical significance. Feature selection was done with principal component analysis. The selected features of each evaluator were subject to 4 machine-learning algorithms. The highest area under the curve (AUC) values was selected for 10 features. Results: A retrospective study of 30 primary carcinoma esophagus patients was done. Patients were followed up after chemo-radiotherapy and they underwent follow-up PET/CT. On the basis of their response, patients were divided into progression group and nonprogression group. Among them, 15 patients showed disease progression and 15 patients were in the nonprogression group. Ten textural analysis parameters turned out to be significant in the prediction of disease progression. Cutoff values were calculated for these parameters according to the ROC curves, GLZLM_long zone emphasis (Gray Level Zone Length Matrix)_long zone emphasis (44.9), GLZLM_low gray level zone emphasis (0.006), GLZLM_short zone low gray level emphasis (0.0032), GLZLM_long zone low gray level emphasis (0.185), GLRLM_long run emphasis (Gray Level Run Length Matrix) (1.31), GLRLM_low gray level run emphasis (0.0058), GLRLM_short run low gray level emphasis (0.005496), GLRLM_long run low gray level emphasis (0.00727), NGLDM_Busyness (Neighborhood Gray Level Difference Matrix) (0.75), and gray level co-occurrence matrix_homogeneity (0.37). Feature selection by principal components analysis and feature classification by the K-nearest neighbor machine-learning model using independent training and test samples yielded the overall highest AUC. Conclusions: Textural analysis parameters could provide prognostic information in carcinoma esophagus patients. Larger multicenter studies are needed for better clinical prognostication of these parameters.

Role of textural analysis parameters derived from FDG PET/CT in differentiating hepatocellular carcinoma and hepatic metastases.

INTRODUCTION: Texture and radiomic analysis characterize the tumor's phenotype and evaluate its microenvironment in quantitative terms. The aim of this study was to investigate the role of textural features of 18F-FDG PET/computed tomography (CT) images in differentiating hepatocellular carcinoma (HCC) and hepatic metastasis in patients with suspected liver tumors. METHODS: This is a retrospective, single-center study of 30 patients who underwent FDG PET/CT for the characterization of liver lesions or for staging a suspected liver tumor. The histological diagnosis of either primary or metastatic tumor was obtained from CT-guided biopsy, ultrasound-guided biopsy, or surgical removal of a liver lesion. The PET/CT images were then processed in commercially available textural analysis software. Region of interest was drawn over the primary tumor with a 40% threshold and was processed further to derive 42 textural and radiomic parameters. These parameters were then compared between HCC group and hepatic metastases group. Receiver-operating characteristic (ROC) curves were used to identify cutoff values for textural features with a P value <0.05 for statistical significance. RESULTS: A retrospective study of 30 patients with suspected liver tumors was done. After undergoing PET/CT, the histological diagnosis of these lesions was confirmed. Among these 30 patients, 15 patients had HCC, and 15 patients had hepatic metastases from various primary sites. Seven textural analysis parameters were significant in differentiating HCC from liver metastasis. Cutoff values were calculated for these parameters according to the ROC curves, standardized uptake value (SUV) Skewness (0.705), SUV Kurtosis (3.65), SUV Excess Kurtosis (0.653), gray-level zone length matrix_long zone emphasis (349.2), gray-level zone length matrix_long zone low gray-level emphasis (1.6), gray-level run length matrix_long run emphasis (1.38) and gray-level co-occurrence matrix_Homogeneity (0.406). CONCLUSION: Textural analysis parameters could successfully differentiate HCC and hepatic metastasis non-invasively. Larger multi-center studies are needed for better clinical prognostication of these parameters.

Recent Advances in Chemical Composition and Transdermal Delivery Systems for Topical Bio-actives in Skin Cancer.

Skin cancer, including basal cell carcinoma, melanoma, and squamous cell carcinoma, is conventionally treated by surgery, phototherapy, immunotherapy, and chemotherapy. For decades, surgical removal of malignant cancers has favored patients' therapeutic options. However, multiple aspects, such as the patient's comorbidities, the anatomical location of the lesion, and possible resistance to recurrent excisions, can influence the decision to conduct surgery. Therefore, topical and transdermal therapy may be a more appropriate option, allowing for higher therapeutic levels at the site of action and reducing toxicity than systemic therapy. The most commonly used topical agents for treating skin carcinoma are- 5-fluorouracil, imiquimod, sonidegib, dacarbazine, etc. However, physicochemical drug characteristics and skin physiological barriers limit the anticancer potency of topical as well as transdermal drug delivery. In recent years, unquestionable signs of progress have been demonstrated to circumvent these challenges. In particular, significant studies have been made, including modification of bio-actives, permeability enhancers, incorporation of advanced nano and microcarriers, and physical enhancement devices. This critical review summarizes the advancement in the chemical composition of bioactives used in skin cancer, such as sinecatechins, BIL-010t, patidegib, gingerol, curcumin, remetinostat, epigallocatechin-3-gallate, etc. Furthermore, this review specifically addresses the progress in transdermal delivery systems for melanoma and nonmelanoma cancer therapy, emphasizing advances in physical and chemical penetration enhancement and nanocarrier-assisted transdermal systems.

Metal nanoparticles against multi-drug-resistance bacteria.

Antimicrobial-resistant (AMR) bacterial infections remain a significant public health concern. The situation is exacerbated by the rapid development of bacterial resistance to currently available antimicrobials. Metal nanoparticles represent a new perspective in treating AMR due to their unique mechanisms, such as disrupting bacterial cell membrane potential and integrity, biofilm inhibition, reactive oxygen species (ROS) formation, enhancing host immune responses, and inhibiting RNA and protein synthesis by inducing intracellular processes. Metal nanoparticles (MNPs) properties such as size, shape, surface functionalization, surface charges, and co-encapsulated drug delivery capability all play a role in determining their potential against multidrug-resistant bacterial infections. Silver, gold, zinc oxide, selenium, copper, cobalt, and iron oxide nanoparticles have recently been studied extensively against multidrug-resistant bacterial infections. This review aims to provide insight into the size, shape, surface properties, and co-encapsulation of various MNPs in managing multidrug-resistant bacterial infections.

Subpial en bloc resection improves extent of resection in infiltrating gliomas - A propensity matched comparative cohort analysis.

BACKGROUND: Surgery remains the mainstay of glioma therapy and extent of resection is an important prognostic factor. Optimization of surgical outcomes is essential and to this end the technique of resection can potentially play an important role. Based on patterns of glioma growth and extrapolating from other solid cancer surgical principles, a subpial dissection combined with an en-bloc resection (SPER) technique appears to have advantages METHODS: We performed a propensity matched analysis comparing gliomas that were resected using SPER versus a standard piecemeal debulking technique at our centre. Potentially confounding factors (including eloquent location, use of intraoperative imaging, surgeon experience) were adjusted for in the matching of the two cohorts. Outcomes included postoperative morbidity and blinded radiological review documented postoperative ischemia (on diffusion weighted MR imaging - DWI) as well as extent of resection. RESULTS: In 57 gliomas (23 SPER and 34 standard), the gross total resection (GTR) rates were significantly higher with SPER (91 vs 65%). Postoperative DWI revealed significant ischemia in almost 50% of cases in either group, though many did not have postoperative deficits. Arterial ischemia was higher in the standard surgery group and this was associated with a significantly higher risk (seven times) of resulting in prolonged neurological deficits. CONCLUSIONS: SPER is a useful technique which increases the GTR rates in gliomas undergoing resection. It is associated with lower incidence of arterial ischemia in the postoperative period and this can result in improved long term functional outcomes.

Paediatric chronic subdural haematoma: what are the predisposing factors and outcomes in management of these cases?

INTRODUCTION: Chronic subdural hematoma (cSDH) is a disease of the elderly population. Incidence in paediatric population is relatively uncommon. Child abuse, birth trauma, coagulopathy and shunt surgeries represent major causes. Major impact of the disease on life of patient due to recurrence and repeat surgical procedure is significant, not to mention the burden on health care system. MATERIAL AND METHODS: We retrospectively reviewed our institute data for chronic sub-dural cases for the past 10 years (2008-2018) and collected data on the demography, clinical features, metabolic workup, mode of treatment, recurrence rates, predisposing factors, laterality, hematoma characteristics and factors associated with recurrence in all cases with less than or equal to 18 years of age. RESULTS: A total of 30 such cases were found in a period of 10 years (2008-2018). The mean patient age was 7.3 years (range 2 months-17 years), with 20 males (66.67%) and 10 females (33.33%). Raised intracranial pressure (n = 9) was the commonest presenting symptom in 30% of cases followed by seizures in 26.67% (n = 8). The previous shunt was the commonest predisposing factor seen in 43.33% (n = 13). cSDHs were unilateral in 56.67% cases (n = 17) and bilateral in 43.33% (n = 13). Burr hole craniostomy was done in 27 cases (90%), and conservative management was done in three cases (10%). Follow up was available for 27 cases (90%) with a mean follow up duration of 24 months. Recurrence rate was 30% (n = 9). Shunt surgery contributed to 77% of bilateral disease (p = 0.009). Child abuse was not reported in our series. CONCLUSION: Presence of paediatric cSDH is alarming, and the physician should be alerted to look for underlying cause and rule out child abuse. Detailed metabolic, skeletal workup is required. Treatment of primary pathology should be the goal as CSF diversion is not the solution to all problems, but can definitely be the cause of all the problems.

Primary Biliary Tuberculosis Masquerading Cholangiocarcinoma in 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Hepatobiliary involvement is a less common manifestation of abdominal tuberculosis. We present the case of a 42-year-old female who presented with fever, abdominal pain, and jaundice of 2 months duration. 18F-fluorodeoxyglucose positron emission tomography/computed tomography done for disease evaluation suggested the likely possibility of cholangiocarcinoma but excision biopsy from periportal lymph node later confirmed a granulomatous etiology and she was successfully treated with antitubercular therapy.

Tetrad of Split Cord Malformation I with Neuroenteric Cyst, Dermoid Cyst, and Thickened Filum Terminale in a 2-Year-Old Child: A Case Report.

INTRODUCTION: Split cord malformations (SCMs) are developmental anomalies that are associated with a number of congenital defects. However, a combination of SCM I with a neuroenteric cyst (NEC) is extremely rare, and only 11 cases have been described in the literature. To the best of authors' knowledge, the combination of the above two with dermoid cyst and thickened filum terminale has never been reported in the literature. CASE PRESENTATION: We present a case of the above combination in a 2-year-old child who underwent microsurgical excision of all 4 pathologies and complete recovery. CONCLUSION: NEC and dermoid should be considered in the differential diagnosis when imaging reveals cystic pathology along with SCM. Expeditious surgical repair resulted in an outstanding functional outcome at 1-year follow-up.

Incidentally Diagnosed Esophago-Pulmonary Fistula on 18F-FDG PET/CT in a Case of Carcinoma Esophagus: A Life-Threatening Emergency.

ABSTRACT: Esophago-pulmonary fistulas are very less reported in literature. 18F-FDG PET/CT scan is routinely used for evaluation of patients of carcinoma esophagus. We present a case of carcinoma esophagus with acquired esophago-pulmonary fistula diagnosed on 18F-FDG PET/CT scan.

Microsurgical subpial resections for diffuse gliomas-old wine in a new bottle.

BACKGROUND: Maximizing resection is an oft-sought-after albeit challenging goal in diffuse gliomas. Microsurgical technique remains the mainstay. METHOD: By virtue of their pattern of growth and spread, gliomas respect anatomical boundaries like the pia. Using subpial dissection, en bloc resections provide the most optimal surgical technique. This paper revisits this technique and describes the rationale and basic principles integrating it in the modern multimodal glioma surgery workflow. CONCLUSION: Subpial resection is a very useful and "anatomical" technique for en bloc resection of diffuse gliomas which is easy to master and execute and optimizes the extent of resection and minimizes complications effectively.

Navigated intraoperative ultrasonography for brain tumors: a pictorial essay on the technique, its utility, and its benefits in neuro-oncology.

Intraoperative imaging has become one of the most important adjuncts in neurosurgery, especially in the surgical treatment of intra-axial tumors. Navigation and intraoperative magnetic resonance imaging have limitations, and intraoperative ultrasonography (IOUS) has emerged as a versatile and multifaceted alternative. With technological advances in ultrasound scanners and newer multifunctional probes, the potential of IOUS is increasingly being utilized in the resection of tumors. The addition of image guidance to IOUS has exponentially increased the power of this technique. Navigated ultrasonography (nUS) can now overcome many of the limitations of conventional standalone two-dimensional ultrasonography. In this pictorial essay, we outline our nUS technique (both two- and three-dimensional) for the resection of intra-axial tumors with illustrated examples highlighting the various steps and corresponding benefits of the technique.

Bilateral anomalous origin of ophthalmic artery from middle meningeal artery and coincidence of bilateral carotid artery aneurysm: Case report and literature review.

Ophthalmic artery (OA) is known for anomalous origin and aberrant course probably attributable to its complex embryology. Anomalous origin of OA can be associated with intracranial aneurysm. Anomalous origins have been reported from middle meningeal artery (MMA), cavernous carotid, posterior communicating, anterior cerebral and basilar artery. Even though bilateral anomalous origin of OA from MMA is a rare finding, to the author's best knowledge, association of above condition with bilateral internal carotid artery aneurysms has not been described in the literature. We present a case of such anomalous bilateral OA originating from MMA and associated with bilateral internal carotid artery aneurysms. We have also reviewed the pertinent literature regarding anomalous OA origin.

Role of repeat CT in mild to moderate head injury: an institutional study.

OBJECTIVE: Patients with traumatic brain injury (TBI) often undergo repeat head CT scans to identify the possible progression of injury. The objective of this study is to evaluate the need for routine repeat head CT scans in patients with mild to moderate head injury and an initial positive abnormal CT scan. METHODS: This is a retrospective study of patients presenting to the emergency department from January 2016 to December 2017 with Glasgow Coma Scale (GCS) scores > 8 and an initial abnormal CT scan, who underwent repeat CT during their in-hospital medical management. Patients who underwent surgery after the first CT scan, had a GCS score < 9, or had a normal initial CT scan were excluded. Demographic, medical history, and physical examination details were collected, and CT scans were reviewed. Radiological deterioration, neurological deterioration, and/or the need for neurosurgical intervention were the primary outcome variables. RESULTS: A total of 1033 patients were included in this study. These patients underwent at least two CT scans on an inpatient basis. Of these 1033 patients, 54.1% had mild head injury and 45.9% had moderate head injury based on GCS score at admission. The most common diagnosis was contusion (43.8%), followed by extradural hematoma (28.8%) and subdural hematoma (26.6%). A total of 2636 CT scans were performed for 1033 patients, with a mean of 2.55 per patient. Of these, 25 (2.4%) had neurological deterioration, 90 (8.7%) had a progression of an existing lesion or appearance of a new lesion on repeat CT, and 101 (9.8%) required neurosurgical intervention. Seventy-five patients underwent surgery due to worsening of repeat CT without neurological deterioration, so the average number of repeat CT scans required to identify one such patient was 21.3. On multiple logistic regression, GCS score at admission (p = 0.024), abnormal international normalized ratio (INR; p < 0.001), midline shift (p = 0.005), effaced basal cisterns (p < 0.001), and multiple hemorrhagic lesions (p = 0.010) were associated with worsening of repeat CT, neurological deterioration, and/or need for neurosurgical intervention. CONCLUSIONS: The role of routine repeat head CT in medically managed patients with head injury is controversial. The authors have tried to study the various factors that are associated with neurological deterioration, radiological deterioration, and/or need for neurosurgical intervention. In this study the authors found lower GCS score at admission, abnormal INR, presence of midline shift, effaced basal cisterns, and multiple lesions on initial CT to be significantly associated with the above outcomes.