Evaluation of Drug-Loaded and Surface-Adsorbed DNase/Tween-80 Solid Lipid Nanoparticles against Staphylococcus aureus Biofilms.

The aim of this study was to explore the suitability of Tween-80 or DNase I adsorbed onto the surface of gentamicin-loaded solid lipid nanoparticles (SLNs) to disrupt Staphylococcus aureus biofilms in vitro. We hypothesized that surface-adsorbed DNase I or Tween-80 of SLNs will degrade the biofilm component, extracellular DNA (e-DNA), and extracellular matrix (ECM) of S. aureus biofilms. The SLNs loaded with drug (core) and surface-adsorbed disruptors (Tween-80 or DNase I) to deliver biofilm disruptors first at the site of action, which will help to break down the biofilm, and further drug release from the core will easily penetrate the biofilm and facilitate the killing of bacteria residing in S. aureus biofilms. The SLNs were synthesized by the double emulsion method; the size was 287.3 ± 7.4 nm for blank SLNs and 292.4 ± 2.36 nm for drug-loaded SLNs. The ζ-potential of blank SLNs was -25.6 ± 0.26 mV and that of drug-loaded SLNs was -13.16 ± 0.51 mV, respectively. The successful adsorption of DNase I or Tween-80 was confirmed by the activity of DNase I in blank surface-adsorbed SLNs and the change in the ζ-potential of SLNs after adsorbing DNase I or Tween-80. The surface morphology and size of the SLNs were further characterized using scanning electron microscopy. The encapsulation efficiency of the drug was 16.85 ± 0.84%. The compatibility of the drug with the excipient was confirmed by Fourier transform infrared spectroscopy and the degree of crystallinity was confirmed by X-ray diffraction (XRD) analysis. SLNs showed a sustained release of the drug up to 360 h. SLNs were easily taken up by A549 cells with minimal or no toxicity. The present study showed that Tween-80- or DNase I-adsorbed SLNs efficiently disrupt S. aureus biofilms and possess no or minimal toxicity against cells and red blood cells (RBCs).

Staphylococcus aureus Biofilm Destabilization by Tween-80 and Lung Surfactants to Overcome Biofilm-Imposed Drug Resistance.

This study is aimed to evaluating the potential of tween-80 and artificial lung surfactant (ALS) to destabilize S. aureus biofilm. The biofilm destabilization was studied by crystal violet staining, bright field microscopy, and scanning electron microscopy (SEM). During the study, S. aureus biofilm was exposed with tween-80 along various concentrations (1%, 0.1%, and 0.05%) or LS (lung surfactant) at (2.5%, 5%, and 15%) for 2 hrs. It was observed that 0.1% of tween-80 destabilized 63.83 ± 4.35% and 15% ALS 77 ± 1.7% biofilm in comparison to without treatment. The combination of tween-80 and ALS was used and showed a synergistic effect to destabilize 83.4 ± 1.46% biofilm. These results showed the potential of tween-80 and ALS as biofilm disruptors, which further needs to explore in an in-vivo animal model to access the actual potential of biofilm disruption in natural conditions. This study could play a pivotal role to overcome the problem of antibiotic resistance imposed due to biofilm formation to combat antibiotic resistance imposed by bacteria.

Synthesis and Evaluation of BSA-Loaded PLGA-Chitosan Composite Nanoparticles for the Protein-Based Drug Delivery System.

The purpose of this study was to synthesize composite nanoparticles (NPs) based on poly(d,l-lactic-co-glycolic acid) (PLGA) and chitosan (CS) and evaluate their suitability for the delivery of protein-based therapeutic molecules. Composite NPs possess a unique property which is not exhibited by any other polymer. Unlike other polymers, only the composite NPs lead to improved transfection efficiency and sustained release of protein. The composite NP were prepared by grafting CS on the surface of PLGA NPs through EDC-NHS coupling reaction. The size of bovine serum albumin (BSA)-loaded PLGA NPs and BSA-loaded PLGA-CS composite NPs was 288 ± 3 and 363 ± 4 nm, respectively. The zeta potential of PLGA NPs is -18 ± 0.23, and that of composite particles is 19 ± 0.40, thus confirming the successful addition of CS on the surface of PLGA NPs. Composite NPs were characterized using dynamic light scattering, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, release profile, and gel electrophoresis. The encapsulation efficiency of PLGA NPs was 88%. These composite NPs were easily uptaken by the A549 cell line with no or minimal cytotoxicity. The present study emphasizes that the composite NPs are suitable for delivery of BSA into the cells with no cytotoxicity or very little cytotoxicity, while maintaining the integrity of the encapsulated BSA.

Nanoparticle and Nanostructure Synthesis and Controlled Growth Methods.

Nanomaterials are materials with one or more nanoscale dimensions (internal or external) (i.e., 1 to 100 nm). The nanomaterial shape, size, porosity, surface chemistry, and composition are controlled at the nanoscale, and this offers interesting properties compared with bulk materials. This review describes how nanomaterials are classified, their fabrication, functionalization techniques, and growth-controlled mechanisms. First, the history of nanomaterials is summarized and then the different classification methods, based on their dimensionality (0-3D), composition (carbon, inorganic, organic, and hybrids), origin (natural, incidental, engineered, bioinspired), crystal phase (single phase, multiphase), and dispersion state (dispersed or aggregated), are presented. Then, the synthesis methods are discussed and classified in function of the starting material (bottom-up and top-down), reaction phase (gas, plasma, liquid, and solid), and nature of the dispersing forces (mechanical, physical, chemical, physicochemical, and biological). Finally, the challenges in synthesizing nanomaterials for research and commercial use are highlighted.

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

A proposal for changing nomenclature from pseudomyxoma peritonei (PMP) to abdomino-peritoneal mucinous carcinoma (APM) based on its long journey and experience from tertiary oncology center in India.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a generalized term, usually known as "jelly belly" since 1884. Incidence is very low, 1-3 per million people per year. Because of its indolent nature, it is usually diagnosed at an advanced stage, thereby impacting the quality of life. The 5-year survival rate varies from 23 to 86% in world literature. Even 10 years and 20 years of survival have been described. With our experience, we like to propose rename of PMP as abdomino-peritoneal mucinous carcinoma (APM) as we strongly feel the time has come to specify the term and standardize the management strategy. METHODOLOGY: In the premier institute of India and as a tertiary referral center, we experienced the maximum number of advanced cases of APM. From 2012 to 2021, we analyzed all the APM patients based on a prospectively maintained computerized database in the department of surgical oncology and found the reasons for renaming from this traditional one. RESULTS: We included a total of 87 patients who underwent surgical intervention. Thirty-five patients underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), and 52 patients underwent debulking. In CRS-HIPEC patients, CC-0 was achieved in 28 patients (80%), CC-1 in 4 patients (11.4%), and CC-2 in 3 patients (8.6%). Palliative intent HIPEC was done in 3 patients (8.6%). Clavien-Dindo grade III and IV morbidity was observed in 18.8% of patients with 90 days mortality of 5.7%. CONCLUSION: With our long-term experience and advancement of scientific evidence, we like to propose a new name for PMP as APM. We strongly believe this paper will give a clear picture of this rare disease and standard management outlines.

Review on Nanoparticles and Nanostructured Materials: Bioimaging, Biosensing, Drug Delivery, Tissue Engineering, Antimicrobial, and Agro-Food Applications.

In the last few decades, the vast potential of nanomaterials for biomedical and healthcare applications has been extensively investigated. Several case studies demonstrated that nanomaterials can offer solutions to the current challenges of raw materials in the biomedical and healthcare fields. This review describes the different nanoparticles and nanostructured material synthesis approaches and presents some emerging biomedical, healthcare, and agro-food applications. This review focuses on various nanomaterial types (e.g., spherical, nanorods, nanotubes, nanosheets, nanofibers, core-shell, and mesoporous) that can be synthesized from different raw materials and their emerging applications in bioimaging, biosensing, drug delivery, tissue engineering, antimicrobial, and agro-foods. Depending on their morphology (e.g., size, aspect ratio, geometry, porosity), nanomaterials can be used as formulation modifiers, moisturizers, nanofillers, additives, membranes, and films. As toxicological assessment depends on sizes and morphologies, stringent regulation is needed from the testing of efficient nanomaterials dosages. The challenges and perspectives for an industrial breakthrough of nanomaterials are related to the optimization of production and processing conditions.

BMP4 enhances anoikis resistance and chemoresistance of breast cancer cells through canonical BMP signaling.

Bone morphogenetic proteins (BMPs) regulate cell fate during development and mediate cancer progression. In this study, we investigated the role of BMP4 in proliferation, anoikis resistance, metastatic migration, and drug resistance of breast cancer cells. We utilized breast cancer cell lines and clinical samples representing different subtypes to understand the functional effect of BMP4 on breast cancer. The BMP pathway was inhibited with the small molecule inhibitor LDN193189 hydrochloride (LDN). BMP4 signaling enhanced the expression of stem cell genes CD44, ALDH1A3, anti-apoptotic gene BCL2 and promoted anoikis resistance in MDA-MB-231 breast cancer cells. BMP4 enhanced self-renewal and chemoresistance in MDA-MB-231 by upregulating Notch signaling while LDN treatment abrogated anoikis resistance and proliferation of anoikis resistant breast cancer cells in the osteogenic microenvironment. Conversely, BMP4 downregulated proliferation, colony-forming ability, and suppressed anoikis resistance in MCF7 and SkBR3 cells, while LDN treatment promoted tumor spheroid formation and growth. These findings indicate that BMP4 has a context-dependent role in breast cancer. Further, our data with MDA-MB-231 cells representing triple-negative breast cancer suggest that BMP inhibition might impair its metastatic spread and colonization.

Impact of COVID-19 Pandemic on Cancer Surgical Services-AIIMS, New Delhi Experience.

COVID pandemic has impacted cancer care delivery and cancer surgical services globally. There is an urgent need to study the extent of the impact of COVID on cancer surgery and individual institutional response and strategies adopted to counter the adverse impact. A review of administrative and clinical policy changes adopted at the tertiary cancer center to combat COVID pandemic and resume cancer surgical services were performed. A retrospective comparative analysis of cancer out-patient census during COVID pandemic affected year and the preceding normal year along with cancer surgery data audit for the same periods was performed to assess the impact of the pandemic on cancer surgery. In addition, COVID infection rates among cancer surgery patients and healthcare workers were evaluated. There was approximately a 50% reduction in cancer outpatient registrations during COVID pandemic affected year. A trend of increasing footfalls was noted with decreasing COVID intensity and opening of lockdowns. There was a 33% reduction in major elective surgery and a 41% reduction in emergency surgery performed during the COVID period. As far as cancer surgeries are concerned, there was a 12-50% reduction in volumes involving different subsites. Overall COVID positivity rates among cancer surgery patients was low (8.17%), and approximately 30% of healthcare workers involved in cancer surgery were tested positive for COVID during the study period. Results of the current study indicate a significant impact of COVID pandemic on cancer surgical services. There was a significant impact on outpatient visits and cancer surgery volumes. However, a multidisciplinary-coordinated team approach, effective administrative and policy implementation, adoption of revised surgical safety and anesthesia protocols, COVID screening, and testing protocols facilitated resumption of cancer surgical services without adverse impact on surgical outcomes.

Biomedical Applications of Carbon Nanomaterials: Fullerenes, Quantum Dots, Nanotubes, Nanofibers, and Graphene.

Carbon nanomaterials (CNMs) have received tremendous interest in the area of nanotechnology due to their unique properties and flexible dimensional structure. CNMs have excellent electrical, thermal, and optical properties that make them promising materials for drug delivery, bioimaging, biosensing, and tissue engineering applications. Currently, there are many types of CNMs, such as quantum dots, nanotubes, nanosheets, and nanoribbons; and there are many others in development that promise exciting applications in the future. The surface functionalization of CNMs modifies their chemical and physical properties, which enhances their drug loading/release capacity, their ability to target drug delivery to specific sites, and their dispersibility and suitability in biological systems. Thus, CNMs have been effectively used in different biomedical systems. This review explores the unique physical, chemical, and biological properties that allow CNMs to improve on the state of the art materials currently used in different biomedical applications. The discussion also embraces the emerging biomedical applications of CNMs, including targeted drug delivery, medical implants, tissue engineering, wound healing, biosensing, bioimaging, vaccination, and photodynamic therapy.

Upfront cytoreductive surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer in Indian patients.

In cases of ovarian carcinoma, primary cytoreductive surgery (CRS) is the standard treatment up to stage IIIB, but patient selection for neoadjuvant chemotherapy (NACT) in selected cases is controversial. A total of 200 patients with advanced ovarian cancer were analyzed retrospectively, according to specific selection criteria. Primary CRS was performed in 95 patients (47.5%) and interval CRS after 3-6 cycles of NACT was performed in 105 patients (52.5%). After median follow-up of 35 months, 5-year overall survival was 53.7% in the upfront CRS group and 42.2% in the NACT group. Primary CRS is the standard in advanced stages of ovarian carcinoma, but in certain subset of patients, NACT is preferred. Identifying that group is challenging but feasible. Proper selection of patients is key to successful outcomes.

Protective Diversion Stoma in Low Anterior Resection for Rectal Cancer: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: With the establishment of the oncological safety and due to the potential of low anterior resection (LAR) with sphincter salvage in improving the quality of life of patients with low and mid rectal cancers, it has become a popular treatment modality. A potential complication of the procedure is anastomotic dehiscence which results in a significant increase in postoperative morbidity and mortality. METHODS: A literature search for randomized controlled trials (RCTs) that compared the role of protective diversion stoma with no stoma in LAR of the rectum was performed in PubMed. The effect size for dichotomous and continuous data was displayed as relative risk (RR) and weighted mean difference (WMD), respectively, with their corresponding 95% confidence intervals. A fixed effect or random effects model was used to pool the data according to the result of a statistical heterogeneity test. RESULTS: Five RCTs were identified and included in the analysis. These yielded 390 patients who had undergone a protective diversion ileostomy at the time of the surgery (LAR) and 378 who had not, resulting in a total of 768 patients, all of whom were included in the meta-analysis. The fashioning of an ileostomy significantly decreased the anastomotic leak (AL) rates (RR 0.33, 95% CI 0.21-0.51, p < 0.000) and the reoperation rates (RR 0.26, 95% CI 0.15-0.45, p < 0.000). CONCLUSION: This meta-analysis found that a protective diversion ileostomy in LAR for rectal cancer decreases the AL rates by one third and the reoperation rates by one fourth. Thus, we conclude that fashioning such a stoma is beneficial.

Milky Mesentery: Acute Abdomen with Chylous Ascites.

BACKGROUND: Clinical presentations of intestinal lymphangiectasia include pitting edema, chylous ascites, pleural effusion, diarrhea, malabsorption and intestinal obstruction. CASE CHARACTERISTICS: An 8-year-old male child presented to the emergency department with clinical features of peritonitis, raising suspicion of appendicular or small bowel perforation. INTERVENTION/OUTCOME: Diagnosis of chylous ascites with primary intestinal lymphangiectasia made on laparotomy. MESSAGE: Acute peritonitis may be a presentation of primary intestinal lymphangiectasia and chylous ascites.

Palliative Surgery for Metastatic Fungating Phyllodes Tumors: A Series of Two Cases.

INTRODUCTION: Local treatment of metastatic cystosarcoma phyllodes is classically viewed with skepticism because it does not provide survival benefit. When these advanced tumors ulcerate, they reduce quality of life dramatically because of associated pain, infection, malodor, massive discharge, and bleeding. CASE PRESENTATIONS: Two patients with metastatic cystosarcoma phyllodes presented to our hospital with recurrent disease featuring foul-smelling, ulcerated chest wall masses that caused physical pain and social exclusion. The first patient underwent radical chest wall resection with pedicled lattisimus dorsi flap reconstruction. The second patient underwent wide local excision with split-thickness skin grafting. There was significant improvement in the quality of life for these patients after the operations. DISCUSSION: Though both patients finally succumbed to progressive metastatic disease, palliative resection allowed them to have good social and family support to the end. Palliative surgery plays an important role in alleviating suffering of patients with metastatic fungating cystosarcoma phyllodes and has the potential to improve their quality of life significantly.