Olfactory Sensitivity in Covid 19 Infection Recovered Subjects.

Sense of smell is a vital perception in mammals. Temporary loss of smell is the main neurological symptom and one of the earliest and most commonly reported indicators of COVID-19. A observational hospital based analytical study carried out at a tertiary care centre for a period of 22 months from January 2021 to October 2022. All the patients were subjected to sniffin stick test and all the data were noted, tabulated and compared to know the correlation of olfactory sensitivity to different parameters. Males were affected with hyposmia slightly more than females. There was not much difference in the olfactory sensitivity in various phases of uterine cycle. Olfactory sensitivity had a negative correlation with serum oestrogen and serum progesterone levels, which was significant. Mean olfactory sensitivity of males for different odours were slightly higher than females. BMI has a negative correlation with olfactory sensitivity in males as well as females, which was significant.

Siderophore of plant growth promoting rhizobacterium origin reduces reactive oxygen species mediated injury in Solanum spp. caused by fungal pathogens.

AIMS: The study aims to explore antifungal properties of bacillibactin siderophore produced by the plant growth-promoting rhizobacterium (PGPR) Bacillus subtilis against fungal phytopathogens Alternaria porri and Fusarium equiseti isolated from Solanum lycopersicum and Solanum melongena plants. METHODS AND RESULTS: Alternaria porri and F. equiseti were isolated from infected plants of eggplant and tomato, respectively. A plate assay was employed to assess the effect of bacillibactin against the phytopathogens. The antifungal potential of the PGPR was evaluated by estimation of dry fungal biomass, visualization of cellular deformity using compound and scanning electron microscopy, antioxidative enzyme assay and analysis of membrane damage via using lipid peroxidation. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis was employed to investigate changes in intracellular iron content. The impact of bacillibactin on pathogenesis was evaluated by infecting detached leaves of S. lycopersicum and S. melongena plants with both the pathogens and treating the infected leaves with bacillibactin. Leaves were further investigated for ROS accumulation, extent of necrosis and cell death. Our findings revealed significant damage to the hyphal structure of A. porri and F. equiseti following treatment with bacillibactin. Biomass reduction, elevated antioxidative enzyme levels, and membrane damage further substantiated the inhibitory effects of the siderophore on fungal growth. ICP-AES analysis indicates an increase in intracellular iron content suggesting enhanced iron uptake facilitated by bacillibactin. Moreover, application of 1500 µg ml-1 bacillibactin on infected leaves demonstrated a substantial inhibition of ROS accumulation, necrosis, and cell death upon bacillibactin treatment. CONCLUSIONS: This study confirms the potent antagonistic activity of bacillibactin against both the phytopathogens A. porri and F. equiseti growth, supporting its potential as a promising biological control agent for fungal plant diseases. Bacillibactin-induced morphological, physiological, and biochemical alterations in the isolated fungi and pathogen-infected leaves highlight the prospects of bacillibactin as an effective and sustainable solution to mitigate economic losses associated with fungal infections in vegetable crops.

The presence/absence of conspecifics modulates the circadian locomotor activity and body mass in spotted munia (Lonchura punctulata).

Biological clocks regulate the behavior and physiology of animals by tracking the local time using diverse time cues. Social cues are relevant in studying the behavior of gregarious animals, but these cues have not been widely studied in birds. Temporal information for circadian timekeeping is socially communicated through visual, physical, olfactory, and auditory means. We examined the efficacy of pulsatile social interactions on locomotor activity and its associated characteristics such as distribution profile of rest and activity, total counts, activity duration, phase shift in activity onset, and circadian periodicity in spotted munia. Besides, we analyzed the effect of such social interactions on their body mass. Spotted munia exhibited phase shift in the onset of activity when subjected to social isolation, but these cues could not affect their circadian periodicity. In Pair as well as in Group, social isolation led to increased activity and activity duration, and decreased body mass in guests relative to the host bird. Our results suggest that the circadian rhythm of locomotor activity in spotted munia is quite sensitive to socialization and isolation, and isolation is detrimental for the birds. Consistent with these observations, the decline in body mass revealed the physiological consequences of social isolation on spotted munia.

Assessment of Nasal Obstruction in Patients Undergoing Functional Endoscopic Sinus Surgery.

Aim & objectives-To assess and compare the nasal obstruction in patients before and after undergoing FESS using Visual analogue scale, Rhinomanometry and Diagnostic nasal endoscopy. Introduction- Chronic Rhinosinusitis with, or without nasal polyps can lead to nasal obstruction. Patients refractory to medical treatment undergo Functional endoscopic sinus surgery (FESS). FESS has been shown to improve subjective quality of life outcomes and objective endoscopic improvement. Material & methods- A prospective study conducted in the department of Ear, Nose & Throat, of a tertiary care medical college and associated Hospital between January 2021 and October 2022. Subjective and objective assessment of nasal obstruction was done using Visual analogue scale, Rhinomanometry and Diagnostic nasal endoscopy before and after surgery at 1st, 3rd and 6th month. Results- Post FESS, there was a significant improvement in nasal obstruction on Visual analogue scale, sinuses were healthy and drainage was adequate on Diagnostic nasal endoscopy, statistically significant (P < 0.05) decrease in nasal resistance was seen on Rhinomanometry. Conclusion- A good subjective outcome on Visual analogue scale and a good objective outcome on Diagnostic nasal endoscopy and Rhinomanometry can be obtained with FESS in patients with Chronic Rhinosinusitis.

Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism.

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased NOD.H2b compared to healthy BALBc mice and Thrombospondin-1-null (TSP-1-/-) compared to TSP-1WTC57BL/6J mice. Inflammasome activation was investigated by immunostaining using the R26ASC-citrine reporter mouse, by Western blotting, and by RNAseq. LPS/Nigericin, IL-1α and chronic inflammation induced inflammasomes in lacrimal gland epithelial cells. Acute and chronic inflammation of the lacrimal gland upregulated multiple inflammasome sensors, caspases 1/4, and interleukins Il1b and Il18. We also found increased IL-1ß maturation in Sjögren's syndrome models compared with healthy control lacrimal glands. Using RNA-seq data of regenerating lacrimal glands, we found that lipogenic genes were upregulated during the resolution of inflammation following acute injury. In chronically inflamed NOD.H2b lacrimal glands, an altered lipid metabolism was associated with disease progression: genes for cholesterol metabolism were upregulated, while genes involved in mitochondrial metabolism and fatty acid synthesis were downregulated, including peroxisome proliferator-activated receptor alpha (PPARα)/sterol regulatory element-binding 1 (SREBP-1)-dependent signaling. We conclude that epithelial cells can promote immune responses by forming inflammasomes, and that sustained inflammasome activation, together with an altered lipid metabolism, are key players of Sjögren's syndrome-like pathogenesis in the NOD.H2b mouse lacrimal gland by promoting epithelial dysfunction and inflammation.

Irreversible Sensorineural Hearing Loss in Post Covid-19 Patients-An Institutional Prospective Study.

SARS-CoV-2 virus could damage the hearing by several mechanisms, it could damage the auditory centre in the temporal lobe and direct peripheral injury to the sensory cells of the cochlear due to neurotropism of the virus. A Prospective hospital-based observational study was carried out at a tertiary care centre for a period of 22 months from January 2021 to October 2022. A total of 100 patients were selected according to inclusion criteria and exclusion criteria. Pure-tone audiometry (PTA) was done as a screening test; patients were followed up till 6 months. Among those patients who had hearing loss, repeat audiological profile (PTA) was done after 1 month, 13(65%) patients were found to have normal hearing. After 3 months, repeat PTA was done, 18 patients (90%) found to have normal hearing and the remaining 2 patients followed up till 6 months and again PTA was done where only 1 patient continued to have sensorineural hearing loss.

LCN2-Fungal siderophore-iron binding and uptake leads to oxidative stress and cell death in hepatocellular carcinoma cell line HepG2.

Microorganisms produce non-ribosomal peptides called siderophores for the purpose of iron acquisition. Mammalian immune system is well-known for producing small secretory proteins called lipocalins upon bacterial infection. These proteins sequester siderophores produced by invading bacterial pathogens rendering them unable to acquire iron from the host. However, this is not their sole function. In addition to transferrin and lactoferrin, lipocalins are also known to transport siderophore-bound iron to the host cells. While binding of bacterial siderophores with human lipocalin is well studied, binding of the fungal counterpart is still not confirmed and fully understood. Apart from pathogen-affected cells, developing cancerous cells also show varying expression level of different proteins including those involved in iron transport. The possibility of exogenous fungal siderophore-mediated iron transport via lipocalin and its receptor in mammalian cells has not yet been explored much. In present investigation we have checked differential expression of human lipocalin, LCN2 in hepatocellular carcinoma cell lines HepG2 as well as its normal counterpart WRL-68 and computationally determined the feasibility of LCN2 binding with fungal siderophore. Further in case of a stable complex being formed, whether this complex has the ability to transport iron through its specific receptor was assessed. Also, we have tried to explore possible mechanism of fungal-siderophore mediated oxidative stress leading to significant cell death in cancerous cells. This study will thus be useful towards finding a new way of treating hepatocellular carcinoma via inducing siderophore-mediated cell death in cancerous cells.Communicated by Ramaswamy H. Sarma.

In silico analysis of comparative affinity of phytosiderophore and bacillibactin for iron uptake by YSL15 and YSL18 receptors of Oryza sativa.

Iron is an important micronutrient for plant growth and development. In the case of Oryza sativa, iron is made available primarily with the help of iron chelators called phytosiderophores i.e. variants of deoxymugineic acid (DMA). They bind with ferric ions and get internalized through Yellow Stripe Like transporters viz. YSL15 and YSL18. However, due to low amount of secretion of phytosiderophores, rice suffers from iron deficiency. Alternatively, siderophores of plant growth promoting rhizobacteria may support iron uptake and make it available to plants via transporting ferric ions possibly through the same transporters. Present study aims to assess comparative binding of DMA and a xenosiderophore (siderophores used by organisms other than the ones producing them) of rhizobacteria i.e. bacillibactin with Fe3+ ion and subsequent transporters of rice. Protein-protein interaction and gene expression analysis predicts uptake of Fe3+ by YSL15 from the rhizosphere region and further distribution through YSL18 with the help of various predicted functional partners. Docking studies confirm the thermodynamically more favourable structure of bacillibactin-Fe3+ complex than DMA-Fe3+ complex. Molecular modelling of YSL15 and YSL18 was done through ab initio method and their evaluation by Ramachandran plot, ProSA, ERRAT value and verify 3 D score revealed a good quality models. Comparative binding assessment through docking and molecular dynamics simulation suggests better binding energies of YSL transporters with bacillibactin-Fe3+ complex as compared to DMA-Fe3+ complex. The current study suggests possible application of xenosiderophores of PGPR origin in supporting plant growth via iron uptake and distribution in rice.Communicated by Ramaswamy H. Sarma.

Combinatorial Effect of Arsenic and Herbal Compounds in Telomerase-Mediated Apoptosis Induction in Liver Cancer.

Tumour illness and its resistance against existing anticancer therapies pose a serious health concern globally despite the progressive advancement of therapeutic options. The prevailing treatment of HCC using numerous antitumor agents has inflated long-lived complete remissions, but a percentage of individuals still die due to disease recurrence, indicating a need for further exploration of possible anti-tumour regimes. We aim to boost the effectiveness of the HCC treatment by conducting current investigations evaluating the effect of arsenic trioxide (ATO) with different herbal compounds like quercetin and aloe-emodin against liver tumour via inhibition of telomerase, a pro-cancer enzyme. The anticancer activity of ATO with herbal compounds was investigated in human control liver cell line (Wrl-68) and cancer liver cell line (HepG2) at different time intervals. Viability and cytotoxicity in response to combinatorial drugs were assessed in vitro by trypan blue dye exclusion assay and MTT and WST assay. Apoptosis was analysed by annexin V/PI assay, and the expression of telomerase and apoptosis-regulating proteins was evaluated by immunoblotting and qRT-PCR. Arsenic trioxide in combination with quercetin and aloe-emodin reduced cell viability in cancerous cells compared to normal cells by inducing apoptosis, downregulating telomerase and Bcl-2 (anti-apoptotic protein) and upregulating the expression of Bax (pro-apoptotic protein). ATO exhibited significant anticancer effects due to the synergistic effects of quercetin and aloe-emodin in liver tumour cells. The current study data collectively suggest that a successful inhibition of cancer growth by the combination of ATO and tested herbal medicines against liver tumour growth is via the inhibition of telomerase activity.

A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells.

Induction of Iron Stress in Hepatocellular Carcinoma Cell Lines by Siderophore of Aspergillus nidulans Towards Promising Anticancer Effect.

Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide and needs efficient and feasible approach of treatment. Present study focuses on exploring the anticancer activity of a secondary metabolite called siderophore of Aspergillus nidulans against hepatocellular carcinoma cell line HepG2. These small peptides are produced by microorganisms including fungi for scavenging iron from its surroundings. Fungi including Aspergillus spp. are known to produce siderophores under iron-limited conditions. Siderophores have high affinity towards iron and are classified into various types. In the present study, siderophore isolated and purified from fungal cultures was confirmed to be of hydroxamate type by chrome azurol sulfonate and Atkin's assay. HPLC analysis confirmed purity while LC-ESI-MS revealed that the siderophore is triacetyl fusigen. Cancerous cells, HepG2, grown under siderophore treatment showed inhibition in growth and proliferation in a dose- and time-dependent manner. Reduction in viability and metabolic activity was evident upon treatment as seen in trypan blue, MTT and WST assay. Fluorescent staining using PI and DAPI confirmed the same while DCFDA staining revealed increased reactive oxygen species production which might have led to cell death and deterioration. Such increase in ROS has been correlated with iron accumulation by assessing intracellular iron level through ICP-MS. To assess the effect of siderophore treatment on normal cells, WRL-68, same assays were carried out but the effect was mostly non-significant up to 48 h. Thus, present work suggests that an optimum dose of siderophore purified from A. nidulans culture might prove a useful anticancer agent.

Antifungal Activity of Siderophore Isolated From Escherichia coli Against Aspergillus nidulans via Iron-Mediated Oxidative Stress.

Microorganisms produce various secondary metabolites for growth and survival. During iron stress, they produce secondary metabolites termed siderophores. In the current investigation, antifungal activity of catecholate siderophore produced by Escherichia coli has been assessed against Aspergillus nidulans. Exogenous application of the bacterial siderophore to fungal cultures resulted in decreased colony size, increased filament length, and changes in hyphal branching pattern. Growth inhibition was accompanied with increased intracellular iron content. Scanning electron microscopy revealed dose-dependent alteration in fungal morphology. Fluorescent staining by propidium iodide revealed cell death in concert with growth inhibition with increasing siderophore concentration. Antioxidative enzyme activity was also compromised with significant increase in catalase activity and decrease in ascorbate peroxidase activity. Siderophore-treated cultures showed increased accumulation of reactive oxygen species as observed by fluorescence microscopy and enhanced membrane damage in terms of malondialdehyde content. Antifungal property might thus be attributed to xenosiderophore-mediated iron uptake leading to cell death. STRING analysis showed interaction of MirB (involved in transport of hydroxamate siderophore) and MirA (involved in transport of catecholate siderophore), confirming the possibility of uptake of iron-xenosiderophore complex through fungal transporters. MirA structure was modeled and validated with 95% residues occurring in the allowed region. In silico analysis revealed MirA-Enterobactin-Fe3+ complex formation. Thus, the present study reveals a promising antifungal agent in the form of catecholate siderophore and supports involvement of MirA fungal receptors in xenosiderophore uptake.

Tolerogenic Nanoparticles Impacting B and T Lymphocyte Responses Delay Autoimmune Arthritis in K/BxN Mice.

Current treatments for unwanted antibody responses largely rely on immunosuppressive drugs compromising overall immunity. New approaches to achieve antigen-specific tolerance are desirable to avoid unwanted side effects. Several nanoparticle-based approaches that utilize different mechanisms to tolerize the B or T cell arms of the humoral immune response have shown promise for induction of antigen-specific tolerance, raising the possibility that they could work synergistically if combined. Earlier we showed that Siglec-engaging tolerance-inducing antigenic liposomes (STALs) that display both an antigen (Ag) and glycan ligands of the inhibitory co-receptor CD22 (CD22L) lead to robust antigen-specific B cell tolerance to protein antigens in naive mice. In another approach, administration of free Ag with poly(lactic-co-glycolic acid)-rapamycin nanoparticles (PLGA-R) induced robust antigen-specific tolerance through production of regulatory T cells. Here we illustrate that coadministration of STALs together with PLGA-R to naive mice induced more robust tolerance to multiple antigen challenges than either nanoparticle alone. Moreover, in K/BxN mice that develop spontaneous autoimmune arthritis to the self-antigen glucose-6-phosphate-isomerase (GPI), co-delivery of GPI-LP-CD22L and PLGA-R delayed onset of disease and in some mice prevented the disease indefinitely. The results show synergy between B cell-tolerizing STALs and T cell-tolerizing PLGA-R and the potential to induce tolerance in early stage autoimmune disease.

Innate Immunity and Biological Therapies for the Treatment of Sjögren's Syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disorder affecting approximately 3% of the population in the United States. This disease has a female predilection and affects exocrine glands, including lacrimal and salivary glands. Dry eyes and dry mouths are the most common symptoms due to the loss of salivary and lacrimal gland function. Symptoms become more severe in secondary SS, where SS is present along with other autoimmune diseases like systemic lupus erythematosus, systemic sclerosis, or rheumatoid arthritis. It is known that aberrant activation of immune cells plays an important role in disease progression, however, the mechanism for these pathological changes in the immune system remains largely unknown. This review highlights the role of different immune cells in disease development, therapeutic treatments, and future strategies that are available to target various immune cells to cure the disease.

Recent developments in siderotyping: procedure and application.

Siderophores are metal chelating secondary metabolites secreted by almost all organisms. Beside iron starvation, the ability to produce siderophores depends upon several other factors. Chemical structure of siderophore is very complex with vast structural diversity, thus the principle challenge involves its detection, quantification, purification and characterisation. Metal chelation is its most fascinating attribute. This metal chelation property is now forming the basis of its application as molecular markers, siderotyping tool for taxonomic clarification, biosensors and bioremediation agents. This has led researchers to develop and continuously modify previous techniques in order to provide accurate and reproducible methods of studying siderophores. Knowledge obtained via computational approaches provides a new horizon in the field of siderophore biosynthetic gene clusters and their interaction with various proteins/peptides. This review illustrates various techniques, bioinformatics tools and databases employed in siderophores' studies, the principle of analytical methods and their recent applications.

Iron: Key player in cancer and cell cycle?

BACKGROUND: Iron is an essential element for growth and metabolic activities of all living organisms but remains in its oxyhydroxide ferric ion form in the surrounding. Unavailability of iron in soluble ferrous form led to development of specific pathways and machinery in different organisms to make it available for use and maintain its homeostasis. Iron homeostasis is essential as under different circumstances iron in excess as well as deprivation leads to different pathological conditions in human. OBJECTIVE: This review highlights the current findings related to iron excess as well as deprivation with regards to cellular proliferation. CONCLUSIONS: Iron excess is extensively associated with different types of cancers viz. colorectal cancer, breast cancer etc. by producing an oxidative stressed condition and alteration of immune system. Ironically its deprivation also results in anaemic conditions and leads to cell cycle arrest at different phases with mechanism yet to be explored. Iron deprivation arrests cell cycle at G1/S and in some cases at G2/M checkpoints resulting in growth arrest. However, in some cases iron overload arrests cell cycle at G1 phase by blocking certain signalling pathways. Certain natural and synthetic iron chelators are being explored from few decades to combat diseases caused by alteration in iron homeostasis.

Siderophore-assisted cadmium hyperaccumulation in Bacillus subtilis.

Siderophores (Gk iron carriers) are low molecular weight secondary metabolites produced by bacteria, fungi, and plants that have strong binding affinity for iron. Owing to their iron-chelating ability, they are produced mainly when the organism faces iron scarcity. The present study empirically investigated the importance of applying hydroxamate siderophore extracted from Aspergillus nidulans to the cells of Bacillus subtilis for bioremediation of cadmium salt. This investigation deals with siderophore-mediated intracellular Cd accumulation by bacterial cells, growth estimation, biochemical assays like lipid peroxidation, total protein content, carbohydrate content, and iron content estimation. In silico docking and STRING analyses revealed specific interaction between Aspergillus siderophore and receptors present on B. subtilis. Estimation of intracellular Cd by atomic absorption spectroscopy showed more accumulation of Cd ions by B. subtilis in the presence of hydroxamate siderophore. This suggests a possibility of confiscating environmental Cd2+ by utilizing metal chelation property of siderophores and hence can lead to emerging bioremediation mechanisms for heavy metals. In silico studies support experimental investigation and suggest higher affinity of siderophore for Cd ions as compared with ferric ions.

Inverse spatially-offset Raman spectroscopy using optical fibers: An axicon lens-free approach.

Inverse spatially offset Raman spectroscopy (I-SORS) seeks to interrogate deep inside a Raman-active, layered, diffusely scattering sample. It makes a collimated laser beam incident onto the sample surface in the form of concentric illumination rings (of varying radii) from whose center the back-scattered Raman signal is collected for detection. Since formation of illumination rings of different sizes requires an axicon to be moved along the axis of the collimated laser beam and axicons below a certain minimum size (~1 inch) are not readily available, this classical configuration incorporating an axicon cannot be used for designing a compact I-SORS probe of narrower diameter. We report a novel scheme of implementing I-SORS which overcomes this limitation by implementing ring illumination and point collection using two multi-mode optical fibers. An important advantage of the proposed scheme is that unlike the previously reported inverse SORS configurations, it does not require physical movement of any of the optical components for generating spatial offsets needed for probing sub-surface depths. Another advantage is its fiber-optic configuration which is ideally suited for designing a compact and pencil-sized I-SORS probe, often desired in many practical situations for carrying out depth-sensitive Raman measurements in situ from a layered turbid sample.

High-dose-rate interstitial brachytherapy in recurrent head and neck cancer: an effective salvage option.

PURPOSE: High-dose-rate (HDR) interstitial brachytherapy has an established role in head and neck malignancies and offers good survival rates; however, there is scant data on improved local control (LC) and treatment-related complications in recurrent cases. We present our results in patients with recurrent head and neck cancers treated with HDR interstitial brachytherapy. MATERIAL AND METHODS: Twenty-five patients with recurrent head and neck cancers were treated with HDR interstitial brachytherapy using Iridium 192 between 2009 and 2016. Of these, 75% received radical brachytherapy, and 25% received external beam radiation therapy (EBRT) followed by brachytherapy boost. Treatment sites included oral cavity (15/25) and oropharynx (10/25). Median dose of 4.5 Gy was administered twice per day, with median total brachytherapy dose of 40.5 Gy in radical and 27 Gy for EBRT cases. RESULTS: With median follow-up of 25 months, 4 local recurrences were observed within first year of follow-up. Two-year local control and overall survival outcomes for the entire group were 75% and 68%, respectively. Local control rate with radical BRT vs. BRT as a boost following EBRT was found to be significant (2-year LCR 62% vs. 85%; p < 0.02). Dosimetric assessment revealed D90 - 4.08 Gy, V100 - 94.1%, V150 - 24.7%, and V200 - 10.1%. Xerostomia, altered taste, and dysphagia were the major complications commonly grade 1 and 2. Grade 3 toxicity was only 2%. Pre-treatment volume > 85 cc had a negative impact on overall survival (26 months vs. 12 months; p = 0.02), and interval time between primary and recurrence more than 15 months had an impact on the local control rate (p < 0.01). CONCLUSIONS: Results of HDR interstitial brachytherapy have shown acceptable local control and overall survival rates along with tolerable toxicities and morbidity in recurrent head and neck cancers.

Hepatitis B Antigen Loaded Biodegradable Polymeric Nanoparticles: Formulation Optimization and In-vivo Immunization in BALB/c Mice.

OBJECTIVE: The incredibly serious problem of Hepatitis B is virus-related chronic liver disease. The conventional preventive treatment of Hepatitis B requires booster dose, which requires repeated administration of the vaccine to the subject. Thus, there is a need to develop a formulation which can eliminate the need of frequent dosing and enhance patient's acquiescence. To prepare single dose nanovaccine of HBsAg by utilizing central composite design for optimization and interaction of independent variables effects on measured response. METHODS: Nanovaccines were characterized for particle size, morphology, integrity, internalization, proliferation response and haemocompatibility. Nanoparticles at single and multiple doses were compared with booster dose of alum-HBsAg vaccine and measure the immunological marker and cytokine (interleukin-2 and interferon-Y) levels by ELISA techniques in BALB/c mice. RESULTS: The designed nanoparticles were found to have nanometric size, high entrapment efficiency and retained antigen integrity. Nanoparticles showed maximum proliferation and efficiently internalized by lymph and spleen cell without eliciting significant toxicity and haemocampatible. CONCLUSION: The comparable data of anti-HBsAg titre between nanovaccine and alum adsorbed HBsAg demonstrated that single dose of nanoparticles is sufficient for production of immunoglobulin plus cytokine levels, maintain immunogenicity at longer period of time and eliminate the booster dose. Nanovaccines trigger immune responses and showing adjuvant properties.