Compositional profile of mucosal bacteriome of smokers and smokeless tobacco users.

INTRODUCTION: Smoked, and especially smokeless, tobacco are major causes of oral cancer globally. Here, we examine the oral bacteriome of smokers and of smokeless tobacco users, in comparison to healthy controls, using 16S rRNA gene sequencing. METHODS: Oral swab samples were collected from smokers, smokeless tobacco users, and healthy controls (n = 44). Microbial DNA was extracted and the 16S rRNA gene profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Differentially abundant taxa were identified using DESeq2, while functional metagenomes based on KEGG orthology abundance were inferred using LIMMA. RESULTS: A significantly higher microbial diversity was observed in smokeless tobacco users and smokers relative to controls (P < 0.05). Compositional differences in microbial communities were observed in all comparisons with healthy controls (PERMANOVA P < 0.05) but not between smokers and smokeless tobacco users. Levels of Fusobacterium spp., Saccharibacterium spp., and members of Shuttleworthia were elevated in smokers when compared to controls (BH adj P < 0.01). In addition, the relative abundance of three bacterial taxa belonging to genera Fusobacterium spp., Catonella, and Fretibacterium spp. was significantly increased in smokeless tobacco users relative to controls (BH adj P < 0.01). Major functional pathways significantly increased in smokeless tobacco users relative to both controls, and smokers were similar and involved amino acid metabolism including glutamate and aspartate biosynthesis and degradation (log FC > 1.5; BH adj P < 0.01). CONCLUSIONS: A distinct taxonomic and functional profile of oral microbiome in smokers and smokeless tobacco users as compared to healthy controls implicates a significant role of microbes and their metabolites in diseases associated with tobacco use including oral cancer. CLINICAL RELEVANCE: Future efforts in preventive, diagnostic, curative, and prognostic strategies for diseases associated with tobacco use in smokers and smokeless tobacco users could incorporate the oral microbiome.

Quality of life among head and neck cancer treated patients in South India: A cross-sectional study.

BACKGROUND AND AIM: The impact of oral health related disease and treatment on the patient's overall well-being and functioning is a topic of growing interest in clinical research and practice. Research shows that there is a significant reduction in the quality of life for the patients throughout the treatment of head and neck cancer. Therefore, the aim of the study is to assess the quality of life among treated head and neck cancer patients. MATERIALS AND METHOD: The cross sectional study was conducted among 225 head and neck cancer patients. The European Organization for Research and Treatment of Cancer (EORTC QLQ C-30), Quality Of Life Head and Neck35" (QLQ-HN35) instruments were used to assess their quality of life. The study population was divided into three groups based on the treatment done: Group I (Surgery), Group II (Surgery and Radiotherapy) and Group III (Surgery, Radiotherapy and Chemotherapy). Independent t-test and one way ANOVA test were done to analyze the data. RESULTS: Trouble with opening mouth (34.66 â€‹± â€‹30.58) was one of the highest rated symptoms among the study population. Salivary dysfunction leading to dry mouth (33.33 â€‹± â€‹34.06), sticky saliva (33.33 â€‹± â€‹26.72) were also found to be severe. Among the three groups, the Global Health Status, Symptom Scale mean scores were more high in Group I, Functional Scale and H&N35 symptoms mean scores was high in Group III however no statistical significance was observed (p â€‹> â€‹0.05). CONCLUSION: Head and neck cancer has severe effects on the quality of life. As observed from the findings of the current study, Global Health Status indicated a healthy level of living among patients who have undergone surgery alone; head and neck symptoms were more severe and problematic among patients who had surgery and radiotherapy. Therefore, assessing health related quality of life can be a factor that is weighed against treatment burden, toxicity, survival benefit. It can be more integral to treatment planning, refining treatment protocols and a better post-operative care and support.

Inhibition of LPS induced pro-inflammatory responses in RAW 264.7 macrophage cells by PVP-coated naringenin nanoparticle via down regulation of NF-κB/P38MAPK mediated stress signaling.

BACKGROUND: Naringenin (NAR) was found to display strong pharmacological properties. Since the clinical relevance of NAR is limited by its low bioavailability, we effectively synthesized and characterized a novel PVP-coated NAR nanoparticle (NAR NP) to enhance the therapeutic efficacy of NAR. The present study was designed to investigate the effects of NAR NP on lipopolysaccharide (LPS) induced inflammatory response in RAW 264.7 macrophage cells. METHODS: In vitro cell culture studies of LPS stimulated RAW 264.7 macrophage cells were used as experimental model. RESULTS: Cytotoxicity studies revealed that NAR NP is safe even at maximum tested concentration of 200µg/ml. Initial dose fixation study in LPS induced RAW 264.7 cells, revealed the minimum optimal concentration required for anti inflammatory effect as 25µg/ml. mRNA expression studies showed that NAR NP significantly down regulated the expressions of NF-κB and P38MAPK, which is paralleled with the inhibition of the nuclear translocation of NF-κB. This in turn led to the blockade of iNOS and COX-2, thereby inhibiting the production of nitric oxide and pro inflammatory cytokines such as TNF-α, IL-6, MCP-1 and IL-1ß. NAR NP was found to be more efficient, when compared with NAR. CONCLUSIONS: Anti-inflammatory effects of NAR NP may be allocated to the down-regulation of COX -2 and iNOS via the suppression of NF-κB and MAPK signaling pathway in RAW 264.7 macrophages. The data suggests that NAR NP can be used as a potent candidate for the treatments of inflammatory diseases by exploiting the nanoscale properties and targeting efficacy.

PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations.

Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.

Gas-sensing properties of needle-shaped Ni-doped SnO2 nanocrystals prepared by a simple sol-gel chemical precipitation method.

The preparation of needle-shaped SnO(2) nanocrystals doped with different concentration of nickel by a simple sol-gel chemical precipitation method is demonstrated. By varying the Ni-dopant concentration from 0 to 5 wt%, the phase purity and morphology of the SnO(2) nanocrystals are significantly changed. Powder XRD results reveal that the SnO(2) doped with a nickel concentration of up to 1 wt% shows a single crystalline tetragonal rutile phase, whereas a slight change in the crystallite structure is observed for samples with nickel above 1wt%. High resolution scanning electron microscopy (HRSEM) results reveal the change in morphology of the materials from spherical, for SnO(2), to very fine needle-like nanocrystals, for Ni-doped SnO(2), annealed at different temperatures. The gas sensing properties of the SnO(2) nanocrystals are significantly enhanced after the nickel doping.

Late outcome after arterial switch operation for complete transposition of great arteries with left ventricular outflow tract obstruction.

BACKGROUND: Long-term follow-up of patients who underwent arterial switch operation for complete transposition of great arteries with anatomic left ventricular outflow tract obstruction (LVOTO) has rarely been brought into the focus. METHODS: Of 299 patients who underwent an arterial switch operation between January 1991 and January 2001, 23 patients had anatomic LVOTO. Age ranged from 4 days to 18 years (median 90 days) and weight ranged from 2.6 to 35 kg (median 4.3 kg). Surgical management included arterial switch operation, closure of ventricular septal defect wherever indicated, and excision of LVOTO. RESULTS: Among patients with preoperative LVOTO there were 2 early deaths and 8 patients had mild neoaortic regurgitation at the time of discharge. Follow-up ranged from 8 months to 9 years (mean 60 +/- 12 months). In 4 patients who had mild neoaortic regurgitation at discharge, the regurgitation progressed to moderate or severe degree after a follow-up of 22 to 72 months. In 1 patient mild mitral regurgitation present at the time of discharge progressed to severe mitral regurgitation. This patient subsequently underwent double valve replacement. CONCLUSIONS: Presence of preoperative anatomical LVOTO in patients undergoing arterial switch operation predicts high incidence of postoperative neoaortic regurgitation.