Urinary Metabolomics Identified Metabolic Perturbations Associated with Gutka, a Smokeless Form of Tobacco.

Gutka, a form of smokeless tobacco, is widely used in the Indian subcontinent and in other regions of South Asia. Smokeless tobacco exposure is most likely to increase the incidence of oral cancer in the Indian population, and metabolic changes are a hallmark of cancer. The development of biomarkers for early detection and better prevention measures for smokeless tobacco users at risk of oral cancer can be aided by studying urinary metabolomics and offering insight into altered metabolic profiles. This study aimed to investigate urine metabolic alterations among smokeless tobacco users using targeted LC-ESI-MS/MS metabolomics approaches to better understand the effects of smokeless tobacco on human metabolism. Smokeless tobacco users' specific urinary metabolomics signatures were extracted using univariate, multivariate analysis and machine learning methods. Statistical analysis identified 30 urine metabolites significantly associated with metabolomic alterations in humans who chew smokeless tobacco. Receiver operator characteristic (ROC) curve analysis evidenced the 5 most discriminatory metabolites from each approach that could differentiate between smokeless tobacco users and controls with higher sensitivity and specificity. An analysis of multiple-metabolite machine learning models and single-metabolite ROC curves revealed discriminatory metabolites capable of distinguishing smokeless tobacco users from nonusers more effectively with higher sensitivity and specificity. Furthermore, metabolic pathway analysis depicted several dysregulated pathways in smokeless tobacco users, including arginine biosynthesis, beta-alanine metabolism, TCA cycle, etc. This study devised a novel strategy to identify exposure biomarkers among smokeless tobacco users by combining metabolomics and machine learning algorithms.

Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation.

Advanced combinatorial treatments of surgery, chemotherapy, and radiotherapy do not have any effect on the enhancement of a 5-year survival rate of oral squamous cell carcinoma (OSCC). The discovery of early diagnostic non-invasive biomarkers is required to improve the survival rate of OSCC patients. Recently, it has been reported that oral microbiome has a significant contribution to the development of OSCC. Oral microbiome induces inflammatory response through the production of cytokines and chemokines that enhances tumor cell proliferation and survival. The study aims to develop saliva-based oral microbiome and cytokine biomarker panel that screen OSCC patients based on the level of the microbiome and cytokine differences. We compared the oral microbiome signatures and cytokine level in the saliva of OSCC patients and healthy individuals by 16S rRNA gene sequencing targeting the V3/V4 region using the MiSeq platform and cytokine assay, respectively. The higher abundance of Prevotella melaninogenica, Fusobacterium sp., Veillonella parvula, Porphyromonas endodontalis, Prevotella pallens, Dialister, Streptococcus anginosus, Prevotella nigrescens, Campylobacter ureolyticus, Prevotella nanceiensis, Peptostreptococcus anaerobius and significant elevation of IL-8, IL-6, TNF-α, GM-CSF, and IFN-γ in the saliva of patients having OSCC. Oncobacteria such as S. anginosus, V. parvula, P. endodontalis, and P. anaerobius may contribute to the development of OSCC by increasing inflammation via increased expression of inflammatory cytokines such as IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF. These oncobacteria and cytokines panels could potentially be used as a non-invasive biomarker in clinical practice for more efficient screening and early detection of OSCC patients.

Ethanol in Combination with Oxidative Stress Significantly Impacts Mycobacterial Physiology.

Here, we investigate the mycobacterial response to the combined stress of an organic oxidant (cumene hydroperoxide [CHP]) and a solvent (ethanol). To understand the interaction between the two stressors, we treated Mycobacterium smegmatis cells to a range of ethanol concentrations (2.5% to 10% [vol/vol]) in combination with a subinhibitory concentration of 1 mM CHP. It was observed that the presence of CHP increases the efficacy of ethanol in inducing rapid cell death. The data further suggest that ethanol reacts with the alkoxy radicals to produce ethanol-derived peroxides. These radicals induce significant membrane damage and lead to cell lysis. The ethanol-derived radicals were primarily recognized by the cells as organic radicals, as was evident by the differential upregulation of the ohr-ohrR genes that function in cells treated with the combination of ethanol and CHP. The role of organic peroxide reductase, Ohr, was further confirmed by the significantly higher sensitivity of the deletion mutant to CHP and the combined stress treatment of CHP and ethanol. Moreover, we also observed the sigma factor σB to be important for the cells treated with ethanol alone as well as the aforementioned combination. A ΔsigB mutant strain had significantly higher susceptibility to the stress conditions. This finding was correlated with the σB-dependent transcriptional regulation of ohr and ohrR In summary, our data indicate that the combination of low levels of ethanol and organic peroxides induce ethanol-derived organic radicals that lead to significant oxidative stress on the cells in a concentration-dependent manner.IMPORTANCE Bacterial response to a combination of stresses can be unexpected and very different compared with that of an individual stress treatment. This study explores the physiological and transcriptional response of mycobacteria in response to the combinatorial treatment of an oxidant with the commonly used solvent ethanol. The presence of a subinhibitory concentration of organic peroxide increases the effectiveness of ethanol by inducing reactive peroxides that destroy the membrane integrity of cells in a significantly short time span. Our work elucidates a mechanism of targeting the complex mycobacterial membrane, which is its primary source of intrinsic resistance. Furthermore, it also demonstrates the importance of exploring the effect of various stress conditions on inducing bacterial clearance.

Inactivation of the organic hydroperoxide stress resistance regulator OhrR enhances resistance to oxidative stress and isoniazid in Mycobacterium smegmatis.

The organic hydroperoxide stress resistance regulator (OhrR) is a MarR type of transcriptional regulator that primarily regulates the expression of organic hydroperoxide reductase (Ohr) in bacteria. In mycobacteria, the genes encoding these proteins exist in only a few species, which include the fast-growing organism Mycobacterium smegmatis. To delineate the roles of Ohr and OhrR in defense against oxidative stress in M. smegmatis, strains lacking the expression of these proteins were constructed by deleting the ohrR and ohr genes, independently and together, through homologous recombination. The OhrR mutant strain (MSΔohrR) showed severalfold upregulation of Ohr expression, which could be observed at both the transcript and protein levels. Similar upregulation of Ohr expression was also noticed in an M. smegmatis wild-type strain (MSWt) induced with cumene hydroperoxide (CHP) and t-butyl hydroperoxide (t-BHP). The elevated Ohr expression in MSΔohrR correlated with heightened resistance to oxidative stress due to CHP and t-BHP and to inhibitory effects due to the antituberculosis drug isoniazid (INH). Further, this mutant strain exhibited significantly enhanced survival in the intracellular compartments of macrophages. In contrast, the strains lacking either Ohr alone (MSΔohr) or both Ohr and OhrR (MSΔohr-ohrR) displayed limited or no resistance to hydroperoxides and INH. Additionally, these strains showed no significant differences in intracellular survival from the wild type. Electrophoretic mobility shift assays (EMSAs) revealed that the overexpressed and purified OhrR interacts with the ohr-ohrR intergenic region with a greater affinity and this interaction is contingent upon the redox state of the OhrR. These findings suggest that Ohr-OhrR is an important peroxide stress response system in M. smegmatis.

Peeping Beyond TNM Stage: Prognostic Factors Affecting Oncological Outcomes in Surgically Treated Early Oral Cancer.

Surgery is the primary modality for the treatment of early oral cancer. The present study aims to evaluate the oncological outcomes, patterns of failure, and prognostic predictors of recurrence in patients of early oral cancer (Stage I and II) treated by surgery alone. It is a single institutional, observational retrospective cohort study conducted from 2012 to 2017.The study was approved by institutional ethics committee. All consecutive patients who underwent upfront curative surgery alone (wide excision of tumour + neck dissection) for pathologically proven early oral cavity SCC(Squamous Cell Carcinoma) pT1-2N0 were included in the study. 113 patients were included in the study after a median follow-up of 58.2 months. The median age was 58.5 years. 25 patients were stage I, and 88 patients were stage II. The most common subsite was buccal mucosa. There were 31 recurrences and 24 deaths. Using Kaplan Meier method, 3 and 5 year overall survival was 92% and 71.8%, respectively, while 3 year and 5 year recurrence-free survival was 77.9% and 69.4%, respectively. Perineural invasion and poor differentiation affected recurrence-free survival significantly (p value < 0.05). More than one-fourth of surgically treated early oral SCC patients developed recurrence. Presence of poorly differentiated histology and the perineural invasion were the high risk factors which hampered the recurrence free survival. High consumption of betel quid consumption in this part of the world leads to differences in the involved subsite from the Western literature. Adding adjuvant treatment in the presence of these adverse histopathological features may improve prognosis. Randomised studies are warranted to answer this dilemma. Level of Evidence IV.

Can Radiological Tumour Thickness Predict Pathological Prognostic Factors in Clinicoradiologically Node-Negative Oral Squamous Carcinoma? A Prospective Study.

Background: This research investigates potential connections between radiological tumour thickness determined by CT scans and various pathological prognostic factors. These factors include pathological tumour thickness (pTT), pathological depth of invasion (DOI), and positive cervical nodal metastasis. This analysis focuses on cases of clinicoradiologically node-negative squamous cell carcinoma of the buccal mucosa. Method: Sixty-one previously untreated clinicoradiologically node-negative squamous cell carcinoma of buccal mucosa were included in the study. The radiological tumour thickness in the preoperative CT scans is correlated with other prognostic factors like pathological tumour thickness, DOI and presence or absence of neck node. Result: Sixty-one patients were included in the study with a median age of 54 years (Range 27-84). Forty-two patients (68.9%) were male, and 19 were females (31.1%). There was no statistically significant difference in mean values of rTT among patients with positive or negative post-operative nodal metastases. However, a significant correlation could be established with rTT to other potential prognostic factors. Conclusion: Tumor thickness in preoperative CT scans can be used to predict post-operative prognostic factors in oral squamous cell carcinoma.

The ΔfbpAΔsapM candidate vaccine derived from Mycobacterium tuberculosis H37Rv is markedly immunogenic in macrophages and induces robust immunity to tuberculosis in mice.

Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Guérin (BCG) vaccine against TB is used in infants but shows variable protection. Here, we introduce a novel approach using a double gene knockout mutant (DKO) from wild-type Mycobacterium tuberculosis (Mtb) targeting fbpA and sapM genes. DKO exhibited enhanced anti-TB gene expression in mouse antigen-presenting cells, activating autophagy and inflammasomes. This heightened immune response improved ex vivo antigen presentation to T cells. Subcutaneous vaccination with DKO led to increased protection against TB in wild-type C57Bl/6 mice, surpassing the protection observed in caspase 1/11-deficient C57Bl/6 mice and highlighting the critical role of inflammasomes in TB protection. The DKO vaccine also generated stronger and longer-lasting protection than the BCG vaccine in C57Bl/6 mice, expanding both CD62L-CCR7-CD44+/-CD127+ effector T cells and CD62L+CCR7+/-CD44+CD127+ central memory T cells. These immune responses correlated with a substantial ≥ 1.7-log10 reduction in Mtb lung burden. The DKO vaccine represents a promising new approach for TB immunization that mediates protection through autophagy and inflammasome pathways.

A serine/threonine phosphatase encoded by MG_207 of Mycoplasma genitalium is critical for its virulence.

BACKGROUND: Bacterial signal transduction systems like two component system (TCS) and Serine/Threonine kinase (STK) and Serine/Threonine phosphatase (STP) play important roles in the virulence and pathogenesis of bacterial pathogens. Mycoplasma genitalium, a mollicute that causes the urogenital diseases urethritis and cervicitis in men and women, respectively, is a pathogen which lacks TCS but possesses STK/STP. In this study, we investigated the biochemical and virulence properties of an STP protein encoded by the gene MG_207 of this species. RESULTS: We overexpressed MG207 in Escherichia coli overexpression system as a recombinant His10MG207 protein and purified it with affinity chromatography. This recombinant protein readily hydrolyzed the substrate p-nitrophenyl phosphate (pNPP) in a dose-dependent manner. Additional studies using synthetic peptides as substrates revealed that the recombinant protein was able to hydrolyze the threonine phosphate. Further, a transposon insertion mutant strain of M. genitalium (TIM207) that lacks the protein MG207 showed differentially phosphorylated proteins when compared to the wild type G37 strain. Mass spectrometry revealed that some of the key proteins differentially phosphorylated in TIM207 strain were putative cytoskeletal protein encoded by the gene MG_328 and pyruvate dehydrogenase E1 α chain encoded by the gene MG_274. In addition, TIM207 was noticed to be less cytotoxic to HeLa cells and this correlated with the production of less hydrogen peroxide by this strain. This strain was also less efficient in inducing the differentiation of THP-1 cell line as compared to wild type M. genitalium. CONCLUSIONS: The results of the study suggest that MG207 is an important signaling protein of M. genitalium and its presence may be crucial for the virulence of this species.

Lymphoepithelial carcinoma of the larynx: A clinical report with pooled analysis and review of published cases.

ABSTRACTS: Lymphoepithelial carcinoma (LEC) of the larynx is a rare tumor comprising 0.2% of all laryngeal neoplasms. To our knowledge, less than 50 cases of LEC of the larynx are reported in the literature. The lack of specific guidelines leads to uncertainty on this rare entity's diagnosis, treatment, and follow-up. The association of Epstein-Barr virus as a predisposing factor of LEC has been proposed in a few reports. Although the occurrence of LEC in the larynx is infrequent, it is essential to differentiate it from squamous cell carcinoma. Immunohistochemistry should be performed to demonstrate cytokeratin expression. It is a very aggressive tumor with high metastatic potential; however, it is hard to comment on the disease outcome of LEC of the larynx because only case reports are available in the literature. Here, we report a case of LEC of the larynx (CK +ve, CD 45 -ve, and EBER-ISH -ve) in a 49-year-old male. Initially, the patient was planned for surgery but defaulted. He reported back after 4 months, and there was clinicoradiological disease progression. Because of the unresectable status and poor general condition, he received palliative radiotherapy only. Additionally, we have conducted a pooled analysis of the individual cases of LEC of larynx available in the literature to understand the clinical behavior to optimize the treatment of these patients.

Pathogenic mycoplasmas of humans regulate the long noncoding RNAs in epithelial cells.

Non-coding RNAs (ncRNAs), specifically long ncRNAs (lncRNAs), regulate cellular processes by affecting gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging evidence indicates that pathogenic microbes dysregulate the expression of host lncRNAs to suppress cellular defense mechanisms and promote survival. To understand whether the pathogenic human mycoplasmas dysregulate host lncRNAs, we infected HeLa cells with Mycoplasma genitalium (Mg) and Mycoplasma penumoniae (Mp) and assessed the expression of lncRNAs by directional RNA-seq analysis. HeLa cells infected with these species showed up-and-down regulation of lncRNAs expression, indicating that both species can modulate host lncRNAs. However, the number of upregulated (200 for Mg and 112 for Mp) and downregulated lncRNAs (30 for Mg and 62 for Mp) differ widely between these two species. GREAT analysis of the noncoding regions associated with differentially expressed lncRNAs showed that Mg and Mp regulate a discrete set of lncRNA plausibly related to transcription, metabolism, and inflammation. Further, signaling network analysis of the differentially regulated lncRNAs exhibited diverse pathways such as neurodegeneration, NOD-like receptor signaling, MAPK signaling, p53 signaling, and PI3K signaling, suggesting that both species primarily target signaling mechanisms. Overall, the study's results suggest that Mg and Mp modulate lncRNAs to promote their survival within the host but in distinct manners.

Orbital Exenteration: Tumour Diversity and Survival-Report from a Cancer Centre of Northeast India.

Orbital exenteration is a mutilating surgery which involves the removal of the entire contents of the bony orbit, including the globe, extraocular muscles and periorbital fat, and many times includes the eyelids. Since it leads to severe disfigurement, it is an infrequent procedure largely indicated in malignant conditions. The current study aims to report the clinicodemographic profile and treatment outcome of orbital exenteration patients done in a cancer care center in Northeast India. This is a hospital-based retrospective study between January 2017 and December 2021, including patients undergoing orbital exenteration. All patient and treatment-related data were retrieved from the record of hospital files. A total of 18 patients were included in the study. The mean age of the patients was 51 ± 18 years and male: female ratio was 1:1. Most patients had primary in orbit (55.6%). The most common histology was squamous cell carcinoma, (8/18, 44.4%), followed by basal cell carcinoma (two patients, 11.1%). After a median follow-up was 25 months (range 3-92), the median DFS of the study population was 31.4 months. The five-year overall survival of the patients was 54%. Orbital exenteration is an infrequent surgery due to the associated disfigurement and hence reserved for conditions where eye preservation is impossible. We tried to report the experience of orbital exenteration from a single cancer center for five years.

Submandibular Gland in Neck Dissection: Necessary Fatality or Unfortunate Prey?

Excision of submandibular gland is currently victim in all neck dissections. In this study we intend to estimate the prevalence of submandibular gland involvement in squamous cell oral carcinomas and identify the factors associated with it. This is a single institutional, retrospective observational study conducted from 22 to 2018 to 28 February 2020. 317 patients were included for analysis as per study criteria. The prevalence of involvement of submandibular gland was 3.8%. Increased risk of submandibular gland involvement was associated with involvement of level-Ib nodes (Odds ratio: 13.6, 2.9-63.3, 95% CI and p = < 0.001) and presence of extra-nodal extension (Odds ratio: 67, 8.4-532, 95% CI and p = < 0.001) and perineurial invasion (Odds ratio: 5, 1.6-16.8 and p = 0.003). In oral cancers, especially early stage carcinoma of buccal mucosa, submandibular gland preservation may be feasible in absence of extra-nodal extension and level-Ib involvement.

Modified nasolabial flap- the nasomentolabial flap: A new arrow in surgeon's quiver.

AIMS AND OBJECTIVES: To describe an inferior extension of a naso-labial flap as an adjunct to a maleo-labial flap in reconstruction of complete thickness defects around the oral commissure in 2 cases that we performed at our institute. METHODS: Two elderly cases of carcinoma buccal mucosa who underwent wide local excision along with neck dissection had moderately large peri-oral defects that are large to cover with nasolabial flap alone. An inferior extension to the maleo-labial flap was added, making it a naso-mento-labial flap to reconstruct the defects with an acceptable outcome aesthetically and functionally. The reconstructed defects' size was around 7 × 7cms and 8.5 × 6cms full-thickness defect in the buccal mucosa, respectively, with the extension of the defect in both the patients being almost the same with anterior extension to commissure, posteriorly to retro-molar trigone (RMT), laterally full-thickness, medially not involving alveolus. RESULTS: The incision at the donor site was closed primarily. The reconstruction did achieve the patient acceptable aesthetics, functionality, color and texture. The mean follow up of the patients is around 1 year with no complications. CONCLUSION: Naso-mento-labial flap, an inferiorly extended inferiorly based nasolabial flap is a useful addition to surgeon's armamentarium for reconstructing the buccal mucosa and peri-oral defects in patients whose general health prevents the using pedicled or free flaps.

Loupe Assisted Thyroidectomy: A Tool for Reducing Complications.

The objective of this study is to assess if the use of magnification can reduce the incidence of hypocalcemia and vocal cord palsy in thyroid surgery. Data of patients who underwent total thyroidectomy (N = 50) for thyroid malignancy were analyzed retrospectively for 1 year. The patients were divided into two groups based on surgery with and without loupes. Hypocalcemia and Vocal cord palsy was assessed pre as well as post-operatively and the observations were noted. Descriptive statistics were performed to assess the proportion of the respective groups. Inferential statistics to find out the difference between the groups was done using the chi-square test. Significance level was kept at 5%. The incidence of hypocalcemia was 36.9% in the group done without loupes compared to 7.6% with loupes. The event of vocal cord injury though transient was 33% when done without loupes (p < 0.05). Magnification is crucial for the visualization of the neurovascular anatomy which is depicted in our study. Although the study includes less number of cases, it is evident that the use of loupe magnification can reduce the morbidity associated with thyroid surgery to a great extent. We recommend the use of loupe magnification during surgery whenever possible.

Pattern of Nodal Metastasis in Relation to Size of the Primary Tumour in Well-Differentiated Thyroid Carcinoma.

This study was conducted to see the pattern of neck node metastasis in relation to the size of primary tumour in Well-differentiated thyroid cancer. A prospective study on 50 patients was carried out in the Department of Head and Neck Surgery, Dr B. Borooah Cancer Institute from 1st August, 2018 to 31st July, 2019. All new cases who had not previously received treatment were included which were histopathogically proven. Residual and recurrent cases were not taken into account. Most common age-group affected was 21-30 years (24%). It was more common in females (84%). Papillary thyroid cancer has been found to be the most common histological type of WDTC (88%), out of which the classical variant of PTC constitute 72%. 46% of them had tumour size > 4 cm 88% cases had cervical neck node metastases, out of which 72% were unilateral and 16% were bilateral. The commonest level involved was level VI. There is a definite correlation (clinical and histological) between increased involvement of positivity of lymph node in relation to size of the primary tumour in well-differentiated thyroid carcinoma.

Patient Reported Outcomes of Scalp and Forehead Reconstruction for Defects Following Oncological Resections (North-East Indian Tertiary Cancer Centre Study).

Background Approximately 1-2% of all scalp tumours are malignant, but they comprise up to 13% of all malignant cutaneous neoplasms. The current study presents our experience of reconstruction of scalp and forehead for malignant tumours treated at our centre. Methods This is a single institutional observational study conducted at a tertiary cancer centre in North East India. Post-operative outcomes related to quality of life of patients were measured with help of FACE-Q scales. Face-Q -Satisfaction with outcome and FACE-Q- appearance related psychosocial distress scores were analysed. Histograms were used for descriptive statistics. Data were checked for normality using Kolmogorov-Smirnova and Shapiro-Wilk test. For non-normal data Wilcoxon test was used. A p value less than 0.05 was considered as statistically significant at 5% level of significance. Results Mean age of patients was 57.6 ± 14.2 years. The mean defect size was 89.036 ± 81.77 cm2. The mean satisfaction with outcome scores and distress scores at 3-months was 54.9 ± 8.6 and 34.8 ± 8.5 respectively with a statistically significant p value of 0.001.Mean satisfaction scores and psychological distress scores were better at the end of three months when compared to at the time of discharge with a statistical significant p value of < 0.0001. Conclusion Scalp and forehead reconstructions for defects following oncological resections are technically challenging and if chosen carefully with meticulous planning, both local and free tissue transfers give satisfactory outcome in long term follow up. There are lots of reconstruction options for scalp and forehead defects and knowledge of the basic bio-geometry of the each flap is must.

Mycoplasma genitalium and M. pneumoniae Regulate a Distinct Set of Protein-Coding Genes in Epithelial Cells.

Mycoplasma genitalium and M. pneumoniae are two significant mycoplasmas that infect the urogenital and respiratory tracts of humans. Despite distinct tissue tropisms, they both have similar pathogenic mechanisms and infect/invade epithelial cells in the respective regions and persist within these cells. However, the pathogenic mechanisms of these species in terms of bacterium-host interactions are poorly understood. To gain insights on this, we infected HeLa cells independently with M. genitalium and M. pneumoniae and assessed gene expression by whole transcriptome sequencing (RNA-seq) approach. The results revealed that HeLa cells respond to M. genitalium and M. pneumoniae differently by regulating various protein-coding genes. Though there is a significant overlap between the genes regulated by these species, many of the differentially expressed genes were specific to each species. KEGG pathway and signaling network analyses revealed that the genes specific to M. genitalium are more related to cellular processes. In contrast, the genes specific to M. pneumoniae infection are correlated with immune response and inflammation, possibly suggesting that M. pneumoniae has some inherent ability to modulate host immune pathways.

Diclofenac versus tramadol for mucositis related pain in head and neck cancer patients undergoing concurrent chemoradiation-a phase 3 study.

BACKGROUND: Oral mucositis related pain during CTRT in head and neck cancers is a common problem. Unfortunately, in spite of it being common, there is limited evidence for selection of systemic analgesic in this situation. Hence, this study was designed to compare the analgesic effect of a non-steroidal anti-inflammatory drug (diclofenac) versus a weak opioid (tramadol). PATIENTS AND METHODS: This was an open-label, parallel design, superiority randomised controlled study. In this study, head and neck cancer patients undergoing radical or adjuvant chemoradiation, who had grade 1 or above mucositis (in accordance with Common Terminology Criteria for Adverse Events version 4.03) and had pain related to it were randomly assigned to either diclofenac or tramadol for mucositis related pain control. The primary endpoint was analgesia after the first dose. The secondary endpoints were the rate of change in analgesic within 1 week, adverse events and quality of life. RESULTS: One hundred and twenty-eight patients were randomised, 66 in diclofenac and 62 in tramadol arm. The median area under the curve for graph of pain across time after first dose of pain medication for the diclofenac arm and the tramadol arm was 348.936 units (range: 113.64-1,969.23) and 420.87 (101.97-1,465.96), respectively, (p = 0.05619). Five patients (8.1%) in the tramadol arm and 11 patients (16.7%) in the diclofenac arm required a change in analgesic within 1 week of starting the analgesic (p = 0.184). There was no statistically significant difference in any adverse events between the two arms. However, the rate of any grade of renal dysfunction was numerically higher in the diclofenac arm (10.6% versus 4.8%, p = 0.326). CONCLUSION: In this phase 3 study, evaluating diclofenac and tramadol for chemoradiation induced mucositis pain, there was no statistical difference in analgesic activity of these two drugs.

Microbial surfactants and their potential applications: an overview.

Biosurfactant or microbial surfactants produced by microbes are structurally diverse and heterogeneous groups of surface-active amphipathic molecules. They are capable of reducing surface and interfacial tension and have a wide range of industrial and environmental applications. The present chapter reviews the biochemical properties of different classes of microbial surfactants and their potential application in different industrial sectors.

Methionine sulfoxide reductase A (MsrA) modulates cells and protects against Mycoplasma genitalium induced cytotoxicity.

Methionine sulfoxide reductase A (MsrA) is a ubiquitous antioxidant repair enzyme which specifically reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Previous studies have shown that lack of or overexpression of MsrA in cells affects the function of proteins and can lead to altered cellular processes. Interestingly, some pathogenic bacteria secrete and/or carry MsrA on their surface, suggesting some key roles for this enzyme in the modulation of host cellular processes. Therefore, we investigated how exogenously added MsrA affects the ability of the host cells in combating infection by using an in vitroMycoplasma genitalium cytotoxicity model. HeLa cells pretreated with MsrA and infected with M. genitalium showed significantly lower necrosis (cytotoxicity) than untreated cells infected with M. genitalium. Intriguingly, necrotic cell death pathway specific real time RT-PCR revealed that M. genitalium infection upregulates the expression of the TNF gene in HeLa cells and that MsrA pretreatment of the cells downregulates its expression significantly. Consistent with this, enzyme linked immunosorbent assay (ELISA) results showed that HeLa cells pretreated with MsrA secreted reduced levels of TNF-α following M. genitalium infection. Also, our study demonstrates that MsrA treatment of cells affects the phosphorylation status of transcriptional regulators such as NF-кB, JNK and p53 that regulate different cytokines. Further, fluorescent microscopy showed the cellular uptake of exogenously added MsrA fused with red fluorescent protein (MsrA-RFP). Altogether, our results suggest that secreted MsrA may help pathogens to modulate host cellular processes.