P16 expression and clinicopathological features of oral and oropharyngeal squamous cell carcinoma

Background: There is an epidemiological shift in head and neck squamous cell carcinoma (HNSCC) attributable to HPV infection. HPV positive HNSCC has unique biology, risk factors, clinicopathological characteristics and outcome. There is a large variation in the published prevalence of HPV-related HNSCCs in India ranging from 7 to 78.7%. This study aims to find the P16 expression in the oral cavity and oropharyngeal SCC, thereby prevalence of HPV in our setting and to define the clinicopathological characteristics of HPV positive tumours in our setting.Methods: 210 specimens of primary Oral squamous cell carcinoma (OSCC) and Oropharyngeal Squamous cell carcinoma (OPSCC) were included. Immunohistochemistry was done using monoclonal mouse p16 antibody. Clinical details of each case were collected. Analysis was done using SPSS software and the association of P16 and clinicopathological variables were calculated using Fishers exact test.Results: P16 positive expression is observed only in 1/122 (0.82%) of OSCC and 8/88 (9%) of OPSCC. P16 positivity showed significant association with Grade of tumor (p= 0.008) and histological variant of SCC (p=0.00). 77.7% of P16 positive tumours are Grade 2 and 66.6% of Basaloid SCC was P16 positive. There is no significant association between p16 expression and other variables (subsite, age, gender, alcoholism, smoking, betel chewing and stage).Conclusions: P16 positivity was higher in oropharyngeal than in oral cancer. However, the HPV positivity rates are lower than other parts of India

AN ANTIMICROBIAL PHTHALATE DERIVATIVE FROM BACILLUS CEREUS, THE SYMBIOTIC BACTERIUM ASSOCIATED WITH A NOVEL ENTOMOPATHOGENIC NEMATODE, RHABDITIS (OSCHEIUS) SP

Objective: To isolate and identify the bioactive metabolites from the culture filtrates of a bacterium (Bacillus cereus) symbiotically associated with a novel entomopathogenic nematode Rhabditis (Oscheius) species.Methods: The bacterium was cultured in three different media and the antimicrobial activity was determined by the well diffusion assay. The ethyl acetate extract of the cell free culture filtrate was then purified by silica gel column chromatography and thin layer chromatography. Identification of the active metabolite was done with HPLC, GC-MS and LC-MS.Results: The cell free culture filtrate of a nematode symbiotic bacterium showed both antibacterial and antifungal activities. Fermentation conditions were standardized and optimum antibacterial activity was observed in tryptic soy broth at 72 h of incubation at 30 °C. When the ethyl acetate extract was purified by silica gel column chromatography and thin layer chromatography, an active fraction was obtained which was subjected to HPLC analysis along with GC-MS and LC-MS leading to the identification of a major compound Bis (2-ethyl hexyl) phthalate. The compound was active against Gram positive bacteria Bacillus subtilis MTCC2756, Staphylococus aureus MTCC902, Gram negative bacteria Escherichia coli MTCC 2622 and fungi such as Aspergillus flavus MTCC277, Candida albicans MTCC183, Fusarium oxysporum MTCC 284, Rhizoctonia solani MTCC 4634.Conclusion: Bis (2-ethyl hexyl) phthalate was identified as one of the metabolites produced by a nematode symbiotic bacterium associated with a novel entomopathogenic nematode Rhabditis (Oscheius) species. Thus similar compounds isolated from novel entomopathogenic bacteria would pave the way for identifying new drugs for the pharmaceutical and agricultural sector.Â

Lupus anticoagulant in systemic lupus erythematosus and its association with complications

Background: The anti-phospholipid antibody which can occur secondary to SLE have a broad spectrum of both thrombotic and non-thrombotic manifestations. Among the three antiphospholipid antibodies, lupus anticoagulant has the strongest association with antiphospholipid syndrome (APS) and increased chance of recurrence of thrombotic events. Hence early screening of lupus anticoagulant is needed.Methods: 72 clinically diagnosed SLE patients were included. The PT, aPTT were done in all patients. The clotting time is assessed by semi-automated coagulation analyser by using dilute russell viper venom time (dRVV) screen and confirm kits. Lupus anticoagulant was considered to be positive if the screen to confirm ratio is ≥1.2. The patients were followed up for a period of 1 year at regular 3 months interval. The various complications like hemolytic anemia, thrombocytopenia, deep vein thrombosis, cerebrovascular accident/transient ischemic attack (CVA/TIA), myocardial infarction, abortions, pulmonary artery hypertension and lupus nephritis were recorded.Results: Lupus anticoagulant was positive in 38.8% among the study group. The most common thrombotic event observed was DVT (16.7%) followed by MI (11.1%) and CVA/TIA (8.3%). There is significant association between lupus anticoagulant positivity with hemolytic anemia, DVT and pulmonary artery hypertension.Conclusions: The lupus anticoagulant has the strongest association with APS in SLE patients and dRVVT is the test of choice in diagnosing APLA. Early recognition of APLA can reduce the risk of thrombotic complications and can prevent further episodes by giving adequate thromboprophylaxis to lupus anticoagulant positive patients

Protection of mice against Plasmodium berghei infection by a tuftsin derivative

In Plasmodium berghei infections, the mortality rate and parasitaemias were significantly reduced and the mean survival time was considerably enhanced by pretreating the animals with a tuftsin derivative, Thr-Lys-Pro-Arg-NH-(CH2)2-NHCOC15H31. This effect of the modified tuftsin was further increased upon its incorporation in the liposome bilayer. These results indicate that tuftsin and its derivatives may prove useful in enhancing nonspecific host resistance against protozoan infections

Messenger RNA expression of pattern recognition receptor proteins in the pearl oyster Pinctada fucata (Gould, 1850) in response to lipopolysaccharide stimulation

Pattern recognition receptor proteins (PRP) are capable of binding specifically to conserved portion of microbial cell wall components and they are involved in the recognition of different immune modulators. Proteins such as F-type lectin, galectin and LGBP play protective role in innate immunity of invertebrates. The time dependent expression of F-type lectin gene as well as galectin and LGBP genes was determined after lipopolysaccharide (LPS) challenge in the pearl oyster Pinctada fucata. A significant increase of mRNA expression levels of all the three genes under study was observed in haemocytes, reaching a maximum level at 8 h post-challenge and then declined to basal levels at 36 h. These results suggest that PRPs play a critical role in the innate immune system of the pearl oyster P. fucata

Molecular cloning, characterization and expression analysis of cytoplasmic Cu/Zn-superoxid dismutase (SOD) from pearl oyster Pinctada fucata

Because of its capacity to rapidly convert superoxide to hydrogen peroxide, superoxide dismutase (SOD) is crucial in both intracellular signalling and regulation of oxidative stress. In this paper we report the cloning of a Cu/Zn SOD (designated as pfSOD) from the pearl oyster (Pinctada fucata) using rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA of this Cu/Zn SOD contains an open reading frame (ORF) of 471 bp coding for 156 amino acids. No signal peptide was identified at the N-terminal amino acid sequence of Cu/Zn SOD indicating that this pfSOD encodes a cytoplasmic Cu/Zn SOD. This is supported by the presence of conserved amino acids required for binding copper and zinc. Semi-quantitative analysis in adult tissues showed that the pfSOD mRNA was abundantly expressed in haemocytes and gill and scarcely expressed in other tissues tested. After challenge with lipopolysaccharide (LPS), expression of pfSOD mRNA in haemocytes was increased, reaching the highest level at 8 h, then dropping to basal levels at 36 h. These results suggest that Cu/Zn SOD might be used as a bioindicator of the aquatic environmental pollution and cellular stress in pearl oyster

Differential and additional expression of proteins in the subcellular organelles of Penaeus monodon (Fabricus) in response to white spot syndrome virus (WSSV) infection

Currently the most common and devastating disease of shrimp is caused by the white spot syndrome virus (WSSV), which has spread throughout the world mainly by different species of crustaceans carrying the virus. Penaeus monodon were challenged with WSSV and the protein expression variation studied over a period of time. The gills, one of the main target organs of WSSV, showed upregulation of 24 proteins and expression of three novel proteins after infection. In the hepatopancreas, 20 upregulated proteins and six novel proteins were observed. The muscle showed upregulation of 11 proteins and one new protein. Subcellular organelles like nuclear and mitochondrial proteins of each tissue showed different profiles with either increased/decreased expression of few proteins or additional expression of novel proteins. The protein profiles resolved in the study provide a rich source of information on proteins in shrimp which may be involved in antiviral response

Clonal emergence of Klebsiella pneumoniae ST14 co-producing OXA-48-type and NDM carbapenemases with high rate of colistin resistance in Dubai, United Arab Emirates

© 2018 Elsevier Ltd Few studies have addressed the molecular epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 to June 2016 were determined. Thirty-three percent of the collection of 70 Klebsiella pneumoniae, 13 Escherichia coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (4 K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM and 22.1% both OXA-48-like and NDM, respectively. Pulsed-field gel electrophoresis clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group.

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives. Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance. Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors. Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research.</p

HIV-1 Promotes Renal Tubular Epithelial Cell Protein Synthesis: Role of mTOR Pathway

Tubular cell HIV-infection has been reported to manifest in the form of cellular hypertrophy and apoptosis. In the present study, we evaluated the role of mammalian target of rapamycin (mTOR) pathway in the HIV induction of tubular cell protein synthesis. Mouse proximal tubular epithelial cells (MPTECs) were transduced with either gag/pol-deleted NL4-3 (HIV/MPTEC) or empty vector (Vector/MPTEC). HIV/MPTEC showed enhanced DNA synthesis when compared with Vector/MPTECs by BRDU labeling studies. HIV/MPTECs also showed enhanced production of β-laminin and fibronection in addition to increased protein content per cell. In in vivo studies, renal cortical sections from HIV transgenic mice and HIVAN patients showed enhanced tubular cell phosphorylation of mTOR. Analysis of mTOR revealed increased expression of phospho (p)-mTOR in HIV/MPTECs when compared to vector/MPTECs. Further downstream analysis of mTOR pathway revealed enhanced phosphorylation of p70S6 kinase and associated diminished phosphorylation of eEF2 (eukaryotic translation elongation factor 2) in HIV/MPTECs; moreover, HIV/MPTECs displayed enhanced phosphorylation of eIF4B (eukaryotic translation initiation factor 4B) and 4EBP-1 (eukaryotic 4E binding protein). To confirm our hypothesis, we evaluated the effect of rapamycin on HIV-induced tubular cell downstream signaling. Rapamycin not only attenuated phosphorylation of p70S6 kinase and associated down stream signaling in HIV/MPTECs but also inhibited HIV-1 induced tubular cell protein synthesis. These findings suggest that mTOR pathway is activated in HIV-induced enhanced tubular cell protein synthesis and contributes to tubular cell hypertrophy