Effect of interleukin-22 on immunogenicity of DNA vaccine encoding TSA gene of leishmania major in BALB/c mice

Background and purpose: Previous Research shows the use of plasmids containing genes TSA to be useful as vaccines for Leishmania major. Recently, the role of interleukin-22 (IL-22) in tissue repair has been demonstrated. In this research, the effect of IL-22 on encoding TSA gene of Leishmania major in BALB/c mice was assessed

Study of malignant tumours of the uterine corpus: histopathology and immunohistochemistry

Background: The uterine corpus represents the second most common site for malignancy in the female genital tract. This study was performed to ascertain the profile of malignant tumours of the uterine corpus reported at our centre.Methods: A retrospective analysis of cases retrieved from the archives of the department of pathology from January 2014 to December 2016. Clinical information of the patients was collected from the hospital records.  Classification and grading of the tumours were done according to the current WHO classification.Results: Nineteen cases were studied. There were ten cases of endometrial adenocarcinoma, five cases of leiomyosarcoma, three cases of endometrial stromal sarcoma and one case of carcinosarcoma(malignant mixed mullerian tumour). The age range of endometrial adenocarcinoma was 55 to 85 years and presented with post menopausal bleeding, whereas endometrial stromal sarcomas occurred in women above 45 years of age. Leiomyosarcomas had age range from 26 to 65 years. All leiomyosarcomas were clinically diagnosed as fibroid. Majority of endometrial adenocarcinomas were well differentiated endometroid type. Out of the three endometrial stromal sarcomas two were high grade, one with metastasis. All leiomyosarcomas showed mitotic rate above 10/10hpf.Conclusions: Endometrial carcinomas form the majority of malignant tumours of uterine corpus and occur in older age group followed by leiomyosarcomas. Endometrial stromal sarcomas are less common and occur in middle aged and older patients. Leiomyosarcomas and stromal sarcomas are usually misdiagnosed as fibroids clinically unless metastases are present

Approach for reporting serous effusion fluid in pleural, peritoneal and pericardial cavity and immunohistochemistry

Background: The aim of this study is to make a detailed cytological study of effusion fluids and compare with cell block study of the representative cases and IHC studies were done.Methods: Prospective study of 216 cases effusion fluids from in and around hospitals, Mangalore. This study conducted over a period of 18 months from October-2014 to April-2016. This study scrutinized and approved by Institutional Ethics Committee. The samples were processed by conventional cytology using Papanicolaou-stain and Cell Block (CB) method using 10% Alcohol-formalin fixative and stained with H and E. The cellularity, architectural patterns, morphological details were studied both smears. Ancillary immunohistochemical staining with calretinin and EMA are done.Results: A total of 216 cases of effusion fluids with cell block study were included, age range of 13 years to 93 years. Pleural fluid comprised of 55.09%, peritoneal fluid of 43.51% and pericardial fluid of 1.38%. 71% were clinically diagnosed as non-neoplastic and 29% were neoplastic condition. In CS study, 84.5% cases were benign/reactive effusion and 8.5% were positive for malignancy. In CB study, 84.5% were benign/reactive effusion and 10.2% were positive for malignancy. In comparison authors found an increase in diagnostic efficacy by 18%. IHC EMA for adenocarcinoma cells has sensitivity of 100% and calretinin for reactive mesothelial cells has specificity of 100%.Conclusions: Authors concluded that cell block technique when used as an adjuvant to routine smear examination in effusion fluids has increased the diagnostic yield and better preservation of architectural pattern. IHC is helpful in differentiating between reactive mesothelial and adenocarcinoma cells

Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

<p><b>Background and Purpose:</b> The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.</p> <p><b>Methods:</b> The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P≤0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.</p> <p><b>Results:</b> The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.</p> <p><b>Conclusions:</b> The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.</p&gt

Streptococcus anginosus bacteremia: a septic IVC thrombus and a large empyema requiring decortication

A previously healthy 39 year old male presented with complaints of cough, fever, abdominal pain and chills. The patient was found to be in active sepsis with hypotension on presentation so was resuscitated while a full septic work-up was ordered. Initial chest X-ray showed only increased broncho-alveolar markings and no consolidations, but blood cultures eventually revealed Streptococcus anginosus bacteremia. Intravenous antibiotics were started and infective endocarditis was ruled out. Computerized tomography scan of the abdomen with contrast revealed findings suggestive of a septic hepatic inferior vena cava thrombus and right lower lung findings suggestive of septic embolization and an empyema. Later on during admission, CT scan of the chest with contrast revealed a moderate-sized empyema of the right lung which eventually required decortication. Discovering such findings concurrently in a single patient is extremely rare, particularly an embolizing septic IVC thrombus with confirmed bacteremia. For this reason it is described in the following case presentatio

Aurora kinase-C-T191D is constitutively active mutant

<p>Abstract</p> <p>Background</p> <p>Aurora kinases (Aurora-A, B and C) belong to a family of conserved serine/threonine kinases which are key regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in somatic cells and involved in cell cycle regulation while aurora-C is meiotic chromosome passenger protein. As Aurora kinase C is rarely expressed in normal somatic cells and has been found over expressed in many cancer lines. It is suggested that Aurora-C-T191D is not hyperactive mutant.</p> <p>Result</p> <p>Aurora-C-T191D variant form was investigated and compared with wild type. The overexpression of Aurora-C-T191D was observed that it behaves like Aurora-C wild type (aurC-WT). Both Aurora-C-T191D and aurC-WT induce abnormal cell division resulting in centrosome amplification and multinucleation in transiently transfected cells as well as in stable cell lines. Similarly, Aurora-C-T191D and aurC-WT formed foci of colonies when grown on soft agar, indicating that a gain of Aurora-C activity is sufficient to transform cells. Furthermore, we reported that NIH-3 T3 stable cell lines overexpressing Aurora-C-T191D and its wild type partner induced tumour formation when injected into nude mice, demonstrating the oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough tumour aggressiveness was positively correlated with the rate of kinase activity, making Aurora-C a potential anti-cancer therapeutic target.</p> <p>Conclusion</p> <p>These findings proved that Aurora C-T191D is not hyperactive but is constitutively active mutant.</p

A Valid and Reliable Instrument for Cognitive Complexity Rating Assignment of Chemistry Exam Items

The design and use of a valid and reliable instrument for the assignment of cognitive complexity ratings to chemistry exam items is described in this paper. Use of such an instrument provides a simple method to quantify the cognitive demands of chemistry exam items. Instrument validity was established in two different ways: statistically significant correlations between expert-based cognitive complexity ratings and student performance (as measured through statistical difficulty of items), and statistically significant correlations between expert-based cognitive complexity ratings and student mental effort ratings. Key benefits associated with instrument use include an enhanced understanding of the cognitive complexity of chemistry assessment tasks and as a means for characterizing exam content for the measurement of cognitive development

Suboptimal Activation of Antigen-Specific CD4+ Effector Cells Enables Persistence of M. tuberculosis In Vivo

Adaptive immunity to Mycobacterium tuberculosis controls progressive bacterial growth and disease but does not eradicate infection. Among CD4+ T cells in the lungs of M. tuberculosis-infected mice, we observed that few produced IFN-γ without ex vivo restimulation. Therefore, we hypothesized that one mechanism whereby M. tuberculosis avoids elimination is by limiting activation of CD4+ effector T cells at the site of infection in the lungs. To test this hypothesis, we adoptively transferred Th1-polarized CD4+ effector T cells specific for M. tuberculosis Ag85B peptide 25 (P25TCRTh1 cells), which trafficked to the lungs of infected mice and exhibited antigen-dependent IFN-γ production. During the early phase of infection, ∼10% of P25TCRTh1 cells produced IFN-γ in vivo; this declined to <1% as infection progressed to chronic phase. Bacterial downregulation of fbpB (encoding Ag85B) contributed to the decrease in effector T cell activation in the lungs, as a strain of M. tuberculosis engineered to express fbpB in the chronic phase stimulated P25TCRTh1 effector cells at higher frequencies in vivo, and this resulted in CD4+ T cell-dependent reduction of lung bacterial burdens and prolonged survival of mice. Administration of synthetic peptide 25 alone also increased activation of endogenous antigen-specific effector cells and reduced the bacterial burden in the lungs without apparent host toxicity. These results indicate that CD4+ effector T cells are activated at suboptimal frequencies in tuberculosis, and that increasing effector T cell activation in the lungs by providing one or more epitope peptides may be a successful strategy for TB therapy