Evaluation of knowledge, attitude and practice about research ethics and research ethics committee among post graduate residents in a tertiary care hospital in Pune, Maharashtra, India

Background: A research ethics committee (REC) is a body responsible for ensuring that medical experimentation and human research are carried out in an ethical manner in accordance with national and international law. It is mandatory that all the research projects should be approved by EC before commencement. Recently Medical council of India has introduced mandatory online research methodology module consisting of assignments followed by mandatory exam.Methods: A cross-sectional study using a self-administered, validated questionnaire was administered among PG residents of a tertiary care hospital in Pune having a functional ethics committee was conducted for 3 months. Number of correct and incorrect responses were noted and calculated in percentage.Results: Total of 125 residents were enrolled and 119 subjects responded. The response rate was 95.2%. The respondents included 59.66% clinical and 40.33% nonclinical post graduate residents. 87.39% knew the role of IEC. 95.79% said informed consent should be mandatory document. 98.31% were aware about the institutional ethics committee (IEC) in the institution. 84.87% think EC and research ethics should be taught as a mandatory PG module.Conclusions: Authors conclude that among the clinical and non-clinical postgraduates participating in study, there is acceptance of IECs and training in research ethics, while there are knowledge gaps in research ethics guidelines and composition of IEC. The updated MCI curriculum imbibes research curriculum but should focus on details about ethics in biomedical research. It can be initiated by workshop/awareness programmes compulsory for UG and PG students

Accidental High Voltage Electrocution: a Case Report

Background: Without electricity, mankind wouldn’t have progressed to the heights we are at now. As much as electricity is helpful, being careless with it can be fatal. The passage of electric current through the body produces wide range of effects, varying from insignificant localised spasm, little or no contact burns, fatality with little or no burns or extreme severe burning.Case Report: This case report discusses the injuries sustained by a young adult, due to accidental contact with high tension wire.Conclusion: This paper also highlights safety rules pertaining to high voltage cables

Suppression of Toll-like Receptor-Mediated Innate Immune Responses at the Ocular Surface by the Membrane-associated Mucins MUC1 and MUC16

Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx, which is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α following exposure of cells to the TLR2 and TLR5 agonists, heat killed Listeria monocytogenes and flagellin, respectively. Since mice express MUC1 (but not MUC16) in the corneal epithelium, a Muc1-/- mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1-/- mice, in comparison to wild type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review

Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting. The efficacy of pembrolizumab in vaginal SCC has never been investigated in any clinical trial. There is established data to support the use of concurrent chemoradiotherapy in gynaecological cancers, however, the data for concurrent use of immunotherapy and radiotherapy is still lacking but is the subject of several clinical trials. We herein present the first reported case of chemotherapy refractory vaginal SCC with complete response to pembrolizumab and concurrent pelvic radiotherapy. We also present wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) as a rare but new immune related adverse event

The Pentameric Vertex Proteins Are Necessary for the Icosahedral Carboxysome Shell to Function as a CO2 Leakage Barrier

BACKGROUND: Carboxysomes are polyhedral protein microcompartments found in many autotrophic bacteria; they encapsulate the CO(2) fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) within a thin protein shell and provide an environment that enhances the catalytic capabilities of the enzyme. Two types of shell protein constituents are common to carboxysomes and related microcompartments of heterotrophic bacteria, and the genes for these proteins are found in a large variety of bacteria. METHODOLOGY/PRINCIPAL FINDINGS: We have created a Halothiobacillus neapolitanus knockout mutant that does not produce the two paralogous CsoS4 proteins thought to occupy the vertices of the icosahedral carboxysomes and related microcompartments. Biochemical and ultrastructural analyses indicated that the mutant predominantly forms carboxysomes of normal appearance, in addition to some elongated microcompartments. Despite their normal shape, purified mutant carboxysomes are functionally impaired, although the activities of the encapsulated enzymes are not negatively affected. CONCLUSIONS/SIGNIFICANCE: In the absence of the CsoS4 proteins the carboxysome shell loses its limited permeability to CO(2) and is no longer able to provide the catalytic advantage RubisCO derives from microcompartmentalization. This study presents direct evidence that the diffusion barrier property of the carboxysome shell contributes significantly to the biological function of the carboxysome

A Metalloproteinase Secreted by Streptococcus pneumoniae Removes Membrane Mucin MUC16 from the Epithelial Glycocalyx Barrier

The majority of bacterial infections occur across wet-surfaced mucosal epithelia, including those that cover the eye, respiratory tract, gastrointestinal tract and genitourinary tract. The apical surface of all these mucosal epithelia is covered by a heavily glycosylated glycocalyx, a major component of which are membrane-associated mucins (MAMs). MAMs form a barrier that serves as one of the first lines of defense against invading bacteria. While opportunistic bacteria rely on pre-existing defects or wounds to gain entry to epithelia, non opportunistic bacteria, especially the epidemic disease-causing ones, gain access to epithelial cells without evidence of predisposing injury. The molecular mechanisms employed by these non opportunistic pathogens to breach the MAM barrier remain unknown. To test the hypothesis that disease-causing non opportunistic bacteria gain access to the epithelium by removal of MAMs, corneal, conjunctival, and tracheobronchial epithelial cells, cultured to differentiate to express the MAMs, MUCs 1, 4, and 16, were exposed to a non encapsulated, non typeable strain of Streptococcus pneumoniae (SP168), which causes epidemic conjunctivitis. The ability of strain SP168 to induce MAM ectodomain release from epithelia was compared to that of other strains of S. pneumoniae, as well as the opportunistic pathogen Staphylococcus aureus. The experiments reported herein demonstrate that the epidemic disease-causing S. pneumoniae species secretes a metalloproteinase, ZmpC, which selectively induces ectodomain shedding of the MAM MUC16. Furthermore, ZmpC-induced removal of MUC16 from the epithelium leads to loss of the glycocalyx barrier function and enhanced internalization of the bacterium. These data suggest that removal of MAMs by bacterial enzymes may be an important virulence mechanism employed by disease-causing non opportunistic bacteria to gain access to epithelial cells to cause infection

Anal canal carcinoma treatment results: the experience of a single institution

<b>Background and Objectives:</b> Prior to the mid-1980s, the treatment of choice for anal cancer was abdominoperineal resection. Currently, combined chemoradiation is the standard of care. Or objective was to analyze results of treatment for anal canal carcinoma treated with combined chemoradiation. <b>Design and Setting:</b> 0Retrospective review of data in local cancer registry at King Faisal Specialist Hospital and Research Centre (KFSHRC) from a 12-year period (1993 to 2005). <b>Methods:</b> We identified patients with confirmed diagnosis of anal canal squamous cell carcinoma. <b>Results:</b> Of 40 patients identified, 33 were considered eligible for our analysis. All patients were treated by concurrent chemoradiation with mandatory treatment break (MTB) There were 10 (30&#x0025;) local recurrences. Five-year progression-free survival (PFS) was 50.9&#x0025;; overall survival (OS) at 5 years was 73.4&#x0025;. Patients with stage II disease had a median PFS period of 10 years, with no relapses until their last follow-up. There was no statistically significant difference in PFS between patients with stage IIIA disease and those with stage IIIB disease-44.7&#x0025; and 45&#x0025;, respectively (<i>P</i>=.8). Five-year PFS according to &#x2032;T&#x2032; stages was as follows: T1, 66&#x0025;; T2, 71&#x0025;; T3, 59&#x0025;; T4, 30&#x0025; (<i>P</i>&gt;.05). The 5-year colostomy-free survival (CFS) for all patients was 74&#x0025;. Distant metastases were observed in 4 patients. <b>Conclusion:</b> Combined chemoradiation in treatment of anal cancer is effective in terms of local control and sphincter preservation. Five-year estimates of PFS, OS, as well as CFS, in patients treated with a MTB were surprisingly comparable to those determined in most non-MTB series. However, we reported a higher local failure rate, for which we are reevaluating our treatment protocol

MUC16 released from epithelial surfaces by SP168 does not bind to a MUC16 cytoplasmic tail antibody indicating ectodomain release.

<p>HCLE cells were cultured with growth culture filtrate obtained from strain SP168 for 1 hour (SP168), and the resultant media was diluted 1∶3 with DMEM/F12, and subjected to a 10 kDa cutoff concentrator. HCLE cell lysate with intact full-length MUC16 (75 µg) was used as a positive control. Western blot of the resulting concentrate and cell lysate using: <b>A</b>) MUC16CT antibody that recognizes full-length MUC16 at >250 kDa and the cytoplasmic tail between 25–37 kDa, or <b>B</b>) MUC16 extracellular domain (ECD) antibody (M11). The MUC16CT antibody binds to the positive control cell lysate only (arrow), but not to the cell culture supernatants after exposure to SP168 (A). Conversely, M11 antibody binds to a band of appropriate molecular weight in culture supernatants as well as the cell lysate (B). These data indicate that the sheddase releases the MUC16 ectodomain into the cell culture media. Molecular weight standards are on the left in kDa.</p