Role of serum interleukin-6 in deciding therapy for multidrug resistant oral lichen planus

Background: Oral lichen planus (OLP) is a T cell mediated immune response. T cells locally present in the involved tissues release cytokines like interleukin-6 (IL-6), which contributes to pathogenesis of OLP. Also IL-6 has been associated with multidrug resistance protein (MRP) expression by keratinocytes. Correspondingly, upregulation of MRP was found in OLP. We conducted this study to evaluate the effects of various drugs on serum IL-6 in OLP; and correlation of these effects with the nature of clinical response and resistance pattern seen in OLP lesions with various therapeutic modalities. Thus we evaluated the role of serum IL-6 in deciding therapy for multidrug resistant OLP. Material and Methods: Serum IL-6 was evaluated in 42 erosive OLP (EOLP) patients and 10 normal mucosa and 10 oral squamous cell carcinoma cases using ELISA technique. OLP patients were randomly divided into 3 groups of 14 patients each and were subjected to Pimecrolimus local application, oral Mycophenolate Mofetil (MMF) and Methotrexate (MTX) alongwith Pimecrolimus local application. IL-6 levels were evaluated before and after treatment. Results: Serum IL-6 levels were raised above 3pg/ml in 26.19% erosive OLP (EOLP) cases (mean- 3.72±8.14). EOLP (5%) cases with IL-6 levels above 5pg/ml were resistant in MTX group. However significant decrease in serum IL-6 corresponding with the clinical resolution was seen in MMF group. Conclusions: Significantly raised IL-6 levels in EOLP reflect the chronic inflammatory nature of the disease. As serum IL-6 levels significantly decreased in MMF group, correspondingly no resistance to treatment was noted. However with MTX there was no significant decrease in IL-6 and resistance to treatment was noted in some, especially plaque type lesions. Thus IL-6 can be a possible biomarker in deciding the best possible therapy for treatment resistant OLP

Visceral Leishmaniasis with Associated Common, Uncommon, and Atypical Morphological Features on Bone Marrow Aspirate Cytology in Nonendemic Region

Objectives. The present study was conducted to categorise the morphological features on bone marrow aspirate cytology into common, uncommon, and atypical features in a nonendemic region which would be helpful in clinching an early and correct diagnosis especially in clinically unsuspected cases. Methods. The morphological features on bone marrow were categorized into common, uncommon, and atypical in cases of leishmaniasis from non endemic region. Results. Out of total 27 cases, 77.7% were residents of places at the height of 500 m or above and fever was the most common presentation followed by hepatosplenomegaly. Plasmacytosis, hemophagocytosis were the common cytological features while dysmyelopoiesis, presence of leishmania bodies in nonhistiocytic cells, and granuloma with necrosis were uncommon features. Aggregates of LD bodies in form of ring, floret, or strap shapes along with giant cells constitute the atypical morphological features. Conclusion. The knowledge of common, uncommon, and atypical features on bone marrow aspirate cytology is helpful in clinching an early and correct diagnosis of leishmaniasis especially in non endemic areas where clinical suspicion is low. These features will guide the pathologist for vigilant search of LD bodies in the marrow for definite diagnosis and thus will also be helpful in preventing unnecessary workups

Cortical Venous Thrombosis

Background Our study retrospectively reviewed the presentation, neuro-radiological findings, and outcomes of eight adult patients presenting at our institution with subarachnoid haemorrhage (SAH), which was subsequently proven to be due to cortical venous thrombosis (CVT). Methods We reviewed the case records and neuroimaging findings of eight patients diagnosed with SAH and CVT over a span of two years at our institution, a tertiary care centre in Western India. All details pertaining to their presentation, clinical findings, neuroimaging, management, and outcome following therapy with anticoagulants were collected until patient discharge. Results There were a total of eight patients, with the average age being 34 years (range 25–42). Only one patient was female. Six patients had a history of recent binge drinking. None of the patients had a past or family history of common risk factors for thrombosis. All patients presented acutely, with headache (n=6) and seizures (n=6) being the most common presenting features, occurring in three-quarters of the patients examined. Non-contrast computed tomography (NCCT) was the initial imaging study for all but one of the patients and showed cortical SAH (cSAH) without basilar haemorrhage. Magnetic resonance imaging/magnetic resonance venography (MRI/MRV) confirmed the underlying CVT. Unfractionated heparin was used in all cases. Seven patients improved and were discharged on oral anticoagulation. The eighth patient died. Conclusion Localised cSAH with sparing of basal cisterns can be a presentation for CVT. In patients with cSAH, MRI/MRV can be useful to make a diagnosis of CVT. Anticoagulation for CVT, even in the presence of SAH was related to seven out of eight patients being discharged

Kinetic Pathway of Pyrophosphorolysis by a Retrotransposon Reverse Transcriptase

DNA and RNA polymerases use a common phosphoryl transfer mechanism for base addition that requires two or three acidic amino acid residues at their active sites. We previously showed, for the reverse transcriptase (RT) encoded by the yeast retrotransposon Ty1, that one of the three conserved active site aspartates (D211) can be substituted by asparagine and still retain in vitro polymerase activity, although in vivo transposition is lost. Transposition is partially restored by second site suppressor mutations in the RNAse H domain. The novel properties of this amino acid substitution led us to express the WT and D211N mutant enzymes, and study their pre-steady state kinetic parameters. We found that the kpol was reduced by a factor of 223 in the mutant, although the Kd for nucleotide binding was unaltered. Further, the mutant enzyme had a marked preference for Mn2+ over Mg2+. To better understand the functions of this residue within the Ty1 RT active site, we have now examined the in vitro properties of WT and D211N mutant Ty1 RTs in carrying out pyrophosphorolysis, the reverse reaction to polymerization, where pyrophosphate is the substrate and dNTPs are the product. We find that pyrophosphorolysis is efficient only when the base-paired primer template region is >14 bases, and that activity increases when the primer end is blunt-ended or recessed by only a few bases. Using pre-steady state kinetic analysis, we find that the rate of pyrophosphorolysis (kpyro) in the D211N mutant is nearly 320 fold lower than the WT enzyme, and that the mutant enzyme has an ∼170 fold lower apparent Kd for pyrophosphate. These findings indicate that subtle substrate differences can strongly affect the enzyme's ability to properly position the primer-end to carry out pyrophosphorolysis. Further the kinetic data suggests that the D211 residue has a role in pyrophosphate binding and release, which could affect polymerase translocation, and help explain the D211N mutant's transposition defect

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements