The role of nonlinear DNA in replication, recombination, and transcription has become evident in recent years. Although several studies have predicted and characterized regulatory elements at the sequence level, very few have investigated DNA structure as regulatory motifs. Here, using G-quadruplex or G4 DNA motifs as a model, we have researched the role of DNA structure in transcription on a genome-wide scale. Analyses of >61,000 open reading frames (ORFs) across 18 prokaryotes show enrichment of G4 motifs in regulatory regions and indicate its predominance within promoters of genes pertaining to transcription, secondary metabolite biosynthesis, and signal transduction. Based on this, we predict that G4 DNA may present regulatory signals. This is supported by conserved G4 motifs in promoters of orthologous genes across phylogenetically distant organisms. We hypothesized a regulatory role of G4 DNA during supercoiling stress, when duplex destabilization may result in G4 formation. This is in line with our observations from target site analysis for 55 DNA-binding proteins in Escherichia coli, which reveals significant (P < 0.001) association of G4 motifs with target sites of global regulators FIS and Lrp and the sigma factor RpoD ( 70 ). These factors together control >1000 genes in the early growth phase and are believed to be induced by supercoiled DNA. We also predict G4 motif-induced supercoiling sensitivity for >30 operons in E. coli, and our findings implicate G4 DNA in DNA-topology-mediated global gene regulation in E. coli.
In conclusion, IOUS is a cheap and useful real-time tool for localizing tumours not seen on the brain surface, for defining their margins and for determining the extent of resection.
Wegener's granulomatosis, Sarcoidosis, Sjög-ren's Syndrome, Behçet disease, Systemic lupus erythematosus, relapsing polychondritis, Churg-Strauss syndrome and Cogan syndromes are rheumatic diseases commonly encountered by otolaryngologists. The present study was designed to assess the understanding and practice about various ENT problems of rheumatic diseases amongst otolaryngologists. A group of 29 otolaryngologists was asked to fill questionnaire which was based on knowledge and practice of otolaryngologists about various otolaryngologic manifestations of rheumatic diseases. Chronic sinusitis was most frequently seen followed by recurrent oral ulcers while spontaneous septal perforation was most infrequently seen symptom by participants. Otolaryngologists showed high index of suspicion and confidence for Wegener's granulomatosis in comparison to other rheumatic diseases. There was no difference noted in practice of otolaryngologists of tertiary care centers and other practitioners. Eighty two percent of participants felt, they were not adequately trained about these diseases. Most of them (93 %) felt that knowledge of such diseases is also necessary for post graduate training in Otolaryngology. Though otolaryngologists are aware of otolaryngologic manifestations of Rheumatic diseases but their index of suspicion, practical implication of knowledge and confidence for evaluation of such diseases is low. Educational sector should define a better medical curriculum for training in Otorhinolaryngology, head and neck surgery.
Decompressive craniectomy in pediatric central nervous infections with refractory intracranial hypertension is less commonly practiced. We describe improved outcome of decompressive craniectomy in a 7-year-old boy with severe herpes simplex encephalitis and medically refractory intracranial hypertension, along with a brief review of the literature. Timely recognition of refractory intracranial hypertension and surgical decompression in children with herpes simplex encephalitis can be life-saving. Additionally, strokelike atypical presentations are being increasingly recognized in children with herpes simplex encephalitis and should not take one away from the underlying herpes simplex encephalitis.
BackgroundIn 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication.MethodsWe conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1–4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months.ResultsFor children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53–0.87] for A versus C, and 0.70 [0.55–0.90] for B versus C).ConclusionsProtection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month.Clinical Trials RegistrationCTRI/2014/09/004979.
Replication of oral poliovirus vaccine (OPV) in the intestine (ie, vaccine take) is associated with seroconversion and protection against poliomyelitis. We used quantitative polymerase chain reaction analysis to measure vaccine shedding in 300 seronegative infants aged 6–11 months and in 218 children aged 1–4 years 7 days after administration of monovalent or bivalent OPV. We found that the quantity of shedding correlated with the magnitude of the serum neutralizing antibody response measured 21 or 28 days after vaccination. This suggests that the immune response to OPV is on a continuum, rather than an all-or-nothing phenomenon, that depends on efficient vaccine virus replication.
We report the first observation of diffuse subendocardial and myocardial delayed enhancement on cardiac MRI in a 50-year-old patient with recurrent multiple myeloma but without evidence of amyloidosis. She presented with advanced heart failure and severe restrictive cardiomyopathy. Myocardial biopsy revealed endomyocardial fibrosis. The case was associated with development of multiple arterial and venous thromboses and a fatal course. Because of the fatal outcome, the prognostic significance of delayed enhancement on MRI in multiple myeloma patients may need to be further investigated.
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